A Case of Immune-Mediated Necrotizing Myopathy With Associated Skeletal Muscle Involvement by Sarcoid Granulomata: A Rare Association

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S69-S69
Author(s):  
Shalla Akbar ◽  
Sandhya Dasaraju ◽  
Osama Elkadi
Keyword(s):  
Skeletal Muscle ◽  
Muscle Weakness ◽  
Inflammatory Myopathies ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Muscle Enzymes ◽  
Muscle Involvement ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Skeletal Muscle Involvement

Abstract Skeletal muscle involvement by noncaseating granulomata occurs in a variety of conditions, including sarcoidosis, infections, and rarely in association with primary inflammatory myopathies such as inclusion body myositis (IBM) and dermatomyositis (DM). Sarcoid myopathy is typically asymptomatic; however, a picture of acute myositis with proximal muscle weakness has been described. Immune-mediated necrotizing myopathy (IMNM) is a subgroup of inflammatory myopathies typically presenting with proximal muscle weakness and markedly elevated muscle enzymes, mostly occurring in the setting of statin treatment. IMNM is associated with positive autoantibodies, but a subset of cases is antibody negative. Here we describe a case of myopathy occurring in association with sarcoidosis with combined features of granulomatous and necrotizing myopathy. The patient was a 54-year-old African American male with medical history significant for statin use 3 years ago, which was discontinued due to myalgia and elevated muscle enzymes and biopsy-proven sarcoidosis diagnosed on a pulmonary lymph node biopsy. He presented with progressive worsening of bilateral proximal weakness involving the upper and lower extremities. Electromyogram showed features of active myopathy with no evidence of peripheral neuropathy. Myositis panel was negative for the following antibodies: anti-Jo1, Mi-2, anti-Ku, PL-7, PL-12, OJ, EJ, and SRP. However, there was elevation of aldolase, CRP, and CK-MB. Biopsy of thigh and deltoid muscle showed necrotic muscle fibers, myophagocytosis with associated minimal inflammation, and multiple well-formed nonnecrotizing granulomas with multinucleated giant cells. Myopathic features include increased internalized nuclei, round atrophic fibers, and scattered split fibers. Specific features of IBM or DM were not present. Conclusion Myopathies developing or worsening after discontinuation of statin are rare. The association of necrotizing myopathy with sarcoidosis is not well described in the literature. Additional studies are warranted to elucidate this association.

scholarly journals THU0365 INCREASED HSP90 IN MUSCLE TISSUE AND PLASMA ASSOCIATES WITH DISEASE ACTIVITY AND SKELETAL MUSCLE INVOLVEMENT IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 414.1-414
Author(s):  
H. Štorkánová ◽  
S. Oreska ◽  
M. Špiritović ◽  
B. Heřmánková ◽  
O. Kryštůfková ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Disease Activity ◽  
Inflammatory Cells ◽  
Healthy Controls ◽  
Inflammatory Myopathies ◽  
Muscle Enzymes ◽  
Muscle Involvement ◽  
Hsp90 Expression ◽  
Muscle Biopsies ◽  
Skeletal Muscle Involvement

