Collaborative research in myositis-related disorders: MIHRA, a global shared community model.

Myositis International Health and Research Collaborative Alliance (MIHRA) is a newly formed purpose-built non-profit charitable research organization dedicated to accelerating international clinical trial readiness, global professional and lay education, career development and rare disease advocacy in IIM-related disorders. In its long form, the name expresses the community's scope of engagement and intent. In its abbreviation, MIHRA, conveys linguistic roots across many languages, that reflects the IIM community's spirit with meanings such as kindness, community, goodness, and peace. MIHRA unites the global multi-disciplinary community of adult and pediatric healthcare professionals, researchers, patient advisors and networks focused on conducting research in and providing care for pediatric and adult IIM-related disorders to ultimately find a cure. MIHRA serves as a resourced platform for collaborative efforts in investigator-initiated projects, consensus guidelines for IIM assessment and treatment, and IIM-specific career development through connecting research networks.MIHRA's infrastructure, mission, programming and operations are designed to address challenges unique to rare disease communities and aspires to contribute toward transformative models of rare disease research such as global expansion and inclusivity, utilization of community resources, streamlining ethics and data-sharing policies to facilitate collaborative research. Herein, summarises MIHRA operational cores, missions, vision, programming and provision of community resources to sustain, accelerate and grow global collaborative research in myositis-related disorders.

The Role of Myositis-Specific Autoantibodies and the Management of Interstitial Lung Disease in Idiopathic Inflammatory Myopathies: A Systematic Review.

OBJECTIVE: To evaluate the role of myositis-specific autoantibodies (MSAs) in interstitial lung disease (ILD), management of idiopathic inflammatory myopathies (IIM) associated ILD, and if there is a role for MSA specific management of ILD. METHODS: A systematic review was performed examining how MSAs relate to ILD manifestations in IIM patients and comparing treatment outcomes with varying immunosuppressive regimens. RESULTS: 112 papers were included in this analysis. Patients with anti-aminoacyl tRNA synthetase (anti-ARS) and anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibodies had consistently higher rates of ILD than other MSA groups. Anti-ARS positive patients had higher rates of chronic ILD whereas anti-MDA5 positive patients had higher rates of rapidly progressive ILD (RP-ILD). The most common high-resolution computed tomography (HRCT) patterns for ILD in anti-ARS and anti-MDA5 positive patients were nonspecific interstitial pneumonia (NSIP) and unclassifiable respectively. Anti-transcription intermediary factor 1-gamma (anti-TIF1-γ), anti-Mi-2, anti-nuclear matrix protein 2 (anti-NXP-2), and anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (anti-HMGCR) antibodies were associated with a decreased risk of ILD. Small sample sizes, a lack of head-to-head trials, and non-randomized designs prevented drawing meaningful conclusions with respect to immunosuppressive management. CONCLUSION: Clear relationships exist with regards to the ILD manifestations of certain MSAs. Standard therapy for IIM associated ILD (IIM-ILD) is glucocorticoids with the addition of others immunosuppressives in patients with or at risk of RP-ILD as well as in refractory cases. Immunosuppressives should be preferentially used in MSA populations in which they have been studied and shown to be efficacious.

Appropriateness of laboratory tests in the diagnosis of inflammatory rheumatic diseases among patients newly referred to rheumatologists.

INTRODUCTION: Autoantibody tests are commonly ordered when screening for rheumatic diseases. Rheumatoid factor (RF) and antinuclear antibody (ANA) have low positive predictive values in general practice. Overuse of diagnostic tests can result in an increase in unnecessary referrals, patient anxiety, and further costs. OBJECTIVE: The objective was to evaluate the utilization patterns, appropriateness, and associated costs of tests including ANA, extractable nuclear antibodies (ENA), anti-double stranded DNA (anti-dsDNA), RF, and HLA-B27 in patients referred to rheumatologists. METHODS: A review was conducted of consecutive referrals (accepted and rejected) using university rheumatologists' practices over one year. Inappropriate investigations, and associated costs were analyzed. Tests were considered appropriate if at least one criterion for a specific disease was provided. RESULTS: Of 638 referrals the most common reported reasons for referral were: spondyloarthropathies (SpA), rheumatoid arthritis (RA), and lupus (SLE). Prior to referral: 61% had undergone ANA testing at least once, ANA was repeated in one third; 19% had ENA and 21% had anti-dsDNA. 20% had ANA testing with no clinical indication. Half of ENA and anti-dsDNA testing was in the context of a negative ANA. RF was requested in 65% and in close to one third, there was no clinical suspicion of inflammatory arthritis. CONCLUSION: Despite the recommendations by CRA Choosing Wisely Campaign, at least 50% of laboratory investigations, including RF, ANA, ENA, and anti-dsDNA, are inappropriately ordered. More selective ordering of the above tests would lead to marked cost reduction.

