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|Year : 2021 | Volume
| Issue : 3 | Page : 638-641
Sporadic Inclusion Body Myositis: A Clinicopathological Study
Sundaram Challa1, Saumya Jakati1, Swethalakshmi Narla1, Megha S Uppin1, Meena A Kannan2, M K Murthy Jagarlapudi3
1 Department of Pathology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
2 Department of Neurology, Nizam's Institute of Medical Sciences, Hyderabad, Telangana, India
3 Institute of Neurological Sciences, Care Hospital, Banjara Hills, Hyderabad, Telangana, India
|Date of Submission||30-Mar-2017|
|Date of Acceptance||30-Dec-2017|
|Date of Web Publication||24-Jun-2021|
Dr. Sundaram Challa
Department of Pathology, Nizam's Institute of Medical Sciences, Hyderabad - 500 082 Telangana
Source of Support: None, Conflict of Interest: None
Background: Sporadic inclusion body myositis (s-IBM) is rare in India.
Aim: The aim of this study was to diagnose s-IBM according to the European Neuromuscular Center (ENMC) IBM research diagnostic criteria 2011.
Materials and Methods: A retrospective review of patient records diagnosed as s-IBM according to the above criteria during the period from January 2010 to May 2015 was done with an emphasis on pattern of muscle weakness.Serumcreatine kinase (CK) andelectromyography (EMG) were noted. Muscle biopsy was evaluated with basic panel of histochemical stains including Congo red stain. Immunohistochemistry (IHC) with ubiquitin was done in 10 biopsies. IHC for major histocompatibility complex-1 and electron microscopy studies were not performed.
Results: The diagnosis of s-IBM constituted 5 clinicopathologically defined, 12 clinically defined, and 10 probable IBM in the study period. There was male predominance with median age at 51 and duration of disease varying from 1–5 years. All the patients presented with insidious onset of muscle weakness of quadriceps and/or forearm flexors. CK varied from 57–2939 IU/L. EMG was myopathic in 22, mixed in 2, and neuropathic in 3. Endomysial inflammation was seen in 23 (85.19%) and rimmed vacuoles in 24 (88.89%). Amyloid was demonstrated in only 5 (18.52%) and ubiquitin in 2 biopsies. Mitochondrial abnormalities were seen in 92.59% biopsies.
Conclusions: Application of the ENMC IBM research diagnostic criteria allowed diagnosis of clinically-defined and probable IBM in the absence of all pathology criteria. Rimmed vacuoles in 88.89% of biopsies indicate presentation at a late stage. Use of ancillary techniques can improve diagnostic yield.
Keywords: ENMC IBM research diagnostic criteria 2011, sporadic inclusion body myositis , muscle biopsy
Key Message: Application of the European Neuromuscular center (ENMC) IBM research diagnostic criteria and muscle biopsy with basic histochemical staining panel allows diagnosis of clinically-defined and probable IBM even in the absence of all pathology criteria. The use of ancillary techniques can improve diagnostic yield. The presence of rimmed vacuoles in 88.89% and absence of inflammation in 14.82% biopsies indicate presentation at a late stage.
|How to cite this article:|
Challa S, Jakati S, Narla S, Uppin MS, Kannan MA, Jagarlapudi MM. Sporadic Inclusion Body Myositis: A Clinicopathological Study. Neurol India 2021;69:638-41
Sporadic inclusion body myositis (s-IBM) is rare but the most common idiopathic inflammatory myopathy (IIM) above the age of 50 years.,, Though initially identified as treatment-resistant polymyositis, it emerged as a distinct clinicopathologic entity. The clinical characteristics of s-IBM include slow progression and insidious-onset weakness of the proximal muscle in the lower limbs and/or distal muscles in the upper limbs., In the criteria proposed by Griggs et al., definite diagnosis of s-IBM was based on muscle pathology, irrespective of clinical features. However, s-IBM has distinct pattern of muscle involvement and pathological features such as rimmed vacuoles, may develop late in the course of the disease. Revised criteria with emphasis on specific clinical features have beenproposed.,, However, muscle biopsy remains an important diagnostic tool.,
s-IBM is reported to be rare in African Americans and nonwhite people. s-IBM is reported to be rare in India and the literature on s-IBM from India is limited.,, Other limiting factors in India are limited facilities for muscle biopsy and the required expertise. Diagnosis of s-IBM is of clinical and prognostic importance. This report presents a case series of s-IBM; the diagnosis was based on the European Neuromuscular center (ENMC) IBM research diagnostic criteria.
| » Materials and Methods|| |
This was a retrospective review of the case records of histologically confirmed cases of IBM according to the ENMC IBM Research Diagnostic criteria 2011 between January 2010 and May 2015. The data collected included demographic details, clinical features with particular emphasis on the pattern of motor weakness in the lower and upper limbs, and laboratory data. Association with autoimmune disease or malignancy, if any, was noted. Magnetic resonance imaging (MRI) and autoantibodies were not routinely performed, however, noted wherever available.
