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STIs Explained: Genital Herpes

FitSugar — Thu, 03 May 2007 17:15:00 -0700

They say love is free, but having unprotected sex in this day and you might be paying the price forever. Did I get your attention? Well I am talking about some serious business since as I learned in high school - Genital Herpes is FOREVER. There is NO cure, so it's really important to take all precautions to prevent getting it.

STIs like Genital Herpes, Chlamydia and Gonorrhea are 100% avoidable, and having no sexual contact would be ideal. Since that might not work, before becoming sexually active with anyone - make sure you and your partner get tested for all STIs before having unprotected sex.

Using latex or polyurethane condoms when having sex is also a great idea, but since a condom can't cover all the infected areas, it's no guarantee that you are 100% protected. Being in a mutually monogamous relationship with someone you know is uninfected is also a great way to keep yourself safe.

Want to hear all about Genital Herpes? Then read more

STI	Symptoms	How do you test for it?	Treatment
Genital Herpes	Small, painful blisters - these can go away after 1-3 weeks but another outbreak can occur weeks or months after Itching or burning before blisters appear	Blood test, or fluid is taken from the blisters and tested	There is NO cure, but antiviral medications can shorten or prevent outbreaks. Although it's rare for a pregnant woman to pass Genital Herpes onto her baby during delivery, a C-Section is usually performed.

STI

Symptoms

How do you test for it?

Treatment

Genital Herpes

Small, painful blisters - these can go away after 1-3 weeks but another outbreak can occur weeks or months after
Itching or burning before blisters appear

Blood test, or fluid is taken from the blisters and tested

There is NO cure, but antiviral medications can shorten or prevent outbreaks.

Although it's rare for a pregnant woman to pass Genital Herpes onto her baby during delivery, a C-Section is usually performed.

Source

STIs Explained: Gonorrhea

FitSugar — Tue, 01 May 2007 17:15:00 -0700

Warm weather has arrived and since Spring Fever is in the air, I thought I'd take the time to talk about Sexually Transmitted Infections (STIs). Fun stuff, I know.

STI stands for "sexually transmitted infection." The reason this term is used instead of STDs (sexually transmitted disease) is because the word "infection" is more accurate since many of these are actually curable (except for Genital Herpes, Genital Warts, and HIV). Also, the word "infection" carries less of a negative social stigma than the word "disease."

STIs like Gonorrhea and Chlamydia are 100% avoidable. Abstaining from sex altogether is the surest way to keep yourself STI-free, but since that's not realistic, definitely have you and your partner get tested before you have sex.

Gonorrhea is spread through contact with the penis, vagina, mouth, or anus, so being in a mutually monogamous relationship with someone you know is uninfected is also a great way to keep yourself safe. When latex or polyurethane condoms are used consistently and correctly, that can also reduce the risk of transmitting gonorrhea.

Make sure to see your gynecologist annually to get tested, because if left untreated, gonorrhea can cause pelvic inflammatory disease (PID) or arthritis.

Want to know about Gonorrhea? Then read more

STI	Symptoms	How do you test for it?	Treatment
Gonorrhea (The #2 STI in the U.S.)	Frequently asymptomatic (no symptoms) Discharge from vagina, penis, or rectum Burning or itching during urination Sore throat	Samples of the infected fluid or urine must be taken	Since gonorrhea is a bacterial infection, several antibiotics can successfully cure it. However, drug-resistant strains of gonorrhea are increasing in many areas of the world, including the United States.

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Sexually transmitted diseases

FitSugar — Wed, 08 Oct 2008 17:34:55 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Sexually transmitted diseases (STDs) are infectious diseases that are spread through sexual contact. STDs are among the most common infectious diseases in the world today. There are over 20 types, affecting more than 13 million men and women in the United States alone each year, and the incidence is on the rise. Some of the most common STDs include chlamydial infection, genital herpes, genital warts, gonorrhea, HIV (human immunodeficiency virus, the microorganism that causes AIDS), and syphilis.

Signs and Symptoms

STDs often occur without symptoms, particularly in women. However, STDs may be accompanied by the following signs and symptoms:

Itching
Discharge
Pustules (pus-containing blisters)
Genital lesions including ulcers, blisters, rashes, and warts. Ulcers may be painful.
Abdominal pain
Rectal infection and inflammation of the rectum
Fever
Muscle pain
Painful urination
Swollen lymph glands in the groin

What Causes It?

STDs are caused by microbial agents and spread primarily (but not exclusively) through sexual contact. Some STDs can also be passed from a mother to her baby during delivery and through breastfeeding while infected. Others may be passed by sharing infected needles. Some of the most common STDs and the microorganisms that cause them are listed below.

AIDS: human immunodeficiency virus (HIV)
Chlamydial infection:Chlamydia trachomatis
Genital herpes: herpes simplex virus (HSV)
Genital warts: human papillomavirus (HPV)
Gonorrhea:Neisseria gonorrhoeae
Syphilis:Treponema pallidum

In addition, there are certain infections classified as STDs that may be sexually transmitted but often are not. Candidal (yeast) infections and Gardnerella (an organism that frequently lives in the vagina) are examples that may cause vaginal inflammation.

Who's Most At Risk?

People with the following conditions or characteristics are at risk for developing STDs:

Having a sexual partner with an STD. In many cases, an STD may be present without symptoms.
Having many sexual partners, or a partner who has many sexual partners.
Having sex without the use of condoms or other protective devices.
Having one STD increases the likelihood of contracting another.
Adolescents are at highest risk for acquiring an STD for the first time.
Living under stress from poverty, poor nutrition, or poor or absent health care.
Practicing anal intercourse increases risk for HIV, gonorrhea, and syphilis.
Having a weakened immune system.
Using intravenous drugs.
Using spermicidal foams and jellies does not protect against STDs and may, in some cases, even promote contraction of certain STDs, including HIV.

What to Expect at Your Provider's Office

Your health care provider will do an examination and check for physical signs. Blood tests and other diagnostic procedures, including cultures from the genitalia, can reveal the microbial agent responsible for the STD and allow the health care provider to select the right therapy.

Treatment Options

Prevention

There are many ways in which people at risk may reduce the likelihood of contracting or spreading STDs:

Have a mutually monogamous sexual relationship with an uninfected partner.
Correctly and consistently use a male or female condom for every act of oral, anal, or vaginal intercourse.
Use clean needles if injecting intravenous drugs.
Prevent and control other STDs.
Have regular checkups for STDs even if you have no symptoms, especially if you are having sex with a new partner or with multiple partners.
Learn the common symptoms of STDs and seek medical help immediately if you develop any symptoms.

Anyone diagnosed with an STD should be treated, avoid sexual activity while being treated, notify all recent sexual partners, complete the course of any medications prescribed, and take a follow-up test.

Drug Therapies

STDs are generally treated with antibiotics and antivirals. See the monograph on HIV and AIDS for details on how that condition is treated.

Complementary and Alternative Therapies

There are some possible applications of CAM therapies in the case of STDs -- as adjunctive treatment (antibacterial and antiviral), as prevention, to improve the immune system, or to reduce certain complications, such as arthritis from gonorrhea. There are also CAM therapies for the treatment of specific STDs, including HIV/AIDs, human papillomavirus, and herpes viral infections. Check with your health care provider about which supplements to use for your condition, and about the interaction of supplements with prescription and non-prescription drugs. It is important to remember that not one of these CAM approaches offers a cure or an isolated treatment option. They should not be used instead of seeing your health care provider. Even during treatment, STDs remain highly contagious -- and you must take the necessary precautions to prevent transmission to sexual partners (see section on Prevention).

Always tell your health care provider about the herbs and supplements you are using or considering using.

Nutrition and Supplements

Following these nutritional tips may help improve general health and wellbeing:

Try to eliminate all suspected food allergens, including dairy, wheat (gluten), soy, chocolate, corn, preservatives, and food additives. Your health care provider may want to test you for food allergies.
Eat more antioxidant-rich foods (such as green, leafy vegetables and peppers) and fruits (such as blueberries, tomatoes, and cherries).
Avoid refined foods, such as white breads, pastas, and sugar.
Eat fewer red meats and more lean meats, cold-water fish, tofu (soy, if no allergy), or beans for protein.
Use healthy cooking oils, such as olive oil or vegetable oil.
Reduce or eliminate trans-fatty acids, found in commercially baked goods such as cookies, crackers, cakes, French fries, onion rings, donuts, processed foods, and margarine.
Avoid coffee and other stimulants, alcohol, and tobacco.
Drink 6 - 8 glasses of filtered water daily.
Exercise moderately, if tolerated, at least 30 minutes daily, 5 days a week.

You may be able to address nutritional deficiencies with the following supplements:

A multivitamin daily, containing the antioxidant vitamins A, C, E, the B-vitamins, and trace minerals, such as magnesium, calcium, zinc, and selenium.
Omega-3 fatty acids, such as fish oil, 1 - 2 capsules or 1 tablespoonful oil two to three times daily, to help decrease inflammation and improve immunity. Cold-water fish, such as salmon or halibut, are good sources.
Vitamin C, 500 - 1,000 mg one to three times daily, as an antioxidant and for immune support.
Coenzyme Q10, 100 - 200 mg at bedtime, for antioxidant, immune, and muscular support.
Acetyl-L-carnitine, 500 mg daily, for antioxidant and antiviral activity.
Probiotic supplement (containing Lactobacillus acidophilus), 5 - 10 billion CFUs (colony forming units) a day, for maintenance of gastrointestinal and immune health. You should refrigerate your probiotic supplements for best results.
L-glutamine, 500 - 1,000 mg three times daily, for support of gastrointestinal health and immunity.
Resveratrol (from red wine), 50 - 200 mg daily, for antioxidant and antiviral effects.
L-theanine, 200 mg one to three times daily, for nervous system support.
Melatonin, 2 - 5 mg one hour before bedtime, for sleep and immune protection.

Herbs

Herbs are generally a safe way to strengthen and tone the body's systems. As with any therapy, you should work with your health care provider to get your problem diagnosed before starting any treatment. You may use herbs as dried extracts (capsules, powders, teas), glycerites (glycerine extracts), or tinctures (alcohol extracts). Unless otherwise indicated, you should make teas with 1 tsp. herb per cup of hot water. Steep covered 5 - 10 minutes for leaf or flowers, and 10 - 20 minutes for roots. Drink 2 - 4 cups per day.

Green tea (Camellia sinensis) standardized extract, 250 - 500 mg daily, for antioxidant, anti-inflammatory and immune effects. Use caffeine free products. You may also prepare teas from the leaf of this herb.
Milk thistle (Silybum marianum) seed standardized extract, 80 - 160 mg two to three times daily, for detoxification support and antiviral effects.
Holy basil (Ocimum sanctum) standardized extract, 400 mg daily, for anti-stress and antiviral protection.
Reishi mushroom (Ganoderma lucidum), 150 - 300 mg two to three times daily, for inflammation and immunity. You may also take a tincture of this mushroom extract, 30 - 60 drops two to three times a day.
Cat's claw (Uncaria tomentosa) standardized extract, 20 mg three times a day, for inflammation and antiviral activity.
Garlic (Allium sativum), standardized extract, 400 mg two to three times daily, for antibacterial or antifungal and immune activity.

Traditional Chinese Medicine (TCM) uses many herb combinations to strengthen and tonify the immune system, and as antiviral agents. Check with your health care provider for more information on TCM.

Homeopathy

Homeopaths use various homeopathic remedies to treat STDs. However, so far no scientific studies have evaluated homeopathy for this purpose. An experienced homeopath would consider each individual case and may recommend treatments to address both the underlying constitution and the specific symptoms of the STD.

Acupuncture

Acupuncture may be used to alleviate symptoms and help enhance our natural ability to fight infection. Acupuncture has been reported to be effective in relieving symptoms of STDs, improving immune function, and decreasing the severity of the STD. Check with your health care provider for more information.

Prognosis/Possible Complications

When they are diagnosed early, many STDs can be treated effectively. However, many possible complications can result from not treating STDs. Some types of STDs commonly recur. Some can result in permanent damage to the reproductive organs and infertility. Having other STDs increases the risk for becoming infected with HIV. Antibiotic resistance by organisms that cause certain STDs may interfere with the effectiveness of treatment.

Following Up

Depending on the type of STD you have, your health care provider may want to see you for follow-up visits to be sure the disease has not recurred or to continue your treatment. If you are pregnant, an STD can cause serious complications for your unborn baby. Your health care provider will discuss treatment options with you.

Supporting Research

Azenabor AA, Mahony JB. Generation of reactive oxygen species and formation of membrane lipid peroxides in cells infected with Chlamydia trachomatis. Int J Infect Dis. 1999;4(1):46-50.

Berger RE. Sexually transmitted diseases: the classic diseases. In: Walsh PC, ed. Campbell's Urology. 7th ed. Philadelphia, Pa: W.B. Saunders Co; 1998.

Bhat KPL, Kosmeder JW 2nd, Pezzuto JM. Biological effects of resveratrol. Antioxid Redox Signal. 2001;3(6):1041-64.

Burnham RC. Diseases caused by chlamydiae. In: Cecil RI, Plum F, Bennett JC, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, Pa: W.B. Saunders Co; 1996.

Cabrera C, Artacho R, Gimenez R. Beneficial effects of green tea--a review. J Am Coll Nutr. 2006;25(2):79-99.

Carillo-Vico A, Reiter RJ, Lardone PJ, et al. The modulatory role of melatonin on immune responsiveness. Curr Opin Investig Drugs. 2006;7(5):423-31.

Chiang LC, Ng LT, Cheng PW, Chiang W, Lin CC. Antiviral activities of extracts and selected pure constituents of Ocimum basilicum. Clin Exp Pharmacol Physiol. 2005;32(10):811-6.

Clancy RL, Gleeson M, Cox A, et al. Reversal in fatigued athletes of a defect in interferon gamma secretion after administration of Lactobacillus acidophilus. Br J Sports Med. 2006;40(4):351-4.

Eo SK, Kim YS, Lee CK, Han SS. Antiviral activities of various water and methanol soluble substances isolated from Ganoderma lucidum. J Ethnopharmacol. 1999;68(1-3):129-36.

Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill; 1998.

Gaby AR. The role of coenzyme Q10 in clinical medicine: Part 1. Alt Med Rev. 1996; 1(1):11-17.

Gore-Felton C, Vosvick M, Power R, Koopman C, Ashton E, Bachmann MH, Israelski D, Spiegel D. Alternative therapies: a common practice among men and women living with HIV. J Assoc Nurses AIDS Care. 2003 May-Jun;14(3):17-27.

Highleyman L. Nutrition and HIV. BETA. 2006;18(2):18-32.

Hitley RJ. Herpes simplex virus infections. In: Cecil RI, Plum F, Bennett JC, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, Pa: W.B. Saunders Co; 1996.

Hook III, EW. Syphilis. In: Cecil RI, Plum F, Bennett JC, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, Pa: W.B. Saunders Co; 1996.

Jernigan JA, Rein MF. Sexually transmitted diseases. In: Reese RE, Betts RF, eds. Practical Approach to Infectious Diseases. 4th ed. Philadelphia, Pa: Lippincott-Raven Publishers; 1996.

Kaplan MS. The abbreviated history and development of acupuncture and moxibustion. North American Society of Acupuncture and Alternative Medicine. Accessed at www.nasa-altmed.com/alterna3.htm on September 18, 2000.

Kimura K, Ozeki M, Juneja LR, Ohira H. L-Theanine reduces psychological and physiological stress responses. Biol Psychol. 2006 Aug 21.

LaValle JB, Krinsky DL, Hawkins EB, et al. Natural Therapeutics Pocket Guide. Hudson, OH:LexiComp; 2000: 452-454.

Li Z, Liu J, Zhao Y. Possible mechanism underlying the antiherpetic activity of a proteoglycan isolated from the mycelia of Ganoderma lucidum in vitro. J Biochem Mol Biol. 2005;38(1):34-40.

Liao SJ, Liao TA. Acupuncture treatment for herpes simplex infections: A clinical case report. Acupunct Electrother Res. 1991;16(3-4):135-142.

Mandel RM, Arguinchona H. Chlamydial sexually transmitted diseases. In: Dambro MR, ed. Griffith's 5 Minute Clinical Consult. Baltimore, Md: Lippincott Williams & Wilkins, Inc.; 1999.

Martin DH. Chancroid. In: Rakel RE, ed. Conn's Current Therapy. 51st ed. Philadelphia, Pa: W.B. Saunders Co; 1999.

Mayer KE, Myers RP, Lee SS. Silymarin treatment of viral hepatitis: a systematic review. J Viral Hepat. 2005;12(6):559-67.

Patrick L. Nutrients and HIV: part three - N-acetylcysteine, alpha-lipoic acid, L-glutamine, and L-carnitine. Altern Med Rev. 2000;5(4):290-305.

Pointer JE, Mulligan-Smith DA. Genital infections. In: Rosen P, Barkin R, eds. Emergency Medicine: Concepts and Clinical Management. 4th ed. St. Louis, Mo: Mosby-Year Book; 1998.

Rotsein OD. Oxidants and antioxidant therapy. Crit Care Clin. 2001;17(1):239-47.

Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr. 2002;21(6):495-505.

Sparling PF. Introduction to sexually transmitted diseases and common syndromes. In: Cecil RI, Plum F, Bennett JC, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, Pa: W.B. Saunders Co; 1996.

Wang HK. The therapeutic potential of flavonoids. Expert Opin Investig Drugs. 2000;9(9):2103-19.

Wang K. 116 Cases of gonococcal arthritis treated with acupuncture. J Tradit Chin Med. 1996;16(2):108-111.

Wang K. Acupuncture for non-gonococcal urethritis: clinical observation of 405 cases. Int J Clin Acupunct. 1997;8(4):359-362.

Williams JE. Review of antiviral and immunomodulating properties of plants of the Peruvian rainforest with a particular emphasis on Una de Gato and Sangre de Grado. Altern Med Rev. 2001;6(6):567-79.

Yoon JH, Baek SJ. Molecular targets of dietary polyphenols with anti-inflammatory properties. Yonsei Med J. 2005;46(5):585-96.

Review Date:
9/8/2006
Reviewed By:
Ernest B. Hawkins, MS, BSPharm, RPh, Health Education Resources; and Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

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STIs Explained: Syphilis

FitSugar — Tue, 15 May 2007 17:15:00 -0700

Since Spring has arrived and romance is in the air, let's talk more about STIs.

STIs like Syphilis, Chlamydia, Gonorrhea, Genital Herpes, and Genital Warts are 100% avoidable, so your best bet is to abstain from vaginal, anal, or oral sex altogether. Since that's not much fun (and not going to happen), it's a good idea for you and your partner to get tested for all STIs before you have sex.

Using latex or polyurethane condoms is also a great idea, but not completely effective. Being in a mutually monogamous relationship with someone you know is uninfected will keep you safe and STI-free.

Make sure to see your gynecologist annually to get tested, because early detection of syphilis (in the first stage) can help prevent permanent organ damage to the heart, eyes, brain, nervous system, bones and joints.

Want to know about Syphilis? Then read more

STI	Symptoms	How do you test for it?	Treatment
Syphilis	Stage 1: One or more painless reddish-brown sores (called chancres) appear on or near the genitals. Sores can also appear on the lips, mouth and fingertips. Stage 2: A skin rash develops anywhere on the body. Flu-like symptoms such as mild fever, fatigue and sore-throat appear. Stage 3: Late stage symptoms include brain damage, mental illness, blindness, organ damage, heart disease and death.	There are 3 ways to test: a doctor's recognition of its symptoms microscopic identification of syphilis bacteria and blood tests	Since syphilis is a bacterial infection, a single injection of Penicillin or other antibiotic will cure a person who has had syphilis for less than 1 year. Additional doses are needed for someone who's had it longer.

STI

Symptoms

How do you test for it?

Treatment

Syphilis

Stage 1: One or more painless reddish-brown sores (called chancres) appear on or near the genitals. Sores can also appear on the lips, mouth and fingertips.
Stage 2: A skin rash develops anywhere on the body. Flu-like symptoms such as mild fever, fatigue and sore-throat appear.
Stage 3: Late stage symptoms include brain damage, mental illness, blindness, organ damage, heart disease and death.

There are 3 ways to test:

a doctor's recognition of its symptoms
microscopic identification of syphilis bacteria
and blood tests

Since syphilis is a bacterial infection, a single injection of Penicillin or other antibiotic will cure a person who has had syphilis for less than 1 year.

Additional doses are needed for someone who's had it longer.

Source

STIs Explained: Trichomoniasis

FitSugar — Fri, 10 Aug 2007 14:30:30 -0700

Since things are heating up everywhere these days, I thought it might be the time to tell you to cool down a little bit and play smart. Yep, it is time to fill you in on a fairly common STI (sexually transmitted infection - it not a disease since it is curable), Trichomoniasis. Tricky to say maybe, but not tricky to prevent!

STIs are considered 100% preventable if you abstain from sex, but let's be reasonable here, that seems pretty unlikely. However you and your partner can both get tested for STIs before you have sex, so you both know you are in the clear.

Since trichomoniasis, also known as trich, is transmitted through genital contact, using latex or polyurethane condoms can greatly reduce your risk in contracting the infection. On the other hand, being in a mutually monogamous relationship is an awesome way to keep yourself safe.

While this may not be a pretty subject, it is good to know what is out there so you can make good decisions and hopefully avoid having to deal with the organ and tissue damage trich can cause. In women, if left untreated trich can cause the fallopian tubes to become inflamed and can also potentially damage your cervix. If your man needs some convincing to get tested tell him that in men, prolonged infection of trich can potentially damage the bladder as well as the prostate. Hopefully that caught your attention!

So for more details about trichomoniasis, then read more

STI	Symptoms	How do you test for it?	Treatment
Trichomoniasis	Can be asymptomatic yellow-green vaginal discharge Vaginal odor Discomfort during intercourse Painful urination or ejaculation	Samples of vaginal discharge or secretions from the penis are examined under a microscope - these protozoan can be seen swimming (eww).	This parasitic infection can be cured with the prescription drug, metronidazole (a pill you take orally)

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Birth control options for women

FitSugar — Wed, 08 Oct 2008 17:34:56 -0700

In This Report

Highlights
Introduction
Oral Contraception
Implant Contraception
Injected Contraception
Intrauterine Devices (IUDs)...
Spermicidal and Barrier Con...
Natural Family Planning Met...
Emergency Contraception
Female Sterilization
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

First "No-Period" Birth Control Pill Approved

In May 2007, the Food and Drug Administration approved Lybrel, the first birth control pill that completely eliminates monthly menstrual periods. Lybrel contains low doses of the estrogen estradiol and the progestin levonorgestrol. The active pills are taken 365 days a year with no inactive pill breaks. In clinical trials, 59% of women who took Lybrel completely stopped having menstrual periods by the end of the first year. Some women, however, continued to experience occasional unscheduled bleeding or spotting during the first 3 - 6 months of use.

Third-Generation Progestins Controversy

In February 2007, the consumer advocacy organization Public Citizen petitioned the Food and Drug Administration to ban the use of desogestrel in oral contraceptives. According to some studies, desogestrel has nearly double the risk for blood clots compared to older, second-generation progestins like levonorgestrel. (However, other studies have not found an increased risk.) Desogestrel is contained in birth control pills such as Mircette.

Oral Contraceptives and Heart Attack Risks

Low-dose oral contraceptives do not increase the risk of heart attack for women in their 30s and 40s, indicates a 2007 study in Fertility and Sterility.

Oral Contraceptives and Cancer Risks

Combination oral contraceptives may reduce the risk for uterine, ovarian, and colorectal cancer, but women who use them for more than 8 years have an increased risk for cervical, breast, and central nervous system cancers, according to a 2007 study in the British Medical Journal.

Birth Control Patch and Blood Clot Risk

Women who use the birth control patch (Ortho Evra) have double the risk for blood clots as women who use oral contraceptives, suggests a 2007 study in Obstetrics & Gynecology. Other studies have reported few differences in risks between the two types of contraceptives. Some experts are concerned that prolonged estrogen exposure with the birth control patch (and ring) increases the risks for blood clots.

Introduction

Contraceptives are devices or methods for preventing pregnancy, either by preventing the fertilization of the female egg by the male sperm or by preventing implantation of the fertilized egg. Contraceptives are not modern inventions. The first prescription for a contraceptive device described a tampon barrier device and was written on papyrus in 1550 BC.

Choosing the appropriate contraceptive varies from individual to individual. Contraceptive options include:

Hormonal contraceptives (oral contraceptives, skin patch, vaginal ring, implant, injection)
Intrauterine devices (IUDs), which contain either a hormone or copper
Barrier devices with or without spermicides (diaphragm, cervical cap, sponge, condom)
Natural family planning methods (basal body temperature, cervical mucus, symptothermal)
Female sterilization (tubal ligation, Essure)

The pill works in several ways to prevent pregnancy. The pill suppresses ovulation so that an egg is not released from the ovaries, and changes the cervical mucus, causing it to become thicker and making it more difficult for sperm to swim into the womb. The pill also does not allow the lining of the womb to develop enough to receive and nurture a fertilized egg. This method of birth control offers no protection against sexually-transmitted diseases.

Contraceptive effectiveness is characterized by "typical use" and "perfect use":

Typical use refers to real-life conditions, in which mistakes (such as forgetting to take a birth control pill at the right time) sometimes happen.
Perfect use refers to contraceptives that are used correctly each time intercourse occurs.

Research has shown that the four most effective standard female contraceptives are surgical sterilization, the intrauterine device (IUD), implants, and injections. They all have an estimated failure rate of less than 1% during the first year of normal (typical) use. Vasectomy (male surgical sterilization) is the only male contraceptive that is equally effective. By comparison, the estimated failure rate of the male latex condom used without spermicide is 14% with typical use and 3% with perfect use. To put these rates into perspective, a sexually active woman of reproductive age who does not use contraception faces an 85% likelihood of becoming pregnant in the course of a year.

Birth control is a controversial subject. In recent years, there has been a growing movement in the United States to restrict a woman's access to contraceptives. In addition to the political battles over non-prescription access to emergency contraception (Plan B), 18 states (as of 2006) are considering legislation that would allow pharmacists to refuse to dispense medications due to moral or religious objections. There have been hundreds of reports of pharmacists refusing to fill birth control prescriptions. In response to this trend, several members of Congress introduced in April 2005 the Access to Legal Pharmaceuticals Act, which would override any state legislation. The bill would require that pharmacies fill birth control prescriptions and would protect women’s legal right to purchase such products.

Oral Contraception

Oral contraceptives are available only by prescription and come in either a combination of estrogen and progestin or progestin alone. Many brands of each form are available. Although both are equally effective with typical use, the combined pill is more effective with perfect use, and most women choose this form.

Some women, however, experience severe headaches or high blood pressure from the estrogen in the combined pill and must take the progestin-only pill. Not all combined pills or progestin-only pills are alike, and brands differ in the amount of estrogen or progestin they contain. Many oral contraceptive combined brands now use lower estrogen doses than previous brands and are proving to be safe and effective while providing a better quality of life than earlier oral contraceptives.

For all oral contraceptive users, a check-up at least once a year is essential. It is also important for women to have their blood pressure checked 3 months after beginning the pill. Former pill users who want to bear children usually regain fertility in 3 - 6 months, but they may regain it even sooner.

Estrogen (Estradiol)

Estrogen is the major female hormone and is responsible for female characteristics. The estrogen compound used in most oral contraceptives is estradiol and is always used with a progestin.

Effects on Reproduction. When used throughout a menstrual cycle with progesterone, estrogen suppresses the actions of other reproductive hormones (luteinizing hormone, or LH, and follicle stimulating hormone, or FSH) and prevents ovulation. Estrogen also changes the cellular structure of the lining of the uterus (the endometrium) and hinders implantation of a fertilized egg.

Side Effects of Estrogen. During the first 2 - 3 months of use of oral contraceptives, side effects from estrogen in the combined pill include:

Nausea and vomiting (can often be controlled by taking the pill during a meal or at bedtime)
Headaches (in women with a history of migraines, they may worsen)
Dizziness
Breast tenderness and enlargement

Progesterone (Progestin)

When used in contraception, progesterone is referred to by one of several names:

Progesterone is the name for the natural hormone.
Progestogen is a synthetic form.
Progestin is the term for any hormone, natural or synthetic, that causes progesterone effects; it is used as the general term in this report.

Progestins may be used alone or with estrogen in oral contraceptives. In addition, certain specific progestins are used in other kinds of contraceptives, such as etonogestrel in the Implanon implant and depo-medroxyprogesterone acetate in the injectable contraceptive Depo-Provera.

Progesterone can prevent pregnancy by itself in several ways:

Blocking luteinizing hormone (LH), one of the reproductive hormones important in ovulation
Maintaining a powerful barrier against the entry of sperm into the uterus by keeping the cervical mucus thick and sticky
Changing the lining of the uterus, making it more difficult for the fertilized egg to implant

Progestins used in contraceptives are referred to as:

Second generation (levonorgestrel, norethisterone).
Third generation (desogestrel, gestodene, norgestimate, drospirenone). The third-generation progestins tend to have fewer male-like side effects. Some studies suggest, however, they may pose a slightly higher risk for blood clots than the older progestins, although the risk is still small.

In 2007, the consumer advocacy group Public Citizen petitioned the Food and Drug Administration (FDA) to ban desogestrel-containing contraceptives, citing studies that indicated a nearly 2-fold increased risk for blood clots compared to second-generation oral contraceptives. Some experts, however, have criticized Public Citizen’s report for relying on older studies. The FDA has said that it will review Public Citizen’s petition.

Side Effects of Progestins. Side effects of progestin occur in both the combination oral contraceptives and any contraceptive that uses only progestin. Side effects may be less or more severe depending on the form and dosage of the contraceptive. Side effects may include:

Changes in uterine bleeding such as higher amounts during periods, spotting and bleeding between periods (called break-through bleeding), or absence of periods
Unexpected flow of breast milk (check with your doctor if this occurs to be sure other conditions are not causing it)
Abdominal pain or cramps
Diarrhea
Fatigue, unusual tiredness, weakness
Hot flashes
Decreased sex drive
Nausea
Trouble sleeping
Acne or skin rash (not all oral contraceptives have this side effect; low-dose oral contraceptives actually improve acne)
Depression, irritability, or other mood changes (although some oral contraceptives are helpful for women with premenstrual dysphoric syndrome)
Swelling in the face, ankles, or feet
Weight gain

Newer formulations of combination pills that use low-dose estrogen, and newer progestins, may reduce and even lower the risk of many of these side effects, including weight gain. Low-dose progestins used in non-oral contraceptives, such as the LNG-IUS IUD, also may not pose as high a risk for these side effects. If side effects continue or are severe, talk to your doctor. For many of those who do have side effects, their bodies eventually adjust.

Click the icon to see an image of a blood clot.

Oral contraceptives that contain both estrogen and progestin are the more common type of oral contraceptive. At least 10 million American women and 100 million women worldwide use combination oral contraceptives. When they were first marketed in the early 1960s, oral contraceptivescontained as much as 5 times the amount of estrogen and up to 10 times the amount of progestins currently used. After reports of severe complications (stroke, heart attack, and pulmonary embolisms) in young women, the hormone amounts were significantly reduced.

The estrogen compound used in most oral contraceptives is ethinyl estradiol (also called estradiol, or EE). Fifty micrograms of estradiol is considered high dose, 30 - 35 micrograms are considered average dose, and 20 micrograms or fewer is low-dose. (The high doses found in current oral contraceptives are still much lower than earlier forms of the pill.) Doctors recommend using the lowest possible progestin and estrogen doses. Estrogen doses should not exceed 50 micrograms, as higher doses increase the risk for complications.

Many different types of progestins are used in combination with estradiol. Some common types of progestin, and popular combination oral contraceptive brands, include:

Desogestrel is the progestrin used in Mircette. Approved in 1998, Mircette was the first oral contraceptive to offer a low estrogen dose and a new type of dosing regimen. Some studies suggest an increased risk for blood clots with desogesterel (see "Hormones Used in Contraceptives").
Drospirenone is used in Yasmin and Yaz. (Yaz contains a lower dose of estrogen than Yasmin.) Because drospirenone increases blood levels of potassium, women should not use Yasmin or Yaz if they have kidney, liver, or adrenal diseases.
Levonorgestrel is used in Seasonale and Seasonique, as well as many other oral and non-oral contraceptives.
Norethindrone is used in Loestrin and Loestrin 24 Fe (which adds iron supplements to the placebo pills).
Norgestrel is used in various generic and brand contraceptives.

Many types of medications and supplements (Tylenol, anti-seizure drugs, antibiotics, vitamin C, St. John's wort) can interact with progestin and reduce its effectiveness. Make sure your doctor is aware of any drugs, vitamins, and herbal supplements that you take.

Types of Regimens. Combination pills are sold in 21-day or 28-day packs:

Each pill in a 21-day pack contains estrogen and progestin. Women take 1 pill a day for 21 days, and then wait 7 days before starting a new 21-day pack.
28-day packs typically start with 21 hormone pills and add 7 placebo pills that do not contain hormones. After taking hormone pills for 21 days, a woman takes the inactive pills for 7 days. Some newer brands, like Yaz, use 24 days of active pills and 4 days of inactive pills. Mircette uses 21 days of low-dose progestin and estrogen, followed by 2 placebo days, and then 5 days of very low-dose estrogen. Loestrin 24 Fe uses 24 days of active pills followed by 4 days of iron-containing placebo pills.

Oral contraceptives may be taken in cycles that include pills of the same or different strengths. These are categorized as monophasic (one-phase), biphasic (two-phase), or triphasic (three-phase). Monophasic pills contain the same amount of hormones in each dose. Biphasic and triphasic pills contain different dosages of hormones within the pill packs. Because monophasic pills have a consistent amount of hormones, they tend to cause fewer hormone-fluctuating side effects than biphasic or triphasic pills. Several 2006 reviews found little difference in effectiveness between these three types of oral contraceptives. Many experts recommend monophasic pills as the best first-choice for birth control pills.

Taking the Pills. A woman usually takes the first pill either on the Sunday after her period starts or during the first 24 hours of her period. (The first pill can be started at any time during the menstrual cycle without affecting the bleeding patterns. Ovulation can occur that month, however.) The remaining pills are taken once a day, ideally at the same time of day, until the pack is used up. If a woman has a 21-day pack, she waits 7 days before starting a new pack. If she is on the 28-day pack, she takes the 7 inactive pills.

If you skip one or more pills, take the following precautions:

Missing the first pill in a new cycle. Take a tablet as soon as you remember and the next one at the usual time. Two tablets can be taken in one day. Use barrier contraception for 7 days after the missed dose. [See "Spermicidal and Barrier Contraception."]
Missing a pill 2 days in a row. Take 2 pills as soon as you remember and then 2 more the following day. Also use back-up barrier contraception until the next pill cycle.
Missing more than 2 days. Discard the pack, use a back-up birth control method, and begin a new cycle on the following Sunday, even if you have started bleeding.

Standard oral contraceptives come in a 28-pill pack that contains 21 active pills and 7 inactive pills. Newer "continuous-dosing" (also called "continuous-use") oral contraceptives aim to reduce -- or even eliminate -- monthly periods and thereby prevent the pain and discomfort that often accompanies menstruation. These oral contraceptives contain a combination of estradiol and the progesterone levonorgestrel, but use extending dosing of active pills.

Seasonale, the first continuous-dosing contraceptive, was approved in 2003. It contains 81 days of active pills followed by 7 days of inactive pills. Women who take Seasonale have on average a period every 3 months. Seasonique, a follow-up to Seasonale, was approved in 2006. As with Seasonale, it produces about 4 periods a year. With Seasonique, a women takes 84 days of levonorgestrol-estradiol pills followed by 7 days of pills that contain only low-dose estradiol.

In 2007, the Food and Drug Administration approved Lybrel, which supplies a daily low dose of levonorgestrol and estradiol with no inactive pills. Because Lybrel contains only active pills, which are taken 365 days a year, it completely eliminates monthly menstrual periods. In clinical trials, 59% of women who took Lybrel completely stopped menstrual periods by the end of the first year. Some women, however, experienced occasional unscheduled bleeding or spotting during the first 3 - 6 months. In clinical trials, women who took Lybrel experienced relief of premenstrual syndrome symptoms within a month of starting the drug.

Progestin-only pill brands include:

Levonorgestrel (Plan B)
Norethindrone (Micronor, Avgestin, Norlutin, Nor-QD). (This progestin is made from male hormones, so may cause more male side effects than others.)
Norgestrel (Ovrette)

Progestin-only pills, which only contain progestins, are always sold in 28-day packs and all the pills are active. (An exception is Plan B, which is emergency contraception.) Progestin-only pills must be taken at precisely the same time each day to maintain top effectiveness. If a woman deviates from her pill schedule by even 3 hours, she should call her doctor about using back-up contraception for the next 2 days. Progestin-only pill users will experience even lighter periods than those taking combination pills. Some may not have periods at all. These hormones should not be used by premenopausal women in their 40s, since they pose a higher risk for adverse effects in this group.

Oral contraceptives are the choice of most American women who use birth control, making them the most popular reversible contraceptives in the U.S. Oral contraceptives are among the most effective contraceptives. Failure rates are very low and are usually due to noncompliance. Some studies have suggested that women who are overweight may have a higher risk for failure. The risk for these women is also still very low, however.

Oral contraceptives also have the following advantages:

More sexual freedom. oral contraceptives do not interfere with intercourse, and in fact, many women report that sex is more pleasurable because they no longer have to worry about pregnancy.
Reduce menorrhagia (heavy bleeding) and, therefore, reduce the risk for anemia.
Reduction in dysmenorrhea (severe pain). High-dose oral contraceptives have been especially helpful, but they carry risks. Specific newer low-dose oral contraceptives that contain certain progestins, such as Yasmin (with drospirenone) and Mircette (with desogestrel), may reduce menstrual pain.
Possible reduction in premenstrual syndrome with specific oral contraceptives, notably Yaz (which was approved for treating premenstrual dysphoric disorder -- premenstrual depression -- in 2006.) Some oral contraceptives, however, are associated with worse emotional changes. Monophasic oral contraceptives may have a more beneficial effect on mood than triphasic oral contraceptives.
Reduction in endometriosis.

Endometriosis is the condition in which the tissue that normally lines the uterus (endometrium) grows on other areas of the body causing pain and irregular bleeding.

Possible protection against multiple sclerosis. Some studies have suggested that women who take oral contraceptives may be less likely to develop multiple sclerosis
Acne improvement with low-dose oral contraceptives. (Some low-dose contraceptives, such as Ortho Tri-Cyclen, have been specifically approved for acne reduction, although most low-dose oral contraceptives reduce testosterone levels and so help reduce acne.)
Possible protection against bone loss with low-dose oral contraceptives. The effect of contraceptives on bone density is unclear and may depend on the specific formulas and types of progestins used.

Common Side Effects. Estrogen and progesterone have different side effects. Women on the combined pill may experience different effects from those on the progestin-only pill. Symptoms of serious problems include severe abdominal pain, chest pain, unusual headaches, visual disturbances, or severe pain or swelling in the legs. In spite of some concerns, combination oral contraceptives do not generally cause weight gain.

[For specific side effects of estrogen and progestin, see "Hormones Used in Contraception."]

