FitSugar

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FitSugar — Thu, 12 Jul 2007 02:30:00 -0700

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Glaucoma

FitSugar — Wed, 08 Oct 2008 17:35:34 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

Bimatoprost (Lumigan) has been approved as a first-line treatment for open-angle glaucoma.

Glaucoma Cases Increasing Worldwide

About 60 million people worldwide will have glaucoma by 2010, and the number will increase to nearly 80 million by 2010, according to a recent study in the British Journal of Ophthalmology.

Weightlifting May Increase Glaucoma Risk

Weightlifting can cause a temporary increase in intraocular eye pressure (IOP), and holding your breath while lifting weights further increases IOP, suggests a 2006 study in the Archives of Ophthalmology. Doctors should ask patients with normal-tension glaucoma if they engage in weightlifting exercise.

IOP and Posture

IOP increases in some people when they are lying prone during sleep, yet glaucoma exams measure IOP in patients while they are sitting upright and awake, notes a 2006 study in the Archives of Ophthalmology. The researchers caution that posture may affect the interpretation of IOP readings.

Pregnancy and Glaucoma

The course of glaucoma is unpredictable during pregnancy -- IOP may remain stable in some women and increase in others, indicates a 2006 study. Although glaucoma eye drops can increase the risk of some pregnancy problems, especially during the first trimester, some pregnant women may need to continue to take glaucoma medication. Be sure your ophthalmologist carefully evaluates your individual case and explains the risks and benefits of taking medication during pregnancy.

Diabetes and Glaucoma

Type 2 diabetes increases the risk for open-angle glaucoma (the most common type of glaucoma). People with type 2 diabetes need to get regular glaucoma screenings.

Glaucoma Surgery

Tube shunts may work better than trabulectomy surgery for some patients with glaucoma, suggests a 2007 study.
Phacoviscocanalostomy, a surgery procedure that combines phacoemulsification (used for cataract surgery) and viscocanalostomy (used for glaucoma surgery), is safe and effective for patients who have both glaucoma and cataracts, indicates a 2006 study.

Introduction

Glaucoma is defined as a disease of the optic nerve, in which the nerve cells in the front of the optic nerve (the ganglion cells) die. The process is irreversible. Previously, it was believed that glaucoma was almost always due to increased intraocular pressure. However, glaucoma has been observed in many patients with normal and even low eye pressure, so the definition now rests on the damage to the optic nerve.

The Aqueous Humor. In understanding of glaucoma, it is important to first consider aqueous humor, the clear, watery fluid that circulates continuously through the front (anterior) chamber of the healthy eye and is a primary focus of glaucoma research. (This fluid is not related to tears, nor is it the dense jelly-like substance called vitreous humor that is contained in the rear chamber.) It serves two important functions in the eye:

It nourishes the area around the colored iris and behind the cornea.
It exerts pressure to help maintain the eye’s shape.

Draining the Fluid and Intraocular Pressure. The aqueous fluid is continuously produced within the front of the eye, causing pressure known as intraocular pressure (IOP). To offset the in-flowing fluid and to maintain normal IOP, the fluid drains out between the iris and cornea (an area known as the drainage angle). It does so through two channels within this angle:

The trabecular meshwork, a sponge-like, porous network, and its connecting passageways are referred to as the "conventional" outflow pathway. Most of the eye fluid outflow occurs in this region and flows from the trabecular meshwork to a group of vessels encircling the anterior chamber, called Schlemm's canal. From here, the fluid enters collection chambers and then flows out into the general blood circulatory system of the body.
The uveoscleral pathway is located behind the trabecular meshwork and is called the "unconventional" pathway. Up to 30% of the fluid flows out through this channel.

Intraocular Eye Pressure. Previously, it was believed that glaucoma was almost always due to an abnormal rise in intraocular pressure.

Glaucoma is a condition of increased fluid pressure inside the eye. The increased pressure causes compression of the retina and the optic nerve which can eventually lead to nerve damage. Glaucoma can cause partial vision loss, with blindness as a possible eventual outcome.

Increased IOP is, indeed, present in most cases of glaucoma, but some patients have normal IOP, which is usually maintained at measurements of 10 - 20 mm Hg. Measurements above this, however, do not necessarily predict glaucoma. For example, only about 10% of people with IOP levels between 21 - 30 mm Hg will actually develop glaucoma. This still puts such individuals at considerable risk for glaucoma, however.

Most people with glaucoma have the form called primary-open-angle glaucoma (also called chronic open-angle glaucoma). Open-angle glaucoma is essentially a plumbing problem.

The disease process may occur as follows:

The drainage angle remains open, but tiny drainage channels in the trabecular meshwork pathway become clogged. This pathway is responsible for most aqueous humor fluid outflow. An imbalance then occurs as fluid continues to be produced but does not drain out efficiently. Experts have still not definitely determined the precise area in the pathway where the blockage is most likely to occur. (In rare instances the pressure is high because the eye produces too much aqueous humor.)
The fluid in the eye’s anterior chamber builds up and increases pressure within the eye. This is called intraocular pressure (IOP).
The intraocular pressure exerts force on the optic nerve at the back of the eye.
Over time, the persistent pressure or other factors irreversibly damages the delicate long fibers of the optic nerve, called axons, which convey images to the brain.
As these axons die, the small cup-like head of the optic nerve may eventually collapse into an enlarged irregular shape.

Optic nerve damage is the basic glaucoma condition. If it is untreated, eventually the nerve deteriorates until a person loses sight, first in the peripheral vision (the vision in the "corner of the eyes"). If it becomes severe, the person loses central vision (in the middle of the eyes), and may eventually become blind. (Blindness is fortunately nearly always preventable with early treatment.)

Primary open-angle glaucoma tends to start in one eye but eventually involves both. In about half of patients the damage in the eye is diffuse, that is the nerve damage is generalized. In the other half the disease is localized, causing wedge-shaped abnormalities in the nerve fiber layers of the retina.

Intraocular eye pressure is normal (between 12 - 22 mmHg) in about 25 - 30% of U.S. glaucoma cases, a condition known as normal-tension glaucoma. (In Japan, the rates may be as high as 70%.) Other factors are present that cause optic nerve damage but do not affect IOP.

Closed-angle glaucoma (also called angle-closure glaucoma) is responsible for 15% of all cases. It is less common than open-angle glaucoma in the U.S., but it constitutes about half of the world's glaucoma cases because of its higher prevalence among Asians. The iris is pushed against the lens, sometimes sticking to it, closing off the drainage angle. This can occur very suddenly, resulting in an immediate rise in pressure. It often occurs in genetically susceptible people when the pupil shrinks suddenly. Closed-angle glaucoma can also be chronic and gradual, a less common condition.

Congenital glaucoma, in which the eye's drainage canals fail to develop correctly, is present from birth. It is very rare, occurring in about 1 in 10,000 newborns. This may be an inherited condition and often can be corrected with microsurgery.

The Light-Processing Parts. To understand sight, one begins with light and its passage through the eye's sensitive camera-like structures:

Light first passes through the cornea, a clear tissue at the front of the eye.
Behind the cornea, the iris (the colored tissues of the eye) opens and closes like a camera shutter to regulate the passage of light.
The lens, located behind the iris, focuses the light, which then hits the retina.
The retina is an electric fragile membrane of nerve cells called photoreceptors that receive light and translate it into signals.
A layer of cells, called the retinal ganglia, receive signals from the retina. These nerve cells are the front ends of the optic nerve cable, which, in turn, receive the signals.
The optic nerve is actually a cable of about 1.2 million nerve fibers called axons. It carries the signals to the brain, which interprets them as images.
They exit the eye through the optic disc, located in the back of the eye.

The Supportive Chambers. To help support and protect these sensitive structures, the eye contains two fluid-filled chambers:

The posterior (rear) chamber is the large area behind the iris.
Fluid passes from the posterior into the anterior (forward) chamber located in the bulging area between the iris and the front of the eye.

Causes

No single factor has been identified as a cause of primary open-angle glaucoma. A number of conditions, alone or in combination, are needed to trigger the processes leading to pressure in the first place and then to the nerve damage that destroys sight. The damage done to the optic nerve in glaucoma is triggered in most cases by the excessive pressure on the optic nerve that, over time, causes damage. Because optic nerve damage occurs in patients with normal as well as high intraocular pressure, however, researchers are investigating several other abnormal events that occur and can damage the optic nerve.

A number of genes have now been identified as possible factors in many cases of glaucoma. A gene called MYOC is of particular interest. Defects in this gene occur in between 3 - 6% of patients with adult-onset and juvenile open-angle glaucoma. They appear to overproduce a sticky protein called myocilin, which clogs the trabecular meshwork. The genes WDR36 and OPTN may cause primary open-angle glaucoma. Researchers hope that identification of genes will help improve screening of high-risk patients.

Specific syndromes have been identified with glaucoma. Many have an inherited component, although in most cases other factors must be present to activate the disease process.

Pseudoexfoliation Syndrome. Pseudoexfoliation (PEX) syndrome (also known as exfoliation syndrome) is the most common identifiable condition associated with glaucoma. In one study, 9% of patients with open-angle glaucoma had the syndrome. PEX occurs when dandruff-like matter flakes off the outer layer of the lens and collects in the drainage angle. The substance is composed of proteins produced by the lens, iris, and other parts of the eye. People can have this condition and not develop glaucoma, but they are at high risk. In one Australian study, 14% of the people with this condition had glaucoma compared to 2% of those without exfoliation. PEX has a strong genetic component but other factors (possibly sunlight, an autoimmune response, or slow virus) may be needed to trigger the disease.

Pigment Glaucoma. Pigment glaucoma starts with a condition called pigment dispersion syndrome, an inherited condition in which granules of pigment (the substance that colors the iris) flakes off into the intraocular fluid. In about 30% of cases, these fragments clog the trabecular meshwork and pressure builds up, causing glaucoma. In one study, 2% of patients had this form of glaucoma.

Irido Corneal Endothelia Syndrome. In irido corneal endothelial syndrome (ICE), cells on the back surface of the cornea spread to the drainage angle, sometimes forming scars that connect the iris to the cornea.

Neovascular Glaucoma. Neovascular glaucoma is always associated with other disorders, usually diabetes, that result in abnormal formation of new blood vessels on the iris and in the drainage system.

Aniridia. Aniridia is a rare inherited disorder (in which the iris is abnormal and increases the risk for glaucoma) that is difficult to treat. (A surgical approach called goniosurgery may help prevent glaucoma in young people with aniridia.)

Congenital Glaucoma. When an infant is born with glaucoma (congenital glaucoma), it is usually caused by an inherited abnormality in the drainage canal. Researchers have identified the gene responsible for 85% of these cases.

A natural process called apoptosis (cellular self-destruction) may contribute to damage in the retinal ganglion nerve cells, the nerve cells that are the front line of the optic nerve. Cell death can occur with or without elevated eye pressure. It is not clear what triggers apoptosis and cell death in such cases, but there are a number of suspects.

Excess Glutamate. Researchers have observed abnormally high levels of glutamate in people and animals with glaucoma. Glutamate is an amino acid that excites nerve cells. In the eye this occurs during vision. Some experts theorize that in glaucoma, either reduced blood flow or increased pressure on nerve cells triggers the release of excess glutamate. In large amounts, glutamate causes the nerve cells to fire intensively, which eventually destroys them.

Reduced Blood Flow. Researchers have observed reduced blood flow to the optic nerve in patients with glaucoma associated with both high and normal IOP. Less blood flow suggests oxygen loss, which may play a role in the destructive process. Some studies suggest that the greatest risk factor for nerve damage in patients is when blood pressure to the eye drops during the night. Ocular pressure at this time is highest, so the risk for nerve damage becomes intensified. Of interest in this regard are reports finding a significant reduction in eye blood pressure at night in patients with normal-tension glaucoma.

Excess Nitric Oxide. Elevated levels of nitric oxide, another nerve-stimulating compound, also plays a role in the nerve-damaging process. Nitric oxide is critical for nerve function and flexible blood vessels, but excess amounts may be toxic to nerves.

Glaucoma and Alzheimer's Disease. Some research has pointed out similarities in the process leading to cell death in glaucoma and Alzheimer's disease. Specifically, in both diseases activation of certain enzymes called caspases occurs and leads to accumulation of fragments of beta amyloid, an insoluble protein that forms sticky patches.

Autoimmunity. Some experts are studying the possibility that normal tension glaucoma may be an autoimmune disease; that is, factors in the immune system, including antibodies, attack cells in the person's own body as if they were foreign substances. In the case of glaucoma, such antibodies would damage parts of the optic nerve.

H. pylori Infection. Some research indicates that glaucoma is associated with Helicobacter (H.) pylori, the bacterium implicated as a major cause of peptic ulcers. Studies have reported over 87% of patients with glaucoma are infected with this bacterium.

People with acute closed-angle glaucoma often have a structural defect that causes a narrow angle between the iris and cornea where the aqueous humor circulates. Conditions that suddenly dilate the pupils may cause this shallow angle to close and precipitate attacks of acute glaucoma in susceptible people. Such conditions may include:

Certain drugs such as antihistamines, tricyclic antidepressants, some asthma medications (nebulized ipratropium), some anti-seizure drugs (topiramate)
Darkness
Emotional stress

When intraocular pressure leading to glaucoma is caused by other diseases or conditions, it is known as secondary glaucoma. Secondary glaucoma may be chronic or acute, mild or severe.

Medical Conditions. A number of diseases can contribute to the development of intraocular pressure leading to glaucoma:

Diseases that affect blood flow to the optic nerve (diabetes, high blood pressure, migraine; people with type 2 diabetes should be regularly screened for glaucoma.)
Hypothyroidism
Sleep apnea
Physical injury in the eye
Extreme nearsightedness (myopia)
Previous eye surgery
Other disorders, including leukemia, sickle cell anemia, and some forms of arthritis

Corticosteroids. Corticosteroids, commonly called steroids, have multiple effects on the trabecular meshwork and may even cause genetic changes. In fact, studying the effects of steroids on the eye is helping researchers understand the glaucoma disease process. Steroids pose a higher or lower risk depending on the form:

Taking topical steroid treatments in the eye poses the highest risk. It must be monitored carefully since, in some cases, damage may be permanent.
Taking oral corticosteroids, particularly in high doses or for long periods, increases the chance of glaucoma. In such cases, the eye disorder typically develops almost immediately and reverses within 2 weeks after the drug has been withdrawn.
Inhaled steroids were not thought to cause glaucoma, but there is some risk in people with a family history of glaucoma and other risk factors.

Symptoms

Chronic glaucoma is insidious. If the pressure increases slowly, it will not produce any symptoms until it has done irreversible damage. In such cases, people may notice visual problems at first only when light is dim. Patients are often sensitive to glare. Eventually they may lose contrast sensitivity; that is, they might have trouble differentiating between varying shades and brightness.

In acute closed-angle glaucoma, the pressure inside the eye increases quickly, and the symptoms are dramatic. Intense pain in the eyebrow area and blurred vision develop usually in one eye, and the patient often feels like the eye will burst (although it won't). The eye usually reddens. A person may see rainbow-like halos around lights. Sometimes nausea and vomiting occur. These symptoms may occur on and off and not appear as a full attack. In either case, they indicate a medical emergency. In chronic closed-angle glaucoma, the process is gradual and painless.

Although congenital glaucoma is usually present at birth, symptoms generally don’t develop in the infant for a few months. If parents notice that an infant’s eyes are enlarging, becoming cloudy, often watering, or tending to close in the presence of light, they should have an ophthalmologist examine the child’s eyes. Port-wine stains on an infant’s face could indicate the Sturge-Weber syndrome, a disorder that occasionally causes glaucoma.

Outlook

Worldwide, glaucoma ranks as one of the leading causes of blindness. Even if people with glaucoma do not become blind, vision can be impaired. In developed countries, most people get treatment in time to preserve their vision. Even so, glaucoma causes between 3 - 6% of blindness cases in Caucasians, and even more cases in African Americans.

In a 20-year study of Caucasian patients with glaucoma, blindness in at least one eye occurred in 27% of patients and blindness in both eyes occurred in 9% of patients. The blindness rates in African Americans are most likely higher. In fact, glaucoma is the leading cause of blindness in African Americans. Despite this higher prevalence, this ethnic group receives surgical treatment at half the rate of Caucasians.

The Process Leading to Vision Loss. Chronic glaucoma is often called “the silent thief of sight," because the afflicted person has no warning sign, no hint that anything is wrong. Untreated, the destruction develops slowly over time:

Over years or decades, the increased pressure compresses nerves at the back of the eyes.
Glaucoma gradually destroys first the outer fibers of the optic nerve, which reduces peripheral vision (the top, sides, and bottom areas of vision), but not central vision.
By the time a person notices that peripheral vision has been lost, permanent damage has already occurred.
If the eye pressure remains high, the destruction can progress until tunnel vision develops, and the person is only able to see objects that are straight ahead.
The last nerve fibers destroyed are those responsible for central vision; if this occurs, the glaucoma victim becomes totally blind.

Although there is no cure for open-angle glaucoma, a number of treatments are available that lower intraocular pressure and slow progression of vision loss.

Risk Factors for Vision Loss. Estimates of progression rates in vision deterioration range from 9 - 30% over a 2 - 7 year period.

According to a study on patients with elevated IOP, for every 1-mm Hg increase in IOP, there is a 10% higher risk of disease progression. A very elevated IOP (above 30 mm Hg) is certainly hazardous. An elevated IOP that is below 30 mm Hg, however, is not necessarily the most important factor in determining the risk for disease progression. Some evidence suggests that frequent and large daily fluctuations in intraocular pressure, not simply high IOP, are associated with the greatest risk for loss of vision. Having normal-tension glaucoma with optic nerve damage also carries a high risk for progression, even if eye pressure is reduced.

In any case, factors other than IOP play a role in increasing the chances for progression and vision loss in patients with slightly elevated IOP and normal tension glaucoma:

Both eyes affected
Pseudoexfoliation (PEX) syndrome. PEX occurs when proteins produced in the eye flake off the outer layer of the lens and collects in the drainage angle.
Bleeding in a specific region called the peripapillary nerve fiber layer
Thin corneas. (People who have thick corneas and elevated IOP may only need to be monitored if they have no other risk factor for vision loss.)
Larger cup-to-optic disc ratio. (The cup of the optic disc is the center portion, which enlarges as nerve damage progresses.)

Non-eye related factors associated with disease progression include being elderly, African American, female, or having a history of migraines.

Acute closed-angle glaucoma is a medical emergency; if the high pressure is not reduced within hours, it may permanently damage vision. Anyone who experiences its symptoms should immediately contact an ophthalmologist or go to a hospital emergency room.

Risk Factors

About 2 million Americans have open-angle glaucoma, but an exact count is unclear. Experts estimate that by 2010, over 60 million people worldwide will have glaucoma, with 74% of these cases due to open-angle glaucoma. Half of people with glaucoma are unaware of this problem because the condition causes no symptoms.

Elevated intraocular pressure in the eye occurs in 5 - 10 million Americans, but only about 10% of such people develop glaucoma because of this pressure. And, in 15% of actual glaucoma cases, IOP is normal. Major studies are helping to clarify the people who are at highest risk for glaucoma and optic nerve damage, including those with normal tension glaucoma.

Elderly. The prevalence of chronic glaucoma increases with age. In a major study, 0.6% of people age 60 - 64 had primary open-angle glaucoma. Among people who were 10 years older, the prevalence had more than doubled to 1.3%, and among those who were age 80 - 84, it had more than doubled again to 3%.

People of African Descent. Across all age groups, according to a 2000 report, the prevalence of glaucoma in African Americans is about 3.5% compared to about 1% in Caucasians. In addition, U.S. studies suggest that glaucoma develops earlier in African American population groups (starting at age 45 instead of age 60 in Caucasians). And, their risk for blindness once they have glaucoma is 14 - 17 times that of Caucasians with glaucoma. African American men are at higher risk than women. African American children who are extremely near-sighted and have relatives with glaucoma should begin regular eye examinations for glaucoma as early as possible.

In a major glaucoma study in Barbados, where most people are of African descent, over 10% of those age 50 and older had open angle glaucoma, and over 15% were afflicted after age 70. About half of the cases had normal or lower eye pressure. An interesting 2001 study suggested that African Americans tend to have significantly thinner central corneas than Caucasians. This could lead to misleadingly lower pressure scores in African American patients who actually may have high IOPs.

Family History. Glaucoma tends to run in families. Brothers and sisters of patients with open angle glaucoma are 5 times more likely to develop glaucoma by the time they are 70 years old than people whose siblings do not have the disease. Previous studies have also found that people with family histories of glaucoma are more likely to already have some vision loss when they are first diagnosed with glaucoma.

Effects of Blood Pressure. The association between a person's blood pressure and intraocular pressure in the eye is not entirely clear. A number of studies have found a higher risk for glaucoma in people with high blood pressure. A 2002 study suggested, however, that people with blood pressure that is low relative to their intraocular pressure may be at higher risk for glaucoma. The same study found no higher risk for glaucoma in people with hypertension, and in fact, high blood pressure was associated with a lower risk.

Having Certain Medical Disorders. Individuals with certain medical or physical conditions, including diabetes, migraine, nearsightedness, and sleep apnea, appear to have a higher risk. Conditions that require the use of any oral or inhaled steroid, particularly high doses for prolonged periods of time, can cause glaucoma. Previous eye surgery also puts people at risk.

Weightlifting. According to a 2006 study, holding your breath while weightlifting can increase the risk for developing normal-tension glaucoma. Weightlifting causes temporary increases in eye pressure; holding your breath during this exercise leads to even greater intraocular pressure.

Risk Factors for Closed-Angle Glaucoma. Chronic closed-angle glaucoma tends to be more common in people of Asian and African descent. Those who have this condition are often extremely farsighted. Acute closed-angle glaucoma occurs much more frequently in women than in men.

Risk Factors for Normal Tension Glaucoma. Risk factors for normal tension glaucoma include Japanese ancestry and a family history of the disease. It is more common in women than in men. A family history of cardiovascular disease also increases the risk.

Risk Factors for Pigmentary Glaucoma. Pigmentary glaucoma occurs three times more often in men then in women and at a younger age.

Risk Factors for Irido Corneal Endothelial Syndrome. This condition occurs more often in light-skinned women.

Diagnosis

A diagnosis of glaucoma no longer simply relies on the presence of pressure within the eye. It requires that there be optic nerve damage or a strong suggestion of damage, which can be clearly seen during a dilated eye examination of the optic nerve. In general, the hallmark sign of this condition is a loss of peripheral vision. With peripheral vision loss, a person can see in front of him- or herself but has lost the vision to the side.

The optic nerve carries the information of vision from the eye to the brain.

Because chronic glaucoma has no warning symptoms, half of its victims are unaware that they have the condition. Early diagnosis, however, is the key to successful treatment of glaucoma. One study reported that the more years since the last visit to an eye professional, the greater the risk for having visual loss.

Everyone over age 65 and African Americans over 40 years old should have periodic eye exams, including tests for glaucoma, every other year.
African Americans between ages 20 - 39 should have eye examinations every 3 - 5 years.
Other people at higher risk (people with diabetes, history of eye injuries, a family history of glaucoma, or those taking corticosteroid medications) should have eye examinations every year after age 35.
People with known glaucoma should have frequent examinations to check peripheral vision and to be sure treatment is maintaining a safe eye pressure. After such examinations, the ophthalmologist will assess current treatment and make necessary adjustments.

Doctors determine the intraocular pressure (IOP) of the aqueous humor inside the eye using tonometry, which measures the force necessary to make an indentation in the eye. There are several methods:

In the Schiotz method, the doctor first anesthetizes the eye with drops, then presses very lightly against it with tonometer, a tiny smooth instrument that is used to measure the pressure.
In the applanation method, the doctor touches a strip of orange-dyed paper to the side of the eye. The stain helps with the examination and rinses out with tearing. The doctor uses a slit-lamp, which is moved forward toward the patient's face until the tonometer touches the eye.
The noncontact approach applies a puff of air and measures the force needed to indent the eye.

Attempting to close the eyelids during the test can increase eye pressure and produce errors in the results.

In general, normal IOP is usually maintained at measurements of 10 - 20 mm Hg. Glaucoma pressure over 21 mm Hg indicates a potential problem. The test is not completely accurate, however. Only about 10% of people with IOP levels between 21 - 30 mm Hg will actually develop glaucoma and optic nerve damage. On the other hand, many people with glaucoma have normal pressure, at least for part of the time.

Changes in posture may also affect IOP. A 2006 study indicated that IOP increases during sleep or when a person is lying down. As IOP tests are generally given in a doctor’s office when a patient is sitting up, they may not provide a completely accurate evaluation of eye pressure.

The cornea thickness may be an important indicator of disease progression in patients with elevated IOP. According to some research, patients with thinner corneas have a significant risk for developing damage from glaucoma, while those with thicker corneas have a low risk.

In order to determine early damage in the optic nerve, a number of diagnostic instruments have been developed to assess the nerve fiber layers at the back of the eye (the fundus) and to check for optic disk cupping. (The cup of the optic disc is the center portion, which enlarges as nerve damage progresses.) The two most common procedures for identifying nerve damage are ophthalmoscopy and fundus photography. Other instruments have been developed, including those that use laser technology and computers, but none have proved to be infallible. No test has proven to be completely accurate, however, and none is routinely performed by all eye professionals.

In order to be accurate, the tests require a skilled professional and there are certain common factors:

The pupils must also be widely dilated using eye drops before the procedure.
Even mild cataracts and a slightly less-than-optimally dilated pupil can degrade the results. Such conditions are common in elderly people, who are the most likely to develop glaucoma.
If the back of the eye is lightly pigmented (colored), the area under observation is less distinct.
If the glaucoma is diffuse and there is a generalized loss of nerve fiber (which occurs in half of patients), it is more difficult to detect than if the glaucoma is more localized.

If IOP is low or normal and tests report optic nerve damage and peripheral visual loss, doctors should also check for other conditions before starting any treatment for glaucoma. Such problems include steroid use, anemia, and previous hemorrhage or severe low blood pressure.

Ophthalmoscopy. The eye professional (or even a primary care doctor) uses an ophthalmoscope to peer through the pupil directly at the optic nerve. The examiner can then check the shape and color of the nerve fibers to evaluate whether they have been damaged by the high pressure of glaucoma. Damaged nerve fibers may be indicated by:

An asymmetrical or elongated cupped optic nerve
The optic nerve color may be pale or an unhealthy-pink

If results show no optic nerve damage in patients who have mild elevations in pressure, the ophthalmologist may want to retest frequently but delay drug treatment, unless the patient has significant risk factors.

Fundus Photography. Fundus photography may be used to take pictures of the optic nerve and can reveal changes years in advance of vision loss. It is an unpleasant procedure requiring drops and a bright flash. This procedure has the same limitations as ophthalmoscopy.

Laser Polarimetry. Polarimetry uses laser technology to scan the eye and does not require any response from the patient. It is reported to be able to measure nerve fiber thickness in the eye and so be able to reveal early signs of deterioration. Preliminary studies have indicated that it has a diagnostic accuracy of over 90% for both confirming and ruling out glaucoma. One study, however, reported that laser polarimetry was sensitive enough to detect glaucoma in only up to 57% of patients with early glaucoma, 71% of those with moderate disease, and 81% of those with severe glaucoma. More research is needed.

Other Devices. Computer-assisted devices, such as the confocal scanning laser ophthalmoscope, are now available that may be useful for evaluating the retinal nerve layer. Another instrument, the optical coherence tomograph, measures the echo time delay of light that is scattered back from different layers in the retina. The value of these tests has not yet been determined.

If there is indication of optic nerve damage, the eye professional will conduct tests of the visual fields (the areas that the patient can see). In most people with glaucoma, the first areas to become noticeably impaired are the peripheral visual fields (areas of sight that are not directly in front of a person but more to the sides).

Click the icon to see an image of the visual field test.

Standard Perimetry Tests. Perimetry tests are used to check peripheral vision. One variation of this test is as follows:

A person sits closely facing a large computer-like monitor.
Small bright white lights flicker on and off hundreds of times, at different places on the screen, while the patient clicks a button whenever one of the lights is seen.
The machine prints out a report that maps any blanked-out areas in the person’s vision.

The test is complex and lengthy; elderly people and those with short attention spans may be inappropriate candidates. Other perimetry tests, some requiring less time to administer and some using "virtual reality" techniques, are currently being developed.

Other Tests. Other visual field tests are being developed that can detect abnormalities years before they can be detected by standard perimetry. Experts recommend some of these tests in selected patients with suspected glaucoma.

For example, a screening test called frequency doubling technology (FDT) checks for changes in particular cells in the retina that are indications of early glaucoma. It takes less than a minute to perform.

Another test called short wave automated perimetry (SWAP) uses colors (blue-on-yellow) and also detects very early abnormalities in the visual field. Testing time is longer than with FDT, however, and the presence of certain types of cataracts can interfere with its accuracy.

ELAM-1. Endothelial leukocyte cell adhesion molecule 1 (ELAM-1) is a molecule that has been found in glaucoma but not in healthy eyes. This molecule may prove to be a "marker" and its presence may be helpful in diagnosing glaucoma.

A simple test using a penlight helps determine the risk for acute closed-angle glaucoma. A beam of light is directed from the side of the face toward the patient's iris. If no shadow appears on the nose, then most likely the angle is wide enough to dilate. Using an instrument called a gonioscope, ophthalmologists can also inspect the front of the eyes and assess the drainage angle between the cornea and the iris and the channels in the trabecular meshwork. This test can differentiate between closed- and open-angle glaucoma.

Treatment

Most treatments for glaucoma aim to reduce ocular pressure and its fluctuations. Early treatment with medications, surgery, or both can nearly always maintain safe pressure of the aqueous humor, thus preventing optic nerve damage and blindness. The choice between surgery and medications and when to start treatment is not always straightforward. For example, with the introduction of beta blockers and newer glaucoma drugs, there has been a decline in surgeries. It is not clear, however, which drugs are more effective than others and if, over time, any will actually prevent surgery. Patients should discuss all issues with their doctors and ophthalmologists.

Many people have high IOP but no sign of nerve damage. Over the course of 20 years, only between 10 - 30% of these people will actually develop glaucoma. Nevertheless, once glaucoma has destroyed optic nerve fibers, no known treatment can reverse the damage.

Indeed, studies suggest that in people with glaucoma, even very small differences in pressure may mean the difference between disease progression and stability. An important trial reported that, on average, treating patients when their glaucoma was first detected reduced IOP by 25%. In addition, treatment reduced the risk for progression by 17%. This study confirmed previous findings supporting early treatment for glaucoma. Another study found that treatment with eye drops halved the risk of developing open-angle glaucoma in African Americans who had elevated IOP. Some evidence suggests that early treatment to lower IOP may be beneficial even in patients with normal tension glaucoma.

However, not all individuals with early signs of glaucoma (elevated IOP or normal-tension glaucoma) develop optic nerve damage and serious vision problems. Nor does treatment prevent progression in a large minority of patients. Medications used for glaucoma also can carry significant side effects and risks.

Some experts suggest that treatment is warranted only in people with early signs of glaucoma who have risk factors for progressive disease and vision loss (thinner corneas, larger cup to optic disc ration, older age, and elevated pressure).

A number of effective drugs are now available for treating glaucoma. The drugs reduce pressure in the eye but all have a number of side effects that affect other parts of the body. Some of these side effects can be quite severe. Many of the drugs used for glaucoma also interact with common medications for other conditions. To compound the difficulties, many patients require multiple drugs. As a result, only about half of patients comply with their treatments.

Experts generally recommend topical drugs first (those that can be used as eye drops or ointments rather than taken by mouth).

Topical beta blockers are the standard first-line drugs, most commonly timolol (Timoptic). Newer beta blockers include betaxolol (Betoptic), levobunolol (Betagan), carteolol (Ocupress), and metipranolol (OptiPranolol). Timolol has been used for years, and these other drugs are also well tolerated.
Topical prostaglandins are alternatives if beta blockers fail. They include latanoprost (Xalatan) and unoprostone (Rescula). Of the standard drugs used for glaucoma, these drugs have the greatest effect on lowering IOPs. They also have fewer widespread effects than the beta blockers.
Topical carbonic anhydrase inhibitors (CAIs) are less effective than standard beta blockers or prostaglandins but have fewer widespread effects than the beta blockers. They may be helpful in certain cases. Topical forms are dorzolamide (Trusopt) and brinzolamide (Azopt). (Oral CAIs are available and more effective, but they have severe side effects and are rarely used for the long term.)
Alpha2-adrenergics, also called selective alpha adrenergics, are effective but may not be as well tolerated as timolol. They include brimonidine (Alphagan).
Miotics, which include pilocarpine and others, were the standard drugs before the introduction of topical beta blockers. They have now been largely replaced by timolol and others, although they are sometimes used in combinations.
Beta blockers and newer drugs (prostaglandins, topical CAIs, and selective alpha adrenergics) are now preferred over the older drugs, which include miotics, oral CAIs, and nonselective alpha adrenergics.

Combinations. Combinations of these drugs can be very effective, because they tend to have different actions. Single medications that contain two drugs are becoming available. For example, Cosopt combines timolol and dorzolamide; Timpilo is a combination of timolol and pilocarpine. Studies of these and other combinations compared to each other to single drugs are ongoing. To date, results on any superior combinations have been mixed. It should be noted that the side effects of each drug apply to any combination.

Treating the Pregnant Patient. Considerations for a pregnant woman with glaucoma can be complicated. All of the drugs used for glaucoma are absorbed by the body, cross the placenta, and are excreted in breast milk. Many have effects that can interfere with or adversely affect pregnancy.

Women should discuss going off medication, particularly during the first trimester, and be monitored during that time for increasing eye pressure. IOP tends to drop during pregnancy, although usually not to a significant degree. In addition, changes in IOP and visual loss vary greatly. Some women experience no IOP change or visual loss during pregnancy, while others may experience an increase in IOP or worsening of visual loss. It is important that your ophthalmologist carefully considers your individual case and discusses with you the risks and benefits of continuing glaucoma medication during pregnancy.

If women need to take medications, they should try to achieve the lowest dose possible. Some drugs have fewer side effects than others. Pregnant women must also be very careful about administering eye drops to allow as little medication as possible to enter the body. When taking eye drops, press your index finger against the corner of the eye near your nose. This helps prevent the eye drop from passing down into the tear duct where it is easily absorbed through the rest of the body. Even this approach, however, does not guarantee complete safety. Women with glaucoma who are planning to become pregnant might want to consider surgery before they conceive.

The object of standard glaucoma surgery is to reduce pressure in the eye by increasing the outflow of the aqueous fluid. Two methods are commonly used:

Filtration surgery (trabeculectomy). This uses standard surgical instruments to open a passage in the eye for draining fluid.
Laser trabeculoplasty. This procedure uses a laser to burn 80 - 100 tiny holes in the drainage area.

Both are effective, but certain patient groups may respond to one more than the other. For example, African Americans may do better with laser surgery while trabeculectomy may be a better choice for Caucasians with no serious medical problems.

