Slicing and dicing myositis for cures and prevention

Abstract

Myositis is a group of conditions that vary greatly in risk factors, clinical manifestations, laboratory markers, presumed pathogenetic mechanisms, treatment responses and prognoses. Approaches to divide myositis into mutually exclusive and stable phenotypes are being considered, but are we thinking comprehensively enough in our attempts at classification?

Figure 1.. The elemental disorder hypothesis.

Disease phenotypes as currently classified (i.e., PM, polymyositis; DM, dermatomyositis; IBM, inclusion body myositis, others) are heterogeneous and composed of multiple elemental disorders (centre circles). Elemental disorders are defined as mutually exclusive and stable phenotypes that result from the interaction of the necessary and sufficient genetic (outer ring of boxes) and environmental (middle ring of hexagons) risk factors, in the relative absence of protective factors, through a distinct pathogenic mechanism (inner circle of triangles). For some elemental disorders, multiple genes are required (indicated by arrows), and for others, multiple environmetnal exposures are needed to induce the mechanisms that lead to elemental disorders. Protective genetic, environmental or mechanistic factors (indicated by an X), can prevent progression to disease in otherwise permissive circumstances.