scholarly journals Immune-Mediated Necrotizing Myopathy, Associated With Antibodies to Signal Recognition Particle, Together With Lupus Nephritis: Case Presentation and Management

2015 ◽  
Vol 7 (6) ◽  
pp. 490-494 ◽  
Author(s):  
John O’Grady ◽  
Len Harty ◽  
Nick Mayer ◽  
Val Critcher ◽  
John Ryan
Keyword(s):  
Lupus Nephritis ◽  
Signal Recognition Particle ◽  
Signal Recognition ◽  
Case Presentation ◽  
Necrotizing Myopathy ◽  
Immune Mediated

scholarly journals Immune checkpoint inhibitor-associated myopathy: a clinicoseropathologically distinct myopathy

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Shahar Shelly ◽  
James D Triplett ◽  
Marcus V Pinto ◽  
Margherita Milone ◽  
Felix E Diehn ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Signal Recognition Particle ◽  
Ocular Involvement ◽  
Signal Recognition ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Coa Reductase

Abstract Immune checkpoint inhibitors have revolutionized the landscape of cancer treatment. Alongside their many advantages, they elicit immune-related adverse events, including myopathy, which potentially result in substantial morbidity if not recognized and treated promptly. Current knowledge of immune checkpoint inhibitor-associated myopathy is limited. We conducted a 5-year retrospective study of patients with immune checkpoint inhibitor-associated myopathy. Clinical features, survival and ancillary test findings were analysed and compared with those of immune-mediated necrotizing myopathy patients without immune checkpoint inhibitor exposure seen during the same time period. We identified 24 patients with immune checkpoint inhibitor-associated myopathy (median age 69 years; range 28–86) and 38 patients with immune-mediated necrotizing myopathy. Ocular involvement occurred in 9/24 patients with immune checkpoint inhibitor exposure, without electrodiagnostic evidence of neuromuscular transmission defect, and in none of the immune-mediated necrotizing myopathy patients (P < 0.001). Myocarditis occurred in eight immune checkpoint inhibitor-associated myopathy patients and in none of the immune-mediated necrotizing myopathy patients (P < 0.001). Median creatine kinase was 686 IU/l in the immune checkpoint inhibitor cohort (seven with normal creatine kinase) compared to 6456 IU/l in immune-mediated necrotizing myopathy cohort (P < 0.001). Lymphopenia was observed in 18 and 7 patients with and without immune checkpoint inhibitor exposure, respectively (P < 0.001). Myopathological findings were similar between patients with and without immune checkpoint inhibitor exposure, consisting of necrotic fibres with no or subtle inflammation. Necrotic fibres however arranged in clusters in 10/11 immune checkpoint inhibitor-associated myopathy patients but in none of the immune checkpoint inhibitor-naïve patients (P < 0.001). Despite the lower creatine kinase levels in immune checkpoint inhibitor-exposed patients, the number of necrotic fibres was similar in both groups. Immune checkpoint inhibitor-associated myopathy patients had a higher frequency of mitochondrial abnormalities and less number of regenerating fibres than immune-mediated necrotizing myopathy patients (P < 0.001). Anti-hydroxy-3-methylglutaryl-CoA reductase or signal recognition particle antibodies were absent in patients with immune checkpoint inhibitor exposure but positive in two-thirds of immune checkpoint inhibitor-naïve patients. Most patients with immune checkpoint inhibitor-associated myopathy responded favourably to immunomodulatory treatments, but four died from myopathy-related complications and one from myocarditis. Intubated patients had significantly shorter survival compared to non-intubated patients (median survival of 22 days; P = 0.004). In summary, immune checkpoint inhibitor-associated myopathy is a distinct, treatable immune-mediated myopathy with common ocular involvement, frequent lymphopenia and necrotizing histopathology, which contrary to immune-mediated necrotizing myopathy, is featured by clusters of necrotic fibres and not accompanied by anti-hydroxy-3-methylglutaryl-CoA reductase or signal recognition particle antibodies. Normal or mildly elevated creatine kinase level does not exclude the diagnosis.

Clinical Characteristics of Immune-Mediated Necrotizing Myopathy with Autoantibodies Recognizing the Signal Recognition Particle: A Retrospective Study of a Chinese Cohort

2021 ◽  
Author(s):  
Qi Tang ◽  
Jinshen He ◽  
Feng Li ◽  
Jinwei Chen ◽  
Jing Tian ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Inflammatory Myopathy ◽  
Signal Recognition Particle ◽  
Idiopathic Inflammatory Myopathy ◽  
Lower Limbs ◽  
Hunan Province ◽  
Signal Recognition ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Chinese Cohort

Abstract Objective: Immune-mediated necrotizing myopathy (IMNM) with autoantibodies recognizing the signal recognition particle (SRP) patients tend to have prominent proximal weakness and infrequent extra-muscular involvement, especially interstitial lung disease (ILD). However, we reported a Chinese cohort of anti-SRP IMNM patients with relatively more frequent ILD.Methods: Anti-SRP IMNM patients from September 2016 to November 2019 were included according to the most recent European Neuromuscular Center criteria for IMNM. All sera for anti-SRP autoantibody and other myositis-related autoantibodies detection were obtained before the treatment initiation. Muscle strength, coexisting autoimmunity, complications including ILD, treatment and follow-up outcomes were also recorded. Univariate logistic regression was performed to determine variables predicting bad outcomes.Results: Of 271 patients with idiopathic inflammatory myopathy tested, we diagnosed 23 (8.5%) patients with anti-SRP IMNM. Muscle weakness was presented in 23 patients (100%) and generally worse in the lower limbs. ILD was observed in 50% anti-SRP IMNM patients. Predictor of bad outcomes identified by univariate logistic regression analysis was complicated ILD (odds ratio, 3.8).Conclusion: ILD tends to be more frequent in this Chinese anti-SRP IMNM cohort from Hunan province. Complicated ILD represents a risk factor for bad outcomes for anti-SRP IMNM.