In general, surgery is a last resort. Doctors may, however, recommend surgery before drug therapies for patients unlikely to comply with difficult drug regimens or for patients who may have severe reactions from the glaucoma drugs. Women who plan on becoming pregnant should also discuss surgery with their doctor.

Some studies indicate that laser treatment performed as the initial treatment for glaucoma is as effective as medications in some cases. Findings in 2003 from a major comparison study suggested that 4 years after surgery there was little difference in visual field loss between trabeculectomy and medical treatment. There was, however, a higher risk for cataracts and loss of vision sharpness with surgery. On the other hand, side effects from medications may be ongoing and troublesome. It is important to note that even surgery does not cure glaucoma, and over half of patients will require medication within 2 years. Experts who are against early surgeries also argue that studies on their success often omitted serious postoperative problems, such as late-onset infection, and quality of life assessments.

Medications

Nearly all glaucoma medications are prescribed for reducing eye pressure. Lowering IOP is even proving to be beneficial for about two-thirds of patients with normal-pressure glaucoma.

Topical beta adrenoceptor blockers (common called beta-blockers) are the drugs most often prescribed to treat glaucoma. They lower the pressure inside the eye by inhibiting the production of aqueous humor.

Brands. These drugs are categorized as either nonselective or selective beta-blockers:

Nonselective adrenoceptor beta-blockers. Timolol (Timoptic, Betimol) has been the standard beta-blocker for years. Newer nonselective drugs include levobunolol (Betagan), carteolol (Ocupress), and metipranolol (OptiPranolol). A few studies suggest some are more beneficial than timolol with similar side effects.
Selective beta1-adrenoceptor blockers. Betaxolol (Betoptic) and levobetaxolol (Betaxon) are selective beta-blockers. These drugs appear to have fewer adverse effects on the heart than the nonselective beta-blockers, although they still have widespread effects. Studies also suggest that they slow progression more than timolol, although timolol is more effective at lowering IOP. selective beta-blockers may also have nerve-protecting properties.

All beta-blockers are effective and generally well tolerated. Because they cause less eye irritation than many other glaucoma medications, they are often prescribed for patients who also have cataracts.

Side Effects and Complications. After the beta-blocker is administered, only a tiny amount of the drug is absorbed by the cornea. Most of it enters in the bloodstream. These drugs, therefore, can cause side effects in parts of the body other than the eyes ("systemic" side effects):

Common systemic side effects include reduced sexual drive, fatigue, depression, anxiety, severe nausea and vomiting, and breathing difficulties.
Beta-blockers affect the heart. They lower heart rate and reduce blood pressure. (The newer selective beta-1 blockers may not have as bad effects on the heart as the nonselective beta-blockers.) They may also cause unhealthy cholesterol and triglyceride changes.
All beta-blockers can worsen severe asthma or other lung diseases. Beta-blockers should only be used very cautiously or not at all by anyone with asthma, emphysema, bronchitis, or heart disease. In one study, lung function was reduced in 40% of elderly people who took timolol, even those without previous symptoms of lung problems. (Selective beta-blockers may produce fewer of these adverse effects.)
If the patient is switching to a beta-blocker from other glaucoma medication, there may be a sudden rise in eye pressure. It is important that the pressure be checked shortly after the other drug has been withdrawn.
When beta-blockers are used to treat one eye, the other (contralateral) eye also experiences a lesser, but still significant reduction in IOP.

Interactions with Other Medications. The effects of the eye medication may be additive to other oral medications, such as oral beta-blockers, calcium-channel blockers, or the antiarrhythmic drug quinidine. People with diabetes who take insulin or hypoglycemic medications should realize that timolol side effects may resemble and mask the symptoms of hypoglycemia (low blood sugar).

Prostaglandins are hormone-like substances that help open blood vessels. Drugs that resemble prostaglandins increase outflow of aqueous humor (the watery substance in the eye). Drainage of aqueous humor helps reduce intraocular pressure.

Brands. Latanoprost (Xalatan) and unoprostone (Rescula) are the standard brands. Latanoprost was the first prostaglandin to be approved as first-line treatment for elevated eye pressure. Two newer prostaglandins, travoprost (Travatan) and bimatoprost (Lumigan), may help some patients who do not respond to latanoprost. These drugs may also benefit patients with normal-tension glaucoma. Latanoprost, travoprost, and bimatoprost need to be taken only once daily. Unoprostone needs to be taken twice a day and is not as effective as others, but it still can reduce IOP significantly and is the least expensive of these drugs.

Latanoprost has been shown to reduce pressure by between 45 - 70%. Some, but not all studies, have suggested that newer prostaglandins travoprost (Travatan) and bimatoprost (Lumigan) are more effective than latanoprost, but the older drug appears to be better tolerated. All of these drugs may be work better than timolol in lowering IOP. The newer prostaglandins may be especially superior to timolol in treating African American patients. In comparison studies, latanoprost achieved better IOP pressure reduction than brimonidine. Studies have suggested that bimatoprost is more effective in lowering eye pressure than a combination of timolol and dorzolamide (Cosopt). Studies have been mixed on whether latanoprost is superior to the combination.

Side Effects. These drugs do not slow down the heart rate and also appear to be safe for people with asthma. Side effects include itching, redness, and burning during administration. Muscle and joint pain may also occur. All of these drugs may permanently change eye color from blue or green to brown. To date, such color changes do not seem to be hazardous. (The only significant problem may be cosmetic in people who treat only one eye, since the color may differ from the other.) These drugs can increase blood flow in the eye and also make eyelashes become thicker and longer in some patients. (These latter effects are more common with bimatoprost and travoprost than with latanoprost.)

Carbonic anhydrase inhibitors (CAIs) decrease eye pressure by reducing the fluid in the chambers of the eye (aqueous humor). Research suggests that CAIs reduce aqueous humor fluid by as much as 40%. These drugs are used for glaucoma when other drugs do not work. They may be combined with other medications.

CAIs may also improve blood flow in the retina and optic nerve (beta-blockers do not). Improving blood flow can keep the disease from getting worse.

Brands and Side Effects. CAIs are available in the following forms:

Eye-drop CAIs include dorzolamide (Trusopt) and brinzolamide (Azopt). About 10% of patients report fatigue, stinging in the eye, and loss of appetite using dorzolamide. Taste changes can occur. Research suggests that dorzolamide can be helpful for children with glaucoma, including those younger than 6 years old. Brinzolamide is a newer medication that was chemically designed to be closer in pH to human tears and may cause less stinging than dorzolamide.
Oral forms include acetazolamide (Diamox), methazolamide (Neptazane), and dichlorphenamide (Daranide). Although they are more effective than eye drops, they have significantly more side effects and are rarely used for long-term treatment. The oral forms have very unpleasant side effects that include frequent urination, depression, stomach problems, fatigue, weight loss, sexual dysfunction, and, in infants, failure to thrive. Long-term use of the oral forms, in rare cases, can cause serious anemia and kidney problems, including the risk for stones. They can also produce a toxic reaction when taken with large doses of aspirin.

Adrenergic agonists activate muscles in the eye that dilate pupils and, therefore, increase outflow of aqueous fluid. Newer variations called alpha 2-adrenergic agonists reduce production of aqueous humor and also increase outflow through the uveoscleral pathway (the alternative channel to the trabecular meshwork). Older adrenergic agonists include epinephrine.

Alpha 2-Adrenergic Agonists. Apraclonidine (Iopidine) and brimonidine (Alphagan) are alpha 2-adrenergic agonists. These have generally been used before glaucoma surgery, but a number of studies are indicating that they may even be useful as primary therapy when used in combination with beta-blockers or other standard drugs.

Brimonidine is proving to be particularly effective for long-term therapy. (Apraclonidine is used for the short term.) It also may have nerve-protecting properties and may be safer than other drugs during pregnancy and for patients with asthma.

The most common side effects of brimonidine and apraclonidine are dry mouth and altered taste. They also commonly trigger an allergic reaction that causes red and itching eyes and lids, a major drawback. Brimonidine causes less of an allergic response than apraclonidine. Unlike apraclonidine, however, it can cause lethargy and mild low blood pressure. It also appears to remain effective longer.

Miotics, also called cholinergic agonists, narrow the iris muscles and constrict the pupil. This action pulls the iris away from the trabecular meshwork and allows the aqueous humor to flow out through the drainage channels, reducing the pressure inside the front of the eye.

Brands. Pilocarpine (Pilocar, Adsorbocarpine, Almocarpine, Isoptocarpine, Ocusert) was the most widely used anti-glaucoma drug before timolol was introduced. It is the preferred miotic. Because pilocarpine is used up by the body fairly quickly, however, patients must take it several times a day; many people, therefore, fail to take their medication regularly. A combination of timolol or latanoprost with pilocarpine is more effective than either drug used alone. Carbachol is another miotic.

Demecarium (Humorsol), isoflurophate (Floropryl), and echothiophate (Phospholine) are a group of long-acting drugs known as anticholinesterase miotics. Because of their potential for serious side effects, however, some authorities even prefer surgery to their use.

Epinephrine and its derivatives are the older anticholinergics. Epinephrine is now rarely prescribed because of side effects. Dipivefrin (Dipivefrin), a newer form of epinephrine, remains inactive until it reacts with enzymes in the cornea. It is effective in low doses and causes few systemic side effects.

Side Effects. Side effects include:

Teary eyes, brow-aches, eye pain, and allergic reactions.
A miotic narrows the pupil and so can cause nearsightedness. Vision can also become dim and it may difficult to see in darkened rooms or at night, when driving could be hazardous. A gel form administered once a day or wafer placed under the lid once a week may help reduce these side effects.
The anticholinesterase miotics increase the risk of cataract development and are therefore used mostly in patients in whom cataracts have already been removed. Retinal detachment is an uncommon but dangerous side effect in susceptible individuals. Excessive use of these miotics may cause toxic reactions, including convulsions, muscular paralysis, and even death from respiratory failure.
Epinephrine can produce burning in the eyes, enlarged pupils, and allergic reactions. Occasionally it can cause anxiety and headaches. Rare side effects include high blood pressure and disturbances in heart rhythm. It is rarely prescribed now. Although dipivefrin, the newer form of epinephrine, has fewer systemic side effects, it still causes problems in the eyes similar to those of epinephrine.

Cannabinoids. Cannabinoids, compounds in marijuana (cannabis), are being studied for their effects on glaucoma. For example, oral or inhaled tetrahydrocannabinol (THC), the active ingredient in marijuana, has been shown to reduce IOP in 60 - 65% of patients. The effects of smoking marijuana on IOP last only 3 hours, however. THC also increases the release of glutamate -- a nerve-protecting chemical. Experts are hoping that topical use of THC or other cannabinoids may help prevent optic nerve damage without the widespread effects of oral or inhaled administration.

Reasons for Noncompliance. Studies indicate that more than 40% of patients miss 10% of their doses, and 15% of patients miss more than 50% of their doses. Noncompliance is very high for many reasons:

People with chronic glaucoma who are on medication must use eye drops or take pills one or more times a day, usually for the rest of their lives.
Many people require a multi-drug regimen, two or more different kinds of medications that can be used in various combinations, such as eye drops, ointments, or time-release wafers inserted under the eyelid. Such regimens can be very confusing.
The side effects of the drugs are more unpleasant than the disease itself, which has no symptoms until vision is lost. Because the treatment does not usually produce any noticeable improvement, the consequence of not taking the drugs (blindness) may seem far in the future.
Skipping even a few doses can greatly increase the risk of visual loss. It is essential that patients tell their doctor if they are not regularly taking their medication. Otherwise, the doctor may increase the dosage, thereby causing unwelcome side effects.

Patients who do not regularly take their glaucoma medication are at high risk for blindness. If you have problems taking your medications or sticking to the dosing regimen, talk with your doctor.

Hints for Managing a Regimen.

Pharmaceutical manufacturers use colored tops, yellow for timolol, for example, and green for pilocarpine, to help prevent mix-ups. Creating a chart scheduling each drug by color can be helpful.
Small electronic timers are available that will signal times for taking the medications. The timing of these combinations is important. For example, the combination of pilocarpine with latanoprost is most effective when pilocarpine is taken four times a day and when the bedtime dose is administered an hour after latanoprost.
Some patients may be candidates for single medications that combine two drugs, such as Cosopt, which contains both dorzolamide and timolol. This medication requires only one drop twice per day. Patients who need additional glaucoma drugs, however, will need to take these two drugs separately.
When using any drug for a long period of time, side effects are a potential problem. If they become intolerable, patients should discuss with the doctor reducing the dosage or trying other drugs.

Administering Eye Drops. A common reason that medicine does not work is that patients do not take it correctly. Patients should ask the ophthalmologist to watch while they place the drops in their own eyes to make sure the procedure is being done correctly. The following are some recommended steps:

If you use both ointments and eye drops, take the eye drops first.
Wash your hands before applying eye drops.
Hold the bottle upside down.
Tilt your head back and, with one hand, pull the lower eyelid down to form a pocket.
With your other hand, hold the bottle as close as possible to your eye. Don’t let the bottle directly touch your eye or eyelid.
After you have placed the drop, close your eye or press your index finger against the corner of the eye near your nose. Gently move the lower lid upward until the eye is closed. Keep your eye closed for at least 1 minute. This prevents the drop from draining out.
Wait at least 5 minutes before applying another drop or a different medication

In this emergency situation, ophthalmologists may administer a combination of two or more anti-glaucoma medications to reduce eye pressure quickly before it can damage the optic nerve and cause visual loss. Apraclonidine (Iopidine) is a powerful drug used before and after laser surgery to prevent an increase in fluid pressure and is more effective than other medications. In addition to standard drugs, doctors may also administer glycerin (Glyrol, Osmoglyn) by mouth or mannitol or acetazolamide intravenously. Surgery is almost always performed once the pressure is reduced.

Most rare forms of glaucoma respond to the same medications and surgery used for open angle glaucoma. Irido corneal endothelial syndrome (ICE) is difficult to treat and if surgery is required, filtering surgery is the best choice. Neovascular glaucoma is also very hard to treat; researchers are investigating drainage implants for this disorder.

Surgery

If medications do not control eye pressure, or if they create intolerable side effects, surgery may be necessary in a small percentage of people with chronic glaucoma. It may be particularly helpful for patients with pseudoexfoliation glaucoma.

The standard procedures are usually one of the following:

Filtration surgery (trabeculectomy). This procedure opens the full thickness of the drainage area.
Laser trabeculoplasty. This procedure partially opens the drainage area. It does not reduce pressure to the extent of trabeculectomy but it has fewer adverse effects.

African Americans may respond better to initial laser surgery than to conventional trabeculectomy, while the opposite may be true in Caucasians. Some experts now recommend that, in most circumstances, African Americans should start with laser surgery and Caucasians who have no serious medical problems should have trabeculectomy first.

In addition, a number of experimental and less invasive procedures are under development.

The Procedure. Filtration surgery has been used for more than 100 years with only minor modifications. It employs conventional surgical techniques known as full-thickness filtering surgery or guarded filtering surgery (trabeculectomy).

The surgeon creates a sclerostomy, a passage in the sclera (the white part of the eye) for draining excess eye fluid.
A flap is created that allows fluid to escape but which does not deflate the eyeball.
The surgeon may also remove a tiny piece of the iris (called an iridectomy) so that fluid can flow backward into the eye.
A small bubble called a bleb nearly always forms over the opening, which is a sign that fluid is draining out. Although surgeons aim for a thick bleb, which poses less risk than a thin one for later leakage, paradoxically the ideal operation would have no bleb at all.

The procedure has a high success rate. About 50% of patients no longer need medication after surgery. Thirty-five to 40% of those who still need medication have better control of their glaucoma.

A new instrument called a trabectome has allowed for a less invasive type of trabulectomy surgery The trabectome procedure appears to be a safe and simple way to lower eye pressure. It can be performed before a traditional trabulectomy, if needed. Results from a small study, presented at the 2005 meeting of the American Academy of Ophthalmology, showed that the new approach successfully reduced eye pressure in 90% of patients with open-angle glaucoma.

Side Effects. Many of the serious side effects or complications that occur with filtration surgery involve blebs (blister-like bumps).

Bleb Leaks and Infections. Blebs, particularly thin ones, commonly leak. Leakage can occur early on or sometimes as late as months or years after surgery. Untreated, such leaks can be serious and even cause blindness. Late-onset leakage significantly increases the risk for infection as well as a number of other serious conditions, including bleeding, a flattening of the eye ball, and harmful inflammation. Surgical repair is the most effective way of managing leaking blebs, although drug therapies, pressure patching, and other nonsurgical techniques may be tried first. Due to the dangers of leaking blebs, experts recommend lifelong monitoring after surgery. Unfortunately, the incidence of late-onset leaking blebs is increasing due to the use of drugs used in filtration surgery to prevent scarring, another complication.
Scarring. In up to 20% of cases, scars form around the incision, closing up the drainage channels and causing pressure to rebuild. These scars are formed from fibroblasts, which are immature collagen cells that form at the surgical site. Scarring is a particular problem in young patients, African Americans, patients who have taken multiple drugs, have had an inflammatory disease, or have had cataract surgery. Releasing the surgical stitches used in the procedure may help prevent scarring and pressure build-up. A second procedure called bleb needling sometimes can open up the scarred area and restore drainage. With this technique, the tip of a very fine hypodermic needle is used carefully to cut loose the particles closing off the drainage area. A new technique that does not require sutures may prove to be effective and have fewer complications.
Cataracts. The procedure is highly associated with the development of cataracts over time. Because cataracts are associated with glaucoma anyway, it is not entirely clear whether the cataracts are caused by the surgery or would develop in any case.

Click the icon to see an illustrated series detailing cataract surgery.

Supportive Medication for Preventing Scarring. Specific drugs, usually mitomycin C, are often used in conjunction with the procedure to prevent scarring and closure. A large review of studies of mitomycin C supported its effectiveness in increasing surgical success in nearly all patients. Fluorouracil (5-FU) appears to be similar in effectiveness but has a high risk for complications and is not used as often as in the past.

The Procedure. Laser trabeculoplasty involves the following steps:

The procedure uses an instrument, usually a YAG laser, to burn 80 - 100 tiny holes in the drainage area.
A tiny scar forms, which increases fluid outflow.
The procedure takes 15 minutes, causes almost no discomfort, and has very few complications.

In a 2-year study, laser surgery of the trabecular meshwork reduced pressure by a third in 70 - 97% of patients. Patients still need to take anti-glaucoma eye drop medications every day.

Laser surgery is not a cure. Within 2 - 5 years, about half of patients need either additional surgery or new medications.

Complications. In about 35% of patients, pressure increases after surgery. In most cases it is temporary, but in rare cases the increased pressure is permanent and vision loss can occur. Use of the drug apraclonidine (Iopidine) or pilocarpine can help prevent this elevated pressure. About a third of patients also develop adhesive-like substances called peripheral anterior synechiae that cause the iris to stick to part of the cornea.

Drainage implants, also known as tube shunts, may be used to drain fluid in certain cases, such as if glaucoma is not responsive to any standard procedure or is caused by certain conditions. A 2007 study suggested that tube shunts work better than filtration surgery (trabulectomy) for some patients. In the study, patients who received tube shunts had more stable IOP over the course of a year than patients who underwent trabulectomy.

Candidates. Success rates are highest (75% pressure control over 5 - 7 years) in appropriate patients. Drainage implants may be useful in the following conditions:

Glaucoma caused by swelling in the iris
Glaucoma caused by abnormal vessel formations
Iridocorneal endothelial (ICE) syndrome

The Procedure. In general, the procedure involves:

An implant, most commonly a 1/2 inch silicone tube, is inserted into the eye's front chamber (anterior). The Molteno implant used with mitomycin C is currently the most effective approach, with reported success rates of 80%. Other implants, such as the Ahmed implant, may have fewer complications.
The tube drains the fluid onto a tiny plate that is sewn to the side of the eye.
Fluid collects on the plate and then is absorbed by the tissues in the eye.

Complications. Complications include:

Hypotony (very low eye pressure) is a serious complication that has been reduced using better techniques and improved implants.
Cataracts, detached retina, breakdown of the cornea, and bleeding are potentially significant complications.
There is also a risk for eye movement disorders, such as strabismus (crossed eyes) or diplopia (double-vision).

The implant often becomes blocked and repeated operations are needed. Some researchers are studying the use of a drug called tissue plasminogen activator (tPA) to open up tubes that have been blocked by blood or blood factors. (This so-called clot-busting drug is normally used to break up blood clots during heart attacks.) In one 2002 study, tPA prevented such blocks in 89% of eyes. Unfortunately, significant complications rates were high (11%).

Deep sclerectomy and viscocanalostomy are less invasive techniques than filtering surgery that leave the anterior chamber (front of the eye) intact and avoid creation of blebs.

In deep sclerectomy, the surgeon removes a deep piece of the sclera (the white part of the eye), part of the trabecular meshwork, and the front of Schlemm's canal (the vessels that return fluid into the bloodstream).

In both deep sclerectomy and viscocanalostomy, the surgeon first creates a flap in the outer part of the sclera (the white part of the eye) and then removes a deep piece of the sclera underneath. This opens up Schlemm's canal (the vessels that return fluid into the bloodstream) and exposes a layer above the anterior chamber called Descemet's membrane. A space has also been created between the inner and outer layers of the sclera.
In deep sclerectomy, this space now serves as a tiny reservoir for aqueous fluid that flows through the membrane and pools here. The fluid then flows out without the surgeon having to open the anterior chamber (as in standard filtering surgery).
In viscocanalostomy, the surgeon typically injects gel-like materials into the ends of Schlemm's canal in order to enlarge the canal for fluid outflow and lower IOP. The tiny reservoir is sewn tightly up.

Many variations are under investigation. In general, the procedures have fewer complications afterward than standard filtering surgery, although they require excellent surgical skill. Nonpenetrating techniques do not lower IOPs as much as conventional surgery does, however. In time, however, these nonpenetrating techniques are expected to be as effective as filtration surgery.

Cataracts and Glaucoma. For patients with both glaucoma and cataracts, experts recommend the following:

In patients with cataracts and poorly controlled glaucoma, a two-step procedure for both eye conditions is needed. Typically the patient will first have a trabeculectomy for glaucoma, followed by cataract surgery such as phacoemulsification (lens removal through ultrasound). Fluid leakage and the presence of blood in the back chamber of the eye are potential complications of this combined procedure.
Phacoemulsification is sometimes combined with viscocanalostomy in a procedure called phacoviscocanalostomy. A 2006 study suggested this approach is safe and effective. The study followed patients for 7 years after they underwent phacoviscocanalostomy and found that no serious complications occurred.
In patients who have cataracts plus either closed-angle glaucoma or open angle glaucoma that is stabilized with medication, the cataract may be able to be extracted and medication continued for the glaucoma.

A major 2002 analysis suggested that the combined approach generally offers better control over eye pressure for patients with both cataracts and glaucoma. However, it is still unclear which specific type of surgical procedure works best. [See In-Depth Report #26: Cataracts.]

Diode laser transscleral cyclophotocoagulation (TSCPC), also called laser cycloablation, reduces aqueous production by destroying the muscles that control the lens for near and far vision (the ciliary body ). There is a chance of vision loss with this procedure, so it is reserved for people with end-stage glaucoma or those who fail to benefit from any other therapies. Nevertheless, researchers continue to explore the possibilities for this effective procedure, especially for people who may not have access to expensive medications. Studies have suggested it may even be suitable as first-line surgery for some patients.

For an acute closed-angle glaucoma attack, emergency microsurgery is usually necessary after reducing pressure with medications.

Iridotomy or Iridectomy. Either laser (iridotomy) or conventional (iridectomy) surgery may be used. With either procedure an ophthalmologist makes a tiny opening in the iris to let the aqueous humor flow out more freely. Because acute glaucoma commonly occurs later in the other eye, surgeons will often recommend surgery in the unaffected eye to prevent a second attack.

Laser iridotomy almost never requires hospitalization, and postsurgical treatment includes only aspirin and eye drops. It has almost completely replaced conventional surgery, which requires anesthesia and hospitalization.

Vision will be blurred, and recovery can take 4 - 8 weeks. Once surgery has been performed, such patients can usually use previously restricted anticholinergic medications, such as antihistamines and certain antidepressants, with safety.

Phacoemulsification and Intraocular Lens Implantation. Phacoemulsification and intraocular lens implantation, a procedure ordinarily used for cataracts, may prove to be beneficial for some patients with acute angle-closure glaucoma requiring surgery. [See In-Depth Report #26: Cataracts.]

Lifestyle Changes

Studies suggest that patients with glaucoma who exercise regularly (at least 3 times a week) may be able to reduce their intraocular pressure by an average of 20%. If they stop exercising for more than 2 weeks, pressure increases again. In one study, those who walked briskly 4 times a week for 40 minutes were able to go off their medications. (Although not confirmed by any evidence, yoga or other exercises that involve head-down or inverted positions may be harmful for patients with glaucoma and should be discussed with the doctor.)

Exercise has no effect on closed-angle glaucoma. It may, in fact, increase eye pressure in patients with pigmentary glaucoma. Vigorous high-impact exercise may cause more pigment to be released from the iris in these patients. Patients should talk to their doctor about an appropriate exercise program.

Antioxidants in Foods and Supplements. Diet most likely plays very little role in glaucoma. For example, a 2003 study found no association between important nutrients associated with protection against other eye disorders, including vitamins C, E, A, and carotenoids.

Caffeine. Some studies have shown that large amounts of caffeine drunk in a short period of time can elevate eye pressure for up to 3 hours. One study suggested that such changes in eye pressure could be significant in patients with both normal eye pressure and high IOP.

Fluids. Drinking large amounts (a quart or more) of any liquid within a short time, about 30 minutes, appears to increase pressure. Patients with glaucoma should have plenty of fluids, but they should drink them in small amounts over the course of a day.

Glaucoma can cause the eyes to be very sensitive to light and glare. Medications can worsen this problem. Sunglasses solve this problem and are important for prevention of cataracts. Protective sunglasses do not have to be expensive. Sunglasses are classified into three categories based on protection against ultraviolet radiation (UV) A or B:

Cosmetic-purpose sunglasses block at least 70% UVB and up to 60% UVA. People should avoid these glasses if they have any risk for cataracts or eye problems.
General-purpose sunglasses block at least 95% UVB and a minimum of 60% UVA. At the very least, people should purchase general purpose sunglasses and they should be labeled "Meets ANSI Z80.3 General Purpose UV Requirements.” Labels should indicate that sunglasses block UV radiation up to 400 nm.
Special-purpose sunglasses block at least 99% UVB and a minimum of 60% UVA rays. These are the optimal sunglasses for people at risk for eye disease. Special purpose glasses should wrap around the head and block light coming from above, below, and both sides of the glasses. They should also fit snugly on the nose.
Lenses that are simply dark but not coated with UV-absorbing material may increase the risk of cataracts because the pupil widens to compensate for the shaded glass. This may allow more harmful ultraviolet waves to enter the eye. Polarized glasses cut glare but have no effect on UV radiation. Mirror finishes without additional processing for UV blockage also are not fully protective. There is some controversy over whether blue light is harmful to the eyes. Some people prefer amber lenses, which block out the blue spectrum.

Meditation, biofeedback, and relaxation methods can help counteract stress, and there are some reports that they may help some people with open-angle glaucoma. A number of herbal and nontraditional remedies have been advertised as glaucoma remedies. A few studies have reported that the herbal remedy ginkgo biloba may have properties that offer benefits to patients with glaucoma, including increasing blood flow in the eye without altering overall blood pressure, heart rate, or intraocular pressure. More research is, however, needed.

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.

The following is of special concern for people with glaucoma:

Bilberry, a European blueberry (Vaccinium myrtillus), is sold in natural food stores as a glaucoma remedy. Studies indicate that it may help some people improve night vision and glare, but it is not at all effective in preventing or treating glaucoma.

Resources

www.glaucoma.org -- Glaucoma Research Foundation
www.nei.nih.gov -- National Eye Institute
www.glaucomafoundation.org -- The Glaucoma Foundation
www.aao.org -- American Academy of Ophthalmology
www.glaucomaweb.org -- American Glaucoma Society
www.lighthouse.org -- Lighthouse International

References

Bottaro M, Ritch R. Intraocular pressure variation during weight lifting. Vieira GM, Oliveira HB, de Andrade DT. Arch Ophthalmol. 2006 Sep;124(9):1251-4.

Brauner SC, Chen TC, Hutchinson BT, Chang MA, Pasquale LR, Grosskreutz CL. The course of glaucoma during pregnancy: a retrospective case series. Arch Ophthalmol. 2006 Aug;124(:1089-94.

Gedde SJ, Schiffman JC, Feuer WJ, Herndon LW, Brandt JD, Budenz DL. Treatment outcomes in the tube versus trabeculectomy study after one year of follow-up. Am J Ophthalmol. 2007 Jan;143(1):9-22.

Hara T, Hara T, Tsuru T. Increase of peak intraocular pressure during sleep in reproduced diurnal changes by posture. Arch Ophthalmol. 2006 Feb;124(2):165-8.

Higginbotham EJ. Managing glaucoma during pregnancy. JAMA. 2006 Sep 13;296(10):1284-5.

Pasquale LR, Kang JH, Manson JE, Willett WC, Rosner BA, Hankinson SE. Prospective study of type 2 diabetes mellitus and risk of primary open-angle glaucoma in women. Ophthalmology. 2006 Jul;113(7):1081-6.

Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006 Mar;90(3):262-7.

Wishart MS, Dagres E. Seven-year follow-up of combined cataract extraction and viscocanalostomy. J Cataract Refract Surg. 2006 Dec;32(12):2043-9.

Review Date:
3/3/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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.

adam.com

Photodermatitis

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

Overview

Signs and Symptoms
What Causes It?
Who's Most At Risk?
What to Expect at Your Provider's Office
Treatment Options
Prognosis/Possible Complications
Following Up
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Photodermatitis is an abnormal skin reaction to sunlight, or more specifically to ultraviolet (UV) rays. It can be acute (sudden) or chronic (ongoing). Photodermatitis occurs when your immune system reacts to the UV rays. You may develop a rash, blisters, or scaly patches. How much exposure to sunlight will cause such a reaction is different for every person. Several factors can make your skin sensitive to light UV rays, including an inherited tendency to photosensitivity or taking certain medications.

Signs and Symptoms

Itchy bumps, blisters, or raised areas
Lesions that resemble eczema
Hyperpigmentation (dark patches on your skin)
Outbreaks in areas of skin exposed to light
Pain, redness, and swelling
Chills, headache, fever, and nausea
Long-term effects include thickening and scarring of the skin and an increased risk of skin cancer, if the cause is genetic.

What Causes It?

Photodermatitis can be caused by certain diseases, such as lupus or eczema, that also make skin sensitive to light; by genetic or metabolic factors (inherited diseases or conditions such as pellagra, caused by lack of niacin, vitamin B-3); by diseases such as polymorphic light eruptions, which is characterized by sensitivity to sunlight; and by reactions to chemicals and medications. Certain chemicals and drugs can cause sunburn, an eczema-like reaction, or hives in reaction to UV rays. The reaction may be related to an allergy or it may be a direct toxic effect from the substance. Below are examples of substances or circumstances that may trigger one or the other type of reaction:

Direct toxic effect:

Antibiotics, such as tetracycline and sulfonamides
Antifungals, such as griseofulvin
Coal tar derivatives and psoralens, used topically for psoriasis
Retinoids, such as tretinoin and medications containing retinoic acid, used for acne
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Chemotherapy agents
Sulfonylureas, oral medications used for diabetes
Antimalarial drugs, such as quinine and other medications, used to treat malaria
Diuretics
Antidepressants, such as the tricyclics, used for depression
Antipsychotics, such as phenothiazines
Anti-anxiety medications, such as benzodiazepines

Allergic reactions:

Fragrances
Sunscreens with PABA
Industrial cleaners that contain salicylanilide

Who's Most At Risk?

People with fair to light skin -- or those with red or blond hair -- and green or blue eyes tend to be most sensitive, regardless of their racial or ethnic background. This is categorized as skin type I.
People with lupus, porphyria, or polymorphous light eruptions
Exposure to UV rays for 30 minutes to several hours increases risk (especially in spring and summer), as does exposure during 11 a.m. to 2 p.m. (50% of UV radiation is emitted during this time).

What to Expect at Your Provider's Office

A physical exam and a detailed history of exposure to chemicals and drugs (see section titled What Causes It?) and UV rays are important for diagnosis. Your health care provider may order blood and urine tests to detect any related diseases. Allergy tests may help identify substances that trigger or worsen the condition.

Treatment Options

Prevention

These measures may help prevent photodermatitis:

Limit skin exposure to sun, especially intense midday sun.
Use PABA-free sunscreens that protect against UVA and have a sun protection factor (SPF) of 30 - 50.
Cover up with a long-sleeved shirt, long pants, and a wide-brimmed hat.
Beware of using any product that causes sun sensitivity. (If you are already taking a prescription medication, however, do not stop taking it without consulting your health care provider.)
Do not use a tanning device (such as a tanning lamp or bed).

Treatment Plan

For blisters or weepy eruptions, apply cool, wet dressings. With certain types of photodermatitis, doctors may actually use phototherapy (controlled exposure to light for treatment purposes) to desensitize the skin or to help control symptoms.

Drug Therapies

For extremely sun-sensitive patients, doctors may prescribe azathioprine to suppress the immune system. Short-term use of glucocorticoids may help control eruptions. For those who cannot be treated with phototherapy, doctors may prescribe hydroxychloroquine, thalidomide, beta-carotene, or nicotinamide (see section entitled Nutrition for details regarding the latter two). Note: Thalidomide causes severe birth defects and should never be used by women who are pregnant or wish to become pregnant.

Complementary and Alternative Therapies

Nutrition and Supplements

If you don't get enough of some nutrients, your skin can become sensitive to sunlight. Pellagra, for example, is caused by a niacin deficiency and causes photosensitivity. Other nutrients, particularly antioxidants and flavonoids, may help protect skin against sun damage in healthy people. Antioxidants help remove free radicals, harmful by-products that result from cells' use and generation of energy. Free radicals are linked to skin damage. Recent studies suggest that antioxidants, especially beta-carotene, may help lessen the symptoms of photodermatitis.

