Polymyositis, invasion of non-necrotic muscle fibres, and the art of repetition

The dispute

The idiopathic inflammatory myopathies are a group of heterogeneous disorders characterised by acquired progressive muscle weakness and inflammatory infiltrates in skeletal muscle tissue. The three main disorders in this group are dermatomyositis, polymyositis, and inclusion body myositis. These diseases differ strongly from each other, both clinically and pathophysiologically. Dermatomyositis seems to be a humorally mediated angiopathy resulting in myositis and a typical dermatitis.1 Polymyositis is traditionally seen as an inflammatory myopathy mediated by cytotoxic T cells, which can occur in the context of another inflammatory connective tissue disease such as systemic sclerosis.1 Inclusion body myositis, which is seen mainly in elderly people and is clinically characterised by slowly progressive asymmetric muscle weakness, is thought to be a degenerative myopathy with secondary inflammation.2 3

Diagnosing dermatomyositis, polymyositis, or inclusion body myositis depends on a combination of clinical characteristics, results of laboratory investigations (including levels of muscle associated enzymes, serology, electromyography, and muscle biopsy), and responses to treatment. Only rarely are all typical features of a disease present simultaneously, and the correct diagnosis may only become apparent over time. Dermatomyositis and polymyositis are, unlike inclusion body myositis, multi-specialty disorders, and patients with these diseases are treated by rheumatologists, neurologists, dermatologists, and specialists in internal medicine.

The diagnoses of dermatomyositis and inclusion body myositis are straightforward, but diagnosing polymyositis is controversial. Over the past year, a dispute, primarily between rheumatologists and neurologists, has erupted over the diagnostic criteria for polymyositis. Rheumatologists tend to rely on clinical signs, symptoms, and serology, whereas neurologists rely more on histopathology in order to exclude other myopathies. This dispute was recently aired in the Lancet by a group of rheumatologists commenting on a review article on polymyositis and dermatomyositis.1 4 Another example is an article accompanied by an editorial, and the correspondence these elicited, published in Neurology in which the authors stated that polymyositis hardly exists.5^–9

While rheumatologists usually use the Bohan and Peter criteria for polymyositis,10 neurologists feel a need to confirm the diagnosis, and to exclude other myopathies, by muscle biopsy. In their view, polymyositis is histologically characterised by the presence of endomysial inflammatory infiltrates consisting of CD8 T cells invading non-necrotic muscle fibres that express major histocompatibility complex class I molecules on the sarcolemma, as shown by the criteria proposed in the recent Lancet review.1

The history examined

To solve this dispute, we not only need rheumatologists and neurologists to understand each other's viewpoint, but we also need to identify the source of the dispute, preferably from a historical perspective. We therefore examined the historical background and validity of the histopathological definition of polymyositis by studying the medical literature in a structured manner.

We started with the recent Lancet article on dermatomyositis and polymyositis.1 The authors write “in polymyositis, multifocal lymphocytic infiltrates surround and invade healthy muscle fibres” and provide six references to support this statement: four review articles and two book chapters (see figure).^w1-w6 We then studied the four reviews (the book chapters did not contain primary records or original data). All these reviews mention the presumed histological feature of polymyositis, and three of them provide references for this statement. In total 20 references are provided, including three of the initial six references.11^–14 ^{w1 w3 w5 w7-w17}

Polymyositis is histopathologically characterised by cellular inflammatory infiltrates with invasion of non-necrotic muscle fibres

Results of reference search to find original data to support the statement “in polymyositis, multifocal lymphocytic infiltrates surround and invade healthy muscle fibres” made by Dalakas et al (numbers refer to references)

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Examination of all journal articles resulted in our being referred to several other articles and book chapters. In total, we were referred to 205 references in order to find the original source of the statement that polymyositis is characterised by invasion of nonnecrotic muscle fibres. Several of the references refer to each other, resulting in 28 original references.11^–14 ^w1-w24 Only four of these references provide original data.11^–14 The other 24 references are review articles (14), books (8), abstracts (1), or non-existent (1). It was remarkable that 19 of the 28 identified references were from just two research groups.12 14 ^{w1 w3 w5-w8 w10 w12-w15 w17-w19 w22-w24}

Conclusions

Several conclusions can be drawn from our review of the medical literature: some are applicable to medicine in general and some to medical literature, and some are important for doctors interested in myositis.

Firstly, an observation made in the past sometimes escapes reassessment of its validity even if recent advances in medical knowledge warrant such a reassessment. This especially seems to be the case if conclusions are cited in review articles and subsequent review articles cite only the first review article instead of the original publication. Through repetition, conclusions—even though they have become invalid over time—become embedded in the medical literature, the pathophysiological concepts of disease, and the minds of clinicians and researchers. Using review articles as references can lead to authors not familiarising themselves with the original publications. The use of review articles as references is strongly encouraged by the editorial limitations placed on the number of references that authors can provide for a manuscript. By lifting the restriction on the number of references, medical journals will probably become slightly thicker, but their quality might increase significantly.

Secondly, some authors have a strong tendency to refer to themselves. Of the 28 references we found in our literature search, 68% were from only two research groups, one of them not providing any original data. This latter group referred to their own work 29 times, all being review articles and book chapters.^{w1 w5-w8 w13-w20 w22 w23} Such repetition affects the opinion not only of readers but also of the authors. By repeating oneself, one can become convinced of the validity of one's own statement. Furthermore, admitting that one's conclusions are incorrect becomes practically impossible because credibility and ego are at stake. Editorial boards of medical journals should be more critical with regard to the use of references, especially because they have limited their number. References should be checked for their validity, and articles (especially review articles) should not unnecessarily refer to other review articles and book chapters but mainly to the original publications. We require detailed descriptions of the methods used for laboratory experiments, but apparently we feel no need for a detailed description of the sources of statements on pathophysiology and concepts of disease.

As for the field of myositis, invasion of non-necrotic muscle fibres by endomysial inflammatory infiltrates is a feature of inclusion body myositis and possibly of polymyositis, but in the latter disease this still needs to be confirmed. Diagnostic criteria in which the presence of this histopathological feature is a prerequisite for a diagnosis of polymyositis are erroneous and are not based on solid original data.

Myositis is a true multi-specialty disorder, and it must be recognised as such by all who deal with myositis patients. The current dispute can be turned into a positive development if we recognise that we now need to bridge the gap between dermatologists, internists, rheumatologists, and neurologists. Internationally agreed criteria, acceptable to all, need to be developed. The recent ENMC (European Neuro Muscular Centre) workshop on idiopathic inflammatory myopathies is a first step in that direction.17 Hopefully, this initiative will be followed so that we finally can agree on diagnostic criteria for these enigmatic diseases.