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ARTICLES: M. F.G. van der Meulen, I. M. Bronner, J. E. Hoogendijk, H. Burger, W. J. van Venrooij, A. E. Voskuyl, H. J. Dinant, W. H.J.P. Linssen, J. H.J. Wokke, and M. de Visser Polymyositis: An overdiagnosed entity Neurology 2003; 61: 316-321 [Abstract] [Full text] [PDF]

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Polymyositis: An overdiagnosed entity

Frederick W. Miller, L.G. Rider, P.H. Plotz, S.B. Rutkove, A. Pestronk, R.L. Wortmann, I.E. Lundberg, Z. Argov, D.A. Isenberg, D. Lacomis, C.V. Oddis   (25 November 2003)

Polymyositis: An overdiagnosed entity

Walter G. Bradley, DM, FRCP   (25 November 2003)

Polymyositis: An overdiagnosed entity

Gerald J.D. Hengstman, Baziel G.M. van Engelen   (25 November 2003)

Reply from authors

Marjon FG van der Meulen, Irene M. Bronner, Jessica E. Hoogendijk, Huib Burger, Walther van Venrooij, Alexandre E. Voskuyl, Huib J. Dinant, Wim H.J.P. Linssen, John H.J. Wokke, Marianne de Visser   (25 November 2003)

