GENERIC NAME: colchicine BRAND NAME: none

DRUG CLASS AND MECHANSIM: Colchicine is a drug for treating acute gouty arthritis. In acute gouty arthritis there is severe inflammation in response to the presence of uric acid crystals that form in the boney joints. This causes severe pain, redness, and swelling of affected joint(s). Colchicine is useful in suppressing the inflammation in acute gouty arthritis. The exact mechanism of action of colchicine is not known. It may involve reduction in uric acid deposition leading to a reduction in the inflammatory response. Colchicine is not an analgesic (pain killer), but it reduces pain in acute gouty arthritis. The FDA approved colchicine in September 1977. PRESCRIPTION: Yes GENERIC AVAILABLE: Yes PREPARATIONS: Tablets: 0.6mg STORAGE: Colchicine should be stored below 86 F (30 C). PRESCRIBED FOR: Colchicine is used to treat acute flares of gouty arthritis and to prevent recurrent acute attacks. It also is used to treat the inflammation of pseudogout, and other uncommon diseases, such as familial Mediterranean fever, amyloidosis, and scleroderma; however, these are unapproved uses of colchicine, and there are few data to support colchicine's effectiveness for treating these diseases. DOSING: Colchicine should be taken with food. The recommended dose for an acute attack is 0.6-1.2 mg. The dose may be repeated every 1-2 hours until symptoms are controlled. The total dose needed to control acute attacks is 4-8 mg. Pain and swelling subside within 12 hours and resolves within 24-48 hours. To prevent attacks, 0.6 mg may be administered daily or every 3-4 days depending on the frequency of attacks. DRUG INTERACTIONS: Erythromycin and clarithromycin (Biaxin) may increase blood levels of colchicine by reducing the metabolism of colchicine. This may increase side effects from colchicine. PREGNANCY: Colchicine can arrest cell division and is avoided in pregnancy because of possible adverse affects on fetal growth; however, there are no adequate studies in pregnant women. NURSING MOTHERS: It is not known if colchicine is secreted in breast milk. SIDE EFFECTS: The most common side effects of colchicine are dose related and include nausea, vomiting, abdominal pain, and diarrhea. One of the most worrisome side effects of colchicine is that it can damage the bone marrow causing severe anemia and low white blood counts. Reduced white blood cell counts can increases the risk of infections. All patients taking colchicine long-term require blood count monitoring. Colchicine can also cause hair loss, weakness, and nerve irritation.

GENERIC NAME: penicillamine

BRAND NAMES: Cuprimine, Depen

DRUG CLASS AND MECHANISM: Penicillamine is an antirheumatic drug used to treat patients with active rheumatoid arthritis. It also is classified as a metal binding (chelating) agent used for treating Wilson's disease, a genetic disease that causes excessive copper to accumulate in the body. The mechanism of action of penicillamine in rheumatoid arthritis is unknown but it may be related to reduction of collagen formation. (Collagen is a type of tissue that forms a part of scar tissue that results from inflammation) and suppression of the immune system. In patients with rheumatoid arthritis, penicillamine appears to slow the progression of the disease (specifically deformities of the joints) and improve function. For this reason it is considered a disease modifying anti-rheumatic drug (DMARD). Penicillamine binds copper, iron, mercury, lead, and cystine which then are excreted in the urine, and this mechanism is important in treating several nonrheumatic diseases including Wilson's disease. The FDA approved penicillamine in December 1970. PRESCRIPTION: Yes GENERIC AVAILABLE: No PREPARATIONS: Capsules: 125 and 250 mg; Tablets: 250 mg. STORAGE: Penicillamine should be stored at room temperature, 15 to 30 C (59 to 86 F). PRESCRIBED FOR: Penicillamine is used to treat active rheumatoid arthritis that has not responded to other drugs. Penicillamine also is used to promote copper excretion from the body in patients with Wilson's disease and is useful for preventing cystine kidney stones in individuals with cystinuria. It has been used in the treatment of lead poisoning. DOSING: Penicillamine should be taken on an empty stomach, at least one hour before meals or two hours after meals 1-4 times daily. The usual adult dose is 125-750 mg daily. Some patients may require up to 1 g daily administered in 4 doses. Wilson's disease is treated with 750-1.5 g daily in 4 doses. Cystinuria is treated with 1-4 g daily in 4 doses.

DRUG INTERACTIONS: Penicillamine should not be taken by patients who are also taking gold [gold sodium thiomalate; aurothiomalate (Myochrysine), auranofin (Ridaura), aurothioglucose (Solganal)], antimalarial [hydroxychloroquine (Plaquenil)], phenylbutazone (Butazolidine), or cytotoxic drugs [cyclophosphamide (Cytoxan), azathioprine (Imuran, Azasan), methotrexate (Rheumatrex, Trexall)] because these drugs also affect the bone marrow and kidney and when combined with penicillamine can seriously reduce bone marrow and kidney function. The absorption of penicillamine is reduced by iron (ferrous sulphate), magnesium and aluminum salts (for example, antacids) because they form unabsorbable complexes with penicillamine in the intestine. Administration of penicillamine and iron containing products or antacids should be separated by 2 hours. PREGNANCY: Penicillamine should not be taken by pregnant women unless it is for a life-threatening condition, because of potential harm to the fetus.

What are eosinophils?

Eosinophils are a particular type of white blood cells, usually representing a small percentage (less than 8% of the total white blood cell population). The number of these cells (eosinophil count) increases in certain illnesses, including allergies, asthma, Addison's disease, sarcoidosis, parasite infections, drug reactions, and connective tissue diseases (such as rheumatoid arthritis and scleroderma).

What is fascia?
The fascia is a lining tissue under the skin that covers a surface of underlying tissues. When the fascia is inflamed, the condition is referred to as "fasciitis."

What is eosinophilic fasciitis?

Eosinophilic fasciitis is a specific disease of the skin that leads to inflammation and thickening of the skin and fascia underneath. In patients with eosinophilic fasciitis, the involved fascia is inflamed with the eosinophil type of white blood cells. This leads to symptoms of progressive thickening and often redness, warmth, and hardness of the skin surface. Occasionally, the onset of eosinophilic fasciitis follows a period of exertional physical activity. Eosinophilic fasciitis is sometimes confused with eosinophilia-myalgia syndrome and scleroderma. Eosinophilic fasciitis sometimes occurs associated with cancers, such as leukemia and lymphoma.

