
==== Front
Am J Case Rep
Am J Case Rep
amjcaserep
The American Journal of Case Reports
1941-5923
International Scientific Literature, Inc.

39219126
10.12659/AJCR.944261
944261
Articles
Statin-Induced Autoimmune Myopathy: A Diagnostic Challenge in Muscle Weakness
Barkhordarian Maryam A B E F https://orcid.org/0000-0002-8927-976X

Grijalva Mark E F
Lee Albert A E
Jarri Amer A B E
Belyayeva Anna B C D F
Weissman Simcha D E F
Department of Internal Medicine, Hackensack Meridian Health, Hackensack, NJ, USA
Corresponding Author: Maryam Barkhordarian, e-mail: marybarkhordar@gmail.com
Authors’ Contribution:

A Study Design

B Data Collection

C Statistical Analysis

D Data Interpretation

E Manuscript Preparation

F Literature Search

G Funds Collection

Financial support: None declared

Conflict of interest: None declared

2024
02 9 2024
25 e944261-1e944261-4
24 2 2024
02 7 2024
25 7 2024
© Am J Case Rep, 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Patient: Male, 69-year-old

Final Diagnosis: Statin-induced rhabdomyolysis

Symptoms: Myalgia

Clinical Procedure: —

Specialty: Cardiology

Objective:

Rare disease

Background:

Statin-induced myopathy can present with symptoms ranging from mild myalgia to significant muscle weakness. Muscle-related adverse effects of statins have been very challenging in clinical practice and they necessitate high clinical suspicion. This case report highlights how statin-induced autoimmune myopathy often goes undiagnosed.

Case Report:

We present a 69-year-old man with a past medical history of coronary artery disease who presented with myalgia and progressive proximal muscle weakness for 2 months, with a creatinine kinase of 8323 U/L. Atorvastatin was held on admission and the patient received intravenous (IV) fluid as treatment for presumed rhabdomyolysis. Although CK was trending down, he did not show significant improvement in muscle weakness or myalgia. At this point, myositis was suspected, so a myositis panel including anti-HMG Co-A reductase antibody was ordered and he was started on IV steroids. Anti-HMG Co-A reductase antibody was positive, and the rest of myopathy workup was negative. Meanwhile, the patient’s muscle weakness significantly improved with IV steroid. He was discharged on methylprednisolone with close outpatient rheumatology follow-up.

Conclusions:

Muscle-related adverse effects of statins, including rhabdomyolysis and myopathy, can fail to respond to conservative management. It is crucial to identify and manage statin-induced autoimmune myopathy as a possible differential diagnosis in patients with muscle weakness and elevated CK while on statin therapy who do not respond to intravenous fluid alone.

Keywords:

Atorvastatin
Muscle Weakness
Myositis
Rhabdomyolysis, Cerivastatin-Induced
==== Body
pmcIntroduction

Statin-class medications are some of the most prescribed medications as they contribute to reduction in low-density lipoprotein cholesterol (LDL-C) via inhibition of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and improve atherosclerotic cardiovascular disease (ASCVD) scores [1]. Approximately 28% of adults age 40 and over are using a statin-class medication, with approximately 78 million US adults estimated to be on this medication [2,3]. The adverse effects profile of this class of medications is well known and muscle adverse-effects range from benign myalgia and myopathy without creatinine kinase (CK) elevation to severe drug-induced myopathy. The prevalence of benign clinical myopathy without evidence of CK increase is estimated to be approximately 10–25%, and it often leads to discontinuation of and aversion to this class of medication [4,5]. However, the incidence of drug-related clinically significant myonecrosis and rhabdomyolysis is less than 0.1% [5]. Here, we present a case report illustrating how statin-induced autoimmune myopathy often remains undiagnosed.

Case Report

A 69-year-old man with a past medical history of coronary artery disease, hypertension, hyperlipidemia, type 2 diabetes mellitus, and heart failure presented to the Emergency Department with muscle weakness and myalgias. About 2 months prior to admission, he began experiencing weakness with activity, which gradually worsened over time. He also reported cramping in the upper and lower extremities. He had been taking atorvastatin 80 mg once nightly for 5 years. Other home medications included carvedilol, sacubitril-valsartan, tamsulosin, finasteride, and aspirin, but no agents that can cause myopathy.