Serious Effects on Heart and Circulation. Combination birth control pills contain estrogen, which can increase the risk for stroke, heart attack, and blood clots in some women. The risk is highest for women who smoke or have a history of heart disease risk factors (such as high blood pressure) or cardiac events. Women who have certain metabolic disorders, such as polycystic ovary syndrome (PCOS), are also at higher risk for heart-related complications associated with these pills.

When birth control pills were first introduced, heart and circulatory risks were higher than they are now. Current brands of combination oral contraceptives contain much lower dosages of estrogen and are safer than those earlier pills. Some studies, however, including a 2005 review, suggest that even low-dose combination birth control pills have some cardiovascular risks. Other research, such as a 2007 study of older women ages 30 - 49, indicate that low-dose oral contraceptives do not increase heart attack risk.

All combination estrogen/progestin birth control products carry an increased risk for blood clots in the veins (venous thromboembolism). The risk is lower for oral contraceptives than for the birth control patch (Ortho Evra) or the ring (NuvaRing), which expose women to higher levels of estrogen than birth control pills. Women who smoke or who have other heart disease risk factors may want to consider using alternatives to combination oral contraceptives, such as progestin-only oral contraceptives ("mini-pills"), intrauterine devices, or barrier contraceptive methods. Discuss your lifestyle and health history with your doctor to determine if combination birth control pills are safe for you.

Click the icon to see an image of stroke.

Overall Cancer Risks. Combination oral contraceptives appear to increase the risk for some types of cancers (cervical) and reduce the risks for others (ovarian and uterine). For other types of cancer, such as breast cancer, the evidence is less clear. According to a 2007 study in the British Medical Journal, current users of high-dose (50 micrograms/day) combination oral contraceptives have a reduced risk for uterine, ovarian, and possibly colorectal cancer. However, women who use estrogen-containing oral contraceptives for more than 8 years have an increased risk for cervical, breast, and central nervous system cancers. Researchers found that once women stopped taking birth control pills, the risks for breast and cervical cancer returned to those of non-users within 10 years.

Breast Cancer. Studies have been conflicting about whether estrogen in oral contraception increases the chances for breast cancer, and if it does, which women are at risk. Some studies indicate that the risk may be higher for premenopausal breast cancer when women use oral contraceptives before their first pregnancy. The most definitive study to date -- the 2002 Women’s Contraceptive and Reproductive Experiences (CARE) study -- evaluated oral contraceptive use and breast cancer among women ages 35 - 64. The CARE study found that current or former oral contraceptive use did not increase the risk for breast cancer.

Cervical Cancer. Several studies have reported a strong association between cervical cancer and long-term use of oral contraception. Women who have taken oral contraceptives for more than 10 years have a much higher risk of human papilloma virus (HPV) infection (up to four times higher) than those who do not use oral contraceptives. Women taking oral contraceptives for less than 5 years have no significantly higher risk. The reasons for this risk from oral contraceptive use are not entirely clear. Women who use oral contraceptives may be less likely to use a diaphragm, condoms, or other methods that offer some protection against sexual transmitted diseases, including HPV. Some experts also suggest that the hormones in oral contraceptives might facilitate entry of the HPV virus in the genetic material of cervical cells. HPV is the main cause of cervical cancer, as well as genital warts.

Ovarian and Uterine Cancers. Evidence clearly indicates that oral contraceptives reduce the risk of ovarian cancer. The risk decreases by 10 - 12% after 1 year of use and by 50% after 5 years of use. Contraceptives with high levels of progestins may reduce ovarian cancer risk more than contraceptives with low levels of progestins. Oral contraceptives also reduce the risk of uterine (endometrial) cancer. The protective effect of oral contraceptives continues for many years after a woman stops taking the pills.

Click the icon to see an image of cervical cancer.

Other Complications. Other complications have been associated with the use of oral contraceptives:

Taking oral contraceptives containing certain progestins (desogestrel in one study) may increase the risk for periodontal disease. Other types of progestins do not pose a risk for gum disease.
There has been some debate over whether the progestin-only pill increases the risk for permanent type 2 diabetes in women who develop a temporary form of diabetes during pregnancy (called gestational diabetes). In any case, the low-dose combination pill does not appear to pose such a risk. Women with a history of gestational diabetes should discuss this controversy with their doctor.
Some evidence suggests that oral contraceptives may reduce lung capacity during exercise. There have been a few reports of worsening asthma symptoms with oral contraceptives, but this is not common.
The pill can affect the liver and, rarely, has been associated with liver tumors, gallstones, or jaundice. Women with a history of liver disease, such as hepatitis, should consider other contraceptive options.

Interactions with Other Medications. Oral contraceptives can interact with many other medications and herbal supplements.

New methods of administering the combination of progestin and estrogen are now available. Failure rates with perfect use (0.1 - 0.6%) are similar to those with combined oral contraceptives. The recommendations and side effects are the same as those for oral contraceptives. None of these methods protect against sexually transmitted diseases.

Skin Patches. Ortho Evra was approved in 2002 as the first birth control skin patch. It contains a progestin (norelgestromin) and estrogen. The patch is placed on the lower abdomen, buttocks, or upper body (but not on the breasts). Each patch is worn continuously for a week and reapplied on the same day of each week. After three weekly patches, the fourth week is patch-free, which allows menstruation. (The patch remains effective for 9 days, so being slightly late in changing it should not increase the risk for pregnancy.)

In 2005, the Food and Drug Administration warned that the Ortho patch exposes women to higher levels of estrogen than most birth control pills, and therefore may increase the risk for blood clots and other serious side effects. A 2007 study reported that women who use the patch have twice the risk of blood clots as women who use estrogen/norelgestromin oral contraceptives. In contrast, other studies in 2006 and 2007 suggested that the patch and oral contraceptives carry similar blood clot risks. Older women (over age 40) and women with risk factors for blood clots (such as cigarette smoking) may find other birth control products to be a safer choice. Discuss with your doctor whether the patch is appropriate for you.

Vaginal Ring. NuvaRing is a 2-inch flexible ring that contains both estrogen and progestin (etonogestrel). It is inserted into the vagina. Women can insert the ring by themselves once a month and take it out at the end of the third week to allow menstruation. It works well and may cause less irregular bleeding than oral contraceptives. Some women find it uncomfortable, and a few have reported vaginal irritation and discharge, but such problems rarely cause a woman to discontinue use. As with the patch, NuvaRing may put women who take it at higher risk for blood clots than oral contraceptives.

Implant Contraception

Implant contraception involves inserting a rod under the skin. The rod releases into the bloodstream tiny amounts of the hormone progestin.

The first implant was the Norplant system, which used six rods that contained levonorgestrel. Due in part to serious complications, Norplant was withdrawn from the U.S. market in 2002. The main complication was difficulty inserting and, in particular, removing the rods. (Many women experienced scarring.) In addition, some women who used Norplant experienced heavy irregular bleeding. A two-rod implant called Jadelle is sold in other countries, but not the United States.

In 2006, the Food and Drug Administration approved Implanon, a new implant contraceptive. In contrast to Norplant:

Implanon uses one rod, not six.
It is not inserted as deeply into the skin.
It uses etonogestrel, a different type of progestin than the levonorgestrel used in Norplant.
Only specially trained health care providers are allowed to insert and remove Implanon.

Implanon insertion takes about a minute and is performed with a local anesthetic in a doctor’s office. The rod remains in place for 3 years, although it can be removed at any time. (The removal procedure takes a few minutes longer than insertion.) After the rod is removed, a new one can be inserted.

Studies indicate that Implanon is safe. Irregular bleeding is the main side effect. However, some doctors are concerned that Implanon may have some of the same risks as Norplant.

Injected Contraception

Injected contraceptives are given once every 3 months. Most injectables are progestin-only. In the United States, depo-medroxyprogesterone acetate (Depo-Provera) is the only approved injected contraceptive. Depo-Provera (also called Depo, or DMPA) uses a progestin called medroxyprogesterone. Like other progestin contraceptives, Depo-Provera prevents pregnancy by halting ovulation, thickening the cervical mucus, and stopping the implantation of fertilized eggs in the uterine lining.

Depo-Provera is very effective in preventing pregnancies. About 3 in 100 women who use it become pregnant. However, Depo also carries the risk for many mild and serious side effects. The most serious side effect is loss of bone density (see "Disadvantages"). Because of this complication, Depo-Provera should not be used for more than 2 years.

Administering Injections:

A physical examination is necessary before beginning the injections.
Depo is injected into a muscle in the patient's arm or buttock. During months between injections, the hormone slowly diffuses out of the muscle into the bloodstream.
Depo requires an injection by the doctor once every 3 months.
If more than 2 weeks pass beyond the regular injection schedules, the woman should have a pregnancy test before receiving the next injection.

Because Depo-Provera does not contain estrogen, it is safe for many women who are not candidates for combination oral contraceptives, such as women smokers over age 35.

Depo-Provera should not be given to women who have a history of:

Current or past breast cancer
Stroke or blood clots
Liver disease
Epilepsy, migraine, asthma, heart failure, or kidney disease (due to the fact that the drug causes fluid retention)
Unexplained vaginal bleeding
Risk for osteoporosis

Because of the long lag time between ending treatments and restoration of fertility, Depo-Provera is not recommended for women who are thinking of becoming pregnant within 2 years.

Provides highly effective reversible protection against pregnancy without placing heavy demands on the user's time or memory.
Does not increase risk for breast, ovarian, or cervical cancer. May protect against endometrial cancer.
May be useful for women with painful periods, heavy bleeding (including heavy bleeding caused by fibroids), premenstrual syndrome, and endometriosis.

Weight gain. Most women gain an average of 5 - 8 pounds.
Other common side effects include menstrual irregularities (bleeding or cessation of periods), abdominal pain and discomfort, dizziness, headache, fatigue, nervousness.
Most users of Depo-Provera stop menstruating altogether after a year. Depo can cause persistent infertility for up to 22 months after the last injection, although the average is 10 months.
Long-term (more than 2 years) use of Depo-Provera can cause loss of bone density. In November 2004, the Food and Drug Administration (FDA) added a “black box” warning to the Depo-Provera label advising of this risk. The warning notes that the decline in bone density increases with duration of use and may not be completely reversible even after the drug is discontinued. Based on this information, the FDA recommends that Depo-Provera should not be used for longer than 2 years unless other birth control methods are inadequate. A 2005 study of young women (age 14 - 18 years) found that adolescents who stop taking Depo-Provera do regain bone density.
The injections do not provide protection against sexually transmitted diseases. According to a 2004 study, women who take Depo-Provera have three times the risk of acquiring chlamydia and gonorrhea as women who do not use a hormonal contraceptive. The reason for this increased risk is unclear. The same study found that oral contraceptive use, in comparison to non-hormonal contraceptives, was not associated with increased risk.

Intrauterine Devices (IUDs)

The intrauterine device (IUD) is a small plastic T-shaped device that is inserted into the uterus. An IUD's contraceptive action begins as soon as the device is placed in the uterus and stops as soon as it is removed. IUDs have an effectiveness rate of close to 100%. They are also a reversible form of contraception. Once the device is removed, a woman regains her fertility.

The intrauterine device (IUD) is one of the safest, least expensive, and most effective contraceptive devices available. In spite of its clear advantages and current safety record, only 1% of American women currently use the IUD. (Over 10% of European women have chosen the IUD.) This low use in America is mainly due to persisting and now unwarranted fears of serious infection and other complications. However, the evidence available today should reassure providers and patients about the following concerns:

Pelvic infections. What was thought to be an increased risk of pelvic inflammatory disease has proven not to be true. Large groups of patients have been evaluated, and their risk does not seem to be any greater than the risk in the general population The risk for infection may be increased around the time of insertion of the IUD, but routine screening before insertion is generally not recommended There is also no evidence that IUD usage increases the risk of HIV infection.
Infertility. IUDs were thought to cause infertility, mostly because of concerns about infections. However, studies have shown that women with a history of using an IUD are no more likely to be diagnosed with infertility than those who have not used IUDs. This seems to be true for women who have never been pregnant or women who have been pregnant previously.
Ectopic pregnancy. Another concern was a presumed increased risk for an ectopic pregnancy. In reality, women using IUDs have a significantly lower rate of ectopic pregnancies than women using no contraception at all. Even for women who have a history of ectopic pregnancies when not using contraception, the IUD is considered safe and may even lower their risk for another one.

The intrauterine device (IUD) shown uses copper as the active contraceptive, others use progesterone in a plastic device. IUDs are very effective at preventing pregnancy (less than 2% chance per year for the progesterone IUD, less than 1% chance per year for the copper IUD). IUDs come with increased risk of ectopic pregnancy and perforation of the uterus and do not protect against sexually transmitted disease. IUDs are prescribed and placed by health care providers.

Two types of intrauterine devices (IUDs) are available in the United States:

Copper-Releasing (ParaGard). This type of IUD can remain in the uterus for up to 10 years. Cooper ions released by the IUD are toxic to sperm, thus preventing fertilization.
Progestin-Releasing (Mirena). This type of IUD can remain in the uterus for up to 5 years. Mirena is also known as a levonorgestrel-releasing intrauterine system, or LNG-IUS. Levonorgestrel impairs sperm motility and viability, thus preventing fertilization. LNG-IUS is long-acting, safe, very effective in preventing heavy bleeding, and helps reduce cramps. In fact, some experts describe it as a nearly ideal contraceptive. This device is also proving beneficial for women with menstrual disorders, particularly heavy bleeding.

With some exceptions, an intrauterine device (IUD) can be inserted at any time, except during pregnancy or when an infection is present. It may be inserted immediately postpartum or after elective or spontaneous miscarriage. It is typically inserted in the following manner by a trained health professional:

A plastic tube containing the IUD (the inserter) is slid through the cervical canal into the uterus.
A plunger in the tube pushes the IUD into the uterus.
Attached to the base of the IUD are two thin but strong plastic strings. After the instruments are removed, the health care provider cuts the strings so that about an inch of each dangles outside the cervix within the vagina.

The strings have two purposes:

They enable the user or health care provider to check that the IUD is properly positioned. (Because the IUD has a higher rate of expulsion during menstruation, the woman should also check for the strings after each period, especially if she has heavy cramps.)
They are used for pulling the IUD out of the uterus when removal is warranted.

The insertion procedure can be painful and sometimes causes cramps, but for many women it is painless or only slightly uncomfortable. Patients are often advised to take an over-the-counter painkiller ahead of time. They can also ask for a local anesthetic to be applied to the cervix if they are sensitive to pain in that area. Occasionally a woman will feel dizzy or light-headed during insertion. Some women may have cramps and backaches for 1 - 2 days after insertion, and others may suffer cramps and backaches for weeks or months. Over-the-counter painkillers can usually moderate this discomfort.

Intrauterine devices are an excellent choice of contraception for women who are seeking a long-term and effective birth control method, particularly those wishing to avoid risks and side effects of contraceptive hormones. The LNG-IUS may be better suited for women with heavy or regular menstrual flow.

Around the time of insertion and shortly afterwards, women should be considered at low risk for sexually transmitted disease (mutually monogamous relationship, using condoms, or not sexually active).

Women with risk factors that preclude hormonal contraceptives should probably avoid progestin-releasing IUDs, although the progestin doses are much lower with LNG-IUS and probably do not pose the same risks.

Women with the following history or conditions may be poor candidates for IUDs:

Current or recent history of pelvic infection
History of menstrual disorders -- mostly for the copper-releasing IUDs, however
Current pregnancy
Abnormal Pap tests
Cervical or uterine cancer
A very large or very small uterus

IUDs have the following advantages:

The IUD is more effective than oral contraceptives at preventing pregnancy, and it is reversible. Once it is removed, fertility returns. (In spite of outdated concerns, studies have found no adverse effects on fertility with the current IUDs.)
Unlike the pill, there is no daily routine to follow.
Unlike the barrier methods (spermicides, diaphragm, cervical cap, and the male or female condom), there is no insertion procedure to cope with before or during sex.
Intercourse can resume at any time, and, as long as the IUD is properly positioned, neither the user nor her partner typically feels the IUD or its strings during sexual activity.
It is the least expensive form of contraception over the long term.

Additional advantages, depending on the specific IUD, include:

The progestin-releasing LNG-IUS (Mirena) is now considered to be one of the best options for treating menorrhagia (heavy menstrual bleeding). (However, irregular breakthrough bleeding can occur during the first 6 months.) It may even be appropriate and protective for women with uterine fibroids.
The copper-releasing IUDs do not have hormonal side effects and may help protect against endometrial (uterine) cancer.

Menstrual Bleeding. Both intrauterine device (IUD) forms have effects on menstruation, although they differ significantly by type:

Copper releasing IUDs can cause cramps, longer and heavier menstrual periods, and spotting between periods. Prescription medications are available to control the bleeding and pain, which, in any event, usually subside after a few months.
Progestin-releasing IUDs produce irregular bleeding and spotting during the first few months. Bleeding may disappear altogether. (This characteristic is a major advantage for women who suffer from heavy menstrual bleeding but may be perceived as a problem for others.)

Menstrual difficulties can be so troublesome with either IUD that, according to one study, they were responsible for a removal rate of 5 - 15% within a year of insertion.

Ovarian Cysts. The LNG-IUS may increase the risk for ovarian cysts, but such cysts usually do not cause symptoms and resolve on their own.

Expulsion. An estimated 2 - 8% of IUDs are expelled from the uterus within the first year. Expulsion is most likely to occur during the first 3 months after insertion. Expulsion rates may be higher than average if the IUD is inserted immediately after delivery of a child. In 1 in 5 cases, the woman fails to notice that the device is gone, and thus faces the risk of unintended pregnancy. The risk for expulsion is highest during menstruation, so women should be sure to check the strings to make sure the IUD is in place.

Effects on Pregnancy. None of the current IUDs increase the risk for infertility. In the very unlikely event that a woman conceives with an IUD in place, however, there is a higher risk of an ectopic pregnancy or miscarriage.

Click the icon to see an image of an ectopic pregnancy.

If the IUD is removed right after conception, the risk for miscarriage is close to average (about 20%). There is no evidence that the IUD in a pregnant woman increases the risk for birth defects in the infant.

Perforation. A potentially serious complication of the IUD is the accidental perforation of the uterus during insertion or later perforation if the IUD shifts position. Such an occurrence is very rare, and the risk is higher or lower depending on the skill of the doctor.

Spermicidal and Barrier Contraception

Barrier contraceptives are devices that provide a physical barrier between the sperm and the egg. Examples of barrier contraceptives include the male condom, female condom, diaphragm, cervical cap, and sponge. [For a description of the male condom, see "Male Condom."] Barrier devices are the only contraceptive methods that can help prevent sexually transmitted diseases (STDs).

Spermicides are sperm-killing substances available as foams, creams, or gels, and are often used in female contraception with barrier and other devices. Spermicides are usually available without a prescription or medical examination.

The active ingredient in U.S.-made spermicides is usually nonoxynol-9, which attacks the surface of the sperm cell. Nonoxynol-9, however, does not provide any additional protection against sexually-transmitted diseases. Research indicates that frequent use can cause vaginal irritation and abrasions and actually increase the risk for HIV transmission in women. In addition, use of a spermicide with a barrier device doubles or triples the risk for a urinary tract infection in women, regardless of whether the device is a condom or diaphragm. Spermicides are no longer recommended with male condoms. (Non-spermicidal lubricated condoms are safe to use.) Some experts think they are not necessary for use with diaphragms, but this issue is still under debate.

In general, spermicides may be an appropriate choice for women who have intercourse only once in a while, or need backup protection against pregnancy (for instance, if they forget to take their birth control pills). Spermicides should not be used alone as the primary method of birth control. Nor should they be used to prevent sexually transmitted diseases.

The diaphragm, which is generally used with a spermicidal cream, foam, or gel, is a small dome-shaped latex cup with a flexible ring that fits over the cervix. The cup acts as a physical barrier against the entry of sperm into the uterus. The spermicide provides added chemical protection but, as stated above, some doctors think they are not necessary for use with diaphragms.

The diaphragm is a flexible rubber cup that is filled with spermicide and self-inserted over the cervix prior to intercourse. The device is left in place several hours after intercourse. The diaphragm is a prescribed device fitted by a health care professional and is more expensive than other barrier methods, such as condoms.

There are three basic rim designs:

The Arcing Spring diaphragm applies strong pressure and easily flips into place. It is useful for women with weak vaginal muscles and for new users who are worried about incorrect placement.
The Coil Spring Rim is useful for women with strong vaginal muscles.
The Flat Spring Rim has a delicate rim and a gentle spring, and may be appropriate for women who have not had children.

Diaphragms come in different sizes and require a fitting by a trained health care provider. The health care provider also advises and prescribes the correct size of diaphragm for the user. Some women will need to be refitted with a different-sized diaphragm after pregnancy, abdominal or pelvic surgery, or weight loss or gain of 10 pounds or more. As a general rule, diaphragms should be replaced every 1 - 2 years.

Although the diaphragm has a relatively high failure rate, even with perfect use, it is considered a good choice for women whose health or lifestyle prevents them from using more effective hormonal contraceptives. Certain conditions of the vagina and uterus, a history of toxic shock syndrome, or a history of recurrent urinary tract infections, may disqualify a woman from using the device. The diaphragm should not be used if either partner is allergic to latex or spermicides.

Using and Inserting the Diaphragm. The diaphragm can be placed in the vagina up to 1 hour before intercourse and can be used even when a woman is menstruating. The following are general guidelines for insertion:

Before or after each use, the woman should hold the diaphragm up to the light and fill it with water to check for holes, tears, or leaks.
A small amount of spermicide (about 1 tablespoon) is usually placed inside the cup, and some is smeared around the lip of the cup.
The device is then folded in half and inserted into the vagina by hand or with the assistance of a plastic inserter.
The diaphragm should fit over the cervix, blocking entry to the womb.
If more than 6 hours pass before repeat intercourse occurs, the diaphragm is left in place and extra spermicide is inserted into the vagina using an applicator.
The diaphragm must remain in the vagina for 6 - 8 hours after the final act of intercourse, and can safely stay there up to 24 hours after insertion.
The diaphragm should be washed with soap and warm water after each use and then dried and stored in its original container, which should be kept in a cool dry place.

Advantages of the Diaphragm. The diaphragm can be carried in a purse, can be inserted up to an hour before intercourse begins, and usually cannot be felt by either partner. It may protect against cervical gonorrhea, Chlamydia, and trichomoniasis, although more research is needed to confirm this. It does not provide protection against sexually-transmitted infections in areas other than the cervix.

Disadvantages and Complications of the Diaphragm. Some disadvantages or complications are as follows:

Failure rates are high, about 20% with typical use.
Some women dislike having to insert the device every time intercourse occurs or have trouble mastering the insertion and removal process.
Frequent urinary tract infections are a problem for some women. This difficulty can sometimes be resolved by a refitting, by urinating before inserting the device, or by urinating after intercourse.
Cases of toxic shock syndrome have been reported among diaphragm users, but it is very rare. To be safe, the diaphragm should not stay in place for more than 24 hours. (It is still important for pregnancy protection, however, to retain the diaphragm for 6 - 8 hours after intercourse.)
It provides protection against sexually transmitted disease only in the cervix, and women should not rely on it for protection against HIV.

The cervical cap (Prentif, FemCap) is a thimble-shaped latex cup that fits over the cervix. It is always used with a spermicidal cream or gel. It is similar to a diaphragm, but smaller, and is available in only four sizes. The cap is sold by prescription and requires a pelvic examination, Pap test, and fitting by a health care provider.

Insertion and Use of the Cervical Cap. After a small amount of spermicide is placed in the cap, the device is inserted by hand. As in diaphragm use, instruction and practice is required. The cap must be kept in the vagina for 8 hours after the final act of intercourse. Caps wear out and should be replaced every 1 - 2 years. A refitting may also be needed when a woman experiences certain changes in her health or physical status.

Click the icon to see an image of a cervical cap.

Candidacy for the Cervical Cap. Because of the restricted range of available sizes, about 1 in 5 woman will not be able to be fitted for the cap. The cap is not widely used, and some women, particularly those who live in sparsely populated areas, may not have access to health care professionals who are trained in fitting this device. Other conditions that can preclude cap use include:

An abnormal Pap test
A history of toxic shock syndrome
A sexually transmitted or reproductive tract infection
Inflammation of the cervix
The cap has little value for women who have had children, because the stretching of the vagina and cervix makes a proper fit more difficult and failure rates are high.

Advantages of the Cervical Cap. Among women who have never given birth, the cap's failure rate, at least with Prentif cervical cap, is similar to that of the diaphragm. (The FemCap appears to have a higher failure rate.) The cap in general is also similar to the diaphragm in terms of cost, ease of use, protection against sexually transmitted diseases (STDs), and also the potential for latex or spermicidal allergies. But unlike the diaphragm, the cap can safely remain in the vagina for up to 48 hours (twice the time limit for a diaphragm), so it can be inserted well in advance of intercourse. The cap is rarely associated with urinary tract infections, and no documented cases of toxic shock syndrome have been reported.

Disadvantages of the Cervical Cap. The following are disadvantages of the cervical cap:

Failure rate with any cap is high in women who have given birth (40%). In general, the FemCap has a higher risk for failure than either the diaphragm or the Prentif cap.
Unlike the diaphragm, the cap cannot be used during menstruation.
Use of the cervical cap (particularly the Prentif cap) poses a higher risk for abnormal cervical cell growth than with the diaphragm.

The female condom (Reality, Femidom) is a lubricated, loose-fitting pouch that lines the vagina. It is designed to create a physical barrier against sperm and sexually transmitted diseases by surrounding the penis during intercourse. The failure rate for the female condom is about the same as for the diaphragm and cervical cap. It is available without a prescription but may be hard to find.

Use and Insertion of the Female Condom. The female condom is about 3 inches wide and 6 - 7 inches long (larger than a male condom), with a flexible ring at both ends. Current products are made of polyurethane.

The ring at the closed end is used to insert the device into the vagina and hold it in place over the cervix.
The ring at the open end remains outside the vagina and partly covers the labia (lips).

The insertion process may seem difficult at first but becomes much easier with practice:

The female condom is inserted by hand into the vagina up to 8 hours before intercourse. (It should never be used in combination with a male condom.)
Although the female condom is prelubricated, extra lubricant is sometimes needed while inserting the device or during intercourse. (It is not made of latex, so oil lubricants will not harm it.)
During intercourse, the woman checks to be sure that the outer ring is lying flat against her labia and then guides her partner's penis into the ring.

The female condom should be removed in the following circumstances:

If it tears during insertion or use
If the outer ring is pushed inside
If it bunches up inside the vagina

The female condom may be the best option for women at risk for sexually transmitted diseases and who are not certain that their male partner will use a condom. There are virtually no obstacles against its use except a negative psychological perception. It is not completely fail-proof against pregnancy or sexually transmitted diseases.

Advantages of the Female Condom. In one study, 75% of the women preferred the female to the male condom. Many men also find it more appealing than the latex male condom. The female condom has a number of advantages over the male condom:

The female condom is an effective barrier to viruses, including HIV, and other sexually transmitted organism, particularly since it covers a large area, including external genitals. However, there are not enough clinical studies at this time to determine its protection against sexually transmitted diseases. No contraceptive device is foolproof.
The standard female condom is made of polyurethane, which is thin and soft but at the same time 40% stronger than the latex male condoms. Polyurethane is not damaged by lubricating oils, as latex is and is also less likely to cause an allergic reaction. It transmits body heat better than latex, providing a more "natural" sensation, and possibly enhancing the pleasure of the sexual act.
The man does not have to withdraw his penis immediately after ejaculation, as is the case with the male condom, but can, if he wishes, withdraw after he has lost his erection.

Disadvantages and Complications of the Female Condom. Compliance rates are low for many reasons. About 25% of women have difficulty on the first attempt at self-insertion. Some women are distressed by self-insertion. The inner ring may be uncomfortable for some women (in which case it can be removed). Some couples complain that the female condom is unpleasant to look at and can be noisy during intercourse. Without sufficient lubrication, it can also be pushed out of place by the penis. Using more lubricant can help keep the female condom in place and reduce the noise. Female condoms are also expensive, and some women wash them out and reuse them to save money. (In such cases, they should be disinfected first and then washed carefully.) Repeated washings can increase the risk for damage and holes. It is not known how many rewashings are safe.

The sponge (Today, Protectaid) is a disposable form of barrier contraception. It is made of soft polyurethane, is round in shape, and fits over the cervix like a diaphragm, but is smaller and easily portable. In 1994, the popular over-the-counter contraceptive was taken off the U.S. market because of problems at the company's manufacturing facility. A new company has since acquired the rights to manufacture the sponge, and has been selling it in Canada and online since 2003. In April 2005, the Food and Drug Administration granted re-approval for the Today sponge to return to the U.S. market.

Use and Insertion. To use the sponge, the woman first wets it with water, then inserts it into the vagina with a finger, using a cord loop attachment. It can be inserted up to 6 hours before intercourse and should be left in place for at least 6 hours following intercourse. The sponge provides protection for up to 12 hours. It should not be left in for more than 30 hours from time of insertion.

The sponge should not be used during menstruation, after childbirth, miscarriage, or termination of pregnancy, or by women with a history of toxic shock syndrome.

Advantages. Because the sponge is not felt during intercourse and can be inserted up to 6 hours before intercourse, it encourages spontaneity. It appears to protect against cervical gonorrhea and Chlamydia.

Disadvantages. Failure rates (about 10%) are higher than with the diaphragm. There is a very small risk for toxic shock using the sponge, as there is for other barrier methods of contraception. The sponge may increase the risk for candidiasis (yeast infection). People who are allergic to spermicides should not use the sponge. The sponge does not protect against HIV or sexually transmitted diseases outside the cervix. The Today sponge contains 10 times the amount of the spermicide nonoxynol-9 than other products, and there is some evidence that this spermicide may increase the risk for HIV. The Protectaid sponge, available in Canada, contains a mix of three spermicides (nonoxynol-9, sodium cholate and benzal konium chloride).

The Lea shield is made of silicone, and its cup-shaped bowl completely surrounds the cervix without resting on it. The shield does not need to be fitted, and is as effective as the diaphragm and cap when used with spermicide. Its advantages are:

One size fits all
Can be left for 48 hours after intercourse
Reusable for 6 months

The condom is still the only reversible form of male contraception currently available.

Pregnancy Protection. The condom should be put on before intercourse when the penis is erect, long before ejaculation, since the male can discharge sufficient semen to cause pregnancy before ejaculation occurs. The average rate of pregnancy for couples that rely only on condoms for protection is high -- about 12%. In adolescents the risk of pregnancy with condoms is even higher, 18%. Even for those who use a good-quality condom correctly, the annual risk for pregnancy is 3%.

Prevention of Sexually Transmitted Diseases. Condoms are important in the prevention of sexually transmitted disease in both male and female partners, but they have limitations. They are more protective in men against fluid-transmitted infections (gonorrhea, Chlamydia, trichomoniasis, and HIV) than in preventing infections transmitted by skin-to-skin contact (herpes simplex virus, human papilloma virus, syphilis, and chancroid). Male condoms, in fact, offer better protection against herpes for women than they do for men. (Men often shed the virus from the skin of the penis, which is covered by the condom. In women the virus is often shed from areas around their genitals, which can contact male skin outside the condom.)

Some condoms come pre-lubricated with the spermicide nonoxynol-9, which is no longer recommended with condoms because of a higher risk for HIV infection. Its use in male condoms also promotes yeast and urinary tract infections in women. Other condoms come pre-lubricated without spermicide. Lubricants can also be purchased and applied separately. Only water-based lubricants (K-Y Jelly, Astroglide, AquaLube, glycerin) should be used with latex condoms. Do not use petroleum jelly or other oil-based lubricant products as these can damage the condom. In general, it's best to use a pre-lubricated condom or to apply a water-based lubricant. Unlubricated condoms may injure vaginal tissue and make it vulnerable to infections.

Condom Materials.

Latex. Condoms made of latex rubber are the most common types. They are less likely to slip or break than those made of polyurethane, and they are contoured for a better fit that can provide fairly effective protection. Some people are allergic to latex, however, and in some cases the reaction can be very dangerous. The latex smell may also be unpleasant for some people.
Polyurethane. Polyurethane condoms (Avanti, eZ-on) are also available. It is hoped that eventually they will prove to be superior to latex in a number of ways, including strength, sensitivity, and durability. At this point, they have good acceptance by couples but have a higher breakage rate (6 - 7.2%) compared to the latex condom (1.1 - 2%). Other synthetic materials are under investigation.
Animal Membranes. Condoms made from animal membrane (such as lambskin) can prevent pregnancy, but they are permeable and do not protect against sexually transmitted infections.

Natural Family Planning Methods

Natural family planning contraceptive methods do not use medication, physical devices, or surgery to prevent pregnancy. Instead, these cycle-based fertility awareness methods rely on tracking the changes in the body that signal fertility. A woman is only fertile during part of her menstrual cycle. By monitoring certain changes in her body, a woman can more or less predict the fertile phase and abstain from sexual intercourse during that time. She can also use barrier methods if they are not prohibited by religious beliefs. The Roman Catholic Church, for example, generally approves of most natural family planning methods.

Natural family planning methods include:

Basal body temperature
Cervical mucus
Symptothermal
Lactational amenorrhea
Calendar

Basal Body Temperature Method. To determine the most likely time of ovulation and therefore the time of fertility, a woman is instructed to take her body temperature, called her basal body temperature. This is the body's temperature as it rises and falls in accord with hormonal fluctuations.

Each morning before rising, the woman takes her temperature with a specialized basal body thermometer and marks the result on a graph-paper chart.
She also notes the days of menstruation and sexual activity.
The so-called "fertile window" is 6 days long. It starts 5 days before ovulation and ends the day of ovulation.
The chances for fertility are considered to be highest between days 10 - 17 in the menstrual cycle (with day 1 being the first day of the period and ovulation occurring about 2 weeks later). However, one study reported that only 30% of women were fertile within that period of time. In the study, women had a 10% chance of ovulating on each day between day 6 and 21. The researchers suggested that each woman track the length of her cycle, which in the general population of women actually runs 19 - 60 days. A long cycle, for example, suggests a delayed ovulation date.
Immediately after ovulation, the body temperature increases sharply in about 80% of cases. (Some women can be ovulating normally yet not show this temperature pattern.)

By studying the temperature patterns over a few months, couples can begin to anticipate ovulation and plan their sexual activity accordingly. To avoid losing spontaneity, couples should try to avoid becoming fixated on the chart in scheduling their sexual activity.

Cervical Mucus Method. The cervical mucus method (also called the ovulation method) requires a woman to take a sample (by hand) of her cervical mucus every day for a least a month and to record its quantity, appearance, feel, and to note other physical signs connected with the reproductive system. Cervical mucus changes in predictable ways over the course of each menstrual cycle:

Six days before ovulation, mucus is affected by estrogen and becomes clear and elastic. Ovulation is likely to occur the last day that mucus has these properties.
Right after ovulation, mucus is affected by progesterone and is thick, sticky, and opaque.

Once a woman's individual pattern is understood, analyzing cervical mucus can provide a highly accurate guide to fertility.

Symptothermal Method. This method uses both the basal body temperature and cervical mucus methods. In addition, the woman tracks symptoms that may identify her fertile period. These symptoms include changes in the shape of the cervix, breast tenderness, and cramping pain.

Prolonged Breast-feeding (The Lactational Amenorrhea Method). Breast-feeding often delays the onset of ovulation and menstruation for about 6 months. A technique called the Lactational Amenorrhea Method (LAM) allows women to rely on breastfeeding for natural family planning. New mothers are candidates for LAM if their periods have not returned after delivery. They must be breastf-eeding the baby on demand, day and night, without regularly substituting other liquids or foods in the baby's diet.

The risk for pregnancy with this method is less than 2% in the early months, although by 6 months after birth it increases to over 5%. The return of menstruation indicates the return of fertility. Bleeding or spotting during the first 56 days is not considered menstruation. After that, 2 or more consecutive days of bleeding are usually an indicator that periods have returned. Ovulation can occur before menstruation resumes, although it is less likely within 6 months of delivery (particularly if the mother is intensively breast-feeding).

Calendar Method. The calendar (rhythm method) is considered the least reliable of natural family planning methods, with an effectiveness rate of about 87%. Women who have very irregular periods may have even less success with this method. In the calendar method, the woman first keeps a record of her menstrual periods for about 6 - 12 months. She then subtracts 18 days from the shortest and 11 days from the longest of the previous menstrual cycles. For example, if a woman's shortest cycle was 26 days and her longest cycle was 30 days, she must abstain from intercourse from day 8 through day 19 of each cycle.

Because of the high risk for pregnancy, natural family planning methods are recommended only for those whose strong religious beliefs prohibit standard contraceptive methods. Couples who are not guided by religious authority, but who simply want a more natural sexual life, should use a barrier contraceptive during the fertile phase and no contraception during the rest of the cycle. To be effective against pregnancy, cycle-based methods require not only training, commitment, discipline, and perseverance, but also the cooperation of the male partner. Cycle-based methods are not recommended for women unless they are in a stable, monogamous relationship, and can count on their partner's willing participation.

Many couples, especially older ones, who have used these methods for a while and are strongly motivated, are able to successfully incorporate fertility awareness into their lives. For those with strong religious beliefs, natural family planning allows them to have a fulfilling sexual life yet still adhere to the rules of their church.

Couples who adopt a cycle-based approach to pregnancy avoidance must often abstain from sex or substitute other kinds of sexual intimacy for vaginal intercourse. Some couples find this self-denial and the need for vigilant tracking of the cycle difficult and stressful for the relationship. Failure rates are high with natural family planning. The risk for sexually transmitted diseases is also of particular concern, because such methods offer no protection against infection and religious beliefs usually preclude barrier protection.

Emergency Contraception

Emergency contraception is available to prevent pregnancy:

After sexual assault
After consensual intercourse in which contraception is not used
When contraception is used but fails (for instance, when a condom breaks or a diaphragm dislodges)

Emergency contraception, also called the “morning after pill,” uses the hormones found in birth control pills to prevent either fertilization or the implantation of a fertilized egg in the uterine lining. The pill known as Plan B contains progestin. Emergency contraception is usually given as hormone pills within 72 hours of unprotected sex. It is not the same thing as the "abortion pill" [See "mifepristone," below]. Emergency contraception is also sometimes prescribed as an intrauterine device (IUD), which is inserted within 5 days of unprotected sex.

In 2006, the Food and Drug Administration approved the Plan B brand as the first over-the-counter emergency contraception. It is available without a prescription at pharmacies and health clinics for women over age 18. Women will need to present proof of age to purchase it. Girls younger than age 18 will still need a prescription from their doctors.

Emergency Oral Contraception. There is one form of emergency oral contraception:

Plan B uses two doses of the progestin levonorgestrel. In one large study, levonorgestrel prevented pregnancy in 85% of women requiring emergency contraception.

The woman takes her first pill or pills within 72 hours of intercourse and a second dose 12 hours later. The sooner the drug is taken, the more effective it is in preventing pregnancy. Some evidence suggests the pills may be effective up to 5 days after sex, although effectiveness is greater if used within 72 hours. Although these regimens are popularly called morning-after pills, they are actually the same oral contraceptives that users of oral contraceptives take regularly.

Side effects of emergency oral contraception include:

Nausea and vomiting
Fatigue
Headaches
Dizziness
Diarrhea
Breast tenderness
Fluid retention
Changes in the timing or flow of the woman's next menstrual period. A 2006 study found that emergency contraceptive pills (such as Plan B) that contain levonorgestrel may alter the menstrual cycle and the length of periods.