A dermatomyositis/lichen planus overlap syndrome presenting with erythroderma: A case report.

This case report describes a novel presentation of a lichen planus and dermatomyositis overlap syndrome. The patient presented with pruritic and painful violaceous erythroderma with biopsy reports suggestive of both lichen planus and dermatomyositis. The patient failed first-line treatment with prednisone and hydroxychloroquine and eventually required treatment with methotrexate and intravenous immunoglobulin to achieve control of her disease. Overlap syndromes have been described between lichen planus and lupus erythematosus; however, to date, little has been described about a dermatomyositis/lichen planus overlap.

Dermatomyositis associated with omalizumab therapy for severe asthma: a case report.

BACKGROUND: Omalizumab is a humanized monoclonal antibody widely used for treatment of persistent allergic asthma and antihistamine-refractory chronic urticaria. Immediate adverse events to omalizumab are well characterized. Delayed anaphylactoid and serum sickness-like reactions have also been described; however, their relationship to the drug remains uncertain, and the frequency is unknown. CASE PRESENTATION: We present a case of a 59-year old female who developed amyopathic dermatomyositis (DM) after receiving omalizumab infusions for steroid-refractory severe asthma. After 6 months of omalizumab, the patient developed an erythematous, intensely pruritic cutaneous eruption. Skin biopsy indicated nonspecific features of dermatitis. However, neither topical corticosteroids nor gabapentin and maximal doses of multiple antihistamines gave her relief. On follow-up clinical exam 8 months later, she had classic cutaneous features of dermatomyositis, with confirmatory repeat skin biopsy. Laboratory investigations revealed negative myositis specific antibodies, positive antinuclear antibody, and negative anti-histone antibodies. Creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase levels and C-reactive protein were also within normal limits. These findings supported the clinical impression of amyopathic DM. The patient's symptoms improved with oral corticosteroid therapy. A malignancy screen was negative. There was no evidence of end organ dysfunction. CONCLUSIONS: Dermatomyositis is not a known adverse effect of omalizumab therapy. DM has a low incidence, but potentially life threatening consequences. Amyopathic DM may represent up to 21% of cases of DM, with similar risks of malignancy and end organ dysfunction. DM has been associated with biologic therapy. Using the Naranjo adverse drug reaction (ADR) probability scale, our patient had a "probable" omalizumab related ADR. A more likely explanation is that the patient had underlying DM that remained occult due to chronic corticosteroid therapy. Our case highlights the need for clinical vigilance and maintenance of a broad differential when patients on biologic therapies present with cutaneous eruptions. In our patient, the cutaneous clinical features of DM became pronounced over serial assessments. Laboratory markers may be deceptively normal, as in amyotrophic DM, or confounded by ongoing corticosteroid therapy. There are important clinical implications of prompt diagnosis, given the association of DM with end organ disease including interstitial lung disease, and possible concomitant malignancy.

Statin-associated immune-mediated myopathy: biology and clinical implications.

PURPOSE OF REVIEW: In the last 6 years, our understanding of statin-associated myopathy expanded to include not only a toxic myopathy with limited and reversible side-effects but also an autoimmune variety in which statins likely induce an autoimmune myopathy that is both associated with a specific autoantibody and responsive to immunosuppression and immune modulation. This review widens the reader's understanding of statin myopathy to include an autoimmune process. RECENT FINDINGS: Statin-associated immune-mediated myopathy provides an example of an environmental trigger (statins) directly implicated in an autoimmune disease associated with a genetic predisposition as well as potential risk factors including concomitant diseases and specific statins. Given a median exposure to statins of 38 months, providers should be aware that anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) myopathy may occur even after several years of statin exposure. SUMMARY: It is important for the reader to understand the clinical presentation of statin-associated immune-mediated myopathy and the difference in its clinical presentation to that of statins as direct myotoxins. Prompt recognition of such an entity allows the clinician to immediately stop the offending agent if it has not already been discontinued as well as to recognize that statin rechallenge is not a likely option, and that prompt treatment with immunosuppression and/or immunomodulation is usually of enormous benefit to the patient in restoring muscle strength and physical function. VIDEO ABSTRACT.