Antioxidants

Beta-carotene and other carotenoids (up to 300 IU per day for beta-carotene) -- Beta-carotene is often used as a standard treatment for photodermatitis, although studies have been mixed. In one trial, though, 20 healthy subjects received either carotenoids alone, mainly from beta-carotene, or carotenoids plus vitamin E. Both groups improved significantly, but vitamin E did not appear to add any benefits. Scientists think the protective effect of beta-carotene comes from its antioxidant effect, so it's possible other antioxidants may also help protect skin from damage.
Vitamin B3 (1 g three times per day) -- Nicotinamide (a form of niacin, or vitamin B3) may make a photosensitive reaction less likely. In a pilot study, it reduced reactions among people with polymorphous light eruptions. Vitamin B3 is an antioxidant, so it may be providing protection in the same way other antioxidants might. You should take this high a dose of vitamin B3 only under a doctor's supervision because of the risk of side effects such as flushing and liver damage.
Vitamin B6 (100 mg per day for 3 months) -- Some case reports suggest that vitamin B6 can help reduce the reaction to sunlight. You should take this high a dose of vitamin B6 only under a doctor's supervision, because of the risk of side effects.
Vitamin C (1 - 3 g per day, lower dose if diarrhea develops) -- Vitamin C is an antioxidant, so it may provide some protection against photodermatitis. One small study showed an improvement in people with polymorphous light eruptions who took vitamin C.
Vitamin E -- Vitamin E is also an antioxidant, and a few studies have shown that it can offer protection from photodermatitis when taken with vitamin C (but not alone). However, other studies have not found the same results.
Vitamin D -- In animal studies, vitamin D helped protect against damage from UVB rays. It is not clear yet whether vitamin D supplements may protect humans in the same way.
Flavonoids -- Some of these plant-based antioxidants may protect skin from sun damage in healthy people. In one recent study, German researchers found that drinking high-flavonol cocoa offered protection from the sun (the cocoa used was a special formulation that is not yet available commercially). In another study, pomegranate fruit extract helped protect skin cells in a test tube from UV light. It isn't yet known whether taking the extract would provide any benefit. However, adding a lot of fruits and vegetables to your diet in order to eat more flavonoids may help.

Other supplements

Melatonin -- Applying melatonin topically seems to offer some protection against sunburn in healthy people, but it isn't known whether melatonin also lessens effects in people with photodermatitis.
Omega-3 fatty acids or fish oil (10 g per day) -- In one small study, fish oil reduced symptoms in people with polymorphous light eruptions. It isn't known whether fish oil helps other kinds of photodermatitis, but it has other health benefits (reduced risk of heart disease, possible reduction in inflammation), so it can be helpful to add to your diet. Fish oil can increase the risk of bleeding, so do not take it if you also take blood-thinning medication.

Herbs

Green tea (Camellia sinensis) -- Green tea has powerful antioxidant properties and may provide protection against reddening of the skin caused by UV light.
Calendula (Calendula officinalis) -- Although there are no scientific studies, this herb has been used historically to treat sunburn. It is often used as a homeopathic remedy for that reason.

Herbs to avoid

Some herbs can cause photodermatitis.

St. John's wort (Hypericum perforatum)
Angelica seed or root (Angelica archangelica)
Arnica (Arnica montana)
Celery stems (Apium graveolens)
Rue ( Rutae folium)
Lime oil/peel ( Citrusaurantifolia)

Homeopathy

Few studies have examined the effectiveness of specific homeopathic remedies. A professional homeopath, however, may recommend one or more of the following treatments for photodermatitis based on his or her knowledge and clinical experience. Before prescribing a remedy, homeopaths take into account a person's constitutional type -- your physical, emotional, and intellectual makeup. An experienced homeopath assesses all of these factors when determining the most appropriate remedy for a particular individual.

Aconitum napellus -- For a sudden rash, when the person feels anxious, frightened, and restless. Exposure to a cold, dry wind or sunlight may cause symptoms. If a rash breaks out suddenly and the person feels extremely anxious and apprehensive, this remedy may be indicated. Exposure to sunlight, or being out on a cold dry windy day, may precipitate symptoms. The rash may feel numb or itch, and stimulants may reduce the itching.
Belladonna -- For a rash that comes on suddenly with a feeling of heat, and the face is flushed and burns. Belladonna is often used for sunstroke.
Natrum carbonicum -- For a blistery rash that appears in patches. They person usually feels ill from exposure to the sun. They can be sensitive to changes in the weather and allergic to milk.
Natrum muriaticum -- For those who feel tired after being in the sun, with headaches and a blotchy, itchy or burning rash. They may be thirsty and have a craving for salt. Symptoms tend to be worse in the morning.

Prognosis/Possible Complications

Most photosensitivity reactions go away eventually and cause no permanent harm. However, symptoms can be serious when there is an underlying disease or when the exposure has been severe. Some photosensitivity reactions can continue for years after exposure ends.

Complications may include:

Ongoing photosensitivity, resulting in chronic photodermatitis
Hyperpigmentation or dark patches on the skin even after inflammation has ended
Premature aging of the skin
Squamous cell or basal cell skin cancer or melanoma

Following Up

People who need steroids to treat photodermatitis must be monitored closely. In addition, anyone with a history of photodermatitis or photoreactivity should keep track of the frequency and duration of symptoms. This information can help determine appropriate treatment.

Supporting Research

Adamski H, Benkalfate L, Delaval Y, et al. Photodermatitis from non-steroidal anti-inflammatory drugs. Contact Dermatitis. 1998;38(3):171-174.

Afaq F, Malik A, Syed D, Maes D, Matsui M, Mukhtar H. Pomegranate fruit extract modulates UVB-mediated phosphorylation of mitogen activated protein kinases and activation of nuclear factor kappa B in normal human epidermal keratinocytes. Photochem Photobiol. 2005 Jan-Feb;81(1):38-45

American Academy of Pediatrics. Ultraviolet light: a hazard to children. Pediatrics. 1999;104(2):328-333.

Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines.Boston, Mass: Integrative Medicine Communications; 1998:35-36; 214-215; 245-249.

Darr D, Dunston S, Faust H, Pinnell S. Effectiveness of antioxidants (vitamin C and E) with and without sunscreens as topical photoprotectants. Acta Derm Venereol (Stockh). 1996;76(4):264-268.

Eberlein-König B, Placzek M, Przybilla B. Protective effect against sunburn of combined systemic ascorbic acid (vitamin C) and d-alpha-tocopherol (vitamin E). J Am Acad Dermatol. 1998;38(1):45-48.

Enta T. Dermacase. Contact photodermatitis. Can Fam Physician. 1995;41:577, 586-587.

Enta T. Dermacase. Photodermatitis reaction to chlorothiazide. Can Fam Physician. 1994;40:1269, 1276.

Fernandez de Corres L, Diez JM, Audicana M. Photodermatitis from plant derivatives in topical and oral medicaments. Contact Dermatitis. 1996;35(3):184-185.

Freedberg IM, Eisen AZ, Wolff K. Fitzpatrick's Dermatology in General Medicine. Vol. 1. 5th ed. New York, NY: McGraw-Hill; 1996:1573-1586.

Fuchs J, Kern H. Modulation of UV-light-induced skin inflammation by D-alpha-tocopherol and L-ascorbic acid: a clinical study using solar simulated radiation. Free Radic Biol Med. 1998;25(9):1006-1012.

Garmyn M, Ribaya-Mercado JD, Russell RM, Bhawan J, Gilchrest BA. Effect of beta-carotene supplementation on the human sunburn reaction. Exp Dermatol. 1995;4(2):104-111.

Goldman L, Bennett JC. Cecil Textbook of Medicine. 21st ed. Philadelphia, Pa: W.B. Saunders; 2000:2295-2296.

Hadshiew I, Stäb F, Untiedt S, Bohnsack K, Rippke F, Hölzle E. Effects of topically applied antioxidants in experimentally provoked polymorphous light eruption. Dermatology. 1997;195(4):362-368.

Hanada K, Sawamura D, Nakano H, Hashimoto I. Possible role of 1,25-dihydroxyvitamin D3-induced metallothionein in photoprotection against UVB injury in mouse skin and cultured rat keratinocytes. J Dermatol Sci. 1995;9(3):203-208.

Heinrich U, Neukam K, Tronnier H, Sies H, Stahl W. Long-term ingestion of high flavanol cocoa provides photoprotection against UV-induced erythema and improves skin condition in women. J Nutr. 2006 Jun;136(6):1565-9

Kamat JP, Devasagayam TP. Methylene blue plus light-induced lipid peroxidation in rat liver microsomes: inhibition by nicotinamide (vitamin B3) and other antioxidants. Chem Biol Interact. 1996;99(1-3):1-16.

Katiyar SK, Matsui MS, Elmets CA, Mukhtar H. Polyphenolic antioxidant (-)-epigallocatechin-3-gallate from green tea reduces UVB-induced inflammatory responses and infiltration of leukocytes in human skin. Photochem Photobiol. 1999;69(2):148-153.

Katiyar SK, Afaq F, Perez A, Mukhtar H. Green tea polyphenol (-)-epigallocatechin-3-gallate treatment of human skin inhibits ultraviolet radiation-induced oxidative stress. Carcinogenesis. 2001 Feb;22(2):287-94.

Leroy D, Dompmartin A, Szczurko C, Michel M, Louvet S. Photodermatitis from ketoprofen with cross-reactivity to fenofibrate and benzophenones. Photodermatol Photoimmunol Photomed. 1997;13(3):93-97.

Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: Wiley and Sons; 1996.

Murata Y, Kumano K, Ueda T, Araki N, Nakamura T, Tani M. Photosensitive dermatitis caused by pyridoxine hydrochloride. J Am Acad Dermatol. 1998;39(2 pt 2):314-317.

Neumann R, Rappold E, Pohl-Markl H. Treatment of polymorphous light eruption with nicotinamide: a pilot study. Br J Dermatol. 1986;115(1):77-80.

Newall CA, Anderson LA, Philpson JD. Herbal Medicines: A Guide for Health-care Professionals. London: The Pharmaceutical Press; 1996.

Pigatto PD, Legori A, Bigardi AS, et al. Multicenter study of allergic contact photodermatitis: epidemiological aspects. Am J Contact Dermat. 1996;7(3):158-163.

Quinones D, Sanchez I, Alonso S, et al. Photodermatitis from tetrazepam. Contact Dermatitis. 1998;39(2):84.

Rhodes LE, Durham BH, Fraser WD, Friedmann PS. Dietary fish oil reduces basal and ultraviolet B-generated PGE2 levels in skin and increases the threshold to provocation of polymorphic light eruption. J Invest Dermatol. 1995;105(4):532-535.

Rhodes LE, White SI. Dietary fish oil as a photoprotective agent in hydroa vacciniforme. Br J Dermatol. 1998;138(1):173-178.

Ross JB, Moss MA. Relief of the photosensitivity of erythropoietic protoporphyria by pyridoxine. J Am Acad Dermatol. 1990;22(2 pt 2):340-342.

Scholzen TE, Brzoska T, Kalden DH, et al. Effect of ultraviolet light on the release of neuropeptides and neuroendocrine hormones in the skin: mediators of photodermatitis and cutaneous inflammation. J Invest Dermatol Symp Proc. 1999;4(1):55-60.

Stahl W, Heinrich U, Jungmann H, Sies H, Tronnier H. Carotenoids and carotenoids plus vitamin E protect against ultraviolet light-induced erythema in humans. Am J Clin Nutr. 2000;71(3):795-798.

Tierney LM, McPhee SJ, Papadakis MA. Current Medical Diagnosis and Treatment 2000. New York, NY: Lange Medical Books/McGraw-Hill; 2000:177-178.

Review Date:
12/10/2006
Reviewed By:
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. Copyright

adam.com

Systemic lupus erythematosus

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

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Complications
Diagnosis
Treatment
Treatment for Cutaneous and...
Treatment for Severe SLE...
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Systematic Lupus Erythematosus (SLE)

SLE is an autoimmune disease that causes a chronic inflammatory condition. The inflammation triggered by SLE affects many organs in the body, including skin, joints, kidneys, lung, and nervous system. Women, especially African-American and Asian women, are at highest risk for developing SLE.

Symptoms and Diagnosis

Not all patients with SLE experience the same symptoms. The most common symptoms are joint pain, skin rash, and fever. Symptoms can develop slowly or appear suddenly. Many patients with SLE have “flares,” in which symptoms suddenly worsen and then disappear for long periods of time. Diagnosing SLE is complicated because symptoms vary widely and can resemble other conditions. A doctor will base an SLE diagnosis on certain specific criteria including symptom history and the results of blood tests for antinuclear antibodies.

Treatment

No drug can cure SLE, but many different drugs can help control symptoms and relieve discomfort. The choice of drugs depends on the severity of the condition as well as other factors. Patients with mild SLE may be helped by nonsteroidal anti-inflammatory drugs (NSAIDs) while patients with more severe SLE may require corticosteroids or immunosuppressants. Researchers are working to develop new drugs and treatments for SLE.

Living with SLE

Patients can make lifestyle changes to help cope with SLE. These include:

Avoid excessive sunlight exposure, and wear sunscreen (ultraviolet light is the one of the main triggers of flares).
Get plenty of rest (fatigue is another common SLE symptom).
Engage in regular light-to-moderate exercise to help fight fatigue and heart disease, and to keep joints flexible.

Introduction

Systemic lupus erythematosus (SLE) is a chronic, often life-long, autoimmune disease. It can be mild to severe, and affects mostly women. SLE may affect various parts of the body, but it most often manifests in the skin, joints, blood, and kidneys. SLE was first described in 1828. Its very name helps define the disease:

Systemic is used because the disease can affect organs and tissue throughout the body.
Lupus is Latin for wolf. It refers to the rash that extends across the bridge of the nose and upper cheekbones and was thought to resemble a wolf bite.
Erythematosus is from the Greek word for red and refers to the color of the rash.

Lupus has many different symptoms. Common ones include:

Fatigue
Joint pain or swelling
Skin rashes

Causes

Systemic lupus erythematosus is a complex disorder that occurs as a consequence of a number of independent processes and factors.

Environmental factors, such as viruses, exposure to chemicals, or sunlight trigger inflammatory or immune activity. This immune activation may begin as an appropriate response to an unwanted "invader." But, because of a combination of genetic factors, an individual with lupus develops an ongoing immune response that does not shut itself off appropriately. This leads to waxing and waning flares of inflammation that can involve various organs of the body, depending on specific features of this self-perpetuating immune response in individual patients.

The exact combination of genes that predispose individuals to SLE may differ somewhat from patient to patient, but probably share certain common features which tend to impair the ability of the body to get rid of immune-triggering particles and which tend to prolong or increase the degree of immune responsiveness to these triggers.

A major characteristic of lupus is that it is an autoimmune response in which immune factors, called autoantibodies, attack the person's own cells. Some autoantibodies are normal in a well-balanced immune system, and serve various roles to help the body dispose of wastes, protect from infectious invaders, and to keep blood vessels clear. In healthy people, autoantibodies tend to be well-regulated and well "masked," or covered up, until needed. Therefore, it is probably the high activity and high detectability of autoantibodies that makes lupus unique, not the fact that they exist.

The Normal Immune System Response. The inflammatory process is a byproduct of the activity of the body's immune system, which fights infection and heals wounds and injuries:

When an injury or an infection occurs, white blood cells are mobilized to rid the body of any foreign proteins, such as a virus.
The masses of blood cells that gather at the injured or infected site produce factors to fight any infections.
In the process, the surrounding area becomes inflamed and some healthy tissue is injured. The immune system is then called upon to repair wounds by clotting any bleeding blood vessels and initiating fiber-like patches to the tissue.
Under normal conditions, the immune system has special factors that control and limit this inflammatory process.

The Infection Fighters. B cells and T cells are two important components of the immune system that play a role in the inflammation associated with lupus. Both B cells and T cells belong to a family of immune cells called lymphocytes. Lymphocytes help fight infection.

B cells and T cells are involved in the immune system's response to infection. Antigens are foreign bodies (such as bacteria and viruses) that stimulate the immune system to produce autoantibodies. When a T cell recognizes an antigen it will produce chemicals (cytokines) that cause B cells to multiply and release many immune proteins (antibodies). These antibodies circulate widely in the bloodstream, recognizing the foreign particles and triggering inflammation in order to rid the body of the invasion.

An antigen is a substance that can provoke an immune response. Typically antigens are substances not usually found in the body.

For reasons that are still not completely understood, both the T cells and B cells become overactive in lupus patients. In lupus, a complex interaction between activated immune cells and an impaired antigen-elimination process leads to a greater than normal range of what the antibodies recognize. Eventually, antibodies are made that recognize more of the body's own tissues in a stronger or more persistent manner than is healthy, and inflammatory responses are mounted in these tissues.

Autoantibodies. In the majority of patients with SLE, antinuclear antibodies (ANA) are detectable. Such autoantibodies may be present in individuals up to 7 years prior to their developing symptoms of lupus. Some subtypes of ANA are found in lupus patients and only rarely in people without lupus. These include:

Anti-ds DNA. An autoantibody called anti-double stranded DNA (anti-ds DNA) may play an important role in some lupus patients.
Anti-Sm antibodies. This antibody is found most often in lupus patients of African descent and is almost never detected in people without lupus.
Anti-Ro (SSA) and Anti-La (SSB)
Antiphospholipid antibodies

Cytokines. Most immune cells secrete or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are indispensable for maintaining the balance of the body during immune responses, including:

Infections
Injuries
Tissue repair
Blood clotting
Clearing of debris from inflamed blood vessels
Other aspects of healing.

If overproduced, however, they can cause serious damage, including dangerous levels of inflammation and cellular injury. Specific cytokines called interferons and interleukins play a critical role in SLE by regulating the secretion of autoantibodies by B cells.

Complement. Another immune factor of high interest in SLE is the complement system. This is comprised of more than 30 proteins and is important for defending and regulating the immune response. Inherited deficiencies in certain complement components (C1q, C1r, C1s, C4, and C2) have long been associated with SLE.

Researchers estimated that 20 - 100 different genetic factors may be involved in the alterations of the immune system set point that could make a person susceptible to SLE.

Research published in 2003 identified a particular set of genes, now commonly called the "interferon signature," that is activated by interferon in patients with severe lupus. This discovery may help doctors identify patients at particular risk for severe disease before they develop symptoms.
A genetic risk factor for lupus in African-American women has been identified.
Other research has identified defects in genes that regulate apoptosis, the natural process by which cells self-destruct.
An abnormal gene identified in some patients with SLE promotes the build-up of immune complexes that can cause kidney damage. HLA (human leukocyte antigen) is a protein that presents antigens to T cells by holding them up from the surface of macrophages or other antigen-presenting cells. Among the types of HLA associated with lupus are HLA-DR2, -DR3, -A1, -B8, and DMA-0104.

In genetically susceptible people, there are various external factors that can provoke an immune response. Possible SLE triggers include colds, fatigue, stress, chemicals, sunlight, and certain drugs.

Viruses. Blood tests reveal that patients with SLE are more likely to have been exposed to certain viruses than the general population. These viruses include the Epstein-Barr virus (the cause of mononucleosis), cytomegalovirus, and parvovirus-B1.

Results from a 2005 study, conducted by researchers at the National Institute of Environmental Health Sciences, suggested a strong association between Epstein-Barr virus (EBV) and increased risk of lupus, particularly for African-Americans. The association was not as strong for whites, but increased with age (patients over 50 years of age had four times higher risk).

The researchers also observed that a genetic variation in CTLA-4, a protein that helps regulate T cell immune system response, appeared to modify the risk of lupus associated with EBV-IgA antibodies. Therefore, an individual’s CTLA-4 genotype could determine the immune system’s responsiveness in fighting repeat episodes of EBV infection.

Click the icon to see an image of mononucleosis.

Some research suggests that different viruses may imprint specific types of SLE. For instance cytomegalovirus may affect blood vessels and cause problems such as Raynaud's phenomenon or blood abnormalities, but may not affect the kidney as much. These are speculations, however, and not a proven association.

Sunlight. Ultraviolet (UV) rays found in sunlight are important SLE triggers. When they bombard the skin, they can alter the structure of DNA in cells below the surface. The immune system may perceive these altered skin cells as foreign and trigger an autoimmune response against them. UV light is categorized as UVB or UVA depending on the length of the wave.

UVB are short waves (280 - 320 nm). The shorter the wavelengths, the more damage they do.
UVA are longer waves (320 - 400 nm). Some research suggests that UVA wavelengths in the longest range, known as UVA1 (340 - 400 nm), may actually repair DNA and normalize immune responses.

Chemicals. Clusters of SLE cases have occurred in populations with high exposure to certain chemicals. Chlorinated pesticides and crystalline silica are two suspects. A number of other chemicals are under investigation. However, it is very difficult to determine a causal role for any specific chemicals. (Silicone breast implants have been under intense scrutiny as a possible trigger of autoimmune diseases, including SLE. The weight of evidence to date, however, finds no support for this concern.) Some drugs have been associated with a temporary lupus syndrome (drug-induced lupus), which resolves when these drugs are stopped.

Hormones. Cytokines, major immune factors that are active in SLE, are directly affected by sex hormones. In general, estrogen enhances antibody production, and testosterone reduces antibody production, although their exact role in SLE may be more complicated than that since there are various ways in which each hormone might influence various immune cells. Women with SLE may have lower levels of several active male hormones (androgens), and some men who are affected by SLE may also have abnormal androgen levels.

Premature menopause, and its accompanying symptoms (such as hot flashes), is common in women with SLE. Hormone replacement therapy (HRT), which is used to relieve these symptoms, increases the risk for blood clots and heart problems. It is not clear whether HRT triggers SLE flares. Women should discuss with their doctors whether HRT is an appropriate and safe choice. Guidelines recommend that women who take HRT use the lowest possible dose for the shortest possible time. Women with SLE who have active disease, antiphospholipid antibodies, or a history of blood clots or heart disease should not use HRT.

Oral Contraceptives. Female patients with lupus used to be cautioned against taking oral contraceptives (OCs) due to the possibility that estrogen could trigger lupus flare-ups. However, recent evidence indicates that OCs are safe, at least for women with inactive or stable lupus. Women who have been newly diagnosed with lupus should avoid OCs. Lupus can cause complications in its early stages. For this reason, women should wait until the disease reaches a stable state before taking OCs. In addition, women who have a history of, or who are at high risk for, blood clots (particularly women with antiphospholipid syndrome) should not use OCs. The estrogen in OCs increases the risk for blood clots.

Risk Factors

The number of people diagnosed with lupus has more than tripled over the past four decades. Some experts believe this may simply indicate a greater degree of doctor training in recognizing the syndrome.

About 90% of lupus patients are women, most diagnosed when they are in their childbearing ages. Hormones may be an explanation. After menopause, women are only 2.5 times as likely as men to contract SLE. Flares also become somewhat less common after menopause in women who have chronic SLE.

African-Americans are three to four times more likely to develop the disease than Caucasians and to have severe complications. Hispanics and Asians are also more susceptible to the disease.

A family history plays a strong role in SLE. A brother or sister of a patient with the disorder has 20 times the risk as someone without an immediate family member with SLE.

The disease is rare in childhood. When it does occur, it is often associated with thrombotic thrombocytopenia purpura, a condition resulting from abnormally low levels of blood platelets. SLE in children may also be caused by certain medications, including minocycline and zafirlukast.

Rheumatoid Arthritis. Studies have investigated the relationship among hormones, SLE, and rheumatoid arthritis, another autoimmune disease. Higher levels of estrogen are associated with SLE, while lower levels are associated with rheumatoid arthritis. Some research suggests that some patients, in fact, progress from one disease to the other, and that such transitions occur during major hormonal shifts, such as the onset of menopause or pregnancy.

Rheumatoid arthritis is a systemic autoimmune disease that initially attacks the lining, or synovium, of the joints.

Many prescription drugs can cause lupus-like skin symptoms. In one study, the most common drugs causing these symptoms were high blood pressure (hypertension) medications, including hydrochlorothiazide, angiotensin-converting-enzyme inhibitors, and calcium-channel blockers. About 40 different drugs have been linked to lupus onset. Anyone diagnosed with cutaneous lupus erythematosus should be sure to tell their doctors all the medications (including herbs and supplements) that they are taking.

Smoking. Smoking may be a risk factor for triggering SLE and can increase the risk for skin and kidney problems in women who have the disease.

Symptoms

SLE symptoms may develop slowly over months or years, or they may appear suddenly. Symptoms tend to be worse during winter months, perhaps because prolonged exposure to sunlight in the summer causes a gradual build-up of factors that trigger symptoms months later.

The most common symptom is joint pain, which occurs in about 90% of patients with SLE. Characteristics of this symptom vary widely:

It is often accompanied by swelling and redness.
It can last from hours to months.
It may be mild or severe.
It can occur in one joint, move from one to another, or flare erratically.
Pain often occurs in the morning and improves during the day, only to return later when the patient tires.
The joints most affected are fingers, wrists, elbows, knees, and ankles. (Joints in the spine and neck are not affected.)

Children may experience these symptoms as growing pains, and, in all patients, they may be the only symptoms for many years.

Fever occurs in 90% of patients with SLE and is usually caused by the inflammatory process of the disease, not by infection. It is low-grade except during an acute lupus crisis.

Three-quarters of patients with SLE have skin inflammation and skin lesions (ulcers, rashes, or other injured areas). About half of these lesions are photosensitive; that is, they are aggravated by ultraviolet (UV) radiation from sunlight, even from light coming through a window. (UV radiation may even trigger systemic flares in patients with SLE.)

A number of different skin conditions have been described in patients with SLE.

Discoid Lupus Erythematosus. About 20% of patients have discoid lesions. In such cases, the condition is often known as discoid lupus erythematosus (DLE). Patients with this condition may have the following skin abnormalities:

Discoid means coin-shaped, so these lesions are round and raised. They are also scaly. Untreated, the margins gradually extend outward as the center dries out and shrivels, causing severe scarring. If discoid lesions appear on the scalp, they can plug hair follicles and cause irreversible hair loss. Discoid lesions can also appear on the upper body.

Lupus, discoid -- view of lesions on the chest: This close-up picture of the neck clearly shows the typical rounded appearance of discoid lupus. The whitish appearance is caused by scaling. The two dark spots are biopsy sites and are not part of the disease.

A butterfly-shaped rash across the face may accompany this condition. This rash causes little scarring, although spidery, branching lines of swollen capillaries (the tiniest blood vessels) may appear.

Click the icon to see an image of systemic lupus erythematosus.

Most patients with this condition have only a limited skin disorder. In only about 10% of cases does discoid lupus develop into full-blown SLE.

Subacute Cutaneous Lupus Erythematosus. Subacute cutaneous lupus erythematosus (SCLE) can cause skin lesions on parts of the body that are exposed to sunlight. These lesions do not cause scarring.

Vasculitis. Patients with SLE sometimes develop inflammation in the blood vessels (vasculitis) that may have the following effects on the skin:

Red welts may form across large areas of the body.
Sometimes deep red bumps may appear, particularly on the leg, where they may ulcerate.
In some people, reddish-purple lesions appear on the pads of fingers and toes or near the nails of fingers and toes.
Lesions caused by vasculitis may ulcerate or blister if they erupt on mucous membranes in the mouth, nose, or vagina and can be painful if they occur on the throat.
Vasulitis can attack blood vessels in almost any other organ, including the brain, the heart, and the gastrointestinal tract.

Click the icon to see an image of vasculitis.

Other symptoms include:

Fatigue
Loss of appetite, nausea, and weight loss
Chest pain
Bruising
Menstrual irregularities
Thought and concentration disturbances
Personality changes
Sleep disorders, such as restless legs syndrome and sleep apnea
Dryness of the eyes and mouth
Brittle hair or hair loss

Hair loss or breakage may also occur in about half of patients with SLE during severe flares or after pregnancy or severe illness. In such cases, hair grows back.

Raynaud's phenomenon is a condition in which cold or stress can cause spasms in impaired blood vessels, resulting in pain in fingers and toes. It occurs as part of the inflammatory response in blood vessels, which can narrow them and reduce circulation. In extreme cases, gangrene can result.

Click the icon to see an image of Raynaud's phenomenon.

A number of conditions may resemble SLE:

Scleroderma: Hardening of the skin caused by overproduction of collagen
Multiple sclerosis: Fatigue, heaviness or clumsiness in the arms and legs
Rheumatoid arthritis: Inflammation of the lining of the joints
Sjögren syndrome: Characterized by dry eyes and dry mouth
Mixed connective tissue disorder: Similar to SLE, but milder
Myositis: Inflammation and degeneration of muscle tissues
Rosacea: Flushed face with pus-filled blisters
Seborrheic dermatitis: Sores on lips and nose
Lichen planus: Swollen rash that itches, typically on scalp, arms, legs, or in the mouth
Dermatomyositis: Bluish-red skin eruptions on face and upper body
Lyme disease: Bulls-eye rash, joint inflammation, and flu-like symptoms

Complications

Systemic lupus erythematosus (SLE) is one of the most serious rheumatic diseases. According to a 2002 government study, the annual number of deaths has risen from 879 - 1,406 since 1979. About a third of these deaths occur in people aged 15 - 44 years, mostly women. Such numbers may be underestimates, since SLE can affect so many organs that a cause of death in some people with SLE may not be directly attributed to the condition. A primary cause of death among patients with lupus is atherosclerosis, a disease of the coronary blood vessels resulting from accelerated buildup of plaque.

SLE is unpredictable and varies greatly form one individual to the next. Severity also appears to differ among ethnic groups and countries. In European and North American patients with SLE for example, overall 5-year survival rates are 93 - 95%, while in Asia or Africa they are considerable lower (60 - 70%). Other research indicates that African-American and Hispanic American patients suffer greater organ damage than Caucasian patients. Genetic factors appear to have some influence on specific effects of SLE on organ damage among ethnic groups. However, the poorer outlook among minority groups and in underdeveloped nations is probably due to less access to good health care.

Mild SLE. About 20 - 30% of cases are mild. For many of these patients, the only symptoms may be the skin rashes of discoid lupus erythematosus (DLE) or subacute cutaneous lupus erythematosus (SCLE) with or without joint aches. The number and intensity of symptoms in mild cases often decrease over time, as does the likelihood of major organ involvement. These skin conditions, however, are not absolute insurance against more severe disease, and patients with mild SLE should be tested for organ involvement.

Widespread SLE. Most commonly, SLE is a chronic, life-long disease, alternating between periods of symptom relapse, (called flares), and remission. The disease may begin in any of the various systems of the body and progress unpredictably to others. The following are typical patterns:

Symptom relapses, or flares, occur on the average of two or three times a year.
Between flares, most patients with SLE function at about 90% of normal capacity.

The degree of severity depends on different factors:

Severity of the inflammatory response
Frequency of episodes
The degree of organ or system involvement

Vital organs or systems, such as lungs, kidneys, nervous system, joints skin, and others are affected in 50 - 75% of patients with SLE. Infections followed by kidney failure are the chief causes of death in patients with SLE.

Because of more effective and aggressive treatment, the prognosis for SLE has improved markedly over the past two decades. Long-term progress of the disease is affected greatly by treatment in the initial acute phase of the disease, so a speedy and accurate diagnosis is all-important. The 10-year survival rate with treatment is now 85 - 95%, and many people have a normal life span. SLE that develops later in life is generally less serious than SLE that strikes in childhood.

Almost 85% of patients with SLE experience problems associated with abnormalities in the blood.

Anemia. About half of patients with SLE are anemic. Causes include:

Iron deficiencies resulting from excessive menstruation
Iron deficiencies from gastro-intestinal bleeding caused by some of the treatments
A specific anemia called hemolytic anemia, which destroys red blood cells
Anemia of chronic disease

Hemolytic anemia can occur with very high levels of the anticardiolipin antibody. It can be chronic or develop suddenly and be severely (acute).

Antiphospholipid Syndrome. Between 34 - 42% of patients with SLE have antiphospholipid syndrome (APS). This is a specific set of conditions related to the presence of autoantibodies called lupus anticoagulant and anticardiolipin. These autoantibodies react against fat molecules called phospholipids, and so are called antiphospholipids. Their actions have complex effects that include causing narrowing and abnormalities of blood vessels.

Patients who have APS have a very incidence of blood clots, which most often occur in the deep veins in the legs (32%). Blood clotting, in turn, puts patients at higher risk for stroke (13%) and pulmonary embolism (clots in the lungs) (9%).

This picture shows a red and swollen thigh and leg caused by a blood clot (thrombus) in the deep veins in the groin (iliofemoral veins). Such a clot prevents normal return of blood from the leg to the heart.

About 22% of patients have thrombocytopenia -- a reduction in blood platelets that can cause bleeding.
The effects on blood vessels have also been associated with confusion, headaches, and seizures. Leg ulcers can also develop.
Patients with APS who become pregnant have a high incidence of pregnancy loss, especially in the late term.

Not all patients with APS carry both of the autoantibodies, and they can also wax and wane and so have varying effects. APS also occurs without lupus in about half of patients with the syndrome.

Thrombocytopenia. In thrombocytopenia, antibodies attack blood platelets. In such cases, blood clotting is impaired, which causes bruising and bleeding from the skin, nose, gums, or intestines. (This condition can also occur in APS, but it is not considered to be one of the standard features of the syndrome.)

Neutropenia. Neutropenia is a drop in the number of white blood cells. Patients with SLE often neutropenia, but the condition is usually harmless unless the reductions are so severe that they leave the patient vulnerable to infections.

Acute Lupus Hemophagocyte Syndrome. A rare blood complication of SLE that occurs primarily in Asians is called acute lupus hemophagocytic syndrome. It is generally of short duration and characterized by fever and a sudden drop in blood cells and platelets.

Lymphomas. Patients with SLE and other autoimmune disorders have a greater risk for developing lymph system cancers such as Hodgkin’s disease and non-Hodgkin’s lymphoma (NHL). A 2005 study reported that patients with SLE were over seven times more likely to develop NHL than healthy patients.

Heart disease is a primary cause of death in lupus patients. The immune response in SLE can cause inflammation and other damaging effects that can cause significant injury to the arteries and tissues associated with the circulation and the heart. In addition, SLE treatments (particularly corticosteroids) affect cholesterol, weight, and other factors that can also affect the heart. For decades, experts questioned the extent to which the drugs used to treat SLE contributed to the high rate of atherosclerosis in such patients. Numerous studies now suggest that something about the disease process itself, possibly the chronic inflammation of the blood vessels, probably lies at the root of this dangerous problem. In any event, patients with SLE, have a higher chance for the following conditions, which put them at risk for heart attack or stroke:

Atherosclerosis, or plaque buildup in the arteries
Increased stiffness in the arteries
Unhealthy cholesterol and lipid (fatty molecules) levels
High blood pressure, most likely because of kidney injury and corticosteroid treatments
Congestive heart failure
Pericarditis, an inflammation of the tissue surrounding the heart (occurs in about 30% of patients)
Myocarditis, an inflammation of the heart muscle itself (rare)

Click the icon to see an image of pericarditis.

Abnormalities in the valves of the heart (rare)
Blood clots

The risk for cardiovascular disease, heart attack, and stroke is much higher than average in younger women with SLE. The risks decline as such women age.

SLE affects the lungs in about 60% of patients:

Recurrent inflammation of the membrane lining the lung (pleurisy) is the most common problem.
In some cases, fluid accumulates, a condition called pleural effusion, and can cause stabbing localized pain that worsens when coughing, sneezing, laughing, or taking a deep breath.
Inflammation of the lung itself in SLE is called lupus pneumonitis. It can be caused by infections or by the SLE inflammatory process. Symptoms are the same in both cases: fever, chest pain, labored breathing, and coughing. Rarely, lupus pneumonitis becomes chronic and causes scarring in the lungs, which reduces their ability to deliver oxygen to the blood.
A very serious and also rare condition called pulmonary hypertension occurs when high pressure develops in the vessels supplying blood to the lungs.

