Immune-mediated necrotising myopathy in asymptomatic patients with high creatine kinase

2020 ◽  
Vol 13 (10) ◽  
pp. e235457
Author(s):  
Izadora Fonseca Zaiden Soares ◽  
Victoria Fernandez Comprido ◽  
Bianca Raquel Ruoh Harn Scovoli Hsu ◽  
Alzira Alves de Siqueira Carvalho
Keyword(s):  
Creatine Kinase ◽  
Muscle Biopsy ◽  
Signal Recognition Particle ◽  
Disease Onset ◽  
Delayed Diagnosis ◽  
Signal Recognition ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Asymptomatic Patients ◽  
Immune Mediated

Subacute symmetrical proximal muscle weakness and persistent elevated creatine kinase levels are typical of immune-mediated necrotising myopathy (IMNM). These conditions are accompanied by copious myofibre necrosis, degeneration and regeneration with minimal to no inflammation on muscle biopsy. We report two cases (case 1 and case 2) of asymptomatic IMNM from different families with hyperCKaemia associated with positive anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies, respectively, and we also reviewed the literature. There are only a few previous descriptions of patients with asymptomatic IMNM.The disease onset could be insidious and lead to delayed diagnosis and treatment. We recommend testing for the anti-HMGCR and anti-SRP antibodies in patients with idiopathic hyperCKaemia because they could show no symptoms of this disorder.

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 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 Diagnostic modelling and therapeutic monitoring of immune-mediated necrotizing myopathy: role of electrical myotonia

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
James D Triplett ◽  
Shahar Shelly ◽  
Guy Livne ◽  
Margherita Milone ◽  
Charles D Kassardjian ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Odds Ratio ◽  
Coenzyme A ◽  
Signal Recognition Particle ◽  
Delayed Diagnosis ◽  
Signal Recognition ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Chronic Course ◽  
Coenzyme A Reductase

Abstract Delayed diagnosis of immune-mediated necrotizing myopathy leads to increased morbidity. Patients with the chronic course without 3-hydroxy-3-methylglutaryl-coenzyme-A reductase-IgG or signal recognition particle-IgG are often challenging to diagnose. Immunotherapy response can also be difficult to assess. We created a statistical model to assist immune-mediated necrotizing myopathy diagnosis. Electrical myotonia versus fibrillations were reviewed as biomarkers for immunotherapy treatment response. Identified were 119 immune-mediated necrotizing myopathy cases and 938 other myopathy patients. Inclusion criteria included all having electrophysiological evaluations, muscle biopsies showing inflammatory/necrotizing myopathies, comprehensively recorded neurological examinations, and creatine kinase values. Electrical myotonia was recorded in 56% (67/119) of retrospective and 67% (20/30) of our validation immune-mediated necrotizing myopathy cohorts, and significantly (P < 0.001) favoured immune-mediated necrotizing myopathy over other myopathies: sporadic inclusion body myositis (odds ratio = 4.78); dermatomyositis (odds ratio = 10.61); non-specific inflammatory myopathies (odds ratio = 8.46); limb-girdle muscular dystrophies (odds ratio = 5.34) or mitochondrial myopathies (odds ratio = 14.17). Electrical myotonia occurred in immune-mediated necrotizing myopathy seropositive (3-hydroxy-3-methylglutaryl-coenzyme-A reductase-IgG 70%, 37/53; signal recognition particle-IgG 29%, 5/17) and seronegative (51%, 25/49). Multivariate regression analysis of 20 variables identified 8 (including electrical myotonia) in combination accurately predicted immune-mediated necrotizing myopathy (97.1% area-under-curve). The model was validated in a separate cohort of 30 immune-mediated necrotizing myopathy cases. Delayed diagnosis of cases with electrical myotonia occurred in 24% (16/67, mean 8 months; range 0–194). Half (8/19) had a chronic course and were seronegative, with high model prediction (>86%) at the first visit. Inherited myopathies were commonly first suspected in them. Follow-up evaluation in patients with electrical myotonia on immunotherapy was available in 19 (median 21 months, range 2–124) which reduced from 36% (58/162) of muscles to 7% (8/121; P < 0.001). Reduced myotonia correlated with immunotherapy response in 64% (9/14) as well as with median creatine kinase reduction of 1779 U/l (range 401–9238, P < 0.001). Modelling clinical features with electrical myotonia is especially helpful in immune-mediated necrotizing myopathy diagnostic suspicion among chronic indolent and seronegative cases. Electrical myotonia favours immune-mediated necrotizing myopathy diagnosis and can serve as an adjuvant immunotherapy biomarker.

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.