Thigh muscle MRI in immune-mediated necrotising myopathy: extensive oedema, early muscle damage and role of anti-SRP autoantibodies as a marker of severity.

OBJECTIVES: The aims of this study were to define the pattern of muscle involvement in patients with immune-mediated necrotising myopathy (IMNM) relative to those with other inflammatory myopathies and to compare patients with IMNM with different autoantibodies. METHODS: All Johns Hopkins Myositis Longitudinal Cohort subjects with a thigh MRI (tMRI) who fulfilled criteria for IMNM, dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) or clinically amyopathic DM (CADM) were included in the study. Muscles were assessed for intramuscular and fascial oedema, atrophy and fatty replacement. Disease subgroups were compared using univariate and multivariate analyses. Patients with IMNM with anti-signal recognition particle (SRP) autoantibodies were compared with those with IMNM with anti-HMG-CoA reductase (HMGCR) autoantibodies. RESULTS: The study included 666 subjects (101 IMNM, 176 PM, 219 DM, 17 CADM and 153 IBM). Compared with DM or PM, IMNM was characterised by a higher proportion of thigh muscles with oedema, atrophy and fatty replacement (p<0.01). Patients with IMNM with anti-SRP had more atrophy (19%, p=0.003) and fatty replacement (18%, p=0.04) than those with anti-HMGCR. In IMNM, muscle abnormalities were especially common in the lateral rotator and gluteal groups. Fascial involvement was most widespread in DM. Fatty replacement of muscle tissue began early during the course of disease in IMNM and the other groups. An optimal combination of tMRI features had only a 55% positive predictive value for diagnosing IMNM. CONCLUSIONS: Compared with patients with DM or PM, IMNM is characterised by more widespread muscle involvement. Anti-SRP-positive patients have more severe muscle involvement than anti-HMGCR-positive patients.

Immune-Mediated Necrotizing Myopathy: Update on Diagnosis and Management.

The idiopathic inflammatory myopathies (IIMs) comprise a group of autoimmune disorders that target skeletal muscle. They are characterized by typical laboratory and clinical features including muscle weakness, elevated muscle enzymes, characteristic histopathology of muscle biopsies, as well as electromyography abnormalities. The IIMs are divided into polymyositis, dermatomyositis, inclusion body myositis, nonspecific myositis, and immune-mediated necrotizing myopathy (IMNM). IMNM is distinguished by the absence of primary inflammation on muscle biopsy. IMNM may be associated with myositis-specific autoantibodies (i.e., anti-SRP and anti-HMGCR) and malignancy, in association with viral infections (HIV or hepatitis C), or in relation to other connective tissue diseases (i.e., scleroderma). Typical clinical findings such as severe muscle weakness, highly elevated creatine kinase (CK) levels, as well as resistance to conventional immunosuppressive therapy are associated with this subtype of IIM. This review provides an overview of this disease entity and focuses on its diagnosis and treatment.

Patients' Experience of Myositis and Further Validation of a Myositis-specific Patient Reported Outcome Measure - Establishing Core Domains and Expanding Patient Input on Clinical Assessment in Myositis. Report from OMERACT 12.

OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) myositis working group was established to examine patient-reported outcomes (PRO) as well as to validate patient-reported outcome measures (PROM) in myositis. METHODS: Qualitative studies using focus group interviews and cognitive debriefing of the myositis-specific Myositis Activities Profile (MAP) were used to explore the experience of adults living with polymyositis (PM) and dermatomyositis (DM). RESULTS: Preliminary results underscore the importance of patient input in the development of PROM to ensure content validity. Results from multicenter focus groups indicate the range of symptoms experienced including pain, fatigue, and impaired cognitive function, which are not currently assessed in myositis. Preliminary cognitive debriefing of the MAP indicated that while content was deemed relevant and important, several activities were not included; and that questionnaire construction and wording may benefit from revision. A research agenda was developed to continue work toward optimizing PRO assessment in myositis with 2 work streams. The first would continue to conduct and analyze focus groups until saturation in the thematic analysis was achieved to develop a framework that encompassed the patient-relevant aspects of myositis. The second would continue cognitive debriefing of the MAP to identify potential areas for revision. There was agreement that further work would be needed for inclusion body myositis and juvenile dermatomyositis, and that the inclusion of additional contributors such as caregivers and individuals from the pharmaceutical/regulatory spheres would be desirable. CONCLUSIONS: The currently used PROM do not assess symptoms or the effects of disease that are most important to patients; this emphasizes the necessity of patient involvement. Our work provides concrete examples for PRO identification.