Lupus

Causes

Lupus is an autoimmune disease, which means that instead of just attacking foreign substances, such as bacteria and viruses, the immune system also turns against healthy tissue. This leads to inflammation and damage to various parts of the body, including the joints, skin, kidneys, heart, lungs, blood vessels and brain.

Why autoimmune diseases occur still isn't well understood. But doctors believe that like many diseases, lupus results from a combination of factors, which may include heredity, environment and hormones. Although lupus isn't directly inherited, it's likely that inheriting certain genes makes you more susceptible to the disease, which then may be triggered by certain factors, such as:

• Infection. It appears that a viral or bacterial infection may trigger SLE in vulnerable people. In particular, lupus may be linked with recurrent infections with the Epstein-Barr virus, the same virus that causes mononucleosis.
• Certain prescription medications. One of the three main forms of lupus ”drug-induced lupus�?results from the long-term use of certain prescription drugs. Although many drugs can potentially trigger lupus, those most clearly linked with the disease include the antipsychotic chlorpromazine, high blood pressure medications such as hydralazine, the tuberculosis drug isoniazid and the heart medication procainamide. Beta blockers have also been associated with lupus, as have some drugs used to treat arthritis and ulcers, and certain antibiotics such as minocycline. It usually takes several months or years of therapy with these drugs before symptoms appear, and even then, only a small percentage of people will ever develop lupus. Unlike SLE, drug-induced lupus affects more men than women, primarily because men are more likely to develop chronic conditions that require long-term treatment. And unlike other types of lupus, symptoms such as joint pain and swelling, fever, and fatigue usually disappear after stopping the medication, although you may require short-term treatment with NSAIDs or corticosteroids.
• Sunlight. Exposure to the sun may bring on lupus skin lesions or trigger an internal response in susceptible people. Exactly why ultraviolet radiation has this effect isn't well understood, but scientists suspect that sunlight may cause skin cells to express certain proteins on their surface. Antibodies that are normally present in the body then latch onto these proteins, initiating an inflammatory response. Damaged skin cells also seem to die more frequently in people with lupus, leading to even more inflammation.
• Hormones. Because so many more women than men have SLE, researchers think that female hormones, particularly estrogen, may play a role in the disease. The exact mechanism isn't known, but some women with lupus report that their symptoms become worse during menstruation and pregnancy and with the use of birth control pills or hormone therapy. On the other hand, although the Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA) trial found a small risk of increased mild to moderate flares of the disease in menopausal women treated with hormone therapy, severe flares were rare. In addition, studies suggest that oral contraceptives are well tolerated by most but not all women with lupus.

Many other factors have been suggested as possible causes of lupus, including stress, certain foods, the artificial sweetener aspartame, silicone breast implants, mercury dental fillings, hair dye, and pesticides and other toxic chemicals. To date, no clear link has been found between these factors and lupus.

Risk factors

Although anyone can develop lupus at any age, common risk factors include:

• Your sex. Women account for the vast majority of lupus cases and are approximately nine times as likely to develop the disease as men are.
• Age. Although lupus affects people of all ages, including infants and children, it's most often diagnosed between the ages of 15 and 45.
• Race. Black Americans are at increased risk of developing lupus. They also tend to develop lupus at a younger age and have more serious complications. Researchers don't know the reason why, but in studies, blacks were found to have many more recurrent Epstein-Barr virus infections. Hispanics, Asians and Native Americans also are at higher risk of developing lupus.
• Family history. Having a relative who has lupus increases your odds of developing the disease.
• Infection with the Epstein-Barr virus. Almost everyone has been infected with the Epstein-Barr virus, a member of the herpes family and one of the most common human viruses. Once the initial infection, which is usually marked by nonspecific symptoms such as fever and sore throat, subsides, the virus remains dormant in the cells of your immune system unless something reactivates it. For reasons that aren't clear, recurrent Epstein-Barr infections seem to greatly increase the chances of developing lupus.
• Pregnancy. Lupus sometimes shows up for the first time during pregnancy or shortly after giving birth. The disease may also flare after a woman who already has lupus gives birth.

When to seek medical advice

If you develop an unexplained rash, ongoing fever, persistent aching or fatigue, see your doctor. If you've already been diagnosed with lupus, meet with your doctor on a regular basis so that your condition and treatment can be monitored. And because people who have lupus can experience different symptoms at different times, see your doctor immediately if new symptoms arise, especially if they include any of the following:

• Blood in your stool
• Severe abdominal pain
• Chest pain from pleurisy or pericarditis
• Seizures
• New fever or a fever much higher than it usually is
• Unusual bruising or bleeding anywhere on your body
• A severe headache with neck pain and fever

Screening and diagnosis

Lupus has been called a disease with a thousand faces because the signs and symptoms vary considerably from person to person. What's more, problems associated with the disease change over time and overlap with those of many other disorders. For these reasons, doctors may not initially consider lupus until the signs and symptoms become more obvious. Even then, lupus can be challenging to diagnose because nearly all people with lupus experience fluctuations in disease activity. At times the disease may become severe and at other times subside completely.