How is eosinophilic fasciitis diagnosed?

The diagnosis of eosinophilic fasciitis is made with a biopsy of a full thickness of involved skin.

How is eosinophilic fasciitis treated?

Treatment of eosinophilic fasciitis is directed at eliminating the tissue inflammation and includes aspirin, other antiinflammatory drugs (NSAIDs), and cortisone. Many patients will improve spontaneously. Others can be afflicted with persistent tissue and joint pain, in addition to thickening of the involved tissues. For aggressive eosinophilic fasciitis, cortisone medications (such as prednisone and prednisolone) are considered along with immune suppression medications (such as cyclophosphamide [Cytoxan] and penicillamine [Depen, Cuprimine]). Recent medical research has shown that the immune-suppression drug methotrexate can provide an added benefit in treating eosinophilic fasciitis. This methotrexate research strongly suggests that methotrexate can reduce both the immune inflammation and the need for continued cortisone medications.

Scleroderma At A Glance
Scleroderma is a disease of the connective tissue featuring skin thickening, that can involve scarring, blood vessel problems, varying degrees of inflammation, and is associated with an overactive immune system. Scleroderma is classified into diffuse and limited forms. CREST syndrome is a limited form of scleroderma. Patients with scleroderma can have specific antibodies (ANA, anticentromere or antitopoisomerase) in their blood which suggest autoimmunity.

Treatment of scleroderma is directed toward the individual's symptom(s) that is(are) most debilitating.

What is scleroderma?
Scleroderma is an autoimmune disease of the connective tissue featuring skin thickening, spontaneous scarring, blood vessel disease, varying degrees of inflammation, associated with an overactive immune system. Autoimmune diseases are illnesses which occur when the body's tissues are attacked by its own immune system. Scleroderma is characterized by the formation of scar tissue (fibrosis) in the skin and organs of the body. This leads to thickness and firmness of involved areas. Scleroderma, when it's diffuse or widespread over the body, is also referred to as systemic sclerosis. The cause of scleroderma is not known. Researchers have found some evidence that certain genes are important factors, but the environment seems to also play a role. The result is activation of the immune system in a susceptible individual, causing injury to tissues that result in injury similar to scar-tissue formation. The fact that genes seem to cause a predisposition to developing scleroderma means that inheritance at least plays a partial role. It is not unusual to find other autoimmune diseases in families of scleroderma patients. Some evidence for the role genes may play in leading to the development of scleroderma comes from the study of Choctaw Native Americans who are the group with the highest reported prevalence of the disease. The disease is more frequent in females than in males.

How is scleroderma classified?

Scleroderma can be classified in terms of the degree and location of the skin involvement. Accordingly, scleroderma has been categorized into two major groups, diffuse and limited. However, the terminology in the literature varies; for example, some investigators term the two major groups localized and systemic. The diffuse form of scleroderma (systemic sclerosis) involves symmetric thickening of skin of the extremities, face, and trunk (chest, back, abdomen, or flanks) that can rapidly progress to hardening after an early inflammatory phase. Organ disease can occur early on and be serious. Organs affected include the esophagus, bowels, and lungs with scarring (fibrosis), heart, and kidneys. High blood pressure can be a troublesome side effect. The limited form of scleroderma tends to have far less skin involvement with skin thickening confined to the skin of the fingers and face. The skin changes and other features of disease tend to occur more slowly than in the diffuse form. Because a characteristic clinical pattern can occur in patients with the limited form of scleroderma, this form has taken another name that is composed of the first initials of the common components. Thus, this form is also called the "CREST" variant of scleroderma. CREST represents the following features: C...Calcinosis refers to the formation of tiny deposits of calcium in the skin. This is seen as hard, whitish areas in the superficial skin, commonly overlying the elbows, knees, or fingers. These firm deposits can be tender, can become infected, and can fall off spontaneously or require surgical removal. This is the least common of the CREST scleroderma variant features. R...Raynaud's phenomenon refers to the spasm of the tiny artery vessels supplying blood to the fingers, toes, nose, tongue, or ears. These areas turns blue, white, then red after exposure to extremes of cold, or even sometimes with extremes of heat or emotional upset. This can lead to tiny areas of damage to the tips of the fingers (digital ulcers) or larger areas of dead skin on the ends of the fingers. E...Esophagus disease in scleroderma is characterized by poorly functioning muscle of the lower twothirds of the esophagus. This can lead to an abnormally wide esophagus that allows stomach acid to backflow into the esophagus to cause heartburn, inflammation, and potentially scarring that narrows the

esophagus. This can eventually lead to difficulty in passing food from the mouth through the esophagus into the stomach. Symptoms of heartburn are treated aggressively in patients with scleroderma in order to prevent injury to the esophagus. S...Sclerodactyly refers to the localized thickening and tightness of the skin of the fingers or toes. This can give them a "shiny" and slightly puffy appearance. The tightness can cause severe limitation of motion of the fingers and toes. These skin changes generally progress much slower that those of patients with the diffuse form of scleroderma. T...Telangiectasias are tiny red areas, frequently on the face, hands, and in the mouth behind the lips. These areas blanch when they are pressed upon and represent widened (dilated) capillaries. Patients can have variations of CREST, for example, CRST, REST, ST, etc. Patients can also have "overlap" illness with features of both CREST and the diffuse form of scleroderma. Some patients have overlaps of scleroderma and other connective tissue diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and polymyositis. When features of scleroderma are present along with features of polymyositis and systemic lupus erythematosus, the condition is referred to as mixed connective tissue disease (MCTD). Finally, scleroderma skin changes can be localized. Morphea is scleroderma skin that is localized to a patchy area of the skin that becomes hardened and slightly pigmented. Sometimes morphea can cause multiple lesions in the skin. Morphea is not associated with disease elsewhere in the body. Linear scleroderma is scleroderma that is localized usually to a lower extremity, frequently presenting as a strip of hardening skin down the leg of a child. Linear scleroderma in children can stunt bone growth of the affected limb. Sometimes linear scleroderma is associated with a "satellite" area of a patch of localized scleroderma skin, such as on the abdomen.

What are scleroderma symptoms and signs?

