Statin-induced adverse effects and malignant hyperthermia susceptibility: Comment on the article by Guis et al
Version of Record online: 31 JAN 2007
Copyright © 2007 by the American College of Rheumatology
Arthritis Care & Research
Volume 57, Issue 1, pages 186–187, 15 February 2007
How to Cite
Vladutiu, G. (2007), Statin-induced adverse effects and malignant hyperthermia susceptibility: Comment on the article by Guis et al. Arthritis & Rheumatism, 57: 186–187. doi: 10.1002/art.22487
- Issue online: 31 JAN 2007
- Version of Record online: 31 JAN 2007
To the Editors:
I read with interest the article by Guis et al (1) describing 11 patients with severe statin-induced rhabdomyolysis who were evaluated in vivo and in vitro for preexisting altered skeletal muscle function. In vitro muscle contracture tests (IVCTs) in the presence of halothane or caffeine were performed in 9 patients. Abnormal IVCT test results occurred in 7 of the 9 patients, suggesting an impairment of calcium homeostasis. A certain malignant hyperthermia (MH) susceptible genotype was suspected to predispose the patient to the severe outcome observed, with statins unmasking latent pathologies.
It is known that neuromuscular disorders render patients at increased susceptibility for MH-like reactions to anesthetics (2, 3) and that medications such as statins and fibrates contribute to the risk for rhabdomyolysis by altering ion homeostasis (4). It would be difficult to prove genetic predisposition for an adverse statin reaction unless specific genetic or contracture testing was performed either before statin therapy was initiated or well after the adverse reaction subsided. Several questions arise from the present study: At what time during the course of the adverse statin reactions were the serum creatine kinase (CK) measurements taken? How long did myopathic symptoms persist in each patient post therapy and before IVCT testing? Were all patients asymptomatic at the time of biopsy? It is possible that statin therapy temporarily rendered patients at increased risk for a positive IVCT test result even in the post-symptomatic period. This interpretation would categorize patients as having acquired MH susceptibility instead of a specific susceptibility genotype.
No genotype analysis was provided in the study by Guis et al. The MH susceptible patients should have been screened for the most common mutations in the RYR1 gene (5) and for the prevalent mutations causing the common triggerable myopathies. We recently reported clinical, histopathologic, and laboratory findings in 136 patients with severe statin myopathy (6). Carrier status for the most prevalent mutations causing McArdle disease and carnitine palmitoyltransferase II deficiency was increased 20-fold and 13-fold, respectively, and 52% of muscle biopsy specimens had significant reductions in mitochondrial proteins. Coenzyme Q10 deficiency was the most prevalent (47% of biopsy samples). Plasma levels of coenzyme Q10 did not reflect muscle levels in statin-treated patients (7). At least 30% of patients exhibited persistent symptoms ≥6 months post therapy, and several patients had severe symptoms for >4 years, which suggests statin-induced symptoms can persist for variable periods of time.
The findings of Guis et al are important and worth pursuing through further research; however, the abnormal contracture results reported do not demonstrate a preexisting MH susceptible genotype or preexisting latent pathology. Clarification of the point at which contracture testing was performed following the adverse reaction, plus genotype analysis for highly suspected disorders, will aid in the interpretation of these findings.
Georgirene Vladutiu PhD*, * State University of New York, Buffalo, New York.