Systemic Lupus Erythematosus (SLE)

Systemic lupus erythematosus (lupus) is a chronic inflammatory connective tissue disorder that can involve joints, kidneys, mucous membranes, and blood vessel walls.
About 90% of people who have lupus are young women in their late teens to 30s, but children (mostly girls) and older men and women can also be affected. Lupus occurs in all parts of the world but may be more common in blacks and in Asians.
The cause of lupus is usually not known. Occasionally, the use of certain drugs (such as hydralazine and procainamide, which are used to treat heart conditions, and isoniazid, which is used to treat tuberculosis) can cause lupus. Drug-induced lupus usually disappears after the drug is discontinued. The number and variety of antibodies that can appear in lupus are greater than those in any other disorder. These antibodies, which are the underlying physiologic problem in lupus, along with other unknown factors, determine which symptoms develop. However, the levels of these antibodies may not always be proportional to the person's symptoms.
Discoid lupus erythematosus is a form of lupus that affects only the skin. In this condition, raised round bumps occur, with scaling and sometimes with scarring and hair loss in affected areas. In 10% of people, manifestations of lupus-for example, those affecting the joints, kidneys, and brain-may occur but are generally mild.

Symptoms
Symptoms vary greatly from person to person. Symptoms may begin suddenly with fever, resembling an acute infection, or may develop gradually over months or years with episodes (called flare-ups) of fever, feeling unwell, or any of the symptoms discussed below alternating with periods when symptoms are absent or minimal. For many women, lupus flare-ups occur during the second half of the menstrual cycle, with symptoms disappearing when menstruation starts. Migraine-type headaches, epilepsy, or severe mental disorders (psychoses) may be the first abnormalities that are noticed. Eventually, however, symptoms may affect any organ system. Joint symptoms, ranging from intermittent joint pains (arthralgias) to sudden inflammation of multiple joints (acute polyarthritis) , occur in about 90% of people and may exist for years before other symptoms appear. In long-standing disease, marked joint deformity may occur (Jaccoud's arthropathy) . However, joint inflammation is generally intermittent and usually does not damage the joints.
Skin rashes include a butterfly-like redness across the nose and cheeks (malar butterfly erythema); raised bumps or patches of thin skin; and red, flat or raised areas on the face and sun-exposed areas of the neck, upper chest, and elbows. Blisters and skin ulcers are rare, although ulcers do commonly occur on mucous membranes, particularly on the roof of the mouth, on the inside of the cheeks, on the gums, and inside the nose. Generalized or patchy loss of hair (alopecia) is common during flare-ups. Mottled red areas on the sides of the palms and up the fingers, redness and swelling around the nails, and flat, reddish-purple blotches between the knuckles on the inner surfaces of the fingers also may occur. Purplish spots (petechiae) may occur because of bleeding in the skin as a result of low platelet levels in the blood. Sensitivity to sunlight (photosensitivity) occurs in 40% of people, particularly in whites.
It is common for the person to feel pain when breathing deeply. The pain is due to recurring inflammation of the sac around the lungs (pleurisy), with or without fluid (effusion) inside this sac. Inflammation of the lungs (lupus pneumonitis) , resulting in breathlessness, is rare, although minor abnormalities in lung function are common. Life-threatening bleeding into the lungs may rarely occur.
Chest pain due to inflammation of the sac around the heart (pericarditis) is often present. More serious but rare effects on the heart are inflammation of the walls of the coronary arteries (coronary artery vasculitis), which can lead to angina (see Coronary Artery Disease: Angina) or inflammation of the heart muscle with scarring (fibrosing myocarditis) , which can lead to heart failure.
Widespread enlargement of the lymph nodes is common, particularly in children, young adults, and in blacks of all ages. Enlargement of the spleen (splenomegaly) occurs in about 10% of people. The person may experience nausea, diarrhea, and vague abdominal discomfort. The occurrence of these symptoms may be the forewarning of a flare-up.
Involvement of the brain (neuropsychiatric lupus) can cause headaches, mild impairment of thinking, personality changes, stroke, epilepsy, severe mental disorders (psychoses), or a condition in which a number of physical changes may occur in the brain, resulting in disorders such as dementia. Blockage of arteries in the brain or lung due to thrombosis or embolism can
also occur. Kidney involvement may be minor and without symptoms or relentlessly progressive and fatal. The most common result of this impairment is protein in the urine. Rarely, the blood vessels at the back of the eye become inflamed (retinitis). Blindness can develop over a few days.