His physical exam was notable for significant weakness in bilateral proximal upper and lower extremities. On laboratory investigation, the patient had controlled diabetes with hemoglobin A1c of 5.3% and creatinine kinase at 8323U/L (reference range, 44–196 U/L). No renal insufficiency or myoglobinuria were noted. In light of the patient’s long history of statin usage, myalgias with muscle weakness, elevated creatinine kinase, and abnormal urinalysis, myopathy secondary to statin use was considered. Atorvastatin was held and the patient received intravenous (IV) fluid for management of rhabdomyolysis. His hospital course was complicated with respiratory failure necessitating intubation secondary to volume overload for a presumed rhabdomyolysis, despite careful monitoring with auscultation and oxygen saturation. He received 4200 cc total intravenous fluid since admission, and prior to intubation had an overall net negative balance. Given the respiratory failure in the setting of volume overload, acute decompensated heart failure was suspected, and the initial echocardiogram reflected heart failure with reduced ejection fraction of 40–45%. He also underwent cardiac catheterization to exclude any ischemic cause of heart failure.

Although the CK trended down to 3248 U/L, there was no significant improvement in muscular symptoms. At this point, given the patient’s muscle weakness and elevated CK, myositis was suspected. A myositis panel including anti-HMG Co-A reductase antibody was ordered and the patient was started on IV methylprednisolone. Anti-HMG Co-A reductase antibody was positive and the rest of myopathy workup was negative and there was no positive antibody against collagen disease. His muscle weakness significantly improved with IV methylprednisolone 40 mg every 8 hours during hospitalization. He was discharged with 60 mg of oral prednisone. On outpatient rheumatology follow-up, given incomplete improvement in myalgia and muscle weakness after 2 months of prednisone 60 mg, the steroid dose was tapered weekly and intravenous immunoglobulin (IVIG) 50 g every 4 weeks for 3 months was initiated. After 3 months of treatment with IVIG and tapering of prednisone, he regained his strength, and the CK level normalized to 28 U/L. A Figure 1 shows his clinical progress.

Discussion

Rhabdomyolysis can occur due to trauma or metabolic and exertional causes. It is important to find the cause and treat accordingly to prevent complications such as acute kidney injury [6]. Drug-induced rhabdomyolysis has been associated with multiple medications such as leflunomide, trabectedin, propofol, and daptomycin [7]. There are a few case reports of diphenhydramine, ecstasy, and baclofen inducing rhabdomyolysis in the pediatric population [8]. Statins can have adverse effects on muscles, including myalgia, myositis, and rhabdomyolysis, which can present with muscle pain, weakness, elevated creatinine kinase, myoglobinuria, and renal failure [9].

In our case, statin use induced rhabdomyolysis, which did not respond to the usual treatment of holding the inductive medication and administering intravenous fluid. Further investigation detected anti-HMGCR antibody and diagnosis of autoimmune myopathy. Statin-induced myopathy can be self-limited non-immune-mediated, which gradually improves after discontinuation of statin. However, immune-mediated myopathy caused by anti-HMGCR antibodies usually requires an immunosuppressant [10]. In a retrospective study in Lahore, about 50% of patients treated with statins had myalgia [11]. The incidence of statin-induced myopathy was reported at 11 cases in 100000 patients and the incidence of rhabdomyolysis caused by statins was reported to be about 4–7 in 100 000 cases [12]. The incidence of statin-associated autoimmune myopathy is estimated at 2–3 new cases per 100 000 patients [13]. Although rare, this etiology must be considered when muscle weakness or pain presents with elevations in CK ranging from 10x to 40x the upper limit of normal, defining myopathy and rhabdomyolysis, respectively [14]. However, the coincidence of autoimmune myopathy secondary to anti-HMG CoA reductase with other autoimmune disorders is not clear. A study of 82 participants with idiopathic inflammatory myopathy (IIM) reported that the prevalence of anti-HMG CoA reductase in these patients was unusually high [15]. It is crucial to have a clinical suspicion of this diagnosis in mind when the originally diagnosed disease is not responding to treatment, as it may not be as rare as thought, but rather may be widely undiagnosed. In patients not responding to statin withdrawal, the general approach is use of immunosuppressants such as steroids and intravenous immunoglobulins [16]. However, use of mycophenolate and tacrolimus in addition to steroids was also reported to be helpful [17,18].