The symptoms of scleroderma depend on the type of scleroderma present and the extent of external and internal involvement in the individual affected. Because scleroderma can affect the skin, esophagus, blood vessels, kidneys, lungs, blood pressure and bowels, the symptoms it causes can involve many areas of the body. Scleroderma affects the skin to cause local or widespread signs of inflammation (redness, swelling, tenderness, itching, and pain) that can lead to skin tightness or hardening. These skin changes can be widespread, but it's most common for them to affect the fingers, feet, face, and neck. This can lead to decreased range of motion of the fingers, toes, and jaw. Tiny areas of calcification (calcinosis), while not common, can sometimes be noticed as hard nodules at the tips of the elbows or in the fingers. Scleroderma affecting the esophagus leads to heartburn. This is directly a result of stomach acid flowing back up into the esophagus. Sometimes this can lead to scarring of the esophagus, resulting in narrowing with difficulty swallowing food and/or localized pain in the central chest. Blood vessels that can be affected include the tiny arterioles of the finger tips, toes, and elsewhere. These vessels can have a tendency to spasm when the areas are exposed to cold, leading to blueness, whiteness, and redness of involved fingers, toes, and sometimes nose or ears. These color changes are referred to as Raynaud's phenomenon. Raynaud's phenomenon can cause inadequate supply of oxygen to the involve tips of fingers or toes, causing tiny ulcers or blackened (dead) skin. Sometimes Raynaud's phenomenon is also associated with tingling. Other blood vessels that can be involved in scleroderma are the tiny capillaries of the face, lips, mouth, or fingers. These capillaries widen (dilate), forming tiny, red blanching spots, called telangiectasias.

Elevated blood pressure is potentially serious and can lead to kidney damage. Symptoms include headache, fatigue, and in severe cases, stroke. Blood pressure monitoring and control is essential. Inflammation of the lungs in scleroderma can cause scarring, resulting in shortness of breath, especially with physical exertion. Elevated pressure in the arteries to the lungs (pulmonary hypertension) can also cause shortness of breath and difficulty getting an adequate breath with activity. Scleroderma affecting the large bowel (colon) most often causes constipation but can also lead to cramping and diarrhea. When this is severe, complete stool blockage (fecal impaction) can result.

How is scleroderma diagnosed?

The diagnosis of the scleroderma syndrome is based on the finding of the clinical features of the illnesses. In addition, nearly all patients with scleroderma have blood tests that suggest autoimmunity, because antinuclear antibodies (ANAs) are usually detectable. A particular antibody, the anticentromere antibody, is found almost exclusively in the limited, or CREST, form of scleroderma. Anti-Scl 70 antibody (antitopoisomerase I antibody) is most often seen in patients with the diffuse form of scleroderma. Other tests are used to evaluate the presence or extent of any internal disease. These may include upper and lower gastrointestinal tests to evaluate the bowels, chest X-rays, lung-function testing (pulmonary function test), and CAT scanning to examine the lungs, EKG and echocardiograms, and sometimes heart catheterization to evaluate the pressure in the arteries of the heart and lungs.

What is the treatment for scleroderma?

Treatment of scleroderma is directed toward the individual feature(s) affecting different areas of the body. Aggressive treatments of elevations in blood pressure have been extremely important in preventing kidney failure. Blood-pressure medications, particularly the angiotensin converting enzyme (ACE) inhibitor class of drugs, such as captopril (Capoten), are frequently used. Recent data indicate that colchicine can be helpful in decreasing the inflammation and tenderness that periodically accompanies the calcinosis nodules in the skin. Skin itching can be relieved with lotions (emollients) such as Eucerin and Lubriderm. Mild Raynaud's phenomenon may require only hand warming and protection. Low-dose aspirin is often added to prevent tiny blood clots in the fingers, especially in patients with a history of fingertip ulcerations. Moderate Raynaud's phenomenon can be helped by medications that open up the arteries, such as nifedipine (Procardia, Adalat) and nicardipine (Cardene), or with topical nitroglycerin applied to the most affected digit (most effective on the sides of the digit where the arteries are). Gently applied finger splinting can protect tender tissues. (It is important to not constrict the tiny arteries on the sides of the fingers when protecting them with splints, braces, or band-aid materials.) A class of medications that is typically used for depression, called serotonin reuptake inhibitors, such as fluoxetine (Prozac), can sometimes improve the circulation of the affected digit. Severe Raynaud's phenomenon can require surgical procedures, such as those to interrupt the nerves of the finger that stimulate constriction of the blood vessels (digital sympathectomy). Ulcerations of the fingers can require topical or oral antibiotics. Esophagus irritation and heartburn can be relieved with omeprazole (Prilosec), esomeprazole (Nexium), or lansoprazole (Prevacid). Antacids can also be helpful. Elevating the head of the bed can reduce the back-flow of acid into the esophagus that causes inflammation and heartburn. Avoiding caffeine and cigarette smoking also helps.

Constipation, cramping, and diarrhea is sometimes caused by bacteria that can be treated with tetracycline or erythromycin. Studies have shown that erythromycin could also be used. Increased fluid intake and fiber intake are good general measures. Irritated, itchy dry skin can be helped by emollients such as Lubriderm, Eucerin, Bag Balm histamine 2 blockers, or trazodone (Desyrel). Telangiectasias, such as those on the face, can be treated with local laser therapy. Sun exposure should be minimized as it can worsen telangiectasias. Approximately 10% of patients with the CREST variant develop elevated pressures in the blood vessels to the lungs (pulmonary hypertension). Abnormally elevated blood pressure of the arteries supplying the lungs is often treated with calcium antagonist medications, such as nifedipine (Procardia), and bloodthinning drugs (anticoagulation). More severe pulmonary hypertension can be helped by continuous intravenous infusion or inhalation of prostacyclin (Iloprost). Taken by mouth, bosentan (Tracleer), is now also available to treat pulmonary hypertension. In addition, sildenafil (Viagra) and tadalafil (Cialis) have been FDA approved to treat pulmonary hypertension. Additionally, medications are used to suppress the overly active immune system that seems to be spontaneously causing the disease in organs. Medications used for this purpose include penicillamine, azathioprine (Imuran, Azasan), and methotrexate (Rheumatrex, Trexall). Recent research has found that low-dose penicillamine (Depen, Cuprimine) (125 mg every other day) is as effective as previously used high doses of penicillamine, with less toxicity. Serious inflammation of the lungs (alveolitis) can require immune suppression with cyclophosphamide (Cytoxan) along with prednisone (Deltasone, Liquid Pred). The optimal treatment of scleroderma lung disease is an area of active research. Stem-cell transplantation is being explored as a possible option. No medication has been found to be universally effective for all patients with scleroderma. In an individual patient, the illness may be mild and not require treatments. In some, the disease is ravaging and relentless.

