Autoimmune Myopathy Research Articles

AUTOIMMUNE MYOPATHIES: P.306 Clinical correlates of KLRG1+ T cells in inclusion body myositis

Recent published data has firmly highlighted the role of immune dysfunction as possibly the primary pathogenic mechanism in inclusion body myositis (IBM), as clonal highly differentiated ``immunosenescent'' CD8+ T cells, phenotypically resembling terminally differentiated effector memory CD45RA+ T cells (TEMRA cells), are seen in circulation in over 75% of cases. The most prominent surface marker of these cells is killer cell lectin-like receptor G1 (KLRG1). The objective of this study is to correlate disease features, such as disease phenotype and severity, in IBM with peripheral blood levels of killer cell lectin-like receptor G1 (KLRG1)-expressing T cells.

AUTOIMMUNE MYOPATHIES: P.307 Evaluation of ACR/EULAR criteria for myositis diagnosis and classification in care pathways of a French neuromuscular reference centre

Idiopathic inflammatory myopathies (IIM or myositis) are a group of heterogeneous diseases with various pathophysiologies, phenotypes and prognosis. In 2017, ACR/EULAR proposed classification criteria to enable diagnosis and sub classification of IIM for clinical practice care and inclusion in clinical trials. This is an observational cohort study, evaluating the ACR/EULAR classification criteria on 160 patients including 128 IIM and 32 non-IIM in the Pitié Salpêtrière hospital reference center.

AUTOIMMUNE MYOPATHIES: P.302 Autoantibodies targeting membrane repair proteins represent a novel pathologic mechanism in idiopathic inflammatory myopathy

Idiopathic inflammatory myopathies (IIM) involve chronic inflammation of skeletal muscle and subsequent muscle degeneration due to an uncontrolled autoimmune response. The mechanisms leading to pathogenesis are not well understood, however IIM may be triggered by increased exposure of intramuscular antigens due to the defective sarcolemmal membrane repair. Sarcolemmal membrane repair involves an active resealing mechanism that restores barrier function of the membrane after injury and is a critical component of maintaining normal cellular physiology.

AUTOIMMUNE MYOPATHIES: P.297 A case of juvenile HMGCR antibody myositis presenting as limb girdle muscular dystrophy

We report another case of HMGCR antibody myositis mimicking limb girdle dystrophy on muscle MRI and even muscle biopsy. Only a few cases of juvenile HMGCR antibody myositis have been published and a recent article expands the spectrum of the disease. We present another case of a 15 yo girl with a progressive severe limb girdle dystrophy showing on muscle biopsy and on muscle MRI no sign of myositis but rather a “typical pattern” of Becker muscular dystrophy. Extended genetic investigations including Exome sequencing, Genome sequencing, transcriptome analysis were negative and reoriented the diagnosis toward acquired HMGCR antibody myositis with great improvement on IVIG treatment.

AUTOIMMUNE MYOPATHIES: P.308 Characteristics of chest CT-scan patterns of idiopathic inflammatory myopathies: association with myositis-specific autoantibodies

Interstitial lung disease (ILD), one of the most common extramuscular manifestations of idiopathic inflammatory myopathies (IIMs), is associated with poor prognosis. Myositis-specific autoantibody (MSA)-positivity is a key finding for IIM diagnosis. To date, no large-scale study on a European IIM population has assessed CT ILD features and MSAs. To identify different lung patterns associated with IIMs and evaluate potential relationships between the CT ILD findings and MSA. All consecutive IIM patients referred to an internal medicine department between 2003 and 2019 were included.

AUTOIMMUNE MYOPATHIES: P.312 ``Amyopathic'' MDA5-positive dermatomyositis with severe lung involvement presents with myositic morphological features

Dermatomyositis (DM) can be associated with the anti-melanoma differentiation-associated gene 5 (MDA5, IFIH1) autoantibody. Of note, patients present with severe extramuscular (notably lung and skin) manifestations and myopathy can be mild or missing, hence termed ``amyopathic'' DM previously. Interstitial lung disease is the leading cause of death in MDA5-DM, and death occurs frequently within one year after diagnosis in roughly 30% of these DM patients. We hereby report the autoptic findings of two male patients (30 and 42 years old) who succumbed to severe ILD in MDA5-related DM.