Conclusions

In our case report, we highlighted the importance of evaluating anti-HMGCR antibodies in patients without adequate response to conservative therapy, including withdrawal of statins, and IV fluid therapy in the setting of rhabdomyolysis and renal injury. It is important to notice that the rarity of this phenomenon may not be due to low incidence but rather due to inadequate clinical suspicion for diagnosis and treatment of this condition.

The case was presented as a poster presentation at the American Heart Association’s 2023 Scientific Sessions. Barkhordarian M, Grijalva M, Jarri A, Belyayeva A, Weissman S. Abstract 16715: Rare or disregarded; A case of autoimmune myopathy. Circulation. 2023;148(Suppl. 1):A16715. https://www.ahajournals.org/doi/abs/10.1161/circ.148.suppl_1.16715

Figure 1. Event series of symptoms, lab data, and treatment plans. (Figure created using Canva.com).

Publisher’s note: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher

Declaration of Figures’ Authenticity

All figures submitted have been created by the authors who confirm that the images are original with no duplication and have not been previously published in whole or in part.
==== Refs
References:

1. Arnett DK Blumenthal RS Albert MA 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: Executive summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines J Am Coll Cardiol 2019 74 10 1376 414 30894319
2. Diana Hla RJ Roger S Blumenthal, Seth Shay Martin Assessing severity of statin side effects: Fact versus fiction 04/09/2018: American College of Cardiology 2018
3. Gu Q Paulose-Ram R Burt VL Kit BK Prescription cholesterol-lowering medication use in adults aged 40 and over: United States, 2003–2012 NCHS Data Brief 2014 177 1 8
4. Ganga HV Slim HB Thompson PD A systematic review of statin-induced muscle problems in clinical trials Am Heart J 2014 168 1 6 15 24952854
5. Mefford MT Tajeu GS Tanner RM Willingness to be reinitiated on a statin (from the REasons for Geographic and Racial Differences in Stroke Study) Am J Cardiol 2018 122 5 768 74 30057227
6. Prendergast BD George CF Drug-induced rhabdomyolysis – mechanisms and management Postgrad Med J 1993 69 811 333 36 8393995
7. Hohenegger M Drug induced rhabdomyolysis Curr Opin Pharmacol 2012 12 3 335 39 22560920
8. Coco TJ Klasner AE Drug-induced rhabdomyolysis Curr Opin Pediatr 2004 16 2 206 10 15021204
9. Abd TT Jacobson TA Statin-induced myopathy: A review and update Expert Opin Drug Saf 2011 10 3 373 87 21342078
10. Selva-O’Callaghan A Alvarado-Cardenas M Pinal-Fernández I Statin-induced myalgia and myositis: An update on pathogenesis and clinical recommendations Expert Rev Clin Immunol 2018 14 3 215 24 29473763
11. Sadeeqa S Maqsood M Ahmad M Prevalence of statin induced myopathy in Lahore, Pakistan Pak J Pharm Sci 2018 31 2(Suppl.) 617 22 29625933
12. Law M Rudnicka AR Statin safety: A systematic review Am J Cardiol 2006 97 8a 52c 60c
13. Mammen AL Statin-asssociated autoimmune myopathy N Engl J Med 2016 374 7 664 69 26886523
14. Newman CB Preiss D Tobert JA Statin safety and associated adverse events: A scientific statement from the American Heart Association Arterioscler Thromb Vasc Biol 2019 39 2 e38 e81 30580575
15. Douglass-Molloy H Limaye V Prevalence of polymyalgia rheumatica in a cohort of patients with idiopathic inflammatory myopathy Clin Rheumatol 2020 39 4 1217 21 31919772
16. Ramanathan S Langguth D Hardy TA Clinical course and treatment of anti-HMGCR antibody-associated necrotizing autoimmune myopathy Neurol Neuroimmunol Neuroinflamm 2015 2 3 e96 25866831
17. Akivis Y Kurup M John S Statin-induced necrotizing autoimmune myositis J Med Cases 2022 13 10 513 16 36407864
18. Cha D Wang F Mukerji B Mukerji V Statin-induced necrotizing autoimmune myositis: Diagnosis and management Cureus 2021 13 3 e13787 33842161
