Indian Journal of Rheumatology

: 2020  |  Volume : 15  |  Issue : 6  |  Page : 209--216

Idiopathic inflammatory myopathies: Contributions from India

Anand Narayan Malaviya 
 Department of Rheumatology, ISIC Superspeciality Hospital, New Delhi, India

Correspondence Address:
Prof. Anand Narayan Malaviya
Flat 2015, Sector B2, Vasant Kunj, New Delhi - 110 070


A careful literature search would reveal significant contributions by Indian clinicians and basic researchers in the field of Idiopathic inflammatory myopathies (IIMs). The main drug used for its treatment, methotrexate (MTX), was synthesized for the first time by an Indian biochemist Yella Pragada Subbarow, working in New York (1948). Its first use for treating IIM patients was also by an Indian physician working in Boston (1968), Anand Narayan Malaviya. Similarly, there are several publications on the different aspects of the disease from India. Although the publications in the 1980s and 1990s were only a few and far between, starting early in this millennium, the pace of publications rapidly picked up. From the early purely clinical-observation-based papers, the area of research that has been covered in more recent papers has become much wider. Epidemiology, different age groups, unusual presentations, mimics of IIM, treatments being used and response to treatments, histoimmunopathological studies, studies of myositis-specific antibodies, basic immunological research in IIM, genetic studies, are now being published frequently. In this 'Introductory' paper, a time-line summary of the Indian contribution in the IIM research from India has been provided.

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Malaviya AN. Idiopathic inflammatory myopathies: Contributions from India.Indian J Rheumatol 2020;15:209-216

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Malaviya AN. Idiopathic inflammatory myopathies: Contributions from India. Indian J Rheumatol [serial online] 2020 [cited 2021 Apr 19 ];15:209-216
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Idiopathic inflammatory myopathies (IIMs) are an uncommon group of systemic immunoinflammatory rheumatic diseases. The epidemiology of IIM has not been studied in India. Figures from developed countries vary between different studies because of the study setting and definitions used. One study using administrative claims data for Quebec, Canada, (approximately 7.5 million beneficiaries) estimated the prevalence of 21.5 (95% confidence interval: 19.4–23.9) per 100,000 patients for dermatomyositis (DM) and polymyositis (PM).[1] Other community-based epidemiological studies have reported a range of prevalence for IIMs, of 5.1/100,000 in the U. S. PM prevalence 3.45/100,000 in Olmsted County, Minnesota, USA and DM prevalence of 21.42. The overall prevalence of myositis, as identified in administrative claims databases, may be in the range of 14–22 cases/100,000 population.[2] These numbers may not be reflective of the true prevalence in the community because of the marked heterogeneity of the clinical and laboratory features of the disease. With protean clinical manifestations and different phenotypic presentations, patients may be presenting in different specialty clinics, e.g., dermatology, neurology, pulmonology, and physiotherapy.

Attempts at classifying idiopathic inflammatory myopathies

Because of the variable clinical picture, several attempts have been in the last four decades to develop a satisfactory classification system for IIM, starting from the Medsger's 1970 to the recent attempt by Lundberg et al.[3] and the latest being the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria.[4] It is important to categorize IIM patients into homogeneous subsets, to achieve uniformity enabling better understanding of the pathogenesis with potentially different therapeutic implications. Even these criteria have limitations and do not encompass recent advances including the discovery of a large number newer myositis-specific antibodies and myositis-associated antibodies (MSA/MAA) and their clinical associations that are being recognized now. Therefore, despite being old, the criteria of Bohan and Peter are robust enough to be still in routine use in most rheumatology departments.[5] Bohan and Peter classified IIMs into the following five categories:

Group 1: Primary, idiopathic PMGroup II: Primary, idiopathic DMGroup III: DM or PM associated with neoplasia (CAM)Group IV: Childhood DM (or PM) associated with vasculitis (J-DM/PM)Group V: PM or DM associated with collagen vascular disease (DM/PM-connective tissue disease [CTD] overlap).