Immediate side effects typically subside within 1 - 2 days of taking the second dose. Family planning experts warn that emergency pill use should not be treated as a substitute for regular contraception.

Copper-Releasing Intrauterine Device. An alternative emergency contraception relies on insertion of a copper-releasing intrauterine device (IUD) within 6 days of intercourse. It can be removed after the woman's next period, or left in place to provide ongoing contraception. The copper IUD reduces the risk of pregnancy by 99.9%.

Female Sterilization

Female surgical sterilization (also called tubal sterilization, tubal ligation, and tubal occlusion) is a low-risk, highly effective one-time procedure that offers lifelong protection against pregnancy. About 700,000 women undergo this procedure each year in the United States.

Female surgical sterilization procedures block the fallopian tubes and thereby prevents sperm from reaching and fertilizing the eggs. The ovaries continue to function normally, but the eggs they release break up and are harmlessly absorbed by the body. Tubal sterilization is performed in a hospital or outpatient clinic under local or general anesthesia.

The uterus is a hollow muscular organ located in the female pelvis between the bladder and rectum. The ovaries produce the eggs that travel through the fallopian tubes. Once the egg has left the ovary it can be fertilized and implant itself in the lining of the uterus. The main function of the uterus is to nourish the developing fetus prior to birth.

Sterilization does not cause menopause. Menstruation continues as before, with usually very little difference in length, regularity, flow, or cramping. (One study suggested that women with a history of Cesarean section may experience slightly heavier bleeding.) Sterilization does not offer protection against sexually transmitted diseases.

Click the icon to see an image of tubal ligation.

Laparoscopy. Laparoscopy is the most common surgical approach for tubal sterilization:

The procedure begins with a tiny incision in the abdomen in or near the navel. The surgeon inserts a narrow viewing scope called a laparoscope through the incision.
A second small incision is made just above the pubic hairline, and a probe is inserted.
Once the tubes are found, the surgeon closes them using different methods: clips, tubal rings, or electrocoagulation (using an electric current to cauterize and destroy a portion of the tube).
Laparoscopy usually takes 20 - 30 minutes and causes minimal scarring. The patient is often able to go home the same day and can resume intercourse as soon as she feels ready.

Click the icon to see an illustrated series detailing tubal ligation.

Minilaparotomy. Minilaparotomy does not use a viewing instrument and requires an abdominal incision, but it is small -- about 2 inches long. The tubes are tied and cut. Generally speaking, minilaparotomy is preferred for women who choose to be sterilized right after childbirth, while laparoscopy is preferred at other times. Minilaparotomy usually takes approximately 30 minutes to perform. Women who undergo minilaparotomy typically need a few days to recover and can resume intercourse after consulting their doctor.

Laparotomy. Laparotomy, a less common approach, requires an extensive 2- to 5-inch incision in the abdomen. It is considered major surgery and can require a hospital stay of a few days followed by recovery at home for several weeks. Resumption of intercourse depends on how quickly one is able to recover.

Culdoscopy. Culdoscopy involves inserting a scope through the vagina and into the pelvic cavity. Although it is less invasive than laparoscopy, a major 2002 analysis reported that it has a higher complication rate than either laparoscopy or minilaparotomy.

Essure. Approved in 2002, the Essure method uses a small spiral-like device to block the fallopian tube. Unlike tubal ligation, the Essure procedure does not require incisions or general anesthesia. It can be performed in a doctor’s office and takes about 45 minutes. A specially trained doctor uses a viewing instrument called a hysteroscope to insert the device through the vagina and into the uterus, and then up into the fallopian tube. Once the device is in place, it expands inside the fallopian tubes. During the next 3 months, scar tissue forms around the device and blocks the tubes. This results in permanent sterilization.

Before undergoing sterilization, a woman must be sure that she no longer wants to bear children and will not want to bear children in the future, even if the circumstances of her life change drastically. She must also be aware of the many effective contraceptive choices available. Possible reasons for choosing female sterilization procedures over reversible forms of contraception include:

Not wanting children and being unable to use other methods of contraception
Health problems that make pregnancy unsafe
Genetic disorders

If married, both partners should completely agree that they no longer want to have children and should also have ruled out vasectomy for the man. Vasectomy is a simple procedure that has a lower failure rate than female surgical sterilization, carries fewer risks, and is less expensive. [See In-Depth Report #37: Vasectomy.]

Even if all these factors are present, a woman must consider her options carefully before proceeding. Studies report that over time, 14 - 25% of women eventually regret this choice. Women at highest risk for regretting sterilization include:

Women who are younger at the time of sterilization. In one long-term study, over 40% of women who had had tubal ligation between the ages of 18 - 24 regretted their choice. (Only about 4% of women over 35 had these regrets.)
Women who had the procedure immediately after a vaginal delivery.
Women who had the procedure within 7 years of having their youngest child.
Women in lower income groups.

If a woman changes her mind and wants to become pregnant, a reversal procedure is available, but it is very difficult to perform and requires an experienced surgeon. Subsequent pregnancy rates after reversal are between 20 - 84%, depending on the surgical skill, the age of the woman, and, to a lesser degree, her weight and the length of time between the tubal ligation and the reversal procedure. Not all insurance carriers cover the cost of reversal.

Women who choose sterilization no longer need to worry about pregnancy or cope with the distractions and possible side effects of contraceptives. Sterilization does not impair sexual desire or pleasure, and many people say that it actually enhances sex by removing the fear of unwanted pregnancy. There is some evidence it may help reduce the risk for ovarian cancer.

Failure is rare, but about 1 in 200 women become pregnant during the first year after sterilization, and failure rate can rise to 5% after 10 years. About a third of these pregnancies are ectopic, which require surgical treatment.
After any of the procedures, a woman may feel tired, dizzy, nauseous, bloated, or gassy, and may have minor abdominal and shoulder pain. In general, there is more postoperative pain with the tubal ring than with electrocoagulation.
Serious complications from female surgical sterilization are rare and are most likely to occur with abdominal procedures. They include bleeding, infection, or reaction to the anesthetic. On rare occasions the bowels or blood vessels are injured and require major surgical repair. The use of electrocoagulation poses a risk for burns in the small intestine and may increase the risk for menstrual disorders afterward.

Resources

www.nichd.nih.gov -- National Institute of Child Health and Human Development
www.plannedparenthood.org -- Planned Parenthood
www.engenderhealth.org -- EngenderHealth
http://ec.princeton.edu -- Emergency Contraception Website
www.acog.org -- American College of Obstetricians and Gynecologists
www.guttmacher.org -- The Alan Guttmacher Institute

References

Archer DF, Jensen JT, Johnson JV, Borisute H, Grubb GS, Constantine GD. Evaluation of a continuous regimen of levonorgestrel/ethinyl estradiol: phase 3 study results. Contraception. 2006 Dec;74(6):439-45. Epub 2006 Sep 18.

Cole JA, Norman H, Doherty M, Walker AM. Venous thromboembolism, myocardial infarction, and stroke among transdermal contraceptive system users. Obstet Gynecol. 2007 Feb;109(2 Pt 1):339-46.

Hannaford PC, Selvaraj S, Elliott AM, Angus V, Iversen L, Lee AJ. Cancer risk among users of oral contraceptives: cohort data from the Royal College of General Practitioner's oral contraception study. BMJ. 2007 Sep 11; [Epub ahead of print]

Jick S, Kaye JA, Li L, Jick H. Further results on the risk of nonfatal venous thromboembolism in users of the contraceptive transdermal patch compared to users of oral contraceptives containing norgestimate and 35 microg of ethinyl estradiol. Contraception. 2007 Jul;76(1):4-7. Epub 2007 May 11.

Jick SS, Kaye JA, Russmann S, Jick H. Risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives containing norgestimate and 35 microg of ethinyl estradiol. Contraception. 2006 Mar;73(3):223-8. Epub 2006 Jan 26.

Jick SS, Kaye JA, Russmann S, Jick H. Risk of nonfatal venous thromboembolism with oral contraceptives containing norgestimate or desogestrel compared with oral contraceptives containing levonorgestrel. Contraception. 2006 Jun;73(6):566-70. Epub 2006 Mar 29.

Kahlenborn C, Modugno F, Potter DM, Severs WB. Oral contraceptive use as a risk factor for premenopausal breast cancer: a meta-analysis. Mayo Clin Proc. 2006 Oct;81(10):1290-302.

MacIsaac L. Intrauterine contraception: the pendulum swings back. Obstet Gynecol Clin North Am. 2007 March;34(1):91-111, ix.

Margolis KL, Adami HO, Luo J, Ye W, Weiderpass E. A prospective study of oral contraceptive use and risk of myocardial infarction among Swedish women. Fertil Steril. 2007 Aug;88(2):310-6. Epub 2007 Jul 10.

Martinez F, Avecilla A. Combined hormonal contraception and venous thromboembolism. Eur J Contracept Reprod Health Care. 2007 Jun;12(2):97-106.

van Vliet HA, Grimes DA, Helmerhorst FM, Schulz KF. Biphasic versus monophasic oral contraceptives for contraception. Cochrane Database Syst Rev. 2006 Jul 19;3:CD002032.

van Vliet HA, Grimes DA, Lopez LM, Schulz KF, Helmerhorst FM. Triphasic versus monophasic oral contraceptives for contraception. Cochrane Database Syst Rev. 2006 Jul 19;3:CD003553.

Review Date:
3/11/2008
Reviewed By:
A.D.A.M. Editorial Team: David Zieve, MD, MHA, Greg Juhn, MTPW, David R. Eltz, Kelli A. Stacy, ELS. Previously reviewed by Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (10/29/2007).

A.D.A.M. Copyright

adam.com

Herpes simplex

FitSugar — Wed, 08 Oct 2008 17:35:02 -0700

In This Report

Highlights
Introduction
Symptoms
Transmission
Risk Factors
Complications
Diagnosis
Similar Conditions
Home Remedies and Preventio...
Treatment for Genital Herpe...
Treatment for Oral Herpes...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Herpes Diagnosis

In 2006, the U.S. Centers for Disease Control (CDC) released updated guidelines for diagnosis and management of sexually transmitted diseases.

For diagnosis of genital herpes, the CDC recommends the use of both skin and blood tests.
Blood (or type-specific serologic) tests must be able to detect antibodies to glycoprotein G (gG). According to the CDC, gG serologic tests are much more accurate than other types of blood tests and are the only ones that should be used. These blood tests can help determine whether genital herpes is caused by herpes simplex virus-1 (HSV-1) or herpes simplex virus-2 (HSV-2).
Although HSV-1 has traditionally been the main cause of oral herpes, and HSV-2 the main cause of genital herpes, HSV-1 is now causing up to 50% of all cases of genital herpes. Prognosis may vary depending on the type of virus involved.

Herpes Treatment

Acyclovir (Zovirax), famiciclovir (Famvir), and valacyclovir (Valtrex) are used for episodic treatment (when herpes outbreaks occur) or suppressive treatment (preventing outbreaks). Valacyclovir may be a particularly good choice for reducing the risk of herpes transmission among heterosexual couples when only one partner is infected with HSV-2.
According to a 2007 review of studies involving over 6,000 patients, these drugs are very effective in reducing herpes recurrences.

Herpes and HIV

Treatment of HSV-2 can help reduce HIV levels in women who are infected with both viruses, indicates a study published in 2007 in the New England Journal of Medicine. In the trial, women who received twice-daily valacyclovir therapy for 12 weeks had reduced genital-track shedding of HIV and blood HIV levels compared to women who received placebo. Researchers are now focusing on the major question: Whether treatment of genital herpes can help prevent HIV transmission.

Introduction

Herpes simplex virus (HSV) commonly causes infections of the skin and mucous membranes. Sometimes it can cause more serious infections in other parts of the body. HSV is one of the most difficult viruses to control and has plagued mankind for thousands of years.

Herpes simplex is part of a group of other herpes viruses that include human herpesvirus 8 (the cause of Kaposi's sarcoma) and herpes zoster (the virus responsible for shingles and chicken pox). They differ in many ways, but the viruses share certain characteristics, notably the word "herpes," which is derived from a Greek word meaning "to creep." This refers to the unique characteristic pattern of all herpes viruses to "creep along" local nerve pathways to the nerve clusters at the end, where they remain in an inactive state for some indeterminate time.

There are two forms of the herpes simplex virus:

Herpes simplex virus 1 (HSV-1)
Herpes simplex virus 2 (HSV-2)

These viruses are distinguished by different proteins on their surfaces. They can occur separately, or they can both infect the same individual. Until recently, the general rule has been to assume that HSV-1 infections occur in the oral cavity (mouth) and are not sexually transmitted, while HSV-2 attacks the genital area and is sexually transmitted. It is now widely accepted, however, that either type can be found in either area and at other sites. In fact, HSV-1 is now responsible for up to half of all new cases of genital herpes.

For infection to occur, the following conditions must apply:

The herpes simplex virus passes moves through bodily fluids (saliva, semen, fluid in the female genital tract) or in fluid from herpes sores.
The virus must have direct access to the noninfected person through injuries in their skin or mucus surfaces (such as in the mouth or genital area).

When herpes simplex virus enters the body, the infection process typically takes place as follows:

The virus enters vulnerable cells in the lower layers of skin tissue and tries to reproduce in the cell nuclei. Scientists are close to decoding the genetic structure of herpes simples virus and to discovering how the virus works its way into specific cells. The virus may have specially shaped proteins called cell adhesion molecules that can allow the virus to enter healthy cells. For example, protein receptors on cells called nectin 1 and 2 may bind to some subtypes of the virus and help the infection move from cell to cell.
Even after it has entered the cells, the virus never causes symptoms in most cases.
However, if the virus destroys the host cells when it multiplies, inflammation and fluid-filled blisters or ulcers appear. Once the fluid is absorbed, scabs form, and the blisters disappear without scarring.
After the first time they multiply, the viral particles are carried from the skin through branches of nerve cells to clusters at the nerve-cell ends (the dorsal root ganglia).
Here, the virus lives in an inactive (latent) form. The virus does not multiply, but both the host cells and the virus survive.
At unpredictable times, the virus begins multiplying again. It then goes through a period called shedding. During those times, the virus can be passed into bodily fluids and infect other people. Unfortunately, a third to half of the times shedding occurs without any symptoms at all.
Eventually, the symptoms return in most cases, causing a new outbreak of blisters and sores.

This close-up view of early herpes outbreak shows small, grouped blisters (vesicles) and lots of inflammation (erythema).

Symptoms

Symptoms vary depending on the stage of the virus, the initial or primary outbreak, and recurrence. Both herpes simplex viruses 1 and 2 produce similar symptoms, but they can differ in severity depending on the site of infection. More than 60% of new herpes simplex virus 2 (HSV-2) infections and about a third of new herpes simplex virus 1 (HSV-1) infections do not produce symptoms.

Skin Eruptions and Pain. Skin eruptions will appear 2 - 12 days after the initial exposure to the virus.

The first sign of infection is fluid accumulation (edema) at the infection site, which is quickly followed by small, grouped blisters -- the characteristic herpes virus lesions.
These form on an inflamed skin base, which is more visible in dry skin areas.
The blisters then dry out and heal rapidly without scarring within 7 - 10 days. Blisters in moist areas heal more slowly than others. The lesions may sometimes itch, but itching decreases as they heal.
When the crust falls off, the lesions are no longer contagious. (Rarely, the virus may still be active in nearby tissue.)
Once the virus gains entry to a site in the body, it can also spread to nearby mucosal areas through nerve cells. This characteristic spreading can cause fairly large infected areas to erupt at some distance from the initial crop of sores.

The primary skin infection with either herpes simplex virus 1 (HSV-1) or herpes simplex virus 2 (HSV-2) lasts up to 2 - 3 weeks, but skin pain can last 1 - 6 weeks in the first (primary) virus attack.

Other Symptoms. Some patients experience other symptoms as well, which may occur before the actual outbreak (called a prodrome).

Fever rising to about 102°F, muscle aches, headache, and flu-like malaise. These general symptoms usually go away within a week.
Lymph glands near the site may be swollen as well.

It may be especially important to identify a first (primary) infection -- if possible -- and to treat it as soon as possible. Some preliminary research suggests that early treatment may limit the number of viruses that remain latent in the body and reduce the frequency of recurrent outbreaks.

Latency. After an outbreak, the herpes simplex virus goes into a stage known as latency. During that time, the virus does not produce symptoms and cannot be transmitted to other people.

Asymptomatic Shedding. At certain times, the virus undergoes shedding. During this phase the virus multiples and can be transmitted through fluids and infect other people. This occurs during an outbreak. However, in a third to half of cases shedding occurs without any symptoms at all (asymptomatic). One study reported that about 40% of all people infected with herpes simplex virus (HSV) had sheeding of the virus without symptoms more than 5% of the time. (Other evidence suggests shedding occurs much more often -- 9 - 28% of the time.) About half of shedding episodes without symptoms happen within a few days before or after an outbreak and can last about 1.5 days. Asymptomatic shedding is much more common with herpes simplex virus 2 (HSV-2) than with herpes simplex virus 1 (HSV-1).

Symptoms of Recurrence. Herpes simplex nearly always recurs. The site on the body and the type of virus influence how often it comes back. The virus usually takes the following course:

Prodrome. The outbreak of infection is often preceded by a prodrome, an early group of symptoms that may include itching skin, pain, or an abnormal tingling sensation at the site of infection. The patient may also have a headache, enlarged lymph glands, and flu-like symptoms. The prodrome, which may be as few as 2 hours or as many as 2 days, steps when the blisters develop. About 25% of the time, recurrence does not go beyond the prodrome stage.
Outbreak. Recurrent outbreaks of herpes simplex virus (HSV) feature most of the same symptoms at the same sites as the primary attack, but they tend to be milder and briefer. After blisters erupt, they typically heal in 6 - 10 days. Occasionally, the symptoms may not resemble those of the primary episode but appear as fissures and scrapes in the skin or as general inflammation around the affected area.

Triggers of Recurrence. It is not completely known what triggers renewed infection, but several different factors may be involved. These include sunlight, wind, fever, local physical injury, menstruation, suppression of the immune system, and emotional stress. Some studies link recurrence in genital herpes to persistent stress (lasting longer than a week) and high levels of anxiety. Oral herpes can be provoked within about 3 days of intense dental work, particularly root canal or tooth extraction, as well as after laser skin resurfacing, a popular form of cosmetic surgery.

Timing of Recurrences. Recurrent outbreaks may occur at intervals of days, weeks, or years. For most people, outbreaks recur with more frequency during the first year after an initial attack. During that period, the body mounts an immune response to HSV, and in most healthy people recurring infections tend to become progressively less severe and less frequent. The immune system, however, cannot kill the virus completely.

Oral herpes (herpes labialis) is most often caused by herpes simplex virus 1 (HSV-1) but can also be caused by herpes simplex virus 1 (HSV-2). It usually affects the lips and, in some primary attacks, the mucous membranes in the mouth. A herpes infection may occur on the cheeks or in the nose, but facial herpes is very uncommon.

Primary Oral Herpes Infection. If the primary (or initial) oral infection causes symptoms, they can be very painful, particularly in small children.

Blisters form on the lips but may also erupt on the tongue.
The blisters eventually rupture as painful open sores, develop a yellowish membrane before healing, and disappear within 3 - 14 days.
Increased salivation and foul breath may be present.
Rarely, the infection may be accompanied by difficulty in swallowing, chills, muscle pain, or hearing loss.

In children, the infection usually occurs in the mouth. In adolescents, the primary infection is more apt to appear in the upper part of the throat and cause soreness.

Recurrent Oral Herpes Infection. Most patients have only a couple of outbreaks a year, although up to 10% of patients experience more frequent recurrences. (HSV-2 oral infections recur less frequently than HSV-1.) Recurrences are usually much milder than primary infections and are known commonly as cold sores or fever blisters (because they may arise during a bout of cold or flu). They usually show up on the outer edge of the lips and rarely affect the gums or throat. (Cold sores are commonly mistaken for the crater-like mouth lesions known as canker sores, which are not associated with herpes simplex virus.)

Genital herpes, which typically affects the penis, vulva, or rectum, is usually caused by herpes simplex virus 2 (HSV-2), although the rate of simplex virus 1 (HSV-1) genital infection is increasing. Studies now report, in fact, that the cases of new symptomatic genital infections are equally split between HSV-1 and HSV-2. Some studies even report a higher incidence of genital HSV-1 cases. While there is no difference in treatment, there can be a difference in disease course. Initial genital infections due to HSV-1 may be more severe than those caused by HSV-2. Recurrences tend to be milder and less frequent than with HSV-2, however.

Primary Genital Herpes Infection. The first outbreak usually occurs in or around the genital area 3 - 14 days after exposure to the virus. If there is a long time between the initial infection and the first outbreak of symptoms, the episode may be quite mild because the immune system has already produced antibodies to the virus. These kinds of first infections are less transmissible, heal faster, and produce fewer symptoms.

In about 80% of initial outbreaks of genital herpes, patients develop symptoms such as flu-like discomfort and fever. The virus sheds for about 3 weeks. Symptoms in men and women are very different from each other.

In women, the pattern of a first infection is often more complicated and severe than in men:

In addition to general flu-like discomfort, women may experience nerve pain, itching, lower abdominal pain, urinary difficulties, and yeast infections before or during the eruption of the skin blisters.
When the outbreak occurs, blisters form raw sores (ulcers) almost immediately. Later they become crusted and fill with a grayish-white fluid. A new crop often occurs during the second week and is accompanied by swollen lymph glands in the groin. The symptoms may last as many as 6 weeks.
Lesions commonly appear around the vaginal opening, on the buttocks, in the vagina, or on the cervix. If lesions occur inside the vagina, they are not visible and pain may be minimal. Such women, then, may be unaware that they have genital herpes. In such cases, the blisters produce a discharge that is still highly infectious.
Lesions develop in places other than the genital region in 10 - 18% of primary HSV-2 infections. In most of these cases, outbreaks occur in the urethra (the channel that carries urine) where they can cause painful burning during urination. Inflammation of the internal reproductive organs, including the uterus lining (endometrium) and the fallopian tubes, is rare.

In men, about 6 - 10 blisters typically develop on the head or shaft of the penis. They rarely occur at the base. In some cases, they can occur on the buttocks, around the anus, or on the thighs.

Recurrent Genital Herpes Infection. In general, recurrences are much milder than the initial outbreak. The virus sheds for a much shorter period of time (about 3 days) compared to in an initial outbreak of 3 weeks. Women may have only minor itching, and the symptoms may be even milder in men.

On average, people have four recurrences a year, although this varies widely depending on the severity of the initial outbreak. Men, for example, have 20% more recurrences of genital herpes than women even though their symptoms are milder. There are also some differences in frequency of recurrence depending on whether HSV-2 or HSV-1 causes genital herpes:

HSV-2 Genital Herpes Recurrences. HSV-2 genital infections recur more often than HSV-1, and they tend to be more severe. Up to 90% of HSV-2 genital infections recur within the first year after primary infection. Many patients report 5 - 8 recurrences in the first year, but some have them as often as every 2 weeks. Some, though, have only one initial outbreak without any subsequent recurrences, a rate more typical of those with HSV-1.
HSV-1 Genital Herpes Recurrences. In one study, 38% of patients with HSV-1 genital infections had no recurrences in the first year after primary infection, 35% had one recurrence, and 27% had 2 or more recurrences. The average time to recurrence was about 7.5 months. Only 7% of those with genital HSV-1 had two or more recurrences annually for at least 2 years.

Patients with genital herpes usually notice a significant reduction in recurrence by the seventh year after infection. Some patients, however, particularly those with genital HSV-2, may actually face an increase in recurrence during the first 5 years.


Location and type	Symptoms	Treatments
*Eye (ocular herpetic infection).* Affects only one eye at a time. Usually caused by HSV-1, but acute cases in the retina are more likely to be due to HSV-2. The incidence has been highest in children, although it is increasing in older individuals.	Primary: Inflammation of the cornea (keratitis), causing sudden and severe pain, blurred vision, or corneal lesions. A cloudy layer can form over the cornea. Swelling may occur around the eyes. Heals within 2 - 3 weeks. Recurrence: About 40% of people have more than one recurrence, usually keratitis in a single eye, but symptoms may be present in the other eye as well. In the experience of some doctors, short, intense exposure to sunlight may trigger a recurrence, but there is no clear evidence concerning sunlight or any other potential triggers. Branching, ulcerous lesions of the cornea may occur later in the disease. Stromal keratitis, inflammation of inner layers of the cornea, occurs in about 25% of patients. It is a late immune response to the infection and can, in some cases, be very serious. In the U.S., it is the major cause of blindness in the cornea (which is still very uncommon).	Medications of Ocular HSV. Ocular HSV should be treated carefully since certain treatments may aggravate the condition. Artificial tears may be appropriate for mild cases. Treatments include trifluridine (Viroptic) eye drops or acyclovir or vidarabine (Vira A) ointments. Adding interferon, an immune system booster, to trifluridine may speed healing. Interferon in combination with debridement is also helpful. With treatment, most HSV ocular infections resolve within 5 - 9 days. Taking long-term oral acyclovir after an initial episode of ocular HSV reduces recurrences by about 45%. Medications for Stromal Keratitis. Oral acyclovir also protects against stromal keratitis in patients with a history of it. Trifluridine or cidofovir may also be protective against it. Neither drug, however, has any effect once stromal keratitis develops. Treatment includes artificial tears for mild cases and topical steroids for moderate-to-severe inflammation. Procedures. Patients with ocular HSV may also need debridement, in which the surgeon scrapes away the injured tissue with a cotton swab. The patient may wear a patch or soft contact lens afterward. Patients with HSV who show scarring in the cornea may need surgery. In rare cases, a corneal transplant may be necessary.
*Brain (HSV encephalitis).* Usually HSV-1, although HSV-2 is typically the cause in newborns. In about 25% of HSV-1 encephalitis cases, the infection may be caused by a new strain of the virus. About a third of cases occur in people under 20 years old, half over age 50, and the balance between ages 20 -50.	Fever, headache, stiff neck, seizures, partial paralysis, stupor, or coma. Other symptoms: smell and taste disturbances, double vision, odd mental states, bizarre or psychotic behavior, loss of the ability to speak or understand, memory loss, confusion, emotional volatility.	Intravenous acyclovir is the treatment of choice for encephalitis and should be started immediately if this complication is suspected. It must be administered for at least 10 days. In rare cases, surgical measures may be needed to relieve the buildup of pressure in the brain.
*Finger (herpetic whitlow)*. One finger, usually thumb or index finger in adults. Any finger in children. HSV-1 the cause in 60% of cases, and HSV-2 in 40% of cases. HSV-1 is usually caused by finger-sucking in children or as an occupational condition in adults (usually health care workers not using gloves). HSV-2 is usually acquired by touching infected genital areas.	Primary: Itching or pain, swelling, flushing of the skin, localized tenderness of the infected finger. Clear-yellowish or pus-filled blisters may appear on fingertip lasting 2 - 3 weeks. Soft tissue around fingernail may become painfully infected. Finger blisters may become secondarily infected with common bacteria, causing fever and swollen glands in the armpit. Recurrence: Sometimes intense burning, nerve pain, or excessive sensitivity.	Topical acyclovir for acute attack and oral acyclovir for prevention of recurrences.
Lower back. Usually caused by HSV-2 and typically occurs in bedridden patients or those with AIDS.	Numbness, tingling of the buttocks or the area around the anus, urinary retention, constipation, and impotence. Weakness or extreme skin sensitivity in the lower extremities, possibly persisting for months. Headaches, stiff neck, and, very rarely, paralysis in lower extremities caused by inflammation of the spinal cord.	Acyclovir, or foscarnet in patients resistant to acyclovir.
Peripheral nervous system. Affecting nerves other than in the brain and spine. Usually caused by HSV-1.	Portion of the face temporarily paralyzed (Bell's palsy). Other areas of the body may exhibit numbness or loss of feeling to the touch.	Acyclovir or similar drugs in combination with oral prednisone.
*Other skin areas (herpetic erythema multiforme).* May follow any form of recurrent HSV. Is relatively rare.	Circular or irregular eruptions on backs of arms and hands. Recurrence of erythema multiforme is common in the same areas. This is actually an allergic reaction that lasts 2 - 3 weeks.	Usually minor and resolves without complications. Acyclovir and symptom relievers (common pain relievers, cold compresses, topical steroids, saline gargles).
Esophagus. Usually caused by HSV-1. Typically occurs in immunocompromised patients or in those taking long-term steroids or other immunosuppressant drugs, but can occur in infected people with normal immune systems.	Difficulty swallowing or burning, squeezing throat pain while swallowing, weight loss, pain in or behind the upper chest while swallowing. Herpes lesions difficult to differentiate from other throat sores.	Intravenous acyclovir may be recommended. Recurrences are rare in patients with healthy immune systems, so preventive therapy is usually unnecessary in these patients.

Click the icon to see an image of herpetic esophagitis.

Transmission

To infect people, the herpes simplex viruses (both HSV-1 and HSV-2) must get into the body through broken skin or a mucous membrane, such as inside the mouth or on the genital area. Each virus can be carried in bodily fluids (saliva, semen, fluid in the female genital tract) or in fluid from herpes sores. The risk for infection is highest with direct contact of blisters or sores during an outbreak.

Once the virus has contact with the mucous membranes or skin wounds, it begins to replicate. The virus is then transported within nerve cells to their roots where it remains inactive (latent) for some period of time. During inactive periods, the virus cannot be transmitted to another person. However, at some point, it often begins to multiply again without causing symptoms (called shedding ). During shedding, the virus can infect other people through exchange of bodily fluids.

Sometimes, infected people can transmit the virus and infect other parts of their own bodies (most often the hands, thighs, or buttocks). This process, known as autoinoculation, is uncommon, since people generally develop antibodies that protect against this problem.

Oral herpes (usually HSV-1) has been detected in both the saliva and blood of patients with active oral infections. It is the most prevalent form of herpes simplex virus, and infection is most likely to occur during preschool years. Oral herpes is easily spread by direct exposure to saliva or even from droplets in breath. Skin contact with infected areas is enough to spread it. Transmission most often occurs through close personal contact, such as kissing. In addition, because herpes simplex virus 1 can be passed in saliva, people should also avoid sharing toothbrushes or eating utensils with an infected person.

Genital herpes is most often transmitted through sexual activity, and people with multiple sexual partners are at high risk. The virus, however, can also enter through the anus, skin, and other areas.

People with active symptoms of genital herpes are at very high risk for transmitting the infection. Unfortunately, evidence suggests about one-third of all herpes simplex virus 2 (HSV-2) infections occur when the virus is shedding but producing no symptoms. Most people either have no symptoms or don't recognize them when they appear.

In the past, genital herpes was mostly caused by HSV-2, but herpes simplex virus 1 (HSV-1) genital infection is increasing, most likely to due to oral sex. Shedding of genital HSV-1 is less common than with HSV-2, but transmission obviously still occurs, as evidenced by the rising prevalence of genital HSV-1. In fact, a person who carries both HSV-1 and HSV-2 poses a greater risk for sexually transmitting HSV-2 than a person who carries only HSV-2. A person who is infected with only HSV-1 has some protection against being infected by HSV-2.

Risk Factors

Everyone is at risk for herpes simplex virus. According to the latest U.S. data from 1999 - 2004, 57.7% of Americans ages 14 – 49 are infected with herpes simplex virus 1 (HSV-1). About 17% of Americans in the same age range test positive for herpes simplex virus 2 (HSV-2). Infection rates for both viruses have declined since the late 1980s. However, infection is lifelong.

Oral herpes is usually caused by HSV-1. The highest incidence of first infection occurs between 6 months and 3 years of age. The incidence in children varies among regions and countries, with the highest rates occurring in crowded and unsanitary regions. Studies suggest that by age 5 more than a third of children in low-income areas are infected compared to 20% of children in middle-income areas. However, by the time children in middle-income areas reach their 30s, about 60% have become infected with HSV-1. After age 40, socioeconomic differences in infection rates become even less pronounced.

The number of Americans with genital herpes increased by 30% from the late 1970s through the early 1990s. However, recent surveys indicate that prevalence is decreasing. A 2006 study in the Journal of the American Medical Association found that among Americans age 14 - 49, the prevalence of herpes simplex virus 2 (HSV-2) decreased by 19% from 1988 - 2004. The decrease was greatest among teenagers age 14 - 19.

The prevalence of herpes virus simplex 1 (HSV-1) also declined, but the percentage of genital herpes infections caused by HSV-1 more than tripled. Among people infected with HSV-1, but not HSV-2, 1.8% were diagnosed with genital herpes from 1999 to 2004 compared with 0.4% from 1988 to 1994. (HSV-2 still causes the majority of genital herpes infections.)

Although the prevalence of genital herpes is declining in the United States, it still remains in epidemic proportions. According to the U.S. Centers for Disease Control and Prevention, at least 45 million Americans age 12 and over have had genital herpes. About 1 in 5 teenagers and adults are infected with genital herpes.

Gender. Anyone who is sexually active is at risk for genital herpes. Studies indicate that around 22% of Americans are infected with HSV-2, with the risk higher in women (26%) than in men (18%). Men, however, have twice as many recurrent infections as women.

Women have an 80 - 90% chance of contracting HSV-2 after unprotected sexual activity with an infected partner and are 4 times more likely to be infected than men. In one study of sexually active American teenagers, 15% of the females had evidence of being infected with HSV-2, compared to none of the males. Having a drinking problem greatly increased the likelihood of infection in these young women.

Ethnicity. Although African-Americans are more likely to test positive for HSV-2, Caucasians have a higher risk for active genital symptoms. Over the past few years, the greatest increase in HSV-2 has occurred in Caucasian teenagers.

Compromised Immune Systems. People with compromised immune systems, notably patients with HIV, are at very high risk for HSV-2. Between 68 - 81% of patients with HIV are infected with HSV-2. These patients are also at risk for more severe complications from herpes. Other immunocompromised patients include those taking drugs that suppress the immune system and transplant patients.

The following are examples of people who are at particularly risk for specific forms of herpes.

Health care providers, including doctors, nurses, and dentists. This group is at higher than average risk for herpetic whitlow, herpes that occurs in the fingers.
Wrestlers, rugby players, and other athletes who participate in direct contact sports without protective clothing. These individuals are at risk for herpes gladiatorum, an unusual form of HSV-1 that is spread by skin contact with exposed herpes sores and usually affects the head or eyes.

Complications

The severity of symptoms depends on where and how the virus enters the body. Except in very rare instances and in special circumstances, the disease is not life threatening, although it can be very debilitating and cause great emotional distress.

Pregnant women who are infected with either herpes simplex virus 2 (HSV-2) or herpes simplex virus 1 (HSV-1) genital herpes have a higher risk for miscarriage, premature labor, retarded fetal growth, or transmission of the herpes infection to the infant while in the uterus or at the time of delivery. Recurrence in women previously infected with herpes is also common during pregnancy.

However, although about 1 million pregnancies occur each year in women who have been infected with HSV-2, complications occur in fewer than 4 in 1,000 infected pregnant women.

Approach to the Pregnant Herpes Patient. The approach to a pregnant woman who has been infected by either HSV-1 or HSV-2 in the genital area is usually determined by when the infection was acquired and the mother's condition around the time of delivery:

If lesions are present at the time of birth, Cesarean section is usually recommended. An important 13-year study confirmed that this approach helps prevent transmission. In the study, the baby became infected in only 1.1% of Cesarean sections compared to 7.7% of vaginal deliveries. (Even a Cesarean section is no guarantee that the child will be virus-free, and the newborn must still be tested.)
If lesions erupt shortly before the baby is due then samples must be taken and sent to the laboratory. Samples are cultured to detect the virus at 3 - 5-day intervals prior to delivery to determine whether viral shedding is occurring. If no lesions are present and cultures indicate no viral shedding, a vaginal delivery can be performed and the newborn is examined and cultured after delivery.

Some doctors now recommend anti-viral medication for pregnant women who are infected with HSV-2. Recent studies indicate that acyclovir (Zovirax) or valacyclovir (Valtrex) can help reduce the recurrence of genital herpes and the need for Cesarean sections. Women begin to take the drug on a daily basis beginning in the 36th week of pregnancy (last trimester).

Although 25 - 30% of pregnant women in the U.S. and Europe have a history of herpes simplex virus (HSV-2) infection, the risk of transmission to the newborn is low, occurring in between one in 3,500 - 20,000 births, depending on the population group.

The greatest danger to the baby is from an asymptomatic infection during a vaginal delivery in women who acquired the virus for the first time late in the pregnancy. In such cases, 30 - 50% of newborns become infected. Recurring herpes and a first infection that is acquired early in the pregnancy pose a much lower risk (less than 1%) to the infant.

The reasons for the higher risk with a late primary infection are:

During a first infection, the virus is shed for longer periods, and more viral particles are excreted.
An infection that first occurs in the late term does not allow the mother to develop antibodies that would help her baby fight off the infection at the time of delivery.

The risk for transmission also increases if infants with infected mothers are born prematurely, if there is invasive monitoring, or if instruments are required during vaginal delivery. Transmission can occur if the amniotic membrane of an infected woman ruptures prematurely, or as the infant passes through an infected birth canal. Very rarely, the virus is transmitted across the placenta, a form of the infection known as congenital herpes.

Infants may acquire congenital herpes from a mother with an active herpes infection at the time of birth. Aggressive treatment with antiviral medication is required, but may not help systemic herpes.

Unfortunately, only 5% of infected pregnant women have a history of symptoms, so in many cases herpes infection is not suspected, or symptoms are missed, at the time of delivery. Occasionally, lesions on the mother's buttocks may help indicate the presence of the virus.

Herpes infection in a newborn is a very serious and even-life threatening condition if it goes undiagnosed and untreated. Fortunately, since the introduction of acyclovir the outlook for these children has significantly improved. In general, there are three categories of herpes in the newborn.

Localized infection affects the skin, eyes, and mucous membranes. Herpes simplex virus 1 (HSV-1) usually causes this temporary. However, in some cases, most often herpes simplex virus 2 (HSV-2) infections, later complications develop in 5 - 10% of infants. If untreated, the virus may lead to very severe complications, notably disseminated or central nervous system infection.
Disseminated disease can affect internal organs, such as the liver, lungs, and adrenal glands. It is fatal in up to 80% of newborns if left untreated, and those who survive are at high risk for complications, particularly in the eyes. If infants are treated, however, survival rates are close to 90%.
Central nervous system infection can cause meningitis or encephalitis. This form is also highly fatal, and complications that affect learning and mental functions are common in surviving children.

Factors that Indicate a Higher Risk for Severe Complications. These may include:

Acute infection in the mother at delivery
Prematurity
Seizures in the infant
Disseminated intravascular coagulopathy, a blood-clotting disorder that can occur in response to infection

Factors that Indicate a Lower Risk for Severe Complications. These may include:

Newborn infection caused by a recurring HSV-2 infection in the mother. (Mothers with such infections appear to pass along protective antibodies to the newborn. However, antibodies to HSV-1 do not appear to offer similar protection to the newborn.)
Newborn infections that are confined to the skin and do not cause frequent outbreaks within the first 6 months.

Tests for the Newborn at Risk for Herpes. Any newborn with an infected or high-risk mother should be tested and checked carefully for symptoms. (Experts are divided, however, over whether the high cost of testing mothers specifically for HSV before delivery, even in high-risk groups, is worth the benefit for such a small group of mothers and infants.)

