The sensitivity and specificity of such findings are limited. With respect to “muscle enzymes”,

only the measurement of serum creatine kinase (sCK) activity is indicated in clinical practice. There is no longer any value in measuring other enzymes, such as aldolase. It must be remembered that AST and ALT are muscle as well as liver enzymes–that they are measured so frequently in routine clinical practice means that their increase may be the first pointer to a muscle disease, Metformin in vivo but they have no advantage over sCK. sCK is often increased in the inflammatory myopathies, and monitoring its fall in response to treatment is undoubtedly helpful. But it is not invariably raised in active disease, either before treatment is initiated, or during relapse when on treatment. In summary, the nearest that we have to any form of gold standard is the immunopathological study of muscle. However, even that has limitations. To

demand the demonstration of such changes may hamper both routine clinical practice and research. Specific changes may be absent simply due to the vagaries of sampling. The same pathological changes may be seen in very different clinical settings. Useful classification systems thus depend upon a combination of clinical, pathological and other laboratory features. As with many areas of myology, historical description of myositis dates back two centuries, but what can be considered the modern era started only in the 1950s–a period when clinicians first made rigorous attempts to classify the different forms of muscle disease and new muscle biopsy staining techniques were being developed. Eaton reported on 41 cases, only including clinical, neurophysiological Src inhibitor and pathological findings [5]. His cases included many with DM or scleroderma. Walton and Adams published a monograph (“Polymyositis”) in which

they reviewed the literature and reported detailed clinical and laboratory findings in 40 patients [6]. As was to be the case for another 30 years they considered DM and PM to be essentially the same, differentiated only by the presence or absence of a rash. Even without a rash they noted that PM could be acute, but also that chronic PM was difficult to distinguish clinically and sometimes pathologically from the dystrophies. The relationship with neoplasia was “sufficiently clear to indicate that a careful search should be made for malignancy in any patient suffering from DM or PM”. They also noted the close relationship with collagen disease–“Sometimes the symptoms and signs of muscle disease are predominant, but in other cases they are obscured by skin changes or the manifestations of an associated collagen disease. Even when the muscle weakness is predominant there may be features such as the Raynaud phenomenon, localised scleroderma of the hands or rheumatoid arthritis…”. Their clinical classification is given in Box 1. As will be seen, it is remarkable how similar this looks to all future attempts at reclassification. 1.