Diagnostic approaches in the past

Bohan and Peter also suggested the diagnostic approach that included:

Typical DM rash including heliotrope rash and Gottron's papulesSymmetric weakness of limb-girdle muscles and anterior neck flexorsMuscle biopsy evidence typical of myositis (histopathology specific for this disease is described in detail in the original paper)[6]Elevated serum levels of sarcoplasmic enzymes(creatine phosphokinase [CPK], aldolase, transaminases, and lactic dehydrogenase – particularly useful is CPK, both for the diagnosis and for following the progression of the muscle disease)Typical electromyographic findings: The following triad is particularly suggestive of PM-DM – (a) Polyphasic, short, small motor unit potentials; (b) fibrillation, positive sharp waves, increased insertional irritability; and (c) bizarre, high-frequency, repetitive discharges.

While the workers around the world are deeply involved in improving the current classification system, there is presently a via-media to group the different serophenotypes into at least 8 (as against 5 of Bohan and Peter) categories as follows:[7]

DMJuvenile DM (JDM).Clinically amyopathic DM (CADM)Cancer-associated DM (CAM)PMAutoimmune (immune-mediated) necrotizing myositis (NAM)Sporadic inclusion body myositis (sIBM)Overlap myositis with CTDs (OM).

Key associations of myositis-specific antibodies with inflammatory myopathies

Specific clinical features of some of the above 8 categories of inflammatory myopathies are typical enough to be summarized here (details will be available in the other papers of this issue of the journal).[8]

Thus, the CADM group has shown high association with interstitial lung disease (ILD) with the presence of either (i) the antisynthetase antibody (a generic name for autoantibodies against histidyl-tRNA synthetase and seven different autoantibodies to other amino acyl-tRNA synthetase, enzymes found in all nucleated cell antibodies against t-RNA synthetase further classified based on eight distinct antibodies, also called amti-Jo-1 and non-Jo-1 autoantibodies) or (ii) antimelanoma differentiation antigen gene 5 (MDA5). Similarly, the CAM group shows high association with cancer (i.e., appearance of cancer between a period from 3 years before till 3 years after the onset of inflammatory myositis). This group shows a high frequency of two MSAs, namely, anti-transcription intermediary factor 1-γ antibodies (anti-TIF1-γ) and antinuclear matrix protein 2 (anti-NXP-2 antibodies). Anti-small ubiquitin-like modifier enzyme (SAE) is the 3rd antibody that has been reported to be associated with cancer. Severe calcinosis cutis is usually associated with the JDM that shows anti-NXP-2 MSA. Antibodies against signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies (anti-HMGCr ab) are associated with necrotizing myositis. Anti-MI2 and SAE antibodies are associated with typical DM with proximal limb muscle neck flexor weakness with heliotrope rash, Gottron's papules and sign, periungual microinfarcts, and other typical skin lesions.

 Inflammatory Myopathies in India: Historical Facts

Myositis in India, methotrexate – the Indian connection

A time-line summary of the Indian contribution in the IIM research from India has been summarized in [Figure 1]. While reading the history of IIM, one would find two major Indian connections with inflammatory myositis, both related to methotrexate (MTX), a major drug being used in the treatment of this disease.[9] It was synthesized by an Indian biochemist working in New York in 1948, Dr. Yella Pragadha Subba Row. The life story of this genius unsung hero Indian Biochemist is worth reading.[10] He hailed from erstwhile “Madras Presidency” (now Andhra Pradesh/Telangana) and had obtained Medical Degree from Madras Medical College (then Madras). He then worked at the Harvard University, Department of Biochemistry in Boston before moving to American Cyanamid Pharmaceuticals, Perl River, Upstate New York. This is where he did most of his work including the synthesis of MTX. Similarly, the first paper on the treatment of DM with MTX published in “The Lancet” in 1968 also has the Indian connection; the first author of this paper, Dr. Anand Narayan Malaviya, then working in Boston, USA, and now in Delhi, is also an Indian.[11]{Figure 1}