In the asymptomatic newborn delivered from an infected mother, cultures should be taken between 24 - 48 hours after birth. A culture taken right at the time of delivery may give a false indication of infection in the baby, simply because it can carry some of the mother's virus from the birth canal.
Testing specimens for viral DNA using a test called polymerase chain reaction is proving to be very important in newborns, particularly when central nervous system infection is suspected, since it eliminates the need for brain biopsies.
While results are pending, the baby should be checked regularly for rashes and blisters, particularly in areas where the skin is broken, along with any signs of illness including fever, lethargy, respiratory distress, and poor feeding.

Symptoms of Herpes in the Newborn. Although treatments have improved the outlook of infected newborns, there has been little change over the past 20 years in the time between the onset of symptoms and the initiation of treatments. Doctors and parents should be suspicious of any signs if there is any risk of infection to the newborn.

When symptoms occur in newborns, they usually become apparent within 5 - 17 days of life, but they may develop as early as 24 hours or as late as 34 days.

An unstable temperature can be the first indication of the infection.
About half of infected infants develop a rash. Lesions may range from raised spots to large isolated blisters. They can be anywhere on the skin or eyes or in the mouth.
The other half of infected infants develop no lesions until later in the course of the infection. The absence of lesions, therefore, in high-risk infants should not be considered a guarantee that HSV has not been transmitted.
Other symptoms to watch for include irritability, blotchy skin, discharge in the eyes, sensitivity to light, tearing, lethargy, jaundice, pallor, coughing, rapid breathing, a swollen abdomen (enlarged spleen), seizures, or tremors. Doctors should suspect infection in any infant with fever, irritability, lethargy, or poor feeding at 1 week of age.

Treatment of Herpes in the Newborn. If doctors suspect herpes virus infection in a newborn, intravenous acyclovir treatment should begin immediately, since the potential dangers of the condition far outweigh any risks associated with the drug.

The following are recommendations for treating infants who have been infected or are at risk for infection:

If disseminated or central nervous system infection has developed or is suspected, intravenous acyclovir treatment should continue for 21 days.
If the infection is limited to the skin, eyes, or mouth and the infant is at low risk for more serious complications, treatment may be given for 10 - 14 days.

The American Academy of Pediatrics Committee on Infectious Diseases now recommends higher-than-standard doses to improve outcome in infants who have any of these infections. Investigators are studying whether giving long-term acyclovir by mouth to newborns following the initial infection will improve the outcome.

Herpes Encephalitis. Each year in the U.S., herpes accounts for 2,100 cases of encephalitis, a rare but extremely serious brain disease. Herpes simplex virus 1 (HSV-1) is usually the cause, except in newborns. In about 70% of cases of infant herpes encephalitis, the disease occurs when a latent herpes simplex virus 2 (HSV-2) is activated. Untreated, herpes encephalitis is fatal over 70% of the time. Respiratory arrest can occur within the first 24 - 72 hours. Fortunately, rapid diagnostic tests and treatment with acyclovir have both significantly improved survival rates (up to about 80%) and reduced complication rates (to nearly 40%). For those who recover, nearly all suffer some impairment, ranging from very mild neurological changes to paralysis. Recovery from herpes encephalitis depends on the patient's age, the level of consciousness, duration of the disease, and the promptness of treatment. The best chances for a favorable outcome occur in patients who are treated with acyclovir within 2 days of becoming ill.

Herpes Meningitis. Herpes meningitis, an inflammation of the membranes that line the brain and spinal cord, occurs in up to 10% of cases of primary genital HSV-2. Women are at higher risk than men for herpes meningitis. Symptoms include headache, fever, stiff neck, vomiting, and sensitivity to light. Fortunately, herpes meningitis usually resolves without complications, lasting for up to a week, although recurrences have been reported.

Click the icon to see an image of the meninges of the brain.

Alzheimer's Disease. Some studies indicate a higher risk for Alzheimer's in people who have both HSV-1 and a gene called ApoE4, a known risk factor for Alzheimer's. Furthermore, a protein found in HSV-1 has been shown to mimic beta amyloid, a protein that is critical in the development of Alzheimer's disease.

Other Neurologic Diseases. Other neurologic syndromes that have been linked to HSV infection include epilepsy, multiple sclerosis, atypical pain syndromes, ascending or transverse myelitis (inflammation of the spinal column), and neuralgia (severe stabbing pain along a nerve or group of nerves).

A form of herpes infection called eczema herpeticum, also known as Kaposi's varicellum eruption, can affect patients with skin disorders and immunocompromised patients. The disease tends to develop into widespread skin infection that resembles impetigo. Symptoms appear abruptly and can include fever, chills, and malaise. Clusters of dimpled blisters emerge over 7 - 10 days and spread widely. They can become secondarily infected with staphylococcal or streptococcal organisms. When treated, lesions heal in 2 - 6 weeks. Untreated, this condition can be extremely serious and possibly fatal.

Herpetic infections of the eye (ocular herpes) occur in about 50,000 Americans each year. In most cases it causes inflammation and sores on the lids or outside of the cornea that go away in a few days.

Click the icon to see an image of the eye.

Stromal Keratitis. Stromal keratitis occurs in up to 25% of cases of ocular herpes. In this condition, deeper layers of the cornea are involved, possibly as an abnormal immune response to the original infection. In these rare cases, scarring and corneal thinning develop, which may cause the eye's globe to rupture, resulting in blindness. Although rare, it is the major cause of corneal blindness in the US.

Iridocyclitis. Iridocyclitis is another serious complication of ocular herpes, in which the iris and the area around it become inflamed.

Herpes can cause multiple painful ulcers on the gums and mucous membranes of the mouth, a condition called gingivostomatitis. This condition usually affects children 1 - 5 years of age. It nearly always subsides within 2 weeks.Rarely, it can lead to a viral infection. Children with gingivostomatitis commonly develop herpetic whitlow (herpes of the fingers).

A herpetic whitlow is an infection of the herpes virus around the fingernail. In children, this is often caused by thumbsucking or finger sucking while they have a cold sore. It is seen in adult health care workers, such as dentists, because of increased exposure to the herpes virus. The use of rubber gloves prevents herpes whitlow in health care workers.

Not least among the damaging effects of genital herpes is its impact on the social and emotional life of patients. In one survey of patients with herpes, 82% felt depressed, and 75% were worried about rejection. Over 25% had suicidal thoughts. In nearly 80% of the respondents, the disease had a profound effect on their sexual lives. The patient must notify sexual partners, past and present, about their condition, a deeply humiliating experience. Guilt and anger are common emotions, and relationships may be shattered. It is important to note that the condition is often dormant for many years and may not have been transmitted by a current sexual partner. Support groups or couple therapy can be very helpful.

Herpes simplex is particularly devastating when it occurs in immunocompromised patients and, unfortunately, coinfection is common. People infected with herpes have a three-fold increased risk for contracting HIV. Furthermore, studies have reported that 68 - 81% of patients with HIV are also infected with herpes simplex virus 2 (HSV-2).

Patients with HIV are particularly vulnerable to complications. When a person has both viruses, there appears to be a synergy between them, with each virus increasing the severity of the other. HSV-2 infection increases HIV levels in the genital tract, which makes it easier for the HIV virus to be transmitted to sexual partners. In addition, episodes of herpes recurrence increase, at least temporarily, HIV viral load. An important 2007 study in the New England Journal of Medicine indicated that treatment of HSV-2 with valacyclovir can help reduce plasma and genital levels of HIV in women who are infected with both viruses. Researchers are continuing to investigate whether treatment of HSV-2 may help reduce the risk of HIV transmission.

Herpes simplex in any patient with a seriously compromised immune system can cause serious and even life-threatening complications, including:

Pneumonia
Inflammation of the esophagus
Encephalitis (inflammation of the brain)
Destruction of the adrenal glands
Disseminated herpes (spread of infection throughout the body)
Liver damage, including hepatitis

Hepatitis caused by primary or recurrent herpes can sometimes develop into a life-threatening condition called fulminant liver failure. This condition is treatable with medications, or even a liver transplant, when diagnosed promptly. Early symptoms may include nausea, vomiting, and abdominal pain. (This is an uncommon complication in HSV-infected people with healthy immune systems, but cases have been reported, such as after surgical procedures.)

Less serious conditions include stomach and anal ulcers, inflammation in the colon, and eczema herpeticum.

Several conditions have been linked to herpes infections, although the association has not been substantiated in most cases.

Arthritis, usually in a single joint, has been sporadically reported as a result of herpes infection.
People with herpes simplex virus 2 (HSV-2) may be more likely to get sexually transmitted hepatitis C.
Some evidence suggests that herpes simplex virus 1 (HSV-1) may slightly increase the risk for certain cancers of the mouth or throat in people who are already at higher risk because of cigarette smoking or infection with another microorganism called human papillomavirus.
Some studies have reported associations between herpes simplex and heart disease, including lower survival rates. Such infections may produce persistent inflammation in the arteries leading to heart trouble. Research is ongoing.
Other rare complications of herpes simplex include erosion or ulcers in the lining of the esophagus and stomach. Certain kidney and blood diseases have also been reported in conjunction with HSV infection. These are very uncommon, however, particularly in people with healthy immune systems.

Diagnosis

The herpes simplex virus is usually identifiable by its characteristic lesion: A thin-walled blister on an inflamed base of skin. However, other conditions can resemble herpes, and doctors cannot base a herpes diagnosis on visual inspection alone. In addition, some patients who carry the virus may not have visible genital lesions. Laboratory tests are essential for confirming herpes diagnosis. These tests include virologic tests (which examine samples of skin taken from the lesion) and serologic tests (blood tests that detect antibodies).

In its 2006 guidelines for sexually transmitted diseases, the U.S. Centers for Disease Control (CDC) recommends that both virologic and serologic tests be used for diagnosing genital herpes. Patients diagnosed with genital herpes should also be tested for other sexually transmitted diseases.

According to the CDC, up to 50% of first-episode cases of genital herpes are now caused by herpes simplex virus 1 (HSV-1). However, recurrences of genital herpes, and viral shedding without overt symptoms, are much less frequent with HSV-1 infection than herpes simplex virus 2 (HSV-2). It is important for doctors to determine whether the genital herpes infection is caused by HSV-1 or HSV-2, as the type of herpes infection influences prognosis and treatment recommendations.

Viral culture tests are made by taking a fluid sample, or culture, from the lesions as early as possible, ideally within the first 3 days of appearance. The viruses, if present, will reproduce in this fluid sample but may take 1 - 10 days to do so. If infection is severe, testing technology can shorten this period to 24 hours, but speeding up the timeframe during this test may make the results even less accurate. Viral cultures are very accurate if lesions are still in the clear blister stage, but they do not work as well for older ulcerated sores, recurrent lesions, or latency. At these stages the virus may not be active enough to reproduce sufficiently to produce a visible culture.

Polymerase chain reaction (PCR) tests are much more accurate than viral cultures, and the CDC recommends this test for detecting herpes in spinal fluid when diagnosing herpes encephalitis (see below). PCR can make many copies of the virus’ DNA so that even small amounts of DNA in the sample can be detected. PCR is much more expensive than viral cultures and is not FDA-approved for testing genital specimens. However, because PCR is highly accurate, many labs have used it for herpes testing.

An older type of virologic testing, the Tzanck smear test, uses scrapings from herpes lesions. The scrapings are stained and microscopically examined for the virus. Findings of specific giant cells with many nuclei or distinctive particles that carry the virus (called inclusion bodies) indicate herpes infection. The test is quick but accurate 50 - 70% of the time. It cannot distinguish between virus types or between herpes simplex and herpes zoster. The Tzanck test is not reliable for providing a conclusive diagnosis of herpes infection and is not recommended by the CDC.

Serologic (blood) tests can identify antibodies that are specific to the virus and its type, herpes virus simplex 1 (HSV-1) or herpes virus simplex 2 (HSV-2). When the herpes virus infects someone, their body’s immune system produces specific antibodies to fight off the infection. If a blood test detects antibodies to herpes, it’s evidence that you have been infected with the virus, even if the virus is in a non-active (dormant) state. The presence of antibodies to herpes also indicates that you are a carrier of the virus and might transmit it to others.

Newer “type-specific” assays test for antibodies to two different proteins that are associated with the herpes virus:

Glycoprotein gG-1 is associated with HSV-1
Glycoprotein gG-2 is associated with HSV-2

Although glycoprotein (gG) type-specific tests have been available since 1999, many of the older nontype-specific tests are still on the market. The CDC recommends only type-specific glycoprotein (gG) tests for herpes diagnosis.

Serologic tests are most accurate when administered 12 - 16 weeks after exposure to the virus. Recommended tests include:

HerpeSelect. This includes two tests: ELISA (enzyme-linked immunosorbent assay) or Immunoblot. They are both highly accurate in detecting both types of herpes simplex virus. Samples need to be sent to a lab, so results take longer than the in-office Biokit test.
Biokit HSV-2 (also marketed as SureVue HSV-2). This test detects HSV-2 only. Its major advantages are that it requires only a finger prick and results are provided in less than 10 minutes. It is very accurate, although slightly less so than the other tests. It is also less expensive.
Western Blot Test. This is the gold standard for researchers with accuracy rates of 99%. It is costly and time consuming, however, and is not as widely available as the other tests.

False-negative (testing negative when herpes infection is actually present) results can occur if tests are done in the early stages of infection. False-positive results (testing positive when herpes infection is not actually present) can also occur, although more rarely than false-negative. Your doctor may recommend that you have the test repeated.

Experts recommend serologic herpes tests especially for:

People who have had recurrent genital symptoms but no negative herpes viral cultures
Confirming infection in people who have visible symptoms of genital herpes
Determining if the partner of someone diagnosed with genital herpes has acquired herpes
People who have multiple sex partners and who need to be tested for different types of STDs

At this time, doctors do not recommend screening for HSV-1 or HSV-2 in the general population.

It make take a number of test to diagnose herpes encephalitis.

Imaging Tests. Electroencephalography traces brain waves and can identify about 80% of cases. Computed tomography or magnetic resonance imaging scans may be used to differentiate encephalitis from other conditions.

Brain Biopsy. Brain biopsy is the most reliable method of diagnosing herpes encephalitis, but it is also the most invasive and is generally performed only if the diagnosis is uncertain.

Polymerase Chain Reaction (PCR). The polymerase chain reaction (PCR) assay looks for tiny pieces of the DNA of the virus, and then replicates them millions of times until the virus is detectable. This test can identify specific strains of the virus and asymptomatic viral shedding. PCR identifies HSV in cerebrospinal fluid and gives a rapid diagnosis of herpes encephalitis in most cases, eliminating the need for biopsies. The CDC recommends PCR for diagnosing herpes central nervous system infections.

Similar Conditions

Canker Sores (Aphthous Ulcers). Common canker sores (known medically as aphthous ulcers) are often confused with the cold sores of herpes simplex virus 1 (HSV-1). Canker sores frequently crop up singly or in groups on the inside of the mouth or on or under the tongue. They are usually white or grayish crater-like ulcers with a sharp edge and a red rim. They usually heal in 2 weeks without treatment.

Canker sores (Aphthous ulcers) are very common. Typically, they are a shallow ulcer with a white or whitish/yellow base surrounded by a reddish border. This ulcer is seen in an individual with AIDS and is located in front and just below the bottom teeth.

Thrush (Candidiasis). Candidiasis is a yeast infection that causes a whitish overgrowth in the mouth. It is most common in infants but can appear in people of all ages, particularly those with impaired immune systems.

Click the icon to see an image of thrush.

Other conditions that may be confused with oral herpes include herpangina (a form of the Coxsackie A virus), sore throat caused by strep or other bacteria, and infectious mononucleosis.

Conditions that may be confused with herpes simplex virus 2 (HSV-2) include bacterial and yeast infections, genital warts, herpes zoster (shingles), molluscum (a virus disease which produces small rounded swellings), scabies, syphilis, and certain cancers.

In a few cases, HSV-2 may occur without lesions and resemble cystitis and urinary tract infections.

Simple corneal scratches can cause the same pain as herpetic infection, but these usually resolve within 24 hours and don't exhibit the corneal lesions characteristic of herpes simplex.

Skin disorders that may mimic herpes simplex include shingles and chicken pox (both caused by varicella-zoster, another herpes virus), impetigo, and Stevens-Johnson syndrome, a serious inflammatory disease usually caused by a drug allergy.

Click the icon to see an image of the shingles.

Click the icon to see an image of chickenpox.

Home Remedies and Prevention

Patients can manage most herpes simplex infections that develop on the skin at home with over-the-counter painkillers and measures to relieve symptoms.

Several simple steps can produce some relief:

Hygiene is important. Avoid touching the sores. Wash hands frequently during the day. Fingernails should be scrubbed daily. Keep the body clean.
Drink plenty of water.
Keep blisters or sores clean and dry with cornstarch or similar product. (Women should not use talcum powder because it may increase their risk for ovarian cancer.)
Some people report that drying the genital area with a blow dryer on the cool setting offers relief.
Avoid tight-fitting clothing, which restricts air circulation and slows healing of the sores.
Choose cotton underwear, rather than synthetic materials.
Local application of ice packs may alleviate the pain and help reduce recurrences by suppressing the virus.
Lukewarm baths may be helpful. (For people who have pain on urination, some experts recommend urinating in the bath water at the end of the bathing time. This dilutes the urine and prevents burning the sores. Urinating in a cool shower is also helpful and is less offensive to many people. )
Wearing sun block helps prevent sun-triggered recurrence of herpes simplex virus 1 (HSV-1).
Avoid sex during both outbreaks and prodromes (the early symptoms of herpes), which include tingling, itching, or tenderness in the infected areas.
Over-the-counter medications such as aspirin, acetaminophen (Datril, Panadol, Tylenol), or ibuprofen (Advil, Medipren, Motrin, Nuprin), can be used to reduce fever and local tenderness. Children should take acetaminophen. Never give children aspirin.

In one study, stress management techniques developed using cognitive-behavioral methods not only were effective in reducing depression in those with hepres simplex virus 2 (HSV-2) but blood test results also revealed lower levels of HSV-2 antibodies, a possible sign of decreased viral activity. In any case, reducing stress using relaxation techniques does no harm.

Many herbal and dietary supplement products claim to help fight herpes infection by boosting the immune system. There has been little research on these products, and little evidence to show that they really work. Some are capsules taken by mouth. Others come in the form of ointment that is applied to the skin. Popular herbal and supplement remedies for herpes simplex include:

Echinacea (Echinacea purpurea )
Siberian ginseng (Eleutherococcus senticosus )
Aloe (Aloe vera )
Bee products that contain propolis, a tree resin collected by bees
Lysine
Zinc

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

The following are special concerns for people taking natural remedies for herpes simplex:

Echinacea can lower white blood cell levels when taken for long periods of time. This herb can also interfere with drugs that are used to treat immune system disorders.
Siberian ginseng can raise blood pressure levels.
Bee products (like propolis) can cause allergic reactions in people who are allergic to bee stings.
Do not take Lysine with certain types of antibiotics.
'Taking zinc in large amounts (more than 200 mg/day) can cause stomach upset.

Infected people should take several steps to avoid transmitting the virus to others. It is almost impossible to defend against the transmission of oral herpes simplex virus 1 (HSV-1) since it can be transmitted by very casual contact.

Preventing Transmission During an Outbreak. When an outbreak of herpes occurs, the following precautions are useful:

Persons carrying any herpes virus should carefully wash their hands and nails after contact with the infected area so as not to transmit the virus to other sites on the body.
Although transmission from objects such as toilet seats and towels is unlikely, keeping personal items separate during an active infection may help to reduce transmission to other household members. The virus can live for up to 2 hours on cloth and for 4 hours on plastic.
If genital lesions are present, infected persons should abstain from sexual intercourse.

Preventing Sexually Transmitted Disease. Any infected man or a partner of an infected woman should wear a condom during any sexual activity, even when symptoms are not present. Condoms are also important during oral sex, as an increasing number of new genital herpes cases are due to HSV-1, particularly among younger people.

The use of condoms for preventing the transmission of herpes simplex virus 2 (HSV-2) is not foolproof. Even a small tear can permit passage of the virus. However, studies show that regular condom use can significantly reduce the risk of HSV-2 infection.

Condoms made of latex are less likely to slip or break than those made of polyurethane. “Natural” condoms made from animal skin do not protect against HSV infection because herpes viruses can pass through them.

Women appear to be better protected than men are by male condoms. The reason may be that men shed HSV-2 from the skin of the penis, which is covered by the condom. However, in women the virus is often shed from skin areas around the genital area, which can have contact to skin areas in the male outside the condom.

The female condom is another option for infected women or partners of infected men. The female condom covers a large area and is an effective barrier to sexually transmitted viruses.

Note on Lubricants and Spermicides. Only water-based lubricants (K-Y Jelly, Astroglide, AquaLube, glycerin) should be used. Oil-based lubricants (petroleum jelly, body lotions, cooking oil) can weaken latex.

Some condoms come prelubricated with sperm-killing substances called spermicides, which are no longer recommended. The standard active ingredient in spermicides is nonoxynol-9, which attacks the surface of the sperm cell. Nonoxynol-9 does not provide any additional protection against sexually transmitted diseases (STDs). It can cause yeast and urinary tract infections in women. In addition, it can cause irritation around the genital areas, which makes it easier for herpes and other STDs to be transmitted. In fact, research indicates that it actually increases the risk for HIV in women.

Treatment for Genital Herpes

No drug can cure herpes simplex virus. The infection may recur after treatment has been stopped, and, even during therapy, a patient can still transmit the virus to another person. Drugs can, however, reduce symptoms and improve healing times.

Antiviral drugs called nucleosides or nucleotide analogues are the main drugs used to treat genital herpes. They are taken by mouth. (Acyclovir is also available as an ointment, but the oral form is much more effective.) These drugs limit herpes viral replication and its spread to other cells. They are not cures, however.

Three drugs are approved to treat genital herpes:

Acyclovir (Zovirax or generic)
Valacyclovir (Valtrex)
Famiciclovir (Famvir)

When a patient has herpes for the first time, the drug is taken several times a day for 7 -10 days. Then the drugs are used either to suppress the virus or to treat outbreaks.

To treat outbreaks, regimens depend on the medication and dosage prescribed:

Acyclovir: 400 mg three times a day for 2 days or 800 mg twice a day for 5 days
Valacyclovir: 500 mg twice a day for 3 days or 1 g once a day for 5 days
Famiciclovir: 125 mg twice a day for 5 days or 1000 mg twice a day for 1 day. (In 2006, famiclovir was approved as the first one-day treatment for recurrent genital herpes.)

To suppress outbreaks, treatment requires taking pills daily on a long-term basis. (Acyclovir and famiciclovir are taken twice a day, valacyclovir once a day.) Suppressive treatment can reduce outbreaks by 70 – 80%. It is generally recommended for patients who have frequent recurrences (6 or more outbreaks per year). Valacyclovir may work especially well for preventing herpes transmission among heterosexual patients when one partner has herpes simplex virus 2 (HSV-2) and the other partner does not. However, valacyclovir may not be as effective as acyclovir or famiciclovir for patients who have very frequent recurrences of herpes (more than 10 outbreaks per year).

Because the frequency of herpes recurrences often diminishes over time, patients should discuss annually with their doctors whether they should stay with drug therapy or discontinue it. Studies suggest that daily drug therapy is safe and effective for up to 6 years with acyclovir, and up to 1 year with valacyclovir or famciclovir.

Side Effects. Nausea and headache are the most common side effects, but in general these drugs are safe. Although there is some evidence these drugs may reduce shedding, they probably do not prevent it entirely. The use of condoms during asymptomatic periods is still essential, even when patients are taking these medications.

Risk for Resistant Viruses. As with antibiotics, doctors are concerned about signs of increasing viral resistance to acyclovir and similar drugs, particularly in immunocompromised patients (such as those with AIDS). Some experts believe, however, that the prevalence of drug-resistant viruses will be low for many years. They feel that widespread use of antiviral drugs will prevent many cases of herpes from developing and will slow the spread of the disease. Even patients on long-term suppressive drug therapy show few signs of drug resistance. However, patients who do not respond to standard regimens should be monitored for emergence of drug resistance.

Some doctors believe that developing an effective herpes vaccine is the only practical way to control the disease and the spread of infection. Furthermore, if such a vaccine becomes available, then universal immunization may be the best approach. Vaccines also hold the potential for eliminating latent, lifelong infections.

In 2002, the National Institute of Allergy and Infectious Diseases (NIAID) launched the Herpevac Trial for Women. The NIAID seeks to enroll 7,500 women between the ages of 18 and 30 who test negative for both herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) infection. The trial is being conducted at more than 40 sites in the United States and Canada. Participants are randomly assigned to receive either three doses of the experimental herpes vaccine or an investigational hepatitis A vaccine. The women will be observed for 20 months following the initial vaccination to determine if they contract genital herpes (or, for the control group, hepatitis A) during this time. The vaccine used in the trial does not contain live virus and will not itself cause infection.

The premise for the Herpevac trial is based on results from two studies published in the New England Journal of Medicine in 2002. In these studies, a glycoprotein D vaccine was effective in preventing genital herpes in women who were not infected with HSV-1 or HSV-2. For uninfected women, the risk of contracting genital herpes was reduced by nearly 75 percent. The vaccine was not useful, however, for women already infected with HSV-1 and was ineffective in men regardless of their virus status.

Treatment for Oral Herpes

Acyclovir (Zovirax), valacyclovir (Valtrex), and famciclovir (Famvir) -- the anti-viral pills used to treat genital herpes -- can also treat the cold sores associated with oral herpes. In addition, acyclovir is available in topical form, as is penciclovir (a related drug).

These ointments or creams help shorten healing time and duration of symptoms. However, none are truly effective in eliminating outbreaks.

Penciclovir (Denavir) heals herpes simplex virus 1 (HSV-1) sores on average about half a day faster than without treatment, stops viral shedding, and reduces the duration of pain. Ideally, the patient should apply the cream within the first hour of symptoms, although benefits have also been noted with later application. It is continued for 4 consecutive days, and should be reapplied every 2 hours while awake.
Acyclovir cream (Zovirax) works best when applied early on (at the first sign of pain or tingling).
Docosanol cream (Abreva) is the only FDA-approved non-prescription ointment for oral herpes. The patient applies the cream five times a day, beginning at the first sign of tingling or pain. Studies have been mixed on the cream’s benefits.
Over-the-counter topical anesthetics may provide modest relief. They include Anbesol gel, Blistex lip ointment, Campho-phenique, Herpecin-L, Viractin, and Zilactin.

Resources

www.ashastd.org -- American Social Health Association
www.niaid.nih.gov -- National Institute of Allergy and Infectious Diseases
www.cdc.gov/std/herpes -- Centers for Disease Control and Prevention
www.herpesdiagnosis.com -- Herpes Diagnosis
www.herpesalliance.org -- International Herpes Alliance
www.gotherpes.com -- Herpes support site
www.niaid.nih.gov/dmid/stds/herpevac -- Herpevac (herpes vaccine) clinical trial information

References

Centers for Disease Control and Prevention, Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006 Aug 4;55(RR-11):1-94.

Lebrun-Vignes B, Bouzamondo A, Dupuy A, Guillaume JC, Lechat P, Chosidow O. A meta-analysis to assess the efficacy of oral antiviral treatment to preventgenital herpes outbreaks. J Am Acad Dermatol. 2007 Aug;57(2):238-46. Epub 2007 Apr 9.

Nagot N, Ouedraogo A, Foulongne V, Konate I, Weiss HA, Vergne L, et al. Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. N Engl J Med. 2007 Feb 22;356(:790-9.

Review Date:
9/9/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Lyme disease and related tick-borne infections

FitSugar — Wed, 08 Oct 2008 17:35:15 -0700

In This Report

Highlights
Introduction
Symptoms
Risk Factors
Complications
Diseases with Similar Sympt...
Diagnosis
Treatment
Prevention
Human Granulocytic Anaplasm...
Babesiosis
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Lyme Disease Rates Double in Past 15 Years

The annual number of people newly infected with Lyme disease has doubled from around 10,000 cases per year in the early 1990s to about 20,000 cases per year now. Improved diagnosis and reporting probably contribute to this increase. In the United States, Massachusetts, New Jersey, and Pennsylvania have reported the highest number of Lyme disease cases in recent years. People ages of 5 - 14 years and 45- 54 years are at highest risk for contracting Lyme disease.

New Guidelines for Treatment of Neurological Lyme Disease

Most cases of Lyme disease can be prevented or cured with prompt antibiotic treatment following a deer tick bite. However, neurological complications can later develop in some patients. In 2007, the American Academy of Neurology released new guidelines for the treatment of nervous system Lyme disease. The guidelines recommend that patients with severe disease receive a 2 - 4 week course of intravenous antibiotics (penicillin, ceftriaxone, or cefotaxime). Patients with milder neurological cases may do well with a 2 - 4 week course of oral doxycycline. No guidelines currently recommend long-term antibiotic treatment for any stage or complication of Lyme disease.

Introduction

Lyme disease is the most commonly reported vector-borne disease in the United States. Vector-borne infections are transmitted by insects.

The Lyme disease infection in the U.S. is caused by a spirochete called Borrelia (B.) burgdorferi. A spirochete is a bacteria-like organism with a cylinder-like shape surrounded by an outer membrane.

Lyme researchers have the completion of DNA encoding of B. burgdorferi. Researchers learned that certain proteins coat its outer surface. These proteins, collectively called Osp, are responsible for attaching the spirochete to cells in humans and other mammals.

The vector that carries B. burgdorferi in the U.S. Northeast and North Central states is the Ixodes scapularis tick. The Ixodes scapularis tick goes through three stages over the course of about two years:

It is born from eggs as a larva.
It develops into the nymph stage.
It develops into the adult stage.

Cycle of Infection in the Northeast and North Central U.S. For Lyme disease to exist in these regions, three factors must come into close contact:

The Borrelia (B.) burgdorferi spirochete
The spirochete's host, the Ixodes scapularis tick
The mammal for the tick to bite

The following describes the most common cycle in the Northeast and North Central U.S. by which the Lyme disease infection eventually reaches a person:

The cycle of infection is related to the tick's life cycle, which requires 2 years to complete. The tick typically first picks up the spirochete during its larva stage, when it needs a blood meal to mature further.
The tick's initial meal is typically blood from the white-footed mouse, which is commonly infected with Borrelia burgdorferi. After it dines on the infected blood, the tick then becomes a carrier of this spirochete.
Borrelia burgdorferi lodges in the tick throughout one of both of its following life stages, nymph and adult. It is during these stages that the infection is passed on to other animals, including humans. Nymph ticks emerge around mid-June and can be about the size of poppy seeds. They are very difficult to spot and are estimated to be responsible for 90% of all Lyme disease cases. Adult ticks can be as large as a raisin after feeding, and easy to spot, but they usually prefer their dinner on the white-tailed deer.
The infected nymph or adult tick crawls (it does not fly or jump) onto another animal, which can be mice or larger animals, such as deer, birds, or humans. If the tick bites these animals, it may then infect them with the B. Burgdorferi spirochete. (It should be noted that infected humans cannot pass the spirochete on to other humans by any means, including infected blood or urine or sexual contact.)
A tick can feed for several days while being imbedded in the skin, after which it falls off. The tick's bite is painless, however, so only about half of people with Lyme disease recall being bitten.

Cycle of Infection in the Northwest. In the Northwest, the infecting insect is the Western blacklegged tick, Ixodes Pacificus. Here, the frequency of Lyme disease is much lower than in the other two regions because the animal carrier of the infection is the dusky-footed wood rat. This animal is bitten and infected by the Ixodes neotomae tick, which does not bite humans. The actual tick that spreads B. burgdorferi to people is Ixodes pacificus, which must feed first on an already infected wood rat.

The two other important infections carried by the Ixodes scapularis tick are human granulocytic anaplasmosis (HGA) and babesiosis. Although they are both borne by the same tick as Lyme disease, all three of these infections are entirely different diseases.

Risk for Coinfection. Because Lyme disease, HGA, and babesiosis can all be carried by the same tick, there is some risk for co-infection with two or more of these organisms. The risk, however, is not wholly known. Studies have reported that 2 - 25% of ticks in several high-tick locations carry both HGA and Lyme. In one study of patients located in high-risk areas in New England, 39% had more than one of these infections transmitted by the Ixodes tick. There is no evidence that co-infection with one or more of these infections causes a more severe condition than either infection separately.

Symptoms

Symptoms of Lyme disease are diverse and often occur in early and late phases. They vary widely from person to person. Any one symptom may fail to appear, and symptoms may overlap in various combinations. Death from Lyme disease is very rare and occurs only in a few cases in which the heart is severely affected.

Stage 1. In the majority of cases, the first sign of early Lyme disease is the appearance of a bull's-eye skin rash. It usually develops about 1 - 2 weeks after the bite, although it may appear as soon as 3 days, and as late as 1 month. In some cases, it is never detected. Flu-like symptoms (joint aches, fever, and general fatigue) commonly develop.
Stage 2. Untreated, the infection spreads through the bloodstream and lymph nodes within days to weeks, involving the joints, nervous system, and possibly the heart. Multiple rashes may erupt in other places. If the infection affects the nervous system in stage 2, it most often causes weakness or paralysis in the nerves of the face (Bell's palsy) or in nerves of the spine.
Stage 3. If the disease remains untreated, a persistent infection can occur after a few weeks or months, leading to prolonged bouts of arthritis and neurologic problems, such as concentration problems or personality changes. Fatigue is a prominent feature of both early and late stages.

Evidence suggests that up to 90% of patients with Lyme disease exhibit a rash a few days to a month after a tick bite. The rash, known as erythema migrans, usually first appears on the thigh, buttock, or trunk in older children and adults, and on the head or neck in young children.

The bull's eye rash, which is commonly believed to be the classic sign of Lyme disease, may take the following course:

It can first appear as a pimple-like spot, which expands over the next few days into a purplish circle. The circle may reach up to 6 inches in diameter with a deeper red rim. In some cases the ring is incomplete, forming an arc rather than a full circle.
The center of the rash often clears or may turn bluish. Or secondary concentric rings may develop within the original ring, creating the bull's-eye pattern. Over the next several weeks, the circular rash may grow to as large as 20 inches across.
Patients often describe the sensation of the rash as burning rather than itching.

It is important to note that in one study, only 9% of patients diagnosed with Lyme disease exhibited this classic pattern. Nearly 60% had a rash that was more general in appearance and 32% had a circular dense red rash.

In most patients, any rash fades completely after 3 - 4 weeks, although secondary rashes may appear during the later stages of disease.

A flu-like condition is the most common sign of Lyme infection, and it can occur with or without a rash. Symptoms can last from 5 - 21 days and may include:

Fatigue
Chills and fever (100 - 103° F)
Headache (usually most prominent at the back of the head)
Joint aches (usually in the large joints)
Stiff neck
Backache
Swollen glands (in the area around the tick bite or elsewhere)
Less often, nausea, vomiting, and sore throat occur

Some experts recommend that children in high-risk areas be tested for Lyme in the summer months if they have the most common Lyme symptoms (fever, headache, joint aches) -- even if they have no tell-tale rash. Severe and sustained flu symptoms without the rash in such patients may indicate the presence of human granulocytic anaplasmosis (HGA) or babesiosis -- the other infections carried by the Ixodes tick.

Joint pain can arise at any time after the appearance of a skin rash. In the absence of a rash, arthritic symptoms may be the first indication of Lyme disease. Or, as suggested by some studies, it can develop months after the disease has been diagnosed. Arthritic symptoms may occur as follows:

Aches, stiffness, and swelling, sometimes massive, of large joints, such as the knee, elbow, or shoulder. One or both knees are affected most often. The ankle, wrist, jaw, and finger joints are involved less often.
Typically, no more than three joints are affected during the course of the disease. If several joints are involved, they tend to be asymmetrically distributed.
Joint pain flare-ups are often accompanied by muscle pain.
Arthritis symptoms usually last for a few days or weeks and are interspersed with longer periods during which the joints feel fine.
The severity and frequency of attacks peak within 1 - 2 years then decrease and usually resolve, even without treatment.

About 15% of untreated patients develop neurologic symptoms. They can occur in all stages of the disease and can affect any part of the nervous system.

Common Early Neurologic Symptoms. Most often, neurologic symptoms first appear while the initial skin rash is still present or within 6 weeks after its disappearance. Sometimes they are the first symptoms that the patient experiences. The most common neurologic symptoms may be headaches, sleep problems, and mood disturbance. Memory problems can also occur. Neurologic symptoms typically improve or resolve within a few weeks or months, even in untreated patients.

Bell's Palsy. In 5 - 10% of untreated Lyme patients, the facial nerve is affected, which results in Bell's palsy. This is a sudden weakness and drooping of the facial muscles and eyelid on one side of the face. Nerves around the facial area may also cause numbness, dizziness, double vision, and hearing changes. Another common neurologic problem is pain in the lower spine. It resembles low back pain from arthritis (although in the case of Lyme disease the skin near the spine may have abnormal sensations). Of note, Lyme disease has been observed in more than half the children who develop Bell's palsy.

Symptoms of Meningitis. In about 10 - 15% of patients, the infection takes place in the membranes that surround the brain and spinal cord (called meningitis). This can cause:

Episodes of headache not relieved by over-the-counter medication
Mild stiff neck
Sensitivity to light

Symptoms of Lyme Encephalopathy. In some cases of untreated disease, the infection causes a condition called Lyme encephalopathy or neuroborreliosis. This causes the following symptoms:

Unexplained mood changes
Depression
Trouble concentration and remembering
Irritability
Feelings of "pins and needles" or numbness in the arms or legs

Other Neurologic Symptoms.

If the infection affects the white brain matter, symptoms resemble multiple sclerosis.
If the infection occurs in the nerves affecting the skin, some patients experience pricking, tingling, or creeping feelings.
Children have a higher risk than adults for neurologic effects on the eye. (This is still rare, however.)

The infection may affect electrical conduction to the heart and cause symptoms suggesting heart rhythm disturbances:

Palpitations
Shortness of breath
Chest pain
Dizziness
Fainting can occur if the infection affects the heart

These symptoms almost never produce serious problems in people without other types of heart disease.

Symptoms in the eyes have been reported at every stage. Conjunctivitis ("pink eye") may be a symptom in the early stages. In late, untreated Lyme disease, neurologic problems can affect the eye, causing pain and sensitivity to light.

Risk Factors

Since 1991, when Lyme disease became a reportable disease, annual cases have doubled. (This increase is probably both due to increased infection rates as well as better diagnosis.) In general, about 21,000 cases of Lyme disease are now reported in the U.S. each year.

Anyone exposed to ticks is at risk for Lyme disease and other tick-borne diseases. Pets are also at risk. Naturally, anyone who is regularly outside in areas where tick rates are high has a greater than average risk for becoming infected.

Age. The highest reported incidence of Lyme disease occurs among children 5 - 14 years old and adults 45 - 54 years old.

Sex. Men and women are equally at risk.

In general, the risk for developing Lyme disease after a tick bite is only between 1 - 3%. The risk varies depending on different factors:

The longer the tick has fed, the greater the risk. In fact, in one study, no individuals developed Lyme disease after being bitten by a nymph tick for fewer than 72 hours. The risk was 25% in people on whom the tick had been feeding for longer than 72 hours.
Nymph ticks carry a greater risk than adult ticks, probably because they are often too small to be detected (about the size of a pinhead). In addition, only nymph ticks that are at least partially swollen when removed pose any significant risk. (This suggests that they have feeding for a prolonged period.)