The cryostat sections of muscle biopsy were reviewed. The basic panel of histochemical stains performed included hematoxylin and eosin (H and E), Masson trichrome (MT), modified Gomori trichrome (MGT), ATPase pre-incubated at pH 9.4 and 4.6, succinic dehydrogenase (SDH), nicotinamide adenine dinucleotide tetrazolium reductase (NADH-TR), cytochrome c oxidase (COX), COX-SDH, and Congo red. Immunohistochemistry (IHC) with ubiquitin (Novocastra, United Kingdom; 1:50) was done in 10 biopsies. Fluorescent stains, IHC studies for other proteins, major histocompatibility complex-1 (MHC-1) and categorization of inflammatory cells. and electron microscopy (EM) studies were not performed.
| » Results|| |
During the study period, 2178 muscle biopsies were done. Of the histologically verified 177 (8.13%) IIM cases, s-IBM was the diagnosis using the ENMC IBM research diagnostic criteria, in 27 cases (15.25%).There were 17 males and 10 females with age ranging from 46 to 70 (median, 51) years. The patients were classified as clinic opathologically defined in 5, clinically defined in 12, and probable in 10. All patients presented with insidious onset of muscle weakness of quadriceps and/or forearm flexors. The duration of disease prior to diagnosis varied between 1 and 5 years. There was dysphagia in 2, quadriparesis in 3, neck muscle weakness in 1, and facial weakness in 3 patients. Weakness was more in the lower limbs than in upper limbs and in the proximal than thedistal group of muscles. Three patients were diagnosed as polymyositis on muscle biopsy at another facility and were unresponsive to steroids. Serum creatine kinase (CK) values ranged from 57 to 2939 IU/L (laboratory normal values, 20–200 IU/L). Electromyography was myopathic in 22, mixed pattern in 2, and neuropathy in 3. MRI was done in 4 patients and the features were suggestive of myositis in 2 with involvement of tibialis anterior, edema in 1, and atrophy of thigh and pelvic muscles in 1.
Muscle biopsy showed variation in fiber size with atrophic, hypertrophic, and split fibers. Adipose tissue infiltration was present in all biopsies. Characteristic rimmed vacuoles were seen in 24 (88.89%), which were highlighted on MGT as red granules rimming the vacuoles. They were occasional in 3 and frequent and multiple in others. Rimmed vacuoles were seen in the absence of inflammation in 4. Endomysial inflammation invading and surrounding non-necrotic muscle fibers was seen in 23 (85.19%) biopsies. Mitochondrial abnormalities in the form of COX negative fibers (25/27; 92.59%) and/or RRF (18) were seen. Amyloid deposition in the vacuoles on Congo red stain was seen in 5 (18.52%) biopsies and ubiquitin in 2 [Table 1] and [Figure 1], [Figure 2]. All patients were unresponsive to steroids.
|Table 1: Demographic, clinical, laboratory and muscle pathology features of sporadic inclusion body myositis|
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|Figure 1: Photomicrographs of s-IBMshowing (a) rimmed vacuole H and E ×100, inset MGT showing red granules rimming the vacuole., MGT ×400; (b) endomysial inflammatory infiltrate surrounding and partially invading non-necrotic muscle fiber H and E ×100, inset H and E ×400|
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|Figure 2: Photomicrographs of s-IBM showing (a and b) congophilic material in the vacuoles, Congo red ×100, ×400; (c) ubiquitin in the vacuole, ubiquitin ×400; (d) Red ragged fiber MGT ×100; (e) cytochrome C oxidase deficient fibers COX ×100, inset COX-SDH ×100|
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| » Discussion|| |
s-IBM is classified as an IIM, however, its clinical presentation is quite distinct from other IIMs. The ENMC IBM research diagnostic criteria include knee extension weakness >hip flexion weakness, and/or finger flexion weakness >shoulder abduction weakness allowing to make clinic opathologically defined, clinically defined and probable IBM subtypes. Slowly progressive quadriceps weakness was present in all our patients. Dysphagia, quad riparesis, neck muscle weakness, and facial weakness, as seen in our patients, were described in patients in the earlier studies., Involvement of tibialis anterior was reported in 10% of patients, as seen on MRI in 2of our patients.
There is only moderate elevation of CK and elevation upto 15 times of upper limit of normal is one of the diagnostic criteria. Electromyography is not a diagnostic criterion as it does not confirm or rule out the diagnosis. However, a myopathic or mixed pattern or neuropathy, as seen in our patients, have been documented. MRI, though not a diagnostic criterion, is useful to identify the specific pattern of muscle involvement.
The pathological changes include both inflammatory and degenerative changes. The muscle pathology criteria include endomysial inflammatory infiltrate invading and surrounding non-necrotic muscle fibers, rimmed vacuoles, MHC-1 up regulation, protein accumulation, and 15–18 nm filaments on EM. Rimmed vacuoles may not be present at initial presentation as they are reported to be a late feature and detected only in second or third biopsy. Rimmed vacuoles were present in 24/27 (88.89%) biopsies in our series. This may reflect the long duration of the disease in our patients. Rimmed vacuoles were present in the absence of inflammation in 4 biopsies. These may be attributed to delay at presentation or patchy nature of inflammatory process in IIMs. A diagnosis of clinic opathologically defined IBM could be made in only 5/27 (18.52%) patients. This is because of failure to demonstrate amyloid in the vacuoles and lack of EM studies. Fluorescent stains and IHC are sensitive techniques to demonstrate amyloid and other proteins. Ubiquitin, another protein implicated in the degenerative process, was found in 2 biopsies. Eosinophilic cytoplasmic inclusions that correspond to the tubulofilamentous inclusions on EM were not observed in our biopsies. Mitochondrial abnormalities in the form of RRF and COX-negative fibers, as seen in our biopsies, are useful and helpful features for the diagnosis.
Lloyd et al. evaluated 24 previously proposed IBM diagnostic criteria and found the ENMC 2013 probable criteria with best performance at 84% sensitivity. The emphasis on highly specific pathology criteria, which are not routinely performed or available, leads to exclusion of many patients. Application of the revised ENMC criteria allowed us to make the diagnosis of probable and clinically defined IBM. The present study though lacking the ancillary techniques could make the diagnosis based on clinical and muscle pathology criteria. We conclude that the use of ENMC IBM research diagnostic criteria and basic histochemical staining panel helps fairly in the diagnosis of s-IBM and subtypes. The diagnosis can be improved with inclusion of MHC-1 staining in routine practice.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]