Early reports on inflammatory myositis from India

On searching the literature on “dermatomyositis/polymyositis” or “idiopathic inflammatory myopathy” or “Idiopathic inflammatory myositis” or “Myositis” in India, one finds that from 1970s till 2006, there were only two major clinical series published on this topic. The first detailed series of 27 cases was published in from All-Indian Institute of Medical Sciences, New Delhi, in 1981.[12] The authors reported 27 cases, of which most cases were classified according to the criteria of Bohan and Peter.[5] Besides muscle biopsy, Electro myogram (EMG), and wherever available, tests for sarcoplasmic enzymes levels were carried out. Other immunological tests included anti-dsDNA antibody, several organ-specific autoantibodies, and rheumatoid factor (RF). Clinical features of 27 patients were reported in detail. There were 6 (22%) patients with “primary idiopathic PM,” 7 (26%) with “primary idiopathic PM,” 4 (15%) with DM associated with neoplasia, 3 (11%) with “childhood type,” and 7 (26%) had overlap syndrome (further categorized into “definite,” “probable,” and “possible” category as per the criteria of Bohan and Peter). Proximal muscle weakness was present in 19 (70%), typical skin rash in 10 (37%), constitutional symptoms in 5 (18.5%), joint pains in 4 (15%), dysphagia in 4 (15%), and vasospastic phenomenon in 2 (7.4%) patients. Ten of the available 13 muscle biopsies were typical of the disease. EMG was done in 11/27 patients, all of them showed typical electrophysiological abnormalities. CK was done only in 4/27 patients, 2 of whom showed elevated levels. Antinuclear antibody, RF, and anti-DNA antibodies were positive in a few patients, all of whom had “overlap” syndrome. All the patients received prednisolone and aspirin, and 9 had also received MTX. One particularly resistant patient was given cyclophosphamide, chlorambucil, as well as levamisole, but she did not survive. Most patients needed low-dose alternate-day prednisolone maintenance. Five patients could be maintained on long-term MTX alone. Three patients achieved drug-free remission. In the follow-up, 12 patients continued in long-term follow-up and in good remission. Six patients had died with different problems including aspiration pneumonia, chest infection, and malnutrition with cachexia (due to inability to swallow). In a few patients, the cause of death was not known.

The second major paper on IIM was published from the Department of Rheumatology, Madras Medical College, Chennai, in 2002,[13] with not many publications in between, except for some case reports. This study reported on 87 patients with inflammatory myopathies encountered over a period of 10 years. There were 24 adults with PM and 26 with DM, 1 with amyopathic DM, and 1 had DM following carcinoma breast. There were 5 patients with juvenile myositis and overlap with other CTDs. There was a female preponderance in the adults (male: female = 1:2.35) that was not prominent in juvenile patients (male: female = 1.5:1). The mean age of onset in years was 33.26 in adult PM, 35.03 in adult DM, 7.4 in JDM, 42 in malignancy-associated DM, and 25.5 years in the overlap group. Proximal muscle weakness was seen in 98.8% of patients, dysphagia in 33.3%, distal muscle weakness in 12.5%, respiratory muscle weakness in 9.2%, and dysphonia in 4.6%. Other features included arthritis in 35.6%, ILD in 9.2%, Raynaud's phenomenon in 5.7%, myocarditis in 4.6%, and conduction disturbances in 1.15%. Elevated muscle enzymes were seen in 85.1% of patients. EMG was positive in 66.6% of patients. Muscle biopsy was positive in 85.29% of patients. Antinuclear antibody was positive in 67.24% of patients. All the patients received glucocorticoids. The non-responders required MTX (13 patients) or azathioprine (11 patients). Death occurred in 10 patients (seven with DM predominantly due to respiratory involvement and three with overlap CTDs).

The next extensive report of IIM from India was in 2010 from the Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum.[14] There were 68 patients in this cohort diagnosed according to Bohan and Peter criteria. The mean age at diagnosis was 36.5 years and females constituted 71%. Of these, 62% of patients had definite IIM, 49% had PM, 20% had DM, and 29% had overlap syndrome. The mean follow-up period was 5.4 years. Prednisolone alone was used in 55 (80%) patients and azathioprine (1–3 mg/kg/day) alone in 12 (17.6%) as the initial treatment. Relapse of IIM with drug withdrawal was seen in 15 (22%) patients; 70% had favorable outcome and 16% expired. The treatment delay of ≤6 months (P = 0.001), absence of cardiac or lung involvement (P < 0.001), and positive biopsy (P = 0.033) were predictive of a favorable prognosis in the univariate analysis. In multivariate analysis, only the duration of illness of ≤6 months (P = 0.008) and the absence of cardiac or lung involvement (P = 0.001) predicted the favorable outcome at the last follow-up. Cumulative survival rate was 95% at 1 year, 86% at the 5th year, and 80% at the 10th year. It is of note that these authors did not use MTX in any patient. A point of note is that this study applied sophisticated statics and attempted to find out the predictive features for a good prognosis.

