Systemic lupus erythematosus: clinical features and pathogenesis

Systemic Lupus Erythematosus (SLE) or also simply called Lupus is an inflammatory connective tissue disease which is manifested in variable signs and symptoms. This condition may affect multiple organ systems with immune complexes and a large array of autoantibodies, particularly antinuclear antibodies (ANAs). There is an excessive deposition of immune complexes and the resultant organ-specific inflammatory response found in the blood vessels, kidneys, connective tissue, and skin. It is characterized by unpredictable exacerbations and remissions with variable clinical manifestations.

There are also genetic factors that play a role in the development and expression of SLE and environmental factors may also trigger the disease in genetically susceptible hosts. In a study done by GE Eroglu and PF Kohler, entitled Familial systemic lupus erythematosus: the role of genetic and environmental factors, an association between SLE and HLA-a, B, C antigens was found. A significant association with HLA-DR2 in white subjects with SLE was also found, but the most striking finding was that HLA sharing was increased among the affected members, that could imply genetic similarities. In their findings seven of 14 sibling pairs (50%) who had concordant SLE were HLA identical as opposed to an expected 25%. There is also another interesting finding in their stud which concludes that 15/18 (83%) patients with SLE and 11/22 (50%) consanguineous relatives had LCA, while 1/9 (11%) spouses, and 2/42 (5%) healthy controls had these antibodies.

The cause of SLE is still unknown. This is an immunologic disorder with the production of autoantibodies. There are different triggering factors of this disease which includes sunlight exposure. Specific medications could also trigger SLE. They initiate immune response in individuals who are susceptible to develop SLE. The two most common of these are Hydralazine and Procainamide. Some anticonvulsants, antiemetics, antituberculars and antibiotics could be among those that trigger this disease.

The pathophysiology of this disease is not completely known. Studies show that the production of abnormal antibodies by B cells remains the hallmark sign of lupus erythematosus. Such autoantibodies like antidouble-stranded DNA and anti-Smith, are very specific for systemic lupus erythematosus. Anti-RNP, anti-Rho and anti-La, are also present in other autoimmune diseases. Whether the B cells themselves are intrinsically abnormal is a subject of current research. One of the underlying deficiencies in SLE may be emphasized on apoptosis, or programmed cell death; cellular antigens exposed during apoptosis incite an immune response

Laboratory studies for SLE include Individual antinuclear antibody tests. A high titer of double-stranded DNA antibodies is the most specific test in active SLE. Most SLE patients have an 1:80 or higher titer. Anti-Smith antigen is observed in 25% of patients with SLE overall, with 10-20% whites and 30-40% blacks and Asians and Lupus erythematosus (LE) preparation is found in most patients with active SLE.

Treating the active phase of the disease without allowing the treatment itself to cause long-term damage to the patient is the major challenge for doctors. As a result of this physicians are now less hesitant to use immunosuppressive drugs such azathioprine (Imuran) or cyclophosphamide (Cytoxan). Treatment for active systemic lupus erythematosus, on the other hand, depends on the organ systems involved and disease severity; this includes a combination of drugs.

Nonsteroidal antiinflammatory drugs are used to reduce inflammation and pain in muscles, joints, and other tissues. These may include aspirin, ibuprofen (Motrin), naproxen (Naprosyn), and sulindac (Clinoril). The most common side effects are stomach upset, abdominal pain, ulcers, and even ulcer bleeding. Corticosteroids are more potent than NSAIDs in reducing inflammation and restoring function in active disease, specially when internal organs are involved. The disadvantage of this is when it is given in high doses over prolonged periods. Physicians should monitor the activity of the disease in order to use the lowest doses that are safe. Side effects include weight gain, thinning of the bones and skin, infection, diabetes, facial puffiness, cataracts, and death (necrosis) of large joints. Another drug used in the treatment of SLE is Hydroxychloroquine (Plaquenil), an antimalarial medication. It is effective for SLE patients with fatigue, skin, and joint disease. Side effects 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.