Sjogren's Syndrome At A Glance

Sjogren's syndrome is an autoimmune disease. Sjogren's syndrome involves inflammation of glands and other tissues of the body. About 90% of Sjogren's syndrome patients are female. Sjogren's syndrome can be complicated by infections of the eyes, breathing passages, and mouth. Sjogren's syndrome is typically associated with antibodies against a variety of body tissues (autoantibodies). Diagnosis of Sjogren's syndrome can be aided by a saliva-gland biopsy. Treatment of patients with Sjogrens syndrome is directed toward the particular areas of the body that are involved and complications, such as infection.

What is Sjogren's syndrome?

Sjogren's syndrome is an autoimmune disease characterized by dryness of the mouth and eyes. Autoimmune diseases feature the abnormal production of extra antibodies in the blood that are directed against various tissues of the body. This particular autoimmune illness features inflammation in glands of the body that are responsible for producing tears and saliva. Inflammation of the glands that produce tears (lacrimal glands) leads to decreased water production for tears and dry eyes. Inflammation of the glands that produce the saliva in the mouth (salivary glands, including the parotid glands) leads to dry mouth and dry lips.

Sjogren's syndrome with gland inflammation (resulting dry eyes and mouth, etc.) that is not associated with another connective tissue disease is referred to as primary Sjogren's syndrome. Sjogren's syndrome that is also associated with a connective tissue disease, such as rheumatoid arthritis, systemic lupus erythematosus, or scleroderma, is referred to as secondary Sjogren's syndrome.

What causes Sjogren's syndrome?

While the exact cause of Sjogren's syndrome is not known, there is growing scientific support for genetic (inherited) factors. The genetic background of Sjogren's syndrome patients is an active area of research. The illness is sometimes found in other family members. It is also found more commonly in families that have members with other autoimmune illnesses, such as systemic lupus erythematosus, autoimmune thyroid disease, type I diabetes, etc. About 90% of patients with Sjogren's syndrome are female.

What are Sjogren's syndrome symptoms and signs?

Symptoms of Sjogren's syndrome can involve the glands, as above, but there are also possible effects of the illness involving other organs of the body (extraglandular manifestations). When the tear gland (lacrimal gland) is inflamed from Sjogren's, the resulting eye dryness can progressively lead to eye irritation, decreased tear production, a "gritty" sensation, infection, and serious abrasion of the dome of the eye (cornea). Dry eyes can lead to infections of the eyes. The condition of having dry eyes is medically referred to as xerophthalmia. Inflammation of the salivary glands can lead to mouth dryness, swallowing difficulties, dental decay, cavities, gum disease, mouth sores and swelling, and stones and/or infection of the parotid gland inside of the cheeks. Dry lips often accompany the mouth dryness. Dry mouth is medically referred to as xerostomia. Other glands that can become inflamed, though less commonly, in Sjogren's syndrome include those of the lining of the breathing passages (leading to lung infections) and the vagina (sometimes causing pain during intercourse or recurrent vaginal infections). Extraglandular (outside of the glands) problems in Sjogren's syndrome include joint pain or inflammation (arthritis), Raynaud's phenomenon, lung inflammation, lymph node enlargement, and kidney, nerve, and muscle disease. A rare serious complication of Sjogren's syndrome is inflammation of the blood vessels (vasculitis), which can damage the tissues of the body that are supplied by these vessels. A common disease that is occasionally associated with Sjogren's syndrome is autoimmune thyroiditis (Hashimoto's thyroiditis), which can lead to abnormal thyroid hormone levels detected by thyroid blood tests. Heartburn and difficulty swallowing can result from gastroesophageal reflux disease (GERD), another common condition associated with Sjogren's syndrome. A rare disease that is uncommonly associated with Sjogren's syndrome is primary biliary cirrhosis, an autoimmune disease of the liver that leads to scarring of the liver tissue. A small percentage of patients with Sjogren's syndrome develop cancer of the lymph glands (lymphoma). This usually develops only after many years with the illness. Unusual lymph node swelling should be reported to the physician.

How is Sjogren's syndrome diagnosed?

The diagnosis of Sjogren's syndrome involves detecting the features of dryness of the eyes and mouth. The dryness of the eyes can be determined in the doctor's office by testing the eye's ability to wet a small testing paper strip placed under the eyelid (Schirmer's test using Schirmer tear test strips). More sophisticated testing can be done by an eye specialist (ophthalmologist).

Salivary glands can become larger and harden or become tender. Salivary-gland inflammation can be detected by radiologic nuclear medicine salivary scans. Also, the diminished ability of the salivary glands to produce saliva can be measured with salivary flow testing. The diagnosis is strongly supported by abnormal findings of a biopsy of salivary-gland tissue. The glands of the lower lip are often used to obtain a biopsy sample of the salivary-gland tissue in the diagnosis of Sjogren's syndrome. The lower lip salivary-gland biopsy procedure is performed under local anesthesia with the surgeon making a tiny incision on the inner part of the lower lip to expose and remove a sample of the tiny salivary glands within. Patients with Sjogren's syndrome typically produce a variety of extra antibodies against body tissues (autoantibodies). These can be detected through blood testing and include antinuclear antibodies (ANA), which are present in nearly all patients. Typical antibodies that are found in most, but not all patients, are SS-A and SS-B antibodies (Sjogren's syndrome A and B antibodies), rheumatoid factor, thyroid antibodies, and others. Low red blood count (anemia) and abnormal blood levels of markers of inflammation (sedimentation rate) are seen.

What is the treatment for Sjogren's syndrome?

