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Idiopathic inflammatory myopathies in adults: A comparative study of Bohan and Peter and European Neuromuscular Center 2004 criteria
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.232296
Keywords: Bohan and Peter criteria, European Neuromuscular Center criteria, idiopathic inflammatory myopathies, muscle biopsy
The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of acquired myopathies affecting skeletal muscle with variable involvement of other organs. They are characterized by muscle weakness and chronic inflammatory infiltrate in muscles. The most commonly used criteria were those proposed by Bohan and Peter in 1975 and include polymyositis (PM) and dermatomyositis (DM) either in isolation or in association with connective tissue disease (CTD) or malignancy.[1] However, there are significant advances in the understanding of the pathogenesis of IIM, and new diagnostic tools have been developed since then. These diseases are autoimmune in nature and potentially treatable. The classification of IIMs remains challenging. The European Neuromuscular Center (ENMC) in its 119th International Workshop formulated clinical, laboratory, and pathological criteria for the diagnosis of different IIMs in adults [excluding sporadic inclusion body myositis (s-IBM)] with detailed inclusion and exclusion criteria to identify homogenous subgroups for possible use in clinical trials.[2] The diagnostic criteria for s-IBM were those proposed by Griggs et al., (1995)[3] and later revised in the 188th ENMC workshop.[4] Muscle biopsy is mandatory for the diagnosis of IIMs. Muscle biopsy evaluation was addressed in the 193rd and 205th ENMC workshops and the recommendations include a panel of histochemical stains (basic, additional, and optional) and the evaluation of muscle in the four domains: muscle fiber, inflammation, connective tissue, and vascular.[5],[6] Presently, the major subgroups of IIMs include: (i) DM, (ii) PM, (iii) s-IBM, (iv) immune-mediated necrotizing myopathy (IMNM), and (v) nonspecific myositis (NM).[2],[5],[6] Subtyping of IIMs is based on the pathologic features on muscle biopsy and these features also help to differentiate IIMs from other disease mimics. Subtyping may help in assessing the treatment options and prognosis.[6],[7],[8] There are few institutes with facilities for muscle biopsy evaluation in India. The focus of majority of studies from India was to diagnose and differentiate IIMs from muscular dystrophies and none except one have used the ENMC criteria to subgroup the IIMs.[9],[10],[11],[12],[13],[14],[15],[16] The Bohan and Peter criteria are still being widely used in clinical practice for the diagnosis of IIMs. In the present study, we aimed to subtype IIMs according to the ENMC criteria and the revised criteria for s-IBM using the basic panel of histochemical stains and attempted comparison of the subgroup identification by the ENMC criteria with those according to the Bohan and Peter criteria.[1],[2],[3],[4],[5],[6] The study aims to highlight the detailed muscle biopsy evaluation in subgroup identification by the ENMC criteria for therapeutic and prognostic purposes. Subgroup analysis and comparison the between the ENMC and the Bohan and Peter criteria were attempted to bring out the limitations of the widely used Bohan and Peter criteria.