AUTOIMMUNE MYOPATHIES: P.305 Clinical onset of sporadic inclusion body myositis after years of immunosuppressive therapy

The pathogenesis of sporadic inclusion body myositis (sIBM) is unclear. Two main hypotheses correspond to the main components of the disorder's pathology: initiation by inflammation versus primarily degenerative process. These ideas are based on (i) an autoimmune attack against muscle fibres with infiltrates, invasion of non-necrotic fibres as well as frequent autoantibodies and (ii) disturbed autophagy and pathological protein aggregation in the general absence of a meaningful clinical response to immunosuppressive therapies.

AUTOIMMUNE MYOPATHIES: P.304 A case of polymyositis associated with diffuse large B cell lymphoma

Inflammatory myopathies consist of heterogenous group of immune-mediated muscle diseases including dermatomyositis, polymyositis and so on. Patients with inflammatory myopathies occasionally have malignancies such as breast, lung, colorectal cancer and nasopharyngeal carcinoma. There have been a few reports of patients with inflammatory myopathy and lymphoma. Herein, we report an unusual case of a 67-year-old male with inflammatory myopathy and diffuse large B cell lymphoma who initially presented with slowly progressive quadriparesis, axial weakness and abnormality in the electromyography and muscle magnetic resonance image (MRI).

AUTOIMMUNE MYOPATHIES: P.300 TSP-1 mediates muscle damage in brachio-cervical inflammatory myopathy and systemic sclerosis

Brachio-cervical inflammatory myopathy (BCIM) is characterized by weakness of proximal muscles of the upper limbs and cervical flexor and/or extensor muscles. The pathogenic mechanism behind BCIM is unknown, but findings on muscle biopsies, consistent with a necrotizing myopathy associated to fibrosis, macrophage and B cell infiltrates and complement deposition, suggest that specific pathways – different to those of the other inflammatory myopathies – are likely involved. To describe the clinical, serological and histological features of a cohort of patients with brachio-cervical inflammatory myopathy (BCIM) associated to Systemic Sclerosis (SSc) and unravel disease-specific pathophysiological mechanisms occurring in these patients.

AUTOIMMUNE MYOPATHIES: P.301 Optimizing hand-function patient outcome measures for inclusion body myositis

Inclusion body myositis (IBM) is the most common acquired myopathy after the age of 45. The slowly progressive and heterogeneous disorder is a challenge for measuring clinical trial efficacy. One current method for measuring progression utilizes the IBM Functional Rating Scale (FRS). We have found that the hand domain scores in the IBM-FRS do not consistently change until there is extreme loss of grip and finger flexor strength. Therefore, we performed a cross-sectional observational study of 83 IBM and 38 control patients recruited at the 2019 Annual Patient Conference of The Myositis Association.

Statin Associated Autoimmune Myonecrosis: Case Report With Delayed Onset and Treatment Challenges

Purpose: A case of delayed statin associated autoimmune myopathy (SAAM) is presented along with review of clinical findings and treatment strategies. Summary: A 54 year old male presented with proximal extremity weakness, difficulty ambulating, and dysphagia. Symptoms began when restarting atorvastatin 40 mg daily for a recent NSTEMI, following 10 years of statin use, interrupted after diagnosis of NASH. Relevant labs included CK of 13,618 IU/L, ALT/ AST of 568/407 IU/L, while additional liver, renal, and toxicology tests were normal. Following treatment response to prednisone 40 mg daily for 3 days, outpatient testing for anti-HMGCR antibodies was ordered. Twelve days from discharge, the patient was readmitted for myalgia and dysphagia, CK = 6042 IU/L, ALT/AST = 360/112 IU/L, and positive anti-HMGCR antibodies. Newly diagnosed with SAAM, symptoms improved with methylprednisolone and intravenous immunoglobulin (IVIG), continuing outpatient as daily prednisone and monthly IVIG. Four days later, the patient relapsed with worsened weakness and dysphagia, CK = 5812 IU/L, and ALT/AST = 647/337 IU/L. After response to methylprednisolone and rituximab, the patient was discharged on a corticosteroid taper, biweekly rituximab, and monthly IVIG. Two weeks later, a final admission involved a syncopal episode and fall, with a CK = 1461 IU/L. Treatment included IVIG, rituximab, and corticosteroid taper, which lead to remission for greater than 6 months. Conclusion: Statin associated autoimmune myopathy occurred when restarting atorvastatin, following 10 years of statin use. Clinical findings and positive anti-HMGCR antibodies confirmed the diagnosis. Recurrent relapses required triple combination therapy including addition of rituximab to achieve remission.