Recent reports on idiopathic inflammatory myopathies from India

The past few years have seen a spurt in publications on the topic of IIM from India. The following section discusses these papers categorized appropriately.

Diagnostic difficulties including myositis due to infections, drugs, and chemicals, tropical pyomyositis, sarcoidosis, and some rare genetic disorders resembling idiopathic inflammatory myopathies

Verma et al. remind us of “tropical pyomyositis” in children, a muscle disease that may create occasional diagnostic problems.[15] They also quote 7 papers on this topic from 1986 to 2000.[6],[7],[8],[9],[10],[11],[12] In their study of 40 patients, they highlight the suppurative nature of the muscle lesions with the formation of microabscesses caused by methicillin-sensitive Staphylococcus aureus in about 40% of the patients, but blood cultures were sterile. Most of the patients were admitted with a short history of fever, pain, and localized muscle swelling. Antibiotics and surgical abscess drainage led to recovery in every case. Related to infective etiology of the muscle disease, Sundaram et al. have recently described biopsy-proven microsporidialmyositis in adult-onset immunodeficiency complicated with Cytomegalovirus viremia.[16] The patient improved slowly on ganciclovir. These authors emphasize that infective PM should be considered in a patient with paucity of clinical and serological autoimmune features. Thulasidoss et al. described a case of a 52-year-old male with generalized muscle weakness, an extremely rare clinical manifestation of sarcoidosis diagnosed using positron emission tomography scan and confirmed by histopathology.[17] He was successfully treated with glucocorticoids and MTX. Thomas et al. described a patient with drug-induced myositis caused by thionamide.[18] These authors describe a 31-year-old female with Graves' disease who developed carbimazole-induced myositis, only the 2nd reported case in the literature. The authors pointed out the difficulties in the diagnosis of drug-induced cases, but the early diagnosis is essential because of the danger of developing rapid muscle damage and rhabdomyolysis and renal failure. They pointed out the importance of being alert to the development of myalgia and muscle weakness in patients with thyroid disorders, especially after being started on antithyroid drugs.

Complications, including calcinosis, involvement of other organs, and unusual presentations of idiopathic inflammatory myopathies and its treatment

Misra et al. recently described a unique case of a woman with PM refractory to high-dose steroid and MTX, because of which she developed miliary tuberculosis.[19] Her myositis went into remission after initiation of antitubercular therapy, despite bringing down the intensity of immunosuppression. The authors pointed out that this was the first reported case of myositis undergoing remission after treating intercurrent infection. They discuss the complex relationship between autoimmune disease and host response to infection and pointed out the problem posed by the opportunistic infections in patients receiving immunosuppressive therapy for the underlying autoimmune diseases.

Saini et al. have recently discussed the problem of calcinosis in JDM; frequency, risk factors and outcome and emphasize the poor outcome associated with extensive calcinosis.[20]

Dhooria et al. described a 62-year-old man with a lethal hemorrhagic myositis.[21] The patient presented with a 3-week history of fever and severe DM with typical symmetrical proximal muscle weakness, skin lesions of DM, tachycardia, tachypnea, hypoxia, and shock. The muscle enzymes were elevated. High-resolution computed tomography of the chest was suggestive of ILD. Despite intravenous methylprednisolone pulses and intravenous immunoglobulin G, he deteriorated with a fall in hemoglobin. Urgent computed tomography was done, which revealed right psoas hematoma with contrast extravasation at the L3 level. Treatment was ineffective in his case and he died.

In a case-report, Mantoo et al. have recently described JDM with IgA nephropathy.[22] The authors reported a 10-year-old boy with JDM who developed renal involvement that was proved to be IgA nephropathy on biopsy. The child responded dramatically to the conventional therapy with steroids and MTX for the primary disease and remained well in the 6 months of follow-up. In the literature review, they found 11 cases of IIMs with renal involvement. Four patients (one JDM, two PM, and one DM) had IgA nephropathy, out of which three patients responded to the conventional therapy of primary disease and only one patient with PM needed hiking immunosuppression targeted for renal condition.