Polymyositis: An overdiagnosed entity 25 November 2003
Frederick W. Miller, Chief, Environmental Autoimmunity Group National Institues of Health, 9000 Rockville Pike, NIH Bldg. 9, Room 1W 107, MSC 0958, Bethesda, MD, L.G. Rider, P.H. Plotz, S.B. Rutkove, A. Pestronk, R.L. Wortmann, I.E. Lundberg, Z. Argov, D.A. Isenberg, D. Lacomis, C.V. Oddis Send Correspondence to journal: Re: Polymyositis: An overdiagnosed entity millerf{at}mail.nih.gov Frederick W. Miller, et al.	The classification of the inflammatory and immune myopathies is a complex issue. While the Bohan and Peter criteria [1] have been used for almost 30 years, recent findings have brought their validity into question. For this reason, we read with interest the study by MFG van der Meulen et al [2] describing a new pathology-driven categorization of these diseases. A biopsy-based approach, however, is not necessarily straightforward. Because the pathology of the inflammatory myopathies is not always homogeneous, such an approach requires extensive study to determine which pathologic criteria are useful and reproducible for the diagnoses of different immune and inflammatory myopathic syndromes. A shortcoming of the van der Meulen et al study is the lack of evidence to suggest that their criteria perform any better than the Bohan and Peter criteria in determining diagnosis, treatment and prognosis. Their new scheme results in polymyositis being condemned to an uncertain status and being replaced with the less-than-helpful categories of “unspecified myositis” and “possible myositis.” The authors’ arguments would be more compelling if they demonstrated that their proposed classifications were more clinically useful than prior ones (i.e., that patients initially classified as polymyositis or dermatomyositis by Bohan and Peter criteria and who did not respond to treatment met their criteria for unspecified myositis). Their proposed classification criteria would leave many myositis patients diagnostically adrift and potentially excluded from receiving effective treatment. The International Myositis Assessment and Clinical Studies Group (IMACS) is a multidisciplinary coalition of over 100 neurologists, rheumatologists, dermatologists and other specialists who care for adults and children with inflammatory myopathies. Currently, the IMACS consensus is that probable or definite Bohan and Peter criteria are appropriate for distinguishing polymyositis from dermatomyositis and enrolling adult subjects in trials as long as the muscle biopsy criteria are met. Bohan and Peter criteria actually incorporate the exclusion of other diagnoses1, which today include pathologic, genetic or other studies in cases suggestive of inclusion body, hereditary or other myopathies. We agree with the conclusion of the accompanying editorial [3]: prospective studies, using up-to-date comprehensive evaluations, including pathology, are needed to redefine the immune myopathies and related systemic disorders in clinically useful ways to address their diagnosis, incidence, associated features and prognosis. To this end, we encourage more research in this area. We hope that other neurologists will join or collaborate with IMACS so that together we can move forward in improving the diagnosis and treatment of these syndromes. References 1. Bohan A, Peter JB. Polymyositis and dermatomyositis. N Engl J Med. 1975;292:344-347, 403-07. 2. Van Der Meulen MF, Bronner IM, Hoogendijk JE et al. Polymyositis: An overdiagnosed entity. Neurology. 2003;61:316-321. 3. Amato AA, Griggs RC. Unicorns, dragons, polymyositis and other mythical beasts. Neurology 2003;61:288-289
Polymyositis: An overdiagnosed entity 25 November 2003
Walter G. Bradley, DM, FRCP, Professor and Chairman, Dept. Neurology Univ. of Miami School of Medicine, Dept. of Neurology, Miami, FL 33101-6960 Send Correspondence to journal: Re: Polymyositis: An overdiagnosed entity wbradley{at}med.miami.edu Walter G. Bradley, DM, FRCP	Van der Meulen et al [1] reported the retrospective analysis of 165 cases of inflammatory myopathy collected in the Netherlands from 1977 to 1998, and concluded that the application of the criteria of Bohan and Peter [2] leads to an over-diagnosis of polymyositis. They applied the criterion of Arahata and Engel [3], namely inflammatory cells infiltrating nonnecrotic muscle fibers, as the hallmark of polymyositis or sporadic inclusion body myositis [s-IBM]. They accepted the diagnosis of dermatomyositis with either typical skin changes or perifascicular muscle atrophy. If these criteria were not met, van der Meulen et al diagnosed either unspecific or possible myositis. It is worth comparing their study with the very similar retrospective analysis we published in 1975 [4] before the publication by Arahata and Engel [3] and the current epidemic of s-IBM. We required for the diagnosis of what is now more generically termed inflammatory myopathy, a typical clinical picture supported by typical findings on muscle biopsy, EMG and/or serum creatine kinase analysis. We showed that the patchy nature of the disease process resulted in not every laboratory abnormality being present in every patient. This point was not emphasized by van der Meulen et al. [1] Overall, van der Meulen et al [1] found a very similar proportion of cases with