Paraneoplastic dermatomyositis: a case report from North-East India

<p>Dermatomyositis is a rare autoimmune myopathy with distinctive cutaneous changes. It has been associated with a wide range of malignancies like carcinoma ovary, lung, breast, gastrointestinal tract and non-Hodgkin’s lymphoma. The malignancy can be concurrent or can occur before or after the onset of myositis. We report a case of dermatomyositis in a 63-year-old Indian male with nasopharyngeal carcinoma. The characteristic cutaneous features and muscle weakness developed concomitantly with the onset of nasopharyngeal carcinoma.</p>

Cardiac and Respiratory Complications of Necrotizing Autoimmune Myopathy

ObjectiveTo characterize the cardiorespiratory abnormalities in patients with necrotizing autoimmune myopathy (NAM). Patients and MethodsCardiopulmonary features of patients with NAM evaluated in our neuromuscular clinic (January 1, 2004, to September 20, 2018) were reviewed retrospectively with respect to autoantibody status and history of cardiac disease. Clinical characteristics and laboratory findings were compared among patient subgroups. ResultsWe identified 109 patients with NAM: 36 anti–3-hydroxy-3-methylglutaryl coenzyme A reductase autoantibody (anti-HMGCR Ab)–positive, 18 anti–signal recognition particle antibody (anti-SRP Ab)–positive (3 dual anti-HMGCR/anti–SRP Ab–positive), and 58 seronegative. Median age at diagnosis was 60 years (range, 18-86 years). Forty-three patients had dyspnea at presentation and 32 patients had preexisting risk for cardiac disease (10 coronary artery disease and 28 hypertension). The electrocardiogram was abnormal in 55 of 86 patients (33 without cardiac risk factors), including prolonged corrected QT interval (QTc) (n=31), conduction blocks (n=19), and atrial or ventricular ectopic beats (n=10). Echocardiography was abnormal in 34 of 72 patients, including 19 of 45 without preexisting cardiac disease risks. Echocardiographic abnormalities included left ventricular diastolic dysfunction (n=31) and systolic dysfunction (n=8). The left ventricular diastolic dysfunction improved in 4 of 11 patients after treatment. Pulmonary function testing showed changes suggestive of neuromuscular respiratory muscle weakness in 51 of 66 patients and reduced carbon monoxide diffusing capacity in 11 of 35 patients. However, only 6 patients had radiographic evidence of interstitial lung disease (2 anti-HMGCR Ab–positive and 4 seronegative). Overnight oximetry revealed desaturations in 24 of 38 patients. Six patients required mechanical ventilation and 7 required noninvasive ventilatory support. ConclusionMost patients with NAM exhibited cardiac and respiratory muscle dysfunction. Immunotherapy can improve echocardiographic abnormalities. Interstitial lung disease was rarely identified. Formal evaluation of cardiac and respiratory status should be integral in assessment of patients with NAM.