The American College of Rheumatology (ACR) has developed clinical and laboratory criteria to help physicians diagnose and classify lupus. If you have four of the 11 criteria at one time or individually over time, you probably have lupus. Your doctor may also consider the diagnosis of lupus even if you have fewer than four of these signs and symptoms. The criteria identified by the ACR include:

• Malar rash: a butterfly-shaped rash that covers the bridge of the nose and spreads across the cheeks
• Discoid rash: raised, scaly patches that may cause scarring
• Marked sensitivity to sunlight
• Oral ulcers
• Arthritis that involves, but doesn't destroy, two or more peripheral joints
• Inflammation of the lining of the heart or lung (serositis)
• Kidney (renal) disease
• A neurological disorder, such as seizures or psychosis
• A blood (hematologic) disorder, such as anemia, low platelets (thrombocytopenia), or a low white cell count (leukopenia)
• Anti-nuclear antibody, an indication that you may have an autoimmune disease
• Immunological disorder: a positive double-stranded anti-DNA test, positive anti-Sm test, positive antiphospholipid antibody or false-positive syphilis test: any one of which may indicate an autoimmune disease

Laboratory tests
In addition to using your clinical history and a physical examination to check for the classification criteria, your doctor will use laboratory tests. These may include:

• Complete blood count. This test measures the number of red blood cells, white blood cells and platelets as well as the amount of hemoglobin, a protein in red blood cells. Results may indicate you have anemia, which commonly occurs in lupus. Low white blood cell or platelet counts may occur as well.
• Erythrocyte sedimentation rate. This blood test determines the rate at which red blood cells settle to the bottom of a tube in an hour. A faster-than-normal rate may indicate a systemic disease such as lupus. The sedimentation rate is not specific for any one disease but may be elevated if you have lupus, another inflammatory condition or an infection.
• Kidney and liver assessment. Blood tests can assess how well your kidneys and liver are functioning because lupus can affect these organs.
• Urinalysis. An examination of a sample of your urine may show an increased protein level or red blood cells in the urine, which may occur if lupus has affected your kidneys.
• Antinuclear antibody (ANA) test. A positive test for the presence of these antibodies: produced by your immune system; indicates a stimulated immune system, which is common in lupus and other autoimmune diseases. A positive ANA doesn't always mean that you have lupus, however. ANA levels can be elevated if you have an infection or if you're taking certain medications. If you test positive for ANA, your doctor may advise more specific antibody testing and refer you to a rheumatologist, a doctor who specializes in musculoskeletal and autoimmune disorders such as arthritis or lupus.
• Chest X-ray. An image of your chest may reveal abnormal shadows that suggest fluid or inflammation in your lungs. It may also show an enlarged heart as a result of a buildup of fluid within the pericardium (pericardial effusion).
• Electrocardiogram (ECG). This test measures the pattern of electrical impulses generated in your heart. It can help identify irregular rhythms or damage.
• Syphilis test. Strange as it may seem, a false-positive result on a syphilis test can indicate anti-phospholipid antibodies in your blood, another indication of lupus. The presence of anti-phospholipid antibodies has been associated with an increased risk of blood clots, strokes and recurrent miscarriages.

Complications

With treatment, most people with lupus can live active, healthy lives. Without treatment, complications from lupus can be life-threatening. These complications include:

• Kidneys. Lupus can cause serious kidney damage, and kidney failure is one of the leading causes of death among people with lupus. Kidney problems are often symptomless, but can be detected through routine urine and blood tests, and if needed, a kidney biopsy. A blood test called serum creatinine level is used to check kidney function.
• Central nervous system. If your central nervous system is affected by lupus, you may experience headaches, dizziness, memory problems, behavior changes, even seizures.
• Blood and blood vessels. Lupus may lead to blood problems, including anemia and increased risk of bleeding or blood clotting. It can also cause inflammation of the blood vessels (vasculitis).
• Lungs. Having lupus increases your chances of developing an inflammation of the chest cavity lining (pleurisy) that can make breathing painful. You may also be more susceptible to a noninfectious form of pneumonia.
• Heart. Lupus can cause inflammation of your heart muscle (myocarditis and endocarditis), your arteries (coronary vasculitis) or heart membrane (pericarditis). Having lupus also greatly increases your risk of cardiovascular disease and heart attacks. Controlling high blood pressure and high blood cholesterol, not smoking, and getting regular exercise are essential to help reduce the risk of heart disease.
• Infection. People with lupus are vulnerable to infection because both the disease and its treatments corticosteroid and cytotoxic drugs, in particular  affect the immune system. And in a vicious cycle, infection can bring on a lupus flare, increasing the risk of infection even more.
• Cancer. Having lupus appears to increase your risk of cancer, especially non-Hodgkin's lymphoma, which affects the lymph system, lung cancer, and liver and bile duct cancers. Immunosuppressant drugs that are sometimes used to treat lupus can also up the risk of cancer.
• Bone tissue death (avascular necrosis). This occurs when the blood supply to a bone diminishes, often leading to tiny breaks in the bone and eventually to the bone's collapse. The hip joint is commonly affected, although avascular necrosis can occur in other bones as well. Avascular necrosis can be caused by lupus itself or by high doses of corticosteroids used to treat the disease.

Risks of complications for younger women
Lupus poses special health risks for women during their childbearing years. Complications may include:

• Increased risk of miscarriage. The risk is usually highest early or late in pregnancy, but careful planning and treatment can minimize the chance of a miscarriage in women with lupus.
• Increased risk of complications during pregnancy. Women with lupus are more likely to experience a flare during pregnancy. They're also at greater risk of high blood pressure, diabetes, kidney problems and preterm birth.
• Limited birth control options. Women with lupus may not tolerate birth control pills well, and intrauterine devices (IUDs) pose an increased risk of infection.