A hitherto undescribed complication of IIM namely, asymptomatic vertebral fractures has been described by Gupta et al.[23] They observed that 46% had asymptomatic vertebral fractures, of whom 19% had >1 fracture. Half the fractures occurred in those with disease duration of <5 years. The 11th–12th thoracic vertebrae together were the most common. Of the 70 who underwent bone mineral density assessment, 62.7% were osteopenic and 26.9% were osteoporotic. Interestingly, gender, age, disease duration, years of corticosteroid intake, body mass index, years postmenopause, and myositis damage index did not correlation with the number of fractures.

Case reports with specific clinical message

In 2017, Kumar et al. described “The Expanding Spectrum of Gottron's Papules in JDM.”[24] They presented a boy where the lesions were present on the forearm that healed leaving thin scars.

Jindal et al. described “reverse Gottron's papules” in JDM in 4 out of 127 patients, where the papules were present over the palmar surface.[25] They pointed out that this is a rare clinical sign and could be associated with ILD.

Emphasis on juvenile idiopathic inflammatory myopathies

Challa et al. conducted a clinicopathological study on Juvenile IIM.[26] Juvenile idiopathic inflammatory myopathy constituted 15.25% of all IIM patients that they studied. They found that JDM was the most common subgroup (24/27) followed by juvenile OM (JOM) (3/27) in association with systemic lupus erythematosus (2) and systemic sclerosis (1). They pointed out that JOM was characterized by autoantibodies and perivascular inflammation and concluded that juvenile IIMs were rare with JDM being the most common subtype. They also observed that the muscle biopsy evaluation as per the European Neuromuscular Centre (ENMC) criteria characterized the subgroups appropriately.

Hussain et al. have recently reported on the autoantibodies in children with JDM that included both the MSAs and the MAAs.[27] Their study included 30 patients, 9 of them (~30%) were positive for one of the 12 autoantibodies tested. Anti-SRP antibody was the most common antibody detected in three patients followed by anti-MDA-5 antibody in two patients, while anti-Jo1 antibody, anti-TIF1-γ antibody, anti-Mi-2 antibody, and anti-PM-Scl antibody were positive in 1 patient each. The authors concluded that the estimation of autoantibodies may serve as an adjunct tool in delineating and defining distinct clinical phenotypes in children diagnosed with JDM. They may also help in prognostication.

Causes of mortality and related publications: Emphasis on juvenile idiopathic inflammatory myopathies

Muhammed et al. recently analyzed the leading cause of in-hospital mortality in Indian patients with inflammatory myopathy. In a study of 38 patients, they found that infections are the leading cause of in-hospital mortality in Indian patients with inflammatory myopathy.[28] Twenty-four (63.2%) patients had infection as the primary cause of death.

Another study presented experience on the mortality of 76 children with JDM over two decades.[29] Of these, 63 had JDM, 3 had PM, while 10 had an overlap syndrome. There were 7 (11.1%) deaths over a 9-year period. The causes included severe muscle weakness needing nasogastric tubes, cutaneous ulcers and superadded infections, gastrointestinal vasculitis, intestinal perforation, and progressive pulmonary disease. The authors opined that survival in JDM has steadily improved, yet the disease remains a serious illness and still carries significant mortality in the context of a developing country.

Prasad et al. compared their experience with JDM patients seen long ago with the more recently diagnosed patients.[30] The authors concluded that compared to their experience in the previous decade, there were more girls, MTX was more often used upfront, but the median duration of illness and prevalence of calcinosis (30%) was the same. Their message was that there was a need to improve awareness about JDM among pediatricians for early referral.

Pregnancy-related issues in idiopathic inflammatory myopathies

In a seminal paper, Gupta et al. recently described the outcomes of pregnancy in women with inflammatory myositis.[31] The question they asked was the effect of disease activity and the treatment given on fertility and the pregnancy outcome. This was an interview-based retrospective study of 81 patients with a median age of 32 years and disease duration of 4 years. There were 45 patients with DM, 20 with PM, and 16 with OM; the history of conception was present in 63 patients before the disease onset, resulting in 205 pregnancies and 155 live births over 315.2 patient-years of follow-up. After disease onset, there were 24 pregnancies (6 live births, 16 spontaneous abortions, and 2 induced abortions) in 7 women over 77.5 patient-years. Of the live births, 1 had cleft palate, 1 had low birth weight, and 1 was preterm. None of the patients who conceived had antiphospholipid antibodies. Obstetric complications and fetal complications occurred more frequently in pregnancies after the onset of myositis, but not in maternal complications. Conception after the onset of myositis had higher risk of abortion. The authors concluded that the pregnancy outcome in IIM patients was characterized by poor fetal outcomes as well as high rates of spontaneous abortion rates in the absence of clinical or serological antiphospholipid syndrome. It is interesting to note that soon after the publication of this paper, a similar paper has been published by Swedish workers with similar findings.[32]