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.

scholarly journals Statins and Immune-Mediated Necrotizing Myopathy

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Mauro Turrin
Keyword(s):  
Present Article ◽  
Signal Recognition Particle ◽  
Intravenous Immunoglobulins ◽  
Pharmacological Therapy ◽  
High Dose ◽  
Signal Recognition ◽  
Drug Induced ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Diagnosis Classification

Statins are a well-recognized cause of a variety of skeletal myopathic effects, which generally resolve when discontinuing the treatment. Among autoimmune manifestations associated with statins, there is immune-mediated necrotizing myopathy (IMNM).The present article summarizes the main features of statin-related IMNM, describing diagnosis, classification, epidemiology, treatment, and the main autoantibodies detected.Statins are a well-recognized cause of a variety of skeletal myopathic effects, which generally resolve when discontinuing the treatment. Among autoimmune manifestations associated with statins, there is immune-mediated necrotizing myopathy (IMNM).The present article summarizes the main features of statin-related IMNM, describing diagnosis, classification, epidemiology, treatment, and the main autoantibodies detected.Although it is impossible to define the precise number, it evident that more than 550 statin-related IMNM cases have been described in the literature. Among IMNM, two forms must be distinguished: with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and with anti-signal recognition particle (SRP) antibodies. The differential diagnosis should be made between the IMNM and self-limited statin-related myopathy, drug-induced rhabdomyolysis, and nonautoimmune myopathies.Patients who have failed to normalize high creatine phosphokinase (CPK) after statin withdrawal should be tested for anti-HMGCR antibodies and, if these are positive, undergo muscle biopsy to confirm the diagnosis of IMNM. Pharmacological therapy of IMNM, not yet based on evidence, involves the use of high-dose corticosteroids, immunosuppressant drugs used alone or in combination, intravenous immunoglobulins (IVIg) or plasmapheresis.

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 Interstitial lung disease is not rare in immune-mediated necrotizing myopathy with anti-signal recognition particle antibodies

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Yongpeng Ge ◽  
Hanbo Yang ◽  
Xinyue Xiao ◽  
Lin Liang ◽  
Xin Lu ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Pulmonary Function Tests ◽  
Signal Recognition Particle ◽  
Ground Glass Opacity ◽  
Signal Recognition ◽  
High Resolution Computed Tomography ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Long Term Follow Up

Abstract Objectives The purpose was to clarify the characteristics of interstitial lung disease (ILD) in immune-mediated necrotizing myopathy (IMNM) patients with anti-signal recognition particle (SRP) antibodies. Methods Medical records of IMNM patients with anti-SRP antibodies were reviewed retrospectively. Results A total of 60 patients were identified. Twenty-seven (45.0%) patients were diagnosed with ILD based on lung imaging: nonspecific interstitial pneumonia (NSIP) in 17 patients (63.0%) and organizing pneumonia in 9 patients (33.3%). Reticulation pattern was identified in 17 patients (63.0%) whereas 10 cases (37.0%) showed ground glass opacity and patchy shadows by high-resolution computed tomography (HRCT). Pulmonary function tests (PFTs) were available in 18 patients, 6 (33.3%) and 10 (55.6%) patients were included in the mild and moderate group, respectively. The average age at the time of ILD onset was significantly older than those without ILD (48.6 ± 14.4 years vs. 41.2 ± 15.4 years, p < 0.05), and the frequency of dysphagia in the ILD group was higher than the group without ILD (p < 0.05). Long-term follow-up was available on 9 patients. PFTs were stable in 8 (88.9%), and the HRCT remained stable in 6 (66.7%) patients. Conclusions ILD is not rare in IMNM patients with anti-SRP antibodies, most being characterized as mild to moderate in severity. NSIP is the principal radiologic pattern, and ILD typically remains stable following treatment.

Immune Mediated Necrotizing Myopathy: Where do we Stand?

2018 ◽  
Vol 15 (1) ◽  
pp. 23-26 ◽  
Author(s):  
Abdel Gaffar A Mohammed ◽  
Ayanda Gcelu ◽  
Farzana Moosajee ◽  
Stella Botha ◽  
Asgar Ali Kalla
Keyword(s):  
Immunosuppressive Treatment ◽  
Signal Recognition Particle ◽  
Signal Recognition ◽  
Proximal Muscle ◽  
Inflammatory Myositis ◽  
Idiopathic Inflammatory Myositis ◽  
Muscle Disorders ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Inflammatory Infiltrates

Immune-mediated necrotizing myopathies (IMNMs) are a group of acquired autoimmune muscle disorders which are characterized by proximal muscle weakness, high levels of creatinine kinase, and myopathic findings on electromyogram (EMG). Muscle biopsy in IMNM differentiates it from the other subgroups of Idiopathic Inflammatory Myositis (IIM) by the presence of myofibre necrosis and prominent regeneration without substantial lymphocytic inflammatory infiltrates. Anti-signal recognition particle (SRP) and anti-3hydroxy-3 methylglutarylcoenzyme A reductase (HMGCR) autoantibodies were found in two-thirds of IMNM patients. In terms of treatment, IMNM is more resistant to conventional immunosuppressive treatment, therefore, other modalities of treatment such as Intravenous Immunoglobulin (IVIG) and rituximab are often required.

Sign in / Sign up

Export Citation Format

Share Document