malignancy (8%) and connective tissue disease (27%) as we did. However their higher frequency of dermatomyositis can be explained by their inclusion of patients simply with perifascicular atrophy. Recalculation of the data of DeVere and Bradley [4] according to the criteria advanced by van der Meulen et al [1] indicates that their experience is in fact similar to ours [Table]. Van der Meulen et al [1] did not provide data on the severity of disease or change with treatment in their patients. In our earlier series, at presentation the average patient was unable to climb stairs, and by five years had returned to no functional impairment. [4] Van der Meulen et al [1] report that five out of nine of their patients with polymyositis later developed probable s-IBM. We have seen both cases of polymyositis and of dermatomyositis progress from treatment-responsive myositis to typical s-IBM. Case 1: A forty-five year old man with difficulty climbing stairs had MRC4- power in the quadriceps, and 5- in the biceps and tibialis anterior. The sedimentation rate was 60mm/1-hour, the serum CK was three times normal, the EMG and quadriceps muscle biopsy showed typical inflammatory myopathy. Treatment with high dose prednisone and methotrexate improved the arm strength to normal and the quadriceps to MRC5-. By age fifty, after five years of stability on treatment, the quadriceps began to deteriorate to MRC3-, and he developed the typical finger flexor weakness of s-IBM. Muscle weakness progressed to the age of fifty-eight, still with some response to prednisone, and he developed a painful peripheral neuropathy. Case 2: A forty-eight year old woman with difficulty climbing stairs had proximal upper and lower limb weakness, normal sedimentation rate and a serum CK of five times normal. Quadriceps muscle biopsy showed typical inflammatory myopathy, and the weakness cleared with high-dose prednisone and methotrexate. At age fifty-three she developed a skin rash typical of dermatomyositis. Muscle weakness relapsed whenever the immunosuppressant therapy was reduced. At age fifty-eight she developed progressive proximal weakness in the upper and lower limb partially unresponsive to increased immunosuppressant therapy. At age sixty-one she developed the typical finger flexor muscle weakness of s-IBM, and quadriceps and biceps muscle biopsies showed the typical changes of s-IBM. I believe that van der Meulen et al [1] are incorrect in concluding that polymyositis is overdiagnosed. It would be more correct to conclude that infiltration of non-necrotic muscle fibers by mononuclear cells is present in only a minority of biopsies of inflammatory myopathy; and that this criterion should not be used as a requisite for diagnosing polymyositis. References 1. Van der Meulen MFG, Bronner IM, Hoogendijk JE, et al. Polymyositis: An overdiagnosed entity. Neurology 2003;61:316-321. 2. Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). NEngl J Med 1975;292:344-347. 3. Arahata K, Engel AG. Monoclonol antibody analysis of mononuclear cells in myopathies. I: Quatitation of subsets according to diagnosis and sites of accumulation, and demonstration and counts of muscle fibers invaded by T cells. Ann Neurol 1984;16:193-208. 4. DeVere R, Bradley WG. Polymyositis: Its Presentation, Morbidity and Mortality. Brain 1975;637-666. Comparison of the findings of DeVere and Bradley [4] with those of van der Meulen et al. [1] Table
Polymyositis: An overdiagnosed entity 25 November 2003
Gerald J.D. Hengstman, Neuromuscular Centre Nijmegen, Institute of Neurology, UMC Nijmegen, Nijmegen, The Netherlands PO Box 9101, 6500 HB Nijmegen, The Netherlands, Baziel G.M. van Engelen Send Correspondence to journal: Re: Polymyositis: An overdiagnosed entity g.hengstman{at}neuro.umcn.nl Gerald J.D. Hengstman, et al.	We read the article by Van der Meulen et al with great interest. [1] The authors state that polymyositis (PM) is an overdiagnosed entity. There are several concerns that need to be addressed. Firstly, the authors formulate their own diagnostic criteria for dermatomyositis (DM) and PM. These criteria are strongly based on the criteria presented by Dalakas [2]. The Dalakas criteria have never been validated, unlike other criteria for which specificity and sensitivity are known [3]. Based on the results of their study, the authors conclude that PM is an overdiagnosed entity. However, the correct conclusion should be that the authors’ diagnostic criteria for PM are too rigid with an extremely low sensitivity. It is not the diagnosis that should be questioned but the diagnostic criteria used. Secondly, the authors stress the importance of histopathological features for the diagnosis of DM or PM. There is however, no gold standard for the diagnosis DM or PM, not even the histopathology which is illustrated by the editorial accompanying the article [4]. The diagnosis of DM or PM cannot be made based on histopathology alone, but should always include the clinical signs and symptoms and results of other additional investigations. Thirdly, the authors state that the presence of endomysial inflammatory infiltrates with invasion of nonnecrotic muscle fibers has been observed in PM and that this feature should be included in the diagnostic criteria. They then review all their myositis cases and