Circulating plakin autoantibodies in a patient with erythema multiforme major: are they pathogenic or a manifestation of epitope spreading?

Erythema multiforme is a well-recognised entity but its pathogenesis remains elusive. Theories hypothesise a cell-mediated immune pathogenesis, however recent case reports have observed autoantibodies to the plakin family of proteins, suggesting a role for the humoral immune system. We present a case of erythema multiforme major with circulating desmoplakin autoantibodies in a 36-year old woman who was previously diagnosed with pemphigoid gestationis. The close correlation between the concentration of these autoantibodies and the severity of clinical disease strongly suggests a pathogenic role in her disease. As previous case reports have proposed, these autoantibodies may be directly pathogenic. Alternatively, the epiphenomenon of epitope spreading must be considered in the subset of patients with erythema multiforme major.