Background:Heat shock proteins (Hsps) are chaperones playing important roles in skeletal muscle physiology, adaptation to exercise or stress, and activation of inflammatory cellsObjectives:The aim of our study was to assess Hsp90 expression in muscle biopsies and plasma of patients with idiopathic inflammatory myopathies (IIM) and to characterize its association with IIM-related features.Methods:Total of 277 patients with IIM (198 females, 79 males; mean age 54.8; disease duration 4.1 years; DM, 104/PM, 108/CADM, 31/IMNM, 25) and 157 healthy individuals (92 females, 65 males; mean age 47.0) were included in plasma analysis. Muscle biopsy samples (PM, DM, IMNM, myodystrophy, myasthenia gravis) were stained for Hsp90α (Thermo Fisher Scientific, USA) and Hsp90β (Abcam, UK). Plasma Hsp90 was measured by ELISA kit (eBioscience, Vienna, Austria). The cytokines/chemokines were analysed by using Bio-Plex ProTMhuman Cytokine 27-plex Assay (BIO-RAD, California, USA.Data are presented as median(IQR).Results:In muscle biopsies, Hsp90 expression of both subunits (alpha and beta) was higher in IIM than in controls. Increased Hsp90 was detected in perifascicular degenerating and regenerating fibers, inflammatory cells (DM, PM), and necrotic and regenerating fibers (IMNM). Plasma Hsp90 levels were increased in IIM patients compared to healthy controls (55.9 (46.9 – 62.5)vs 9.76(7.5 – 13.8), p<0.0001), and in individual subgroups of IIM vs. healthy controls (DM-22.01(14.1 – 41.2), PM-19.7(14.3 – 42.2), CADM-18.9(11.7 – 29.7), IMNM-19.6(16.3 – 45.5), p<0.0001 for all). Hsp90 was higher in males compared to females (p=0.040) and in patients with ILD (p=0.003), cardiac involvement (p=0.004), dysphagia (p=0.018) and presence of anti-Ro52 (p=0.036). Hsp90 levels in all patients positively correlated with muscle enzymes (Tab.1). Hsp90 was associated with disease activity and skeletal muscle involvement (Tab.1). Out of all clinical parameters listed in above-mentioned univariate analysis, in multiple regression analysis Hsp90 levels in IIM patients were significantly affected by muscle enzymes only (p<0.0001, β=0.345). Furthermore, Hsp90 positively correlated with some crucial cytokines involved in pathogenesis of myositis (Tab. 1).Tab 1Clinical parametersSpearman’s rp – valueLDH; AST; ALT0.554; 0.383; 0.181< 0.0001; < 0.0001; 0.003PtDGA; PhDGA; MITAX; MYOACT0.223; 0.217; 0.175; 0.159< 0.001; < 0.001; 0.004; 0.012Pulmonary disease activity0.2010.001Muscle disease activity0.1460.018MMT8, total score; m. biceps brachii; m. gluteus maximus; m. iliopsoas-0.126; -0.125; -0.159; -0.1430.042; 0.043; 0.011; 0.023MDI – Myositis damage index – severity0.1500.041Current Prednisone equivalent dose0.1830.006Cytokines:IL-1b; IL-2; IL-4; IL-6; IFN-γ0.188; 0.269; 0.190; 0.182; 0.2290.002; < 0.0001; 0.002; 0.003; < 0.0001Conclusion:We demonstrate increased Hsp90 expression in IIM muscle biopsy samples, specifically in inflammatory cells, degenerating, regenerating and/or necrotic fibers. Increased Hsp90 plasma levels in IIM patients are associated with disease activity and damage, and with the involvement of proximal skeletal muscles, heart and lungs.Acknowledgments:Supported by AZV-16-33542A, MHCR 023728 and SVV – 260373.Disclosure of Interests:Hana Štorkánová: None declared, Sabina Oreska: None declared, Maja Špiritović: None declared, Barbora Heřmánková: None declared, Olga Kryštůfková: None declared, Heřman Mann: None declared, Martin Komarc: None declared, Josef Zámečník: None declared, Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Jiří Vencovský: None declared, Ladislav Šenolt: None declared, Michal Tomcik: None declared

scholarly journals Isolated Oropharyngeal Dysphagia as the Initial Presentation of Anti-SRP Immune-Mediated Necrotizing Myopathy

2020 ◽  
Author(s):  
Pat Korathanakhun ◽  
Thanyalak Amornpojnimman
Keyword(s):  
Muscle Weakness ◽  
Clinical Course ◽  
Signal Recognition Particle ◽  
Oropharyngeal Dysphagia ◽  
Signal Recognition ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Electrodiagnostic Study

A 51-year-old male initially presented with a progressive course of isolated oropharyngeal dysphagia prior to the clinical course of painful symmetrical proximal muscle weakness without sensory deficit which rendered him to wheelchairbound status within 5 months. The physical examination revealed symmetrical proximal muscle weakness without sensory symptoms. The initial serum creatine kinase was extremely high and the electrodiagnostic study revealed a myopathic pattern. A muscle biopsy of the left biceps suggested a diagnosis of immune-mediated necrotizing myopathy (IMNM) and the serum anti-signal recognition particle (SRP) autoantibody was finally detected. This case presented a rare form of anti-SRP IMNM in which isolated oropharyngeal dysphagia preceded the onset of proximal muscle weakness.

scholarly journals Statin-associated anti-HMGCR immune-mediated necrotizing myopathy with dermatomyositis-like features: A case report

