Returning to DM, PM and allied IIM, insight into pathogenic mechanisms (but not into specific aetiologies) came from the outstanding immunopathological studies of Arahata and Engel

in the 1980s [15], [16], [17], [18], [19] and [20]. In very brief summary, their detailed analysis of mononuclear cell subsets and related phenomena indicated that despite all of the clinical and superficial pathological similarities, PM and DM have fundamentally different efferent immune mechanisms (but as noted no clues as to the afferent process–i.e. what triggers these events). DM is due to complement-mediated mechanisms that lead to loss of intramuscular capillaries, and is thus a form of microangiopathy. PM on the other hand is related to T-cell-mediated cytotoxicity. It would

PI3K inhibitor be incorrect to say that all of the immunopathological observations have been fully explained. For example, it is not clear why in DM there is widespread up-regulation of MHC-1 expression. In PM such expression is a pre-requisite to T-cell-mediated cytotoxicity, but that does not occur in DM. In everyday clinical practice it is not always easy to firmly classify the biopsy findings as PM or DM, and clinical Selleckchem FRAX597 correlation is vital. As discussed earlier, this may simply reflect the vagaries

of sampling. On the other hand, the not infrequent lack of specific pathological changes has led some to conclude that PM is an overdiagnosed entity (see below) [21]. A review in 2003 summarised developments in the field and emphasised the central importance of the immunopathological over findings [4]. This viewpoint was challenged with the suggestions that immunopathological testing was not widely available, that muscle biopsy had low sensitivity, and that there was no evidence of the performance characteristics of the proposed new diagnostic criteria [22]–implicit in the latter was that the long-used Bohan and Peter criteria were “clinically practical, sensitive, specific”, and that any new criteria should be compared to those and be “derived from well-designed, prospective, comprehensive studies”. It was an obvious irony that the Bohan and Peter criteria had themselves not been derived in such a fashion. Dalakas and Hohfeld responded that of course the biopsy immunopathological techniques are relatively simple and widely available, and that the Bohan and Peter criteria had been a “source of constant error”. Elements of the dispute linger, possibly in part because rheumatologists, immunologists and myologists are seeing somewhat different populations of patients.