Locations in the U.S. Lyme disease has been reported in nearly all U.S. states. However, most Lyme disease cases are concentrated in the northeastern, mid-Atlantic, and north central states. Although Lyme disease was named for a town in Connecticut where the first American cases of the disease were described, in recent years Massachusetts, New Jersey, and Pennsylvania have reported the greatest number of cases.

Worldwide Locations. Pockets of Lyme disease exist around the world. The disease is common in Europe, particularly in forested areas of middle Europe and Scandinavia. The Borrelia family is also responsible for tick infections in Europe, but different subspecies (B. garinii and B. afzelii) may be more common there and cause slightly different symptoms. The infection has also been reported in Russia, China, and Japan.

Deer ticks thrive in grassy areas that have low sunlight and high humidity. Woodlands and fields are prime habitats, but these ticks can also be found in the long grasses adjacent to beaches. The ticks are not confined to rural settings. In suburban areas, they can live in overgrown lawns, groundcover plants, and leaf litter.

The exact time of year for risk depends on a geographic region’s seasons and how they affect the tick’s breeding cycle. In general, the highest risk for Lyme disease onset is from June through August, and the lowest risk is from December through March.

Complications

Prompt treatment with antibiotics is very effective in curing Lyme disease in nearly all infected people, including children. One study showed that the long-term outcome of patients with Lyme disease who are treated with antibiotic therapy is excellent. However, even if Lyme disease has been successfully treated, it may be possible to become reinfected with Lyme disease again at a later date. The risk appears to occur only in patients who had been treated for the rash. In those who also developed arthritic symptoms, the antibody response appears to persist and prevent reinfection.

People at highest risk for persistent symptoms are those who go the longest before treatment. Fortunately, public vigilance has significantly reduced the rates of late-stage Lyme disease. Antibiotics given at late stages will relieve symptoms in most people, although about 5% may continue to have problems. Also at risk for persistent symptoms are those who show evidence of having severe infections. Retreatment at later stages has been shown to be effective in about three quarters of these patients.

Left untreated, Lyme disease can spread (disseminate). The infection may affect almost any part of the body and cause the following complications:

Severe arthritis
Persistent fatigue
Mood disturbances and loss of concentration
Neuropathy (numbness, tingling, or other odds sensations in the hands, arms, feet or legs)
Life-threatening disorders affecting the heart, lungs, or nervous system can occur, but are very rare.

Arthritis. Without treatment, 60% of patients develop intermittent joint inflammation, especially in the knees. Lyme arthritis usually responds to a 28-day course of oral antibiotics (doxycycline, amoxicillin, or cefuroxime). A small number of patients may require intravenous antibiotics.

If the arthritis persists or joint swelling recurs after several months, patients may be treated by another 4-week course of oral antibiotics or 2 - 4 weeks of intravenous antibiotics (ceftriaxone). If symptoms still persist, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroid injections, or disease-modifying antirheumatic drugs may be recommended by a rheumatologist. In severe cases, patients may require surgery (synovectomy) to reduce joint inflammation.

Persistent Neurological Disorders. In general neurological problems persist in 5% of patients, although some studies have reported much higher rates of up to 50%. Persistent symptoms usually include headache, attention and memory problems, and depression. Patients may also experience neurologic pain, numbness, or abnormalities in the face. Neurologic symptoms generally resolve and improve within a year.

Heart Problems. About 5% of untreated patients experience acute heart events from electrical conduction problems caused by the infection. Heart symptoms can appear within a few days to several months after the onset of disease. They include:

Arrhythmias (irregular heartbeats)
Pericarditis (inflammation of the lining of the heart), which occurs in about 5% of patients

Lyme-related heart problems almost always resolve without serious consequences within a week. About 30% of patients may need a temporary pacemaker, however. In very rare cases, these heart rhythm abnormalities have been fatal. There is some debate about whether there are any long-term consequences to the heart, such as the development of heart failure in some patients. One study of patients who had Lyme-related heart effects reported no greater long-term risk for heart problems than in people without a history of Lyme disease.

Miscellaneous Complications. Other complications reported include:

Problems in the eye, including swelling that can cause pain and sensitivity to light
Hepatitis (inflammation in the liver)
Respiratory difficulties

Infections in the Pregnant Patient. The occurrence of any infection during pregnancy is of special concern. While the current research indicates that complications during pregnancy due to Lyme disease are very rare, pregnant women should still adhere scrupulously to preventive measures.

Some studies indicate that Borrelia burgdorferi may be transmitted to the fetus during pregnancy, with the risk highest during the first trimester. If this occurs, however, it is likely to be very rare and not an issue of great concern. There is no evidence of any severe effects in the offspring of infected pregnant women.
There are no reports of human infant Lyme disease infection from breast-feeding. Studies on animals, however, have reported transmission of the organism to infant mice through breast milk, but these findings do not appear to be applicable to people.

Lyme disease is a curable condition. Nearly all patients (95%) improve after a short course of antibiotics. In very rare cases, patients continue to complain of persistent non-specific symptoms, such as fatigue, muscle aches, cognitive problems, and headache lasting years after completing antibiotic treatment for the initial infection.

This syndrome, which resembles chronic fatigue syndrome (CFS) or fibromyalgia, is referred to as post-Lyme disease syndrome. In the past, it has been called “chronic Lyme disease.” However, based on many reviews of scientific literature, experts strongly believe that Lyme disease does not have a chronic state. According to the 2006 guidelines from the Infectious Diseases Association of America, post-Lyme disease syndrome is the preferred name for this condition.

Patients are considered to have this syndrome if they still have symptoms 6 months after treatment. Most importantly, there must be definitive evidence that the patient was originally infected by the B. burgdorferi spirochete. If there is no documented evidence of infection, it could be that the patient never had Lyme disease, or may be experiencing a new or different type of illness. If the patient did have Lyme disease, symptoms should eventually resolve without additional antibiotic treatments.

Experts strongly advise against prolonged antibiotic treatment. There is no evidence that long-term antibiotics help treat post-Lyme disease syndrome symptoms. In addition, long-term antibiotic treatment carries its own serious risks, such as the development of antibiotic-resistant superbugs.

Diseases with Similar Symptoms

Many other illnesses can mimick various features of Lyme disease. Depending on the symptoms, a doctor may be able to perform the evaluations necessary to rule out other conditions.

Other infections can produce fever, headache, muscle aches, fatigue, and some of the neurologic or cardiac features of early Lyme disease. Some are transmitted by the same tick as Lyme disease.

Co-Infections Transmitted by the Ixodes Tick. Babesiosis and human granulocytic anaplasmosis (HGA) are transmitted by the same tick that carries Lyme disease. People may be co-infected with one or more of these infections, all of which can cause flu-like symptoms. If these symptoms persist and there is no rash, it is less likely that Lyme disease is present. Still, diagnosing a co-infection is difficult.

Other Spirochete Infections. Leptospirosis is a spirochete infection spread through animals or contaminated water that most often affects young people during the summer or fall.

Other Tick-Borne Infections. A number of other tick-borne diseases may resemble Lyme disease, although they are more common in parts of the U.S. where Lyme disease is less prevalent.

Tick-borne relapsing fever (TBRF), a flu-like illness that occurs in mountainous areas of the West during the summer, may be misdiagnosed as Lyme disease. The antibiotic doxycycline may be prescribed to patients who have been bitten by ticks suspected of carrying TBRF, to help prevent development of the disease.
Rocky Mountain spotted fever, which is also transmitted by ticks, is most prevalent in the south central and southeastern parts of the United States, but occurs throughout North and South America. The most characteristic symptom is a spotty rash that appears 5 - 10 days after infection. The disease is caused by ticks that carry the bacterial organism Rickettsia rickettsii, and is considered the most severe tick-borne illness in the United States. Unlike Lyme disease, which is rarely fatal, Rocky Mountain spotted fever causes death in 10% of all cases. Recent outbreaks of Rocky Mountain spotted fever have been linked to increases in wild dog populations.
A tick-borne infection called by human monocyte ehrlichiosis (HME), carried by the Lone Star tick, strongly resembles Lyme disease, including a similar rash. It is not caused by the Lyme spirochete, however, and has been identified in patients who live in the southern United States.

Researchers speculate that ticks may be responsible for other diseases not previously thought to be carried by these vectors. For example, the Bartonella family of bacteria causes cat-scratch fever (which is transmitted from cat to cat by fleas) and trench fever (historically transmitted by lice).

Allergic Reaction to the Tick. If a rash, even ring-shaped, appears hours rather than days after a tick bite, it is most likely an allergic reaction to the tick, not a symptom of Lyme disease.

Other Insect Bites. Not every rash seen in regions where Lyme disease is common is caused by a tick. The bites of many insects and spiders can cause a skin reaction.

A number of autoimmune diseases have chronic and low-level symptoms that may be confused with Lyme disease.

Systemic lupus erythematosus (SLE) produces a rash (usually on the face), flu-like symptoms, and arthritis, but they usually develop very slowly over time.
Rheumatoid arthritis or Reiter syndrome causes pain, swelling, or stiffness of the joints that may be confused with post-Lyme disease syndrome.
Scleroderma has a limited form of the disease called morphea, which produces hard patches of skin. Some studies have even reported an association between B. burgdorferi and some cases of morphea. However, the evidence is weak and if it exists it is possibly limited to a specific variant in Europe and Asia. There is no association between severe scleroderma and Lyme disease.
In children, juvenile rheumatoid arthritis or rheumatic fever, which follows strep throat, should be considered.

A number of conditions cause chronic fatigue and joint and muscle aches that resemble descriptions of post-Lyme disease syndrome:

Mononucleosis -- this viral infection is common in adolescents
Chronic fatigue syndrome (CFS)
Fibromyalgia
Depression (may include persistent fatigue and vague aches and pains)

The early neurologic symptoms of Lyme disease (headache, stiff neck, and fatigue) can easily be mistaken for viral meningitis. Children with viral meningitis are more likely to have a higher fever. Patients with Lyme disease often have other symptoms, such as the bull's-eye rash.

Diagnosis

Proper diagnosis of Lyme disease is important. A diagnosis of Lyme disease is straightforward if the patient meets the following criteria:

Lives in an area of tick-infestation
Has the tell-tale bulls-eye rash
Has other symptoms (headache, joint aches, malaise, flu-like symptoms)

If the patient meets all the criteria, except the rash, the doctor may undertake the enzyme-linked immunosorbent assay (ELISA) or the Western Blot test.

In some cases, if the patient seeks a diagnosis within the first 2 - 3 weeks, the doctor may take a sample of the skin or of the blood. If Lyme spirochete is present, it may be identified in the laboratory in a culture medium (a substance in which the organism can thrive and reproduce). This is necessary only if a doctor suspects Lyme but the diagnosis is not clear.

If the infection is not obvious from the patient's history and physical symptoms, but Lyme disease is suspected, the doctor may run tests for evidence of specific factors that suggest infection with B. burgdorferi. Such factors include:

Proteins referred to as Osps. These proteins (referred to as Osp A through F) coat the outer surface of the B. burgdorferi spirochete and then attach to human cells after infection.
Antibodies that attack these Osps. Antibodies are the weapons of the immune system that are launched when foreign invaders (called antigens) are detected. In the case of Lyme disease, these antigens are the Osps.

Specific Tests.

The U.S. Centers for Disease Control (CDC) recommends a two-step process for Lyme disease blood tests:

ELISA and Other Initial Tests. The first tests used are either enzyme-linked immunosorbent assay (ELISA) or an indirect fluorescent antibody (IFA) test. ELISA is the immune test used most often for Lyme disease. (The IFA test is less accurate but may be used when ELISA isn't available.) ELISA measures antibodies that are directed against the B. burgdorferi spirochete. A newer variant is a rapid test (PreVue) that can provide results within an hour. Positive results from any of these tests still require confirmation with a Western blot test. Negative results do not require further testing.
Western Blot. If any of these tests is positive or uncertain, they are followed by the Western immunoblot (WB). This test is more accurate and is very helpful in confirming the diagnosis. The Western blot creates a visual graph showing bands of different colors or shading that experts use to interpret the immune response.

The CDC recommends only these tests. In 2005, the CDC warned against tests -- such as urine antigen, immunofluroescent staining, and lymphocyte transformation -- that do not have enough scientific evidence to support their use.

Accuracy of the Tests. These tests are very expensive, and none are completely accurate in either identifying Lyme or ruling it out. They should never be used to make a primary diagnosis of Lyme disease in patients who do not have obvious symptoms of the disease.

Both false positive and false negative results are common with these tests.

False positive results occur when the test suggests the presence of the disease, but the person does not actually have an active infection. This may occur in different ways:

The antibodies to the infectious organism triggering the antibodies are not the Lyme spirochetes. Other organisms that can trigger such antibodies include syphilis and relapsing fever. Dental infections may trigger a false positive response.
The patient may have been infected with Lyme disease previously and harbor antibodies to the disease.

False negative results miss the actual presence of the disease. These results are also common. (If the results are negative but Lyme disease is highly suspected, the doctor will probably prescribe antibiotics anyway.) False negative results occur for a number of reasons:

The test is taken too early in the course of Lyme disease. In such cases, the antibodies that fight the spirochete might not have reached a level that is high enough to be detected. (Only about 20 - 30% of patients can be identified using immune system tests in the first 2 - 4 weeks. By the fourth week, up to 80% of patients will have detectable antibodies.)
The patient has taken certain medications, such as steroids or certain anti-cancer drugs, which reduce the immune system's ability to produce antibodies, including those in response to Lyme disease.
There are too many infection-fighting antibodies attached to the bacteria. In this case, there are not enough loose antibodies in the blood sample to trigger a response.
The laboratory itself has set its sensitivity point too high. Some laboratories establish a standard of very high antibody levels before the test results will trigger a finding of Lyme disease. (They do this to avoid too many false-positive responses.) In so doing, however, their tests may miss the disease in patients with lower antibody levels. A related diagnostic problem concerns the possibility of missing persistent Lyme disease after antibiotic treatments, when antibody levels would be low.

All of this means that a negative blood test does not rule out a diagnosis of Lyme disease, particularly if symptoms strongly suggest its presence. Conversely, a weakly positive blood test does not prove that Lyme disease is causing the symptoms. A second blood test, taken several weeks later, may help.

The polymerase chain reaction (PCR) test detects the DNA of the bacteria that causes Lyme disease. However, it requires technical expertise and expensive equipment, and can be performed only in a few laboratories in the country. The test also has a high risk of false-positive results. Research indicates that blood or urine samples do not provide accurate results, but skin biopsies may be useful in some cases. At this point, the PCR test is reserved for certain patients with specific diagnostic problems. For most patients, standard antibody tests are preferred.

Analysis of Spinal Fluid. In patients who have neurologic symptoms, a lumbar puncture (a spinal tap) may be used to test for the bacteria in spinal fluid and may be useful for an early diagnosis of Lyme disease.

Treatment

Antibiotics are the drugs of choice for all phases of Lyme disease. In nearly all cases they can cure Lyme, even in later stages.

According to the 2006 guidelines from the Infectious Diseases Society of America (IDSA), people bitten by deer ticks should not routinely receive antibiotics to prevent the disease.

A single dose of the antibiotic doxycycline may be given in situations that meet all of the following conditions:

The tick is still attached to the patient and is positively identified as an adult or nymphal I. scapularis (the tick that carries the Lyme disease B. burgdorferi spirochete).
Doxycycline treatment can be started within 72 hours of the tick bite.
There is proof that at least 20% of ticks in that geographic area are infected with B. burgdorferi.
It is safe for the patient to receive doxycycline (this drug should not be given to pregnant women or children younger than 8 years of age).

In general, the risk of developing Lyme disease after being bitten by a tick is only 1 - 3%. However, patients who have removed attached ticks from themselves should inform their doctors. Patients who have been bitten by a tick should be monitored for up to 30 days to make sure they do not develop symptoms of Lyme disease, especially the tell-tale bull’s-eye rash. If you do develop a skin lesion or flu-like illness during this time, be sure to tell your doctor.

The early stages of Lyme disease usually involve classic bull’s-eye rash (erythema migrans) and flu-like symptoms of chills and fever, fatigue, muscle pain, and headache. In rare cases, patients develop an abnormal heartbeat (Lyme carditis).

All of these conditions are treated with 10 - 28 days of antibiotics. The exact number of days depends on the drug used, and the patient’s response to it. Antibiotics for treating Lyme disease generally include:

Doxycycline. This antibiotic is effective against both Lyme disease and human granulocytic anaplasmosis (HGA) and so is the standard antibiotic for any patient over 8 years old (except pregnant women). Doxycycline cannot be used routinely in children under 8 years old. It is a form of tetracycline and as such discolors teeth and inhibits bone growth. It can also cause birth defects, so it should not be used during pregnancy.
Either amoxicillin (one of the penicillins) or cefuroxime (Ceftin) -- a drug known as a cephalosporin -- are the alternative treatments for young children and some adults. Amoxicillin is the first choice and also probably the best antibiotic for pregnant women. Unfortunately, many people are allergic to penicillin. In addition, strains of bacteria are emerging that are resistant to penicillins.
Intravenous ceftriaxone -- another cephalosporin -- may be warranted if there are signs of infection in the central nervous system (the brain or spinal region) or heart problems.
Other types of antibiotics, such as macrolides, are not recommended for first-line therapy.

Side Effects of Antibiotics. The most common side effects of nearly all antibiotics are gastrointestinal problems, including cramps, nausea, vomiting, and diarrhea. Allergic reactions can also occur with all antibiotics, but are most common with medications derived from penicillin or sulfa. These reactions can range from mild skin rashes to rare but severe, even life-threatening, anaphylactic shock. Some drugs, including certain over-the-counter medications, interact with antibiotics. Patients should report to their doctors all medications they are taking.

Most cases of Lyme disease involve a rash and flu-like symptoms that resolve within 1 month of antibiotic treatment. However, some patients go on to develop late-stage Lyme disease, which includes Lyme arthritis and neurologic Lyme disease.

Slightly more than half of patients infected with B. burgdorferi develop Lyme arthritis. About 10 - 20 % of patients develop neurologic Lyme disease. A very small percentage of patients may develop acrodermatitis chronica atrophicans, a serious type of skin inflammation. These conditions are treated for up to 28 days with antibiotic therapy. If arthritis symptoms persist for several months, a second 2 - 4 week course of antibiotics may be recommended. Oral antibiotics (doxycycline, amoxicillin, or cefuroxime) are used for Lyme arthritis and acrodermatitis chronica atrophicans. (In rare cases, patients with arthritis may need intravenous antibiotics.)

A 2 - 4 week course of intravenous penicillin, ceftriaxone, or cefotaxime is used for treating severe cases of neurological Lyme disease. For milder cases, 2 - 4 weeks of oral doxycycline is an effective option.

In about 5% of cases, symptoms persist after treatment, a condition referred to as post-Lyme disease syndrome. The treatment of post-Lyme disease syndrome is a controversial issue. Most experts do not recommend continuing antibiotic therapy beyond 30 days. Scientific studies do not show any evidence that the benefits of long-term antibiotic treatment outweigh its risks. Long-term antibiotic treatment can lead to a serious and difficult-to-treat infection called Clostridiumdifficile, and can also cause the patient to become resistant to all types of antibiotics.

Experimental and alternative remedies are also not recommended. However, some patients may benefit from learning pain control and cognitive behavioral techniques to help them cope with and manage their symptoms.

Some people use vitamin B complex, omega-3 and omega-6 fatty acids (found in primrose oil and fish oils), and magnesium supplements (magnesium L-lactate dihydrate) to help relieve symptoms. No evidence suggests that they are beneficial. Any such therapies should be discussed with a doctor. Newsletters and Internet sites have cropped up in recent years advertising untested treatments to patients with symptoms of Lyme disease who are frustrated with traditional medical channels. Some remedies are dangerous, and most are ineffective.

In 2006, the Food and Drug Administration (FDA) warned people not to use an alternative medicine product called bismacine (also known as chromacine). This injectable product contains high amounts of bismuth, a heavy metal that can be poisonous. People who have taken bismacine have experienced heart and kidney failure, and one death has been reported. Although some people claim that bismacine can help treat Lyme disease, it is not approved for the treatment of any illness or condition.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Prevention

Everyone should avoid specific tick-infested areas, including tall grass, woods, and bushes where ticks tend to congregate. If this is not possible, people should take additional preventive measures. The U.S. Centers for Disease Control (CDC) also recommends:

Use of tick repellant.
Routine tick checks -- removal of infected ticks within 48 hours of attachment substantially reduces the likelihood of transmission.
Prompt antibiotic prevention for tick bites -- although this method is controversial, the CDC concludes that it is probably beneficial.
Removing brush and leaves -- such landscaping measures can reduce transmission rates by 50 - 90%.
Applying pesticides to yards once or twice per year, which can decrease the number of ticks by 68 - 100%

Mowing the grass regularly, clearing away leaves, and placing wood chips as a barrier around a lawn can help greatly reduce the tick population.

Permethrin for the Lawn. Insecticides can reduce tick infestation by 90%. Insecticides should be applied in late spring or early fall in a strip a few feet wide along the perimeter of the lawn where small animals are likely to enter or live.

The most commonly used insecticides are pyrethrins, which are compounds derived from the Chrysanthemum family. They are available as natural products or in synthetic forms (permethrin). They are poisons that affect the nerve system of insects. They are safe, particularly the natural products, for humans and pets. All pyrethrins are highly toxic for certain fish and slightly toxic for birds, such as mallard ducks. Some people do experience an allergic reaction to them. As with all insecticides, there is some concern about the possible consequences of long-term exposure, but to date there is no evidence of any harm.

Damminix, available in hardware stores, consists of cardboard tubes stuffed with permethrin-treated cotton. The tubes are placed where mice can find them (dense, dark brush) and collect the cotton for lining their nests. The pesticide on the cotton kills any immature ticks that are feeding on the mice. Best results are obtained with regular applications early in the spring and again in late summer. As many neighbors as possible should use it to be effective.

Other Pesticides. Other tick-killing spray pesticides that have been used include those containing diazinon, chlorpyrifos, and carbaryl. Animal studies have reported severe toxic effects associated with these chemicals. Some of these chemicals are being phased out for home use. Parents should balance the effects of a very negligible risk for a highly treatable infection versus excessive use of possibly harmful chemicals.

Fencing. Deer fencing, a wire fence about 3 - 4 yards high, or electrified fencing can be helpful, but it is costly to put up and maintain.

Ivermectin. Corn that is laced with the anti-parasite medication ivermectin (Ivomec and others) and then eaten by deer helps prevent ticks from feeding on them. Ivermectin is present in a number of products used by veterinarians to control parasites, such as heartworm. It has potential toxic effects in collie or collie mixed breeds, however.

Hiking and camping in the Northeastern woods carries a significant risk for tick bites and Lyme disease (3% in one study). Anyone out in the woods during tick season should wear protective clothing, including:

Light-colored clothing -- makes it easier to spot ticks
Long-sleeved shirts and long pants with cuffs tucked into shoes or socks
High boots, preferably rubber boots
Tick-collars for small dogs -- can be worn around a person's ankles over socks or pants

Simply washing clothes will not kill ticks. After venturing outdoors, people should run their clothes through a dryer at high temperature for a half hour. Spraying clothes with solutions containing permethrin (Permanone, Duranon, Permakill) affords additional protection. Keep in mind that these sprays should not be applied to the skin. Clothes should not be retreated with permethrin for 48 hours unless they are washed.

DEET. Most insect repellents contain the chemical DEET (N,N-diethyl-meta-toluamide), which remains the gold standard of currently available mosquito and tick repellents. DEET has been used for more than 40 years and is safe for most children when used as directed. Comparison studies suggest that DEET preparations are the most effective insect repellents now available.

Concentrations range from 4% to almost 100%. The concentration determines the duration of protection. Experts recommend that most adults and children over 12 years old use preparations containing a DEET concentration of 20 - 35% (such as Ultrathon), which provides complete protection for an average of 5 hours. (Higher DEET concentrations may be necessary for adults who are in high-risk regions for prolonged periods.)

DEET products should never be used on infants younger than 2 months. According to the Environmental Protection Agency, DEET products can safely be used on all children age 2 months and older. The EPA recommends that parents check insect repellant product labels for age restrictions.

If there is no age restriction listed, the product is safe for any age. The American Academy of Pediatrics recommends that children use concentrations of 10% or less; 30% DEET is the maximum concentration that should be used for children. In deciding what concentration is most appropriate, parents should consider the amount of time that children will be spending outside, and the risk of mosquito bites and mosquito-borne disease.

When applying DEET, take the following precautions:

Do not use on the face, and apply only enough to cover exposed skin on other areas.
Do not over apply and do not use under clothing.
Do not apply over any cuts, wounds, or irritated skin.
Parents or an adult should apply repellent to a child and not let the child apply it. They should first put DEET on their own hands and then apply it to the child. They should avoid putting DEET not only near the child's eyes and mouth but also on the hands (since children frequently touch their faces).
Wash any treated skin after going back inside.
If using a spray, apply DEET outdoors -- never indoors. Spray repellents should not be applied inside or directly on anyone's face.

Other Insect Repellent Products. In 2005, the CDC added two new mosquito repellents to its list of recommended products:

Picaridin. Picaridin, also known as KBR 3023 or Bayrepel, is an ingredient that has been used for many years in repellents sold in Europe, Latin America, and Asia. A product containing 7% picaridin is now available in the United States. Picaridin can safely be applied to young children and is also safe for women who are pregnant or breastfeeding. According to the CDC, insect repellents containing DEET or picaridin work better than other products.
Oil of lemon eucalyptus. In scientific tests, oil of lemon eucalyptus, also known as PMD, worked as well as low concentrations of DEET. However, oil of lemon eucalyptus is not recommended for children under the age of 3 years.

Self-Inspection. The tick is unlikely to transmit the infection within 3 days of the bite, but prompt removal is still important. The following tips are important for self-inspection:

Ticks responsible for Lyme disease are very small and may resemble freckles or scabs.
People spending time in tick-infested locations should inspect themselves several times a day, including at bedtime.
Check nonexposed areas, such as the back of the knee, as well as exposed areas. Someone else should check the scalp, back of the neck, and other difficult to reach areas.
Check clothing as well as skin. A tick on can be hidden in folds or creases.

Tick Removal. If an attached tick is discovered, there is no reason to panic. Do not put a hot match to the tick or try to smother it with petroleum jelly, nail polish, or other noxious substances. This only prolongs exposure time and may cause the tick to eject the Lyme organism into the body.

The safest and most effective way to remove an attached tick is:

Grasp the tick's mouth area with clean tweezers as close to the skin as possible. (Take care not to handle it with bare fingers as this can also spread infection.)
Next, pull upward with a steady even pressure. Do not twist, crush, or squeeze the body area of the tick, because this region contains the infectious organism. In fact, do not be alarmed if some of the mouth parts remain in the skin. They are not infectious.
Put the tick in a jar or container of alcohol, which will kill it. Some people lay a piece of adhesive tape to the top of the tick and fold it over, without touching the insect. Then they simply throw it away. Tape is also effective for trapping a tick that has not yet attached to the skin.
Once the tick is removed, wash the bite area with soap and water or with an antiseptic to destroy any contaminating microorganisms. Wash hands as well.

The LYMErix Vaccine. The LYMErix vaccine, previously approved, was taken off the market because of poor sales and because of problems encountered with its use. A primary limitation was that the vaccine was effective only in about 75% of cases, and the effects were not long lasting. There were also reports of arthritic and neurologic symptoms in a few vaccinated people. There is no definitive evidence, however, that the vaccine was responsible for these symptoms.

Other Vaccines. Deer ticks lay their eggs on mice and other small rodents. These eggs develop into larvae that feed on these small animals. When the larvae develop into nymphs, they seek a larger host like a deer or human. Scientists are exploring the idea of vaccinating mice and other rodents against B. burgdorferi. Inserting an oral vaccine into these animals’ food supply helps reduce the number of nymph ticks and may be a more effective preventive strategy than vaccinating humans. Recent studies suggest that vaccination of mice produces 89 - 100% protection from B. burgdorferi infection.

Since dogs, cats and even horses can get Lyme disease, inspect pets for ticks regularly. Symptoms in animals include lameness and lethargy. Dogs are much more likely to get Lyme disease than cats, but both are susceptible. In dogs, symptoms occur 2 - 5 months after a tick bite and include fever, lameness, and lack of appetite. In rare cases, Lyme disease can cause kidney damage in dogs if it is left untreated.

Preventive Products. Products containing permethrin (Bio Spot, EXspot), amitraz (Preventic), or fipronyl (Frontline) can be used safely on dogs. Not all of these products are safe in cats. Only permethrin is also effective against fleas. Some veterinarians suggest that the combination of BioSpot and Preventic is very effective. [Another product-- selamectin (Revolution) --is sold for flea and tick control, but it appears to have very limited effect against ticks.]

Pet Vaccines. Lyme disease vaccines are available for dogs, but they do not offer total protection. Veterinarians vary in their use of the vaccines.

Treatment. As with people, antibiotics almost always cure the infection in animals.

Human Granulocytic Anaplasmosis (HGA)

In addition to Lyme disease, I. scapularis deer ticks can carry other types of infections that cause disease in humans. Human granulocytic anaplasmosis (HGA) is another illness spread by the deer tick. (HGA was formerly called human granulocytic ehrlichiosis. Another type of ehrlichiosis, human monocytic ehrlichiosis, is carried by a different type of tick.)

Typical HGA symptoms appear very suddenly within 4 - 14 days of being bitten by an infected tick. Symptoms include headache, fever, chills, headache, and muscle pains. Vomiting, diarrhea, and loss of appetite are also common. Blood tests may indicate a low blood platelet count, low white blood cell count, and increased liver enzyme levels.

HGA is caused by a species of bacteria called Anaplasma phagocytophilum. A blood test can identify the presence of this bacterium.

All patients who show signs of symptoms should be treated with doxycycline to reduce the risk of complications. Another type of antibiotic, rifampin, is an alternative option for pregnant women, children younger than 8 years of age, or patients who are allergic to doxycycline. Treatment is not recommended for people who do not exhibit symptoms, even if they test positive for antibodies to A. phagocytophilum.

Babesiosis

The tick that carries Lyme disease and human granulocytic anaplasmosis (HGA) can also carry babesiosis. Babesiosis is caused by a parasite called protozoa. It has been detected in about 10% of Lyme disease patients, and has been reported in Massachusetts, New York, Connecticut, Rhode Island, New Jersey, Minnesota, Wisconsin, Georgia, California, and Washington.

When babesiosis is acquired from ticks, the infection occurs only in the summer. However, unlike in Lyme disease, blood transfusions have also been known to transmit babesiosis, so it can also occur other times of the year. The disease is still very rare, but people in tick-infested areas should be aware of it.

Symptoms of babesiosis occur 1 - 4 weeks after a tick bite and are similar to those of malaria. Most cases are very mild and nearly unrecognizable. More severe symptom may resemble those in malaria and include:

Headache
Fever and chills, with night sweats
Nausea and vomiting
Muscle aches
Anemia

In healthy people, babesiosis generally causes only mild and temporary problems, but research indicates that the infection might persist in some people and may be spreading faster than previously reported. In rare cases, it can be severe and even life-threatening, particularly in elderly people or those with chronic health problems or compromised immune systems. In such cases, the infection can cause altered mental states, anemia and other blood abnormalities, very low blood pressure, respiratory distress, and kidney insufficiency. Coinfection with Lyme disease may also increase its severity. Unfortunately, it is very difficult to diagnose.

Babesiosis is caused by a protozoon parasite, not a bacteria, so antibiotics alone won’t cure the disease. Treatment involves a two-drug combination of an anti-malaria medication and an antibiotic. The standard drug combinations are atovaquone (Mepron) plus azithromycin (Zithromax, Zmax) or clindamycin plus quinine. About 25% of patients cannot tolerate quinine. Adverse effects associated with quinine include hearing loss, tinnitus, stomach upset, diarrhea, and dizziness.

Resources

www3.niaid.nih.gov -- National Institute of Allergy and Infectious Disease
www.cdc.gov/ncidod/dvbid/lyme -- Centers for Disease Control
www.idsociety.org -- Infectious Diseases Society of America
www.aldf.com -- American Lyme Disease Foundation
www.rheumatology.org -- American College of Rheumatology
www.arthritis.org -- The Arthritis Foundation

References

Centers for Disease Control and Prevention. Lyme disease -- United States, 2003-2005. MMWR Morb Mortal Wkly Rep. 2007 Jun 15;56(23):573-6.

Feder HM Jr, Johnson BJ, O'Connell S, Shapiro ED, Steere AC, Wormser GP; Ad Hoc International Lyme Disease Group. A critical appraisal of "chronic Lyme disease." N Engl J Med. 2007 Oct 4;357(14):1422-30.

Halperin JJ, Shapiro ED, Logigian E, Belman AL, Dotevall L, Wormser GP, et al. Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2007 Jul 3;69(1):91-102. Epub 2007 May 23.

Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, et al. The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006 Nov 1;43(9):1089-134.

Review Date:
1/26/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Crohn's disease

FitSugar — Wed, 08 Oct 2008 17:35:29 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Complications
Risk Factors
Diagnosis
Dietary Factors
Symptom Management
Medications
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Biologic Drugs

In February 2007, the FDA approved adalimumab (Humira) for treatment of adult patients with moderate-to-severe Crohn’s disease. Adalimumab and infliximab (Remicade) are now the two biologic drugs approved for Crohn’s disease. Infliximab is approved for treating both adults and children.
As of August 2007, the FDA was considering approving natalizumab (Tysabri) for moderate-to-severe Crohn’s disease in patients who have not responded to, or cannot tolerate, other therapies. However, natalizumab has serious risks -- in 2007, the European medicine agency rejected natalizumab for Crohn’s disease treatment.
Certolizumab (Cimzia) is another biologic drug that is showing promise for Crohn’s disease, according to several 2007 studies in the New England Journal of Medicine.
The risks of biologic drugs need to be weighed against their potential benefits, according to a 2007 consensus statement from the American Gastroenterological Association. These drugs may be appropriate as initial treatments for select patients who have fistulas or for patients who have not been helped by corticosteroid drugs.

Genetic Research

In 2006 and 2007, scientists achieved major breakthroughs in identifying specific genes associated with Crohn’s disease. Among these recent discoveries:

The interleukin-23 receptor (IL23R) gene is associated with variations that can either increase or decrease the risk for Crohn’s disease and ulcerative colitis.
The ATG16L1 gene regulates a process called autophagy, which involves how a cell digests itself. Scientists think that waste build-up from improperly regulated autophagy may play a role in the inflammatory response associated with Crohn’s disease.
Other recently identified genes that may be linked with Crohn’s disease include PHOX2B and NCF4.

Pregnancy Complications

According to a 2007 review in Gut, inflammatory bowel disease significantly increases the risk for pregnancy complications, such as premature birth, low birth weight, and birth defects. Women who experience disease flares during pregnancy are especially at risk.

Introduction

Inflammatory bowel disease (IBD) is a general term that covers two disorders:

Ulcerative colitis (UC)
Crohn's disease (CD)

Some evidence suggests that these two diseases are part of a biologic continuum. At this time, however, they are considered distinct disorders with somewhat different treatment options. The basic distinctions between UC and CD are location and severity. However, as many as 10% of patients with IBD have features and symptoms that match the criteria for both disorders, at least in the early stages. (This is called indeterminate colitis.)

Crohn's disease, also called regional enteritis, is a chronic inflammation of the intestines which is usually confined to the terminal portion of the small intestine, the ileum. Ulcerative colitis is a similar inflammation of the colon, or large intestine. These and other IBDs (inflammatory bowel disease) have been linked with an increased risk of colorectal cancer.

Crohn's Disease. Crohn's disease is an inflammation that extends into the deeper layers of the intestinal wall. It is found most often in the area bridging the small and large intestines, specifically in the ileum and the cecum, sometimes referred to as the ileocecal region. Crohn's disease occurs less frequently in other parts of the gastrointestinal tract, including the anus, stomach, esophagus, and even the mouth. It may affect the entire colon or form a string of contiguous ulcers in one part of the colon. It may also develop as multiple scattered clusters of ulcers throughout the gastrointestinal tract, skipping healthy tissue in between.

Click the icon to see an image of Crohn's disease.

Ulcerative Colitis. Ulcerative colitis is an inflammatory disease of the large intestine. Ulcers form in the inner lining, or mucosa, of the colon or rectum, often resulting in diarrhea, blood, and pus. The inflammation is usually most severe in the sigmoid and rectum and typically diminishes higher in the colon. The disease develops uniformly and consistently until, in some people, the colon becomes rigid and foreshortened. [See In-Depth Report #69: Ulcerative colitis.]

Click the icon to see an image of the structure of the colon.

The gastrointestinal tract (the digestive system) is a tube that extends from the mouth to the anus. It is a complex organ system that first carries food from the mouth down the esophagus to the stomach and then through the small and large intestine to be excreted out through the rectum and anus.

Esophagus. The esophagus, commonly called the food pipe, is a narrow muscular tube, about 9 1/2 inches long, that begins below the tongue and ends at the stomach.

Stomach. In the stomach, acids and stomach motion break food down into particles small enough so that nutrients can be absorbed by the small intestine.

Small Intestine. The small intestine, despite its name, is the longest part of the gastrointestinal tract and is about 20 feet long. Food that passes from the stomach into the small intestine first passes through three parts:

First it enters the duodenum
Then the jejunum, and
Finally the ileum

Most of the digestive process occurs in the small intestine.

Large Intestine. Undigested material, such as plant fiber, is passed to the large intestine, mostly in liquid form. The large intestine is approximately 6 feet long and is the final portion of the digestive tract. It follows the small intestine and includes the cecum, the appendix, the colon, and the rectum, which extends to the anus.

Cecum and Appendix. The cecum and the appendix are located in the lower-right quadrant of the abdomen.

Colon. The colon absorbs excess water and salts into the blood. The remaining waste matter is converted to feces through bacterial action. The colon is divided into four major sections.

The first section, the ascending colon, extends upward from the cecum on the right side of the abdomen.
The second section, the transverse colon, crosses the upper abdomen to the left side.
The third section extends downward on the left side of the abdomen toward the pelvis and is called the descending colon.
The final section is the sigmoid colon.

Rectum and Anus. Feces are stored in the descending and sigmoid colon until they are passed through the rectum and anus. The rectum extends through the pelvis from the end of the sigmoid colon to the anus.

Click the icon to see an image of the digestive system.

Click the icon to see an image of the stomach.

Click the icon to see an image of the structure of the small intestine.

Click the icon to see an image of the structure of the colon.

Causes

Inflammatory bowel disease has many different causes. It is due in many cases to a genetic susceptibility that enables an organism such as a virus or bacteria to trigger an abnormal immune reaction, which in turn, causes an inflammatory response in the intestines. Although Crohn's disease has features that resemble an autoimmune disease (in which the body's immune system attacks its own cells), some researchers think that it may be due to initial immune deficiencies.

The Immune System's Infection Fighters. The primary infection-fighting units are two types of white blood cells: lymphocytes and leukocytes.

Lymphocytes include two subtypes known as T cells and B cells. Both types of cells are designed to recognize foreign invaders (antigens) and to launch an offensive or defensive action against them:

B cells produce antibodies, which are separate substances that can either ride along with a B cell or travel on their own to attack the antigen.
T cells have special receptors attached to their surface that recognize the specific antigen.