2020 ◽  
Vol 8 ◽  
pp. 2050313X2098412
Author(s):  
Darosa Lim ◽  
Océane Landon-Cardinal ◽  
Benjamin Ellezam ◽  
Annie Belisle ◽  
Annie Genois ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Muscle Weakness ◽  
Inflammatory Myopathy ◽  
Idiopathic Inflammatory Myopathy ◽  
Intravenous Immunoglobulins ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Therapeutic Implications ◽  
Necrotizing Myopathy ◽  
Immune Mediated

Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) immune-mediated necrotizing myopathy is a subtype of idiopathic inflammatory myopathy which may be associated with statin exposure. It presents with severe proximal muscle weakness, high creatine kinase levels and muscle fiber necrosis. Treatment with intravenous immunoglobulins and immunosuppressants is often necessary. This entity is not commonly known among dermatologists as there are usually no extramuscular manifestations. We report a rare case of statin-associated anti-HMGCR immune-mediated necrotizing myopathy with dermatomyositis-like cutaneous features. The possibility of anti-HMGCR immune-mediated necrotizing myopathy should be considered in patients with cutaneous dermatomyositis-like features associated with severe proximal muscle weakness, highly elevated creatine kinase levels and possible statin exposure. This indicates the importance of muscle biopsy and specific autoantibody testing for accurate diagnosis, as well as significant therapeutic implications.

scholarly journals Juvenile Dermatomyositis and the Inflammatory Myopathies

2020 ◽  
Vol 40 (03) ◽  
pp. 342-348
Author(s):  
Collin Swafford ◽  
E. Steve Roach
Keyword(s):  
Muscle Weakness ◽  
Muscle Injury ◽  
Juvenile Dermatomyositis ◽  
Inflammatory Myopathies ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Rimmed Vacuoles ◽  
Immune Mediated ◽  
Primary Disorder ◽  
Tissue Changes

AbstractThe inflammatory myopathies comprise disorders of immune-mediated muscle injury. The histopathology and clinical features help distinguish them. Juvenile dermatomyositis (JDM) is the most common form of myositis in children and adolescents. Children with JDM present with proximal muscle weakness and characteristic rashes. The presentation is similar in children and adults, but JDM is a primary disorder and the adult form often is concerning for a paraneoplastic syndrome. Proximal muscle weakness occurs with dermatomyositis, polymyositis, and immune-mediated necrotizing myopathy, but the latter two conditions have no dermatologic findings or distinct tissue changes which set them apart from dermatomyositis. Inclusion body myositis, also included in the inflammatory myopathies, presents with more distal involvement, and microscopically exhibits identifiable rimmed vacuoles. We review key features of these disorders, focusing in more detail on JDM because it is more often encountered by the child neurologist.

scholarly journals Symptomatic muscle involvement in neurosarcoidosis: a clinicopathological study of 5 cases

2001 ◽  
Vol 59 (2B) ◽  
pp. 347-352 ◽  
Author(s):  
Rosana Herminia Scola ◽  
Lineu Cesar Werneck ◽  
Daniel Monte Serrat Prevedello ◽  
Priscila Greboge ◽  
Fábio Massaiti Iwamoto
Keyword(s):  
Side Effects ◽  
Normal Values ◽  
Clinical Course ◽  
The Other ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Muscle Enzymes ◽  
Muscle Involvement ◽  
Clinicopathological Study ◽  
Steroid Side Effects

We report on the clinical course and histopathologic muscle alterations of five patients diagnosed with neurosarcoidosis, who underwent biopsy due to their muscle manifestations. The five patients were females and only one was less than 40 years of age. Proximal muscle weakness was presented by all and only two patients complained of myalgia. Only normal values of serum muscle enzymes were detected. Electromyography revealed diverse findings such as normal, myopathic and neuropathic patterns. Granuloma was not present in one muscle biopsy. Two patients thoroughly recovered by taking only prednisone and one patient required a methotrexate addition for 3 months before becoming asymptomatic. The other two patients received azathioprine, one due to steroid side effects but without a satisfactory evolution, and the other to strengthen the prednisone régime, with excellent results.