Factors associated with refractory autoimmune necrotizing myopathy with anti-signal recognition particle antibodies

BackgroundAutoimmune necrotizing myopathy with anti-signal recognition particle antibodies (ANM-SRP) is regarded as refractory myositis, whereby some patients respond poorly to conventional immunosuppression and require B cell depletion treatment. This study aimed to evaluate factors associated with refractory ANM-SRP.ResultsClinical and pathological data from 48 patients with ANM-SRP were collected. We followed up clinical symptoms and image changes over 12 months. Univariate and multivariate analyses were undertaken to determine the associations between variables of interest and poor response to therapy. Refractory ANM-SRP appeared in 32.5% of patients who showed no or minimal improvement after 12 months of steroid therapy. The clinical risk factors for refractory patients were being male (OR, 19.57; P < 0.001), severe muscle weakness (OR, 7.51; P < 0.001) and concurrent interstitial lung disease (OR, 39.70; P < 0.001). The imaging refractory-related factor was the fatty infiltration rate of thigh muscles over 3 months (P = 0.022) and the pathological factor associated with refractory ANM-SRP was the high expression of B cell activating factor receptor (BAFF-R) in muscle (P = 0.036).ConclusionBeing male, severe muscle weakness, concurrent interstitial lung disease, quick development of muscle fatty infiltration and more BAFF-R and B lymphocyte infiltration in muscle indicate a poor response to immunosuppressive therapy in patients with ANM-SRP.

Idiopathic Inflammatory Myopathies

Myositis is a rare and an extremely heterogeneous autoimmune disease, that causes muscle weakness. Currently, "idiopathic inflammatory myopathies (IIM)" is the preferred umbrella-term used to describe the disease complexity within individuals. IIM include dermatomyositis, polymyositis, inclusion body myositis, autoimmune necrotizing myopathy, overlap myositis and antisynthetase syndrome. Research activity concerning myositis was very intense over the past ten years and led to new diagnostic approach as well as to novel therapeutic strategies. Correct classification is the key for successful management. One single treatment regime for every possible organ involvement in all different forms of IIM is still not existing.

Proceedings of the 2019 Canadian Inflammatory Myopathy Study Symposium: Clinical Trial Readiness in Myositis.

The Canadian Inflammatory Myopathy Study (CIMS) is a multicenter prospective cohort recruiting in 8 centers across Canada. One of the aims of CIMS is to conduct and participate in clinical trials in autoimmune inflammatory myopathies (AIM). Conducting clinical trials in rare diseases such as AIM presents challenges. During this symposium, experts in the field presented different solutions to successfully conduct clinical trials in AIM, including the importance of collaboration and careful trial design, as well as training and mentoring of young investigators.

An In-Depth Analysis of Our Myositis Cohort Following the Example of the EuroMyositis Registry

Background To describe our myositis cohort in-depth. Methods From January 2006 to December 2018, all newly diagnosed myositis patients were retrospectively enrolled in the study. We performed a subtype reclassification using the 2017 EULAR/ACR criteria, following the example of the EuroMyositis registry. Disease activity and damage were measured by the newest standardized assessment-tools for clinical studies. Comparisons between myositis subgroups were conducted using Fisher’s exact test. Results We enrolled 32 patients (25 were female): six patients with dermatomyositis, six with polymyositis, eleven with overlap myositis, six with antisynthetase syndrome, one with autoimmune necrotizing myopathy, one with juvenile antisynthetase syndrome and one with juvenile dermatomyositis. The overall median follow-up period was 23-months (9-44.75). Interstitial lung disease (ILD) was most frequently seen in patients with antisynthetase syndrome. Patients with overlap myositis were more likely to have polyarthritis mimicking rheumatoid arthritis, reduced capillary density in the nail fold capillaroscopy and Raynaud syndrome. Ovarian cancer during the follow-up period occurred in two patients (one with polymyositis and one with dermatomyositis). Myositis-related death was reported in two patients: acute respiratory failure in autoimmune necrotizing myopathy and dysphagia-related complications in polymyositis. Cyclophosphamide, methotrexate and rituximab demonstrated a significant steroid-sparing effect. In 22 of 32 patients, the myositis subgroup classifications made on the basis of our opinion and the new EULAR/ACR classification criteria were different, showing strong disagreement, especially in the subtype polymyositis. Conclusion Our analysis highlights the heterogeneity in myositis subgroups and shows the steroid-sparing effect of cyclophosphamide, methotrexate and rituximab.