T cells are further categorized as killer T cells or helper T cells.

Killer T cells directly attack antigens that occur in any cells that contain a nucleus.
Helper T cells also recognize antigens, but their role is two fold. They stimulate B cells and other white cells to attack the antigen. They also produce cytokines, powerful immune factors that have an important role in the inflammatory process.

Helper T cells and Inflammatory Bowel Disease. The actions of the helper T cells (TH cells) are of special interest in inflammatory bowel disease:

TH cells stimulate other white blood cells called B cells to produce antibodies. In this case, however, they appear to direct the B cells to produce autoantibodies, which are directed against the body's own cells.
TH cells also secrete or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are indispensable for healing. If overproduced, however, they can cause serious damage, including inflammation and cellular injury. Cytokines, particularly specific ones known as tumor necrosis factor, interferon-gamma, and interleukins, cause intestinal inflammation and damage, which, in a vicious cycle, attract even more helper T cells.

Helper T cells are further categorized as TH1 and TH2. An imbalance in these two types appear to occur in IBD, although each disorder has a different balance:

Ulcerative colitis patients favor a TH2 response, which activates the interleukins IL-5, IL-6, and IL-10. These mostly affect mucosal areas in the intestine.
Research indicates that patients with Crohn's disease have increased activity in TH1 cells, activating interleukin-2 (IL-2) and interferon-gamma, which affect intestinal cells. Tumor necrosis factor (TNF) may be a particularly potent immune factor in Crohn's disease. It is important in properties that regulate inflammation and cell proliferation. If genetic or other factors increase production of this immune compound, it can lead to great harm.

Interleukin 6 appears to play a part in both IBDs, by inhibiting a natural process called apoptosis, in which cells self-destruct. As a result, cells proliferate faster than they die, causing an excessively strong immune response.

Adhesion Molecules. Increased levels of certain molecules called E-selectin and intercellular adhesion molecule-1 (ICAM-1) also appear to play a major role in the inflammatory process by causing damaging immune factors to build up on intestinal cells.

Matrix Metalloproteinase. Greater activity of enzymes called matrix metalloproteinase has been detected in the colons of patients with IBD. These increased levels tend to break down the extracellular matrix, a barrier composed of structural proteins and elastic fibers that surrounds and supports cells, in this case in the colon. Researchers suggest that this activity may cause persistent damage once the inflammatory process has triggered IBD.

Although the causes of inflammatory bowel disease are not yet known, genetic factors certainly play some role. Between 10 - 20% of people with ulcerative colitis have family members with the disease. Several identified genes and chromosome locations play a role in the development of ulcerative colitis, Crohn's disease, or both. Genetic factors appear to be more important in Crohn's disease, although there is evidence that both forms of inflammatory bowel disease have common genetic defects.

Specific Genes Involved. The first important genetic discovery for Crohn’s disease was the identification of the genetic variant CARD15 (also called NOD2), which alters the immune system so that it launches an over-reaction in response to bacteria, causing inflammation. However, this genetic factor only affects a small percentage of Crohn’s disease cases and is not involved with ulcerative colitis.

In 2006, scientists made a significant genetic research breakthrough by identifying the interleukin-23 receptor (IL23R) as a major link to the development of both Crohn’s disease and ulcerative colitis. Interleukin 23 is a cytokine that plays an important part in the inflammatory response and inflammatory diseases. Interestingly, scientists found that certain variations in the IL23 receptor gene can either increase or decrease the risk for inflammatory bowel disease. Further research in 2007 indicated that IL23R gene variants may also increase or decrease the risk for Crohn’s disease in children.

Also in 2007, scientists identified several other genetic risk factors for Crohn’s disease, including the genes PHOX2B, NCF4, and ATG16L1. Scientists are particularly interested in the ATG16L1 gene. This gene regulates autophagy, the process in which a cell digests its own cytoplasm, including cellular waste products such as bacteria. Problems with autophagy may lead to a build-up of unprocessed waste products within the cell. This build-up may then provoke the inflammatory response associated with Crohn’s disease. Mutations of the ATG16L1 gene have been linked to increased susceptibility to Crohn’s disease in both adults and children.

Future genetic research may help develop targeted drug therapy for treatment of inflammatory bowel disease.

One theory suggests that viruses or bacteria within the intestine may alter properties in the lining and intestinal tract. Over time, these changes may trigger the processes that lead to inflammatory bowel disease.

Measles. Some studies report that children with IBD may have had more and earlier childhood infections. The measles virus has been of particular interest. According to the U.S. Centers for Disease Control, and many studies, the measles virus does not cause Crohn’s or IBD.

Much publicity has centered on whether the vaccine for measles, mumps, and rubella (the MMR vaccine) causes conditions such as autism and Crohn’s disease. This theory has been rigorously reviewed and refuted in many well-conducted studies, including several published in 2006. The evidence clearly indicates that the MMR vaccine does not increase the risk of Crohn’s disease, other inflammatory bowel disease, or autism.

Mycobacteria. A type of bacterium associated with tuberculosis is another possible candidate for an infectious cause of Crohn’s disease.

Escherichia coli. The intestine normally harbors E. coli bacteria. In most cases, the bacteria are harmless and even protective. Some E. coli strains, however, can bind to the intestinal walls and penetrate the lining. These damaging strains may be associated with Crohn’s disease.

Cytomegalovirus. Cytomegalovirus (CMV) is a common virus that is also under suspicion as a contributor to severe cases of IBD.

Inflammatory bowel disease is much more prevalent in industrialized nations and in higher-income groups. Diet may play some role, although studies have been conflicting over its importance.

Symptoms

The two major inflammatory bowel diseases (IBDs), ulcerative colitis and Crohn's disease, share certain characteristics:

Symptoms usually appear in young adults.
Symptoms can develop gradually or have a sudden onset.
Both are chronic. In either disease, symptoms may flare up (relapse) after symptom-free periods (remission) or symptoms may be continuous without treatment.
Symptoms can be mild or very severe and disabling.
The severity of symptoms and relapse rates of both IBDs vary with seasons, with the highest risk in the winter and autumn and lowest in summer.

The two disorders, however, have different symptom profiles and is it important to differentiate between them, since they require different treatments.


Symptoms	Ulcerative Colitis	Crohn's Disease
Diarrhea	Recurrent diarrhea is very common, but onset may be very gradual and mild or it may not be present. Feces may also contain mucus.	Recurrent diarrhea is fairly common.
Rectal Bleeding	Blood is almost always present in stools. It may be readily visible or visible only using a microscope (called occult blood).	Bleeding not as common as in UC, but can occur.
Constipation	Constipation can be a symptom of UC, but not as common as diarrhea. Can occur during flare-ups. May occur when the inflamed rectum triggers a reflex response in the colon that causes it to retain the stool.	Constipation in Crohn's disease is usually a symptom of obstruction in the small intestine.
Abdominal Symptoms	Pain is not prominent symptom, but can vary. May cause vague discomfort in the lower abdomen, an ache around the top of the hipbone, or cramps in the middle of the abdomen. Severe pain can occur during flare-ups. Vomiting and nausea.	Main symptom is recurrent episodes of pain in the lower right part of the abdomen or above the pubic bone. Often preceded by and relieved by defecation. Bloating, nausea, and vomiting may also occur. Intestinal pain may also be an indication of a serious condition, such as an abscess, or a perforation of the intestinal wall.
Fever	May occur with severe attacks.	Usually low-grade. Spiking fever and chills indicates complications.
Loss of appetite, weight loss, and impaired growth in children	Often not evident in mild or even moderately severe UC. Occasionally impairs growth in children and teenagers.	Common. Typical weight loss is 10 - 20% of normal. Commonly impairs growth in children and teenagers.
Abnormal defecation: Increased frequency, a feeling of incomplete evacuation, and tenesmus (a painful urge for a bowel movement even if the rectum is empty). Fecal incontinence.	Symptoms may be mild or severe.	Can occur in active stages.
Anal ulcers and fistulas: (channels that can burrow between organs, loops of the intestine, or between the intestines and skin).	Almost never a symptom.	Fistulas and ulcers around the anus may be early symptoms.
Neurologic or psychiatric symptoms	No.	May be early signs of Crohn's disease when accompanied by gastrointestinal problems.

There are three body views (front, back and side) that may be helpful if you are uncertain of a body area. Many areas are referred to by both descriptive and technical names. For example, the back of the knee is called the popliteal fossa. However, areas like the "flank" may not have both names, so the location may be unclear.

Click the icon to see a depiction of an anorectal fistula.

Complications

The outlook for Crohn's disease varies widely. Crohn's disease can range from being benign (such as when limited Crohn's disease occurs only around the anus in older people) or it can be very severe. At the extreme end, some patients may experience only one episode and others suffer continuously. Although recurrences tend to be the norm, disease-free periods can last for years or decades in some patients. Although Crohn's disease cannot be cured even with surgery, treatments are now available that can offer significant help to most patients. Crohn's disease is rarely a direct cause of death, and most people can live a normal lifespan with this condition.

Mild Crohn's Disease. The fewer bowel movements, the milder the disease. In mild disease, abdominal pain is absent or minimal. The patient has a sense of well-being that is normal or close to normal. There are few, if any, complications outside the intestinal tract. The doctor does not detect any mass when pressing the abdomen. The red blood cell count is normal or close to normal, and the patient is not underweight.

Severe Crohn's Disease. In severe Crohn's disease, the patient has bowel movements frequent enough to require opiates or other potent anti-diarrhea medication. Abdominal pain is severe and usually located in the lower right quadrant of the abdomen. (The location of the pain might not indicate the site of the actual problem, a phenomenon known as referred pain.) The red blood cell count is low. The patient has a poor sense of well-being and experiences complications that may include weight loss, joint pain, inflammation in the eyes, reddened or ulcerated skin, fistulas, abscesses, and fever. The surgical and medical treatments of Crohn's disease, as with ulcerative colitis, have complications of their own that can be severe.

Malabsorption and malnutrition. Malabsorption is the inability of the intestines to absorb nutrients. In IBD, this occurs as a result of bleeding and diarrhea, as a side effect from some of the medications, and as a result of surgery. Malnutrition usually develops slowly and tends to become severe, with multiple nutritional deficiencies. It is very common, ranging from 25 - 80% of patients with Crohn's disease.

Ulcer, Fistulas, and Abscesses. Between 30 - 40% of patients with Crohn's disease experience complications around the anal area from inflammation. Fistulas (channels beneath the skin) frequently develop from the deep ulcers that can form with Crohn's. If fistulas develop between the loops of the small and large intestines, they can interfere with absorption of nutrients. They often form pockets of infection or abscesses, which may become life threatening without treatment.

Bleeding. Massive bleeding can occur in 1 - 2% of cases and may be recurrent. Bleeding is usually from a localized area in the intestine. Surgery may be performed to remove the bleeding sites.

Colorectal Cancers. Patients with inflammatory bowel disease have a slightly higher risk for colorectal cancer. The risk is greater for patients with severe ulcerative colitis than for those with Crohn’s disease. Patients with Crohn’s disease do have a 40-fold increased risk for small bowel cancer. (However, small bowel cancer is a very rare type of cancer.) The risk increases with the severity of the condition and the length of time the patient has had Crohn’s. [See In-Depth Report #55: Colon and rectal cancers.]

Intestinal Blockage. Inflammation from Crohn's disease produces scar tissue known as strictures that can constrict the intestines, causing bowel obstruction with severe cramps and vomiting. Strictures usually occur in the small intestine but can also occur in the large intestine.

Intestinal Infections. Inflammatory bowel disease can increase patients’ susceptibility to Clostridium difficile, a species of intestinal bacteria that causes severe diarrhea. As its name implies, C. difficile is difficult to treat and is resistant to many types of antibiotics. It is usually acquired in a hospital. However, several 2007 studies indicated that C. difficile is increasing among patients with inflammatory bowel disease and that many patients acquire this infection outside of the hospital setting. Patients with ulcerative colitis are at particularly high risk.

People with inflammatory bowel disease have a higher risk of developing other inflammatory diseases that affect the lungs and central nervous system.

Asthma. According to a 2005 study, people with IBD are 1.5 times more likely to have asthma than people without IBD. Of all the conditions that can accompany IBD, asthma is the most common. People with IBD are also at increased risk for bronchitis and other lung inflammations

Eyes. Inflammation in the eyes may sometimes be an early sign of Crohn’s disease. Retinal disease, including detachment, can occur but is rare. People with accompanying arthritic complications may be at higher risk for eye problems.

Joints. Inflammation causes arthritis and stiffness in the joints. The back is commonly affected. Patients with Crohn’s disease are also at risk for clubbing (abnormal thickening and widening at the ends of fingers and toes).

Click the icon to see an image of nail clubbing.

Bones. Crohn’s disease, and the corticosteroid drugs used to treat it, can cause osteopenia (low bone density) and osteoporosis (bone loss).

Anemia. Internal blood loss from ulcers in the intestine is a particular problem in Crohn's disease because of the impaired ability to absorb vitamins and minerals necessary for blood production.

Liver and Gallbladder Disorders. Patients have a higher than average risk for mild but not severe liver problems. They have double the normal risk for gallstones.

Click the icon to see an image of gallstones.

Mouth Sores. Canker sores are common, and when they occur they persist. Those at higher risk are males and younger people. Mouth yeast infections also common in people with Crohn's disease.

Skin Disorders. Patients with Crohn’s disease are likely to develop red knot-like swellings. Such swellings or other skin lesions, such as ulcers, may spread to sites far removed from the colon, (including the arms and legs). People with Crohn's disease have an increased risk for psoriasis.

Thromboembolism (Blood Clots). Clots may occur, most likely in the legs and pelvic area.

Click the icon to see an image of a thrombus.

Urinary Tract and Kidney Disorders. Urinary tract infections are common. Patients have an increased risk for kidney stones. Amyloidosis (deposits of a protein called amyloid in the kidney or other organs) is a rare but very serious kidney condition.

Click the icon to see an image of kidney stones.

Delayed Growth and Development in Children. Up to half of children with Crohn’s disease have impaired physical growth, and nearly all are underweight. About 30% reach puberty late, but once it occurs, hormonal cycles tend to be normal.

Infertility. Infertility rates are only slightly lower than average. Active disease at conception increases risk for miscarriage or prematurity. Men may have lower sperm count during active disease or because of impaired nutrition, but in general fertility is normal.

Pregnancy. Inflammatory bowel disease doubles the risk of pregnancy complications. According to a 2007 review, women with inflammatory bowel disease are nearly twice as likely to give birth prematurely. Children born to mothers with this disease are more than twice as likely to be below normal weight and to have birth defects. If a woman experiences active bouts of disease during the course of her pregnancy, her risk for complications increases.

Menstrual Problems. Menstrual problems in women are common, including premenstrual disorder, abnormal bleeding, and pain. Pain with intercourse occurs in about half of patients. Sexual function may be impaired, not only because of the emotional impact, but also by treatment side effects and complications of the disease, such as fistulas.

Neurologic Factors. Inflammatory bowel disease has been associated with neurologic complications, including a higher risk for dementia, movement disorder, and stroke. People with IBD have a higher risk for developing multiple sclerosis and inflammation of the optic nerve (optic neuritis).

Emotional Factors. The emotional consequences of UC cannot be overestimated, particularly in children. Eating becomes associated with fear of abdominal pain before the end of the meal. Frequent attacks of diarrhea can cause such a strong sense of humiliation that social isolation and low self-esteem may result. Adolescents with IBD may have added problems that increase emotional distress, including weight gain from steroid treatments and delayed puberty.

Risk Factors

About 1 - 2 million Americans suffer from inflammatory bowel disease (IBD), and about 400,000 of these patients have Crohn's disease. (This wide variation is due to the difficulty in diagnosing these disorders and because people in remission may not be identified.) The number of people with Crohn's disease may be increasing, and Crohn's disease is now considered to be the second most common chronic inflammatory disorder (after rheumatoid arthritis).

IBD often runs in families. The incidence may vary depending on gender, age, and geography:

Women may be slightly more at risk for Crohn's disease than men. Both genders are equally at risk for ulcerative colitis.
IBDs in general are diagnosed most often in young people age 10 - 19, but they can occur at any age. Another lesser peak onset occurs in people ages 50 - 80. About 2% of IBD cases appear in children below age 10. Between 10 - 15% of patients with Crohn's are children, and the childhood prevalence appears to be increasing.
IBD occurs four times more often in Americans of Northern European descent than in African-Americans. Scandinavia has the highest rate of Crohn's disease in the world. Studies in Britain suggest, however, that Asians may have a higher rate of IBD than people of European descent. Ashkenazi Jewish people have an even higher risk, five times that of the general population.
IBD seems to be more common among city than country dwellers and occurs more frequently in developed than in less developed nations, indicating that both genetic factors and environmental conditions, such as diet, may be involved in its development.
People who are left-handed have a significantly higher risk for both IBDs as well as certain other diseases associated with problems in the immune system.

Diagnosis

The doctor will take a history and perform a thorough physical examination. The disease is particularly difficult to diagnose in children. In children, IBD may be mistaken for an infection or even depression if other characteristic symptoms, such as bloody diarrhea and weight loss, are not present. Slow growth may be a key feature in making a diagnosis, particularly of Crohn's disease, in children.

Several laboratory tests may be performed:

Blood tests are used for various purposes. An increased number of white blood cells may indicate the presence of inflammation. Blood tests are used to determine the presence of anemia and to measure liver enzymes. (They are abnormal in about 3% of ulcerative colitis patients.) New blood tests that measure certain antibodies may make it easier to differentiate Crohn's disease from ulcerative colitis in children.
A stool sample is taken and examined for blood, infectious organisms, or both.

Standard Endoscopic Procedures. Flexible sigmoidoscopy and colonoscopy are procedures that involve snaking a fiberoptic tube called an endoscope through the rectum to view the lining of the colon. The doctor can also insert instruments through it to remove tissue samples.

Sigmoidoscopy, which is used to examine only the rectum and left (sigmoid) colon, lasts about 10 minutes and is done without sedation. It may be mildly uncomfortable, but it is not painful.
Colonoscopy allows a view of the entire colon and requires a sedative, but it is still performed on an outpatient basis. It is important in differentiating between Crohn's disease and ulcerative colitis and in screening for colon cancer.

There are three basic tests for colon cancer: a stool test (to check for blood); sigmoidoscopy (inspection of the lower colon); and colonoscopy (inspection of the entire colon). All three are effective in catching cancers in the early stages, when treatment is most beneficial.

The procedures may help the doctor to distinguish between ulcerative colitis and Crohn's disease, as well as other diseases. A variation called chromoendoscopy uses a blue stain during the process to reveal fine details on the intestinal lining. It might prove to be useful for identifying areas that may be precancerous and need to be biopsied.

Wireless Capsule Endoscopy. Wireless capsule endoscopy (WCE) is a newer imaging approach that is very useful for diagnosing Crohn's disease. With WCE, the patient swallows a capsule containing a tiny camera that records and transmits images as it passes through the gastrointestinal tract. Some studies have found it to be much more accurate for evaluating small bowel disease than barium x-rays or CT scans. Patients also find it easier to tolerate than standard endoscopy.

Ultrasound. Intestinal wall ultrasound is proving to be useful for identifying the extent and severity of Crohn's disease. It is uncertain if ultrasound is useful for an initial diagnosis.

Upper and Lower Gastrointestinal Barium X-Rays. An upper gastrointestinal barium x-ray may be used if Crohn's disease is suspected in the small intestine. Swallowed barium passes into the small intestine and shows up on an x-ray image, which may reveal inflammation, ulcers, and other abnormalities.

Click the icon to see an image of the barium enema procedure.

Positron Emission Tomography (PET) and Computed Tomography (CT) Scans. PET/CT scans are proving to be extremely useful in evaluating active IBD. With Crohn's disease, CT scans may show thickened walls and complications, such as fistulas, which occur outside the intestine.

Magnetic Resonance Imaging (MRI). Magnetic resonance imaging is another advanced imaging technique that may be useful for detecting abscesses and other injuries related to Crohn's disease in the pelvis. A variant called magnetic resonance spectroscopy (MRS) may prove to be useful for differentiating between Crohn's disease and ulcerative colitis.


Endoscopy	Ulcerative colitis almost always involves the lower left colon and rectum and can be diagnosed using sigmoidoscopy. Crohn's disease may require colonoscopy as well. Endoscopy often reveals ulcers, diseased regions that have a cobblestone-like appearance in Crohn's disease, but not in ulcerative colitis.
X-Rays (Barium Enema) or Computed Tomography Scans	In ulcerative colitis, inflammation is usually evenly distributed on the surface lining of the intestine, and the bowel wall bleeds easily when touched with a swab. The pattern observed in Crohn's disease is usually one of scattered patches of ulcers that are deep, thick, and large. Crohn's disease produces pockets (fissures) or channels (fistulas). They do not occur with UC. In ulcerative colitis the ileum (the lower part of the small intestine) is often dilated while it is narrowed in Crohn's disease.
Laboratory Tests	Tissue samples obtained from a patient with Crohn's disease may reveal granulomas, small collections of inflammatory cells. Granulomas may also be present in other conditions, however. Tissue samples should also be examined for the presence of cancerous cells. About 70% of antibody tests for patients with UC will show immune factors called perinuclear-staining antineutrophil cytoplasmic antibodies, and over 50% of Crohn's patients have anti-Saccharomyces cerevisiae antibodies. Each antibody group shows up only occasionally in the other disorder. Researchers are also investigating other antibodies, such as antilaminaribioside and antichitobioside, which may serve as new markers for Crohn’s disease.

Irritable Bowel Syndrome. Irritable bowel syndrome (IBS), also known as spastic colon, functional bowel disease, and spastic colitis cause many of the same symptoms as inflammatory bowel disease (IBD). (However, it is NOT the same as inflammatory bowel disease.) Bloating, diarrhea, constipation, and abdominal cramps are all symptoms of IBS. Irritable bowel syndrome is not caused by inflammation, however, and no fever or bleeding occurs. Behavioral therapy may be helpful in treating IBS. (Psychological therapy does not improve inflammatory bowel disease.)

Microscopic Colitis. Microscopic colitis causes chronic watery diarrhea, but the colon lining shows little or no signs of inflammation. It may be genetically linked to celiac sprue. Most patients can expect to improve.

Celiac Sprue. Celiac sprue, or celiac disease, is an intolerance to gluten (found in wheat) that triggers inflammation in the small intestine and causes diarrhea, vitamin deficiencies, and stool abnormalities. It occurs in a significant number of people with inflammatory bowel disease and is usually first noticed in children.

Click the icon to see foods to avoid if you have celiac sprue.

Interstitial Cystitis. Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost exclusively in women. Some evidence suggests that the risk for IBD in these patients is 100 times above that in the general population and that there may be some common factor to both conditions. The average age of patients with interstitial cystitis is 40, but 25% of cases occur in women under age 30. Symptoms are very similar to urinary tract infections, but no bacteria are present. Pain during sex is a very common complaint in these patients, and stress may intensify symptoms.

Infections. If endoscopy reveals inflammation, a doctor must always rule out possible infections before confirming a diagnosis of inflammatory bowel disease.

Acute Appendicitis. Crohn's disease may cause tenderness in the right lower part of the abdomen, where the appendix is located, that resembles an appendicitis.

Click the icon to see an image of the appendix.

Cancer. Colon or rectal cancers must always be ruled out when symptoms of IBD occur.

Intestinal Ischemia. Symptoms similar to IBD can be caused by blockage of blood flow in the intestine. This is more likely to occur in elderly people.

Dietary Factors

The role of diet and nutrition is very important in Crohn's disease and should be considered for four separate situations:

As important add-on treatment to medical therapies for maintaining nutrition and correcting any nutritional deficiencies
As primary treatment for reducing disease activity
As maintenance therapy on a long-term basis in the case of severe intestinal failure or short-bowel syndrome
For reversing growth-failure in children

Malnutrition is very common in Crohn's disease. In fact, patients with Crohn's appear to burn fat calories at a higher rate than the general population and most patients are underweight. Some experts recommend that children with inflammatory bowel disease increase their calorie and protein intake by 150% of the daily recommended allowance for their specific ages and heights. Studies indicate that nutritional support in children is as important as medications for achieving remission. People whose weights are normal or no less than 90% of normal do not need to add extra calories.

Fluids (non-caffeinated). Drinking plenty of water is extremely important. Vegetable juice and sports drinks may be helpful for restoring important minerals. People with inflammatory bowel disease (IBD) should avoid caffeinated beverages in general, although green tea may have some benefits for Crohn's disease.

Protein. Proteins are very important for growth in children and for repair of cells. Diarrhea can cause protein deficiency, and patients with inflammatory bowel disease may need more protein than the general population. Oily fish, such as salmon and tuna, may be particularly beneficial in Crohn's disease. Other options are poultry and lean meats. Dried beans and legumes also provide protein.

Complex Carbohydrates. Complex carbohydrates, found in whole grains, fruits, and vegetables, should make up half of a patient's calories. Fresh fruit (such as apples, grapefruit, oranges, plums, blueberries, raspberries, and strawberries) may actually be specifically protective for IBD and may possibly reduce the risk for colon cancer. (Simple sugars can increase inflammation, however, so patients should avoid dried fruits and high-sugar fruits, such as grapes, pineapple, and watermelon.)

Foods made up of complex carbohydrates are also often a good source of fiber, which may help reduce damage in the intestinal tract caused by inflammation. However, high-fiber foods can cause gas, bloating, and pain, particularly in IBD patients. Commercial products (such as Beano) are available that can reduce gas. Eating small, frequent meals can also help.

Liquid Supplements. Over-the-counter liquid diets that meet full nutritional needs and are absorbed in the upper intestine, such as Ensure, Sustacal, and other products, may be helpful for some patients with Crohn's. However, it is important to note that no studies have determined this.

Potassium-rich Foods. Examples are potatoes, avocados, and bananas.

Exclusion Diets. Exclusion diets are those that eliminate certain foods that may cause allergies or irritate the intestine. To determine these foods, patients use an "elimination/challenge" approach. First, they remove all suspect foods from their diet for 2 weeks and then reintroduce one food every 3 days. Patients then watch for any symptoms that might indicate an allergic or irritant response, including gastrointestinal problems, headaches, and flushing. This approach, however, may be very difficult, and studies are weak in confirming its value for maintaining remission.

Typical foods people with inflammatory bowel disease (IBD) may avoid include:

Fats. Fats appear to worsen intestinal inflammation in Crohn's disease. Patients should limit fats, particularly saturated fats, found in meat and dairy products. However, certain fatty acids, such as those found in fish oil, may be helpful. The optimal balance between a low-fat diet with addition of these fatty acids is under investigation.
Milk products. Some people with IBD are lactose intolerant (unable to digest the sugar lactose, found in milk products). However, milk, along with the calcium it contains, has been associated with a lower risk for colon cancer. Taking lactase tablets or specially prepared dairy products may help. (Many lactose-intolerant patients are still able to eat yogurt with active cultures, which could be helpful for IBD.)
Foods associated with inflammation (alcohol, simple sugars, and caffeine).
Fruits may be protective, but patients should avoid dried fruits or high-sugar fruits, such as grapes, watermelon, or pineapple.
Products containing corn or gluten (those made from wheat, oats, barley, or triticale).
Common allergenic foods, such as soy, eggs, peanuts, tomatoes.
Foods that may irritate the intestine, particularly so-called Brassica vegetables (cabbage, Brussels sprouts, broccoli, cauliflower, kale).

Kidney stones are painful and common complications in inflammatory bowel disease (IBD), particularly in patients who have had intestinal surgery. IBD patients are at risk for the most common types of kidney stones -- those composed of either calcium oxalate or uric acid crystals. The following are some considerations in reducing the risk for stones:

The most important dietary recommendation is to increase fluid and restrict sodium intake.
Limiting protein is recommended for reducing kidney stones. However, people with IBD who have frequent diarrhea are protein deficient. Having enough protein in the diet, particularly in children with IBD, is very important. Patients should weigh the importance of protien against any risk for kidney stones.
Patients should eat more potassium-rich foods (bananas, watermelon, cantaloupe, oranges, tomatoes, beans).
Patients should try to correct any dietary habits that cause acidic or alkaline imbalances in the urine that promote stone formation.
Many kidney stones are formed from calcium-oxalate stones. Patients should avoid or limit intake of oxalate-rich foods, such as beets, beet tops, black tea, chenopodium, chocolate, cocoa, dried figs, ground pepper, lamb quarters, lime peel, nuts, parsley, poppy seeds, purslane, rhubarb, sorrel, spinach, and Swiss chard. A high calcium diet does not appear to increase the risk for kidney stones as long as it also contains plenty of fluids, dietary potassium, and phosphate. Importantly, calcium is associated with protection against colon cancer and osteoporosis -- two conditions that are associated with IBD.
Patients who have stones associated with short-bowel syndrome should eat less fat and foods that contain oxalates. In these people, calcium may bind to unabsorbed fat instead of to oxalates, which increase oxalate levels.

The general recommendations for avoiding kidney stones need to be tailored to the dietary requirements of IBD. Patients should work with their doctors to develop a plan.

Researchers are currently investigating bacteria (called probiotics) and specific foods (called prebiotics) that are metabolized by these bacteria, and the compounds they produce (called synbiotics). Some evidence suggests that alone or in combination, they may have significant benefits in the intestine.

Probiotics are bacterial strains that by themselves may provide a barrier against harmful bacteria, possibly through various mechanisms such as excreting certain acids (lactate, acetate) that inhibit harmful bacteria or compete with them for nutrients. It has been suggested that probiotics may help maintain remission in patients with inflammatory bowel disease (IBD). The specific bacterial strains that might be beneficial, however, are not fully known. The most well-known probiotics are the lactobacilli strains, such as acidophilus, which are found in yogurt and other fermented milk products. Others, however, may prove to be more important, such as bifidobacteria and GG lactobacilli. Other probiotics that may be beneficial for patients with IBD include lactobacilli rhamnosus, casel, plantarium, bulgaricus, and salivarius, and also Enterococcus faecium and Streptococcus thermophilus.
Prebiotics are specific non-digestible molecules called fructo-oligosaccharides, which stimulate the growth of probiotics. These molecules are found in many foods, including Jerusalem artichokes, onions, salsify, bananas, honey, garlic, and leeks. (However, some of these foods can irritate the intestine in patients with IBD.)

Researchers are investigating probiotics, prebiotics, or both for intestinal protection, including benefits for patients with IBD. Foods and supplements containing these substances are available in the U.S. and are heavily marketed in Europe, Japan, and Australia. To date, however, no studies have determined any clear benefits of any specific organism or formulation.

Crohn's disease and surgical procedures that remove parts of the small intestine can inhibit absorption of vitamins, fats, and other important supplements. Taking certain supplements -- such as fish oil, antioxidants, and mineral supplements -- may be beneficial for patients with Crohn's disease.

Vitamins. Deficiencies of vitamins A, C, D, E, B12, and folate (a B vitamin) may result from malabsorption. In general, vitamin supplements may be recommended for everyone with inflammatory bowel disease (IBD), particularly for children to avoid growth retardation. Vitamins A, C, and E are antioxidants, which are scavengers of damaging particles in the body. Folic acid supplements are particularly important for patients who must restrict fresh fruits and vegetables and for those taking sulfasalazine. Folate deficiencies may contribute to the increased risk for colon cancer. Monthly injections of vitamin B-12 may be necessary. Vitamin D is necessary for bone protection. Because some vitamins, such as A and D, can be toxic at high doses, patients should discuss specific dosages with their doctors.

Omega-3 Fatty Acids. The role of fats in inflammatory bowel disease is complex and not fully known. Some evidence suggests that patients with Crohn's burn fat calories at a higher rate than the general population. Patients with IBD may be deficient in essential fatty acids, particularly omega-3 fatty acids (polyunsaturated fats found in oily fish and certain vegetable products such as flaxseed and canola oils). Such fatty acids are also available in supplements as docosahexaenoic (DHA) and eicosapentaneoic (EPA) acids, which are specific compounds found in fish oil.

Omega-3 fatty acids, found plentifully in oily fish and flaxseed and canola oils, are beneficial to people afflicted with inflammatory bowel disease.

Mineral Supplements. Supplements of calcium, magnesium, zinc, selenium, and iron may be needed to offset deficiencies in patients with severe IBD.

Calcium and magnesium are critical for health and strong bones. Many patients with IBD suffer from calcium and vitamin D deficiencies, which cause low bone density. Studies indicate that calcium and vitamin D supplements may be adequate to increase bone density without drugs.
Selenium is a potent antioxidant.
Zinc is important for wound healing, and deficiencies may promote fistulas in Crohn's disease.
Iron supplements may be required for anemia. However, iron overdose is very dangerous. As few as three adult iron tablets can poison children, even fatally. No one, even adults, should take a double dose of iron if one is missed. A doctor should advise patients on correct dosage.

Enteral Nutrition. Enteral nutrition uses a feeding tube that is inserted either through the nose and down through the throat or directly through the abdominal wall into the gastrointestinal tract. It is the preferred method for feeding patients with malnutrition who cannot tolerate eating by mouth. The nutritional formulas used in enteral administration include:

Polymeric diets (containing a balance of standard nutrients).
Elemental diets (predigested nutrients that are absorbed in the first meter of the small intestine). These diets are used less commonly than polymeric diets.

In children, enteral nutrition is given for 6 - 8 weeks. Simple foods are then introduced (chicken, potato, rice), and more complex foods (milk, fiber, wheat-based foods) are then added gradually. However, relapse is still common.

Total Parenteral Nutrition. Total parenteral nutrition (TPN), or hyperalimentation, is the intravenous administration of nutrients through an indwelling catheter (tube). It is used for very severe IBD when patients cannot tolerate any nutrition by mouth or with a feeding tube, and may even be useful as a primary therapy for patients with Crohn's (although not for those with fistulas). It is usually given in the hospital, although increasingly people are giving it to themselves at home. The procedure carries a risk for complications, some serious, including infection, blood clots, and liver failure.

Symptom Management

The following are some ways of managing diarrhea, constipation, or both:

Mild-to-moderate diarrhea may be reduced by taking 1 teaspoon of psyllium hydrophilic colloid (Metamucil) twice a day in a glass of water.
Antidiarrheal drugs include loperamide (Imodium) and a combination of atropine and diphenoxylate (Lomotil). In very ill patients, large doses of some antidiarrheal drugs, such as Lomotil, can trigger the onset of toxic megacolon. Toxic megacolon is a life-threatening complication of other intestinal conditions. It is characterized by a very inflated colon, abdominal distention, and sometimes fever, abdominal pain, or shock.
Opiates or drugs used to relax muscle spasms may help relieve mild-to-moderate diarrhea and abdominal cramps, but they should be used for very short periods and not for severe cases.
Cholestyramine (Questran) has been found to be useful for reducing diarrhea in patients who have had ileal resections.
Bulk-type laxatives can help constipation.

Iron supplements may be required for anemia. Intravenous iron with or without erythropoietin (a hormone that acts in the bone marrow to increase the production of red blood cells) is effective for severe anemia in IBD that does not respond to iron alone. Patients with Crohn's disease benefit most from the combination.

Antidepressants may help relieve emotional problems. However, inflammatory bowel disease is not a psychological disorder, and these drugs will not affect the basic illness.

Acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs) are used for relieving mild pain. NSAIDs include aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), and celecoxib (Celebrex), the only COX-2 inhibitor left on the market. NSAIDs have been thought to cause symptom flare-ups in patients with inflammatory bowel disease (IBD). However, a comprehensive 2006 study concluded that these drugs are as safe for patients with IBD as for other people, and that they can help prevent relapse as well as provide short-term pain relief. Still, long-term use of NSAIDs can cause stomach bleeding and, with the exception of aspirin, may increase the risks for heart attack and stroke. Acetaminophen can cause liver damage if taken in high doses or combined with alcoholic drinks. Discuss with your doctor whether acetaminophen, NSAIDs, or other pain relievers are appropriate for you.

Although stress is not a cause of inflammatory bowel disease, there are reports of an association between stress and symptom flare-ups. Although no evidence exists to confirm that stress reduction techniques such as relaxation methods, meditation, or cognitive therapy, manage the disease, they might be helpful.

The effects of exercise in Crohn's disease are uncertain. Some research indicates that moderate exercise may trigger excess production of chemicals that could cause flare-up. One small study, however, reported significant improvement in patients who had been sedentary but then embarked on a 12-week exercise program. They walked a little over 2 miles three times a week. During that period there were no flare-ups, and they felt physically and emotionally better than before.

Medications

The primary goal of drug therapy is to reduce inflammation in the intestine. Drugs are effective in reducing the inflammation and accompanying symptoms in up to 80% of patients. Unfortunately, relapses are still frequent, and researchers continue to look for the optimal treatments that will both control symptoms and prevent relapse.

Drugs Used for Crohn's Disease. Drug therapies for Crohn’s disease aim to resolve symptoms (induce remission) and prevent flare-ups (maintain remission). The drugs used depend on the severity of the condition:

Mild-to-moderate Crohn's disease is generally treated with antibiotics and an oral aminosalicylate, such as mesalamine or sulfasalazine. (Some researchers suggest, however, that corticosteroids may be more effective than these drugs in patients with disease in the small intestine and ascending colon. Furthermore, new forms of oral corticosteroids, such as budesonide, may have a lower risk for adverse effects.)

Moderate-to-severe Crohn's disease is treated with corticosteroids, immunosuppressants, or biologic drugs such as infliximab or adalimumab. These drugs may be used alone or in combinations. Some patients with severe Crohn's may be candidates for surgery.

Determining Success. Therapy is considered successful if it can push the disease into remission (and keep it there) without causing significant side effects. The patient's condition is generally considered in remission when the intestinal lining has healed, and symptoms, such as diarrhea, abdominal cramps, and tenesmus (painful defecation), are normal or close to normal. It is sometimes difficult to define remission in Crohn's disease because diagnostic test results do not always correlate with a patient's symptoms or complications outside the intestine.

Aminosalicylates contain the compound 5-aminosalicylic acid, or 5-ASA, which helps reduce inflammation. These drugs are used to prevent relapses and maintain remission in mild-to-moderate Crohn’s disease.

The standard aminosalicylate drug is sulfazine (Azulfidine). This drug combines the 5-ASA drug mesalamine with sulfapyridine, a sulfa antibiotic. While sulfazine is cheap and effective, the sulfa component of the drug can cause unpleasant side effects, including headache, nausea, and rash.

Patients who cannot tolerate sulfazine, or who are allergic to sulfa drugs, have other options for aminosalicylate drugs, including mesalamine (Asacol, Pentasa), olsalazine (Dipentum), and balsalazide (Colazal). These drugs, like sulfazine, are available as pills. Mesalamine is also available in enema (Rowasa) and suppository (Canasa) forms.

Mesalamine can cause kidney problems and should be used with caution by patients with kidney disease. Common side effects of aminosalicylate drugs include:

Abdominal pain and cramps (mesalamine, balsalazide)
Diarrhea (mesalamine, olsalazine)· Gas (mesalamine)
Nausea (mesalamine)
Hair loss (mesalamine)
Headache (mesalamine, balsalazide)
Dizziness (mesalamine)

All mesalamine preparations, including sulfasalazine, appear to be safe for children, and for women who are pregnant or nursing.

General Guidelines. Corticosteroids (commonly called steroids) are powerful anti-inflammatory drugs used for treating Crohn's disease in adults. Because of their severe side effects, steroids should be reserved for those with moderate-to-severe disease or those who relapse after other therapies. Steroids appear to be safe for pregnant women and can be used if necessary during pregnancy.

