Chapter 289 SYSTEMIC LUPUS ERYTHEMATOSUS

Peter H. Schur

Systemic lupus erythematosus (SLE) is a disease of unknown cause that may produce variable combinations of fever, rash, hair loss, arthritis, pleuritis, pericarditis, nephritis, anemia, leukopenia, thrombocytopenia, and central nervous system (CNS) disease. The clinical course is characterized by periods of remissions and acute or chronic relapses. Characteristic immune abnormalities, especially antibodies to a number of nuclear and other cellular antigens, develop in patients with SLE. The diagnosis is facilitated by determining whether the patient has 4 of the 11 clinical and/or laboratory criteria developed for the classification of SLE(Table 289-1).

EPIDEMIOLOGY.

SLE can occur at any age but has its onset primarily between ages 16 and 55. It occurs more frequently in women. In children, the female-male ratio is 1.4 to 5.8:1; in adults, it ranges from 8:1 to 13:1; and in older individuals, the ratio is 2:1. The prevalence of SLE is estimated to be between 4 and 250 cases per 100,000 population. In theUnited States, the highest incidence is among Asians inHawaii, blacks, and certain Native Americans (Sioux, Crow, Arapahoe). The risk of SLE developing in a black American female has been estimated to be 1:250. The prevalence is about the same worldwide; the disease appears to be common inChina, in Southeast Asia, and among blacks in the Caribbean, but is seen infrequently in blacks inAfrica. Limited observations suggest that the incidence of discoid lupus erythematosus is the same as that for SLE.

ETIOLOGY.

The cause of SLE remains unknown, although many observations suggest a role for genetic, hormonal, immune, and environmental factors. The evidence for a genetic role is summarized inTable 289-2. Some of these genetic marker associations are found more frequently in SLE patients of different races and ethnicities. It has been calculated that at least four genes are involved in predisposing individuals to SLE. Each gene presumably affects some aspect of immune regulation, protein degradation, peptide transport across cell membranes, immune response, complement, the reticuloendothelial system (including phagocytosis), immunoglobulins, apoptosis, and sex hormones. Thus combinations of dissimilar gene defects may result in distinct abnormal responses and produce separate pathologic processes and different clinical expression.

The evidence for hormonal abnormalities is based primarily on the observation that SLE is much more common among women in their childbearing years. In addition, SLE has been observed in some males with Klinefelter's syndrome, and some abnormalities of estrogen metabolism have been noted in both men and women with SLE. However, the clinical expression of SLE is the same in men and women. Furthermore, a lupus-like disease ofNew Zealandmice is more common and more severe and has an earlier onset in females--and is ameliorated by oophorectomy or treatment with male hormones. However, in other strains of mice with a lupus-like disease, this gender difference is not noted.

Numerous immune abnormalities occur in patients with SLE, the etiology of which remains unclear; nor do we know which are primary and which are secondary. Some of these immune defects are episodic, and some correlate with disease activity. SLE is primarily