The treatment of patients with Sjogren's syndrome is directed toward the particular areas of the body that are involved and prevention of complications such as infection. There is no cure for Sjogren's syndrome. Dryness of the eyes can be helped by artificial tears, using eye-lubricant ointments at night, and minimizing the use of hair dryers. When dryness becomes more significant, the ophthalmologist can plug the tear duct closed so that tears cover the eye longer. Cyclosporine eyedrops (Restasis) are approved medicated eyedrops that can reduce the inflammation of the tear glands, thereby improving their function. Signs of eye infection (conjunctivitis), such as pus or excessive redness or pain, should be evaluated by the doctor. Dietary addition of flaxseed oil may also benefit eye dryness. The dry mouth can be helped by drinking plenty of fluids, humidifying air, and good dental care to avoid dental decay. The glands can be stimulated to produce saliva by sucking on sugarless lemon drops or glycerin swabs. Additional treatments for the symptom of dry mouth are prescription medications that are saliva stimulants, such as pilocarpine (Salagen) and cevimeline (Evoxac). These medications should be avoided by people with certain heart diseases, asthma, or glaucoma. Artificial saliva preparations can ease many of the problems associated with dry mouth. Many of these types of agents are available as over-the-counter products, including toothpaste, gum, and mouthwash (Biotene). Numoisyn liquid and lozenges are also available for the treatment of dry mouth. Vitamin E oil has been used with some success. Infections of the mouth and teeth should be addressed as early as possible in order to avoid more severe complications. Diligent dental care is very important. Saltwater (saline) nasal sprays can help dryness in the passages of the nose. Vaginal lubricant should be considered for sexual intercourse if vaginal dryness if a problem. Hydroxychloroquine (Plaquenil) has been helpful for some manifestations of Sjogren's syndrome. Serious complications, such as vasculitis, can require immune-suppression medications, including cortisone (prednisone and others) and/or azathioprine (Imuran) or cyclophosphamide (Cytoxan). Infections, which can complicate Sjogren's syndrome, are addressed with appropriate antibiotics. Cancer of the lymph nodes (lymphoma), a rare complication of Sjogren's syndrome, is treated independently.

Systemic Lupus Erythematosus At A Glance

Systemic lupus erythematosus (SLE) is an autoimmune disease.

SLE is characterized by the production of unusual antibodies in the blood. SLE is eight times more common in women than men. The cause(s) of SLE is (are) unknown, however, heredity, viruses, ultraviolet light, and drugs all may play some role. Up to 10% of people with lupus isolated to the skin will develop the systemic form of lupus (SLE). Eleven criteria help doctors to diagnose SLE. Treatment of SLE is directed toward decreasing inflammation and/or the level of autoimmune activity. People with SLE can prevent "flares" of disease by avoiding sun exposure and not abruptly discontinuing medications and monitoring their condition with their doctor.

What is lupus? What are the types of lupus?

Lupus is an autoimmune disease characterized by acute and chronic inflammation of various tissues of the body. Autoimmune diseases are illnesses that occur when the body's tissues are attacked by its own immune system. The immune system is a complex system within the body that is designed to fight infectious agents, such as bacteria and other foreign microbes. One of the ways that the immune system fights infections is by producing antibodies that bind to the microbes. People with lupus produce abnormal antibodies in their blood that target tissues within their own body rather than foreign infectious agents. Because the antibodies and accompanying cells of inflammation can affect tissues anywhere in the body, lupus has the potential to affect a variety of areas. Sometimes lupus can cause disease of the skin, heart, lungs, kidneys, joints, and/or nervous system. When only the skin is involved, the condition is called lupus dermatitis or cutaneous lupus erythematosus. A form of lupus dermatitis that can be isolated to the skin, without internal disease, is called discoid lupus. When internal organs are involved, the condition is referred to as systemic lupus erythematosus (SLE). Both discoid and systemic lupus are more common in women than men (about eight times more common). The disease can affect all ages but most commonly begins from 20-45 years of age. Statistics demonstrate that lupus is somewhat more frequent in African Americans and people of Chinese and Japanese descent.

What causes lupus? Is it hereditary?

The precise reason for the abnormal autoimmunity that causes lupus is not known. Inherited genes, viruses, ultraviolet light, and certain medications may all play some role. Genetic factors increase the tendency of developing autoimmune diseases, and autoimmune diseases such as lupus, rheumatoid arthritis, and autoimmune thyroid disorders are more common among relatives of people with lupus than the general population. Some scientists believe that the immune system in lupus is more easily stimulated by external factors like viruses or ultraviolet light. Sometimes, symptoms of lupus can be precipitated or aggravated by only a brief period of sun exposure. It also is known that some women with SLE can experience worsening of their symptoms prior to their menstrual periods. This phenomenon, together with the female predominance of SLE, suggests that female hormones play an important role in the expression of SLE. This hormonal relationship is an active area of ongoing study by scientists.

More recently, research has demonstrated evidence that a key enzyme's failure to dispose of dying cells may contribute the development of SLE. The enzyme, DNase1, normally eliminates what is called "garbage DNA" and other cellular debris by chopping them into tiny fragments for easier disposal. Researchers turned off the DNase1 gene in mice. The mice appeared healthy at birth, but after six to eight months, the majority of mice without DNase1 showed signs of SLE. Thus, a genetic mutation in a gene that could disrupt the body's cellular waste disposal may be involved in the initiation of SLE.

What is drug-induced lupus?

Dozens of medications have been reported to trigger SLE. However, more than 90% of cases of "druginduced lupus" occurs as a side effect of one of the following six drugs: hydralazine (used for high blood pressure), quinidine and procainamide (used for abnormal heart rhythms), phenytoin (used for epilepsy), isoniazid ([Nydrazid, Laniazid] used for tuberculosis), and d-penicillamine (used for rheumatoid arthritis). These drugs are known to stimulate the immune system and cause SLE. Fortunately, drug-induced SLE is infrequent (accounting for less than 5% of all people with SLE) and usually resolves when the medications are discontinued.

What are the symptoms and signs of lupus?