Polymyositis Presenting as Rhabdomyolysis After the Initiation of Omeprazole

Rhabdomyolysis is a clinical syndrome with a wide range of presentations; it results in muscle necrosis and release of intracellular muscle contents into the circulation. Inflammatory myopathies are a rare cause of rhabdomyolysis. We present a case of a 46-year-old male with a two-week history of progressively worsening diffuse muscle pain after he had been prescribed omeprazole one month prior. A creatine phosphokinase (CPK) elevation was noted, which persisted despite treatment with IV fluids, sodium bicarbonate, and close correction of electrolytes. Further workup, including autoimmune and infectious etiologies, was notable for elevated antinuclear antibodies (ANA), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Furthermore, a muscle biopsy showed evidence of endomysial inflammatory cells, consistent with a diagnosis of polymyositis. Steroids were initiated with significant improvement in symptoms and a decrease in CPK levels. The patient was discharged on a tapering dose of steroids and, on follow-up with the rheumatologist, transitioned to methotrexate with control of symptoms. In patients with rhabdomyolysis who do not respond to first-line therapy, obtaining a detailed medication history and screening with ANA and ESR are encouraged. Given the link between medication and autoimmune disease, clinicians should consider autoimmune myopathy in the differential for cases with persistently elevated creatine kinase. Prompt diagnosis with early initiation of immunosuppressive medication may improve outcomes and avoid complications associated with untreated rhabdomyolysis or polymyositis.

Dermatomyositis as a presenting feature of locally advanced breast cancer

Breast cancer is the most common malignancy in women in India. Although it is a common malignancy, it may sometimes present with rare manifestations of idiopathic autoimmune inflammatory myopathy. The diagnosis can be challenging as the skin manifestations may be masked by the advanced nature of the disease. Here, we present a case of a postmenopausal lady who presented with a breast lump with overlying skin rash extending up to the neck. It was initially considered to be a part of locally advanced breast cancer. However, subsequently, she presented with proximal muscle weakness with typical electromyographic features and raised muscle enzymes. Her symptoms started resolving with neoadjuvant chemotherapy and radiotherapy.

Inflammatory myositis in systemic lupus erythematosus.

The coexistence of inflammatory myositis in systemic lupus erythematosus (SLE) has not been extensively studied. In this study, we describe the incidence, distinct types of inflammatory myositis, and risk factors for this finding in a cohort of pediatric and adult SLE patients. We identified SLE patients with coexisting myositis followed between 2010 and 2019 at two pediatric hospitals and one adult hospital. Demographic, clinical, laboratory, and pathological features of myositis were collected, and descriptive statistics were applied. A total of 1718 individuals were identified as having SLE (451 pediatric and 1267 adult patients). Of these, 108 were also diagnosed with inflammatory myositis (6.3%). People of black race had a significantly higher prevalence of inflammatory myositis, as did those with childhood-onset SLE compared to adult-onset disease. In the majority of patients (68%), SLE and inflammatory myositis presented concurrently. Overlapping features of systemic sclerosis occurred in 48%, while dermatomyositis-specific rashes were present in a third. Arthralgias and inflammatory arthritis were seen in >90%. Thrombotic events and significant pregnancy-related morbidity were present in more than a third of patients. Lymphopenia, hypocomplementemia, and a positive RNP were the most common laboratory features noted. Myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) were present in >40% of patients. A review of 28 muscle biopsy reports revealed a wide array of pathological features, including nonspecific changes, dermatomyositis, polymyositis, and necrotizing auto-immune myopathy. In our SLE patient population, 6.3% presented with concurrent inflammatory myositis. Dermatomyositis-specific rashes, clinical features of systemic sclerosis, arthralgias and arthritis, and cytopenias were common coexisting clinical manifestations. A high frequency of RNP, MSA, and MAA were found. People of black race and with childhood-onset disease had a higher prevalence of myositis. Our findings suggest that SLE patients of black race, with childhood-onset SLE, and who possess MSA or MAA should be routinely screened for myositis.