Skeletal Muscle Ultrastructural Alterations In Alcoholism

1999 ◽  
Vol 5 (S2) ◽  
pp. 1162-1163
Author(s):  
B. Müller ◽  
H.J. Finol ◽  
I. Montes de Oca ◽  
A. Mayorca.
Keyword(s):  
Internal Medicine ◽  
Skeletal Muscle ◽  
Muscle Weakness ◽  
Lipid Droplets ◽  
Chronic Alcoholism ◽  
University Hospital ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Alcoholic Myopathy ◽  
Transmission Electron

Two forms of muscular alterations have been described in alcoholic patients, one acute, the so called Hypokalemic alcoholic Myopathy; focal or diffuse pain, swelling, tenderness and weakness of skeletal muscle are the main clinical features, and the chronic one with proximal muscle weakness wich progresses slowly in a period of weeks or months Ultrastructurally myofibril disorganization and necrosis where described.In this work we present a systematic study of skeletal muscle alterations in four alcoholic patients who attended the Department of Internal Medicine at Caracas University Hospital . The patients were males, ages between 56 and 62 years old, and presented chronic alcoholism with muscle weakness with a more distal distribution and polymyalgia. Biopsies were taken from quadriceps femorismuscle with a percutaneous neddle and processed for routine transmission electron microscopy.Muscle fibers showed different degrees of atrophy with myofibril disorganization (Fig.l) and disappearence (Fig.2). Myonuclei were hyperchromatic and intermyofibrilar spaces were widened and exhibited abundant lipid droplets.

Polymyositis and Dermatomyositis

2019 ◽  
pp. 187-189
Author(s):  
Josephina A. Vossen
Keyword(s):  
Muscle Biopsy ◽  
Clinical Examination ◽  
Immune Suppression ◽  
Imaging Modality ◽  
Idiopathic Inflammatory Myopathies ◽  
Inflammatory Myopathies ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Muscle Enzymes ◽  
Muscle Enzyme

Chapter 42 discusses polymyositis and dermatomyositis, which are idiopathic inflammatory myopathies characterized by muscle inflammation, proximal muscle weakness, and elevated muscle enzymes. Idiopathic inflammatory myopathies represent a heterogeneous group of muscle diseases. Diagnosis is based on clinical examination, muscle enzyme laboratory values, electromyography (EMG), and muscle biopsy. MRI is the most important imaging modality used in diagnosis and management. Radiographs and CT may detect calcinosis. Treatment is primarily by immune suppression.

scholarly journals Rituximab in the treatment of immune-mediated necrotizing myopathy: a review of case reports and case series

2021 ◽  
Vol 14 ◽  
pp. 175628642199891
Author(s):  
Anji Xiong ◽  
Guancui Yang ◽  
Zhuoyao Song ◽  
Chen Xiong ◽  
Deng Liu ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Case Reports ◽  
Signal Recognition Particle ◽  
High Dose ◽  
Signal Recognition ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Coa Reductase

Immune-mediated necrotizing myopathy (IMNM) is a group of immune-related myopathies characterized by progressive proximal muscle weakness, extremely high serum creatine kinase (CK) levels, and necrotic muscle fibers with a relative lack of inflammation. Treatment of IMNM is challenging, with most cases refractory to high-dose steroids in combination with multiple immunotherapies. The role of rituximab (RTX) for IMNM has been explored in isolated case reports and small series. The aim of this article was to perform a literature review of patients with IMNM treated with RTX and to evaluate RTX efficacy and safety. A total of 34 patients with IMNM were reviewed: 52.9% (18/34) with anti-signal recognition particle (SRP) antibodies and 47.1% (16/34) with anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies. Patient age at onset varied from 11 years to 81 years (mean 41 years). The majority of patients presented as a severe proximal muscle weakness and the peak level of CK varied from 3900 IU/L to 56,000 IU/L (mean 18,440 IU/L). Prior to RTX administration, all patients were treated with high-dose steroids and most were treated with multiple immunotherapies. The reason for initiating RTX was that 64.7% (22/34) of patients showed no improvement after previous treatments, and 35.3% (12/34) of patients relapsed when attempting to wean steroids or other immunosuppressive agents. With regard to RTX efficacy, 61.8% (21/34) of patients presented a response to RTX. Our data may support the use of RTX as an effective treatment strategy against IMNM resistant to steroids and multiple immunotherapies. Meanwhile, RTX as a first-line therapy could be a choice in IMNM, particularly in African Americans with anti-SRP antibody-positive subsets. ANA, antinuclear antibody; CK, creatine kinase; HMGCR, 3-hydroxy-3-methylglutaryl-CoA reductase; IMNM, immune-mediated necrotizing myopathy; MAC, membrane attack complex; MHC-I, major histocompatibility complex-I; RTX, rituximab; SRP, signal recognition particle.

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