Click the icon to see an image of primary pulmonary hypertension.

The kidneys are a crucial battleground in SLE because it is here that the debris left over from the immune attacks is most likely to be deposited. About 50% of patients with SLE exhibit inflammation of the kidneys (called lupus nephritis).This condition occurs in different forms and can vary widely in severity.

Click the icon to see an image of the kidney.

Proliferative nephritis is a serious variant of lupus nephritis. It occurs when the inflammatory process causes widespread damage and scarring in the blood vessels of the kidneys, which filters waste products, water, and salts out of the blood. The condition is associated with high blood pressure and kidney deterioration.
Membranous lupus nephritis is another variant that is often associated with a good outlook. In some cases, however, if the kidney is persistently exposed to high protein levels, the disorder can progress to fatal end-stage kidney (renal) disease.

Serious complications occur eventually in about 30% of patients. If kidney injury develops, it almost always occurs within 10 years of the onset of SLE, rarely after that.

Nearly all patients with SLE report some symptoms relating to problems that occur in the central nervous system (CNS), which includes the spinal cord and the brain. Most of these symptoms are minor and some, such as headache, may be related to depression rather than the disease itself. CNS involvement is more likely to occur in the first year, usually during flare-ups in other organs. Symptoms vary widely and may be indistinguishable from psychiatric or neurologic disorders or from the side effects of some medications used for SLE. Central nervous system symptoms are usually mild, but there is little effective treatment available for them. CNS symptoms get worse as the disease progresses.

The most serious CNS disorder is inflammation of the blood vessels in the brain, which occurs in 10% of patients with SLE. Fever, seizures, psychosis, and even coma can occur. Other CNS side effects include:

Irritability
Emotional disorders (anxiety, depression)
Mild impairment of concentration and memory
Migraine and tension headaches
Problems with the reflex systems, sensation, vision, hearing, and motor control

Infections are a common complication and a major cause of death in all stages of SLE. The immune system is indeed overactive in SLE, but it is also abnormal and reduces the ability to fight infections. Patients are not only prone to the ordinary streptococcal and staphylococcal infections, but they are also susceptible to fungal and parasitic infections (called opportunistic infections), which are common in people with weakened immune systems. They also face an increased risk for herpes, salmonella, and yeast infections. Corticosteroid and immunosuppressants, treatments used for SLE, also increase the risk for infections, thereby compounding the problem.

About 45% of patients with SLE suffer gastrointestinal problems, including nausea, weight loss, mild abdominal pain, and diarrhea. Severe inflammation of the intestinal tract occurs in less than 5% of patients and causes acute cramping, vomiting, diarrhea, and, rarely, intestinal perforation, which can be life-threatening. Fluid retention and swelling can cause intestinal obstruction, which is much less serious but causes the same type of severe pain. Inflammation of the pancreas can be caused by the disease and by corticosteroid therapy.

Arthritis caused by SLE almost never leads to destruction or deformity of joints. The inflammatory process can, however, damage muscles and cause weakness. Patients with SLE also commonly experience reductions in bone mass density (osteoporosis) and have a higher risk for fractures, whether or not they are taking corticosteroids (which can increase the risk for osteoporosis). Women who have SLE should have regular bone mineral density scans to monitor bone health.

Click the icon to see an image of osteoporosis.

Inflamed blood vessels in the eye can reduce blood supply to the retina, resulting in degeneration of nerve cells and a risk of hemorrhage in the retina. The most common symptoms are cotton-wool-like spots on the retina. In about 5% of patients sudden temporary blindness may occur.

In one study, 40% of patients with SLE quit work within 4 years of diagnosis, and many had to modify their work conditions. Significant factors that predicted job loss included high physical demands from the work itself, a more severe condition at the time of diagnosis, and lower educational levels. People with lower income jobs were at particular risk for leaving them.

Women with lupus who conceive face high-risk pregnancies. It is important for women to understand the potential complications and plan accordingly. The most important advice is to avoid becoming pregnant when lupus is active.

Research suggests that the following factors predict a successful pregnancy:

Disease state at time of conception. Experts strongly recommend that women wait to conceive until their disease state has been inactive for at least 6 months.
Kidney (renal) function. Women should make sure that their kidney function is evaluated prior to conception. Poor kidney function can worsen high blood pressure and cause excess protein in the urine. These complications increase the risk for preeclampsia and miscarriage.
Lupus-related antibodies. Antiphospholipid and anticardiolipin antibodies can increase the risks for preeclampsia, miscarriage, and stillbirths. Anti-SSA and anti-SSB antibodies can increase the risk for neonatal lupus erythematosus, a condition that can cause skin rash and liver and heart damage to the newborn baby. Levels of these antibodies should be tested at the start of pregnancy. Certain medications (aspirin, heparin) and tests (fetal heart monitoring) may be needed to ensure a safe pregnancy.
Medication use during pregnancy. Women with active disease may need to take low-dose corticosteroids, but women with inactive disease should avoid these drugs. Steroids appear to pose a low risk for birth defects, but can increase a pregnant woman’s risks for gestational diabetes, high blood pressure, infection, and osteoporosis. For patients who need immunosuppressive therapy, azathioprine (Imuran) is an option. Methotrexate (Rheumatrex) and cyclophosphamide (Cytoxan) should not be taken during pregnancy.

Pregnancy Risks

Women with lupus are 20 times more likely to die during pregnancy than women without the disease. The risk for maternal death is due to the following serious conditions that can develop during pregnancy:

Miscarriages. About 25% of lupus pregnancies result in miscarriage. The risk is highest for patients with antiphospholipid antibodies, active kidney disease, or high blood pressure.
Blood clots. Women with lupus have a 6 times greater risk for developing deep vein thrombosis (blood clots) than women without the disease.
Clotting complications. Low blood platelet count and anemia are also risks. Women with lupus are 3 times more likely to need a transfusion during pregnancy than women without lupus.
Infections. Blood infections (sepsis), pneumonia, and urinary tract infections are more common in pregnant women with lupus.
Preeclampsia. Women with lupus are three times more likely than healthy women to develop preeclampsia (pregnancy-related high blood pressure), which can be potentially life threatening.

Birth Complications

Pre-term birth. Women with lupus are 2.5 times more likely to have pre-term labor than women without lupus. Pre-term labor increases the risk for giving birth to low-weight babies.
Stillbirths. A 2005 study reported that the risk of still births was 10 times greater for women who had not yet been diagnosed with lupus, and 4 times greater for women with diagnosed lupus, compared with healthy women. This suggests that lupus may have a pre-disease state.
Caesarean section. Thirty-seven percent of women with lupus require a C-section compared with 22% of women without the disease.

Despite these obstacles, many women with lupus have healthy pregnancies and deliver healthy babies. To increase the odds of a successful pregnancy, it is important for women to plan carefully before becoming pregnant. Be sure to find knowledgeable doctors with whom you can communicate and trust. Experts recommend that pregnant women with lupus assemble an interdisciplinary health care team that includes a rheumatologist, high-risk obstetrician, and (for patients with kidney disease) a nephrologist.

Diagnosis

No single test can confirm or rule out SLE. A number of tests are required before SLE can be diagnosed definitively. The first symptoms of SLE can resemble one of many syndromes or disorders, including rheumatoid arthritis, Still's disease, rheumatic fever, Lyme disease, multiple sclerosis, thrombotic thrombocytopenia purpura, cryoglobulinemia, Weber-Christian disease, viral infections, vasculitis, psychosis, and other conditions. Other autoimmune disorders, such as Sjögren syndrome or scleroderma, may even be present at the same time as SLE.

1. Characteristic rash across the cheek

2. Discoid lesion rash

3. Photosensitivity

4. Oral ulcers

5. Arthritis

6. Inflammation of membranes in the lungs, the heart, or the abdomen

7. Evidence of kidney disease

8. Evidence of severe neurologic disease

9. Blood disorders, including low red and white blood cell and platelet counts

10. Immunologic abnormalities

11. Positive antinuclear antibody (ANA)

Note: A patient must experienced four of the criteria before a doctor can classify the condition as SLE. These criteria, proposed by the American College of Rheumatology, are not to be relied upon solely for diagnosis, however.

Methods for measuring the antibodies involved with SLE vary, and the range of results can be bewildering. Repeat tests may be needed.

Antinuclear Antibodies (ANAs). A primary test for SLE checks for antinuclear antibodies (ANA), which attack the cell nucleus.

High levels of ANA are found in more than 98% of patients with SLE. A number of other conditions, however, also cause high levels of ANA, so a positive test is not a definite diagnosis for SLE:

Antinuclear antibodies may be strongly present in other autoimmune diseases (such as scleroderma, Sjögren syndrome, or rheumatoid arthritis).
They also may be weakly present in about 20 - 40% of healthy women.
Some drugs can also produce positive antibody tests, including hydralazine, procainamide, isoniazid, and chlorpromazine.

A negative ANA test makes a diagnosis of SLE unlikely but not impossible. High or low concentrations of ANA also do not necessarily indicate the severity of the disease, since antibodies tend to come and go in patients with SLE.

In general, the ANA test is considered a screening test:

If SLE symptoms are present and the ANA test is positive, other tests for SLE will be administered.
If SLE symptoms are not present and the test is positive, the doctor will look for other causes, or the results will be ignored if the patient is feeling healthy.

ANA Subtypes. In some cases, doctors may test for specific ANA subtypes.

Anti-double stranded DNA (Anti-ds DNA) is usually found only in patients with SLE. It may play an important role in injury to blood vessels found in SLE, and high levels often indicate kidney involvement. Anti-ds DNA levels tend to fluctuate over time and may even disappear.
Anti-Sm antibodies are also usually found only with SLE. They are more constant and are more likely to be detected in African-American patients. Although the antibody is not usually seen in lupus patients, its confirmed presence almost always indicates SLE.
When the ANA is negative but the diagnosis is still strongly suspected, a test for anti-Ro (also called anti-SSA) and anti-La (also called anti-SSB) antibodies may identify patients with a rare condition called ANA negative, Ro lupus. These autoantibodies may be involved in the sun-sensitive rashes experienced by patients with SLE and are also found in association with neonatal lupus syndrome, in which a pregnant mother's antibodies cross the placenta and cause inflammation in the developing child's skin or heart.

Antibodies to SR Proteins. An advance in diagnosing SLE has been the detection of antibodies to molecules called SR proteins, which are carried by most patients. The test accurately detects lupus in 50 - 70% of patients who test positive for these antibodies.

Antiphospholipid Antibodies. In patients with SLE in whom blood abnormalities are suspected, tests may be able to detect the presence of the two major antiphospholipid antibodies:

A quarter to a half of patients with SLE may have these antibodies. They attack blood-clotting regulator proteins that stick to phospholipids, fatty compounds found in cell membranes throughout the body. Antiphospholipid antibodies increase the risks for blood clots and may be responsible for narrowing of (and irregularities in) blood vessels. Antiphospholipid antibodies are linked with miscarriages and other pregnancy complications, strokes, heart attacks and blood clots in almost any part of the body, including kidneys, legs, lungs, and eyes.
The test for the lupus anticoagulant antibody measures the time it takes blood to clot. A longer than normal blood clotting time indicates a higher chance for clotting in the body and, therefore, the presence of lupus anticoagulant.
An ELISA test (enzyme-linked immunosorbent assay) is performed to detect the anticardiolipin antibody.

As with the ANA, these antibodies also have a tendency to appear and disappear in a single patient. Patients who have these autoantibodies as well as blood clotting problems or frequent miscarriage are diagnosed with antiphospholipid syndrome (APS), which often occurs in SLE but can also develop independently.

Complement. Blood tests of patients with SLE often show low levels of serum complement, a protein in the blood that aids the body's infection fighters. Individual proteins are termed by the letter "C" followed by a number. Common complement tests measure C3, C4, C1q, and CH50. There is some evidence that complete deficiencies of C1q may be a key factor in the inability of the immune system to contain the autoimmunity process. Complement levels are especially low if there is kidney involvement or other disease activity.

LE Cell Tests. The first blood test ever used for SLE called LE (lupus erythematosus) cell test is positive in only about half of patients with SLE and is no longer used that often.

Blood Count. White and red blood cell and platelet counts are usually lower than normal and, depending on severity, are used to determine complications, such as anemia or infection.

Click the icon to see an image of the formed elements of blood.

If a skin rash is present, the doctor may take a biopsy (a tissue sample) from the margin of a skin lesion. A test known as a lupus band detects antibodies known as immunoglobulin G (IgG), which are located just below the outer layer of the tissue sample. They are present in about 80% of patients with active SLE and in 30 - 40% of those with inactive disease. The biopsy will not differentiate between systemic and discoid lupus, but it can rule out other diseases. Tests for other antibodies will rule out or confirm discoid lupus and subacute cutaneous lupus.

Kidney Damage and Lupus Nephritis. Kidney damage in patients already diagnosed with SLE may be detected from the following tests:

Blood tests that measure creatinine, a protein metabolized in muscles and excreted in the urine. High levels suggest kidney damage, although it can also be present with normal creative levels.
Tests for detecting anti-ds DNA antibodies and complement. High levels of anti-ds DNA and low levels of complement C3 suggest kidney damage. (It should be noted, however, that some patients with severe kidney damage show low levels of anti-ds DNA.) Testing for anti-C1q antibodies now appears to be an even more reliable indicator of lupus nephritis.
Urine analysis. Urine analyses should be performed at 4- to 6-month intervals to check for signs of kidney involvement.
A kidney biopsy. This may be performed to determine if lupus nephritis is present when less invasive tests indicate kidney involvement. It is not absolutely accurate but it helps determine treatment. Electron microscopy (very high-powered electronic microscopes) may be especially important in obtaining critical information on the degree of kidney damage.

Lung and Heart Involvement. A chest x-ray may be performed to check lung and heart function. An electrocardiogram and an echocardiogram are administered if heart disease is suspected.

Click the icon to see an image of an electrocardiogram.

Central Nervous System Complications. SLE occurring in the central nervous system (CNS) can be difficult to diagnose because its symptoms are easily confused with other psychiatric and neurologic conditions.

Tests of the cerebrospinal fluid (CSF) for elevated levels of autoantibodies are the most reliable ways to detect CNS complications caused by a faulty immune system.
Additional tests, including electroencephalograms (EEGs), magnetic resonance imaging (MRI), computed tomography (CT), or x-rays may be useful when blood vessel blockage in the brain is suspected.
If the doctor suspects that CNS symptoms are caused by infection, especially for patients who are receiving immunosuppressant therapy, a lumbar puncture should be performed.

Osteoporosis. To detect early osteoporosis in patients with SLE whose disease has lasted more than 3.5 years, experts recommend an imaging test called dual energy x-ray absorptiometry (DEXA) to measure bone mineral density.

Treatment

No treatment cures systemic lupus erythematosus, but many therapies can suppress symptoms and relieve discomfort. Treatment of SLE varies depending on the extent and severity of the disease.

Only three drugs are FDA-approved for the treatment of lupus:

Prednisone
Aspirin
Hydroxychloroquine

However, none of these drugs are the current standard of care. In everyday practice, numerous other drugs are commonly used. Researchers are conducting numerous clinical studies and drug investigations. Genetic research in lupus is progressing very rapidly, and hopefully new drugs will be approved in the future. There are also different drugs available to treat some of the conditions associated with lupus.

Less intensive treatments may be effective for symptoms of mild lupus. They include:

Creams and sunblocks for rashes
Nonsteroidal anti-inflammatory drugs for fever, arthritis, and headache
Antimalarial drugs for pleurisy, mild kidney involvement, and inflammation of the tissue surrounding the heart

More aggressive treatment is needed if there is serious disease progression, as evidenced by:

Hemolytic anemia
Low platelet count with an accompanying rash (thrombocytopenia purpura)
Major involvement in the lungs or heart
Significant kidney damage
Acute inflammation of the small blood vessels in the extremities or gastrointestinal tract
Severe central nervous system symptoms

The primary approach to treating severe SLE is to suppress the immune factors, most often first with corticosteroids and other immunosuppressant drugs. Investigational drugs and procedures are also showing promise.

The major complications of the disease must be treated as separate problems, keeping in mind the specific aspects of SLE. They are discussed elsewhere in this report.

Treatment for Cutaneous and Mild SLE

Creams. Steroid creams are often used for skin lesions. However, many patients with discoid lupus do not respond to steroids, particularly if they have eruptions that are caused by sun sensitivity. A cream derived from vitamin A (Tegison) may help some lesions that do not clear up with steroid creams.

Sun Protection. Sun protection is essential. Patients should always use sunblock creams (not just sunscreens) and always wear hats and clothing made of tightly woven fabrics.

Common NSAIDs. NSAIDs block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. There are dozens of NSAIDs.

Over-the-counter NSAIDs include aspirin, ibuprofen (Motrin, Advil), naproxen (Aleve), ketoprofen (Actron, Orudis KT).
Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), dexibuprofen (Seractil).

For people with lupus, NSAIDs may help relieve:

Joint pain and swelling
Muscle pain

Side Effects. Regular, long-term use of NSAIDs can cause ulcers and gastrointestinal bleeding, which can lead to anemia. To avoid these problems, it’s best to take NSAIDs with food or immediately after a meal. Long-term use of NSAIDs (with the exception of aspirin) can also increase the risk for heart attack and stroke.

Other NSAID side effects may include:

Upset stomach
Dyspepsia (burning, bloated feeling in pit of stomach)
Drowsiness
Skin bruising
High blood pressure
Fluid retention
Headache
Rash
Reduced kidney function

Patients who have kidney problems associated with lupus (lupus nephritis) should be especially cautious about using NSAIDs. Experts recommend that patients with lupus who take NSAIDs on a regular basis should have their liver and kidney function tested every 3 - 4 months.

An ulcer is a crater-like lesion on the skin or mucous membrane caused by an inflammatory, infectious, or malignant condition. Patients can take certain medicines to suppress the acid in the stomach causing the erosion of the stomach lining. Endoscopic therapy can be used to stop bleeding from the ulcer.

Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is the second most common cause of ulcers. Ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs) are more likely to bleed than those caused by the bacteria Helicobacter pylori.

Those at high risk for bleeding include people over age 60, anyone with a history of ulcers or gastrointestinal bleeding, patients with serious heart conditions, people who abuse alcohol, and those who take medications such as anticoagulants (blood thinners) and corticosteroids.

Proton-pump inhibitor (PPI) drugs may help prevent and heal ulcers caused by NSAIDs. PPIs include omeprazole (Prilosec), esomeprazole (Nexium), and lansoprazole (Prevacid).

A doctor may prescribe antimalarial drugs for discoid lupus (skin sores) or mild lupus when skin problems and joint pains are the predominant symptoms:

Hydroxychloroquine (Plaquenil) is the most common antimalarial drug used for lupus. This drug is effective as maintenance therapy to reduce flares in patients with mild or inactive disease. Hydroxychloroquine may help protect against blood clots in people with antiphospholipid syndrome, high cholesterol levels, and bone loss.
Other antimalarial drugs include chloroquine (Aralen) or quinacrine (Atabrine).

Treatment may start initially with high doses in order to accumulate high levels of the drug in the bloodstream. It is not known exactly why antimalarials work. Some researchers believe they inhibit the immune response, and others think they interfere specifically with inflammation.

A 2006 study suggested that anti-malarial drugs work best in patients who have genetic predispositions to certain types of immune-fighting proteins. The study found that patients who had genetic variations causing abnormally high levels of tumor necrosis alpha (TNF-alpha) and abnormally low levels of interleukin-10 (IL-10) responded best to these drugs.

Side Effects. Side effects of antimalarials may include:

Skin rash
Change in skin color (yellow in the case of quinacrine)
Gastrointestinal problems
Headache
Hair loss
Muscle aches
Eye damage

The most serious is damage to the retina, although this is very uncommon at low doses. Eye damage after taking hydroxychloroquine is reversible when caught in time and treated, but it is not reversible if the damage develops after taking chloroquine. An eye exam is advisable about every 6 months.

Antimalarials may also be used in combination with other anti-SLE drugs, including immunosuppressants and corticosteroids. It should be noted that smoking significantly reduces the effectiveness of antimalarial drugs.

Treatment for Severe SLE

Severe SLE is treated with corticosteroids, also called steroids, which suppress the inflammatory process. Steroids can help relieve many of the complications and symptoms, including anemia and kidney involvement.

Oral prednisone (Deltasone, Orasone) is usually prescribed. Other drugs include methylprednisolone (Medrol, Solumedrol), hydrocortisone, and dexamethasone (Decadron).

Some people need to take oral prednisone for only a short time; others may require it for a long duration. An intravenous administration of methylprednisolone using "pulse" therapy for 3 days is proving useful for flare-ups in the joints. Combinations with other drugs, particularly immunosuppressants, may be beneficial.

Regimens vary widely, depending on the severity and location of the disease. Most patients with SLE can eventually function without prednisone, although some may have to choose between the long-term toxicity of corticosteroids and the complications of active disease.

Side Effects of Long-Term Oral Corticosteroids. Unfortunately, serious and even life-threatening complications have been associated with long-term steroid use. The bone-thinning condition osteoporosis is a common and particularly severe long-term side effect of prolonged steroid use. Medications that can prevent osteoporosis include calcium supplements, parathyroid hormone, alendronate etidronate, risedronate, or hormone replacement therapy in post-menopausal women. Vitamin C and E may help reduce the risk of cataracts.

Other side effects associated with prolonged use of oral steroids include:

Cataracts
Glaucoma
Diabetes
Fluid retention
Susceptibility to infections
Weight gain
High blood pressure
Acne
Excess hair growth
Wasting of the muscles
Menstrual irregularities
Irritability
Insomnia
Psychosis

Withdrawal from Long-Term Use of Oral Corticosteroids. Long-term use of oral steroid medications suppresses secretion of natural steroid hormones by the adrenal glands. After withdrawal from these drugs, this so-called adrenal suppression persists and it can take the body a while (sometimes up to a year) to regain its ability to produce natural steroids again. A few cases of severe adrenal insufficiency have occurred when patients switched from oral to inhaled steroids, which, in rare cases, has resulted in death.

No one should stop taking any steroids without consulting a doctor first, and if steroids are withdrawn, regular follow-up monitoring is necessary. Patients should discuss with their doctors measures for preventing adrenal insufficiency during withdrawal, particularly during stressful times, when the risk increases.

Drugs known as immunosuppressants are often used, either alone or with corticosteroids for very active SLE, particularly when kidney or neurologic involvement or acute blood vessel inflammation is present. These drugs suppress the immune system by damaging cells that grow rapidly, including those that produce antibodies. About a third of patients take immunosuppressants at some point in the course of the disease.

Specific Immunosuppressants. The most common immunosuppressants are:

Cyclophosphamide (Cytoxan) used to be considered the gold standard of treatment for lupus kidney disease (lupus nephritis). Cyclophosphamide is given intravenously and is sometimes used in combination with corticosteroids or other drugs. It has been used for lupus since the 1970s. Side effects are very severe and include nausea, vomiting, hair loss, infertility, and infections.
Mycophenolate mofetil (CellCept) is now becoming the new standard. Many recent studies have shown that CellCept works better than cyclophosphamide and causes far fewer severe side effects (diarrhea is the main side effect). Unlike cyclophosphamide, it is taken by mouth. Most doctors now recommend CellCept as a first-line treatment for newly diagnosed patients with mild or moderate lupus kidney disease. It may not be appropriate for patients with kidney failure or rapidly progressing kidney disease.
Azathioprine (Imuran) has the lowest toxicity, but is less effective than other immunosuppressants.
Cyclosporine (Sandimmune) has been used for years, mostly for SLE associated with kidney involvement. High blood pressure is common, however, with this drug.

The most frequent side effects of immunosuppressants include:

Stomach and intestinal problems
Skin rash
Mouth sores
Hair loss

Serious side effects of immunosuppressants include:

Low blood cell counts
Anemia
Menstrual irregularity
Early menopause
Ovarian failure
Infertility
Herpes zoster (shingles)
Liver and bladder toxicity
Increased risk of cancer

In general, immunosuppressants should not be used alone unless corticosteroids are ineffective or inappropriate. Grapefruit juice has an enzyme that may enhance the effects of some immunosuppressants.

Monoclonal Antibodies (MAbs). A MAb is a laboratory-made protein that targets specific immune cells, such as B cells. B cell over-activation has been identified as a key component of the lupus disease process. Promising MAbs in development for SLE treatment include:

Epratuzumab is being investigated for treatment of moderate-to-severe lupus. It is currently in Phase III trials.
Belimumab (Lymphostat-B) is also in Phase III trials.
Rituximab (Rituxan), a lymphoma cancer and rheumatoid arthritis drug, has shown good results in early trials in improving lupus symptoms. Researchers think it may affect how T cells and B cells interact. However, in December 2006 the FDA warned of several cases of progressive multifocal leukoencephalopathy (PML) in patients with lupus who took this drug. PML is a life-threatening brain infection. Some patients developed PML as late as 12 months after their last dose of rituximab. Two patients with lupus died from PML.

Intravenous Immunoglobulins. Intravenous immunoglobulins (IVIG) are sometimes used for patients who have not responded to other SLE treatments. Immunoglobulins are antibodies produced by immune system B-lymphocyte cells. IVIG is a blood product that contains these antibodies.

Dehydroepiandrosterone (DHEA). Dehydroepiandrosterone (DHEA) is a natural steroid hormone that is produced by the adrenal glands and converted into estrogen and androgen. The synthetic equivalent of DHEA, prasterone (Prestara), is being investigated as a potential treatment for SLE. Several clinical trials have indicated promising, although mixed, results for prasterone’s effect on preventing bone mineral density loss in women who take prednisone. Prasterone is still in the drug development stage and it is not clear when, or if, it will be commercially available.

Autologous Stem Cell Transplantation. Some patients with severe lupus have achieved at least short-term remission after undergoing autologous transplantation of stem cells and high-dose drug therapy to suppress the damaging immune factors. Stem cells are the early forms for all blood cells in the body. An autologous transplant is one in which marrow or blood cells used are the patient's own. (The advantage to an autologous transplant is that the patient's own cells are not at risk for rejection by the immune system.)

The procedure first removes the cells from the patient, who then receives high-dose immunotherapy. The stem cells are then reintroduced. Early results of small studies are encouraging, especially for treatment of antiphospholipid syndrome. Evidence suggests that these re-introduced stem cells do not repeat the original autoimmune errors. A 2006 study in the Journal of the American Medical Association indicated that autologous stem cell transplantation can help boost the immune system and lead to remission. Patients in the study had severe lupus that was resistant to standard treatments. Results were long-lasting. Researchers calculated that patients had a 50% chance of remaining disease-free after 5 years.

UVA-1 Phototherapy. A promising treatment uses ultraviolet A-1 (UVA-1) radiation, long UVA wave lengths that do not promote sunburn and may actually block inflammatory immune factors. Small studies have suggested that UVA-1 phototherapy may have some benefits for lowering disease activity in SLE.

Plasmapheresis. Plasmapheresis is a process in which the fluid part of the blood, called plasma, is removed from blood cells. The procedure involves first taking blood from the patient. The plasma, which contains the inflammatory antibodies and other immunologically active substances, is discarded and replaced with other fluids. The blood is then returned. Plasmapheresis is not useful for routine management of patients but may have some benefits for patients who do not respond to standard treatments or in specific cases, such as lupus patients with hemolytic anemia.


Infections, Inflammation, or Hypertension in the Lungs	Preventive Measures. Immunizations with inactive viruses and preventive antibiotics should be considered for patients with SLE who are at high risk for infection. Treating Infections. Lung infections need to be treated aggressively with antibiotics. However, antibiotic drugs such as penicillin or the sulfa drugs may cause sensitivity rashes that can be confused with SLE rash. Treating Lung Inflammation. While inflammation of the lung (pneumonitis) resembles pneumonia, it is not an infection but is a result of the autoimmune process. This condition needs to be treated with corticosteroids or immunosuppressants, but only if the doctor is sure infection is not present. Treating Pulmonary Hypertension. Pulmonary hypertension is very serious. Drugs known as prostacylins -- which include epoprostenol, iloprost, and treprostinil -- are standard drugs. Bosentan (Tracleer) is the first oral drug approved for pulmonary hypertension. An inhaled iloprost formulation (Ventavis) was approved in 2004. Sildenafil (Viagra, Revatio) may also be used for this condition. Lung transplantation may be required.
Bleeding and Clotting Disorders	Antiphospholipid Syndrome and Clotting Disorders. Hydroxychloroquine or aspirin may help prevent blood clots in women with antiphospholipid syndrome (APS). (Aspirin does not appear to be protective in men who carry the autoantibodies responsible for APS.) In patients who have experienced blood clots, treatment with the anticoagulant warfarin (Coumadin) is advisable. This blood-thinning drug may be needed lifelong. Scientists are investigating other treatment options, including autologous stem cell transplantation. The procedure has shown promise in studies for treating lupus-associated APS, but it is still experimental. Excess Bleeding from Thrombocytopenia (Drop in Blood Platelets). Treatments that may be effective for thrombocytopenia include combinations of a corticosteroid and either danazol (a male hormone) or the antimalarial hydroxychloroquine. Immunosuppressants or intravenous immunoglobulin IgG may be helpful in some patients. Surgical removal of the spleen may be advisable if bleeding disorders are a serious problem, but this option should be considered carefully, because the spleen provides one line of defense against infection. (Abnormal spleen function, in any case, appears to be fairly common in SLE.)
Kidney Disease	Drugs. Mycophenolate mofetil (CellCept), a newer drug, can help treat kidney disease associated with SLE and has fewer side effects than other immunosuppressants. It is taken by mouth. Recent studies suggest that it works better than cyclophosphamide. CellCept may be best for patients with mild-to-moderate lupus kidney disease and may not be appropriate for patients with advanced kidney disease. Intravenous cyclophosphamide is the most effective drug at this time for proliferative lupus nephritis, and, in combination with a steroid, has been shown to control advanced kidney disease in 60 - 90% of patients. It has severe side effects, including nausea, vomiting, hair loss, and infertility. Steroids are also useful for treating active kidney disease and for managing milder forms of nephritis. Procedures. Kidney transplant or dialysis should be considered for patients with SLE with severe kidney damage. For unknown reasons, SLE does not generally recur in the transplanted kidneys. Studies are conflicting, however, over whether SLE transplant patients have higher organ-rejection rates than other kidney-transplant recipients. Both transplantation and dialysis have potentially serious complications. Plasmapheresis. It is not clear if plasmapheresis is beneficial for SLE kidney disease.
Osteoporosis	Treatments for osteoporosis include calcium, vitamin D, bisphosphonates, parathyroid hormone, and selective estrogen-receptor modulators (SERMs). [For more information, see In-Depth Report #18: Osteoporosis.]
Heart Disease	The need for aggressive treatment of high blood pressure often accompanies kidney disease. SLE is also accompanied by high cholesterol levels, which requires diet changes and drug therapies. [For more information, see In-Depth Reports #3: Coronary artery disease; #14: High blood pressure; #23: Cholesterol; and #43: Heart healthy diet.]

The spleen is an organ that helps produce and maintain red blood cells. It also aids the body's immune system by producing white blood cells that destroy harmful substances in the body. Removal of the spleen makes a person more susceptible to infection.

Click the icon to see an illustrated series detailing kidney transplant.

Lifestyle Changes

People with SLE should try to maintain a healthy and active lifestyle. Light-to-moderate exercise, interspersed with rest periods, is good for the heart, helps fight depression and fatigue, and can help keep joints flexible.

Patients should minimize their exposure to crowds or people with contagious illnesses. Careful hygiene, including dental hygiene, is also important.

It is very important that patients with SLE avoid excessive exposure to sunlight. Simple preventive measures include avoiding overexposure to ultraviolet rays and wearing protective clothing and sunblocks. There is some concern that allergy shots may cause flare ups in certain cases. Patients who may benefit from them should discuss risks and benefits with an SLE specialist. In general, patients with SLE should use only hypoallergenic cosmetics or hair products.

Chronic stress has profound physical effects and influences the progression of SLE. Getting adequate rest of at least 8 hours and possibly napping during the day may be helpful. Maintaining social relationships and healthy activities may also help prevent the depression and anxiety associated with the disease.

Resources

www.lupus.org -- Lupus Foundation of America
www.lupusny.org -- SLE Foundation of America
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.rheumatology.org -- American College of Rheumatology
www.lupusresearchinstitute.org -- Lupus Research Institute

References

Bernatsky S, Ramsey-Goldman R, Isenberg D, Rahman A, Dooley MA, Sibley J, et al. Hodgkin's lymphoma in systemic lupus erythematosus. Rheumatology (Oxford). 2007 May;46(5):830-2. Epub 2007 Jan 25.

Crosbie D, Black C, McIntyre L, Royle PL, Thomas S. Dehydroepiandrosterone for systemic lupus erythematosus. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005114.

D'Cruz DP, Khamashta MA, Hughes GR. Systemic lupus erythematosus. Lancet. 2007 Feb 17;369(9561):587-96.

Dörner T, Kaufmann J, Wegener WA, Teoh N, Goldenberg DM, Burmester GR. Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of systemic lupus erythematosus. Arthritis Res Ther. 2006;8(3):R74. Epub 2006 Apr 21.

Gompel A, Piette JC. Systemic lupus erythematosus and hormone replacement therapy. Menopause Int. 2007 Jun;13(2):65-70.

Harel-Meir M, Sherer Y, Shoenfeld Y. Tobacco smoking and autoimmune rheumatic diseases. Nat Clin Pract Rheumatol. 2007 Dec;3(12):707-15.

Khamashta MA. Systemic lupus erythematosus and pregnancy. Best Pract Res Clin Rheumatol. 2006 Aug;20(4):685-94.

Klareskog L, Padyukov L, Alfredsson L. Smoking as a trigger for inflammatory rheumatic diseases. Curr Opin Rheumatol. 2007 Jan;19(1):49-54.

Kocis P. Prasterone. Am J Health Syst Pharm. 2006 Nov 15;63(22):2201-10. Lane NE. Therapy Insight: osteoporosis and osteonecrosis in systemic lupus erythematosus. Nat Clin Pract Rheumatol. 2006 Oct;2(10):562-9.

Mackillop LH, Germain SJ, Nelson-Piercy C. Systemic lupus erythematosus. BMJ. 2007 Nov 3;335(7626):933-6.

Mease PJ, Ginzler EM, Gluck OS, Schiff M, Goldman A, Greenwald M, et al. Effects of prasterone on bone mineral density in women with systemic lupus erythematosus receiving chronic glucocorticoid therapy. J Rheumatol. 2005 Apr;32(4):616-21.

Sabahi R, Anolik JH. B-cell-targeted therapy for systemic lupus erythematosus. Drugs. 2006;66(15):1933-48.

Sánchez-Guerrero J, González-Pérez M, Durand-Carbajal M, Lara-Reyes P, Jiménez-Santana L, Romero-Díaz J, et al. Menopause hormonal therapy in women with systemic lupus erythematosus. Arthritis Rheum. 2007 Sep;56(9):3070-9.