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.

scholarly journals Statin and fibrate associed myopathy: study of eight patients

2004 ◽  
Vol 62 (2a) ◽  
pp. 257-261 ◽  
Author(s):  
Alzira A. Siqueira Carvalho ◽  
Ürsula Waleska Poti Lima ◽  
Raul Alberto Valiente
Keyword(s):  
Creatine Kinase ◽  
Muscle Weakness ◽  
Muscle Biopsy ◽  
Clinical Course ◽  
Lipid Lowering ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Inflammatory Infiltration ◽  
Lipid Lowering Drugs ◽  
Ragged Red Fibers

Lipid-lowering drugs have been occasionally associated with neuromuscular symptoms and muscle biopsy changes. We reported the clinical course and the muscle biopsy in eight patients with hyperlipoproteinemia, treated with lipid -lowering drugs (statins/fibrates). Five patients had myalgias while; in two cases there was proximal muscle weakness. All patients became asymptomatic after the withdrawal of the drug, although creatine kinase remained elevated. We performed muscle biopsy in six cases from three months to two years after suspension of the drug. We found variation in fibers diameters in all cases, with necrosis of fibers in five cases, inflammatory infiltration in one case, the presence of vacuolated fiber in one patient and ragged-red fibers in three subjects. We concluded that although the muscle biopsy findings were not specific, the prolonged use of statins and or fibrates might induce a chronic myopathy even in the absence of symptoms.

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.

Autoimmune necrotising myopathy and HMGCR antibodies

2018 ◽  
Vol 18 (2) ◽  
pp. 151-155 ◽  
Author(s):  
Kushan Karunaratne ◽  
Dimitri Amiras ◽  
Matthew C Pickering ◽  
Monika Hofer ◽  
Stuart Viegas
Keyword(s):  
Creatine Kinase ◽  
Clinical Course ◽  
Serum Creatine Kinase ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Immunomodulatory Treatment ◽  
Lower Serum ◽  
Immune Mediated ◽  
Lower Serum Cholesterol ◽  
Asymptomatic Elevation

Statins lower serum cholesterol concentrations by inhibiting the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). Muscle side effects are relatively common and include asymptomatic elevation of serum creatine kinase (CK), myalgia, proximal muscle weakness and rhabdomyolysis. More recently, a subset of cases of immune-mediated necrotising myopathy has been found to have antibodies against HMGCR. It is often an aggressive and debilitating myopathy and has a complex pathogenesis characterised by fibre necrosis, usually with minimal associated inflammation. Not all such patients are taking statins. The general consensus is that best treatment involves withdrawing the statin and giving immunosuppressive and immunomodulatory treatment. We describe three cases of HMGCR-related immune-mediated necrotising myopathy, detailing their clinical course and subsequent management, illustrating the spectrum of this disorder.

scholarly journals Statin-induced necrotising autoimmune myopathy and autoimmune hepatitis presenting with dysphagia

2020 ◽  
Vol 13 (2) ◽  
pp. e232391 ◽  
Author(s):  
Osama Qasim Agha ◽  
Sukhdeep Kaur ◽  
Nirmal Vijayavel
Keyword(s):  
Creatine Kinase ◽  
Autoimmune Hepatitis ◽  
Complete Resolution ◽  
Oropharyngeal Dysphagia ◽  
Liver Function Tests ◽  
Unknown Aetiology ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Autoimmune Myopathy ◽  
Smooth Muscle Antibodies

Statin-induced necrotising autoimmune myopathy (SINAM) is a rare disease characterised by proximal muscle weakness and elevated creatine kinase levels that is usually in the thousands. Anti-3-hydroxy-3-methyl glutaryl co-enzyme A reductase (HMGCR) antibodies are associated with SINAM. Autoimmune hepatitis (AIH) is an inflammatory disease of the liver that is usually of unknown aetiology but can also be associated with concurrent extrahepatic autoimmune disorders. We are reporting a case of biopsy proven AIH associated with SINAM in a patient presenting with oropharyngeal dysphagia. The patient had elevated anti-HMGCR antibodies and anti-smooth muscle antibodies. SINAM and AIH were confirmed by muscle biopsy and liver biopsy, respectively. The patient had complete resolution of his symptoms and complete normalisation of his liver function tests after 6 months of the treatment.

scholarly journals Hypothyroidism Presenting as Hoffman’s Syndrome – A Case Report

2015 ◽  
Vol 16 (2) ◽  
pp. 112-114
Author(s):  
NS Neki ◽  
Ishu Singh ◽  
Jasbir Kumar ◽  
Ankur Jain ◽  
Tamil Mani
Keyword(s):  
Case Report ◽  
Thyroid Function ◽  
Muscle Weakness ◽  
Muscle Biopsy ◽  
Muscle Hypertrophy ◽  
Thyroid Function Tests ◽  
Proximal Muscle Weakness ◽  
Proximal Muscle ◽  
Muscle Enzyme ◽  
Marked Elevation

Hoffman syndrome is characterized by pseudohypertrophy of muscles, muscle’s weakness & stiffness complicating hypothyroidism. We describe the disorder in a 45 years old female admitted with complaints of myalgia, proximal muscle weakness & calf muscle hypertrophy since 11 months. Thyroid function tests, marked elevation of muscle enzyme, electromyogram & muscle biopsy established the diagnosis of thyroid myopathy with Hoffman’s syndrome. Therapy with levothyroxine resulted in marked clinical & biochemical improvements.J MEDICINE July 2015; 16 (2) : 112-114

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