scholarly journals Challenges in Treating Statin-Associated Necrotizing Myopathy

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Patrick Webster ◽  
Nicholas Wiemer ◽  
Abdalhamid Al Harash ◽  
Cody Marshall ◽  
Nazia Khatoon ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Case Series ◽  
Immunosuppressive Drugs ◽  
Diabetic Patients ◽  
Muscle Enzymes ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Immunosuppressant Medications ◽  
Autoimmune Myopathy ◽  
Coa Reductase

Myalgia and mild elevation in muscle enzymes are common side effects of statin therapy. While these symptoms are generally self-limited, in rare cases, statin use is associated with an immune-mediated necrotizing myopathy caused by development of autoantibodies against HMG-CoA reductase. The primary presenting symptom of this condition is progressive symmetric proximal weakness that does not abate or worsens even after cessation of statin therapy and is associated with markedly elevated creatine kinase (CK) levels. To date, no randomized controlled trials have been conducted to identify the most effective treatment for statin-associated autoimmune myopathy. Treatment recommendations involve a combination of steroids and immunosuppressive drugs. This single-center case series highlights the clinicopathologic features diagnostic for statin-associated autoimmune myopathy as well as treatment challenges for the patient population. The series highlights a range of potential presentations, from mildly symptomatic despite highly elevated CK, to severe muscle weakness including dysphagia. Multiple patients required several immunosuppressant medications as well as intravenous immunoglobulin (IVIG) to achieve disease control. In this case series, marked improvement was noted in several diabetic patients with IVIG.

scholarly journals Statin-Induced Autoimmune Necrotizing Myopathy

2021 ◽  
Vol 12 ◽  
pp. 215013272110287
Author(s):  
Sahani Jayatilaka ◽  
Kunal Desai ◽  
Swarup Rijal ◽  
Debra Zimmerman
Keyword(s):  
Renal Failure ◽  
Statin Therapy ◽  
Initial Presentation ◽  
Autoimmune Reaction ◽  
Necrotizing Myopathy ◽  
Starting Dose ◽  
Key Enzyme ◽  
Risk Patients ◽  
Autoimmune Myopathy ◽  
Coa Reductase

Statin therapy is a widely prescribed medication class for hypercholesterolemia. In statin-induced autoimmune myopathy, genetically predisposed and at-risk patients can develop antibodies against hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the key enzyme in the production of cholesterol. As a result, an autoimmune reaction causing weakness, myalgia, with possible severe rhabdomyolysis, renal failure, and myonecrosis also can occur. A 73-year-old female presented to clinic with myalgia and fatigue. She was on atorvastatin 20 mg/day for over 1 year, which she stopped 1 week prior to her initial presentation. Patient did experience rhabdomyolysis as well as a transaminitis. She underwent an autoimmune workup which was positive for HMG-CoA reductase antibodies. Patient was initially treated on a prednisone taper, starting dose 50 mg/day. Without remission of symptoms, methotrexate 15 mg/week was initiated.

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.

Use of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Statin‐Associated Immune‐Mediated Necrotizing Myopathy: A Case Series

2019 ◽  
Vol 71 (10) ◽  
pp. 1723-1726 ◽  
Author(s):  
Eleni Tiniakou ◽  
Erika Rivera ◽  
Andrew L. Mammen ◽  
Lisa Christopher‐Stine
Keyword(s):  
Case Series ◽  
Proprotein Convertase ◽  
Necrotizing Myopathy ◽  
Immune Mediated

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 High-dose cyclophosphamide without stem cell rescue in immune-mediated necrotizing myopathies

2017 ◽  
Vol 4 (5) ◽  
pp. e381 ◽  
Author(s):  
Christopher A. Mecoli ◽  
Arash H. Lahouti ◽  
Robert A. Brodsky ◽  
Andrew L. Mammen ◽  
Lisa Christopher-Stine
Keyword(s):  
Stem Cell ◽  
Signal Recognition Particle ◽  
Infectious Complications ◽  
Response To Therapy ◽  
High Dose ◽  
Muscle Enzymes ◽  
Stem Cell Rescue ◽  
Immune Mediated ◽  
Coa Reductase

Objective:To describe the experience managing treatment-refractory immune-mediated necrotizing myopathies (IMNM) with high-dose cyclophosphamide (HiCy) therapy.Methods:Five patients with severe refractory IMNM who were treated with HiCy without stem cell rescue were identified. Their medical records were reviewed to assess demographic, clinical, and histologic characteristics as well as response to therapy.Results:Three patients with anti–signal recognition particle (SRP) and 2 patients with anti-HMG-CoA reductase autoantibodies were included. The mean follow-up time after HiCy therapy was 37 ± 28 months. Two patients demonstrated substantial response, evidenced by improved muscle strength and decreased muscle enzymes after HiCy therapy; both of these patients were anti-SRP positive. Four patients experienced febrile neutropenia after HiCy therapy, one of which required a prolonged intensive care unit stay for infectious complications, from which they eventually recovered.Conclusions:These data suggest that HiCy therapy without stem cell rescue may be considered as an alternative for the treatment of refractory IMNM.