This was a retrospective review of case records of histologically confirmed IIM diagnosed on muscle biopsies in adult (>18 years) patients using the criteria proposed by the ENMC in 2004 and the revised criteria for s-IBM, and also by the Bohan and Peter criteria.[1],[2],[4] The study period was between January 2014 and May 2015. Patients were referred for muscle biopsy from both the neurology and rheumatology departments, of a university hospital in South India – and from the other hospitals in the city and state. This is the only department of pathology with the facilities for a detailed evaluation of muscle biopsy in the state in South India. The data collected included demographic details, onset of the disease, clinical features including skin rash and other skin lesions, pattern of muscle involvement, involvement of other organs, presence of CTD, and malignancy. The laboratory data collected included serum creatine kinase and electro-diagnostic findings. Serum autoantibodies and magnetic resonance imaging of muscles were not done routinely as part of the workup, but were noted wherever available. Muscle biopsy was done by the open method from vastus lateralis muscle in all patients. The cryostat sections were evaluated for the presence of perifascicular atrophy (PFA), necrotic fibers, rimmed vacuoles, ragged red fibers, cytochrome oxidase negative fibers, presence of inflammatory cells, scattered in the endomysium, surrounding and/or invading nonnecrotic muscle fibers, or the perivascular structures in the perimysium. Muscle biopsy was evaluated in the four domains: muscle fiber, inflammatory, connective tissue, and vascular, with the basic panel of histochemical stains.[6] The stains included hematoxylin and eosin (H and E), Masson's trichrome, modified Gomori trichrome, ATPase preincubated at pH 9.4 and 4.6, succinic dehydrogenase (SDH), nicotinamide adenine tetrazolium reductase, cytochrome c oxidase (COX), and combined COX-SDH stains. Periodic acid Schiff, oil red O, and Congo red stains were done wherever necessary. Acid phosphatase, alkaline phosphatase, and nonspecific esterase stains were not performed. The Bohan and Peter criteria define muscle pathology as only the presence of inflammatory cells, whereas the ENMC criteria elaborates on detailed muscle pathology apart from presence or absence of inflammatory cells [Table 1].
In this study, immunohistochemical (IHC) studies for major histocompatibility complex-1, membrane attack complex, characterization of inflammatory cells, and electron microscopic studies were not done as part of the routine workup of IIMs. Other disease mimics were excluded based on clinical, laboratory, and muscle biopsy features with appropriate histochemical and immunohistochemical stains (for dystrophy and metabolic diseases). Patients were classified into subgroups using clinical, laboratory, and histological features on muscle biopsy proposed by the ENMC 2004 criteria [Table 1].[2] The ENMC criteria identify amyopathic and sine dermatitis subgroups of DM as well as the NM and IMNM subgroups of IIMs. The same patient groups were also classified into subgroups using clinical, laboratory, and histological features on muscle biopsy using the criteria proposed by Bohan and Peter.[1] A comparison between the subgroups according to the ENMC and the Bohan and Peter criteria was done. Patients with s-IBM were classified according to the ENMC IBM research diagnostic criteria.[4] Subgroup analysis and comparison between these two criteria were attempted to highlight the limitations of the widely used Bohan and Peter criteria.
During the study period, 652 muscle biopsies were done and histological diagnosis of IIMs in adults was done in 69 (10.58%) patients, including 53 (76.81%) by the ENMC criteria and 16 (23.19%) diagnosed as s-IBM according to the ENMC IBM Research Diagnostic Criteria 2011.[2],[4] Among the 53 IIMs diagnosed by the ENMC criteria, when analyzed according to the Bohan and Peter criteria; only 35 (66.04%) could be diagnosed as IIM.[1],[2] s-IBM is not a subgroup of IIM in either the ENMC or the Bohan and Peter criteria.[1],[2] The subgroup diagnosis of IIMs by the ENMC 2004 criteria was: DM in 30 (56.60%), PM in 2 (3.77%), IMNM in 9 (16.98%), and NM in 12 (22.64%) patients.[2] The subtypes of DM diagnosed by the ENMC 2004 criteria were: definite DM in 10 (33.33%); probable DM in 10 (3.33%); possible DM sine dermatitis in 16 (53.33%); and amyopathic DM in 3 (10%) patients. The subgroup diagnosis by the Bohan and Peter criteria was: DM in 9 (25.71%); PM 21 (60%); and PM with CTD in 5 (14.29%) patients [1] [Figure 1]. The under diagnosis of DM by the Bohan and Peter criteria could be explained by the presence of clinico-histopathological subtypes in the ENMC criteria. The over-diagnosis of PM with and without CTD by the Bohan and Peter criteria occurred in 26 patients. The error in the over-diagnosis of PM by the Bohan and Peter criteria was due to misdiagnosis of possible DM sine dermatitis as PM in 10, NM as PM in 9, and DM and NM in association with CTD as PM with CTD in 2 and 3 patients, respectively. In this study, the diagnosis of IIMs was made in 18 (33.96%) more patients by the ENMC criteria when compared to the Bohan and Peter criteria: DM in 9 (16.98%) and IMNM in 9 (16.98%) patients [Table 2].
