Elsevier

Neuromuscular Disorders

Volume 23, Issue 11, November 2013, Pages 945-951
Neuromuscular Disorders

Workshop report
193rd ENMC International workshop Pathology diagnosis of idiopathic inflammatory myopathies 30 November – 2 December 2012, Naarden, The Netherlands

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Introduction

The 193rd ENMC International Workshop brought together 21 researchers from nine countries: Belgium, Finland, France, Germany, The Netherlands, Spain, Sweden, United Kingdom, and United States of America. The group was joined by a patient representative from the Dutch working group of myositis patients. The participants discussed the idiopathic inflammatory myopathies (IIM), that comprise a number of different entities recognized on clinical, pathological and immunological/serological grounds. Consensus documents on clinical and pathological classification criteria have been issued following previous ENMC and MRC workshops, but there remains a strong need to revise and re-classify. The present workshop aimed, by combining the input from people with diverse background, to draft a set of muscle biopsy diagnostic features and criteria that will gain wide acceptance in the clinical and scientific communities involved in IIM diagnosis. The workshop aimed at identifying crucial variables in muscle biopsies and how these should be evaluated qualitatively and quantitatively in routine histopathological studies, leading to a consensus classification and scoring system to be employed in diagnostic laboratories reading IIM diagnostic muscle biopsies.

Traditionally, adult dermatomyositis (DM), juvenile dermatomyositis (JDM), polymyositis (PM) and sporadic inclusion body myositis (IBM) have been the main subsets of the IIM [1], [2], [3]. The definition of the PM entity has been variable between centers, more particularly between rheumatologic and neurological clinicians and neuropathologists involved in the diagnosis and management of these patients. Recent studies have even cast doubt on the very existence of the PM entity, suggesting that most patients diagnosed with PM either have IBM or an overlap disease between myositis and an identifiable connective tissue disorder, often with an immunopathological profile more akin to DM [4], [5].

Depending on the presenting symptoms and signs and local habits, patients suffering from IIM are cared for by rheumatologists or neurologists with special expertise in neuromuscular diseases. These two groups have based their diagnosis and classification on partly different criteria. Rheumatologists have long been using the Bohan and Peter criteria published in the early seventies, mainly for research purposes [6]. Neurologists have based their diagnosis to a far larger extent on muscle biopsy findings. This divergent practice has lead some authors to suggest that “neurologists are from Mars and rheumatologists are from Venus” [7]. This different classification has hampered the comparison of clinical and basic research publications and the set-up of international multicenter studies including patients with different presentations of a probable spectrum of disease manifestations.

As research in the field has moved on in the past 10 years, it became clear that (1) the Bohan and Peter criteria, by not using strict muscle biopsy criteria, did not adequately deal with the rather common entity of IBM, and that usage of these criteria led to indiscriminate inclusion of probably different subsets of patients in clinical trials [8]; (2) strictly pathologically defined PM represents a rare entity, (3) many patients have mild necrotizing myopathy as the sole biopsy manifestation of their illness; (4) some biopsies lack inflammatory cells but exhibit other changes that indicate a pathology secondary to inflammation, e.g., major histocompatibility class I (MHC-I) expression on muscle fibers; (5) the increased recognition of myositis specific antibodies allows in at least some instances to define certain clinico-pathological subsets of IIM patients [9]. Conversely, the antibody profile may identify a specific disease causing agent, such as in statin induced necrotizing autoimmune myopathy (NAM) [10].

Although consensus documents on classification criteria had been issued on previous ENMC [11] and MRC [12] workshops, there remains a need to revise and re-define the pathological criteria and eventually confront them with the evolving data from the other fields, e.g., serology. By bringing together researchers from different backgrounds, i.e., neurologists, rheumatologists, immunologists and pathologists, the workshop aimed to combine this input in order to draft a set of diagnostic features and criteria that will gain wide acceptance across sub-specialties. Because a recent ENMC workshop dealt with IBM, the focus was on the other IIM. State-of-the-art lectures covering recent developments, a pathological discussion session around the microscope and round-table discussions on methodological aspects were held.

