Pathogenesis of cutaneous lupus erythematosus

Antibody-dependent mechanisms of tissue damage are the principle mechanism of disease in systemic and cutaneous lupus erythematosus. Antibody-dependent mechanisms of keratinocyte damage appear to be a primary pathogenetic factor in all forms of papulosquamous cutaneous lupus. Photosensitive papulosquamous lupus syndromes, such as subacute cutaneous LE, neonatal LE, "ANA-negative" LE, and complement-deficient LE are all strongly associated with antibodies to the ribonucleoprotein SSA. Evidence is accumulating that antibodies to SSA (and perhaps to SSB) induce antibody-dependent cell-mediated cytotoxicity (ADCC) of basal keratinocytes in all of these lupus syndromes. Evidence is also growing that autoantibodies in cutaneous LE syndromes are directly involved in disease pathogenesis, and are not simply markers of disease subsets. The relationship of the photosensitive anti-SSA-associated LE syndromes to more classical discoid LE or to acute papulosquamous LE in SLE patients remains to be studied. In both discoid LE and acute LE, basal keratinocyte damage can be seen, just as in the anti-SSA-associated photosensitive LE syndromes, but other antigen-antibody systems may be involved in initiating keratinocyte damage, or other cytotoxic mechanisms may produce keratinocyte damage characteristic of these syndromes.