scholarly journals Immune mediated necrotizing myopathy: A rare complication of statin therapy

2020 ◽  
Vol 10 (2) ◽  
Author(s):  
Shady Piedra Abusharar ◽  
Prashanth Moku ◽  
Sharon Banks ◽  
Fahad M. Khalid ◽  
Charles S. Specht ◽  
...  
Keyword(s):  
Creatine Phosphokinase ◽  
Rare Complication ◽  
Elevated Serum ◽  
Inflammatory Myopathies ◽  
Necrotizing Myopathy ◽  
Immune Mediated ◽  
Serum Creatine Phosphokinase ◽  
Elevated Creatinine ◽  
Coa Reductase ◽  
Proximal Myopathy

Immune mediated necrotizing myopathy (IMNM) is part of the inflammatory myopathies group of diseases and presents with muscle weakness, myalgias and elevated serum creatine phosphokinase (CPK). Statin-induced IMNM is a rare complication. We present a patient with IMNM secondary to simvastatin use. The patient presented with proximal myopathy, dysphagia, and elevated creatinine kinase levels, and was subsequently found to have anti-3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) autoantibodies with a necrotizing process on muscle biopsy. This patient’s case was further complicated by sequelae of multiple disease processes, ultimately leading to deterioration of his health.

scholarly journals Nonspecific interstitial pneumonia: A rare adverse reaction of atorvastatin

2018 ◽  
Vol 5 (4) ◽  
pp. 16
Author(s):  
Jack Xu ◽  
Steven Verga ◽  
Jonathan Stoll ◽  
Lauren Pioppo ◽  
Eileen Shanahan ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Statin Therapy ◽  
Interstitial Pneumonia ◽  
Case Series ◽  
Pulmonary Complications ◽  
Drug Induced ◽  
Cardiovascular Morbidity And Mortality ◽  
Nonspecific Interstitial Pneumonia ◽  
Coa Reductase

Introduction: Statins have been shown to effectively prevent both cardiovascular morbidity and mortality by inhibiting the hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase enzyme. Pulmonary complications are very rare, and can include pneumonitis, pleural effusion, and nonspecific interstitial pneumonia (NSIP). There have been very few previously documented cases of statin-induced fibrotic NSIP.Case report: We present a female with a history of hyperlipidemia on atorvastatin who presented with shortness of breath. Computed tomography scan of the chest revealed interstitial infiltrates with bilateral ground-glass opacities. She underwent a surgical lung biopsy which showed uniform fibrous alveolar septal thickening, scattered collections of alveolar macrophages and inflammation, along with areas of fibrosis. The findings were most suggestive of fibrotic NSIP. Atorvastatin was stopped and she was started on mycophenolic acid with improvement of her symptoms.Discussion: Although rare, the clinician should be aware of possible pulmonary complications of statin therapy. The exact mechanism of injury is unclear, however immunological or toxicological mechanisms are implicated. One case series of statin induced interstitial lung disease showed some improvement of dyspnea with systemic glucocorticoids and termination of statin therapy. Statins, specifically pravastatin, lovastatin, and simvastatin have been associated with drug induced pneumonitis and interstitial lung disease.

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 Intermittent fasting: is there a role in the treatment of diabetes? A review of the literature and guide for primary care physicians

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Michael Albosta ◽  
Jesse Bakke
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Treatment Option ◽  
Primary Care Physicians ◽  
Case Series ◽  
Current Evidence ◽  
Intermittent Fasting ◽  
Diabetic Patients ◽  
Medicinal Treatment

Abstract Background Type 2 Diabetes is a metabolic disorder characterized by hyperglycemia that causes numerous complications with significant long-term morbidity and mortality. The disorder is primarily due to insulin resistance particularly in liver, skeletal muscle, and adipose tissue. In this review, we detail the hormonal mechanisms leading to the development of diabetes and discuss whether intermittent fasting should be considered as an alternative, non-medicinal treatment option for patients with this disorder. Methods We searched PubMed, Ovid MEDLINE, and Google Scholar databases for review articles, clinical trials, and case series related to type 2 diabetes, insulin resistance, and intermittent fasting. Articles were carefully reviewed and included based on relevance to our topic. We excluded abstracts and any non-English articles. Results The majority of the available research demonstrates that intermittent fasting is effective at reducing body weight, decreasing fasting glucose, decreasing fasting insulin, reducing insulin resistance, decreasing levels of leptin, and increasing levels of adiponectin. Some studies found that patients were able to reverse their need for insulin therapy during therapeutic intermittent fasting protocols with supervision by their physician. Conclusion Current evidence suggests that intermittent fasting is an effective non-medicinal treatment option for type 2 diabetes. More research is needed to delineate the effects of intermittent fasting from weight loss. Physicians should consider educating themselves regarding the benefits of intermittent fasting. Diabetic patients should consult their physician prior to beginning an intermittent fasting regimen in order to allow for appropriate oversight and titration of the patients medication regimen during periods of fasting.

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