Section snippets

Classification of the inflammatory myopathies

Jan De Bleecker opened the workshop by presenting an overview of the classical pathological subdivision of inflammatory myopathies and the basic immunopathological features as they have been outlined in studies dating from the mid-eighties to just recent. DM is characterized by a complement-mediated endotheliopathy. The immune effector mechanism in PM and IBM is different and is characterized by cell-mediated cytotoxicity with infiltration of MHC-I expressing nonnecrotic muscle fibers by CD8+

Standardization and interpretation of muscle biopsies

Janice Holton and Lucy Wedderburn explained how the international scoring system for JDM came to shape [21]. The scoring tool breaks down into the description of four domains to which the myopathological changes can be localized: muscle fibers, blood vessels, inflammation, and connective tissue. It was stressed that the approach was developed as an assessment tool to score severity of pathological change permitting clinical correlations rather than as a diagnostic tool. The necessity for large

Differential tissue changes in inflammatory myopathies

Romain Gherardi summarized the vascular changes associated with IIM. The intramuscular vasculature branches off from the feeding arteries (epimysium) to the arcade arteries (perimysium), to the transverse and subsequently terminal arteries (endomysium). Each terminal artery feeds a muscle microvascular unit, i.e. a group of capillaries. Six to eight capillaries perfuse five muscle fibers. During muscle development, fiber size increases together with capillary density, while the numbers of

Novel findings on auto-antibodies and immune regulators in the IIM

Myositis-specific auto-antibodies (MSA) are diagnostically and prognostically useful, as they often represent specific clinical subgroups. Andrew Mammen shared his views on the clinical relevance of auto-antibody typing in the IIM [28]. Anti-HMGCR antibodies, initially named anti-200/100 kD antibodies, are typically associated with NAM, and 67% of cases with this auto-antibody can be attributed to statin use [18]. The pathology includes capillary damage and MAC deposits on muscle fibers. The

Group evaluation of biopsies

The practical session was held at the pathology department of the Amsterdam Medical Centre and led by Marianne de Visser and Anthony Amato. Participants brought typical and less typical biopsies suspected to be IIM, from which it quickly became clear that there was strong agreement on the pathological hallmarks to be evaluated. There was a strong consensus regarding definitions of the various myositis-related tissue alterations. The evaluation of atypical muscle biopsies alerted the

Consensus building though Delphi phase I

Although not pre-planned, the individual viewpoints of the participants on how a biopsy diagnostic workup of suspected IIM patients should be organized was polled. The answers of a brief list of questions were discussed, and under the experienced leadership of Lucy Wedderburn and Janice Holton a preliminary effort was made to build consensus through the nominal group technique, with 80% being the cut off for agreement to retain a given item within the consensus.

Conclusions

After exchange of state-of-the-art knowledge regarding classical and alternative classification criteria, new developments, and a preview of possible methodological ways to arrive at a uniform and valid pathological classification and scoring system for IIM biopsies, the views of the participants were tested via a microscopy session and through a short open-answer list of questions. A contrast was noted between the largely unanimous ideas on the interpretation of the specimens under the

Participants2

Anthony Amato, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA.

Olivier Benveniste, Hopital Pitié-Salpétrière, Paris, France.

Lisa Christopher-Stine, Johns Hopkins University Hospital, Baltimore, USA.

Jan De Bleecker, Ghent University Hospital, Belgium.

Boel De Paepe, Ghent University Hospital, Belgium.

Marianne de Visser, Academic Medical Centre, Amsterdam, The Netherlands.

Mazen Dimachkie, Kansas University Medical Centre, Kansas City, USA.

Dalia Dimitri, Mondor Institute for

Acknowledgements

This workshop was made possible by the financial support of the European Neuromuscular Centre (ENMC) and its main sponsors: Association Française contre les Myopathies, Deutsche Gesellschaft fur Muskelkrankheiten, the U.K. Muscular Dystrophy Campaign, Muskelsindfonden Denmark, Prinses Beatrix Spierfonds and Vereniging Spierziekten Nederland, Schweizerische Stiftung fur die Erforschung der Muskelkrankheiten, Telethon Foundation Italy, and the associate member The Finnish Neuromuscular Association

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References (31)

  • M.F. Van der Meulen et al.

    Polymyositis: an overdiagnosed entity

    Neurology

    (2003)
  • Y. Troyanov et al.

    Novel classification of idiopathic inflammatory myopathies based on overlap syndrome features and autoantibodies: analysis of 100 French Canadian patients

    Medicine

    (2005)
  • A. Bohan et al.

    Polymyositis and dermatomyositis

    N Engl J Med

    (1975)
  • L. Christopher-Stine

    Neurologists are from Mars, rheumatologists are from Venus: differences in approach to classifying the idiopathic inflammatory myopathies

    Curr Opin Rheumatol

    (2010)
  • A.L. Mammen

    Autoimmune myopathies: autoantibodies, phenotypes and pathogenesis

    Nat Rev Neurol

    (2011)
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    1

    Members of the ENMC Myositis Muscle Biopsy Study Group are listed at the end of the report.

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