The subtyping of s-IBM was 'clinico-pathologically defined' in 3 (18.75%) patients; 'clinically defined' in 9 (56.25%) patients; and was 'possible' in 4 (25%) patients.
There has been a controversy regarding which classification is best for subgrouping IIMs. The primary goal of any classification should be in differentiating the subgroups of IIMs, and in differentiating IIMs from mimics.[17] A comparative study of the different classifications of IIMs currently available suggested that the Bohan and Peter criteria were too inclusive and nonspecific.[18] The same study demonstrated 71% sensitivity and 82% specificity for the ENMC criteria. In spite of these observations, the Bohan and Peter criteria are still widely used for establishing the clinical diagnosis of IIMs. In the present study, more (33.96%) number of patients could be grouped into various subgroups of IIMs, mostly treatable, using the ENMC criteria. Similar were the observations in the study by Danielsson et al.[19] In their study, they suggested that the ENMC criteria were more restrictive and led to a difference in the groups defined by the Bohan and Peter classification.[19] Using the Bohan and Peter criteria, 26 (74.29%) patients were grouped into PM with or without CTD group, whereas it was only 2 (3.77%) by the ENMC 2004 criteria. By the Bohan and Peter classification, s-IBM, IMNM, and NM could be wrongly grouped in the PM group.[1],[3],[20],[21],[22] The ENMC groups DM into various subtypes which may have therapeutic and prognostic implications. The typical rash in patients with DM may precede, occur simultaneously, or follow muscle weakness.[21] Moreover, the rash may be transient or poorly recognized.[21] Approximately 6% of DM patients may have no skin involvement and 20% of DM patients develop skin rash but no muscle weakness.[22],[23] Amyopathic and myopathic DM are a part of the range of DM affecting skin and muscle to a varying degree.[21] Muscle biopsy is essential to make a diagnosis of DM sine dermatitis to avoid the misdiagnosis of PM.[21] By the ENMC criteria, 30 (56.60%) patients could be subgrouped into the DM group, group, whereas only 9 (25.71%) patients could be classified into the DM group by the Bohan and Peter criteria. Perifascicular atrophy (PFA) detectable on muscle biopsy is an important feature for establishing the diagnosis of DM by the ENMC criteria, whereas this feature has not been described in the Bohan and Peter criteria.[1],[2] The diagnostic criteria proposed by Griggs et al.,[3] for the diagnosis of s-IBM places emphasis on the histological features. However, it was realized on a long-term follow-up that many patients with s-IBM do not show all the histological features, especially, rimmed vacuoles.[24] The revised diagnostic criteria were proposed with emphasis on specific clinical features.[4] In this study, these revised criteria for the diagnosis of s-IBM were used. In this study, only the basic panel of stains was used to evaluate all the four domains of muscle.[5],[6] Ancillary investigations on muscle biopsy are important for the accurate identification of subgroups. However, IHC and electron microscopy studies could not be performed in the present study. We could have missed out the accurate diagnosis in some patients because of the lack of these studies; however, the systematic evaluation of muscle biopsy according to the ENMC criteria, based on light microscopy with histochemical stains improved the diagnostic yield significantly when compared to the Bohan and Peter criteria. We plan to include immunohistochemistry for routine practice in the future. To conclude, the classification of IIMs by the ENMC criteria with a detailed muscle biopsy evaluation leads to a better diagnostic yield as well as a better subgroup identification to guide the treatment options. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
[Figure 1]
[Table 1], [Table 2]
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