People with SLE can develop different combinations of symptoms and organ involvement. Common complaints and symptoms include fatigue, low-grade fever, loss of appetite, muscle aches, arthritis, ulcers of the mouth and nose, facial rash ("butterfly rash"), unusual sensitivity to sunlight (photosensitivity), inflammation of the lining that surrounds the lungs (pleuritis) and the heart (pericarditis), and poor circulation to the fingers and toes with cold exposure (Raynaud's phenomenon). Complications of organ involvement can lead to further symptoms that depend on the organ affected and severity of the disease. Skin manifestations are frequent in lupus and can sometimes lead to scarring. In discoid lupus, only the skin is typically involved. The skin rash in discoid lupus often is found on the face and scalp. It usually is red and may have raised borders. Discoid lupus rashes are usually painless and do not itch, but scarring can cause permanent hair loss (alopecia). Over time, 5%-10% of those with discoid lupus may develop SLE. Over half of the people with SLE develop a characteristic red, flat facial rash over the bridge of their nose. Because of its shape, it is frequently referred to as the "butterfly rash" of SLE. The rash is painless and does not itch. The facial rash, along with inflammation in other organs, can be precipitated or worsened by exposure to sunlight, a condition called photosensitivity. This photosensitivity can be accompanied by worsening of inflammation throughout the body, called a "flare" of the disease.

Typically, with treatment, this rash can heal without permanent scarring. Most people with SLE will develop arthritis during the course of their illness. Arthritis in SLE commonly involves swelling, pain, stiffness, and even deformity of the small joints of the hands, wrists, and feet. Sometimes, the arthritis of SLE can mimic that of rheumatoid arthritis (another autoimmune disease). More serious organ involvement with inflammation occurs in the brain, liver, and kidneys. White blood cells and blood-clotting factors also can be characteristically decreased in SLE, known as leukopenia (leucopenia) and thrombocytopenia, respectively. Leukopenia can increase the risk of infection and thrombocytopenia can increase the risk of bleeding. Inflammation of muscles (myositis) can cause muscle pain and weakness. This can lead to elevations of muscle enzyme levels in the blood. Inflammation of blood vessels (vasculitis) that supply oxygen to tissues can cause isolated injury to a nerve, the skin, or an internal organ. The blood vessels are composed of arteries that pass oxygen-rich blood to the tissues of the body and veins that return oxygen-depleted blood from the tissues to the lungs. Vasculitis is characterized by inflammation with damage to the walls of various blood vessels. The damage blocks the circulation of blood through the vessels and can cause injury to the tissues that are supplied with oxygen by these vessels. Inflammation of the lining of the lungs (pleuritis) and of the heart (pericarditis) can cause sharp chest pain. The chest pain is aggravated by coughing, deep breathing, and certain changes in body position. The heart muscle itself rarely can become inflamed (carditis). It has also been shown that young women with SLE have a significantly increased risk of heart attacks due to coronary artery disease. Kidney inflammation in SLE can cause leakage of protein into the urine, fluid retention, high blood pressure, and even kidney failure. This can lead to further fatigue and swelling of the legs and feet. With kidney failure, machines are needed to cleanse the blood of accumulated waste products in a process called dialysis.

Involvement of the brain can cause personality changes, thought disorders (psychosis), seizures, and even coma. Damage to nerves can cause numbness, tingling, and weakness of the involved body parts or extremities. Brain involvement is referred to as lupus cerebritis. Many people with SLE experience hair loss (alopecia). Often, this occurs simultaneously with an increase in the activity of their disease. The hair loss can be patchy or diffuse and appear to be more like hair thinning. Some people with SLE have Raynaud's phenomenon. In this condition, the blood supply to the fingers and/or toes becomes compromised upon exposure to cold, causing blanching, whitish and/or bluish discoloration, and pain and numbness in the exposed fingers and toes.

How is lupus diagnosed?

Since individuals with SLE can have a wide variety of symptoms and different combinations of organ involvement, no single test establishes the diagnosis of systemic lupus. To help doctors improve the accuracy of the diagnosis of SLE, 11 criteria were established by the American Rheumatism Association. These 11 criteria are closely related to the symptoms discussed above. Some people suspected of having SLE may never develop enough criteria for a definite diagnosis. Other people accumulate enough criteria only after months or years of observation. When a person has four or more of these criteria, the diagnosis of SLE is strongly suggested. Nevertheless, the diagnosis of SLE may be made in some settings in people with only a few of these classical criteria, and treatment may sometimes be instituted at this stage. Of these people with minimal criteria, some may later develop other criteria, but many never do. The 11 criteria used for diagnosing systemic lupus erythematosus are malar (over the cheeks of the face) "butterfly" rash, discoid skin rash (patchy redness with hyperpigmentation and hypopigmentation that can cause scarring), photosensitivity (skin rash in reaction to sunlight [ultraviolet light] exposure), mucous membrane ulcers (spontaneous ulcers of the lining of the mouth, nose, or throat), arthritis (two or more swollen, tender joints of the extremities), pleuritis or pericarditis (inflammation of the lining tissue around the heart or lungs, usually associated with chest pain upon breathing or changes of body position), kidney abnormalities (abnormal amounts of urine protein or clumps of cellular elements called casts detectable with a urinalysis), brain irritation (manifested by seizures [convulsions] and/or psychosis), blood-count abnormalities (low counts of white or red blood cells, or platelets, on routine blood testing), immunologic disorder (abnormal immune tests include anti-DNA or anti-Sm [Smith] antibodies, falsely positive blood test for syphilis, anticardiolipin antibodies, lupus anticoagulant, or positive LE prep test),

antinuclear antibody (positive ANA antibody testing [antinuclear antibodies in the blood]).

In addition to the 11 criteria, other tests can be helpful in evaluating people with SLE to determine the severity of organ involvement. These include routine testing of the blood to detect inflammation (for example, tests called the sedimentation rate and C-reactive protein), blood-chemistry testing, direct analysis of internal body fluids, and tissue biopsies. Abnormalities in body fluids and tissue samples (kidney, skin, and nerve biopsies) can further support the diagnosis of SLE. The appropriate testing procedures are selected for the patient individually by the doctor.

What is the treatment for systemic lupus erythematosus?