Vigna-Perez M, Hernández-Castro B, Paredes-Saharopulos O, Portales-Pérez D, Baranda L, Abud-Mendoza C, et al. Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study. Arthritis Res Ther. 2006;8(3):R83. Epub 2006 May 5.

Walsh M, James M, Jayne D, Tonelli M, Manns BJ, Hemmelgarn BR. Mycophenolate mofetil for induction therapy of lupus nephritis: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2007 Sep;2(5):968-75. Epub 2007 Aug 8.

Walsh M, Jayne D. Rituximab in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis and systemic lupus erythematosus: past, present and future. Kidney Int. 2007 Sep;72(6):676-82. Epub 2007 Jul 4.

Review Date:
1/21/2008
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

Psoriasis

FitSugar — Wed, 08 Oct 2008 17:35:27 -0700

In This Report

Highlights
Introduction
Types of Psoriasis
Causes
Risk Factors
Diagnosis
Treatment
Topical Medications
Systemic Medications
Phototherapy
Managing Psoriasis
Outlook
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Treatment

Psoriasis that develops on the hands or feet is often very difficult to treat. However, an advanced clinical trial showed that a medication called efalizumab (Raptiva) effectively cleared or nearly cleared moderate-to-severe symptoms in adults after 12 weeks.

Several studies have shown that most people with severe psoriasis who are treated with infliximab (Remicade) have significant improvement in symptoms by week 10. The findings were presented at the 2007 annual meeting of the American Academy of Dermatology.

Continuing etanercept (Enbrel) after 12 weeks improves disease severity without an increase in infections or side effects, according to a study published in the Archives of Dermatology.

Disease classification

The National Psoriasis Foundation has proposed a new way to classify psoriasis. Instead of being grouped as mild, moderate, or severe, the group suggests a new two-tiered system that classifies patients as needing either local or body-wide (systemic) treatment.

Coexisting conditions

Studies from Newfoundland and Germany have revealed increased cases of diabetes, obesity, arthritis, and cancer in patients with psoriasis. Previous research has found an increased risk of heart disease in psoriasis patients. Research is underway to determine if there are genetic links between psoriasis and these conditions.

Severe psoriasis has been linked to a significant increase in a patient's risk of death. A study of more than 713,000 patients showed that severe psoriasis increased mortality by 50%. Such patients should receive comprehensive health examinations to reduce the risk, the authors recommended. Study participants were considered to have severe psoriasis if they required systemic treatment.

Smoking and psoriasis

Introduction

Psoriasis is a chronic skin disorder marked by periodic flare-ups of sharply defined red patches, covered by a silvery, flaky surface. The main disease activity leading to psoriasis occurs in the epidermis, the top five layers of the skin.

The process starts in the basal (bottom) layer of the epidermis, where keratinocytes are made. Keratinocytes are immature skin cells that produce keratin, a tough protein that helps form hair, nails, and skin. In normal cell growth, keratinocytes grow and move from the bottom layer to the skin's surface and shed unnoticed. This process takes about a month.

In persons with psoriasis, the keratinocytes multiply very rapidly and travel from the basal layer to the surface in about 4 days. The skin cannot shed these cells quickly enough, so they build up, leading to thick, dry patches, or plaques. Silvery, flaky areas of dead skin build up on the surface of the plaques before being shed. The underlying skin layer (dermis), which contains the nerves and blood and lymphatic vessels, becomes red and swollen.

Types of Psoriasis

Various forms of psoriasis exist. Some can occur alone or at the same time as other types, or one may follow another. The most common type is called plaque psoriasis, also known as psoriasis vulgaris.

Plaque psoriasis leads to skin patches that start off in small areas, about one-eighth of an inch wide. They usually appear in the same areas on opposite sides of the body.

The patches slowly grow larger and develop thick, dry plaque. If the plaque is scratched or scraped, bleeding spots the sizes of pinheads appear underneath. This is known as the Auspitz sign.

Some patches may become ring shaped (annular), with a clear center and scaly raised borders that may appear wavy and snake-like.

As the disease progresses, eventually separate patches may join together to form larger areas. In some cases, the patches can become very large and cover wide areas of the back or chest. This is known as geographic plaques because the skin lesions resemble maps.

Plaque psoriasis may persist for long periods. More often it flares up periodically, triggered by certain factors such as cold weather, infection, or stress.

Patches most often occur on the:

Elbows
Knees
Lower back

The may also be seen on the:

Upper pelvic bone area
Bottom of the feet
Calves and thighs
Genital areas
Palms of hands

Psoriasis of the scalp affects about 50% of patients. In some cases, the psoriasis may cover the scalp with thick plaques that extend down from the hairline to the forehead.

Psoriasis patches rarely affects the face in adulthood. In children, psoriasis is most likely to start in the scalp and spread to other parts of the body. Unlike in adults, it also may occur on the face and ears.

Psoriatic arthritis (PsA) is an inflammatory condition characterized by stiff, tender, and inflamed joints. Estimates on its prevalence among those with psoriasis range from 2 - 42%. AIDS patients and those with severe psoriasis are at higher risk for developing PsA.

About 80% of PsA patients have psoriasis in the nails. Arthritic and skin flare-ups tend to occur at the same time. It is not clear whether psoriatic arthritis is a unique disease or a genuine variation of psoriasis, although evidence suggests they are both caused by the same immune system problem.

Although patients with psoriatic arthritis tend to have mild skin symptoms, the disease affects the entire body. PsA, therefore, is more serious than the more common plaque psoriasis. Infrequently, the course of PsA has been associated with a syndrome known by the acronym SAPHO, which stands for:

Synovitis (inflammation in the joints)
Acne
Pustule eruptions
Hyperostosis (abnormal bony growths)
Osteolysis (bone destruction)

Some experts group PsA into five forms. The forms differ according to the location and severity of the affected joint:

Symmetric PsA: Symptoms occur in the same location on both sides of the body. It usually affects multiple joints. In about half of the cases, the condition will get worse. The condition is very similar to, but less disabling than, rheumatoid arthritis. The psoriasis itself is often severe.
Asymmetric PsA: This form involves periodic joint pain and redness, usually in only one to three joints, which can be the knee, hip, ankle, wrist, or one or more fingers. The pain does not occur in the same location on both sides of the body.
Distal interphalangeal predominant (DIP): DIP involves the joints of the fingers and toes closest to the nail. It occurs in about 5% of PsA cases.
PsA in the spine: Inflammation in the spinal column (spondylitis) is the primary symptom in about 5% of PsA cases. Such patients may have stiffness and burning sensations in the neck, lower back, sacroiliac, or spinal vertebrae. The spine can be involved in many patients with PsA, even though stiffness and burning sensations in these areas are not the primary symptoms. When it affects the spine, psoriatic arthritis most frequently targets the sacrum (the lowest part of the spine). Movement is difficult.
Arthritis mutilans: This is a severe, deforming, and progressive form of arthritis. It affects less than 5% of PsA cases. It mainly affects the small joints of the hands and feet, but it can also be found in the neck and lower back. Arthritic and skin flares and remissions tend to coincide.

People who start to smoke after developing psoriasis may delay the onset of psoriatic arthritis, according to research presented at the 2007 annual meeting of the Society for Investigational Dermatology. Researchers found that in nonsmokers, the time between psoriasis diagnosis and psoriatic arthritis development was 13 years, compared to 23 among those who started smoking after the onset of psoriasis. Study participants who smoked before developing psoriasis had psoriatic arthritis occur in about 8 years. However, smoking causes serious health problems and should not be considered as a way to delay this type of psoriasis.


Psoriasis Form	Description of Skin Patches	Comments
Guttate Psoriasis	The patches are teardrop-shaped and appear suddenly, usually over the trunk and often on the arms, legs, or scalp. They often disappear without treatment.	Guttate psoriasis can occur as the initial outbreak of psoriasis, often in children and young adults 1 - 3 weeks after a viral or bacterial (usually streptococcal) respiratory or throat infection. A family history of psoriasis and stressful life events are also highly linked with the start of guttate psoriasis. Guttate psoriasis can also develop in patients who have already had other forms of psoriasis, most often in people treated with widely-applied topical (rub-on) products containing corticosteroids.
Inverse Psoriasis	Patches usually appear as smooth inflamed patches without a scaly surface. They occur in the folds of the skin, such as under the armpits or breast, or in the groin.	Inverse psoriasis may be especially difficult to treat.
Seborrheic Psoriasis	Patches appear as red scaly areas on the scalp, behind the ears, above the shoulder blades, in the armpits or groin, or in the center of the face.	Seborrheic psoriasis may be especially difficult to treat.
Nail Psoriasis	Tiny white pits are scattered in groups across the nail. Toenails and sometimes fingernails may have yellowish spots. Long ridges may also develop across and down the nail. The nail bed often separates from the skin of the finger and collections of dead skin can build up underneath the nail.	Over half of patients with psoriasis have abnormal changes in their nails, which may appear before other skin symptoms. In some cases, nail psoriasis is the only symptom.
Generalized Erythrodermic Psoriasis (also called psoriatic exfoliative erythroderma)	This is a rare and severe form of psoriasis, in which the skin surface becomes scaly and red. The disease covers all or nearly all of the body.	About 20% of such cases evolve from psoriasis itself. The condition may also be triggered by certain psoriasis treatments, and other medications such as corticosteroids or synthetic antimalarial drugs.
Pustular Psoriasis	Patches become pus-filled and blister-like. The blisters eventually turn brown and form a scaly crust or peel off. Pustules usually appear on the hands and feet. When they form on the palms and soles, the condition is called palmar-plantar pustulosis.	Pustular psoriasis may erupt as the first occurrence of psoriasis, or it may evolve from plaque psoriasis. A number of conditions may trigger pustular psoriasis, including infection, pregnancy, certain drugs, and metal allergies. It can also accompany other forms of psoriasis and be very severe.

Causes

The precise causes of psoriasis are unknown. It is generally believed to be due to damage in factors in the immune system, enzymes, and other materials that control skin cell division. This prompts an abnormal immune response, which causes rapid production of immature skin cells and inflammation.

The Normal Immune System Response. The inflammatory process is the result of the body's immune response, which fights infection and heals wounds and injuries:

When an injury or an infection occurs, white blood cells are mobilized to rid the body of any foreign invaders, such as bacteria or viruses.
The masses of blood cells that gather at the injured or infected site produce factors to repair wounds, clot the blood, and fight infections.
In the process, the surrounding area becomes inflamed (red and swollen), and some healthy tissue is injured.

The 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 substances (antigens) and launch an offensive or defensive action against them:

B cells produce antibodies, which are designed to attack the antigens. Antibodies can either ride along with a B cell or travel on their own.
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 (TH cells).

Killer T cells directly attack antigens found on bacteria or other cells.
Helper T stimulate B cells and other white cells to attack the antigen.

The actions of the helper T cells are of special interest. Researchers have found high numbers of helper T cells in psoriatic plaques. Helper T cells normally stimulate B cells to produce antibodies. In psoriasis, however, they appear to direct the B cells to produce autoantibodies ("self" antibodies), which attack skin cells. In psoriatic arthritis, cells in the joints also come under attack.

Helper T cells also release or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are very important for healing. If overproduced, however, they can cause serious damage, including inflammation and injury during the psoriasis disease process. In psoriasis, researchers are particularly interested in cytokines known as GRO-alpha, tumor necrosis factor, and certain interleukins.

Cytokines attract large numbers of other large white blood cells known as neutrophils. Neutrophils stimulate the production of arachidonic acid, producing two key players in the inflammatory process:

Leukotrienes: These chemicals attract even more white blood cells to the inflamed area.
Prostaglandins: These chemicals widen blood vessels and increase blood flow.

A combination of genes is involved with increasing a person's susceptibility to the conditions leading to psoriasis.

HLA Molecules. The processes leading to all autoimmune diseases involve the human leukocyte antigen (HLA) system. HLA molecules pick off parts of antigens and present them on the surface of a cell so that the various infection-fighting factors in the immune system can recognize and destroy them. Most immune disorders, including psoriatic arthritis, are due to problems with this system. For example, psoriasis patients with an HLA genetic factor called HLA-CW6 tend to develop psoriasis at an earlier than average age. However, only 10% of people who have this gene develop psoriasis. Other genetic and environmental factors are required to actually trigger the disease.

PSORs. Researchers have now identified four key genes (named PSOR 1 - 4) that are involved with psoriasis. Of particular interest are the genes located in regions on specific chromosomes that are linked to HLA and tumor necrosis factor, another immune factor strongly associated with psoriasis.

Weather, stress, injury, infection, and medications, while not direct causes, are often important in triggering the disease process leading to the start and worsening of psoriasis.

Weather. Cold, dry weather is a common trigger of psoriasis flare-ups. Hot, damp, sunny weather helps relieve the problem in most patients. However, some people have photosensitive psoriasis, which actually improves in winter and worsens in summer when skin is exposed to sunlight.

Stress and Strong Emotions. Stress, unexpressed anger, and emotional disorders, including depression and anxiety, are strongly associated with psoriasis flare-ups. In one study, nearly 40% of patients remembered a specific stressful event that occurred within a month of a psoriasis flare. Other research has suggested that stress can trigger specific immune factors associated with psoriasis flares.

Infection. Infections caused by viruses or bacteria can trigger some cases of psoriasis. For example:

Streptococcal infections in the upper respiratory tract, such as tonsillitis, sinusitis, and strep throat, are known to trigger guttate psoriasis in children and young adults. The infections may make ordinary plaque psoriasis worse.
Human immunodeficiency virus (HIV) is also associated with psoriasis.
An uncommon form of human papillomaviruses (HPV) called EV-HPV has been associated with psoriasis. Although EV-HPV is probably not a direct cause, it may play a role in the continuation of psoriasis. This HPV form is not the virus associated with cervical cancer and genital warts.

Skin Injuries and the Köbner Response. The Köbner response is a delayed response to skin injuries, in which psoriasis develops later on at the site of the injury. In some cases, even mild abrasions can cause an eruption, which may be a factor in the frequency of psoriasis on the elbows or knees. It should be noted that psoriasis can develop in areas with no history of skin injury.

Medications. Drugs that can trigger the onset of the disease, worsen symptoms, or cause a flare-up include:

Angiotensin-converting enzyme (ACE) inhibitors, drugs used to treat high blood pressure and heart problems
Beta-blockers, drugs used to treat high blood pressure and heart problems
Chloroquine, a medicine used to treat malaria
Lithium for bipolar disorder treatment
Indomethacin, a nonsteroidal anti-inflammatory drug (NSAIDs) -- Note: Other NSAIDs, such as meclofenamate, may actually improve the condition.
Progesterone, used in female hormone therapies

Flare-ups of severe psoriasis may occur in persons who stop taking steroids taken by mouth, or who discontinue use of very strong steroid ointments that cover wide skin areas. The flare-ups may be of various psoriatic forms, including guttate, pustular, and erythrodermic psoriasis. Because these drugs are also used to treat psoriasis, this rebound effect is of particular concern.

Medications that cause rashes, a side effect of many drugs, can trigger psoriasis as part of the Köbner response.

Risk Factors

Between 5.8 and 7.5 million Americans have psoriasis. Risk factors for psoriasis include:

Age under 20. About 40% develop the condition before age 20. Psoriasis (most often plaque psoriasis) can even occur in infants.
Climate. Some studies have found that the disorder develops earlier and more frequently in colder climates. For example, psoriasis occurs more frequently in African-Americans and in Caucasians who live in colder climates than in people of any ethnicity who live in Africa.
Ethnicity. Psoriasis is uncommon in Native Americans of either North or South American descent.
Family history of the disease. About 35% of those with psoriasis have one or more family members with the disorder.
Male gender. Some studies have indicated that more men than women have psoriasis.

Diagnosis

A microscopic examination of tissue taken from the affected skin patch is needed to make a definitive diagnosis of psoriasis and to distinguish it from other skin disorders. Usually in psoriasis, the examination will show a large number of dry skin cells, but without many signs of inflammation or infection. Specific changes in the nails are often strong signs of psoriasis.

Several conditions produce symptoms that resemble those of psoriasis. For example:

Seborrheic psoriasis is hard to distinguish from seborrheic dermatitis (dandruff is one form of this condition). Seborrheic dermatitis patches are usually greasy, yellowish, and crusty. Nail involvement may also help differentiate psoriasis.
Generalized erythrodermic psoriasis may be confused with drug allergic reactions, atopic eczema, and symptoms of lymphomas.
Fungal infections, other skin conditions, or circulation problems may also cause nail changes typical of psoriasis.

Symptoms of psoriatic arthritis may also resemble the following:

Rheumatoid arthritis (RA). As in rheumatoid arthritis, psoriatic arthritis can cause pain or tenderness in one or more joints, and morning stiffness is common. People with psoriatic arthritis, however, lack a particular antibody, called rheumatoid factor, which is found in the blood of many people with rheumatoid arthritis.
Systemic lupus erythematosus (SLE). Symptoms of SLE may include both a psoriasis-like rash and arthritis, which could make the diagnosis difficult.
Reiter's disease. Reiter's disease is a syndrome that includes arthritis and inflammation in the eyes and urinary tract. It also causes skin lesions that are very similar to psoriasis, which are usually raised patches on the lips, penis, palms, and soles.
Gout. Gout causes pain, often in the fingers and toes.

Some evidence now indicates that inflammation in psoriatic arthritis may be distinguished from other arthritic conditions by its occurrence in sites where muscle tissue inserts into the bone (called enthesitis) rather than in the joint, which is a common site in other inflammatory arthritic conditions.

Severity of psoriasis itself ranges from one or two flaky inflamed patches to widespread pustular psoriasis that, in rare cases, can be life threatening. To help determine the best treatment for a patient, doctors usually classify the disease as mild to severe. The classification depends on how much of the skin is affected:

Mild psoriasis affects less than 3% of the body surface. Most cases of psoriasis are limited to less than 2% of the skin.
Moderate psoriasis covers 3 - 10% of the skin.
If more than 10% of the body is affected, the disease is considered severe.

The palm of the hand equals 1% of the body. The severity of the disease is also measured by its effect on a person’s quality of life.

However, the National Psoriasis Foundation has proposed a new classification method. The group suggests a new two-tiered system that classifies patients as needing either local or body-wide (systemic) treatment.

While disease severity impacts treatment success, some forms of psoriasis can be very resistant to treatment even though they are not categorized as severe. They include:

Any psoriasis on the palms and soles (hand and foot psoriasis)
Inverse psoriasis (which occurs in the folds of the skin)
Scalp psoriasis
Psoriatic arthritis

Treatment

Many creams, ointments, lotions, and pills are available for the treatment of psoriasis. Many patients require only over-the-counter treatment, or even none at all during relapses.

About a third of patients with psoriasis, however, do not respond to over-the-counter remedies and lifestyle changes, and require aggressive treatments. In some cases, such treatments need to be lifelong.

In general, there are three treatment options for patients with psoriasis.

Topical medications such as lotions, ointments, creams, and shampoos
Body-wide (systemic) medications, which involve pills or injections that affect the whole body, not just the skin
Phototherapy, which uses light to treat psoriasis lesions

Individual requirements vary widely, and treatment selection must be carefully discussed with the doctor.

Giving treatment in a particular order is a strategy for providing both quick relief of symptoms and long-term maintenance. It involves three main steps:

The quick fix, to clear the psoriatic lesions during an acute outbreak (for example, a high-strength topical steroid in mild-to-moderate psoriasis, or an oral immunosuppressant in more severe cases)
The transitional phase, intended to gradually introduce the maintenance drug
Ongoing maintenance therapy

Choices for transitional or maintenance treatments depend on the severity of the condition. Some examples are described in the following sections.

In severe chronic cases, a doctor may recommend rotational therapy. This approach alternates treatments. The goal is to prevent severe side effects or build-up of resistance from long-term use of a single medicine. An example of a rotational schedule may be the following:

The patient gets phototherapy for about 2 years.
The patient then takes one or two powerful body-wide drugs for 1 - 2 years and stops.
Phototherapy starts again, and the cycle repeats.

Some doctors use the Koo-Menter Psoriasis Instrument (KMPI) to decide which patients should receive a pill or an injection. The KMPI’s questions include:

Does psoriasis cover at least 5% of the patient’s body?
Is the patient disabled by psoriasis?
Does psoriasis affect the patient’s quality of life?

If the answer to these questions is "yes," three additional questions are considered:

Is light therapy inappropriate for the patient?
Is the patient’s psoriasis resistant to light therapy?
Does the patient have psoriatic arthritis?

If the answer to these questions is “yes,” a doctor may decide to prescribe a pill or injected drugs.

Doctors increasingly use combinations of pills, creams, ointments, and phototherapy instead of single medications. Combinations of oral treatments are particularly useful, since the doses of each drug can be reduced. This lowers the risk of severe side effects. Thousands of combinations are possible, and the patient and doctor should discuss the best treatment for individual needs.

Topical Medications

Topical medications are those applied only to the surface of the body. They come in the following forms:

Creams
Foams
Gels
Lotions
Occlusive tapes
Ointments
Shampoos
Solutions
Sprays

In general, topical treatments are the first line for mild-to-moderate psoriasis, but they may also be used, alone or in combination, with more powerful treatments for moderate-to-severe cases. Topical medicines rarely produce complete clearance, however.

Corticosteroid topical treatments are the mainstay of psoriasis treatments in the United States. They work for most patients. Such treatments:

Decrease inflammation
Block cell production
Relieve itching

Corticosteroids are available in a wide range of strengths, and are generally given as follows:

Less potent drugs are used for mild-to-moderate psoriasis.
Stronger drugs are reserved for more severe disease.

In the past, topical steroids have been used twice a day. Studies are reporting, however, that certain drugs may work just as well if taken once a day. Most studies have evaluated high-potency steroids, but one study suggested that those of medium strength, such as triamcinolone (Aureocort, Tri-Adcortyl), may be equally beneficial as a once-daily treatment. However, corticosteroids used alone clear psoriasis in only 4 - 36% of patients.

Combination therapy. Combinations with other drugs are often needed. For example, an effective, topical regimen uses the following combination for maintenance therapy:

A high-potency steroid (such as halobetasol) on the weekend
A vitamin D3 topical medication called calcipotriene, twice daily on weekdays

In one study, more than 75% of patients with mild-to-moderate psoriasis remained in remission for at least 6 months with this regimen.

Side Effects. The more powerful the corticosteroid, the more effective it is. But it also has a higher risk for severe side effects. Side effects may include:

Burning
Irritation
Dryness
Acne
Thinning of the skin; skin may become shiny, fragile, and easily cut
Dilated (widened) blood vessels
Loss of skin color

Loss of Effectiveness. In most cases, the patients become tolerant to the effects of the drugs, and the drugs no longer work as they should. Some experts recommend using intermittent therapy (also called weekend or pulse therapy). This type of treatment involves applying a high-potency topical medication for 3 full days each week.

Note: This list is not all inclusive.
Low potency (some are available over the counter)	Desonide (Tridesilon, DesOwen) Flumethasone pivalate (Locorten) Fluocinolone acetonide (Synalar, Derma-Smoothe) Hydrocortisone (Hytone, Penecort, Synacort, Cort-Dome, Nutracort, Westcort) Triamcinolone acetonide (Aristocort)
Low to medium potency	Alclometasone dipropionate (Aclovate) Hydrocortisone (Locoid, Pandel) Hydrocortisone valerate (Westcort) Prednicarbate (Dermatop)
Medium to upper-mid potency	Clocortolone pivalate (Cloderm) Fluticasone propionate (Cutivate) Mometasone furoate (Elocon) Triamcinolone acetonide (Aureocort, Tri-Adcortyl, Kenalog)
High potency	Betamethasone (Diprosone) Amcinonide (Cyclocort) Desoximetasone (Topicort) Diflorasone diacetate (Florone, Maxiflor) Fluocinonide (Lidex) Halcinonide (Halog)
Very high potency	Halobetasol propionate (Ultravate) Betamethasone (Diprolene, Luxiq) Clobetasol propionate (Temovate, Olux) Diflorasone diacetate (Florone, Maxiflor, Psorcon)

Coal tar preparations have been used to treat psoriasis for about 100 years, although their use has declined with the introduction of topical vitamin D3-related medicines. Crude coal tar stops the action of enzymes that contribute to psoriasis, and helps prevent new cell production. Tar is often used in combination with other drugs and with ultraviolet B (UVB) phototherapy.

Side Effects. Preparations have the following drawbacks:

Stains on clothing
Skin irritation
Sun sensitivity and increased risk of sunburn for up to 24 hours after use

Anthralin (Dritho-Scalp, Drithocreme, Micanol) is related to a medication called chrysarobin, in use since the early 1900s. Anthralin slows skin cell reproduction and can produce remissions that last for months. It is recommended only for chronic or inactive psoriasis, not for acute or inflamed eruptions. Persons with kidney problems should use anthralin with caution.

As with tar, its use has also declined with introduction of the topical vitamin D-related medicines, but newer formulations, such as Micanol, have made its use more tolerable. Micanol (Psoriatec) is an anthralin formulated in microcapsules, which dissolve and allow the drug to be delivered directly to the target skin areas. It is particularly useful for scalp psoriasis, and it is less likely to stain.

Side Effects. Anthralin may cause the following side effects:

Skin irritation and burning
Staining of clothes, hair, fabrics, plastics, and other household products

Patients should not use anthralin on their faces. Fair skinned people should generally avoid it. Triethanolamine (CuraStain) is a chemical that can neutralize anthralin and help reduce irritation from short-contact anthralin treatment. It should be applied 1 or 2 minutes before washing off the anthralin. It is then reapplied after drying the skin.

Washing stained items with hypochlorite (Clorox) detergents can help remove stains. Many people use disposable gloves while applying the treatment to avoid staining hands.

Application. Apply anthralin only to the psoriasis plaques. Rub the cream in well, and wipe off any excess. Wash off only with lukewarm water, not soap. Using hot water will trigger the staining action. A technique called short-contact anthralin therapy (SCAT), also called minute therapy, is useful for local areas of psoriasis. In such cases, anthralin is applied for only 10 minutes to an hour.

A topical form of vitamin D3, calcipotriene (Dovonex) is proving to be both safe and effective. It is now available in a foam preparation, which makes compliance even easier. Several other topical vitamin D3 related drugs showing promise include maxacalcitol (Oxarol), tacalcitol, and calcitriol (Silkis).

Calcipotriene appears to:

Block skin cell reproduction
Enhance the maturity of keratinocytes (the impaired skin cells in psoriasis)
Acts as an anti-inflammatory

It works just as well as moderate topical corticosteroids, short-term anthralin, and coal tar in improving mild-to-moderate plaque psoriasis. Unlike steroids, patients do not develop thinning of the skin or tolerance to the drug.

Using the drug in combination with other topical and systemic treatments may improve effectiveness. Calcipotriene doesn't work as well as the highest potency corticosteroids, but products or regimens that combine both medications are proving to be more effective than either one alone. Taclonex, an ointment containing both calcipotriol and betamethasone, was approved by the U.S. Food and Drug Administration (FDA) in January 2006 for the treatment of adults with psoriasis. Studies show the combination works better than either drug alone.

Combining vitamin D ointments with systemic medicines, notably methotrexate, acitretin, or cyclosporine, increases effectiveness and allows lower doses or either medication, thereby reducing side effects.

Studies also report success in some patients who use vitamin D ointments in combination with phototherapy treatment.

Side Effects. Calcipotriene may cause the following side effects:

A possible lowering of vitamin D levels, which may affect bone growth in some children
A possible increase in blood calcium levels (seen in some people who apply calcipotriene to large areas)
Skin irritation in about 20% of patients, particularly on the face and in skin folds

Calcipotriene appears to cause greater skin irritation than potent corticosteroids. Diluting the drug with petrolatum or applying topical corticosteroids to sensitive areas may prevent this problem.

Retinoids are related to vitamin A. They are used for various skin disorders. Tazarotene (Tazorac) is the first topical retinoid found to be effective for mild-to-moderate psoriasis. It is available in cream or gel form.

Unlike steroids, patients do not develop thinning of the skin or tolerance to the drug. Only a very small amount is needed on each lesion. It can be used on the scalp and nails, but it is not recommended for the genital areas or around the eyes. The gel should be used on only 20% of the body at anytime; the cream on up to 35%. (Note: The palm of the hand is about 1% of the body surface.)

Combining topical retinoids with other psoriasis treatments, such as with topical steroids, works better than using the drug by itself.

Side Effects. Tazarotene may cause dryness and irritation of healthy skin. Applying zinc oxide and moisturizer around the treated area can protect the healthy skin.

At levels high enough to be effective for psoriasis, tazarotene can cause severe skin irritation on treated areas. This medicine, then, is usually used in combination with other treatments, therefore allowing a lower dose. Mixing the drug in equal amounts with petroleum jelly (Vaseline) initially and then gradually increasing the amount of tazarotene may help the skin areas become less sensitive. It should be noted that the skin can become very red while it is actually improving.

Vitamin A derivatives (drugs related to vitamin A) have been associated with birth defects and should not be used by women who are pregnant, who wish to conceive, or who are nursing.

Salicylic acid applied to the skin helps remove scaly plaque and enhance the actions of other medications. It should not be used to cover wide areas of the body, since it can cause nausea and ringing in the ears. Combinations with high potency steroids, such as mometasone furoate (Combisor), clobetasol propionate, and betamethasone, are proving to be very helpful. Only Combisor is available in the United States.

Watertight (occlusive) tapes or wrappings may help heal psoriasis. Occlusive tapes are particularly useful for psoriatic cuts on the palms and soles. In such cases, the tape should be applied across the cuts until they heal.

Occlusive tapes retain sweat, which helps restore moisture to the outer skin layer and prevent scaling. They also protect against abrasion and irritation.

High-Potency Corticosteroid Tapes. Applying a corticosteroid beneath an occlusive tape, or using a tape that already has a potent corticosteroid (Cordran Tape) such as flurandrenolide may be especially beneficial. Studies are showing that high-potency corticosteroid-containing tapes are more effective than using high-potency corticosteroid ointments alone.

However, the tapes are expensive and are associated with a high rate of skin irritation, increased secondary infections, and a greater chance of symptoms relapse after treatment is stopped. Infection risk may be reduced by changing tapes every 12 hours.

The use of corticosteroids under occlusive tapes on large areas of psoriasis also increases the risk for adrenal insufficiency, a sometimes dangerous condition that occurs because the body loses its ability to produce natural steroids. Children are especially vulnerable to this effect.

Other Medications with Occlusive Tapes or Wrappings. The tapes may be used in combination with other medications, such as fluorouracil. Occlusive wrappings are not usually used with tazarotene (Tazorac) and should never be used without a doctor's recommendation.

Numerous topical medications are under investigation. One such medication, tacrolimus (Protopic), is an immunosuppressant that is proving to be useful in allergic skin disorders and is being studied for psoriasis. Studies have been mixed on its benefits, although new delivery methods may make it more effective. It may prove to be safe for sensitive areas, such as the face. Pimecrolimus (Elidel), a similar medication, is also being studied.

Systemic Medications

Systemic treatment uses various medications that affect the whole body, not just the skin. Many systemic drugs used for psoriasis are also used for other severe diseases, including autoimmune diseases (especially rheumatoid arthritis) and cancer.

Systemic treatments for psoriasis may be taken by mouth or injection. The medicines can have significant side effects and are generally reserved for severe psoriasis.

At this time, the only systemic medications specifically approved for psoriasis are:

Cyclosporine
Methotrexate
Retinoids

As with all medications for psoriasis, the patient should use the lowest strength medication first. The primary treatment is called a first-line treatment, the next is known as a second-line treatment, and so on. Combinations of medications are often used.

Methotrexate (Rheumatrex) is a biologic drug that interferes with cell reproduction and has anti-inflammatory properties. It is a first line, or primary, systemic drug used to treat adults with severe psoriasis. The medicine is one of the few systemic drugs proven to help patients with psoriatic arthritis.

The drug is taken weekly, not daily. (Deadly reactions have been reported in people who mistakenly took it once a day.)

Side Effects. Common side effects of methotrexate include:

Anemia
Headache
Mild hair loss
Mouth sores
Nausea
Possible muscle aches
Rash
Vomiting

Many of these side effects are due to folic acid deficiency. Patients should ask their doctor if folic acid supplements (generally recommended at 1 - 5 mg daily) are necessary.

More serious side effects include:

Increased risk for infections, particularly shingles and pneumonia. Methotrexate suppresses the immune system. Patients with active infections should avoid this drug.
Infertility, miscarriage, and birth defects. If used during pregnancy, the drug can cause miscarriages or birth defects in the baby. It may harm fertility in men.
Kidney complications.
Liver damage. In one study, 25% of patients taking methotrexate for 5 years developed scarring of the liver. Those with existing liver problems should not take this medicine, if possible. Regular monitoring for liver toxicity, including blood tests and liver biopsies, is important in patients who take the drug.
Lung disease. This side effect can be sudden and severe, and occurs in up to 5% of people who take methotrexate. Risk factors include diabetes, existing lung inflammation, protein in urine, and use of rheumatoid arthritis drugs called DMARDs.
Lymphomas. A few cases have been reported, which are most likely related to the drug's immune-suppressing (lowering) effects. In most instances, the disease has gone into remission when the drug was stopped. Most studies have found no significant risk for cancers in patients taking methotrexate.
Osteoporosis. Low doses of methotrexate do not appear to have any significant effect on bone loss, but long-term studies are needed to confirm this.
Radiation recall: An uncommon side effect in patients who have previously been burned by radiation cancer treatments or sunburns. In such cases, a flare-up of symptoms occurs in the previously affected skin areas.
Severe anemia. Folic acid supplements can offset this effect.
Toxic effects on bone marrow. This can cause reduced blood cell production.

Despite its side effects, some experts view methotrexate as the best therapy for widespread plaque psoriasis. It may also be effective for some patients with other severe forms of the disease, including psoriatic arthritis, generalized erythrodermic, and pustular psoriasis.

Methotrexate appears to be effective in children, but more safety research is needed.

Drug Interactions. Many drugs interact with methotrexate, occasionally with harmful results. For example, the antibiotic trimethoprim-sulfamethoxazole increases the toxicity of methotrexate.

A serious, harmful reaction can occur if methotrexate is taken with common, nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen, or naproxen. Other NSAIDs, namely ketoprofen, flurbiprofen, and piroxicam, appear to be safe when given with methotrexate and may be used in patients with psoriatic arthritis. Rheumatoid arthritis (RA) patients who take methotrexate often take NSAIDs as well, but methotrexate doses in psoriasis patients are usually much higher than those in RA.

People Who Should Avoid Methotrexate. Pregnant and nursing mothers should never take methotrexate because it increases the risk for severe, even fatal, birth defects and miscarriage. The drug should be discontinued several months before planning a pregnancy. It may also cause temporary impairment of fertility in men.

Persons with the following conditions should also avoid taking methotrexate:

Alcoholism
Anemia or other blood abnormalities
Immunosuppression
Kidney problems
Liver problems (including hepatitis)
Rheumatoid arthritis
Peptic ulcers

Patients at risk for liver complications include those with diabetes and obesity. Anyone with a history of hepatitis should have a liver biopsy before taking methotrexate.