Report of idiopathic inflammatory myopathy patients with a specific clinical subtype – Necrotizing autoimmune myopathy

Ayesha et al. carried out a clinicopathological study of a clinically homogeneous group of IIM patients belonging to the category of “necrotizing autoimmune myopathy.”[33] Theirs was a retrospective study including 15 patients of NAM diagnosed on muscle biopsy over a period of 2 years. Overall, they had 15 patients with NAM of a total of 110 patients (~14%). These were grouped into CTD-associated NAM, statin-associated NAM, paraneoplastic NAM, and idiopathic NAM, which was the common type. All cases presented with progressive proximal muscle weakness and had markedly elevated CPK levels. Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase and anti-SRP antibodies were seen to be positive in six patients. Muscle biopsies showed predominant fiber necrosis with significant fiber degeneration and regeneration in the absence of inflammation. All patients received immunotherapy with significant improvement seen in six patients with two mortalities.

Indian studies comparing different (old, new, and the latest) criteria for idiopathic inflammatory myopathies

Challa et al. have recently published a study on adult IIM patients comparing the old Bohan and Peter criteria of 1976 with the ENMC 2004 criteria.[34] The authors report on 69 patients who fulfilled the ENMC criteria. According to these criteria, the 53 of the 69 patients could be categorized as follows: DM, 30; PM, 2; immune-mediated necrotizing myopathy, 9; and nonspecific myositis, 12 patients. In contrast, subgrouping by the Bohan and Peter criteria was as follows: DM in 9 and PM with and without CTD in 26 patients only. The authors report that DM was underdiagnosed because perifascicular atrophy was not recognized as a diagnostic histological feature, and there was also an overdiagnosis of PM with and without CTD due to poor characterization of histological features in PM by the Bohan and Peter criteria. The study was interesting as it reported 16 patients with s-IBM. These authors concluded that the ENMC criteria with basic panel of histochemical stains improved the diagnostic yield of IIM significantly when compared to the Bohan and Peter criteria.

In a recent paper, Pinto et al. studied the performance of the 2017 EULAR/ACR criteria in a retrospective cohort of adult and juvenile IIM comparing the same with the older Bohan and Peter criteria.[35] The study included 111 patients (87 females), 11 were juveniles. Ninety-three (83.8%) patients were classified as probable/definite myositis using the Bohan and Peter criteria. Eighty-nine (80.2%) patients were classified as having probable/definite inflammatory myositis using the new criteria. Agreement between the two criteria was weak in our cohort (κ-0.331). Complete details of muscle biopsy were available in 52 patients. In this subgroup, 96% were classified by Bohan and Peter and 80.8% by EULAR/ACR criteria. Bohan and Peter classified 73% and EULAR/ACR 82% of patients when biopsy was excluded (n = 111). Both criteria classified over 90% of the patients with DM. Forty-two patients were clinically diagnosed as PM, of these 32 patients had myositis overlap syndrome. Bohan and Peter classified 66.7% and EULAR/ACR classified 64.3% in this subset. Bohan and Peter criteria had high sensitivity in the presence of muscle biopsy compared with EULAR/ACR. The authors concluded that the performance of the EULAR/ACR criteria was similar to Bohan and Peter in the absence of muscle biopsy. Both criteria had poor sensitivity in PM.