There is no permanent cure for SLE. The goal of treatment is to relieve symptoms and protect organs by decreasing inflammation and/or the level of autoimmune activity in the body. Many people with mild symptoms may need no treatment or only intermittent courses of anti-inflammatory medications. Those with more serious illness involving damage to internal organ(s) may require high doses of corticosteroids in combination with other medications that suppress the body's immune system. People with SLE need more rest during periods of active disease. Researchers have reported that poor sleep quality was a significant factor in developing fatigue in people with SLE. These reports emphasize the importance for people and physicians to address sleep quality and the effect of underlying depression, lack of exercise, and self-care coping strategies on overall health. During these periods, carefully prescribed exercise is still important to maintain muscle tone and range of motion in the joints. Nonsteroidal anti-inflammatory drugs (NSAIDs) are helpful in reducing inflammation and pain in muscles, joints, and other tissues. Examples of NSAIDs include aspirin, ibuprofen (Motrin), naproxen (Naprosyn), and sulindac (Clinoril). Since the individual response to NSAIDs varies, it is common for a doctor to try different NSAIDs to find the most effective one with the fewest side effects. The most common side effects are stomach upset, abdominal pain, ulcers, and even ulcer bleeding. NSAIDs are usually taken with food to reduce side effects. Sometimes, medications that prevent ulcers while taking NSAIDs, such as misoprostol (Cytotec), are given simultaneously. Corticosteroids are more potent than NSAIDs in reducing inflammation and restoring function when the disease is active. Corticosteroids are particularly helpful when internal organs are affected. Corticosteroids can be given by mouth, injected directly into the joints and other tissues, or administered intravenously. Unfortunately, corticosteroids have serious side effects when given in high doses over prolonged periods, and the doctor will try to monitor the activity of the disease in order to use the lowest doses that are safe. Side effects of corticosteroids include weight gain, thinning of the bones and skin, infection, diabetes, facial puffiness, cataracts, and death (necrosis) of the tissues in large joints. Hydroxychloroquine (Plaquenil) is an antimalarial medication found to be particularly effective for SLE people with fatigue, skin involvement, and joint disease. Consistently taking Plaquenil can prevent flareups of lupus. Side effects are uncommon but include diarrhea, upset stomach, and eye-pigment changes. Eye-pigment changes are rare but require monitoring by an ophthalmologist (eye specialist) during treatment with Plaquenil. Researchers have found that Plaquenil significantly decreased the frequency of abnormal blood clots in people with systemic lupus. Moreover, the effect seemed independent of immune suppression, implying that Plaquenil can directly act to prevent the blood clots. This fascinating study highlights an important reason for people and doctors to consider Plaquenil for long-term use, especially for those SLE people who are at some risk for blood clots in veins and arteries, such as those with phospholipid antibodies (cardiolipin antibodies, lupus anticoagulant, and false-positive venereal disease research laboratory test). This means not only that Plaquenil reduces the chance for re-flares of SLE, but it can also be beneficial in thinning the blood to prevent abnormal excessive blood clotting. Plaquenil is commonly used in combination with other treatments for lupus.

For resistant skin disease, other antimalarial drugs, such as chloroquine (Aralen) or quinacrine, are considered and can be used in combination with hydroxychloroquine. Alternative medications for skin disease include dapsone and retinoic acid (Retin-A). Retin-A is often effective for an uncommon wart-like form of lupus skin disease. For more severe skin disease, immunosuppressive medications are considered as described below. Medications that suppress immunity (immunosuppressive medications) are also called cytotoxic drugs. Immunosuppressive medications are used for treating people with more severe manifestations of SLE, such as damage to internal organ(s). Examples of immunosuppressive medications include methotrexate (Rheumatrex, Trexall), azathioprine (Imuran), cyclophosphamide (Cytoxan), chlorambucil (Leukeran), and cyclosporine (Sandimmune). All immunosuppressive medications can seriously depress blood-cell counts and increase risks of infection and bleeding. Other side effects are specific for each drug. For examples, Rheumatrex can cause liver toxicity, while Sandimmune can impair kidney function. In recent years, mycophenolate mofetil (CellCept) has been used as an effective medication for lupus, particularly when it is associated with kidney disease. CellCept has been helpful in reversing active lupus kidney disease (lupus renal disease) and in maintaining remission after it is established. Its lower sideeffect profile has advantage over traditional immune-suppression medications. In SLE patients with serious brain or kidney disease, plasmapheresis (a process of removing and treating the blood before it is returned to the body) is sometimes used to remove antibodies and other immune substances from the blood to suppress immunity. Rarely, people with SLE can develop seriously low platelet levels, thereby increasing the risk of excessive and spontaneous bleeding. Since the spleen is believed to be the major site of platelet destruction, surgical removal of the spleen is sometimes performed to improve platelet levels. Other treatments have included plasmapheresis and the use of male hormones. Plasmapheresis has also been used to remove proteins (cryoglobulins) that can lead to vasculitis. End-stage kidney damage from SLE requires dialysis and/or a kidney transplant. Most recent research is indicating benefits of rituximab (Rituxan) in treating lupus. Rituximab is an intravenously infused antibody that suppresses a particular white blood cell, the B cell, by decreasing their number in the circulation. B cells have been found to play a central role in lupus activity, and when they are suppressed, the disease tends toward remission. This may particularly helpful for people with kidney disease. Scientists have also found that low-dose dietary supplementation with omega-3 fish oils could help patients with lupus by decreasing disease activity and possibly decreasing heart-disease risk.

Lyme Disease At A Glance

Lyme disease is a bacterial illness that is spread by tick bites. Lyme disease can affect the skin, joints, heart, and the nervous system. Lyme disease occurs in phases -- the early phase beginning at the site of the tick bite with an expanding ring of redness. Lyme disease is diagnosed based on the patient's clinical signs of illness and the detection of Lyme antibodies in the blood. Lyme disease is treated with antibiotics.

What is Lyme disease? What causes Lyme disease?

Lyme disease is a bacterial illness caused by a bacterium called a "spirochete." In the United States, the actual name of the bacterium is Borrelia burgdorferi. In Europe, another bacterium, Borrelia afzelii, also causes Lyme disease. Certain ticks found on deer harbor the bacterium in their stomachs. Lyme disease is spread by these ticks when they bite the skin, which permits the bacterium to infect the body. Lyme

disease is not contagious from an affected person to someone else. Lyme disease can cause abnormalities in the skin, joints, heart, and nervous system.

What is the history of Lyme disease?