Oral retinoids are vitamin A-related medications taken by mouth. This group of medicines is also a first-line treatment for adults with severe psoriasis. Oral retinoids used for psoriasis include acitretin (Soriatane) and isotretinoin (Accutane).

Acitretin is the retinoid of choice and may be dramatically effective for severe psoriasis, particularly pustular or erythrodermic variants. When used alone, it is much less effective against more common forms, such as plaque or guttate psoriasis. However, combinations with PUVA phototherapy can markedly improve the response even in these patients.

Accutane, more commonly used to treat acne, is far less potent than acitretin, but may still be effective against pustular psoriasis and also be effective with phototherapy.

Oral retinoids help control cell reproduction and have anti-inflammatory properties. They may even improve arthritis that accompanies psoriasis.

Combination therapy. Acitretin may work the best when combined with other treatments, usually topical drugs and especially phototherapy. Combination therapy allows lower doses of oral retinoids to be used, which diminishes many skin and mucous membrane side effects. Acitretin combined with phototherapy has some of the highest clearance rates of any treatment.

Side Effects. All retinoids have the same potentially serious toxicities as do high doses of vitamin A. Side effects include:

Bone and joint pain
Bruising
Depression and possible suicide risk (with isotretinoin)
Eye problems, including blurred vision, cataracts, conjunctivitis, and a sudden deterioration in night vision
Fatigue
Headache
Increased bone growth, particularly in the ankles, pelvic area, and knees
Increased triglyceride levels
Liver damage
Nail problems
Skin and mucous membrane problems, including dry nose, nosebleeds, dry eyes, chapped lips, thinning hair, dry or "sticky" feeling skin, and peeling of the palms and soles

In rare cases, retinoids, particularly isotretinoin, may cause a condition called benign intracranial hypertension (pseudotumor cerebri), which occurs in the brain. Symptoms include headache, nausea, vomiting, and blurred vision. Patients experiencing these symptoms should call a doctor immediately and stop taking the drug.

Oral retinoids should not be taken during pregnancy.

Despite these side effects, oral retinoids remain among the safest systemic therapies for psoriasis. A low-fat diet, aerobic exercise, and fish oil supplements may help reduce the side effects. Certain cholesterol-lowering drugs, including gemfibrozil (Lopid) or certain statins, such as atorvastatin (Lipitor), may help control triglyceride levels.

Maintenance doses should be as low as possible and should be taken every second or third day.

Taking retinoids during pregnancy significantly increases the risk for severe birth defects in the unborn child. Pregnant or nursing women or those planning to become pregnant should not use these drugs. Women of childbearing age who take retinoids should have regular pregnancy tests.

Doctors recommend that acitretin should not be given to any woman who may become pregnant within 3 years of taking it. Drinking alcohol changes acitretin to a retinoid that is stored in fat cells for 3 years. It may have the potential for causing birth defects during that time. It's important to note that cooking products and over-the-counter preparations, such as cough syrup, may contain alcohol and be inadvertently consumed.
Women who are pregnant or plan to become pregnant should not use isotretinoin. As of December 31, 2005, everyone who takes, prescribes, or dispenses the drug must enroll in a national registry called iPLEDGE.

Cyclosporine (Neoral, Sandimmune, SangCya) blocks certain immune factors and may be effective for all forms of psoriasis. It is also a first line, or primary, systemic drug used to treat adults with severe psoriasis. Neoral is the preparation used most often for psoriasis and clears psoriasis in many patients within 8 - 12 weeks.

Side Effects. Cyclosporine has significant side effects if used for a long time, notably kidney problems and non-melanoma skin cancers. It should be reserved for patients who do not respond to phototherapy or less potent systemic medications (for example, methotrexate or acitretin).

Common and temporary side effects include:

Fatigue
Gingivitis
Gout
Hair growth
Headaches
Joint pain
Tremor

More serious complications may include:

Kidney damage
High blood pressure (Some doctors advise treating high blood pressure with calcium channel blockers, since other standard blood pressure drugs may worsen psoriasis. Calcium channel blockers also help prevent kidney problems.)
High cholesterol and lipid levels
High levels of calcium and low levels of magnesium
Increased risk for infections
Liver problems
Lymphomas
Skin cancers (Patients who have taken cyclosporine after PUVA therapy have a higher incidence of squamous cell skin cancer. According to a 2003 study, the risk is six times that of the general population. The risks are highest with long use and previous use of PUVA, methotrexate, or other immunosuppressants.)

To reduce complications of cyclosporine, the dosage is decreased after improvement occurs. Maintenance therapy is usually limited to a year, although some experts believe that a microemulsion form of Neoral (Neoral-Neo) may be safe for up to 2 years. Patients should be monitored regularly for high blood pressure and signs of kidney or liver problems and skin cancers.

Patients Who Should not Use Cyclosporine. Because the drug suppresses the immune system, people with active infections or cancer should avoid it. Patients with uncontrolled high blood pressure and impaired kidney function should also not use this medication. Cyclosporine therapy for children with psoriasis has not been well studied.

Drug and Food Interactions. Cyclosporine interacts with numerous drugs -- both prescription and over-the-counter preparations -- and also grapefruit and grapefruit juice.

Biological response modifiers, sometimes called "biologics," belong to a new class of drugs that are considered the most exciting development in psoriasis treatment. Biologics are genetically engineered drugs that interfere with specific components of the autoimmune response. Because of their precise targets, these drugs do not damage the entire immune system the way that general immunosuppressants do.

Biologics are considered second- or third-line treatments, and may be used alone or sometimes in combination with first-line systemic drugs.

There are different types of biologics used to treat psoriasis:

T cell blockers block immune cells linked to inflammation.
Tumor necrosis factor (TNF) blockers target the chemical messenger TNF-alpha, which is released during the inflammatory response.

Types of T-cell blockers:

Alefacept (Amevive). This drug is approved for the treatment of moderate-to-severe plaque psoriasis. Studies suggest that the drug produces 50 - 75% improvement in symptoms. Alefacept is given in a doctor's office or clinic. Patients receive weekly injections for 12 weeks. Patients need weekly blood tests to make sure T cell levels do not drop too low. Side effects are generally mild and include sore throat, dizziness, and cough. There have been a few reports of serious infection and cancer.
Efalizumab (Raptiva). This drug is approved for the treatment of moderate-to-severe plaque psoriasis. Many patients experience 50 - 75% improvement in symptoms within 4 - 6 weeks of starting the drug. Patients give themselves shots of this drug for 12 weeks. Some clinical trials suggest that a longer course of treatment (24 weeks) may also be safe and effective for patients with chronic plaque psoriasis. Some patients have flare-ups of psoriatic lesions after stopping efalizumab. Very serious, but rare, side effects include hemolytic anemia and antibiotic-resistant infections.

Types of TNF blockers:

Etanercept (Enbrel) is approved for the treatment of psoriatic arthritis and moderate-to-severe plaque psoriasis. The drug is given either alone or in combination with methotrexate. Side effects include infections and lymphoma, a type of cancer. Patients inject themselves under the skin, once or twice a week for 12 weeks. However, a 2007 study published in the Archives of Dermatology found that continuing etanercept after 12 weeks lowers the severity of disease without increasing infections or side effects. Study participants randomly received 50 milligrams of the drug or a placebo biweekly up to 84 weeks. Strongest improvements were noted at 48 weeks among those who received the drug.
Infliximab (Remicade) is approved for the treatment of psoriatic arthritis. Patients receive three intravenous infusions during the first 6 weeks of treatment. After the initial treatment period, patients receive an infusion every 8 weeks. Therapy takes 2 hours and is given in a doctor’s office or clinic. Patients with a history of infection or heart failure should not take this drug. Several studies have shown that symptoms improve significiantly by week 10 in the majority of patients with severe psoriasis who are treated with infliximab.
Adalimumab (Humira) is being tested in clinical trials for treatment of psoriasis and psoriatic arthritis. Results from a Phase III (late-stage) study show that the drug works better than methotrexate in the treatment of moderate-to-severe psoriasis.
Efalizumab (Raptiva) appears to effectively clear or nearly clear moderate-to-severe hand and foot psoriasis after 12 weeks. This type of psoriasis is often very difficult to control and treat.

Interleukins (IL) being investigated as sources or targets of therapy include IL-4, IL-2, IL-8, IL-11, and IL-12. For example, in a 2003 study, 75% of patients with severe psoriasis who were treated with interleukin-4 (rhuIL-4) experienced improvement rates of more than 68%.

A study of 180 patients with moderate-to-severe plaque psoriasis has shown that an investigational medicine called ABT-874 greatly reduced symptoms in most patients. ABT-874 targets proteins that are responsible for psoriasis-related inflammation.

Leflunomide. Leflunomide (Arava) is a disease-modifying antirheumatic drug (DMARD), which blocks autoimmune antibodies and is a powerful anti-inflammatory medication. It is proving to be active against psoriatic arthritis. Reports of adverse effects are comparable to those with methotrexate. Common problems include nausea, diarrhea, hair loss, and rash. Potentially serious side effects include infections and liver injury.

Sulfasalazine. Sulfasalazine (Azulfidine) is sometimes used for psoriasis. In one major analysis, sulfasalazine and methotrexate were the only medications proven to help patients with psoriatic arthritis. Many people, however, stop taking the drug because of common side effects that include headaches, gastrointestinal complaints, and rash. Benefits, if any, should be apparent in 4 - 6 weeks.

Immunosuppressants. Some immunosuppressants being studied for psoriasis include tacrolimus (Prograf), pimecrolium, and sirolimus. In one study, for example, tacrolimus showed an 83% reduction in symptoms in patients with psoriasis who used the drug. Studies have been limited, however. Side effects of these medications are similar to those of cyclosporine. Pimecrolimus may specifically target the skin and so have fewer side effects. (Some are also being studied as topical treatments.)

Phototherapy

Phototherapy means to treat with light.

When sunlight penetrates the top layers of the skin, this ultraviolet radiation bombards the DNA inside skin cells and injures it. This can cause wrinkles, aging skin, and skin cancers. However, these same damaging effects can destroy the skin cells that form psoriasis patches.

Phototherapy for psoriasis can be given as ultraviolet A (UVA) light in combination with medications, or as variations of ultraviolet B (UVB) light with or without medications. Not everyone is a candidate. For example, it may not be appropriate for patients who should avoid sunlight or those with very severe psoriasis.

Ultraviolet A (UVA) is a main part of sunlight. UVA phototherapy uses a photosensitizing medication (usually psoralen) in combination with UVA radiation to be effective. A photosensitizing medication makes a person more sensitive to light. Treatment with psoralen and UVA is referred to as PUVA. This approach is very powerful and effective in more than 85% of patients who use it. However, it poses a higher risk for skin cancers than UVB.

PUVA treatments cause inflammation and redness in the skin to develop within 2 - 3 days after treatment. Such damage inhibits skin cell proliferation and reduces psoriasis plaque formation.

Forms of psoralen include methoxsalen, 8-methoxypsoralen (8-MOP), or bergapten (5-MOP). The effectiveness of the treatment is based on a chemical reaction in the skin between the psoralen and light, which creates redness and inflammation that prevents the psoriasis disease process.

People should avoid this treatment if they are taking drugs or have conditions that cause them to be light sensitive. They should also take protective measures before, during, and after each treatment.

Initial PUVA Treatment Phase. The initial phase typically follows these steps:

Psoralen is typically taken by mouth in the form of 8-methoxypsoralen (for example, Oxsoralen) 75 minutes to 2 hours before the treatment starts. Psoralen reaches the skin through the bloodstream, where it increases the skin's sensitivity to UVA radiation.
Topical preparations of psoralen are alternatives to pills. They can be "painted on" or applied to the affected areas by soaking or bathing in a psoralen solution. PUVA-bath therapy may be especially useful for persistent psoriasis on the palms and soles or for patients with liver disease or who get severe nausea from taking the pill form. UVA should be given within 15 minutes of using topical psoralen.
The patient enters and stands in a light box, a unit lined with ultraviolet lamps. The initial UVA exposure time is very short (seconds to several minutes), and then increases to 20 minutes or longer. The amount of time a person is exposed to UVA rays depends on the skin type, with the shortest times recommended for fair-skinned patients.
Treatments may be repeated two or three times a week. They should never be performed more frequently than once every other day, since the full effects of the treatments are not evident for 48 hours.

It takes an average of about 25 PUVA treatments for full effect, but during that period, treatment intensity may vary.

If there is no response after 10 treatments, the doctor may increase the UVA energy.
If there is still no response after 15 treatments, the psoralen dosage may be increased.
If a patient's skin does not improve at all or worsens after these changes, the treatment is temporarily stopped. PUVA may be causing a toxic response in such cases, and, often, the condition gradually improves over the following 2 weeks.
If the skin does not improve over the following 2 weeks, PUVA treatment has failed. If skin improves during this resting period, treatment resumes.

Maintenance Phase. Once the psoriasis has improved by about 95%, the patient may be put on a maintenance schedule. Often only one or two treatments a month are needed, but some people may need more frequent treatments. As maintenance continues and the interval between treatments lengthens, the patients may become more susceptible to tanning and sunburn. They should reduce exposure to natural sunlight during this time.

Success Rates. Nearly 90% of patients achieve marked improvement or clearing within 20 - 30 treatment sessions.

Combinations. Combining acitretin, calcipotriene, methotrexate, or tazarotene gel with PUVA may enhance effectiveness or increase response. In addition, combinations may allow for lower doses of radiation or medications to be used, minimizing side effects. Retinoids may also help protect against skin cancers, while methotrexate may increase the risk. In some cases, patients resistant to PUVA or UVB may respond when the phototherapies are combined.

Side Effects and Complications of PUVA.

The psoralen methoxsalen causes a general ill-feeling and nausea in 20% of patients. Dividing up the dose and taking it in 15-minute intervals with food, or taking ginger 20 minutes before taking the drug, may be helpful.
Skin reactions, including itching, sunburn, and blistering, are common. These can generally be avoided with careful administration of PUVA therapy and protective measures. Antihistamines, baths with special oatmeal preparations (Aveeno), and capsaicin ointment (Zostrix) may be helpful.
After treatment, white spots commonly develop where psoriasis plaques had been, particularly in people with naturally darker skin. If they are troublesome, tanning products may help darken them. Small, dark raised spots called PUVA lentigines may also develop in affected areas with long-term treatment
Prolonged standing may trigger fainting in people with certain heart or blood pressure problems.
People with liver disease should discuss using topical psoralens, since oral forms may have adverse effects on the liver.
UVA penetrates the skin more deeply than UVB, so there is a greater danger of deep skin damage, accelerated skin aging, and skin cancers. Anyone who needs to avoid sunlight should not get this treatment.
The procedure increases the risk for cataracts if eyes are not protected for up to 24 hours after treatment.

Special Warning on PUVA and Skin Cancers. It has been known for some time that PUVA can change DNA and cause genetic mutations. PUVA is known to increase the risk for squamous cell skin cancer and slightly increase the risk for basal cell skin cancer, both of which are nearly always curable. One study reported an increased risk of melanoma. The risk for skin cancers is higher in persons who have:

A family or personal history of skin cancer
Light skin and fair or red hair
Received radiation or x-ray treatments or taken immunosuppressant drugs
Received over 200 PUVA treatments

Discussions are under way about discontinuing PUVA for psoriasis. The arguments generally are as follows:

Opponents of PUVA argue that studies suggest a long-term risk for melanoma, starting about 15 years after treatment, particularly in people who receive more than 250 treatments. In one long-term study, only 9 out of 1,380 patients developed melanoma. However, 7 of these cases occurred in the last 5 years of the study, indicating that the danger persists and more patients in this study are likely to develop this serious skin cancer as time goes on.
Supporters of PUVA argue that it is not yet known if the people who developed melanoma experienced sunburn during the procedures or if they already had risk factors for skin cancers. If so, then properly given treatments could still be considered safe for patients without risk factors. They also argue that PUVA is still the most effective treatment for severe psoriasis, and the alternatives are usually very powerful and relatively new drugs that may have even more serious side effects. Furthermore, the addition of retinoids may protect against skin cancers while proving to be a very effective combination.

Side effects of UVA radiation can be severe. Protective measures are needed during, before, and after treatment. Patients should avoid prolonged exposure to the sun for 24 hours before the oral treatment starts.

Protective Measures During Treatment:

Patients should wear specially designed goggles to protect the eyes from UVA radiation.
Sensitive areas, such as genitals, abdominal skin, and breasts, should be covered until tanning occurs in the exposed areas, after about a third of the treatment period. Note that PUVA is associated with a high risk for genital skin cancers, so male genitals must be covered throughout the process.

The following safety features should be available in the PUVA chamber:

Lamps with protective shields
A viewing window for a health professional to check the patient periodically
A door that can be opened by the patient easily and with little pressure
A timer that terminates the session automatically
An accessible alarm device

Protective Measures After Treatment. The drugs used in PUVA increase susceptibility for a natural sunburn for hours after treatment. The patient should take the following precautions:

Patients should wear UVA absorbing wrap-around sunglasses that are designed to completely block out stray radiation. They should begin wearing them as soon as they take the drug, and for at least 12 hours after the treatment. This is important to prevent a PUVA reaction around the eyes that can cause cataracts. There is no need to wear these glasses after sundown.
For about 8 hours after taking the drug, patients must also avoid exposure to daylight, even if the day is cloudy or exposure occurs through windows.
Patients who must go out should wear heavy opaque clothing (clothes that do not let light through), including hats and gloves.
Patients should apply sunblock over all exposed areas, including the lips. The sunblock should have an SPF (sun protection factor) of more than 15 and include ingredients that block both UVB and UVA radiation.
No patient should spend a long time in sunlight for at least 2 days after the combined treatment.

Ultraviolet B is another main part of sunlight, and is the main cause of sunburn. It generally affects the outer skin layers. UVB radiation reduces the abnormally rapid skin cell growth that occurs with psoriasis.

Types of UVB therapy:

Broadband UVB
Narrowband UVB (NB-UVB)
Laser treatments

Broad spectrum or broad band UVB is radiation in the wavelength of 290 - 350 nanometers, and is the standard UVB phototherapy treatment in the United States. It is not as potent as the treatments that use narrow-band UVB or PUVA, and is not useful for chronic psoriasis.

Broadband UVB may be given with or without medications. When used without medication (known as selective ultraviolet phototherapy), UVB treatment generally is given as follows:

Treatment starts in the doctor's office or another medical setting. Once the disease has stabilized, the patient can obtain a prescription for equipment that can be used at home. Even at home, treatment must always be supervised.
In preparation, the patient fully undresses, although unaffected areas may be covered to avoid overexposure.
The initial session may last as little as a few seconds, depending on whether the patient has a lighter or darker skin, with the lightest skin exposed to the briefest session. The duration increases with each treatment until the skin clears or the patient experiences itching or irritation. It should be noted that the condition may worsen initially.
UVB therapy usually requires about 20 - 40 treatments (about three per week). Full results take about 3 weeks.

Use of Medication. UVB was commonly used with coal tar (the Goeckerman regimen) in past decades, and then with anthralin (the Ingram regimen). Other medications are being studied with some success, and may prove to be tolerated better.

The Goeckerman regimen requires daily treatments for up to 4 weeks. The coal tar or anthralin are applied once or twice each day and then washed off before the procedure. Studies indicate that a low-dose (1%) coal tar preparation is as effective as high dose (6%). Such regimens are unpleasant, but still useful for some patients with severe psoriasis, since they can achieve long-term remission (up to 6 - 12 months).

Some evidence suggests that using a simple emollient (such as Vaseline or mineral oil) that enhances UVB light penetration can be effective. This addition to the treatment increases the risk for sunburns, however, and patients must be careful to avoid sun exposure. Researchers are tring combinations of other topical and oral medications. For example, combining UVB with methotrexate, or retinoids such as a tazarotene gel or oral acitretin, is producing positive results. Combinations with any of these drugs, however, must be supervised carefully to avoid serious reactions.

Side Effects of UVB. The treatment can cause itching and redness. UVB radiation from sunlight is known to increase the risk for skin cancers. There is no strong evidence, however, that UVB treatments pose any risk for skin cancers except on male genitalia. This risk, however, can be significant (4.5%) at high doses.

Narrow band radiation may be safer than other approaches, and some experts now believe it should be the first option for patients with chronic plaque psoriasis.

NB-UVB is used without medications and is very strong. Whether it has any affect, however, on the disease process itself is unclear. The light wavelength is between 310 - 312 nanometers, which, theoretically, is the most beneficial part of sunlight.

Exposure times are shorter but of higher intensity than with broadband UVB. This therapy is probably less likely than PUVA to cause skin cancers.

Clearance of 75% typically occurs after 10 - 12 treatments. NB-UVB treatments performed three times a week achieve results that are equal to twice-weekly PUVA treatments. Weekly NB-UVB treatments are not effective. Studies so far are mixed on whether NB-UVB remission rates are equal to those of PUVA.

Patients prefer NB-UVB over other PUVA treatments because they do not have to wear protective eyewear, take medications, or experience unpleasant side effects, notably nausea. It is also safe for pregnant women and children.

Combinations with topical medications, such as tazarotene or psoralens, may help NB-UVB therapy work better.

Laser UVB Treatment. A recent variation of a device called an excimer laser (Xtrac) delivers a precise UVB wavelength of 308 nanometers. The laser is more effective than narrow-band UVB for localized psoriasis, since it allows very specific areas of skin to be targeted. (Note: The therapy is not suitable for the scalp.) Generally, 8 - 10 treatments given twice a week will clear psoriasis. Remission rates are similar to NB-UVB, but the excimer laser can clear the psoriasis faster and at lower doses. It also spares the healthy skin around it. Blistering is a common side effect. More comparison studies are needed to determine risk and benefits compared to NB-UVB, particularly any long-term risk for skin cancer.

Pulsed-Dye Lasers. Pulsed-dye lasers give off high-intensity yellow light, which destroys the tiny blood vessels that make up psoriatic plaques. This treatment has been used for years to remove birthmarks, such as port wine stains and unsightly blood vessels on the skin. Some studies have reported significant (but not complete) improvement, and remissions that have lasted up to 13 months. Treatment sessions last up to 30 minutes and can feel uncomfortable (similar to being repeatedly snapped with a rubber band). It typically takes up to six sessions to clear the target areas. Bruising is common, and there is a small risk for scarring.

Home tanning devices and tanning salons are not usually recommended, but they may be helpful for patients without access to a medical unit. In a 2003 study, many patients achieved a significant reduction in symptoms when taking acitretin and exposed to a UVB commercial tanning unit (specifically, a Wolff tanning bed).

However, UV outputs can vary widely among tanning beds and salons. Some units emit UVA radiation, which poses a higher risk for skin cancers. Adverse effects of tanning salons that use UVA or UVB radiation are the same as with any UV phototherapies, including a risk for skin cancer.

Managing Psoriasis

Although sunburn carries a risk for skin cancer and can make psoriasis worse, regular exposure to the sun helps clear psoriasis in people with mild-to-moderate conditions. People should cover non-affected areas with clothing or sunscreen and sun bath only until the skin starts to tan.

Vacations in sunny areas, such as Hawaii or the Caribbean, can offer relief. For those who can afford it, a prolonged stay of several weeks at the Dead Sea in Israel has proven to significantly improve or clear 88% of those with psoriasis who go there. The region offers a unique combination of intense but naturally filtered UVA radiation combined with minerals and salts from the sea.

Because of the association between negative emotions and psoriatic flare-ups, relaxation and anti-stress techniques may be helpful. A small 1999 study found that hypnosis aimed at reducing stress may relieve symptoms.

Another study found that some patients with psoriasis had a traumatic or stressful event coincide with the appearance of psoriasis. Talking to a psychiatrist about the issue resulted in significant symptom improvement in 62% of study patients who recalled such an event.

If skin becomes dry and itchy, the patient may try the following:

Soak in a warm bath for about 15 minutes.
Afterward, apply salicylic acid first, which removes scaly skin and may promote the penetration of both moisturizers and topical prescription medications.
Then, apply a thick moisturizer or emollient, such as Vaseline, Cetaphil cream, or Eucerin cream. Lotions are not good enough moisturizers.
Special gloves made of Gore-Tex (DermaPore) may be worn at night over a thick moisturizer cream. These gloves are protective but also allow moisture to escape.

Some experts suggest that many common moisturizers may actually increase water loss in psoriasis, but studies still have to confirm this. In the meantime, if moisturizers help relieve the condition, patients should use them.

Capsaicin (Zostrix) is an ointment prepared from the active ingredient in hot chili peppers. It is used to relieve arthritic pain and may help relieve psoriatic itching. Capsaicin should be handled using a glove and applied to affected areas three or four times daily. The patient will usually have a burning sensation when the drug is first applied, but this sensation lessens with use.

Folic Acid. Patients should be sure they get enough of the B vitamin folate (folic acid). Folate-rich foods include liver, asparagus, fruits, green leafy vegetables, dried beans and peas, orange juice, and yeast. Many types of bread and other commercial grain products now have added folic acid.

Omega-3 Fatty Acids. Omega-3 fatty acids, particularly those found in some fish oil, have anti-inflammatory properties that may benefit some patients with psoriasis and other autoimmune conditions.

Patients with persistent psoriasis may be tempted to try alternative or untested treatments, including herbs and other nontraditional therapies. Researchers at the Medical College of Georgia say green tea slowed the growth of skin cells in animal studies and may one day prove to be useful in treating psoriasis. More research is needed.

Several traditional remedies for psoriasis include various other herbal supplements, but to date no clinical studies have been reported on these substances. No one should use any unproven therapy without consulting a doctor to be sure such treatment is not harmful, and does not interfere with any standard medications they take.

Herbal remedies and dietary supplements are not regulated by the FDA. This means that manufacturers and distributors do not need FDA approval to sell their products. In addition, any substance that affects the body's chemistry can, like any drug, produce side effects that may be harmful. There have been many reported cases of serious and even deadly side effects from herbal products.

The following are special concerns for people taking natural remedies for psoriasis:

Zinc pyrithione is sometimes used, but its effectiveness is doubtful. A number of so-called natural psoriasis products (Skin-Cap, Blue Cap, Miralex) that contain this compound also contain prescription-strength corticosteroids. Such steroids have the same side effects as those in standard psoriasis agents. These products have been banned in the U.S. and Canada, but similar untested medications are available over the Internet.
Gotu Kola (Centella asiatica) is sometimes applied in a cream for psoriasis. The oral form of the herb has serious side effects, however, including increasing the risk for miscarriage in pregnant women.

Outlook

Psoriasis is lifelong and not curable. Although it is also marked by rapid cell growth, psoriasis is neither cancerous nor contagious.

In general, studies report the following features of its course:

The condition almost always relapses. In a few cases, large areas of plaque can persist for years.
Psoriasis nearly always goes into remission, however, often clearing on its own. In one study, 30% of patients reported untreated psoriasis going into remissions that lasted 1 - 54 years.
Psoriasis can improve during pregnancy, especially during the second and third months. Increased levels of estrogen may be responsible for this improvement. Relapse may occur after giving birth.

The emotional and social consequences of psoriasis should not be underestimated.

Many patients suffer severe humiliation and depression if plaques are visible. Some even withdraw from society and become isolated.
Some patients are forced to leave their jobs and go on disability if the condition becomes incapacitating.

Researchers have reported the following:

Surveys of patients with psoriasis report a negative mental and physical impact that is nearly equivalent to that of other major chronic conditions, including cancer, high blood pressure, diabetes, heart disease, and depression.
In one study, 75% of patients reported that psoriasis hurt their confidence.
Another study reported that 8% of people with psoriasis felt their life was not worth living.

Some patients, particularly men, use alcohol and smoking as self-medication to reduce the emotional consequences of psoriasis. In fact, studies have found that people with psoriasis have higher mortality rates, mostly from heavy drinking. Smoking has also been cited as a major risk, particularly for pustular psoriasis. Some experts believe that drinking and smoking may actually cause biological damage that contributes to psoriasis itself.

However, smoking may delay the onset of psoriatic arthritis in some patients, depending on when they started the habit. Psoriatic arthritis tends to occur about a decade after psoriasis develops. The review of 281 psoriasis patients showed that the condition appeared after about 13 years in nonsmokers, compared to 23 years in those who began smoking after the first onset of psoriasis. Psoriatic arthritis appeared after 8 years in people who smoked before developing psoriasis.

Folate Deficiency in Severe Psoriasis. Severe psoriasis can also cause folate deficiency. Folate is a B vitamin that is important for nerve function, preventing birth defects. It also prevents elevations of homocysteine, a factor that may play a critical role in heart disease.

Skin Cancers. In one study, patients with severe psoriasis (who receive medications that affect the whole body) were at higher than normal risk for developing cancers, primarily skin cancers and lymphomas. The risk was not any higher for patients with milder psoriasis. There is some indication, however, that patients with psoriasis have a higher risk for non-melanoma skin cancers regardless of treatments.

Heart Attacks. A study released in October 2006 shows an increased risk of heart attacks in people with psoriasis. The risk was highest in young patients with severe psoriasis.

Other Coexisting Conditions: Studies done in Newfoundland and Germany have also revealed increased cases of diabetes, obesity, arthritis, and cancer in patients with psoriasis. Research is underway to determine if there are genetic links between psoriasis and these conditions.

Increased Risk of Death. Severe psoriasis has been linked to a significant increase in a patient's risk of death. A study of more than 713,000 patients showed that severe psoriasis increased mortality by 50%. Study authors encourage patients to receive comprehensive health examinations to reduce the risk. Study participants were considered to have severe psoriasis if they required systemic treatment.

Impaired Temperature Regulation. Erythrodermic psoriasis, in which psoriasis covers the entire skin, can cause abnormalities in the body's ability to regulate temperature.

Zumbusch Psoriasis. A combination of erythrodermic and pustular psoriasis causes a serious condition called Zumbusch psoriasis:

The condition can develop abruptly.
Symptoms may include fever, chills, weight loss, and muscle weakness.
Patients may develop excessive fluid build-up, protein loss, and electrolyte imbalances. In such cases, hospitalization is required. Fluid and chemical balances must be restored and temperature stabilized as soon as possible.

Zumbusch psoriasis can be life threatening, particularly in the elderly. The condition is very rare in children and, if it occurs, tends to improve more quickly than in adults, possibly even without medication.

Most cases of psoriatic arthritis (PsA) are mild, but complications can occur:

Severe joint deformity and destruction (called arthritis mutilans) may develop, generally in the small joints of the hands and feet. Studies report this happens in about 5 - 16% of patients. Psoriasis patients with other arthritic conditions (osteoarthritis or rheumatoid arthritis) in the joints of the fingers tend to have a higher risk.
People with PsA may have a higher risk for respiratory illnesses.

Some earlier studies indicated that patients with psoriatic arthritis had a shorter lifespan than the general population, but more recent studies found no significant difference.

Resources

www.psoriasis.org -- National Psoriasis Foundation
www.aad.org -- American Academy of Dermatology
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.clinicaltrials.gov -- Find clinical trials

References

Gelfand JM, Neimann AL, Shin DB, et al. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006 Oct 11;296(14):1735-41.

U.S. Food and Drug Administration. CDER Drug and Biologic Approvals for Calendar Year 2006 -- Updated through August 31, 2006. Last accessed on 15 October, 2006.

FDA Announces Strengthened Risk Management Program to Enhance Safe Use of Isotretinoin (Accutane) for Treating Severe Acne. US Food and Drug Administration. Rockville, MD: National Press Office; August 12, 2005.

Anstey AV and Kragballe K. Retrospective assessment of PASI 50 and PASI 75 attainment with a calcipotriol/betamethasone dipropionate ointment. Int J Dermatol. 2006 Aug;45(:970-5.

National Psoriasis Foundation. About Psoriasis: Statistics. Last Accessed 9 October, 2006.

Antoni CE, Kavanaugh A, Kirkham B, Tutuncu Z, Burmester GR, Schneider U. Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT). Arthritis Rheum. 2005;52(4):1227-1236.

Bowcock AM, Cookson WO. The genetics of psoriasis, psoriatic arthritis and atopic dermatitis. Human Mol Genet. 2004;13 Spec No 1:R43-55.

Feldman SR, Koo JY, Menter A, Bagel J. Decision points for the initiation of systemic treatment for psoriasis. J Am Acad Dermatol. 2005;53(1):101-107.

Murase JE, Chan KK, Garite TJ, Cooper DM, Weinstein GD. Hormonal effect on psoriasis in pregnancy and post partum. Arch Dermatol. 2005;141(5):601-6.

Review Date:
9/19/2007
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

Multiple sclerosis

FitSugar — Wed, 08 Oct 2008 17:35:12 -0700

In This Report

Highlights
Introduction
The Autoimmune Disease Proc...
Symptoms
Causes
Risk Factors
Complications
Diagnosis
Treatment
Drug Treatment
Other Treatments
Treating the Complications...
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Gender and Multiple Sclerosis (MS)

MS is increasingly affecting women, according to research presented at the 2007 annual conference of the American Academy of Neurology. Researchers found that in the 1940s, women were twice as likely as men to be diagnosed with MS. By 2000, women were about four times more likely than men to develop MS. Experts are uncertain why this ratio is growing.

Family History

If MS runs in your family, there’s a chance you may develop the disease at the same age that other family members did, suggests a 2007 Neurology study. However, family history does not predict disease course or severity.

Vitamin D

Higher blood levels of vitamin D may reduce the risk for MS, at least among Caucasians, indicates a 2007 study in the Journal of the American Medical Association. (The researchers found no protective effect for African-Americans or Hispanics.) However, until further research is conducted, doctors do not recommend taking vitamin D supplements for MS prevention.

Infections and Symptom Relapse

Both viral and bacterial systemic infections can trigger relapses, according to a study in Neurology. Researchers found that relapses and new brain lesions appeared within 2 weeks after an infection.

Drug Research

Natalizumab (Tysabri) may help reduce vision loss in patients with relapse-remitting MS, indicates a 2007 Neurology study. In 2006, the FDA enforced safety restrictions on the use of this drug due to cases of progressive multifocal leukoencephalopathy (PML), a rare brain disorder. Since the restrictions were put in place, no new cases of PML have been reported.
Glatiramer acetate (Copaxone) shows little benefit for primary progressive MS, according to a 2007 study in Annals of Neurology.
Testosterone gel may help men with relapse-remitting MS, suggests a small study published in 2007 in the Archives of Neurology.

Introduction

Multiple sclerosis (MS) is a disease of the central nervous system (CNS), the nerves that comprise the brain and spinal cord. It has two major features:

Destruction of myelin, a fatty insulation covering the nerve fibers, is the main characteristic of MS. The end results of this process, called demyelination, are multiple patches of hard, scarred tissue called plaques. (Multiple sclerosis is well named. Sclerosis comes from the Greek word skleros, which means hard.)
Destruction of axons, the long filaments that carry electric impulses away from a nerve cell, is also a major factor in the permanent disability that occurs with MS.

Myelin is the layer that forms around nerves. Its purpose is to speed the transmission of impulses along nerve cells.

