Uncertainties in the pathogenesis of adult dermatomyositis

Dermatomyositis is an inflammatory disorder of muscle affecting both children and adults. The pathogenesis of adult dermatomyositis is reviewed here, with particular attention to gaps and uncertainties in our current understanding of this disease, in order to focus attention on the outstanding research questions with regard to disease mechanisms.

The conceptual model of the pathophysiology of dermatomyositis has been based on work extending back over at least 35 years, with important findings related to the deposition of membrane attack complex, the character of the inflammatory infiltrate, and the primacy of capillary abnormalities established over 10 years ago. The lack of significant additions to the understanding of this disease over the past few years suggests a state of contentment with current knowledge. Accordingly, we emphasize the uncertainties of this knowledge and the need for re-addressing some of its basic tenets.

Although evidence remains strong that dermatomyositis is a disorder with an early involvement of the capillaries, the concept that it results from an antibody-mediated attack upon the endothelium is uncertain. It is not clear whether membrane attack complex is activated by antibody-dependent or independent means, whether or not intramuscular B cells are antigen specific and synthesize significant quantities of antibodies, whether the presence of tubuloreticular inclusions precedes, follows, or is independent of membrane attack complex deposition, what is the mechanism of perifascicular atrophy, and what is the relationship of dermatomyositis to systemic lupus erythematosus.