observe that these features are rarely encountered and that nearly all cases in which these features are present are atypical steroid-resistant PM patients--in other words--probable IBM patients. What were the clinical characteristics of the “PM” patients in which the initial histological observation was made? Next, the medical scientific concept of a diagnosis exists for more than one reason. It is important for pathogenetic investigations and therapeutic intervention studies, but is also important for the clinical treatment of the individual patient. The clinical diagnosis serves as a guide to treatment and prognosis, and it is in this form that the diagnosis PM serves us very well. Finally, the authors cite us erroneously. They state that myositis specific autoantibodies (MSAs) are not useful in differentiating the myositis subtypes, including IBM. They cite our recent article in which we conclude that MSAs can aid in the differential diagnosis of the myositis subtypes by virtually excluding IBM [5]. This conclusion is clearly reflected in the subtitle of the article. Nevertheless, we would like to thank the authors for their time-consuming effort and for reminding us again of the importance of valid definitions of disease entities. Unicorns and dragons are mythological, but the problem with this study and PM is methodological. References 1. Van der Meulen MFG, Bronner IM, Hoogendijk JE, et al. Polymyositis, an overdiagnosed entity. Neurology 2003;61:316-321. 2. Dalakas MC. Polymyositis, dermatomyositis and inclusion-body myositis. N Eng J Med 1991;325:1487-1498. 3. Tanimoto K, Nakano K, Kano S, et al. Classification criteria for polymyositis and dermatomyositis. J Rheumatol 1995;22:668-674. 4. Amato AA, Griggs RC. Unicorns, dragons, polymyositis, and other mythological beasts. Neurology 2003;61:288-290. 5. Hengstman GJD, Brouwer R, Vree Egberts WTM, et al. Clinical and serological characteristics of 125 Dutch myositis patients. Myositis specific autoantibodies aid in the differential diagnosis of the idiopathic inflammatory myopathies. J Neurol 2002;249:69-75.
Reply from authors 25 November 2003
Marjon FG van der Meulen, University Medical Center Utrecht, dept. Neurology Heidelberglaan 100, 3584 CX Utrecht, The Netherlands, Irene M. Bronner, Jessica E. Hoogendijk, Huib Burger, Walther van Venrooij, Alexandre E. Voskuyl, Huib J. Dinant, Wim H.J.P. Linssen, John H.J. Wokke, Marianne de Visser Send Correspondence to journal: Re: Reply from authors m.f.g.vdMeulen{at}neuro.azu.nl Marjon FG van der Meulen, et al.	We thank Drs Miller et al., Bradley, and Hengstman and van Engelen for their interest in our study. [1] We would like to emphasize that the aim of our study was to investigate the applicability of generally accepted criteria for diagnosing polymyositis (PM) and dermatomyositis, not to validate a new classification. Applying Bohan and Peter’s criteria, all patients with an inflammatory myopathy who do not have a rash are designated as polymyositis. Other myopathies, currently also inclusion body myositis (IBM), are excluded. [2] We also took into account the specified muscle biopsy findings. Very few of Bohan and Peter’s PM patients showed mononuclear cells surrounding and invading normal muscle fibers, designating them as PM histopathologically. [3] In our material, the majority of Bohan and Peter’s PM patients showed either nonspecific perimysial/perivascular cell infiltrates or a necrotizing myopathy without inflammation. The different biopsy findings reflect pathogenetic heterogeneity of the clinical syndrome of PM. Disregarding this would be a missed opportunity: acknowledging the differences in biopsy findings in patients with Bohan and Peter’s PM is necessary for further investigation into pathogenesis and targeted treatments. Dr. Bradley’s cases contribute nicely to the discussion. Case 2 is remarkable because of the initial effect of immunosuppressive treatment. Case 1 would have been excluded from our study because of suspected IBM at onset. Our approach will not result in withholding treatment to patients as suggested by Miller et al. On the contrary, our findings emphasize that a necrotizing myopathy may be immune-mediated, responding well to immunosupressive treatment. We applaud Miller et al's intention to collaborate with neurologists closely. A joint meeting on trial design in idiopathic inflammatory myopathies, held under the auspices of the European Neuromuscular Centre on 10-12 October, 2003, has shown to be enlightening and constructive. [4] References 1. Van der Meulen MFG, Bronner IM, Hoogendijk JE et al. Polymyositis, an overdiagnosed entity. Neurology 2003;61:316-321 2. Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med 1975;292:344-347 3. Arahata K, Engel AG. Monoclonal antibody analysis of mononuclear cells in myopathies. I: Quantitation of subsets according to diagnosis and sites of accumulation and demonstration and counts of muscle fibers invaded by T cells. Ann Neurol 1984;16:193-208 4. www.enmc.org/workshops/reports.cfm?p=143 See further correspondence related to this article and accompanying editorial: Anthony A. Amato and Robert C. Griggs Unicorns, dragons, polymyositis, and other mythological beasts Neurology 2003; 61: 288-289 at: http://www.neurology.org/cgi/eletters/61/3/288