The symptoms, severity, and course of MS vary widely depending partly on the sites of the plaques and the extent of the demyelination. Experts generally group multiple sclerosis into two major symptom categories:

Relapsing-remitting
Chronic-progressive

Chronic-progressive MS is often subcategorized as primary-progressive, secondary-progressive, and progressive-relapsing.

Recent evidence suggests that the disease process starts long before symptoms begin. By the time symptoms appear, there are often already signs of brain and spinal cord atrophy. The cause of MS is unknown, and it cannot be prevented or cured. It is not fatal, however, and great progress is being made in treating it and identifying underlying mechanisms that trigger this disease.

Relapsing-remitting multiple sclerosis generally occurs in younger people and is the most common form of MS. It generally follows this course:

Most patients first experience a single attack of symptoms called a clinical isolated syndrome, which typically occurs between the ages of 20 - 40 years. Once a second attack occurs, the patient is considered to have relapsing-remitting multiple sclerosis.
The characteristic feature of relapsing-remitting MS is the attack (also referred to as relapse, flare-up, or exacerbation), which is a bout of specifically MS symptoms (facial pain, Lhermitte’s sign, or bladder instability) that lasts at least 24 hours and typically several days. Such attacks are fairly mild in about half of patients with this form of MS.
The disease then goes into remission (when symptoms improve or disappear), usually for about 4 - 8 weeks. To be considered in remission, attacks need to be separated by at least 30 days. Remission periods may be spontaneous or induced by immunosuppressive drugs. A person with multiple sclerosis in remission may have subtle attacks and not realize it. For example, hands may be a little numb for a few days, or there may be slight awkwardness in gait or coordination.
Remissions are almost always followed by relapses, in which symptoms flare-up or the patient experiences a period of deteriorating ability.

About 20% of patients with relapsing-remitting MS experience little or no progression after a first attack for long periods of time, although by 25 years most patients have converted to a progressive phase.

The term chronic-progressive multiple sclerosis is used to describe cases in which symptoms continue to worsen slowly without remission. About 20% of multiple sclerosis patients (usually those whose first symptoms occur after age 45) have the chronic-progressive form without first developing relapsing-remitting MS. Chronic-progressive MS generally follows a downhill course, but its severity varies widely. Three variants are commonly used to define this patient group:

Secondary-Progressive MS (SPMS). SPMS is the natural evolution of relapsing-remitting MS and develops in about half of patients during the first 10 years and nearly all of them within 25 years. It follows a progressive course of nerve and muscle deterioration with occasional acute flare-ups, remissions, and plateaus.
Primary-Progressive MS (PPMS). PPMS progresses continuously and gradually from the first onset of symptoms and has no remissions. It occasionally levels off, and minor improvement is even possible. This occurs in about 10% of patients, who tend to be older than average at the time of diagnosis.
Progressive-Relapsing MS (PRMS). PRMS is progressive from the start with acute symptom flare-ups, but may have some relapses with continued deterioration between them. It occurs in less than 5% of patients.

Because the natural courses of primary-progressive and progressive-relapsing MS are similar, some experts believe this distinction is unnecessary.

Click the icon to see an image depicting multiple sclerosis.

The Autoimmune Disease Process

Multiple sclerosis is referred to as an autoimmune disease. The general theory for the development of MS is that a genetically damaged immune system is unable to distinguish between virus proteins and the body’s own myelin and so produces antibodies that attack. In other words, the body becomes allergic to itself, a condition known as autoimmunity.

Autoimmunity may develop when the body's immune system is damaged by genetic or environmental factors or both, causing it to attack its own tissues. In the case of MS, the immune system attacks the tissues that make up myelin:

Myelin is made from layers of cell membranes that are produced in the brain and spinal cord by specialized cells called oligodendrocytes. The destruction of this myelin sheath during the disease process is the hallmark for multiple sclerosis.
The myelin coat is distributed in segments along the axons, the long filaments that carry electric impulses away from a nerve cell.
The segments are separated from each other by tiny clusters called nodes of Ranvier, which house channels for sodium ions. These sodium ions are important for boosting the electrical charge required to pass signals from one nerve to another.
As the myelin insulation is destroyed, signals transmitted from nerve cell to nerve cell throughout the central nervous system are disrupted.
Experts once believed that axons themselves were spared during the disease process. Research, however, has shown that many are severed in MS and, in fact, axon destruction appears to start at an early stage in the disease and may be a major cause of its irreversibility.

The body often makes corrective actions to offset the effects of the nerve cell destruction:

For example, researchers have observed an increase in the density of the sodium channels, which carry electric charges. By increasing their numbers, the nerve cells can continue to communicate, in spite of the loss of myelin.
The nerves also retain some capacity to remyelinate (to restore the insulating myelin).

Such processes are probably responsible for the remissions that most patients experience. Unfortunately, the disease process nearly always eventually outpaces these corrective actions.

The Normal Immune Response.

The most important critical immune factors in the disease process are white blood cells called lymphocytes, which consist of T cells and B cells. These cells are the warriors in the immune defense system.
Receptors on T cells acquire the ability to recognize specific molecules called antigens. Antigens are typically proteins from infecting organisms, such as bacteria or viruses, and perceived as a threat to the body.
Once the antigen is identified, specific T cells, called helper T cells, trigger the B cells to release antibodies. These molecules are designed to attach to and destroy the targeted antigen.

Autoimmunity.

Multiple sclerosis, and probably all autoimmune diseases, involves an error in the education of T cells, which makes them unable to distinguish self from non-self.
In multiple sclerosis, the miseducated T cells mistake molecules in the body's own myelin as a foreign antigen. Such targets are referred to as self-antigens.
In response to detection of these self-antigens, the T cells set off the usual cascading immune events, including the release of B lymphocytes, to rid the body of the perceived threat.
The B lymphocytes fire off antibodies as usual, but in this case they are referred to as autoantibodies, because they are attacking antigens that belong to the body's own self.
In MS, the immune system is tricked into targeting self-antigens that are myelin proteins, the fatty insulation covering the nerve fibers. Another autoantibody target may be the oligodendrocytes themselves -- the specialized cells that make up myelin.
To make matters worse, the process perpetuates through a cascading series of events in which the B cells and T cells continue to interact, creating numerous different self-antigens. The attacks continue and, in the process, the original self-antigen is unrecognizable.

Cytokines and the Inflammatory Response. The inflammatory response is the product of an overactive immune system and is a major destructive force in an autoimmune disease.

Once the lymphocytes have launched a response to an antigen, they also release masses of other white blood cells to gather at the injured or infected site.
The major players in this response are white blood cells called leukocytes. Researchers are particularly interested in leukocytes called cytokines. These are small powerful proteins that, in tiny amounts, are indispensable for healing. When they are overproduced, however, which occurs in MS, they play a major role in the destructive process.
Their intensive convergence on the affected area causes it to become inflamed and injurious to the very cells they are designed to protect. Under normal conditions, this inflammatory process is controlled and self-limiting, but in people with autoimmune diseases such as multiple sclerosis, the process persists and damage occurs in the surrounding tissues.

Important cytokines in MS appear to be tumor necrosis factors, interleukin-12, and interferon-gamma. Other cytokines, including interleukin-10 and transforming growth factor beta, may play a protective role and help block inflammatory activity.

The inflammatory response may trigger the disease, but afterward a progressive course takes over that does not appear to be related to inflammation. Experts have found that destruction of axons, the long filaments that carry electric impulses away from a nerve cell, is a major feature of multiple sclerosis. In fact, it may be the major cause of permanent disability that occurs with this disease. Microscopic studies reveal that axons are injured early on as "bystanders" while myelin is being peeled off. As the disease progresses, these weakened and exposed axons degenerate further. Most of the damage occurs early in the disease process and decreases over time, although some destruction can still be observed years and decades afterward. Such evidence is having significant effect on approaches to treatment and research.

Symptoms

Most patients first experience multiple sclerosis as a single attack of symptoms called a clinical isolated syndrome, which typically occurs between the ages of 20 - 40 years. Once a second attack occurs, the patient is considered to have relapsing-remitting multiple sclerosis. Much less commonly, the disease is progressive from the start and symptoms are more or less continuous.

Early symptoms may include the following:

Optic neuritis and other problems in the eye. Optic neuritis, which is inflammation of the nerves in the eye, affects over 50% of patients and is the first symptom in about 16% of patients. Symptoms include unclear or doubled vision, usually in one eye. Some people see a shimmering effect. Patients may also experience pain or involuntary jerking or movement of the eye (called nystagmus). In 20% of people with this condition, MS develops within 2 years after the onset. In 45 - 80%, MS develops within 15 years. About 17% of people eventually experience impaired eye movement.
Fatigue. Fatigue is typically worse in the afternoon and may be accompanied by an increase in body temperature. At the onset, this occurs in about 20% of patients, but as the disease progresses, this is a significant symptom in nearly all patients.
Changes in sensations in the arms and legs. Patients can experience heaviness, weakness, or clumsiness in the limbs. Tingling or loss of sensations can also occur, most commonly in the legs. The first symptoms for patients with primary progressive MS often develop slowly in the upper legs.
Muscle weakness in the legs and poor coordination.
Lhermitte’s sign. This is an electrical sensation that runs down the back and into the legs, which is produced by bending the neck forward.
Spasticity. Spasticity is the inability to control muscle tone and leads to spasms and stiffness. It is very common in MS.
Disturbances in the bladder.

In addition to the persistence of early symptoms, some patients experience the following symptoms as the disease progresses:

Imbalance and dizziness.
Tremors.
Facial pain.
Spasm-related symptoms. They include burning, itching, aching, quivering sensations. They usually occur in the extremities and last seconds to minutes.
Speech difficulties.
Difficulty swallowing.
Symptoms in the gastrointestinal, urinary, and genital tracts. Possible sexual dysfunction and loss of bowel and bladder control in severe cases.
Emotional mood swings. Depression is very common. About 10% of patients suffer from psychosis (manic depression and paranoia). About 5% of patients with severe MS experience uncontrolled and extreme mood swings called the laughing/weeping syndrome.
Problems in concentration and memory.
Hearing loss.

Infections. Viral infections have long been known to worsen MS symptoms. An important 2006 study indicated that bacterial infections can also trigger MS relapses. In the study, relapses appeared within 2 weeks of a viral or bacterial infection.

Heat. Heat, whether generated by ambient temperature, infection, or physical activity, worsens MS symptoms in about 60% of patients.

Stress. There is a strong correlation between severe stress and exacerbation of MS symptoms. For example, in one study, 85% of instances of MS exacerbations were associated with stressful events that occurred within an average of 14 days before the episode. Stress is not a cause of MS, however.

Trauma. Some experts believe that injury (trauma) to the head, neck, or upper back may trigger new or recurrent symptoms by disrupting the blood-brain barrier and allowing immunological attacks on the brain. This is a highly controversial theory, however, with very little supporting evidence.

Causes

The cause, or causes, of multiple sclerosis remains a mystery. Genetic factors certainly play a role in MS. No single gene, however, is likely to be responsible for causing MS. Rather, the current theory is that the disease occurs in people with a genetic susceptibility who are exposed to some environmental assault (a virus or a toxin) that disrupts the blood-brain barrier. Immune factors converge in the nerve cells and trigger inflammation and an autoimmune attack (a self-attack) on myelin and axons. Still, a number of disease patterns have been observed in patients, and some experts believe that MS may prove to be not a single disorder, but may represent several diseases with different causes.

Some research suggests that all autoimmune diseases are basically due to the same genetic error. A 2001 study found, for example, that the T cell immune factors in type 1 diabetes target the same self-antigens as in multiple sclerosis (MS). Many questions are unanswered, however. It is not known why the diseases develop in different locations to cause separate disorders. Nor, why some autoimmune events occur in everyone but not everyone develops an autoimmune disease.

Genetic factors probably play some role in making a person susceptible to the disease process leading to multiple sclerosis. In particular, abnormalities in the human leukocyte antigen (HLA) region located on chromosome 6 appear to be more prevalent among people with MS. Researchers theorize, however, that a combination of genes (not a single gene) is implicated in the development of MS, and the risk for someone inheriting all of these genetic factors is less than 5%. Advanced techniques called microarray technologies are now making it possible to scan hundreds of genes and identify those most likely to be contributors to MS. Genetic research may also pave the way for the development of new drugs to treat this disease. For example, researchers have recently identified the Olig1 gene as a key regulator in repairing damaged myelin-producing cells.

Infectious organisms, most likely viruses, are the top suspects for triggering the autoimmune response in people genetically susceptible to MS. There are a number of reasons for this belief:

The geographical distribution of the disease. The number of MS cases increases the further one gets from the equator in either direction.
Multiple sclerosis clusters. Four separate clusters of multiple sclerosis outbreaks occurred between 1943 - 1989 in the Faroe Islands, located between Iceland and Scandinavia. During World War II, this region was occupied by British troops. The incidence of MS increased each year for 20 years after the war, leading some researchers to think that the troops might have brought with them some disease-causing organism. In fact, one theory suggests that these findings offer evidence that MS is a sexually transmitted infection that occurs during adolescence. For example, the disease clusters observed in the Faroe Islands could be related to high sexual activity between the troops and local young women. A high incidence of MS is found in countries with a high degree of sexual permissiveness. MS is very rare in traditional cultures, but increases in people from these regions when they immigrate to industrialized Western nations.
Viral similarity to myelin. Some viruses are strikingly similar to the myelin protein and may therefore cause confusion in the immune system, causing the T cells to continue to attack their own protein rather than the viral antigen. More than one antigen may be involved; some may trigger the disease, and others may keep the process going.

Infectious Organisms Under Suspicion. Although many infectious microorganisms have been investigated, no one organism has emerged as a proven trigger. It is possible that different patients may be affected by different organisms, and that infections cause some, but not all, cases of MS. Organisms that are at the top of the suspect list are those that can affect the central nervous system. The following are three primary suspects:

HHV-6. Herpesvirus 6 (a form of herpesvirus that causes roseola, a benign disease in children) is also known to cause encephalitis (brain inflammation) in patients with impaired immune systems. A number of studies have reported higher than normal rates of HHV-6 infection in patients, and some experts believe that may be important in MS. Other experts argue, however, that nearly everyone harbors this virus and there is still no evidence of a causal relationship. Other herpes viruses can also infect brain cells. They include herpes simplex 1 and 2 (the causes of oral and genital herpes), varicella-zoster virus (the cause of chicken pox and shingles), and cytomegalovirus.
Epstein-Barr virus (EBV). Evidence suggests an association between EBV, the cause of mononucleosis, and MS. EBV is an extremely common virus and another member of the herpes virus family. Nearly all people have been exposed to EBV. However, researchers have discovered that people who are especially sensitive to the virus and have unusually high levels of EBV antibodies may have a greater risk of developing MS. Scientists are still uncertain if EBV is a cause of MS. EBV has also been linked to other autoimmune diseases such as lupus.
Chlamydia Pneumoniae. This atypical bacterium has been associated with persistent inflammation. A few studies have reported significantly higher rates of previous Chlamydia infection in patients with MS than in individuals without MS. An important group of 2000 studies reported no connection at all between Chlamydia and MS, and any experts now believe there is no strong evidence linking the microbe to MS. It is still possible, however, that the infection, which can cause widespread inflammation, plays a role early in the course of the disease in some individuals.

Other viruses that have been investigated include measles virus, adenovirus, and the retroviruses (HIV, HTLV-I, and HTLV-II), but none have emerged as having any importance.

Note on Vaccinations: Concerns about a link between the hepatitis B vaccine and MS led France to halt a major vaccination program in 1998. Subsequent research investigating whether the hepatitis B vaccine is indeed associated with an increased risk of MS has yielded mixed results. It appears that the vaccine would be, at most, a contributing -- but not the sole -- factor in MS development. At present, the evidence has not warranted any change in American immunization policies. Research has ruled out a link between any other vaccinations, such as or influenza or tetanus, and relapses of MS.

Risk Factors

An estimated 400,000 Americans and 2.5 million people worldwide suffer from MS.

Age. Onset occurs between the ages of 20 - 40 years in 70% of patients with the average age being 30 and the peak incidence occurring in the mid-twenties. The disease can still occur in both younger and older individuals. It rarely develops before age 15 or after age 60, however.

Gender. MS is more common among women than men. The gender gap is strongest among people who develop MS at a younger age. According to research presented at the 2007 American Academy of Neurology annual conference, the ratio between women to men has been growing. Researchers found that in the 1940s, the ratio of women to men with MS was 2 to 1. By 2000, the ratio had grown to 4 to 1. However, some research indicates that men may be more disabled by the disease than women.

Ethnicity. Multiple sclerosis occurs worldwide but is most common in Caucasian people of northern European origin, especially those of Scottish descent. It is extremely rare among Asians, Africans, and Native Americans. Specific groups (gypsies, Eskimos, Bantus) have never reported a case. While the risk of MS for African-Americans is around half of that for Caucasians, a recent study suggested that African-Americans are more likely to develop a more aggressive form of the disease and to suffer impaired mobility.

Geography. The risk for MS is higher in different regions of the world. In general, MS is more prevalent in temperate regions than in the tropics. Specifically, prevalence is highest in northern and central Europe (except northern Scandinavia), Italy, southern Australia, and northern regions of North America. Middle-risk areas include southern Europe (except Italy), southern US, northern Australia, and northern Scandinavia. Low-risk areas include parts of Africa and Asia, the Caribbean, Mexico, and possibly northern South America. It is unclear whether this pattern is attributable to environmental factors, genetics, or both.

Family History. A family history of the disease also puts people at risk for MS, although the risk for someone inheriting all the genetic factors contributing to MS is only about 2 - 4%. A 2007 study indicated that family members who have MS tend to develop the disease at around the same age. However, family history does not predict whether one family member will experience the same disease severity as another family member.

Cow's Milk During Early Infancy. Breast milk contains factors that may help regulate the immune response, and there is some evidence that infants fed only on cow's milk may have a higher risk for either diabetes type 1 (another type of autoimmune disease) or multiple sclerosis later in life. Studies on national differences in diabetes suggest that the risk may vary with different milk proteins, suggesting that not all cow's milk is the same and that some proteins carry higher risks than others.

The Hygiene Theory: Early Infections as Protection Against Allergies and Autoimmune Diseases. Over the past decades, there has been a dramatic increase in asthma, allergies, and autoimmune diseases, such as multiple sclerosis, Crohn's disease, and type 1 diabetes. One theory blames this rise on the reductions in childhood infections that have occurred with modern hygiene and antibiotic use. Studies supporting this have observed a higher incidence of allergies and autoimmune diseases, including MS, among populations with good hygiene and in animals that have been raised in a germ-free environment. The basic theory rests on the idea that early infections stimulate production of specific immune factors that protect against allergies and autoimmune diseases. The exact mechanisms of these effects are as yet unknown.

Vitamin D. Higher blood levels of vitamin D have been associated with a lower risk for MS, at least among Caucasians. (Studies have not shown that vitamin D has a protective effect for other racial groups.) However, there is not yet enough evidence to indicate that taking vitamin D supplements can help prevent MS.

Exposure to Sunlight. In a 2003 study, higher exposure to sunlight during childhood and early adolescence was associated with a lower risk for MS, perhaps because UV radiation produces higher levels of vitamin D, which has been associated with protection against MS. The effect of sunlight during winter seemed to be more protective than summer light. Unfortunately, higher exposure to sunlight also coincides with a higher risk for skin cancer, which is far more common than MS.

Estrogen and Oral Contraceptives. Higher estrogen levels may temporarily lower the risk of developing multiple sclerosis. Studies indicate that oral contraceptives (which contain estrogen) and pregnancy delay the onset of multiple sclerosis. The risk for a first clinical attack increases, however, in the 6 months after a woman gives birth.

Complications

Multiple sclerosis is not a fatal disease. Some data suggest that it shortens the average life span by only about 6 or 7 years. Still, in about half of MS cases, patients die of complications of the disease, and the disease has significant negative emotional and physical consequences. Suicide rates among patients with MS are higher than average.

The severity of the disease varies widely from patient to patient and is unpredictable. About 20% of patients remain asymptomatic or become only mildly symptomatic after an initial clinical event. Another 20% experience a rapidly progressive condition. Most patients, however, will experience some degree of progression.

Women tend to have a better outlook than men. Factors the determine a higher risk for a severe condition include:

Age over 40 years at the time of onset of symptoms
Initial symptoms that affect motor control, mental functioning, or urinary control, or initial symptoms affect multiple regions
Attacks in the first years that are frequent or interval between the first two attacks is short
Incomplete remissions
Rapid progression to disability
MS that is progressive from the beginning or becomes progressive shortly after the onset

Doctors and researchers often use a scale called the Kurtzke Disability Status Scale to assess and predict future disability. The system uses a score of 1 to 10 to rate the degree of walking disability. Experts have used the scale to attempt to predict average times for progression from one stage to the next depending on whether patients have relapsing-remitting or chronic progressive MS.


Score	Disability Description	Relapsing-Remitting MS: Average time until onset of symptoms*	Chronic Progressive MS: Average time until onset of symptoms*
1	No disability and minimal neurologic symptoms.	11.4 years from Score 1 to Score 4	0 years from Score 1 to Score 4
2	Minimal disability in one or two functional areas. Slight weakness or stiffness, mild walking impairment or visual disturbances
3	Moderate disability in one functional area, such as vision or the urinary tract, and possibly more than one minimal disability in several others. Either a part of one of the limbs or a whole side can be partially paralyzed. May stagger at times.
4	Disability is relatively severe but there is full ability to walk without aid. Patients are self-sufficient and can be active 12 hours a day and carry on normal activities. Can walk without aid or rest for 300 to 500 meters.
5	Disability is severe enough to impair or even preclude a full day's activities. Able to walk unaided and without rest for 100 to 200 meters.	23.1 years from Score 1 to Score 6	7.1 years from Score 1 to Score 6
6	Can walk unaided for about 100 meters only with assistance or devices, such as two canes, crutches, or braces.	23.1 years from Score 1 to Score 6	7.1 years from Score 1 to Score 6
7	Mostly restricted to wheelchair, although can manage the wheelchair and leave it unassisted. Can walk with aids no further than about five meters.	33.1 years from Score 1 to Score 7	13.4 years form Score 1 to Score 7
8	Mostly restricted to wheelchair or even bed, but still has effective use of arms remains and able to perform many self-care functions.	(Data not available)	(Data not available)
9	Bedridden. Patient can communicate or eat.
10	Fatality occurs from complications.
* Data taken from Relapses and Progression of Disability in Multiple Sclerosis, The New England Journal of Medicine, November 16, 2000, Vol. 343, No. 20

Because the effects of nerve injury are widespread, complications can be very severe and affect all parts of the body. Although not all patients experience all of the following problems, any of them can negatively impair quality of life.

Fatigue. Fatigue is one of the most common and debilitating MS symptoms and affects at least two-thirds of patients with MS. Fatigue specifically attributed to MS and not to other causes is defined as abnormal fatigue that lasts at least half of the time or more than 6 weeks. It causes a general lack of energy that significantly limits daily functioning regardless of any neurologic symptoms or specific muscle weaknesses. Up to 40% of patients describe fatigue as the most disabling MS symptom, which is higher than weakness, spasticity, motor control, or bowel or urinary problems. Many conditions that are common in MS (sleep disorders, depression, hypersensitivity to sensation, hypothyroidism, medications, heat) may contribute to fatigue. None fully explain the consistent presence or severity of this problem in MS. Researchers using imaging techniques have identified possible changes in part of the brain in MS that may play a role in the fatigue of MS.

Loss of Mobility and Spasticity. Nearly every patient loses some mobility, which may take the form of less or impaired motor control, muscle weakness, impaired balance, and, importantly, spasticity. Spasticity is one of the primary symptoms of MS. It is characterized by weakness, loss of dexterity, and the inability to control specific movements. It is usually more severe in the legs and torso. (Ironically, mild spasticity actually helps improve muscle tone in the legs, which is important in supporting the patient’s weight when walking.) Mobility can be affected by many non-physical factors, including mental well-being, social networks, fatigue, and even the weather.

Pain. About two-thirds of patients experience pain at some point during the course of the disease, and 40% are never pain free. MS causes many pain syndromes; some are acute while others are chronic. Some worsen with age and disease progression. Pain syndromes associated with MS are trigeminal (facial) pain, powerful spasms and cramps, optic neuritis (pain in the eye), pressure pain, stiffened joints, and a variety of sensations, including feelings of itching, burning, and shooting pain.

Bowel Dysfunction. Bowel dysfunction, which can include constipation or fecal incontinence, is a serious problem for many patients. Constipation may be caused by the disorder itself or by medications used to treat spasms or other symptoms.

Sexual Dysfunction. Sexual dysfunction is a common problem, occurring in over 70% of patients. Men are likely to have impotence and women, problems with vaginal lubrication. It appears to be highly associated with urinary dysfunction.

The nerves that branch off the central nervous system (CNS) provide messages to the muscles and organs for normal function. When there is CNS damage, the function of these organs and tissues may be compromised. In multiple sclerosis, the demyelinization of nerve cells may lead to bowel incontinence, bladder problems and sexual dysfunction.

Urinary Dysfunction. Urinary problems from bladder dysfunction occur in two-thirds of patients. Some patients have difficulties in urinating at will, called urinary retention. Often it takes the form of urge incontinence (also called hyperactive or irritable bladder). People with urge incontinence need to urinate frequently or are unable to reach the bathroom before leakage. In such cases, the bladder is overactive. Complications in the urinary tract also produce a high rate of urinary tract infections.

Difficulty Swallowing. A third to a half of patients experience difficulty in chewing or swallowing, problems that may be caused or made worse by many MS medications.

Speech and Hearing Problems. Problems in speech may occur because of difficulty in controlling the quality of the voice and articulating words. (Problems with language itself, however, are very rare in MS.) Hearing problems also occur in MS and may affect speech.

Problems in the Lungs. As the muscles that control breathing weaken, the ability to cough is impaired and the patient is at higher risk for pneumonia and other complications in the lungs.

Osteoporosis. Osteoporosis (loss of bone density) and subsequent fractures are common and under-recognized problems among patients. Osteoporosis is caused and worsened by immobility and by some MS medications. Fractures caused by falls can be far more serious in patients than in the normal population, leading to problems, including deconditioning or even inability to walk, obstruction of the intestines (from pain-relieving medications), and respiratory complications.

Cognitive problems, such as having trouble concentrating and solving problems, affect about half of patients. More people with MS leave work because of such cognitive difficulties than because of physical problems, according to a 2000 study. In about 10% of cases, mental dysfunction may be severe and resemble dementia. The severity of such mental changes appears to be associated with the degree of loss of brain tissue. This offers another argument for early treatment as interferon medications may improve these symptoms.

Between 40 - 60% of patients suffer from depression at some point over the course of the illness, and studies have reported risks for suicide ranging from 3 - 15%. Some evidence suggests that depression in multiple sclerosis is not only due to the social and psychologic impact of MS but also to the disease process itself. Depression may have biologic effects, such as increasing production of inflammatory cytokines, that could exacerbate the disease itself. Doctors should assess patients for depression, even if there are no obvious signs of it. The risk for suicide may be present even in patients who are not obviously depressed. People at highest risk for suicide are those who live alone, those with a history of an emotional disorder (depression, anxiety, alcohol abuse), a family history of mental illness, and people with high social stress.

Diagnosis

Multiple sclerosis is characterized by recurring neurologic episodes that are due to multiple lesions (injured areas) in different locations in the central nervous system. The diagnostic challenges in multiple sclerosis are two-fold:

Making an initial diagnosis as early as possible in order to slow down the disease progression. Most patients first seek medical help after an initial inflammatory event (known as a clinically isolated syndrome) originating from demyelination in the eye, the spinal cord, or the brain. About 30% of these individuals will develop progressive MS within the year. At this time, however, experts cannot predict who among these patients are at highest risk for rapid progression.
Predicting the severity of the disease. Once MS has been diagnosed, the pattern of the disease is uncertain. It can be very benign to rapidly progressive and severe. Magnetic resonance imaging (MRI) is able to detect lesions in the brain indicating MS. But, the severity of the disease does not appear related to the number of lesions, the rate of their appearance, or their location. Researchers are hoping to identify some biologic marker, possibly certain antibodies, that will enable doctors to accurately determine the onset and severity of the problem once a diagnosis has been made.

The McDonald Criteria. There is no single test that can accurately diagnose MS, and a number of other conditions may mimic its symptoms. Some doctors use a set of factors, called the McDonald criteria, for diagnosing multiple sclerosis in early stages. The criteria include the presence of specific symptoms, spinal fluid evaluation, and magnetic resonance imaging techniques for detecting lesions within the central nervous system and tracking them over time. The criteria show high reliability in identifying MS in patients with a variety of disease stages or states, including having only one episode, a typical relapsing-remitting course, or a slow insidious progression without clear attacks or remissions. Depending on the MRI and other findings, the patient is then categorized as having MS, possible MS, or no MS.

The symptoms of MS are similar to a number of other diseases, which must be ruled out. These include stroke, alcoholism, emotional disorders, Lyme disease, chronic fatigue syndrome, fibromyalgia, AIDS, and certain other autoimmune disorders (hypothyroidism, scleroderma, Sjögren syndrome, and systemic lupus erythematosus).

Doctors and investigators generally use a test called the Expanded Disability Status Scale (EDSS) to rate the severity of symptoms. It is also used after a diagnosis to gauge the status of the disease, and score the effectiveness of treatments. The scale ranges from 0 to 10 with higher scores indicating more severe symptoms. These are subjective ratings that require doctor observation skills.

Objections to the use of the EDSS are that it assesses only limp and walking problems and does not assess other important complications, including fatigue, sexual function, and mental function.

No reliable single laboratory procedure or test can establish the diagnosis of multiple sclerosis. Several are necessary before a diagnosis can be made.

Analysis of Cerebrospinal Fluid (CFS). Obtaining a sample of spinal fluid requires a lumbar puncture, or spinal tap. Testing spinal fluid is becoming increasingly important for detecting abnormal proteins, tiny fragments of myelin, or specific white blood cells that can help in making a diagnosis. For example, high levels of the immunoglobulin IgG is useful for making a diagnosis and may be a marker for disease progression. (Immunoglobulins are protein chains that are part of the immune system.)

A lumbar puncture, or spinal tap, is a procedure to collect cerebrospinal fluid to check for the presence of disease or injury. A spinal needle is inserted, usually between the 3rd and 4th lumbar vertebrae in the lower spine. Once the needle is properly positioned in the subarachnoid space (the space between the spinal cord and its covering, the meninges), pressures can be measured and fluid can be collected for testing.

Evoked Potential (EP) Test. This is a simple and painless electrical test of nerve function that assesses how long it takes nerve impulses from the eye, ear, or skin to reach the brain.

Magnetic resonance imaging (MRI) scans are important diagnostic tools in MS and are used for diagnosing multiple sclerosis, tracking changes over time, and helping to determine treatment effectiveness.

Click the icon to see an image of a brain MRI.

Making a Diagnosis and Tracking the Disease. Magnetic resonance imaging (MRI) scans can detect bright patches that indicate injured tissue (lesions) caused by MS. Such lesions may also indicate other conditions, such as infections, migraines, or clots. Importantly, a very sensitive MRI technique using enhancement by a contrast material called gadolinium can indicate recent activity by showing if the blood-brain barrier has been broken down (the first step in the development of MS lesions). Detecting lesions and treating MS early in the disease process may help reduce progression. Many experts therefore now advocate performing a brain MRI as soon as symptoms appear.

Once diagnosed, periodic follow-up MRIs can be used to track the disease and effectiveness of treatments in two ways:

By distinguishing new lesions from old ones
Revealing increasing or decreasing numbers of lesions within the central nervous system over time

Unfortunately, neither the rate nor the number of new or growing lesions necessarily predicts whether symptoms will worsen or if the patient will develop secondary progressive MS.

Measuring Atrophy in Brain and Spinal Cord. As myelin, axons, oligodendrocytes, and neurons are destroyed, the brain begins to shrink. Processing MRI images to determine brain volume may be a useful way to monitor progression and treatment effects. MRI can also detect shrinkage in the spinal cord, which is proving to be a very strong marker of disease progression. A variation of MRI, magnetic resonance spectroscopy (MRS), provides information on the biochemistry of the brain, and may be particularly helpful in detecting this destructive aspect of MS.

Detecting Black Holes.Severe disease progression can be gauged by the presence of so-called "black holes.” These are lesions in the brain that emit very low signals on an MRI scan. Some evidence suggests that they may represent iron deposits in the brain.

Researchers are continuously searching for biologic markers that might help make an accurate diagnosis, predict outcome, or both. Promising markers are antibodies that target two key protein components of myelin: Myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP). If future studies confirm the predictive value of these antibodies, scientists may be able to develop a blood test for MOG and MBP.

Treatment

Patients diagnosed with multiple sclerosis face great uncertainty, since the course of the illness varies so widely among patients. Experts recommend a multidisciplinary approach to the disease, which might involve a neurologist, a nurse or social worker expert in MS, and possibly a specialist in mental health (since depression is so common and the suicide rate is higher than average).

Evidence now strongly suggests that the most destructive changes from multiple sclerosis in the brain occur very early on in the disease process -- and may cause considerable damage even before symptoms begin.

Many experts are now urging treatment after a first episode of relapsing MS (a clinically isolated syndrome) using medication called disease-modifying drugs. They include three interferons -- IFN1b (Betaseron) and IFN1a (Avonex, Rebif) -- and glatiramer (Copaxone). These drugs are all effective and may help slow down or even prevent progression in some patients. Definitive studies comparing them are ongoing.

The best current approach is to use specific findings from advanced MRI techniques to help determine which patients are at highest risk for progression and would be likely candidates for early treatment with disease modifying drugs.

Interferons and other disease-modifying drugs can have significant side effects and are expensive. Furthermore, a significant number of patients have a mild course that can be managed with less toxic drugs. Nevertheless, strong evidence suggests that delaying treatment in most patients increases the risk for severe disability.

Corticosteroids are the standard drugs for treating an acute relapse and hastening recovery. Typically, intravenous methylprednisolone (IVMP) is given once a day for 3 days. Sometimes this is followed by oral prednisolone for a few days.

Disease Modifying Drugs. Since the introduction of disease modifying drugs -- interferons beta (Betaseron) and alpha (Avonex, Rebif) and glatiramer (Copaxone) -- relapsing-remitting multiple sclerosis is now considered a treatable disease. In patients with very active MS, some experts start with Betaseron or Rebif. For patients with possible or probable MS, they begin with Avonex. This drug is slightly less effective than Rebif and Betaseron but has fewer side effects. Copaxone is also a reasonable choice for early mild MS. It appears to have the fewest side effects, longer relapse-free rates than interferons, and its benefits persist for years.

The newest drug, the monoclonal antibody natalizumab (Tysabri), was approved in November 2004 for treatment of relapsing forms of MS. The FDA withdrew it from the market, however, in February 2005 following reports of serious neurological events. In June 2006, the FDA allowed natalizumab back on the market but with special restrictions (see Drug Treatment section).