Basic molecular research including the basis of the inflammatory pathology in the muscles and its immunogenetics – Reports from India

In an immunological investigation of IIM, Gupta et al. studied B cell survival factors, namely, the serum levels of BAFF and APRIL and correlated the clinical features of IIM and with the MSA/MAA antibodies.[36] Their study included 75 patients (51 females and 24 males) classified by Bohan and Peter criteria and 25 healthy controls. Their blood samples were analyzed for BAFF, APRIL and interleukin (IL)-17 by ELISA, and MSA/MAA) using line immunoblot assay. Of the 75 patients, 59 were adults, 42 had DM and 17 PM. The median disease duration was 5 (3–12) months. BAFF levels were significantly higher in IIM than healthy controls and in children with jDM than adults. BAFF levels were also significantly higher in adults with arthritis, weight loss, and pulmonary arterial hypertension. Among the various MSAs, lowest levels were seen in those with anti-SRP. The median follow-up duration was 145 patient years. Twelve patients relapsed, while nine were in drug-free remission. BAFF levels were similar between these groups. Serum APRIL levels were elevated in limited number of patients with myositis, and the levels did not differ among the clinicoserological phenotypes. IL-17 levels were significantly higher in individuals positive for anti-SRP. Serum BAFF levels are elevated in IIM, more so in children. The authors concluded that the BAFF levels may be useful as a biomarker for PAH and arthritis. Furthermore, they suggested that the anti-SRP positivity association with elevated IL-17 levels could suggest a role in pathogenesis.

A few years ago, Nagapp et al. had reported on the major histocompatibility complex (MHC) and inflammatory cell subtype expression in inflammatory myopathies and muscular dystrophies from India.[37] These workers noted MHC-I upregulation in all samples of PM and DM. Interstitial and perivascular inflammation in PM consisted predominantly of the CD8 + cells. In DM, the interstitial and perimysial perivascular inflammatory cells were predominantly CD4 + T cells. The CD8 + T cells in DM were seen around endomysial vessels. It was of interest that the MHC-I upregulation was seen in all 16 cases of muscular dystrophy with the presence of inflammation. The authors concluded that the pattern of MHC-I and II expression appeared to be similar in both inflammatory myopathies and in muscular dystrophies with inflammation. Therefore, differentiating IIM with muscular dystrophies on the basis of MHC-I expression was difficult.

“Update” articles on idiopathic inflammatory myopathies from India

Recently, two review articles describing the state-of-the-art on MSA/MAA and their clinical correlation with IIM subsets have been published from India.[9],[38] These articles are targeted mainly for general physicians to update them on the newer antibodies and how they impact the clinical presentations and may also direct the best option for the treatment for patients with IIM. They also give a glimpse of the future of possible 'precision medicine' where patients with specific antibodies may get treated with a specific targeted drug.


Reviewing the subject of IIM as reported from India, it is observed that from the 1980s to 2010, only three major clinical series were published based on patients classified by Bohan and Peter criteria and more recently on the ENMC criteria. However, in the last 5 years or so, a large number of publications related to IIM have appeared. Most of them are case reports describing unusual presentations, muscle disease caused by infections, drugs, and chemicals that resemble IIM. Some major papers on JDM have also appeared describing the clinical features in detail. More encouragingly, in the last 2 years, more in-depth studies on MSAs/MAAs have appeared with their clinical correlations. Early characterization of the abnormalities in the components of the immune system has also been published. It is suggested that now the main thrust of work in the field of IIM in India should be an all-India multicenter study of a large cohort of patients with IIM from different parts of the country carefully analyzing the clinical features, electrophysiological characteristics, sarcoplasmic profile, detailed study of all the known MSAs/MAAs, detailed immunohistochemical analysis the muscle histology. Based on these characteristics, their appropriate categorization according to the ACR/EULAR criteria. Serious attempt must be made to study the clinicoserological features, which may help us in developing a truly clinico–immuno–histopathological classification of inflammatory muscle diseases. Once that is achieved, the homogeneous subsets of IIM categorized according to these features may then be used for targeted drug trials. It is hoped that the “Myositis-India” initiative by a group of active young rheumatologists will be able to achieve these goals in the next few years.

Another intriguing aspect of muscle disease is the gray-area between inflammatory–metabolic–genetic muscle diseases. How many of the patients with muscle disease appear like an inflammatory disease, but turn out to be uncommon genetic abnormalities or unusual metabolic problems? This area requires urgent attention as very often we are faced with patients where, despite detailed investigations, diagnosis remains a dilemma.


The author would like to thank Dr. Latika Gupta, Associate Professor, Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Research, Lucknow, for the help in the literature search for the relevant articles that are the basis of this paper.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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