Interestingly, the disease only became apparent in 1975 when mothers of a group of children who lived near each other in Lyme, Connecticut, made researchers aware that their children had all been diagnosed with rheumatoid arthritis. This unusual grouping of illness that appeared "rheumatoid" eventually led researchers to the identification of the bacterial cause of the children's condition, what was then called "Lyme disease" in 1982. Ticks are carriers of the Lyme bacterium in their stomachs. The ticks then are vectors that can transmit the bacterium to humans with a tick bite. The number of cases of the disease in an area depends on the number of ticks present and how often the ticks are infected with the bacteria. In certain areas of New York, where Lyme disease is common, over half of the ticks are infected. Lyme disease has been reported most often in the northeastern United States, but it has been reported in all 50 states, as well as China, Europe, Japan, Australia, and parts of the former Soviet Union. In the United States, it is primarily contracted in the Northeast from the states of Maine to Maryland, in the Midwest in Minnesota and Wisconsin, and in the West in Oregon and Northern California.

Picture of a deer tick

What are symptoms and signs of Lyme disease?

Lyme disease affects different areas of the body in varying degrees as it progresses. The site where the tick bites the body is where the bacteria enter through the skin. As the bacteria spread in the skin away from the initial tick bite, the infection causes an expanding reddish rash that is often associated with "flulike" symptoms. Later, it can produce abnormalities in the joints, heart, and nervous system. Lyme disease is medically described in three phases as: (1) early localized disease with skin inflammation; (2) early disseminated disease with heart and nervous system involvement, including palsies and meningitis; and (3) late disease featuring motor and sensory nerve damage and brain inflammation as well as arthritis.

In the early phase of the illness, within days to weeks of the tick bite, the skin around the bite develops an expanding ring of unraised redness. There may be an outer ring of brighter redness and a central area of clearing, leading to a "bull's-eye" appearance. This classic initial rash is called "erythema migrans" (formerly called erythema chronicum migrans). Patients often can't recall the tick bite (the ticks can be as small as the periods in this paragraph). Also, they may not have the identifying rash to signal the doctor. More than one in four patients never even develop a rash. The redness of the skin is often accompanied by generalized fatigue, muscle and joint stiffness, swollen lymph nodes ("swollen glands"), and headache, resembling symptoms of a virus infection. The redness resolves, without treatment, in about a month. Weeks to months after the initial redness of the skin the bacteria and their effects spread throughout the body. Subsequently, disease in the joints, heart, and nervous system can occur. The later phases of Lyme disease can affect the heart, causing inflammation of the heart muscle. This can result in abnormal heart rhythms and heart failure. The nervous system can develop facial muscle paralysis (Bell's palsy), abnormal sensation due to disease of peripheral nerves (peripheral neuropathy), meningitis, and confusion. Arthritis, or inflammation in the joints, begins with swelling, stiffness, and pain. Usually, only one or a few joints become affected, most commonly the knees. The arthritis of Lyme disease can look like many other types of inflammatory arthritis and can become chronic. Researchers have also found that anxiety and depression occur with an increased rate in people with Lyme disease. This is another important aspect of the evaluation and management of this condition.

How is Lyme disease diagnosed?

In early Lyme disease, doctors can sometimes make a diagnosis simply by finding the classic red rash (described above), particularly in people who have recently been in regions in which Lyme disease is common. The doctor might review the patient's history and examine the patient in order to exclude diseases with similar findings in the joints, heart, and nervous system. Blood testing for antibodies to Lyme bacteria is generally not necessary or helpful in early stage disease, but it can help in diagnosis in later stages. (Antibodies are produced by the body to attack the bacteria and can be evidence of exposure to the bacteria. These antibodies can be detected using a laboratory method called an enzymelinked immunosorbent assay [ELISA].) Antibodies, however, can be false indicators of disease, since they can persist for years after the disease is cured. Moreover, false-positive tests in patients with nonspecific findings (those that are not specifically suggestive of Lyme disease) can lead to confusion. Currently, the confirmatory test that is most reliable is the Western Blot assay antibody test. More accurate tests are being developed. Generally, Lyme blood testing is helpful in a patient who has symptoms compatible with Lyme disease, who has a history of a tick bite at least a month prior, or who has unexplained disorders of the heart, joints, or nervous system that are characteristic of Lyme disease.

What is the treatment for Lyme disease?

Most cases of Lyme disease are curable with antibiotics. This is so true that some authors of Lyme disease research have stated that the most common cause of lack of response of Lyme disease to antibiotics is a lack of Lyme disease to begin with! The type of antibiotic depends on the stage of the disease (early or late) and what areas of the body are affected. Early illness is usually treated with medicines taken by mouth, for example, doxycycline (Vibramycin), amoxicillin (Amoxil), or cefuroxime axetil (Ceftin). Of note, doxycycline should not be used in pregnancy. Therefore, if a person finds a typical bull's-eye skin rash (described above) developing in an area of a tick bite, they should seek medical attention as soon as possible. Generally, antibiotic treatment resolves the rash within one or two weeks with no long-term consequences. Later illness such as nervous-system disease might require intravenous drugs; examples are ceftriaxone (Rocephin) and penicillin G.

For the relief of symptoms, pain-relieving medicines might be added. Swollen joints can be reduced by the doctor removing fluid from them (arthrocentesis). An arthrocentesis is a procedure whereby fluid is removed from a joint using a needle and syringe under sterile conditions. It is usually performed in a doctor's office. Rarely, even with appropriate antibiotics, the arthritis continues. It has been suggested by researchers that sometimes joint inflammation can persist even after eradication of the Lyme bacteria. This has been explained as an ongoing autoimmune response causing inflammation of the joint that was initially stimulated by the original bacterial infection. The doctor also can use oral medications such as ibuprofen (Motrin, Nuprin) to reduce inflammation and improve function. If a person is bitten by the classic tick (Ixodes) that has been attached for at least 36 hours, a single dose of doxycycline (200 mg) can be helpful for prevention of Lyme disease. This therapy is not recommended if the tick is acquired in an area where these ticks are not commonly infested (infection rate less than 20%) with the bacterium (Borrelia) that causes Lyme disease. Also, doxycycline should not be used in pregnancy. Vaccines were formerly on the market; however, as of Feb. 25, 2002, the manufacturer announced that the LYMErix Lyme disease vaccine would no longer be commercially available. Further studies of vaccines are needed.