Other Approaches. Some research has reported benefits from the use of pulsed administration of intravenous methylprednisolone (IVMP) or intravenous immunoglobulin, although there is not enough evidence for either approach to recommend them as first-line choices. Other drugs showing promise include azathioprine (an immunosuppressant) and laquinimod (an oral immune-modulating drug).

Treating Secondary Progressive Multiple Sclerosis (SPMS). Interferons and other standard treatments for relapsing-remitting MS may be helpful for patients with SPMS who are still experiencing relapses. It is not clear if they help those whose condition has become continuously progressive.

Mitoxantrone (Novantrone) was the first drug approved for SPMS. The drug is an immunosuppressant and is proving to delay relapse and progression. Side effects, however, can be serious in some cases. Some experts recommend using mitoxantrone when evidence suggests progression to SPMS, and continuing the interferons Betaseron or Rebif for maintenance.

Other immunosuppressants, such as cyclophosphamide, methotrexate, and cladribine, may help some patients with SPMS. They can have very toxic side effects, however, and there must be clear treatment indications for patients who take these drugs.

Treating Primary Progressive Multiple Sclerosis. No treatments have been proven yet to slow progressive multiple sclerosis. Studies using interferons and glatiramer are under way.

A number of treatments are available for managing symptoms and complications.

Drug Treatment

Corticosteroids (commonly called steroids) are mainstay treatments for acute relapses patients with relapse-remitting MS. High-dose methylprednisolone given intravenously (IVMP) is typically administered for major relapse, often followed by oral prednisone for a few days. Steroids reduce inflammation in the central nervous system and may help suppress the immune system's attack on myelin and even improve electrical conduction.

Steroids, in general, do not improve the long-term course of the disease and can lose effectiveness if overused. They are not generally used for maintenance therapy. Some research, however, is reporting benefits from the use of pulsed administration of intravenous methylprednisolone. Such an approach typically administers the steroid daily for 5 days every 4 months for 3 years, then every 6 months for 2 years. Some research suggests that this approach might reduce destruction in central nervous system, although more evidence is needed before it can be recommended. They can also have considerable adverse effects when used over time.

Side Effects. Side effects of long-term use of steroids include weight gain and facial fullness, hypertension, diabetes, osteoporosis, cataracts, intestinal bleeding, and increased susceptibility to infections. In addition, side effects of steroids on the central nervous system (sleeplessness, memory loss, anxiety, and depression) can be particular problems for patients. It is extremely important to taper withdrawal very carefully after continuously taking steroids for a prolonged period of time. This gives the body time to recover its own ability to produce natural steroids. A serious condition known as adrenal insufficiency can otherwise develop.

Interferons (so-called because they “interfere” with viral replication) both suppress important inflammatory factors in the immune system and have anti-viral properties. Interferons specifically block immune factors known as class II MHC molecules, which are associated with the attack on myelin and the breach in the blood-brain barrier that allows the destructive T cells to pass through.

Specific Interferons Used for MS. Interferon drugs used for MS are IFN1b (Betaseron) and IFN1a (Avonex, Rebif). They are now the treatments of choice for relapsing-remitting MS. Expert organizations urge that they be used early in the course of the disease and continued indefinitely, unless they produce no benefits or have severe side effects.

Successes and Drawbacks. Interferons can reduce flare-ups overall by 30% and have an even greater effect on reducing major relapses. Disease activity, as measured by MRI scanning, is reduced by over 80%. They appear to be about equal in reducing disability. To date, only Avonex has demonstrated slowing progression of mental impairment. It also appears to be better tolerated than other interferons. Studies on their effects on quality of life are limited. None of the interferons are a cure, in any case, and when the drug is discontinued, disease activity may increase. All of these drugs need to be injected. (Oral forms are under investigation.)

Side Effects and Complications. Side effects include:

Pain at the injection site. Many patients taking Betaseron complain of severe pain at the injection site caused by damaged tissue. Experts recommend taking acetaminophen (Tylenol) before the injection and then every 6 hours after each injection for 24 hours during the first 6 months of treatment.
Skin injury at the injection site. Black dead tissue may form around the site, and many patients taking Betaseron have reported severe skin eruptions. These skin injuries heal after the drug is withdrawn, but scarring can occur. This side effect is least severe with Avonex, followed by Rebif.
Other physical side effects. Both drugs cause flu-like symptoms, nausea, vomiting, headaches, and dizziness. Such side effects usually fade after 2 - 3 months.
Depression. Early studies associated taking interferon with a higher risk for depression during the first 2 - 6 months following initial therapy. More recent studies, however, have reported no greater risk for depression in patients taking any of these drugs. MS itself, in any case, is highly associated with depression.
Thyroid abnormalities. Interferon has been associated with autoimmune thyroiditis, a cause of hypothyroidism. Some experts recommend monitoring for thyroid function, particularly in the first year and in those with a history of thyroid problems. If there is no evidence of the condition during that period, the risk for its occurrence appears to be very low.
Liver damage. Interferon may cause liver damage and, in rare cases, liver failure. Patients should avoid alcohol and have regular liver function tests while taking this drug

Neutralizing Antibodies That Reduce Effectiveness. Over time, people taking interferons develop antibodies to the drugs, some of which can neutralize their effects. The risk for neutralizing antibodies (NAbs) increases with higher doses and greater frequency of use. Interferons injected under the skin (Betaseron, Rebif) are more likely to produce neutralizing antibodies than Avonex, which is injected into a muscle. Patients who experience this, however, often can be effectively treated with an alternative interferon or with glatiramer, which has an extremely low risk, for NAbs. In many cases, after switching drugs, NAb levels decline, and the patient may be able to return to the original interferon.

Glatiramer acetate (Copaxone) is a synthetic molecule that resembles a basic protein found in myelin. It is used as a decoy to trick white blood cells into attacking it instead of myelin. It is approved to help reduce the frequency of relapses in patients with relapse-remitting MS. The best results are in patients in early stages, but the longer patients remain on the drug, the greater the improvement. Benefits have persisted for years. Glatiramer acetate can also help reduce the number of new brain lesions.

Glatiramer acetate is also being studied for its effects in patients with primary progressive MS. A 2007 study indicated that while the drug had little benefit for most patients with this type of MS, it may help slow disease progression and delay disability in men with primary progressive MS.

Side Effects. Side effects occur in about 15% of patients, usually right after the injection. They include pain at the injection site, chest pain, rapid heartbeat, flushing, anxiety, and shortness of breath.

Monoclonal antibodies (MAbs) are drugs that target specific antibodies involved with the immune response. In 2004, natalizumab (Tysabri) became the only MAb approved for treatment of MS. Shortly afterwards, reports emerged of progressive multifocal leukoencephalopathy (PML) occurring among patients who took natalizumab for more than 2 years. PML is a rare neurological disease that can affect people with compromised immune systems. Based on these reports, the FDA suspended marketing of natalizumab in February 2005 and recommended that patients discontinue its use.

In June 2006, the FDA allowed natalizumab to return to the market with certain safety restrictions. Doctors can prescribe the drug only to patients who have failed to respond to or who cannot tolerate other MS treatments. Natalizumab can only be taken alone, not in combination with other immune-modifying drugs. Patients who take natalizumab must enroll in a special program called TOUCH, which is run by the drug’s manufacturer. Patients need to get magnetic resonance imaging (MRI) brain scans before they begin taking the drug, and they are evaluated regularly during drug treatment to make sure they are not at risk of developing PML. In the year after these restrictions were implemented, no new cases of PML were reported.

Clinical trials indicate that natalizumab’s benefits may outweigh its risks. Several studies published in 2006 in the New England Journal of Medicine showed that natalizumab, alone or in combination with IFN1a (Avonex) can help prevent disability in patients with multiple sclerosis. Another study suggested that the risk of PML is very low if patients use natalizumab for less than 18 months.

Natalizumab is also being studied for treating complications associated with MS. In a 2007 study, natalizumab helped reduce vision loss in patients with relapsing MS. Vision loss is one of the most common symptoms associated with MS.

Other MAbs under investigation for MS include daclizumab (Zenapax), alemtuzumab (Campath), and rituximab (Rituxan). Results from a 2005 phase II trial for alemtuzumab indicated that the drug helped prevent relapse but also caused serious side effects. Patients who took the drug had a high risk for developing a serious bleeding disorder caused by a low blood platelet count. Daclizumab is currently in phase II trials as is rituximab. Unlike other MAbs, which affect T cells, rituximab targets and depletes B cells. In several studies presented at the 2007 meeting of the American Academy of Neurology, rituximab showed promising results in reducing relapse frequency and number of brain lesions in patients with relapse-remitting MS.

Intravenous immunoglobulin treatments are monthly infusions of natural antibodies. They appear to have some modest benefits for relapsing-remitting MS. Studies suggests that intravenous immunoglobulin reduces relapse rates and occurrences of new lesions and slows disease progression in relapsing-remitting MS. It does not appear to reduce disability. It is extremely expensive and does not appear to have any benefits for patients with secondary progressive MS.

Many drugs being investigated for chronic progressive multiple sclerosis are immunosuppressants, which block certain factors in the immune system that contribute to the inflammatory process. Each of these drugs can produce serious side effects, including susceptibility to infection. Evidence on benefits is uncertain, mainly because of high toxicity or study limitations. Still, some immunosuppressants may help certain patients with severe MS. Among immunosuppressant drugs or procedures that have been investigated with little or no obvious benefits or unacceptably high side effects are total lymphoid irradiation, sulfasalazine, cyclosporine, acyclovir, and oral bovine myelin.

Mitoxantrone. Mitoxantrone (Novantrone) was the first drug approved specifically for secondary progressive MS. Studies suggest that it may help reduce progression and relapse rates. Cumulative doses can have toxic effects on the heart, however, so the drug is only used for a limited period. Mitoxantrone is also being studied in combination with glatiramer acetate. In one preliminary study, initial treatment with mitoxantrone, followed by maintenance treatment with glatirimer acetate, helped reduce relapses for up to 5 years.

Methotrexate. In some patients, low doses of the immunosuppressant methotrexate may slow the course of chronic-progressive MS, particularly in those with secondary progressive MS. To date, studies have found beneficial effects only on the upper body, however. Although this drug, like all immunosuppressants, can have toxic side effects, it may be taken in low doses for MS and so side effects are generally minimal.

Cyclophosphamide. Cyclophosphamide (Cytoxan) blocks cell growth and also suppresses the immune system. Some studies, but not all, have reported benefits for patients with chronic progressive MS. Small studies suggest that monthly intravenous administration or a combination with interferon-beta may help some patients with rapidly deteriorating MS. Cyclophosphamide has many side effects, including hair loss, nausea, vomiting, infertility, lung scarring, and blood abnormalities, and should be used for patients who do not respond to methotrexate.

Azathioprine. Azathioprine (Imuran) is designed to suppress the immune system and reduce the number of cells attacking the CNS myelin. It is used with or without steroids and is sometimes used as an alternative to patients with relapsing-remitting MS who do not respond to either interferon beta or glatiramer acetate. One study reported that 40% of patients had not experienced a relapse after taking the drug for 3 years, although others report only modest benefits. The drug has no effect on progression of disability.

Cladribine. Cladribine (Leustatin) may be effective in delaying progression in patients with chronic progressive MS. It has no significant effect on relapsing-remitting MS.

A number of treatments are under investigation that may prove to be helpful for multiple sclerosis. Those discussed below are only some of them.

Immune-Modulating Drugs. Most MS drugs are injected, but researchers are developing several new drugs that can be taken by mouth. Four of the most promising candidates are cladibrine (Mylinax), fingolimod (FTY720), teriflunomide, and fumarate (BG00012). In late-stage clinical trials, these drugs have shown positive results in the treatment of relapse-remitting MS.

Sex Hormones. Women with MS have a reduced risk of experiencing relapses during pregnancy, probably because of their high levels of the female sex hormones estrogen and progesterone. Because of this association, researchers have investigated whether oral estrogen therapy (estriol) can help prevent relapses. Some small studies have indicated that estriol treatment may help reduce lesions and disease activity, but the overall evidence is still inconclusive. The male sex hormone testosterone is also being studied as a treatment for men with relapse-remitting MS. A small 2007 pilot study suggested that treatment with testosterone gel is safe and may help improve cognitive function, slow brain degeneration, and increase muscle mass.

Cannabinoids. Cannabinoids are compounds in marijuana (cannabis), which may have properties that protect nerve cells. Cannabis has been found to improve pain, mobility, tremor, mood, appetite, fatigue, vision, sexual and urinary function, and memory. In a 2003 study, patients reported less pain and improved mobility (although spasticity itself did not improve). Not all patients respond. The drug may also worsen balance and posture in patients with spasticity. Synthetic versions are being investigated that allow rapid delivery without the unwanted side effects of natural cannabis.

Potassium Channel Blockers. Aminopyridines are potassium-blocking compounds that appear to improve nerve conduction through demyelinated areas. In small, preliminary trials, 4–aminopyridine (also called AP) was associated with mild-to-marked improvement in vision, strength, and coordination and was well tolerated. Beneficial effects, however, lasted only a few hours. A related compound, 3,4–diaminopyridine, or DAP, is being studied for relieving fatigue associated with MS.

Statins. Statins are currently the most important drugs for lowering cholesterol. They are also showing additional possible benefits, including anti-inflammatory and nerve protecting properties, which may help patients with neurologic conditions, including multiple sclerosis.

Plasmapheresis. Plasmapheresis with plasma exchange is a procedure in which blood is removed from the body. Blood cells are separated from plasma (the liquid portion of blood) and mixed with replacement plasma, which is then returned to the body. The replacement plasma is thought to dilute antibodies and other immunologically active substances that may trigger MS. Small studies suggest this procedure may have significant benefits for some patients with severe MS, particularly if they are younger and have an early response to this treatment. Side effects include risk of infection and blood clotting problems.

Stem Cell Transplantation. Investigators are studying the benefits of stem-cell transplantation procedures. Stem cells are produced in the bone marrow and are the early forms for all blood cells in the body (including red, white, and immune cells). Early studies indicate that stem cell transplantation may slow progression, although at this point it is not a cure.

Oligodendrocyte Implants. A newly developed, minimally invasive method to transplant modified oligodendrocyte cells directly into the brain is under investigation. Such cells stimulate nerve and axon growth. If feasible, this approach might be helpful in patients whose MS is not caused by an autoimmune response (where the new cells would be attacked, just as the patient's own cells were).

Other Treatments

Nearly 60% of patients try some form of nontraditional remedies. Research on any benefits is slim, and there may be some danger with many remedies commonly used by patients. The following are a few alternative remedies sometimes used for MS.

Relaxation and Meditation Techniques. Generally harmless, and possibly helpful, nontraditional therapies for MS are relaxation and meditation techniques and Eastern martial art exercises. Such techniques include biofeedback, music therapy, yoga, tai chi, and massage therapy.

Acupuncture. Some patients report benefit from acupuncture, which does carry a very small risk, usually for infection.

Acupuncture, hypnosis, and biofeedback are all alternative ways to control pain. Acupuncture involves the insertion of tiny sterile needles, slightly thicker than a human hair, at specific points on the body.

Electromagnetic Stimulation. A few centers have studied pulses of weak electromagnetic fields applied to the brain. Very small studies have reported improvement in fatigue, tremors, depression, and other symptoms in patients who were severely affected by MS. In one controlled study, this approach relieved symptoms more effectively than placebo. The effect was small however and more research is needed.

Linoleic Acid. Linoleic acid, commonly known as evening primrose oil, is a polyunsaturated fatty acid believed by some people to be helpful because myelin is composed of fatty acids. No study has proven that it is beneficial, but supplements sold in health food stores do not appear to be harmful.

Oral Enzymes. Oral drugs containing various natural enzymes, including bromelain, trypsin, papain, and rutin, have been used overseas to treat arthritic pain. They appear to reduce inflammation and are also being studied in patients with MS. Such enzymes have been marketed alone and in combinations (Wobenzym, Phlogenzym). In one small study, Phlogenzym was associated with a decline in complications and longer remission. They are not painkillers; any benefits derived from them may take several weeks. As with any natural remedy, there are few clinical studies on these products and no U.S. regulation of quality, safety, or effectiveness.

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. Patients should check with their doctor before using any herbal remedies or dietary supplements

The following warnings are of particular importance for people with multiple sclerosis:

Antioxidants. Some patients use antioxidant vitamins or supplements (A, E, C, Q10, pycnogenol, OPC, grape seed extract), since the destruction in the MS disease process may be partly due to oxidation (chemical damage from particles called oxygen-free radicals). Theoretically, however, antioxidants can trigger T cells and macrophages (inflammatory components of the immune system) and, therefore, may pose some danger to patients. Small studies to date have not found any worsening of the disease from taking vitamin supplements, but patients should be cautious. No vitamins studied for MS, including carotenoids, vitamin C, vitamin E, B12 injections or vitamin D, have been proven to be beneficial.

Gingko. Although the risks for gingko appear to be low, there is an increased risk for bleeding at high doses. Ginkgo can also interact with high doses of vitamin E, anti-clotting medications, aspirin, and NSAIDs. Large doses have also been known to cause convulsion. Commercial gingko preparations may contain colchicine, a drug that can be harmful in pregnant women and people with kidney or liver problems.

Bee Venom. For years, anecdotal reports have claimed that bee stings relieve some MS symptoms, although a study on mice indicated that it may worsen MS. Bee venom contains many chemicals, some of which can cause severe and sometimes deadly allergic reactions in some people.

Other Remedies. Herbal or natural remedies that supposedly boost the immune system (echinacea, ginseng, garlic, zinc) may worsen MS. Melatonin has been associated with worsening of some autoimmune diseases. Toxic effects have also been reported with herbal remedies such as borage seed oil, chaparral, and comfrey.

Treating the Complications

Fatigue affects at least two-thirds of patients. It is among the most disabling problems in MS and is difficult to treat. Treating any problem (depression, hypothyroidism) that may be causing fatigue is important. Aerobic exercise programs scheduled early in the day have been helpful for patients who can participate. Preventing overheating can improve fatigue.

Modafinil (Provigil, Alertec) is a promising drug that promotes long-lasting wakefulness and is currently used in narcolepsy. Small studies report that it is effective in reducing fatigue and sleepiness, with lower doses (200 mg) being more effective than higher ones. Studies also suggest that the antiviral drug amantadine (Symmetrel) may be helpful.

Managing pain and spasticity in the lower limbs can be difficult. Although many drugs are used to reduce spasticity and lower-limb pain, most studies investigating these drugs have been poorly designed and no treatment has emerged as a front-runner.

Exercise. Mild spasticity actually helps improve muscle tone in the legs, which is important in supporting the patient’s weight when walking. This benefit can be lost with drug treatment. Mild spasticity, then, should be treated with exercises several times a day that improve range of motion.

Drugs Used for Spasticity.

Baclofen (Lioresal) has long been the drug of choice to alleviate more severe spasticity. It is available both orally and infused through an implanted pump. Distressing side effects include confusion, drowsiness, and a rubbery-like sensation in the legs that makes it hard to stand.
Antiseizure medications, such as gabapentin (Neurontin) or levetiracetam (Keppra), may help reduce spasticity without increasing fatigue or impairing concentration. Studies on gabapentin also suggest that it also have other specific benefits for patients, including reducing facial pain and improving vision.
Tizanidine (Zanaflex) is an oral drug that works after one week. In one study, 75% of patients taking tizanidine reported improvement without the leg-muscle weakness experienced using baclofen. The drug does not appear to be any more effective than baclofen, however. Side effects include dizziness, drowsiness, dry mouth, and fatigue. Liver function must be monitored.
Diazepam (Valium) is also used for spasticity and may be particularly useful for patients who also experience anxiety. Drug dependence is the primary problem with diazepam, as well as dizziness, drowsiness, and confusion. The medication should not be used by people who are seriously depressed.
Botulinum toxin (Dysport) injections are being investigated for spasticity in specific regions such as the hip.
Dantrolene (Dantrium) may be an effective alternative for patients who cannot tolerate diazepam or baclofen. Because dantrolene causes muscle weakness, however, it is best suited for either patients who are wheelchair bound but still suffer from spasticity, or for those whose muscles are still strong so that the drug-induced weakness isn't unduly debilitating. It also causes nausea, vomiting, and anorexia, and with high dosages it can cause dangerous liver damage.

Surgery. In very severe cases where medication and exercise are not helpful, surgery may be considered. In such cases, the surgeon cuts the tendons that are involved with spasticity.

Spinal Injections. In very severe cases, administering phenol using spinal injections in the lower back may reduce pain and spasms for some patients with severe conditions. Most patients are not appropriate candidates for this approach.

Other Treatments. Researchers are also investigating non-drug treatments for spasticity. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive method that uses a magnet placed on the scalp to generate a magnetic field that stimulates the cortex of the brain. In a small 2007 study, rTMS showed promise in improving lower-limb spasticity in patients with relapse-remitting MS.

Urge Incontinence. Urge incontinence (the need to urinary frequently) is common in patients. To help reduce social difficulties, patients should not drink fluids before going to places where restrooms are not easily available. When possible, they should urinate every 3 - 4 hours. A number of medications are available for urge incontinence, including anticholinergic drugs, such as propantheline bromine (Pro-Banthine), tolterodine (Detrol), or oxybutynin (Ditropan). Sacral nerve stimulation (InterStim) sends electrical pulses to help retrain nerves in the pelvic area, and is also proving to be helpful. Botulinum toxin injection into the urinary tract muscles is being investigated and may be helpful for incontinence caused by spasticity. [See In-Depth Report #50: Urinary incontinence.]

Urinary Retention. Urinary retention occurs in some patients. Sometimes urination can be stimulated simply by pressing the bladder area with the fist or hand, by tapping against it, or by straining. Drugs being tried with some success for this problem are desmopressin (DDAVP), ordinarily used for bed wetting in children, and maprotiline (Ludiomill), an antidepressant. If medication is ineffective, a catheter may be needed, either one used intermittently by the patient or placed in the urinary tract. Various new surgical procedures that reconstruct the bladder or divert urine flow may be effective in severe cases of bladder dysfunction. Because urinary symptoms usually remain intermittent for years, treatment approaches for bladder dysfunction should be limited to medications and other reversible therapies, for as long as possible.

Urinary Tract Infections. Urinary tract infection is common in patients, and a urinalysis should be performed with any symptom flare-ups, fever, or change in bladder symptoms. Treatment uses appropriate antibiotic regimens. Some evidence suggests that cranberry juice may help prevent infections. [See In-Depth Report #36: Urinary tract infection.]

In addition to maintaining a high-fiber diet and drinking plenty of fluids, bulk fiber such as psyllium (Metamucil), with or without a stool softener, may be needed. Going to the bathroom the same time every day, particularly after a meal and waiting there for a movement, reduces the risk of losing control later in the day. Exercise helps patients avoid becoming dependent on laxatives, enemas, or colonic irrigation, which can eventually slow down the bowel and cause imbalances in electrolytes. Biofeedback techniques may be helpful in some patients with limited multiple sclerosis.

Major tremors can be very distressing and are particularly hard to treat. Carbamazepine and glutethimide have some possible benefits, but in general drug therapy has been disappointing. Weight applied to the affected limb has been beneficial in about 20% of cases. Surgery is very controversial.

Trigeminal neuralgia is facial pain, usually on one side, that can be very severe and may be triggered by an event as mild as a breeze or teeth brushing. If nonprescription painkillers fail to alleviate facial pain, it can be treated with anticonvulsive medications. Carbamazepine (Tegretol) is currently the drug of choice. Carbamazepine is also effective on other types of MS pain and spasm-related symptoms, including itching and aching. Another antiseizure drug, gabapentin (Neurontin), however, may be particularly effective for MS. This drug also appears to improve blurred vision associated with MS and may help spasticity in general.

Other drugs used for this symptom include phenytoin (Dilantin), diazepam (Valium), or pimozide (Orap), and the antidepressant amitriptyline (Elavil). If severe pain persists and interferes with function, some patients elect to have a section of a nerve surgically removed or blocked. This relieves pain but causes numbness. Before patients commit to such a procedure, they should ask the doctor to temporarily block the nerve with an anesthetic in order to experience the effect of numbness before undergoing irreversible surgery.

A small percentage of patients suffer from pseudobulbar affect (uncontrollable laughing or crying). Neurodex is an investigative drug that is showing promise in controlling these symptoms. The drug combines dextromethorphan (an ingredient contained in many cough suppressants) and the enzyme inhibitor quinidine.

Sildenafil (Viagra) may help improve sexual dysfunction in some patients. Corticosteroids, which are sometimes used for other MS symptoms, also improve sexual function. Other treatments are available that might be very beneficial. Patients should not be shy about discussing sexuality with their doctor. [See In-Depth Report # 15: Erectile dysfunction.]

Techniques for helping patients with swallowing problems include using specific head and tongue positions to assist swallowing, and preparing pureed food. Patients may need to work with otolaryngologists (doctors specializing in ear, nose, and throat disorders) to address swallowing problems. Left untreated, swallowing problems can increase a patient's risk of aspiration pneumonia, malnutrition, dehydration, and other problems.

MS is a strong risk factor for osteoporosis. In addition to calcium and vitamin D supplements, a number of drugs are now available to help prevent bone loss and reduce the risk of fractures due to osteoporosis. [See In-Depth Report #18: Osteoporosis.]

Treating Depression. Treating depression may not only improve mood but may also have direct benefits for patients.

Antidepressants known as tricyclics may have specific benefits for MS in addition to managing severe depression. Amitriptyline (Elavil), for example, may be effective in alleviating the extreme mood swings that frequently occur in patients. This “emotional incontinence,” the inability to control emotions, can distress some patients more than physical symptoms. Other tricyclics include desipramine (Norpramin, Pertofrane) and imipramine (Tofranil), which have additional effects that improve bladder symptoms in some patients. These drugs, however, can have severe side effects.
Newer antidepressant drugs, known as SSRIs (serotonin-reuptake inhibitors), which include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil), may be better tolerated. A study on sertraline suggested that it may also reduce the immune system's inflammatory response.

Stress Reduction and Supportive Measures. Stress can worsen symptoms, and may worsen the disease itself. Reducing stress is an important part of general health maintenance. Studies on methods for reducing stress report improved well-being in patients. A sense of control and connection appears to be extremely important for patients. Relaxation or meditation exercises can be beneficial, although cognitive-behavioral methods may be more effective in these patients. [See In-DepthReport # 31: Stress.]

Support for Caregivers. Many patients require long-term physical, financial, and psychological support from family and friends. The physical and mental health of the caregiver are critical. In one study, caregivers reported that among the most distressing aspects were the psychological impact of MS on the patient and the incurability of the disease. Most caregivers identified the best form of support to be practical help, cooking, cleaning, and better availability of medical and financial advice. Therapeutic help for family members may also be helpful.

Interferon, used to treat MS, may improve mental function. Other medications and therapies may also be helpful. For example, drugs called cholinesterase inhibitors, such as donepezil (Aricept), which are used for Alzheimer's disease, may help improve mental functioning. Vocational programs for the patient may also be helpful. Therapeutic programs for both patients and their families can help them better understand and cope with cognitive weaknesses such as concentration and problem solving.

Lifestyle Changes

People with multiple sclerosis should make every effort to preserve their general health. A healthy diet, sufficient rest, establishing priorities to conserve energy, and developing emotional support networks can all be very helpful.

Some dietary suggestions for patients with MS include:

Drink two quarts of water a day and avoid caffeine-containing beverages, which are actually dehydrating. This helps avoid constipation (although may cause difficulties in patients who also have urge incontinence).
Eat a diet rich in fiber, particularly from whole grains (especially bran, oats, or flax), fruits (particularly prunes), and vegetables.
Low-fat diets have not proven to have much effect on MS but are, in any case, generally healthy.
Fish and fish oil. Omega-3 fatty acids, which are found in oily fish, have been associated with protection against inflammation and some reduction in symptoms in people with various autoimmune conditions. Such fatty acids are also available in supplements as docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids. Standards for optimal amounts and forms of omega-3 fatty acids have not yet been established, however. Some experts recommend that people with MS eat three fish meals a week.

Special diets, such as those that are gluten- or yeast-free, have not shown to have any direct effect on the symptoms or course of MS.

Exercise is an important component in managing MS. An active patient with MS is less likely to develop certain complications, such as bladder and bowel dysfunction, osteoporosis, permanent muscle contractions, ulcerations of the skin, or abnormal blood clotting. MS symptoms can temporarily worsen during physical activity, however, so any program must be planned carefully. A health professional should be consulted to determine the best form of physical activity. One study reported that physical rehabilitation for 3 weeks in a hospital setting was significantly more effective in achieving functional independence than home exercise. It is not known if the same benefits can be achieved with a similar program outside the hospital.

Some suggestions include:

Exercise programs must be designed to stimulate working muscles, but at the same time avoid overload and overheating, which can block nerve conduction.
Stretching and range-of-motion exercises are important because they can relieve muscle spasticity.
Pool exercises are particularly helpful. Water supports the body, and cool water dissipates heat.
Specific exercises that strengthen and increase the endurance of muscles that control breathing functions may be helpful. However, it is unclear if such exercises reduce lung complications over the long-term.
Gradually, patients may be able to build up to more complex exercise programs.

Body overheating causes demyelinated nerves to function less efficiently than usual. Although this effect is resolved within a few hours of regaining normal body temperature, active cooling can help reduce fatigue and improve stability. As a result, researchers are studying the effectiveness of cooling suits.

The following measures may be helpful:

Use air conditioners in the summer.
Keep the home slightly cool in winter.
Avoid swimming in heated pools.
A portable helmet that uses cold liquid to cool the head and neck and therefore lower core body temperatures may help MS symptoms during daily activities.

MS symptoms worsen during a cold or the flu, probably because of increased immune system activity. Experts recommend that patients with MS receive a flu shot in the fall. However, experts warn that patients should not take the nasal spray version of the flu vaccine (FluMist Intranasal). Unlike the flu injection vaccine, which uses an inactivated virus, FluMist contains a live virus. Live virus vaccinations may be harmful for people with MS, especially those who take immune-suppressing drugs.

Resources

www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.aan.com -- American Academy of Neurology
www.msaa.com -- Multiple Sclerosis Association of America
www.nmss.org -- National Multiple Sclerosis Society
www.msfacts.org -- Multiple Sclerosis Foundation
www.www.fda.gov/cder/drug/infopage/natalizumab -- FDA information on natalizumab (Tysabri)
www.myelin.org -- The Myelin Project
www.abledata.com -- National database of assistive devices and rehabilitation equipment

References

Balcer LJ, Galetta SL, Calabresi PA, Confavreux C, Giovannoni G, Havrdova E, et al. Natalizumab reduces visual loss in patients with relapsing multiple sclerosis. Neurology. 2007 Apr 17;68(16):1299-304.

Boggild M. .Rationale and experience with combination therapies in multiple sclerosis. J Neurol. 2006 Nov;253 Suppl 6:vi45-vi51.

Centonze D, Koch G, Versace V, Mori F, Rossi S, Brusa L, et al. Repetitive transcranial magnetic stimulation of the motor cortex ameliorates spasticity in multiple sclerosis. Neurology. 2007 Mar 27;68(13):1045-50.

Correale J, Fiol M, Gilmore W. The risk of relapses in multiple sclerosis during systemic infections. Neurology. 2006 Aug 22;67(4):652-9. Epub 2006 Jul 26.

Hensiek AE, Seaman SR, Barcellos LF, Oturai A, Eraksoi M, Cocco E, et al. Familial effects on the clinical course of multiple sclerosis. Neurology. 2007 Jan 30;68(5):376-83.

Kappos L, Antel J, Comi G, Montalban X, O'Connor P, Polman CH, et al. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med. 2006 Sep 14;355(11):1124-40.

Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006 Dec 20;296(23):2832-8.

Sicotte NL, Giesser BS, Tandon V, Klutch R, Steiner B, Drain AE, et al. Testosterone treatment in multiple sclerosis: a pilot study. Arch Neurol. 2007 May;64:683-688.

Wolinsky JS, Narayana PA, O'Connor P, Coyle PK, Ford C, Johnson K, et al. Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol. 2007 Jan;61(1):14-24.

Review Date:
5/26/2007
Reviewed By:
Harvey Simon, M.D., Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital

A.D.A.M. Copyright

adam.com

Lip moisturizer poisoning

admin — Thu, 04 Sep 2008 18:59:38 -0700

Overview

Definition
Alternative Names
Poisonous Ingredient
Where Found
Symptoms
Home Treatment
Before Calling Emergency
Poison Control, or a local emergency number
What to expect at the emergency room
Expectations (prognosis)

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

This poisoning is from eating or swallowing lip moisturizers containing para-aminobenzoic acid.

For information regarding allergic reactions to this substance, see para-aminobenzoic acid allergy.

Alternative Names

Chapstick poisoning

Poisonous Ingredient

Para-aminobenzoic acid is a naturally occurring substance that can absorb ultraviolet (UV) light. It is often used in sunscreen products, including lip moisturizers containing sunblocks.

Where Found

Lip balm and moisturizers containing a sunblock. Chapstick is one name brand.

Symptoms

Diarrhea
Eye irritation (if the product touched the eye)
Intestinal blockage
Nausea
Shortness of breath (with extremely high doses)
Vomiting

Home Treatment

DO NOT make a person throw up unless told to do so by Poison Control or a health care professional.

Before Calling Emergency

Determine the following information:

The patient's age, weight, and condition
The name of the product (ingredients and strengths, if known)
The time it was swallowed
The amount swallowed

Poison Control, or a local emergency number

The National Poison Control Center (1-800-222-1222) can be called from anywhere in the United States. This national hotline number will let you talk to experts in poisoning. They will give you further instructions.

This is a free and confidential service. All local poison control centers in the United States use this national number. You should call if you have any questions about poisoning or poison prevention. It does NOT need to be an emergency. You can call for any reason, 24 hours a day, 7 days a week.

Take the container with you to the hospital, if possible.

See: Poison control center - emergency number

What to expect at the emergency room

The health care provider will measure and monitor the patient's vital signs, including temperature, pulse, breathing rate, and blood pressure. The patient may receive:

Activated charcoal
Fluids through an IV
Medicines to treat symptoms

Expectations (prognosis)

Recovery is very likely, since the ingredients are generally considered nontoxic.

Review Date: 10/24/2007

Reviewed By: Stephen C. Acosta, MD, Department of Emergency Medicine, Portland VA Medical Center, Portland, OR. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com

Source Doc: 1_002723

I HEART TREADMILL

FitSugar — Tue, 07 Nov 2006 02:30:00 -0800

When it comes to running on a treadmill indoors, some people love it and some don't. But personally, I love it.
If you fall in the don't category and are hesitant to hop on the treadmill, read more

Here are some reasons to love the treadmill:

Watching TV.
Listening to your iPod as loud as you want without having to worry about safety issues.
Adjusting the incline for better body sculpting.
Raining? Snowing? Who cares.
Getting lost is not an issue.
Leaving traffic lights and stop signs for drivers.
Scorching and harmful UV rays aren't luring above your treadmill.
Having a heart rate monitor at your fingertips.
Looking at the display screen and seeing how hard you've worked.
If you're at the gym, being motivated by everyone else working out around you.

Source