Characteristics of Lupus
At least four of the following symptoms are generally present for a diagnosis to be made:

• Red, butterfly-shaped rash on the face, affecting the cheeks
• Typical skin rash on other parts of the body
• Sensitivity to sunlight
• Mouth sores
• Joint inflammation (arthritis)
• Fluid around the lungs, heart, or other organs (serositis)
• Kidney dysfunction
• Low white blood cell count, low red blood cell count due to hemolytic anemia, or low platelet count
• Nerve or brain dysfunction
• Positive results of a blood test for antinuclear antibodies
• Positive results of a blood test for antibodies to double-stranded DNA
  

Diagnosis
Doctors suspect lupus mainly on the basis of its symptoms and findings on a careful physical examination, particularly if they occur in a young woman. Nonetheless, because of the wide range of symptoms, distinguishing lupus from similar diseases can be difficult for a doctor at first. Laboratory tests can help doctors confirm the diagnosis. A blood test can detect antinuclear antibodies, which are present in almost all people who have lupus. However, these antibodies also occur in other diseases. Therefore, if antinuclear antibodies are detected, a test for antibodies to double-stranded DNA is also performed. A high level of these antibodies almost definitely means the person has lupus, but not all people who have lupus have these antibodies. Other blood tests may be performed to predict the activity and course of the disease. A blood test to detect antibodies to phospholipids can help identify people at risk for thrombosis. Blood tests can also indicate anemia, a low white blood cell count, or a low platelet count.
Laboratory tests can detect the presence of protein or red blood cells in the urine or an elevation of creatinine in the blood; these findings indicate kidney damage caused by glomerulonephritis. Sometimes a biopsy of kidney tissue must be performed to help the doctor plan treatment.

Prognosis and Treatment
Lupus tends to be chronic and relapsing, often with symptom-free periods that can last for years. Flare-ups occur less often after menopause. Because many people are being diagnosed earlier than in the past and because better treatment is available, the prognosis has improved markedly over the last two decades. However, because the course of lupus is unpredictable, the prognosis varies widely. Usually, if the initial inflammation is controlled, the long-term prognosis is good. Early detection and treatment of kidney damage reduces the incidence of severe kidney disease. Treatment depends on which organs are affected and whether the lupus is mild or severe.
Mild lupus may require little or no treatment. Aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) often can relieve joint pain. Aspirin is used in low doses if the person's blood has a tendency to clot, as happens in some people with lupus (aspirin reduces the tendency of blood to clot by reducing the tendency of blood platelets to stick together); aspirin or NSAID doses that are too high can harm the liver and kidney. Hydroxychloroquine, chloroquine, or quinacrine, sometimes taken in combination, helps relieve joint and skin symptoms. Sunscreen lotions (with a sun protection factor of at least 30) should be used, especially by people who have skin rashes.
Severe lupus is treated immediately with a corticosteroid such as prednisone. The dose and duration of treatment depend on which organs are affected. Sometimes an immunosuppressive drug such as azathioprine or cyclophosphamide is given to suppress the body's autoimmune attack.
Mycophenylate mofetil is another new alternative immunosuppressive drug. The combination of a corticosteroid and an immunosuppressive drug is most often used for severe kidney disease or nervous system disease and for vasculitis. Once the initial inflammation is controlled, a doctor determines the dose that most effectively suppresses inflammation over the long term. Usually, the dose of prednisone is gradually decreased when symptoms are controlled and laboratory test results improve. Relapses or flare-ups can occur during this process. For most people who have lupus, the dose of prednisone can eventually be decreased or occasionally discontinued. Surgical procedures and pregnancy are more complicated for people who have lupus, and they require close medical supervision. Miscarriages and flare-ups after childbirth are common, but pregnancy need not be avoided if conception is delayed until after flare-ups subside. If inflammation of the blood vessels at the back of the eye occurs, doctors give prompt treatment with an immunosuppressive drug because of the high risk of blindness.
(Merck)