MENSES AND PREGNANCY.

Some patients think that their SLE flares with menses. Some patients have heavy menses, which may reflect antiphospholipid antibodies, the use of NSAIDs or steroids, or hormonal abnormalities. Lupus often becomes less active after menopause.

Approximately 25 to 30% of SLE pregnancies result in miscarriage; overall fetal loss approaches 35%, and patients are more likely to have a premature delivery. Increased fetal mortality is more likely (three times) to occur in the presence of major organ involvement, especially renal disease. Antiphospholipid antibodies predispose to recurrent midtrimester fetal loss. Preeclampsia is a frequent complication and is difficult to distinguish from a lupus flare.

Neonatal lupusis a rare condition characterized by typical skin lesions shortly after exposure to UV light in a nursery. The rash generally clears within months; SLE rarely develops later in life. Sera from the infants (and their mothers) have antibodies to Ro andLa.The risk of neonatal lupus developing is about 1 to 5% in mothers with anti-Ro antibodies. If the mothers have other specific antibodies, hemolytic anemia or thrombocytopenia may ensue. Congenital heart block is very rare but is associated with anti-Ro, anti-La, and HLA-DR3 in the mother.

DRUG-INDUCED LUPUS.

Some medications such as sulfonamides, penicillin, and oral contraceptives may exacerbate lupus. Hydralazine and procainamide can induce a lupus-like disease, especially in those who are slow acetylators and/or HLA-DR4+. Other medications may possibly induce lupus or just ANAs, but the evidence is less convincing(Table 289-6). The symptoms and serology of drug-induced lupus are quite similar to those of SLE, with notable differences(Table 289-7). Furthermore, the disease tends to be mild, is not life threatening, and is reversible. ANAs develop in between 50 and 100% of patients taking procainamide, whereas lupus develops in only 25% of those with ANAs. Therefore, the presence of a positive ANA test does not preclude continued use of these medications. The mechanism for drug-induced lupus is unknown.

DIFFERENTIAL DIAGNOSIS.

SLE usually begins with the non-specific or specific symptoms and signs listed inTable 289-4, but can also first present with easy bruising, splenomegaly, peripheral neuritis, myoendocarditis and endocarditis, interstitial pneumonitis, aseptic meningitis, or a positive Coombs' test. The presence of anemia (71%), leukopenia (56%), thrombocytopenia (11%), proteinuria, hematuria, pyuria, azotemia, hypergammaglobulinemia, immune complexes, cryoglobulins, antiphospholipid antibodies, and the Biologic False-Positive Serologic Test for Syphilis should also make one suspect SLE. On first examination, patients are often thought to have other connective tissue, rheumatic, or immune disorders(Table 289-8). Children tend to have more renal disease; older-onset patients have less rash, arthritis, and renal disease but more sicca; and males tend to have more serositis and less arthritis.

Most physicians use the American Rheumatism Association criteria for the classification of SLE (seeTable 289-1)to help make a diagnosis--it should be noted that these criteria were developed for theclassificationof SLE, not for individual diagnoses. The sensitivity and specificity of these criteria are approximately 96% when compared with other rheumatic syndromes when patients

have four of these criteria; however, their predictive value is less. The diagnosis in patients with three criteria should be "probable" SLE, and in those with two criteria, "possible" SLE.

The ANA test is a useful screening test. If the test is negative, the patient has a 0.14% probability of having SLE. A positive test has a 15 to 35% predictive value for SLE (seeTable 289-3)--seeTable 289-9for a list of other diseases associated with a positive ANA test. Low titers (i.e., 1/40 to 1/80) have less predictive value. If the ANA test is positive, it is useful to test for antibodies to double-stranded DNA and the Sm, RNP, Ro (SS-A), and La (SS-B) nuclear RNA proteins. Their sensitivity, specificity, and predictive value for SLE (as well as for some other specific ANAs) are detailed inTable 289-3.

Determining serum complement levels is also often helpful, both diagnostically and to assess lupus activity. Complement levels are rarely depressed in other rheumatic diseases. Levels of CH50 (total hemolytic complement), C4, and C3 tend to parallel or even precede activity, especially renal disease.