A positive ANA test alone is not sufficient to establish the diagnosis. Survival rates in SLE are much better today than 50 years ago. Morbidity comes from disease itself, as well as a greater risk of cancer, infections, cardiovascular disease, and osteoporosis.

ETIOLOGY AND PATHOGENESIS

The presence of a large number of autoantibodies against self-constituents indicates a failure of self-tolerance. Several genes have been associated with SLE susceptibility, each of them displaying a small effect, suggesting the need of gene-gene and/or geneenvironment interactions. Environmental factors, both external (e.g., infectious agents, exposure to ultraviolet light) and internal (e.g., gender and hormonal profile) may influence disease manifestations. The end result is a defective clearance of chromatin material, which triggers an immune response, facilitated by defective elimination of self-reactive B lymphocytes in the bone marrow.

Family members of patients with SLE have an increased risk of developing SLE. As many as 20% of unaffected first-degree relatives reveal antibodies, and there is a higher rate of concordance (>20%) in monozygotic twins when compared with dizygotic twins (1%-3%).

Almost 80% of SLE patients are women. High estrogen levels have been associated with increased number of autoreactive B lymphocytes, a predominantly Th2 response, and increased antibody production.

CLINICAL PRESENTATION

Manifestations of SLE are protean and can affect any organ system. Typically, the patient is a young woman with some, or more, of the following features: a butterfly rash over the face, fever, joint pain and swelling, pleuritic chest pain, and photosensitivity. It is important to note that many patients, especially women between 20 and 40 years of age, present to their internist or rheumatologist with fatigue, arthralgias, myalgias, slight erythema after sun exposure, light-headedness, and fatigue along with a positive ANA test. These patients feel disturbed by bright lights, which irritate them and make them feel light-headed and cause a brief transient rash. A careful history in these patients will elicit a number of other stress-related symptoms, along with depression, anxiety, and poor sleep. These patients suffer from fibromyalgia and are often misdiagnosed as having SLE. It is important therefore to stress that the diagnosis of SLE relies, besides the findings of a positive ANA test, on objective findings of SLE-related organ involvement, such as (but not limited to): a persistent rash triggered by sun exposure that shows features of interface dermatitis on biopsy, objective swollen joints, objective evidence of pleuritis and pericarditis, and abnormal urine sediment suggestive of glomerular damage.

Mucocutaneous Manifestations. Mucocutaneous involvement is almost universal in SLE. Cutaneous lesions can be further classified as acute, subacute, and chronic lesions. One of the most widely recognized features of lupus is the malar or butterfly rash that can last for several weeks after brief sun exposure. Discoid lupus erythematosus (DLE) lesions are chronic and occur in 25% of patients with SLE but may also occur in the absence of other clinical features of SLE. Patients with isolated DLE have a 10% risk of developing SLE. DLE lesions expand slowly and leave depressed central scars. Other rashes seen in SLE include lupus profundus, lupus tumidus, and livedo reticularis.

Hair loss occurs in most patients with lupus and may involve the scalp, eyebrows, eyelashes, beard, and body hair. Scarring alopecia is a complication of DLE.

Musculoskeletal Manifestations. Diffuse arthralgias and myalgias are extremely common in SLE patients. Some develop Jaccoud arthropathy, a reducible arthropathy due to capsular laxity, involving the same joints as rheumatoid arthritis.

Isolated monarthritis should prompt consideration of other causes such as osteoarthritis, septic arthritis, or avascular necrosis.