Corticosteroids are frequently combined with other drugs, such as 5-aminosalicylic acid (or 5-ASA) drugs, to produce more rapid symptom relief and to allow quicker withdrawal, although such combinations do not improve remission time.

In general, corticosteroids are recommended only for short-term use for achieving remission in active Crohn's disease. The lowest possible dose should be used for the shortest amount of time. Long-term treatments cause significant side effects, and alternative drugs exist. Corticosteroids do not prevent flare-ups and are rarely used for maintenance treatment.

Patients who are malnourished are less likely to respond to steroids, and those who had an initial inadequate response to steroids are also less likely to do well with repeat therapy. Some patients who have had Crohn's disease for a long time may have partial or complete resistance to corticosteroids.

Corticosteroid Types. Prednisone (Deltasone), methylprednisolone (Medrol), and hydrocortisone (Cortef, Cortisol) are the most common corticosteroids. Newer steroids, such as budesonide (Entocort), affect only local areas in the intestine and do not circulate throughout the body. Such drugs may avoid the widespread side effects that are a serious problem with long-term treatment using older conventional steroids. Recent studies suggest that budesonide can help prolong and maintain remission periods in patients with Crohn’s disease.

Administering Corticosteroids. Most corticosteroids can be taken as a pill. For patients who cannot take oral forms, methylprednisolone and hydrocortisone may also be given intravenously or rectally as a suppository, enema, or foam. The severity or location of the condition often determines the form.

Side Effects of Corticosteroids. Standard steroids can have distressing and sometimes serious long-term side effects, including:

Susceptibility to infection
Weight gain (particularly increased fatty tissue on the face and upper trunk and back)
Acne
Excess hair growth
High blood pressure (hypertension)
Weakened bones (osteoporosis)
Cataracts and glaucoma
Diabetes
Muscle wasting
Menstrual irregularities
Upper gastrointestinal ulcers
Personality change, including irritability, insomnia, psychosis, and depression; such emotional changes are sometimes severe enough to produce suicidal thoughts

Withdrawing from Corticosteroids. Once the intestinal inflammation has subsided, steroids must be withdrawn very gradually in order to give the body time to recover its own ability to produce natural steroids. Withdrawal symptoms, including fever, malaise, and joint pain, may occur if the dosage is lowered too rapidly. If this happens, the dosage is increased slightly and maintained until symptoms are gone. More gradual withdrawal is then resumed.

For very active inflammatory bowel disease that does not respond to standard treatments, immunosuppressant drugs are used for long-term therapy. Such drugs suppress or limit actions of the immune system and therefore its inflammatory response, which causes Crohn's disease. Immunosuppressants may help maintain remission in Crohn's disease and heal fistulas and intestinal ulcers caused by this disease. These drugs are sometimes combined with a corticosteroid drug for treating active disease flares.

Azathioprine (Imuran, Azasan) and 6-mercaptopurine (6-MP, Purinethol) are the standard oral immunosuppressant drugs. However, it can take 3 - 6 months for these drugs to have an effect. To speed up the response, they are sometimes prescribed along with a corticosteroid drug. Lower steroid doses are then needed, resulting in fewer side effects. Corticosteroids may also be withdrawn more quickly. For this reason, immunosuppressants are sometimes referred to as steroid-sparing drugs.

Other pill forms of immunosuppressants include cyclosporine A (Sandimmune, Neoral) and tracrolimus (Prograf). These drugs are quicker-acting than azathiopine and 6-mercaptopurine. Cyclosporine A generally takes 1 - 2 weeks to take effect. For patients who have Crohn’s disease accompanied by fistulas, Cyclosporine A may be given intravenously. For patients whose condition affects the mouth or area around the anus, tracrolimus is available as a topical ointment.

Methotrexate (MTX, Rheumatrex, Mexate) is another fast-acting type of immunosuppressant. It is given by weekly injections and may be an option for patients with severe Crohn’s disease who have not been helped by other immunosuppressant drugs. However, methotrexate can cause miscarriages and birth defects. Because of these pregnancy complications, both men and women who take methotrexate should use birth control.

General side effects of immunosuppressants may include nausea, vomiting, and liver or pancreatic inflammation. Patients should receive frequent blood tests to monitor bone marrow, liver, and kidneys. Patients who take cyclosporine A or tacrolimus need to have their blood pressure and kidney function checked regularly.

Antibiotics are often used to induce remission in mild-to-moderate Crohn's disease. They are also important for treating fistulas, bacterial overgrowth, abdominal abscesses, and any infections around the anus and genital areas. Stopping antibiotics brings on relapse, so long-term therapy is required, carrying a risk for side effects.

The standard antibiotics used for inducing remission in Crohn's disease are ciprofloxacin (Cipro) and metronidazole (Flagyl). Ciprofloxacin is the antibiotic of choice. Over time, metronidazole can cause peripheral neuropathy, a nerve disorder that can cause numbness and tingling in the hands and feet. Other side effects associated with netronidazole include nausea, vomiting, diarrhea, loss of appetite, dizziness, and headaches.

Although ciprofloxacin causes fewer side effects than metrondizaole, it can interact with antacids (Rolaids, Tums) and vitamin and mineral supplements that contain calcium, iron, or zinc. Do not take antacids or vitamin supplements at the same time as the ciprofloxacin dose.

Biologic response modifiers are genetically engineered drugs that target specific proteins involved with the body’s inflammatory response. Of special interest for patients with Crohn's disease are drugs such as infliximab and adalimumab, which target the inflammatory immune factor known as tumor necrosis factor (TNF).

According to a 2007 consensus statement from the American Gastroenterological Association, biologic drugs are generally not used as first-line treatment for most patients with Crohn’s disease. However, some patients -- especially those who have not responded to corticosteroids or who suffer from fistulas -- may benefit from initial treatment with infliximab or other biologic drugs. In all cases, the benefits of biologic drugs need to be weighed against their potential risks, which can include increased risk for infections, lymphoma, and drug-related side effects.

Infliximab (Remicade) acts against TNF and was the first biologic drug approved for treating adults with Crohn's disease. It is made from a genetically designed antibody called a monoclonal antibody (MAb) that blocks the activity of tumor necrosis factor-alpha (TNF-a). In 2006, the FDA approved infliximab for children with active Crohn’s disease.

Infliximab cannot cure Crohn’s disease, but it can help control symptoms and, possibly, keep the disease in remission. Studies suggest that up to 80% of patients respond initially, and about a third of all patients remain in remission after a single infusion. Remissions last a few weeks to several months. A 6-week course of infliximab helps close and heal fistulas in half of patients and reduces drainage in 70%. The drug is also being studied for maintenance therapy, although given some significant side effects, it will most likely be reserved for active disease that does not respond to other treatments.

Infliximab’s severe side effects may include tuberculosis, pneumonia, and other infections; lymphoma (a type of cancer); liver failure; and aplastic anemia.

Adalimumab (Humira) was approved early in 2007 for treating adult patients with moderate-to-severe Crohn's disease. Like infliximab, adalimumab blocks TNF. Also approved for treating symptoms of rheumatoid arthritis, adalimumab requires injections to initiate treatment, followed by a maintenance shot every other week.

Adalimumab's label includes a boxed warning. The medicine has been associated with serious, sometimes fatal, infections, including tuberculosis and sepsis. Other severe side effects may include lymphoma, upper respiratory infections, sinusitis, and nausea.

Several other TNF modifiers are being investigated. Among the most promising, according to several 2007 studies in the New England Journal of Medicine, is certolizumab (Cimzia).

Selective adhesion molecule inhibitors block the genetic expression of cell adhesion molecules (CAMs). CAMs play an important role in the accumulation of immune factors that cause the inflammatory response. Natalizumab (Tysabri) is a monoclonal antibody that blocks alpha4 integrin, a protein that binds to CAMs. This drug is approved to treat multiple sclerosis and is also being studied for Crohn’s disease. Studies have suggested that natalizumab can help patients with Crohn’s disease achieve and maintain remission.

However, natalizumab is associated with severe side effects, including a rare neurological condition called progressive multifocal leukoencephalopathy (PML). A 2006 study found that patients who take natalizumab have a very low risk for PML. Still, the potential benefits of natalizumab need to be weighed against its risks for serious side effects. As of summer 2007, the FDA was considering approving natalizumab for treatment of moderate-to-severe Crohn’s disease in patients who have failed or cannot tolerate other therapies

Other Biologic Therapies. Investigators are researching other biologic therapies that target other types of immune factors that play a role in the inflammatory response. These factors include interferons, anti-interferon antibodies, anti-interleukin antibodies, p65 anti-sense oligonucleotides, growth factors, and others. Several 2006 studies indicated that fontolizumab (HuZaf), an anti-interferon gamma monoclonal antibody, shows promise as a treatment for Crohn’s disease. Sargramostim (Leukine), a granulocyte-macrophage colony stimulating factor, is another biologic drug that may help improve symptoms and quality of life for patients with active Crohn’s disease. Visilizumab (Nuvion), which targets the CD3 receptor on T cells, is another biologic drug being investigated. More research in each of these areas is needed.

Parasites. Inflammatory bowel disease is rare in countries where intestinal infection with parasites called helminthes is common. Small studies have reported significant remission rates in patients with Crohn's disease or ulcerative colitis who have swallowed the eggs of a specific parasitic worm. The parasite does not invade tissue or spread other diseases. The parasite induces production of specific T cells, called TH-2, which are immune factors that may be protective against overactivity of cytokines that trigger Crohn's. More research is needed.

Growth Factors. Growth factor hormones increase immune factors, so one would think they might be harmful for patients with Crohn's disease. However, some research suggests that growth factors may be helpful for speeding healing in certain patients, including children. More research, however, is needed.

Surgery

Between two-thirds to three-quarters of patients with Crohn's eventually need surgery when medication cannot control symptoms. Among children with Crohn's, half require surgery within 5 years of diagnosis.

In general, surgery is used to remove damaged areas of the colon:

The entire colon (proctocolectomy) or a section of it (subtotal colectomy) may need to be removed in cases of extensive disease in the large intestine.
Resection or strictureplasty, which removes limited sections of the colon, may be appropriate for many patients.

Surgery is useful only for reducing symptoms. It cannot cure Crohn's disease because new disease can appear in other areas of the intestine. Surgery may be helpful for relieving symptoms and to correct blockage, perforation, fistulas, or bleeding.

Surgery has reportedly improved the quality of life in most patients, except for those who continued to have active disease. Many children with Crohn's who have suffered growth problems catch up to near-normal growth levels after surgery. Some experts urge, in fact, that many patients should consider surgery in the early stages of the disease.

Some patients may be candidates for a procedure called strictureplasty, which involves cutting and stitching only the areas obstructing the intestine, so that it widens the intestine without removing sections of it. It involves the following:

A balloon attached to a catheter (a thin tube) is passed along the intestine.
If it becomes blocked, then a stricture (an obstruction) is indicated.
The surgeon widens the intestine at the point, but does not remove sections of it.
The procedure is by no means foolproof. Nearly half of patients require re-operation, but strictureplasty in the jejunum and ileum of the small intestine is safe and generally effective over the long term. It may not be useful for Crohn's disease in duodenum (the first section of the small intestine).

The invasiveness of the surgical procedure to remove damaged portions of the colon depends on the severity of the disease.

Resection of the Colon. In most cases of Crohn's disease, only a part of the colon needs to be removed, a procedure called resection.

Click the icon to see an illustrated series depicting large bowel resection surgery.

Subtotal Colectomy. Subtotal colectomy is more extensive than resection and removes more of the colon. Disease in the upper parts of the small intestine tends to require more extensive surgery than in the lower small intestine.

In general, either procedure requires a general anesthetic and involves the following:

An incision is made in the abdomen.
The diseased portion of the colon is identified and removed. (Strictureplasty is sometimes used alone with resection.)
Once a diseased segment of the colon is removed, the two ends are reconnected, and this connection is called an anastomosis.

Open Surgery or Laparoscopy. Resection or subtotal colectomy may be performed using one of two surgical approaches:

Open surgery, which requires a wide abdominal incision.
Laparoscopy, which uses a few small incisions through which a tube is inserted containing a tiny camera for viewing the area. To date, however, this procedure is best suited for patients with short-segment disease in the ileum who also have no other complications, such as fistulas and abscesses.

Click the icon to see an image of a laparoscopy procedure.

Short-bowel syndrome. If large segments of the small intestine are removed, the patient is at higher risk for short-bowel syndrome, a complication in which there is a problem absorbing nutrients. The risk is far lower with strictureplasty. The condition used to be fatal, but patients now can live normal and productive lives using total parenteral nutrition (the intravenous administration of nutrients), which can be self-administered at home in many cases.
Leakage or obstruction in the areas where the colon has been reconnected (the anastomosis).
Infections. In a 2003 study, the use of drugs that modify the immune system (azathioprine, 6-MP, methotrexate, and infliximab) was effective in reducing the risk for serious infection in the abdomen.

Proctocolectomy with ileostomy is removal of the entire colon and creation of an ileostomy. It involves the following:

To perform proctocolectomy, the surgeon removes the entire colon, including the lower part of the rectum and the sphincter muscles that control bowel movements.
To perform ileostomy, the surgeon makes a small opening in the lower right corner of the abdomen called a stoma. The surgeon then connects cut ends of the small intestine to this opening. A bag is placed over the opening and accumulates waste matter. It requires emptying several times a day.

Recurrence of Crohn's disease is very common after any procedure. The risk may be 7 - 25% for each year after resection, with an average risk of 50% at 5 years after resection. (Even if the entire colon is removed, there is still a high chance of recurrence in the rectum and a somewhat lower risk for recurrence in the small intestine.)

Patients at highest risk for recurrence include:

Smokers
Those whose disease occurred in the ileum (the lowest part of the small intestine) and colon
Those with abscesses or fistulas
Those have had previous surgeries

Various drugs are used to prevent recurrence. They include the antibiotic metronidazole (Flagyl), mesalamine, infliximab, and mercaptopurine. These drugs can have severe side effects. And, it is not clear if these or any other drugs are effective in preventing recurrence. Even if medications can help prevent recurrence in some patients, it is not yet known how to identify this subset of patients. (In any case, steroids do not appear to help prevent recurrence.)

In some cases, surgery is needed for emergency conditions that can occur with Crohn's disease. Emergency surgery is used to:

Stop severe intestinal bleeding
Clear small bowel obstruction
Drain and heal abscesses or fistulas
Repair perforation

Procedures for transplanting the small intestine in patients with intestinal failure are under investigation. These are still experimental and are being tested in patients who have lost so much of their small intestine that they must rely on total parenteral nutrition (intravenous administration of nutrition). Small-bowel transplantation is a more difficult procedure than some other transplants, because of the high rate of potential complications, including infection and organ rejection. Patients who have transplants must take immunosuppressant drugs for the rest of their lives. Furthermore, there is some evidence that Crohn's disease recurs in the transplanted bowel.

Resources

www.ccfa.org -- Crohn's & Colitis Foundation of America
www.gastro.org -- American Gastroenterological Association
www.acg.gi.org -- American College of Gastroenterology
www2.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse

References

Baldassano RN, Bradfield JP, Monos DS, Kim CE, Glessner JT, Casalunovo T, et al. Association of the T300A non-synonymous variant of the ATG16L1 gene with susceptibility to paediatric Crohn's disease. Gut. 2007 Aug;56(:1171-1173.

Baldassano RN, Bradfield JP, Monos DS, Kim CE, Glessner JT, Casalunovo T, et al. Association of variants of the interleukin-23 receptor gene with susceptibility to pediatric Crohn's disease. Clin Gastroenterol Hepatol. 2007 Jul 5; [Epub ahead of print]

Clark M, Colombel JF, Feagan BC, Fedorak RN, Hanauer SB, Kamm MA, et al. American gastroenterological association consensus development conference on the use of biologics in the treatment of inflammatory bowel disease, June 21-23,2006. Gastroenterology. 2007 Jul;133(1):312-39.

Cornish J, Tan E, Teare J, Teoh TG, Rai R, Clark SK, et al. A meta-analysis on the influence of inflammatory bowel disease on pregnancy. Gut. 2007 Jun;56(6):830-7. Epub 2006 Dec 21.

Cummings JR, Cooney R, Pathan S, Anderson CA, Barrett JC, Beckly J, et al. Confirmation of the role of ATG16l1 as a Crohn's disease susceptibility gene. Inflamm Bowel Dis. 2007 Aug;13(:941-6.

Dotan I, Fishman S, Dgani Y, Schwartz M, Karban A, Lerner A, et al. Antibodies against laminaribioside and chitobioside are novel serologic markers in Crohn's disease. Gastroenterology. 2006 Aug;131(2):366-78.

Dubinsky MC, Wang D, Picornell Y, Wrobel I, Katzir L, Quiros A, et al. IL-23 receptor (IL-23R) gene protects against pediatric Crohn's disease. Inflamm Bowel Dis. 2007 May;13(5):511-5.

Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006 Dec 1;314(5804):1461-3. Epub 2006 Oct 26.

Issa M, Vijayapal A, Graham MB, Beaulieu DB, Otterson MF, Lundeen S, et al. Impact of Clostridium difficile on inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007 Mar;5(3):345-51.

Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet. 2007 May;39(5):596-604. Epub 2007 Apr 15.

Rodemann JF, Dubberke ER, Reske KA, Seo da H, Stone CD. Incidence of Clostridium difficile infection in inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007 Mar;5(3):339-44.

Sandborn WJ, Feagan BG, Stoinov S, Honiball PJ, Rutgeerts P, Mason D, et al. Certolizumab pegol for the treatment of Crohn's disease. N Engl J Med. 2007 Jul 19;357(3):228-238.

Schreiber S, Khaliq-Kareemi M, Lawrance IC, Thomsen OO, Hanauer SB, McColm J, et al. Maintenance therapy with certolizumab pegol for Crohn's disease. N Engl J Med. 2007 Jul 19;357(3):239-250.

Tremaine WJ. Inflammatory bowel disease and Clostridium difficile-associated diarrhea: a growing problem. Clin Gastroenterol Hepatol. 2007 Mar;5(3):310-1.

Tremelling M, Cummings F, Fisher SA, Mansfield J, Gwilliam R, Keniry A, et al. IL23R variation determines susceptibility but not disease phenotype in inflammatory bowel disease. Gastroenterology. 2007 May;132(5):1657-64. Epub 2007 Feb 24.

Review Date:
8/30/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Cervical cancer

FitSugar — Wed, 08 Oct 2008 17:34:57 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Prognosis
Symptoms
Prevention
Diagnosis
Treatment for Cervical Intr...
Treatment for Cervical Canc...
Treatment for Invasive Cerv...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Human Papilloma Virus (HPV) Prevalence

About 25% of women age 14 - 59 are infected with the human papilloma virus (HPV), indicates a 2007 study in the Journal of the American Medical Association (JAMA). HPV prevalence is highest (45%) among women age 20 - 24. HPV is the main cause of cervical cancer.

Immunization Guidelines

In 2006, the FDA approved the first vaccine to prevent cervical cancer. Gardasil protects against human papilloma virus (HPV) 16 and 18, the strains most likely to cause cervical cancer, and HPV 6 and 11, the strains most likely to cause genital warts. In 2007, several expert groups released immunization guidelines for the cervical cancer vaccine. Guidelines from the U.S. Centers for Disease Control’s Advisory Committee on Immunization Practices recommend:

Routine vaccination for girls age 11 - 12 with a vaccine series of 3 doses. Girls as young as 9 years old may be vaccinated at their doctors’ discretion.
Catch-up vaccination for girls and women age 13 - 26 who have not been previously vaccinated or who have missed doses.

Vaccine Effectiveness

The vaccine prevents human papilloma virus (HPV) infection caused by four HPV strains but cannot treat pre-existing HPV infection, confirms a 2007 JAMA study
The vaccine is nearly 100% effective in preventing cervical cancer and genital warts when it is administered before females become sexually active, indicate several 2007 studies.

HPV and Throat Cancer

Human papilloma virus (HPV) 16 increases the risk of oropharyngeal cancers of the throat, tonsils, and back of the tongue, according to several 2007 studies. HPV can be transmitted during oral sex, causing infection in the mouth. (However, not all people who engage in oral sex or who have oral HPV infection will develop throat cancer. The virus usually goes away on its own.) Previously, alcohol and tobacco use were considered the main risk factors for oropharyngeal cancer.

Introduction

The cervix is the lower third portion of the uterus (womb). It serves as a neck to connect the uterus to the vagina. The opening of the cervix, called the os, remains small and narrow, except during childbirth when it widens to allow a baby to pass from the uterus into the vagina.

Cervical cancer develops in the thin layer of cells called the epithelium, which cover the cervix. Cells found in the this tissue have different shapes:

Squamous cells (flat and scaly). Most cervical cancer arises from changes in the squamous cells of the epithelium (squamous cell carcinoma).
Columnar cells (column-like). These cells line the cervical glands and cancers here are known as adenocarcinomas.
In rare cases, cancer can occur in cells that form the supportive tissue around the cervix (the stroma).

Cervical cancer usually begins slowly with precancerous abnormalities, and even if cancer develops, it generally progresses very gradually. Cervical cancer is the most preventable type of cancer and is very treatable in its early stages. Regular Pap tests and human papilloma virus (HPV) screening can help detect this disease early.

Dysplasia. Dysplasia is a term that refers to a precancerous condition. It may become cancerous, but not always. In the case of cervical cancer, dysplasia indicates that the layer of cells that covers the cervix (squamous epithelial cells) are abnormal in size and shape and are beginning to grow.

Cervical Intraepithelial Neoplasia. Dysplastic changes seen on a Pap smear may indicate the presence of cervical intraepithelial neoplasia (CIN). This means precancerous changes are found within the lining of the cervix. The changes are categorized according to severity: CIN I, CIN II, and CIN III.

With CIN I, there are mild abnormalities that rarely develop into cervical cancer. This condition may progress if untreated but often goes away without treatment.
In CIN II, the lesions often appear more aggressive under the microscope and may turn into cancer unless treated.
CIN III is the most aggressive form of dysplasia. If not removed, there is a high chance that it will turn into invasive cancer. CIN III includes carcinoma in situ (CIS). CIS is an early stage of non-invasive cancer -- the cells are confined within the tissue where they grew and have not yet invaded surrounding tissue. However since CIS can progress to invasive cancer, this condition should be treated as soon as possible.

Click the icon to see an image of cervical dysplasia.

The cells of the epithelium rest on a very thin layer called the basement membrane. Invasive cervical cancer occurs when cancer cells in the epithelium cross this membrane and invade the stroma, the underlying supportive tissue of the cervix.

In later stages, the original cancer may spread to areas surrounding the uterus and cervix or near organs such as the bladder or rectum. It may also spread to distant sites in the body through the bloodstream or the lymph nodes.

Causes

The human papillomavirus (HPV) has been detected in virtually all invasive cervical cancers and has been confirmed as the major cause of this cancer.

How HPV Is Transmitted. HPV is spread primarily by having sex with an infected partner. Most sexually active young women become infected with this virus, but only 10% remain infected for more than 5 years. Only those infected for longer than 5 years have a higher risk (about 50% above normal). Other factors are then needed to trigger the disease.

How HPV Contributes to Cervical Cancer. Researchers believe that most cervical cancers develop when various aggressive genetic HPV strains activate certain oncogenes (cancer-causing genes). Oncogenes called E6 and E7 are particularly important because they interfere with certain protective proteins, such as p53 and pRb, respectively. Under normal conditions, these proteins limit cell growth. Once they are blocked, cell growth can run rampant, leading to tumor development and cancer.

HPV Genetic Types. More than 30 genetic variants of human papillomaviruses can be passed through sexual contact form one person to another. The severity, however, varies widely according to genetic type. (Women initially infected by one type of HPV are still at risk for infection from other types.)

In women with cervical intraepithelial neoplasia I , the HPV viruses that are present are often types 6 and 11, which are low risk. Other low-risk HPV genetic types are 40, 42, 43, 44, 54, 61, 70, 72, and 81. These viral types often produce genital warts (condylomata) that rarely lead to cancer. (These warts usually affect the woman's genitals, the vagina, and vulva, rather than the cervix.)

Of the high-risk types, HPV types 16 and 18 have long been known to be particularly dangerous. These two genetic types and six others (31, 33, 35, 45, 52, and 58) account for 95% of HPV-related cervical cancers. Other high-risk types are 39, 51, 56, 59, 68, 73, and 82. All are associated with moderate cervical intraepithelial neoplasia II and cervical intraepithelial neoplasia III. Types 26, 53, and 66 are also considered high-risk.

In 2007, several studies indicated that HPV-16 infection in the mouth is associated with increased risk for oropharyngeal cancer. (Oropharyngeal cancer develops in the throat, just behind the mouth. It includes the base of the tongue, soft palate, tonsils, and side and back walls of the throat.) Prior to this research, alcohol and tobacco were thought to be the main risk factors for this type of cancer. According to the studies, oral sex (both fellatio and cunnilingus) significantly increases the risk of HPV-16 transmission and, therefore, the risk of developing oropharyngeal cancer. While the risk of HPV-16 causing oropharyngeal cancer is lower than the risk of it causing cervical cancer, experts think that the HPV vaccine may help reduce the incidence of throat, tonsil, and tongue cancers, as well as cervical cancer.

High-risk types of HPV have also been associated with an increased risk for other cancers, including other genital and lung cancers. The high-risk viruses generally produce flat and nearly invisible growths, compared to the usually harmless warts caused by low-risk HPV viruses.

Herpes viruses. Certain herpes viruses, including herpes simplex virus 6, 2, 7, and cytomegalovirus, have been detected in women with cervical cancer. herpes simplex virus 6 is under particular suspicion for playing a role in activating the papilloma virus gene. The presence of these very common viruses, however, may simply be coincidental, and they may serve no purpose other than being bystanders.

Chlamydia Trachomatis. Studies are finding an especially strong association between the incidence of Chlamydiatrachomatis, a sexually transmitted infection, and HPV. (Chlamydia trachomatis should not be confused with Chlamydia pneumoniae, a common cause of mild pneumonia in young adults. Chlamydia pneumonia e is not associated with cervical cancer.)

Other Sexually Transmitted Diseases. Other sexually transmitted diseases that have been associated with cervical cancer include HIV and gonorrhea. These infections, however, also may only be markers of increased sexual activity and may not themselves cause cancer.

Risk Factors

According to the American Cancer Society, about 11,150 new cases of invasive cervical cancer will be diagnosed in the U.S. in 2007. However, the number of new cervical cancer cases has been declining steadily over the past decades. Fifty percent of cervical cancer diagnoses occur in women ages 35 - 55, and slightly more than 20% occur in women over 65 years of age.

Some women (15%) develop cervical cancer before the age of 30. Although cervical cancer is rare in women under age 20, cancer rates in younger women are on the rise. Many young women are infected with multiple types of human papillomavirus, which can increase their risk of getting cervical cancer. Young women with early abnormal changes who do not have regular examinations are at high risk for localized cancer by the time they are age 40, and for invasive cancer by age 50.

Although it is the most preventable type of cancer, cervical cancer is ranked as the second most common cause of female death. Each year it kills an estimated 3,700 women in the U.S. and nearly 300,000 women worldwide.

In the United States, cervical cancer mortality rates plunged by 74% from 1955 - 1992 thanks to increased screening and early detection with the Pap test.

Although the rate of cervical cancer has declined in both Caucasian and African-American women over the past decades, it remains much more prevalent in African-Americans -- whose death rates are twice as high as Caucasian women. Hispanic American women have more than twice the risk of invasive cervical cancer as Caucasian women, also due to a lower rate of screening.

These differences, however, are almost certainly due to social and economic differences. Numerous studies report that high poverty levels are linked with low screening rates. In addition, lack of health insurance, limited transportation, and language difficulties hinder a poor woman’s access to screening services. Researchers are investigating programs that provide screening and treatment for women with abnormal Pap smears in a single visit.

The human papilloma virus (HPV) is the primary cause of cervical cancer. According to a 2007 study in the Journal of the American Medical Association, about 1 in 4 U.S. females ages 14 - 59 are infected with HPV. The prevalence of HPV is highest (45%) in women age 20 - 24.

The risk for cervical cancer in infected women appears to be highest in those infected with HPV for more than 6 months. In most people, the virus goes away within a year. However, it persists in about 10% of infected women.

High Sexual Activity. In adults, the most important risk factor for HPV is sexual activity with an infected person. Women most at risk for cervical cancer are those with a history of multiple sexual partners, sexual intercourse at 17 years or younger, or both. A woman who has never been sexually active has a very low risk for developing cervical cancer. Sexual activity with multiple partners increases the likelihood of many infections in addition to human papilloma virus.

Douching. Women who douche on a weekly basis are more likely to contract cervical cancer than those who do not. Douching may destroy the natural antiviral substances normally present in the vagina, making women more susceptible to HPV.

Pessaries. Use of a pessary (a ring-shaped plastic device that keeps the vagina and uterus from collapsing) increases the risk of chronic inflammation and viral infection at the insertion site and therefore may increase the risk for cervical cancer.

Risk Factors for HPV in Children and Infants. HPV also can occur in children and even newborns. The virus may also be transmitted by an infected mother. In children, HPV is usually the harmless form that cause skin warts.

In one analysis, 15 - 20% of women with cervical cancer had at least one close relative with the disease. Two studies have also reported that in families with cervical cancer there have also been higher rates of other human papilloma virus-related and smoking-associated cancers. Inherited factors in such cases most likely cause changes in the immune system that make such people more susceptible to human papilloma virus or other viruses.

Several studies, including a major analysis, have reported a strong association between cervical cancer and long-term use of oral contraception (OC). Women who have taken OCs for more than 10 years have a much higher risk of human papilloma virus (HPV) infection (up to four times higher) than those who do not use OCs. (Women taking OCs for fewer than 5 years have no significantly higher risk.) The reasons for this risk from OC use are not entirely clear. Women who use OCs may be less likely to use a diaphragm, condoms, or other methods that offer some protection against sexual transmitted diseases, including HPV. Some researchers also suggest that the hormones in OCs might help the virus enter the genetic material of cervical cells.

Studies indicate that having many children increases the risk for developing cervical cancer, particularly in women with human papilloma virus.

Smoking is associated with a higher risk for precancerous changes (dysplasia) in the cervix and for progression to invasive cervical cancer. Smoking may cause human papilloma virus (HPV) to grow faster and increase its likelihood of causing cancer. According to a 2006 study, women smokers who have HPV-16 are 14 times more likely to develop cervical pre-invasive cancer than smokers who do not have the virus. By contrast, non-smokers with HPV-16 were only 6 times more likely to develop cancer than those who were not infected.

Secondhand smoke is also linked to increased risk for cervical cancer tumors. It is not clear if this association is due to cigarette smoke’s direct cancer-causing effects or general damage to the immune system. Cigarette smokers are also deficient in folate, a B vitamin. Folate deficiency may play a role in the development of dysplasia.

Diethylstilbestrol. From 1938 - 1971, diethylstilbestrol, an estrogen-related drug, was widely prescribed to pregnant women to help prevent miscarriages. The daughters of these women face a higher risk for cervical cancer, genital tract abnormalities, and miscarriage.

Environmental Chemicals. Long-term exposure to certain types of agricultural and industrial chemicals may increase the risk for cervical cancer.

Prognosis

The following are some examples of the time it takes for early stages of cervical dysplasia to progress to the next stage:

Only about 1% of untreated mild cervical dysplasia (CIN I) cases progress to severe dysplasia or cancer each year.
In women with untreated moderate dysplasia (CIN II), 16% will progress to the next stage in 2 years, while 25% will progress after 5 years.
Most untreated pre-invasive cancer will develop into invasive cancer over a period of 10 - 12 years.

Over the past 30 years, the death rate from cervical cancer has declined significantly. In general, 71% of women with invasive cervical cancer survive for 5 years or more. African-American women tend to have poorer 5-year survival rates than Caucasian women, although survival rates have significantly increased in African-American women in recent years.

The outlook for specific women varies depending on different factors:

In women who receive treatment when cervical cancer is still local, the cure rate is about 90%. Experts say universal screening could essentially reduce the cervical cancer death rate to zero. Still, only 12 - 15% of women have routine Pap smears. As a result, only 55% of Caucasian women and 44% of African-American women are diagnosed at early stages.
If the cancer cells have spread beyond the cervix, the average 5-year survival rates may drop to 50% and below, depending on how much it has spread and the type of cancer cell.

Identifying what type of human papilloma virus (HPV) a woman has may help determine outlook and the severity of cervical cancer. For example, HPV-18 and HPV-16 are associated with severe cases. HPV-16 has also been linked to a rare form of cervical and uterine cancers.

Other biochemical markers in the body may also help predict outcome and treatment. For example, women with cervical cancer who have high levels of an enzyme called cyclooxygenase (COX-2) may need more aggressive treatments than those with low levels.

The treatments for advanced cervical cancer also add to the emotional burden in premenopausal women, because they nearly always prevent future childbearing.

Symptoms

Most women with dysplasia or pre-invasive cancer have no symptoms. Screening tests, therefore, are very important.

When the cancer becomes invasive, unusual bleeding can occur. Bleeding may stop and start again between regular periods or there may be bleeding after menopause. Unexpected bleeding can also occur after intercourse or a pelvic exam. Periods sometimes last longer or are heavier than usual. Increased vaginal discharge may be noticeable as well. Pelvic pain can occur, but it is not common.

These symptoms are not exclusive to cervical cancer. Sexually transmitted diseases, for instance, can cause similar symptoms.

Prevention

The best way to prevent cervical cancer is to avoid getting infected with human papilloma virus (HPV). Because HPV is sexually transmitted, practicing safe sex and limiting the number of sexual partners can help reduce risk. A vaccine can protect against the major cancer-causing HPV strains. Regular Pap tests remain the most effective way of preventing the development of invasive cervical cancer.

In 2006, the FDA approved the first human papilloma virus (HPV) vaccine to prevent cervical cancer. Gardasil has been tested in more than 12,000 uninfected girls and women in 13 countries. Studies show it provides nearly 100% protection against HPV-16 and HPV-18, the viruses that cause 70% of cases of cervical cancer. Gardasil also protects against HPV-6 and HPV-11, which cause 90% of cases of genital warts.

Gardasil is approved for girls and women ages 9 - 26. Current immunization guidelines recommend:

Routine vaccination for girls ages 11 - 12 years. The vaccine should be administered in 3 doses, with the second and third doses administered 2 and 6 months after the first dose. The HPV vaccine can be given at the same time as other vaccines.
Girls as young as age 9 can receive the vaccine at their doctors’ discretion.
Girls and women ages 13 - 26 who have not been previously immunized or who have not completed the full vaccine series should get vaccinated to catch up on missed doses. [The U.S. Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) recommend catch-up doses for ages 13 - 26. The American Cancer Society (ACS) recommends catch-up for ages 13 - 18. The ACS suggests that women ages 19 - 26 discuss with their doctors the relative risks and benefits of vaccination.]
Women should not get the vaccine during pregnancy.

The HPV vaccine can only prevent -- not treat -- HPV infection, genital warts, and cervical cancer. Because the vaccine cannot protect females who are already infected with HPV, doctors recommend that girls get vaccinated before they become sexually active. Several 2007 studies indicated that the vaccine is nearly 100% effective in preventing cervical cancer and genital warts when given prior to HPV exposure. However, young women who are sexually active may still derive some benefit from the vaccine, at least for protection against any of the four HPV strains that they have not yet acquired.

The FDA is considering approving another type of cervical cancer vaccine (Cervarix). Cervarix protects against HPV-16 and HPV-18, as well as the cancer-causing strains HPV-31 and HPV-45. It does not protect against genital warts.

The FDA is not yet sure how long Gardasil’s protection lasts or when patients may need a booster shot. A 2006 study of the Cervarix vaccine found that protection lasted for at least 4.5 years.

These vaccines do not protect against all types of cancer-causing HPV. The FDA still recommends that women receive annual screening to detect any early signs of cervical cancer. For girls and women who have been sexually active before they receive the vaccine, screening still provides the best protection against cervical cancer.

Use of barrier contraceptives such as condoms is associated with a reduced risk of cervical cancer, even in women already infected with human papilloma virus (HPV). HPV can exist outside the area protected by the male condom, so this method is not foolproof in preventing an initial infection. However, a 2006 New England Journal of Medicine study found that when men used condoms every time they had sexual intercourse, their female partners had less than half the rate of HPV infection as women whose partners used condoms less than 5% of the time. The female condom is becoming increasingly popular in developing countries. It may prove to be particularly effective against sexually transmitted diseases in these regions.

A 2002 study reported that men who are circumcised have a lower risk for carrying human papilloma virus (HPV) and therefore reduce the risk for cervical cancer in their female partners.

Some studies have suggested possible protective benefits against cervical cancer from certain vitamins.

High blood levels of vitamins E and C have been linked with lower rates of some cancers, including cervical cancers.

Although vitamin E is a fat-soluble vitamin, there are no known toxic effects of megadoses.

Click the icon to see sources of food which contain vitamin E.

Click the icon to see the benefits of vitamin C.

Click the icon to see sources of food which contain vitamin C.

Folic acid, a B vitamin, prevents birth defects and may also lower the risk for development of dysplasia (precancerous changes) leading to cervical cancer. It is not clear how strong this association is, or why this would occur. Some evidence points to its actions in reducing levels of homocysteine, a compound associated with a higher risk of cervical cancer.

There is no definitive evidence, however, that taking vitamins can prevent any cancer. Eating healthy foods rich in such vitamins and other important nutrients is, in any case, the best approach for overall good health.

Diagnosis

The changes that lead to cervical cancer develop slowly. Screening tests performed during regular gynecologic examinations can detect early changes.

Every year in the U.S. about 50 million women have a Papanicolaou test (the Pap smear). Use of the Pap smear has reduced the annual death rate from cervical cancer from 26,000 in 1941 to 3,700 in 2005.

Forty percent of women who have a Pap smear fail to follow-up for retesting and treatment. Most cases of cervical cancer occur in women who have not had regular Pap tests.

The Procedure. The most accurate test results are obtained 12 - 14 days after menstruation begins. Women should not douche or have intercourse within 48 hours of the test. Douches and spermicidal creams may clean out abnormal cells and interfere with the results of a Pap smear. (In general, douching is not recommended at all.) A Pap smear is usually painless, although some women may have some discomfort.

The test is done in a doctor's office. The woman removes her clothes from the waist down and puts on a medical gown. She lies on her back on the examination table, bends her knees, and puts her feet in supports (called stirrups) at the end of the table.
A doctor inserts a metal device into her vagina to widen it.
Using a spatula, brush, or both, the doctor gently scrapes the surface of the cervix, and sometimes the upper vagina, to gather living cells. The doctor will also obtain cells from inside the cervical canal. Such cells include squamous and glandular cells and those that lie higher up in the cervical canal (known as the endocervix). Using both a brush and spatula helps gather better samples to detect the presence of cancer.
The cells are preserved, stained for microscopic viewing, and then analyzed under a microscope by a specialist known as a cytopathologist.

A Pap test is a simple, relatively inexpensive procedure that can easily detect cancerous or precancerous conditions.

Reliability and Accuracy. Over the course of a lifetime of regular screening, a woman faces a 40% chance of being told her Pap smear is abnormal. The Pap smear is not, however, a perfectly reliable measure of a woman's risk for cervical cancer.

