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 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 Different statins produce highly divergent changes in gene expression profiles of human hepatoma cells: a pilot study.

2011 ◽  
Vol 58 (4) ◽  
Author(s):  
Agata Leszczynska ◽  
Monika Gora ◽  
Danuta Plochocka ◽  
Grazyna Hoser ◽  
Anna Szkopinska ◽  
...  
Keyword(s):  
Gene Expression ◽  
Statin Therapy ◽  
Hepg2 Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
High Dose ◽  
Human Hepatoma ◽  
Human Hepatoma Cells ◽  
Key Enzyme ◽  
Coa Reductase

Statins are inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), the key enzyme of the sterol biosynthesis pathway. Statin therapy is commonly regarded as well tolerated. However, serious adverse effects have also been reported, especially during high-dose statin therapy. The aim of our study was to investigate the effect of statins on gene expression profiles in human hepatoma HepG2 cells using Affymetrix Human Genome U133 Plus 2.0 arrays. Expression of 102, 857 and 1091 genes was changed substantially in HepG2 cells treated with simvastatin, fluvastatin and atorvastatin, respectively. Pathway and gene ontology analysis showed that many of the genes with changed expression levels were involved in a broad range of metabolic processes. The presented data clearly indicate substantial differences between the tested statins.

The Natural Products as Hydroxymethylglutaryl-Coa Reductase Inhibitors

2019 ◽  
Vol 16 (10) ◽  
pp. 1130-1137
Author(s):  
Hayrettin Ozan Gulcan ◽  
Serkan Yigitkan ◽  
Ilkay Erdogan Orhan
Keyword(s):  
Natural Products ◽  
Cardiovascular System ◽  
High Cholesterol ◽  
Chemical Structures ◽  
Reductase Inhibitors ◽  
Key Enzyme ◽  
Serious Disease ◽  
Coa Reductase ◽  
Hydroxymethylglutaryl Coa Reductase ◽  
Alternative Drugs

High cholesterol and triglyceride levels are mainly related to further generation of lifethreating metabolism disorders including cardiovascular system diseases. Therefore, hypercholesterolemia (i.e., also referred to as hyperlipoproteinemia) is a serious disease state, which must be controlled. Currently, the treatment of hypercholesterolemia is mainly achieved through the employment of statins in the clinic, although there are alternative drugs (e.g., ezetimibe, cholestyramine). In fact, the original statins are natural products directly obtained from fungi-like molds and mushrooms and they are potent inhibitors of hydroxymethylglutaryl-CoA reductase, the key enzyme in the biosynthesis of cholesterol. This review focuses on the first identification of natural statins, their synthetic and semi-synthetic analogues, and the validation of hydroxymethylglutaryl-CoA reductase as a target in the treatment of hypercholesterolemia. Furthermore, other natural products that have been shown to possess the potential to inhibit hydroxymethylglutaryl-CoA reductase are also reviewed with respect to their chemical structures.

Role of N-Acetylcysteine in the Prevention of Radiocontrast-Induced Nephropathy

2002 ◽  
Vol 36 (9) ◽  
pp. 1466-1470 ◽  
Author(s):  
Donald F Brophy
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Large Scale ◽  
English Language ◽  
Small Animal ◽  
Human Studies ◽  
Animal Trials ◽  
Study Selection ◽  
Risk Patients

OBJECTIVE: To examine the role of N-acetylcysteine (NAC) in the prevention of radiocontrast—induced nephropathy (RIN). DATA SOURCES: A literature search of MEDLINE (1966–December 2001) was performed using the following search terms: N-acetylcysteine, nephropathy, acute renal failure, and radiocontrast. STUDY SELECTION: Pertinent English-language animal and human studies were reviewed. DATA SYNTHESIS: Few small animal trials have demonstrated that NAC significantly prevents the development or reduces the severity of acute renal failure. Two human studies demonstrated NAC significantly reduces the occurrence of RIN. CONCLUSIONS: NAC may reduce the occurrence of RIN in high-risk patients. Further large-scale studies are needed to corroborate findings from earlier trials.

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.

scholarly journals A RARE CASE OF STATIN-INDUCED NECROTIZING AUTOIMMUNE MYOPATHY

2020 ◽  
Vol 6 (2) ◽  
pp. e86-e89
Author(s):  
Shirley Shuster ◽  
Sara Awad
Keyword(s):  
Differential Diagnosis ◽  
Statin Therapy ◽  
Alternative Therapy ◽  
Pcsk9 Inhibitors ◽  
Pcsk9 Inhibitor ◽  
Lipid Panel ◽  
Exposed Individual ◽  
Necrotizing Autoimmune Myopathy ◽  
Autoimmune Myopathy ◽  
Work Up

Objective: Necrotizing autoimmune myopathy (NAM) is a rare side-effect of statin therapy. We report the case of a patient who developed statin-induced NAM with a review of the clinical presentation and management of this rare entity. The case illustrates the importance of including NAM in the differential diagnosis of persistent myopathy in a statin-exposed individual. Methods: A 74-year-old male was referred to endocrinology for hypercholesterolemia management in the context of a statin contraindication. He previously developed myositis and rhabdomyolysis secondary to statin therapy, but continued to have persistent proximal lower limb muscle weakness despite statin discontinuation. Rheumatologic and metabolic work-up were negative and neurologic work-up was negative except for a myopathic pattern in the glutei found on electromyography. Results: Due to the persistence of proximal myopathy despite statin discontinuation and myopathic pattern seen on electromyography, NAM was suspected and antibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase were sent and came back positive. The patient was treated with the immunosuppressant azathioprine, which resulted in clinical improvement. The patient was started on a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolucumab for hypercholesterolemia, which resulted in significant improvement in his lipid panel. Conclusion: The case illustrates the presentation and management of statin-induced NAM. We demonstrate the necessity for prompt diagnosis and timely management, as statin therapy is contraindicated and immunosuppressive therapy is warranted. Statin-induced NAM is rare however, it should be included in the differential diagnosis of persistent myopathy despite statin discontinuation. PCSK9 inhibitors are the only alternative therapy for hypercholesterolemia management in patients with statin-induced NAM.

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