In general, about 10% of Pap smears have abnormal results, but only about 0.1% of the women who have these results actually have cancer. In most cases, abnormal cells are low grade and not likely to progress to cancer or are due to benign conditions, including natural cell changes after menopause.

No test is 100% accurate, and it is possible for the Pap smear to miss the presence of cancer. However, if abnormal cells are missed on one test they are likely to be spotted during the next one without a significant danger.

Newer, thin-layer liquid based tests (ThinPrep, SurePath) use the original cervical sample, which is rinsed in a special solution to thin the mucus (rather then dried). The result is a clear, clean sample that may be able to accurately reveal abnormal cells. The fluid can also be examined for evidence of human papilloma virus (HPV) and other early abnormalities. Some -- but not all -- studies have found this test to be more accurate than the standard Pap smear. A rigorous 2006 review of 56 studies found that liquid-based tests were no more accurate than conventional Pap smears.

The U.S. Preventive Service Task Force (USPST), the American Cancer Society (ACS), and the American College of Obstetricians and Gynecologists (ACOG) have all released guidelines for cervical cancer screening. ACOG and ACS have established separate screening criteria for women below and above 30 years of age. Although there are some small differences between these three sets of guidelines, they generally make similar recommendations as summarized below:

Recommendations for Initial Screening. Women should begin to undergo Pap tests within 3 years of onset of sexual activity or at age 21 (whichever comes first).

Women with no history of sexual activity should still have Pap smears. They are at low risk for squamous cell carcinoma, but adenocarcinoma (cancer that occurs in cervical glands) can occur, although this is very uncommon.

Women Up to Age 30. Women under age 30 should receive annual screening with the conventional Pap smear. The American Cancer Society (ACS) offers the alternative of screening every 2 years using the newer liquid-based testing. HPV testing is not recommended for this age group because HPV infections in women under age 30 tend to resolve on their own.

Women Age 30 and Over. Women in this age group who have received three consecutive negative (normal) annual Pap tests have two screening options:

Screening with standard or liquid-based Pap tests every 2 - 3 years. Women in high-risk groups (DES exposure, HIV infection, weakened immune system, or previous diagnosis of cervical cancer) should continue to receive annual tests.
Screening with Pap test plus HPV DNA test. If a woman tests negative on both of these tests, then she can be rescreened no more frequently than once every 3 years. If one of the tests is positive, she will need to be screened more frequently.

Elderly Women. In its 2003 guidelines, the U.S. Preventive Service Task Force recommended against routine screening in women over age 65 with low or no risk factors. (The ACS recommends stopping at age 70, while the American College of Obstetricians and Gynecologists declines to set an upper age limit.) Such women have had at least three previous normal screenings and have had no abnormal results for at least 10 years. According to the guidelines, older women should be screened if they have not been screened before or if there is a possibility that they have not been screened (for example, if the woman is from a country that does not do routine screening). However, a 2006 study of more than 15,000 postmenopausal women recommended continued screening for elderly women who are sexually active but not monogamous. (Women in the study had a uterus.) The researchers note that about 25% of new cervical cancer cases, and 41% of cervical cancer deaths, occur among women 65 years and older.

After a Hysterectomy. The 2003 guidelines recommend against routine screening for women who have undergone a total hysterectomy for benign causes. Women who have had a hysterectomy that preserves the cervix (called a supracervical hysterectomy) should continue with Pap screening.

If Pap smear results are normal for 3 consecutive years, most expert groups recommend a Pap test every 2 - 3 years thereafter in most women over 30 years of age. (The American Cancer Society suggests that such women wait until they are 30 before extending the interval to 3 years.)

Both the American Cancer Society and the American College of Obstetricians and Gynecologists recommend that annual screening should continue in women in high-risk categories. High risk categories may include the following, depending on the medical group:

Women who have had multiple sexual partners or whose male sexual partners have had multiple partners.
Women who engaged in sexual activity at a young age.
Women whose male sexual partners have had other sexual partners with cervical cancer.
Women with current or prior HPV infection.
Women who are HIV-positive or who are immunosuppressed.
Women with a history of sexually transmitted diseases.
Smokers and substance or drug abusers.
Women who have a history of cervical dysplasia or cervical, endometrial, vaginal, or vulvar cancer.
Women in lower socioeconomic groups, particularly if they have not been able to obtain regular gynecologic screening and care.

Any abnormal result, even a mild abnormality, requires follow-up visits and additional tests. The extent of these tests depends on the degree of abnormalities.

New tests and methods have been developed to improve the accuracy of the Pap smear in detecting cancer cells. For example, there are several computerized Pap test systems (FocalPoint, PAPNET) that are used to rescreen the original smear. These systems are either used to detect abnormal samples that may have been missed by manual review methods or are used in place of a human cytotechnologist. According to the U.S. Preventive Services Task Force (USPSTF), there is not yet enough evidence to know whether or not computerized methods are superior to conventional Pap testing.

There are tests for identifying the high-risk types of human papilloma virus (HPV) that are known to cause cervical cancer. The presence of these types is a strong predictor of high-grade aggressive abnormalities or cancer itself. Testing for HPV does not replace the Pap smear, but when used adjunctively with the Pap test this screening combination may help to more accurately detect cervical cell abnormalities than either test alone.

In 2003, the FDA approved the Hybrid Capture 2 (HC2) HPV DNA test for use with the Pap test for cervical cancer screening in women over 30 years of age. The HPV DNA test can identify 13 types of the high-risk HPV that are most frequently implicated in the development of cervical cancer. At this time, the test is recommended as an adjunct to the Pap test but not as the sole method for primary screening.

Other screening tests are being investigated for use in combination with the Pap smear for improving accuracy. For example, combinations with human papilloma virus (HPV) DNA tests or cervicography may prove to be more effective for detecting cervical intraepithelial neoplasia I and II dysplasia (potentially invasive cells) than Pap smears alone.

Cervicography. Cervicography uses a photograph of the cervical region (a cervigram), which is then highly magnified and examined. It may prove to be a useful companion to a Pap test, particularly in high-risk younger women. It is painless, easy to use, provides documentation of the area, and is highly sensitive to abnormal changes. (It also, however, picks up abnormalities that are not cancerous.)

Acid Test. A diluted solution of acetic acid (similar to vinegar) is applied to the cervix. When viewed through a special green lens, this solution makes abnormal cells look white, whereas normal cells appear pink. Skilled doctors may also be able to spot abnormal blood vessel patterns indicative of cancer areas on the cervix. This is an inexpensive and simple test.

Fluorescence Spectroscopy. Small noninvasive probes that can be swept across the surface of the cervix to detect cancer are showing promise as an effective screening tool for cervical cancer. One probe emits a laser light. The head of the probe catches the return signals from the woman's cervical cells and compares them with a computer library of cancer cells. In one comparison test, fluorescent spectroscopy was more accurate than the Pap smear but not as effective as other screening methods.

Other Investigative Tests. Experts are working on an antibody-based method for improving the identification of true cancerous cells in a cervical smear, which could significantly reduce the need for expensive and distressing tests in women who do not actually have cancer. In addition, they are looking for biologic markers to improve diagnosis, such as specific proteins that indicate the presence of cancer cells.

The cells viewed in a cervical smear sample are classified on a scale representing the spectrum of cell changes from normal to cancerous. The smear is first characterized as either "normal" or "abnormal."

Once abnormal cells are identified, the doctor must decide whether the patient needs only repeat Pap smears, a test for the human papilloma virus (HPV) virus, or colposcopy (a procedure used to magnify the cervix and permit detection of lesions for biopsy). To help the doctor make the decision, the abnormal cells are divided into categories, depending on the degree of abnormality. These classifications are based on the 2001 Bethesda System (TBS), which is formulated to standardize the reporting of Pap test results.

Atypical Squamous Cells. Atypical squamous cells (ASC) are mildly abnormal cells on the surface of the cervix. They may simply represent inflammation. Over 80% of these cells normalize, but unfortunately, between 5 - 17% of these women have a chance for having cervical intraepithelial neoplasia II and III dysplasia (potentially invasive cells). Researchers have further categorized atypical squamous cells as the following:

ASCUS. These atypical squamous cells of undetermined significance are the lowest risk abnormal cells. Women with these cells should be tested for human papillomavirus infection (HPV). If results indicate they are infected with HPV, they should receive colposcopy, a more invasive diagnostic procedure, to determine if the condition is actually at a more aggressive stage. If they do not have HPV they are simply monitored with repeat Pap smears.
ASC-H. This category refers to the presence of atypical squamous cells, but a doctor cannot exclude possible high-grade squamous intraepithelial lesions. Such women have a 24 - 94% chance of having cervical intraepithelial neoplasia II and III. All are referred for colposcopy.

Among those with atypical squamous cells, immunosuppressed women and those with high-risk human papilloma virus infections are at higher risk for cervical intraepithelial neoplasia II and III and should always be given colposcopy. Postmenopausal women with normal immune systems have a lower risk than younger women. It should be strongly noted, however, that actual risk for cervical cancer in general in women with atypical squamous cells is only 0.1 - 0.2%.

Low Grade Squamous Intraepithelial Lesions. Low-grade squamous intraepithelial lesions (LSIL) are typically associated with human papilloma virus changes, with or without early dysplasia. Between 15 - 30% of women with LGIL, however, may have cervical intraepithelial neoplasia II or III on biopsy. Women with LSIL are either monitored with repeat Pap smears or given colposcopy. Doctors recommending colposcopy argue that these are high-risk women who risk delaying a diagnosis of cancer using only repeat Pap smears.

High-Grade Squamous Intraepithelial Lesions. High-grade squamous intraepithelial lesions (HSIL) are associated with moderate dysplasia and other cervical intraepithelial neoplasia II or III. Such women are always referred to colposcopy for biopsy. Even if colposcopy results report only cervical intraepithelial neoplasia I, over a third of these women are likely to have cervical intraepithelial neoplasia II or III. Experts, therefore, recommend a careful review of the tests in such cases. Pregnancy poses a problem since it increases the chance in HSIL for both normal and abnormal results. In nonpregnant women, particularly when fertility is not an issue, immediate treatment with loop electrosurgical excision procedure may be appropriate.

Atypical Glandular Cells. Atypical glandular cells are uncommon, but pose a higher risk for cancerous changes than atypical squamous cells or low-grade squamous intraepithelial lesions. Between 9 - 54% have some cervical intraepithelial neoplasia, 0 - 8% have pre-invasive cancer, and 1 - 9% have invasive cancer. Doctors recommend that the next step should be a colposcopy (rather than a repeat Pap smear).

The Pap smear shows only the presence of abnormal cells. It is useful simply as a screening test that identifies women who may have preinvasive or early cancerous changes. For a definitive diagnosis, the next step is usually colposcopy, during which the cervix is visualized under low power magnification. The surgeon takes samples of suspicious cells for biopsies. A biopsy will determine the stage of the precancerous growth or whether invasive cancer is present.

The Procedure. Colposcopy can be performed in a doctor's office without anesthesia in 10 - 15 minutes. It causes about as much discomfort as mild menstrual cramps:

First, using a speculum to keep the vagina open, the doctor aims a light at the cervix.
The doctor then looks through the eyepiece of a special microscope, known as a colposcope, to view the cervix. (Some colposcopies include a TV attachment that transmits the picture to a nearby monitor for easier viewing.)
A biopsy (a sampling of the tissue) is taken of suspicious areas, of the endocervical canal (the inner part of the cervix and uterus), and any abnormal-looking areas. This may cause cramping or pinching.

Click the icon to see an image of a colposcopy-directed biopsy.

After the colposcopy, the woman may have a brownish discharge from an iron solution called Monsel's solution, which the doctor applies to prevent bleeding. The doctor usually advises sexual abstinence for 1 - 2 weeks.

Follow-Up Procedures. Women with evidence of cervical intraepithelial neoplasia (CIN) or cervical cancer require treatment. Women with biopsies that show low-grade abnormal cells (LGSIL), but whose cervix is otherwise normal, are generally given follow-up colposcopies.

Treatment for Cervical Intraepithelial Neoplasia and Pre-invasive Cancer

Treatment of cervical intraepithelial neoplasia (CIN), including pre-invasive cancer, depends on the type and extent of abnormal changes. Some of the treatments for CIN are also used for early-stage cancer.

CIN I often goes away on its own. Careful follow up is required to make certain that the Pap smear and colposcopic exam return to normal.
CIN II or CIN III may turn into invasive cancer if the suspicious area is not removed. This is often done using an outpatient technique called loop electrosurgical excision procedure (LEEP). [See next section.]
If doctors cannot see extensive areas of CIN II or III with colposcopy or if they sthese areas pread into the mucous membrane in the cervical canal, a more aggressive procedure called conization (cone biopsy) may be required.

The cold cone biopsy is a surgical procedure that requires general anesthesia. It is performed when there are severe precancerous changes in the cervix.

Treatment for Adenocarcinoma. An adenocarcinoma is cancer inside tissue that looks like or functions as a gland. (A gland is a group of cells that secretes a substance to be used by or removed from the body.) Adenocarcinomas tend to be more aggressive than the more common pre-invasive cancer, which grows in the lining of tissue (mucous membrane). Some evidence suggests that adenocarcinomas develop in numerous sites rather than a single location. Hysterectomy is generally recommended. For women who wish to retain fertility, a docotor may perform a cone biopsy, although this procedure sometimes causes sterility and it does not always remove all adenocarcinomas.

Follow-Up. Patients treated for CIN need to be monitored. Testing for human papilloma virus (HPV) may prove to be useful in determining whether repeat colposcopies may or may not be needed. One study strongly suggested that if both HPV and Pap smear tests are normal on two consecutive visits, treatment most likley was successful. If either the HPV or Pap smear is abnormal, it may be reasonable to consider another colposcopy.

Loop electrosurgical excision procedure (LEEP), also called large loop excision of the transformation zone (LLETZ), uses a high frequency electrical current to cut away diseased tissue.

A local anesthetic is applied to the cervix, and a wire loop is inserted into the vagina.
A button-sized slice of tissue is removed from the cervix for examination.
A deeper slice is used to evaluate the endocervical canal.

The procedure is done in one office visit. Extensive and deep sections of damaged tissue can be effectively removed in this visit. Disease can be cured in one treatment. When used for dysplasia, it appears to be as effective as more invasive procedures.

The only downside of LEEP may be its simplicity. Doctors may be tempted to use it for more serious conditions best treated by a procedure called conization. It also may impair the ability to detect hidden invasive cancer. Patients should be monitored closely if the biopsies on the cervical tissue removed by LEEP suggest that the cells may become invasive.

LLETZ is becoming increasingly popular as a treatment for cervical intraepithelial neoplasia. However, women of child-bearing age should be aware that it may later cause pregnancy problems, such as preterm delivery and low birth weight. Women who have this procedure may also be more likely to break their water too early (premature rupture of membranes).

Conization is a surgical procedure that removes suspicious sections of cells covering an abnormally large area, or those extending into the cervical canal. Conization is preferred over Loop electrosurgical excision procedure (LEEP) or large loop excision of the transformation zone (LLETZ) for lesions that are so big they require a larger biopsy for their complete removal. As in LEEP, patients should be monitored closely if patients are infected with human papilloma virus (HPV) virus or the biopsies on the cervical tissue removed show aggressive-grade cells.

The surgery can be performed under general anesthesia in the operating room with either traditional surgical instruments or lasers.

A technique called frozen section examination (FSE) freezes the margins of the area being removed. Studies suggest that FSE allows immediate and precise evaluation of areas that may harbor invasive cancer cells, and may be an important addition to this procedure in women with high-grade cervical intraepithelial neoplasia.

With conization, the ability to become pregnant can be preserved in many (but not all) cases. In women who do become pregnant, some studies have indicated that this procedure increases the risk for low-birth weight infants, so careful prenatal care is essential. Conization can also increase the risk for preterm delivery and Cesarean section. Patients who have this treatment must have follow-up evaluations.

Cryosurgery is not usually feasible for large abnormal areas. The procedure removes abnormal, but noncancerous, tissue by freezing it. Cryosurgery can be performed in a doctor's office in 15 minutes without medication.

The vagina is opened with a speculum and a probe transmits gas (either nitrous oxide or carbon dioxide), which freezes the surface of the cervix.
The gas is applied for 3 minutes or until ice crystals form on the targeted tissue.
After waiting 3 minutes, freezing can be repeated for another 3 minutes.

Click the icon to see an image of cervical cryosurgery.

Side effects from this procedure include cramping, sometimes painful, for a few hours or days and a heavy, watery discharge for 2 - 4 weeks. The discharge can be irritating, have a bad odor, and may be blood-tinged. Symptoms that may indicate serious complications are fever and chills, heavy clotted bleeding, or extreme pain in the abdomen or back.

The patient may have a temporary change in menstrual periods. The menstrual periods may be heavier or lighter, or come later or earlier. Tampons, douching, bathing, swimming, and intercourse should be avoided for several weeks after cryosurgery to prevent infection.

Patients who have this treatment must be willing to commit to regular follow-up examinations.

Treatment for Cervical Cancer

In contrast to cervical intraepithelial neoplasia, cervical cancer represents true invasion of cells beyond the epithelium into surrounding tissue. Cervical cancer may be detected in a biopsy performed during colposcopy for an abnormal Pap smear, or it may be visible to the naked eye when the doctor performs a speculum exam.

Imaging Tests to Determine Extent of Tumor Spread. If a biopsy detects invasive cancer, the patient will need additional tests to find out how far the cancer has spread. How fart the cancer has spread determines whether the cancer is operable.

An abdominal computed tomography (CT) scan is commonly used to check for spread of the disease to lymph nodes and areas around the pelvic area.

In computed tomography (CT), a thin x-ray beam rotates around the area of the body. Using very complicated mathematical processes called algorithms, a computer is generates a 3-D image of a section of the body.

Other procedures may be used to find out if cancer has spread to areas around the uterus. X-ray images are taken of the bladder and urinary system (known as intravenous pyelography, or IVP) or of the lower intestinal tract (known as a barium enema).

Click the icon to see an image of intravenous pyelography.

Click the icon to see an image of a barium enema.

If these tests detect cancer in any of these surrounding sites, the patient will need more tests :

Cystoscopy is performed to examine and take tissue from the bladder for biopsy.

Click the icon to see an image of cystoscopy.

Sigmoidoscopy is used to evaluate the rectum. (In this procedure and a cystoscopy, a tube with a lighting device is inserted to view internal areas.)

Click the icon to see an image of sigmoidoscopy.

Magnetic resonance imaging (MRI) is a sensitive and noninvasive procedure that is occasionally useful for finding tumors in the tissues surrounding the uterus.

Click the icon to see an image of a MRI.

Sentinel Node Biopsy. One technique is called a sentinel node biopsy. It has been used in patients with breast cancer to help determine if cancer has spread beyond the lymph nodes. It is now being investigated for patients with early cervical cancer and may be helpful in determining which patients need to have lymph nodes removed in their pelvic area:

The procedure uses an injection of a tiny amount of a blue dye, into the tumor site.
These substances then flow via the lymphatic system into the sentinel node. This is the first lymph node to which any cancer would spread.
The sentinel lymph node and possibly one or two others are then removed.
If these nodes do not show signs of cancer, the rest of the lymph nodes may be cancer-free, making further removal of lymph nodes unnecessary.

After making a diagnosis, the doctor will classify the stage of the cancer according to how far the disease has spread into the lining of the cervix, throughout the cervix, or beyond. Doctors use these classifications to determine treatment and outlook.

Patients who have been diagnosed with cervical cancer need to know the normal treatments for their particular stage, so they may compare their doctor's suggestions with these norms.

Stage 0 is pre-invasive cancerconfirmed by biopsy and confined to the first layer of cervical tissue (the epithelium). Treatment options include loop electrosurgical excision procedure (LEEP), laser therapy, conization, and cryotherapy.

Stage I is invasive cancer, but the tumor is confined to the cervix. This stage is further categorized as IA and IB.

Stage IA. Five-year survival rates for stage IA can be 95% or more.

In stage IA1 cancer cells are microscopic, there is minimal invasion (less than 3 mm) into the supportive tissue around the cervix (the stroma), and the horizontal extent of the tumor is less than 7 mm. Treatment is usually a simple hysterectomy. Conization is sometimes possible for women who want to remain fertile and who have a nonaggressive tumor that has spread less than 3 mm, with no lymph or blood vessel involvement. Trachelectomy has been investigated for women who want to preserve fertility. More research is needed.
In stage IA2 there is deeper invasion (greater than 3 mm but less than 5 mm) and the horizontal extent of the tumor is less than 7 mm. Radical hysterectomy with surgical lymph node removal (lymphadenectomy) is a common treatment.

Note on Stage IA2 through IIA: Postoperative concurrent radiation and platinum-based chemotherapy may be considered for stages IA2 through IIA tumors if the following high risk features are found at the time of primary surgery: lymph node involvement, cancerous cells found in the margins of the tumor, and involvement of the parametrium.

Stage IB and Locally Advanced Cancer. Five-year survival rates for stage IB can be 80 - 90% with either radiation or surgery. Survival rates are lower if the cancer has spread to the lymph nodes.

In stage IB1 the tumor is typically visible (not usually microscopic), and the diameter may be up to 4 cm. Radical hysterectomy with pelvic lymph node removal (lymphadenectomy) is the recommended treatment. Primary radiation can be used instead of surgery in patients who eitehr are poor surgical candidates or do not plan on being sexually active.
In stage IB2 the tumor is more than 4 cm and considered "bulky." Relapse rates after surgery are higher than in stage 1B1. Primary treatment with radiation therapy with concurrent platinum-based chemotherapy is reasonable. Some women in stage IB may receive combinations of radiation and surgery, although the benefits of such combinations are unclear for most women, particularly given a higher risk for severe side effects.

Note on Locally Advanced Cervical Cancer: Stages IB2 through IVA are often referred to collectively as locally advanced cancer and are frequently treated similarly. Standard treatment includes radiotherapy with concurrent platinum-based chemotherapy. Experimental approaches for some women with locally advanced cervical cancer use radiation therapy with hyperthermia (high heat often provided by ultrasound) and neoadjuvant (preoperative) chemotherapy and radical surgery. More research is necessary.

Stage II invasive cancer has spread beyond the cervix, but it has not spread to the pelvic side wall. This stage is further categorized as IIA and IIB.

Stage IIA. Cure rates for stage IIA can be as high as 75 - 80% with either radiation or radical hysterectomy. Survival rates are lower if cancer has spread to the lymph nodes. In stage IIA, cancer has spread to the upper two thirds of the vagina but not to the parametrium (the connective tissue between the pelvic floor and upper part of the cervix). Radical hysterectomy with pelvic lymph node removal (lymphadenectomy) is the recommended treatment. Primary radiation can be used instead of surgery in patients who eitehr are poor surgical candidates or do not plan on being sexually active. If the tumor is bulky, however, primary treatment with radiation therapy with concurrent platinum-based chemotherapy is reasonable. Some women in stage IB may receive combinations of radiation and surgery.

Stage IIB. For stage IIB 5-year survival rates are about 60%. In stage IIB the cancer has spread to the parametrium. Recommended treatment is radiation therapy with concurrent cisplatin-based chemotherapy.

In stage III, the cancer is invasive, extending to the lower third of the vagina (stage IIIA) or to the side walls of the pelvis (stage IIIB). The kidney may be affected. Recommended treatment is radiation therapy with concurrent cisplatin-based chemotherapy. Five-year survival rates are about 40%.

In stage IV, invasive cancer has spread beyond the pelvis or to the mucosal lining of the bladder or rectum. Five-year survival rates are less than 20%.

Stage IV. In stage IVA, the cancer has spread to the inner lining of the bladder or rectum. Recommended treatment is radiation therapy with concurrent cisplatin-based chemotherapy.

Stage IVB. In stage IVB, the cancer has spread beyond the pelvis. Recommended treatment is radiation therapy to relieve symptoms and chemotherapy (usually cisplatin or carboplatin combined with other drugs such as topotecan). Platinum-based chemotherapy yields short-lived response in 20% of patients. Clinical trial participation is reasonable.

Cervical cancer may recur locally in the lymph nodes near the cervix, it may spread to distant sites, such as the lung or bones, or it may appear both locally and in distant locations.

Recommended treatment is pelvic exenteration if cancer has spread to only local areas. (This involves removal of the cervix, uterus, vagina, and perhaps the bladder, lower colon, or rectum. It is an aggressive surgical approach that may lead to cure in a small percentage of patients with recurrent cervical cancer.) Radiotherapy is another option if it is technically possible -- generally if patients did not have it previously. If cancer has spread, platinum-based chemotherapy is reasonable. Other drugs may be useful under certain circumstances.

Only 1% of cervical cancers occur during pregnancy or shortly afterwards. To diagnose the condition, a cervical biopsy, in which a small amount of tissue is removed for diagnosis, can be performed anytime during the pregnancy. However, a cone biopsy, which removes larger amounts of tissue, is typically delayed until after the first trimester to reduce the risk of abortion. Treatment options may be as follows:

If the abnormality is diagnosed as dysplasia or even pre-invasive cancer, treatment is sometimes delayed until a few weeks after the mother gives birth, and vaginal delivery may still be possible. The pregnant woman should discuss the risks and benefits of this approach, however, with her doctor.
If early-stage cancer is diagnosed in the late second or third trimester, a woman may sometimes be able to delay treatment until the baby is delivered. A Cesarean section is the preferred delivery method. The cancer treatment of choice is started shortly afterward.
More locally advanced invasive cancer is nearly always treated, particularly if is diagnosed within the first 20 weeks of the pregnancy.

Treatment for Invasive Cervical Cancer

Radiation therapy and surgery are about equally effective as a single option for treating very small cervical cancers in their earliest stages. Survival rates in the appropriate patients can be about 85 - 90%. Factors influencing the choice between radiation therapy and surgery in women with invasive cancer include the patient's age and health and the amount of cancer. Both surgery and radiation therapy eliminate the possibility of having children in premenopausal women.

Although treatments for cervical cancer have several potentially severe side effects, they are usually well-tolerated. Women undergoing any of these treatments should feel free to seek support groups and counseling, which can be as important for their outlook as medical therapies.

Surgery. Surgery almost always involves a hysterectomy, an operation that removes the uterus and sometimes other areas in the pelvic region as well. It does not, however, usually impair sexual activity.

In general, surgery is the better choice when small cancers are confined to the cervix in women who wish to remain sexually active.

Radiation. Radiation treatments to the pelvis often inhibit ovarian function. Early menopause often occurs. Radiation also may cause vaginal scarring. Treatments are available that may reduce these problems, and women should not be shy about discussing them with their doctor. Radiation therapy is usually the choice under the following circumstances:

Cancers have spread beyond the cervix to the pelvis, lower vagina, and urinary tract.
When certain tumor features indicate a high risk for recurrence after surgery.

Important studies now strongly suggest that radiation along with chemotherapy can improve survival rates improve in patients with stages IB to IVA compared to radiation alone. The benefits are greatest in stages I and II.

In the early stages of cervical cancer, surgery is often the preferred primary treatment approach since it preserves normal sexual function. Some patients desiring fertility who have early stage I cancer may be candidates for cervical cone biopsy.

Hysterectomy. A hysterectomy attempts to eliminate the cancerous tissue by removing the uterus. There are several variations of this operation, depending on the location of the tumor. In women of childbearing age, the ovaries can usually be left intact. Although a woman who has a hysterectomy but retains her ovaries cannot bear children, she will not go into premature menopause. (Studies indicate that leaving the ovaries intact is safe for most women and does not pose any greater risk for cervical cancer recurrence.)

A simple hysterectomy involves the removal of the uterus and the cervix, but leaves the parametrium (tissue surrounding the uterus) and vagina intact. Lymph nodes in the pelvis are not usually removed.

Click the icon to see an illustrated series detailing a hysterectomy.

A radical hysterectomy removes not only the uterus and the cervix but also the parametrium, the supporting ligaments, the upper vagina, and some or all of the local lymph nodes (a procedure called lymphadenectomy).

If the cancerous tumor recurs within the pelvis after primary treatment, the patient may need a more extreme procedure called a pelvic exenteration, which combines radical hysterectomy with removal of the bladder and rectum. (In such cases, plastic surgery may be needed afterward to recreate an artificial vagina.) Patients undergoing this procedure are physically and psychologically screened in advance to determine whether it is an appropriate choice. The success rate for pelvic exenteration in halting the progression of the disease is about 25 - 45%.

Any form of hysterectomy is major surgery and requires at least a 3 - 5 day hospital stay. Although hysterectomy typically uses a wide abdominal incision, less invasive techniques that allow shorter recovery time may be possible for some women with early stage cancers if performed by experienced surgeons.

Side effects include difficulty emptying the bladder or bowels and a painful lower abdomen. Urinary tract infections are very common. Complications include fistulas (abnormal channels within the pelvis, which in this case are a result of surgery), bladder dysfunction, and cysts.

Normal activity, including intercourse, can be resumed in about 4 - 8 weeks. Once the uterus is removed, menstruation will cease. If the ovaries are removed, the symptoms of menopause will begin. These symptoms are likely to be more severe in surgical menopause than in natural menopause. The pateint should discuss the benefits and risks of hormone replacement therapy with her doctor.

Trachelectomy. An experimental procedure called trachelectomy is being investigated for preserving fertility in certain women in early-stage cervical cancer, but it is highly controversial and appropriate in only about 5% of patients. In the procedure, only the cancerous portion of the cervix is removed, while the uterus and the rest of the cervix are left intact. The cervix is closed with a suture.

The procedure is primarily performed outside the U.S., and few American surgeons are skilled in this surgery at this time. Throughout the world, in fact, only about a few hundred of these procedures have been performed to date. Larger and longer-term studies are needed to confirm its long-term safety.

Radiation therapy is an alternative approach for early stage cervical cancer. Radiation with concurrent cisplatin-based chemotherapy is now the standard treatment for locally advanced cervical cancer. Radiation therapy uses high-energy rays aimed at the body from an outside machine (external beam radiation) and radioactive materials placed inside the body against the cervix (intracavitary radiation).

External beam radiation is given first and aimed at the lymph nodes along the pelvic wall. It usually involves a short period of direct-radiation 5 days a week for about 6 weeks in an outpatient setting.
Intracavitary radiation (also called brachytherapy) follows and is designed to deliver high doses of radiation to the local tumor area. Radioactive material, typically cesium-137, is encapsulated in both gold and platinum. These capsules are inserted in a long stainless steel tube called a tandem, which is inserted in the uterus. and in small stainless steel cylinders, called colpostats, which are placed against the cervix as close to the cancerous cells as possible. Commonly, two or more radiation treatments are administered for about 35 hours each time. Radiation implants may also be inserted directly into the tumor using a needle.

In order to be effective, radiation therapy must be powerful enough to destroy the cancer cells' capacity to grow and divide. This means that normal cells are also affected, which may cause significant side effects. Fortunately, healthy cells usually recover quickly from the damage, whereas abnormal cells do not.

Advanced methods that target radiation more precisely and limit the damage to healthy tissue are now available. They include 3-D conformal radiation and intensity-modulated radiation therapy (IMRT):

3-D conformal techniques use computers and a three-dimensional image of the cervix to provide precise targeting of the tumor using multiple high-dose radiation beams.
IMRT also uses 3-D techniques and employs very thin and precise beam at various intensities.

Side Effects. Side effects of radiation therapy include fatigue, redness or dryness in the treated area, diarrhea, frequent or uncomfortable urination, and vaginal dryness, itching, or burning. After treatment, side effects usually disappear.

Long-Term Complications. Complications include proctitis (inflammation of the rectum) and cystitis (inflammation of the bladder). Bowel obstruction is an uncommon complication. Radiation therapy may also cause vaginal scarring, sexual difficulties, and premature menopause in younger women. Occasionally an abnormal tunnel between the bladder and the vagina, known as a vesicovaginal fistula, will develop and may require surgery.

Click the icon to see an image of the female anatomy.

Investigative temporary silicone implants or a noninvasive device called the belly board may protect the small intestine during radiation therapy and help reduce complications.

Radiation itself may increase the risk for later development of cancer in the area surrounding the treated tissue. Although newer more precise radiotherapy approaches should reduce this risk, there is some concern that IMRT may double the incidence of secondary cancers over time compared to 3-D conformal techniques. This is of particular concern in younger patients.

Radiation and Hyperthermia. Investigators are studying hyperthermia (use of high heat often provided by ultrasound) in combinations with radiation therapy. This approach has shown some promise in achieving significant response rates in small studies. Comparison studies are important to determine if this approach would be as beneficial with radiation therapy as concurrent chemotherapy.

Chemotherapy uses cell-killing drugs called cytotoxic drugs to destroy widespread cancer cells that have spread from the primary tumor and can no longer be treated with surgery or radiation.

For many years, chemotherapy was only used to reduce symptoms in women with very advanced disease. Today, platinum-based chemotherapy drugs (see below) are being used in many situations for cervical cancer, such as:

In combination with radiation therapy to improve survival rates in certain women, including some with locally advanced cancer.
In some women with locally advanced cancer to reduce tumors to the point where the cancer may be operable.
When cancer has spread (metastasized), mostly to reduce symptoms such as pain.

Platinum-Based Drugs. Platinum-based drugs cisplatin and carboplatin are often used for treating various stages of cervical cancer. These drugs are usually used in combination with radiation therapy or other chemotherapy drugs. In 2006, the FDA approved a combination of cisplatin and topotecan (another type of chemotherapy drug) for treatment of late-stage cervical cancer in women who are unlikely to be helped by surgery or radiation therapy. Women with stage IVB cervical cancer who received the combination treatment survived around 3 months longer (9.5 months versus 6.5 months) than women who received only cisplatin.

Other drugs. Other drugs, mostly used in combinations, have also been investigated with some promise. They include epirubicin, irinotecan, paclitaxel, bleomycin, mitomycin, vinorelbine, gemcitabine, and doxifluridine.

Administration. Chemotherapy may be given by mouth or as an injection. This may be done at a medical center, doctor's office, or even a patient's home. Some patients receiving chemotherapy may need to remain in the hospital for several days so the effects of the drugs can be monitored. The drugs are often given in cycles with a period of rest following a period of treatment, to allow recovery from the side effects.

Side Effects. Chemotherapy affects all fast-growing cells, including healthy ones. So, side effects are inevitable. Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment.

Common side effects include the following:

Nausea and vomiting. Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve these side effects in nearly all patients given moderate drugs and in most patients who take more powerful drugs.
Diarrhea
Temporary hair loss
Weight loss
Fatigue
Anemia
Depression

Complications. Serious short- and long-term complications can also occur and may vary, depending on the specific drugs used. They include:

Increased chance for infection. Chemotherapy suppresses the immune system.
Severe drop in white blood cell count (neutropenia). Certain drugs, such as taxanes, pose a higher risk for this than other chemotherapeutic drugs. White blood cell count may be improved with the addition of a type of drug called granulocyte colony-stimulating factor (either filgrastim or lenograstim).
Liver and kidney damage.
Abnormal blood clotting (thrombocytopenia).
Allergic reaction, particularly to platinum-based drugs. (A simple skin test that may identify people with a potential allergic response is under investigation .)
Menstrual abnormalities. These are common. Premature menopause occurs in about 30% of women, particularly in those over 40.
Secondary cancers such as leukemia (rare).
Problems in concentration, motor function, and memory, which may be long-term. Between a quarter and a third of women report such problems. This may be due to a drop in estrogen levels after treatments.

Resources

www.cancer.gov -- National Cancer Institute
www.cancer.org -- American Cancer Society
www.acog.org -- American College of Obstetricians and Gynecologists
www.ashastd.org -- American Social Health Association
www.arhp.org -- Association of Reproductive Health Professionals
www.nccc-online.org -- National Cervical Cancer Coalition
www.cervicalcancercampaign.org -- Cervical Cancer Public Education Campaign
www.fda.gov/womens/getthefacts/hpv.html -- FDA HPV Fact Sheet
www.thegcf.org -- Gynecologic Cancer Foundation
www.wcn.org -- Women's Cancer Network
www.plwc.org -- People Living with Cancer
www.gothpv.net -- HPV Support Site

References

Ault KA; Future II Study Group. Effect of prophylactic human papillomavirus L1 virus-like-particle vaccine on risk of cervical intraepithelial neoplasia grade 2, grade 3, and adenocarcinoma in situ: a combined analysis of four randomised clinical trials. Lancet. 2007 Jun 2;369(9576):1861-8.

Committee on Infectious Diseases. Prevention of human papillomavirus infection: provisional recommendations for immunization of girls and women with quadrivalent human papillomavirus vaccine. Pediatrics. 2007 Sep;120(3):666-8.

Davey E, d'Assuncao J, Irwig L, Macaskill P, Chan SF, Richards A, et al. Accuracy of reading liquid based cytology slides using the ThinPrep Imager compared with conventional cytology: prospective study. BMJ. 2007 Jul 7;335(7609):31. Epub 2007 Jun 29.

D'Souza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C, Koch WM, et al. Case-control study of human papillomavirus and oropharyngeal cancer. N Engl J Med. 2007 May 10;356(19):1944-56.

Dunne EF, Unger ER, Sternberg M, McQuillan G, Swan DC, Patel SS, et al. Prevalence of HPV infection among females in the United States. JAMA. 2007 Feb 28;297(:813-9.FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007 May 10;356(19):1915-27.

Garland SM, Hernandez-Avila M, Wheeler CM, Perez G, Harper DM, Leodolter S, et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases. N Engl J Med. 2007 May 10;356(19):1928-43.

Gunnell AS, Tran TN, Torrang A, Dickman PW, Sparen P, Palmgren J, et al. Synergy between cigarette smoking and human papillomavirus type 16 in cervical cancer in situ development. Cancer Epidemiol Biomarkers Prev. 2006 Nov;15(11):2141-7. Epub 2006 Oct 20.

Hildesheim A, Herrero R, Wacholder S, Rodriguez AC, Solomon D, Bratti MC, et al. Effect of human papillomavirus 16/18 L1 viruslike particle vaccine among youngwomen with preexisting infection: a randomized trial. JAMA. 2007 Aug 15;298(7):743-53.

Markowitz LE, Dunne EF, Saraiya M, Lawson HW, Chesson H, Unger ER; Centers for Disease Control and Prevention (CDC); Advisory Committee on Immunization Practices (ACIP). Quadrivalent human papillomavirus vaccine: Recommendations of the AdvisoryCommittee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007 Mar 23;56(RR-2):1-24.

Ronco G, Cuzick J, Pierotti P, Cariaggi MP, Dalla Palma P, Naldoni C, et al. Accuracy of liquid based versus conventional cytology: overall results of new technologies for cervical cancer screening: randomised controlled trial. BMJ. 2007 Jul 7;335(7609):28. Epub 2007 May 21.

Saslow D, Castle PE, Cox JT, Davey DD, Einstein MH, Ferris DG, et al. American Cancer Society Guideline for human papillomavirus (HPV) vaccine use to prevent cervical cancer and its precursors. CA Cancer J Clin. 2007 Jan-Feb;57(1):7-28.

Sturgis EM, Cinciripini PM. Trends in head and neck cancer incidence in relation to smoking prevalence: an emerging epidemic of human papillomavirus-associated cancers? Cancer. 2007 Aug 27; [Epub ahead of print]Weller SC, Stanberry LR. Estimating the population prevalence of HPV. JAMA. 2007 Feb 28;297(:876-8.

Review Date:
9/1/2006
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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