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Colchicine triggered severe rhabdomyolysis after long-term low-dose simvastatin therapy: a case report
- Clara Frydrychowicz†1Email author,
- Bastian Pasieka†2,
- Matthias Pierer2,
- Wolf Mueller1,
- Sirak Petros2 and
- Lorenz Weidhase2
© The Author(s). 2016
Received: 24 March 2016
Accepted: 5 December 2016
Published: 4 January 2017
Rhabdomyolysis is a widely recognized yet rare complication in statin use. Rhabdomyolysis might be triggered by the prescription of high doses of statins or by statin accumulation due to interactions with concomitant medication. Muscle cell destruction as evidenced by myoglobin elevation can induce potentially life-threatening acute renal failure.
We report a case of a 70-year-old obese white man with sudden onset of severe rhabdomyolysis with consecutive renal failure. His medication included low-dose simvastatin, which he had taken for 6 years up until the event. The statin was withdrawn immediately. After 3 days of veno-venous hemofiltration his renal function was completely restored.
Clinicians in both primary and special care might be unaware that side effects of statins do occur even after a long uneventful statin medication; they should be advised not to exclude that possibility upfront, even if a patient has tolerated the medication for years.
Diagnosis of statin-induced myopathy
Occurrence within 4 weeks from the start of statin therapy
Symptoms resolving with withdrawal of therapy
Family history of statin-induced myopathy
Elevation of creatine kinase
Positive re-challenge test
Histological confirmation of statin-induced myopathy
A 70-year-old obese white man presented with acute kidney failure after a 1-year history of progressive muscle weakness and severe generalized myalgia, with difficulty in walking and climbing stairs. His past medical history was significant for chronic renal dysfunction (Kidney Disease Outcomes Quality Initiative IV), chronic heart failure (New York Heart Association III), coronary heart disease with acute myocardial infarction and coronary artery bypass, chronic atrial fibrillation, diabetes type 2, hyperlipoproteinemia, gout, and obstructive sleep apnea syndrome. He had a 6-year history of low-dose simvastatin medication with a daily dose of 40 mg. Further medication included acetylsalicylic acid, rivaroxaban, metoprolol, ramipril, furosemide, molsidomine, isosorbide dinitrate, pantoprazole, and insulin. Colchicine was prescribed as required (0.5 to 1 mg). He had no past medical history of muscular toxicity with statin use.
On admission he was in poor general condition. A clinical examination revealed symmetric proximal muscle weakness of all extremities (level of strength 3/5). Electroneurographic and myographic diagnostics showed chronic myopathic alterations in all of the examined muscles of his upper and lower extremities. Alterations were more pronounced in proximal muscle groups of his lower extremities. He had dyspnea induced by light exercise, edema of lower extremities, no fever, and no rashes.
Patient laboratory data on hospitalization
In clinical practice up to 10% of patients with statin medication develop at least mild forms of myopathy . This constitutes an underestimated side effect as was underlined in the Primo Trial; an observational study of muscular symptoms in a randomized population of 7924 patients with hyperlipidemia . In 2012, Germany registered more than 3.2 billion statin prescriptions, which leads to an expectation of a large number of affected or symptomatic patients . For patients with long-term statin usage, a recently published meta-analysis by the Cholesterol Treatment Trialists’ Collaboration states the risk of myopathy to be as low as 0.5 per 1000 patients over 5 years of statin treatment . Almost 30% of statin-associated incidences occur within the first year of treatment . However, onset of muscular side effects has been documented between 2 months and up to 10 years after initiation of statin therapy . Our case confirms and underscores these observations. Six years after well tolerated and uneventful simvastatin medication, our patient suddenly developed a severe statin-associated rhabdomyolysis, which was histologically compatible with the diagnosis of SAM. To date, however, the definition of SAM remains unclear; in particular, the diagnostic criteria of SAM are ill defined, which may explain different data concerning the prevalence and seriousness of SAM . There is general consent that statin can cause several muscle-related complaints. These may range from mild myalgia, may lead to manifest myopathy and myositis-mimicking symptoms, and may culminate in severe rhabdomyolysis. The latter may – when not recognized early enough – induce crush kidney with consecutive renal failure and death .
Colchicine triggered simvastatin-induced myopathy: review of the literature
Age in years
Hsu et al. 2002 
Symmetrical proximal muscle weakness 3–4/5
0.5 mg daily
Baker et al. 2004 
40 mg daily
0.6 mg daily
Justiniano et al. 2007 
40 mg daily
0.6 mg daily
Sahin et al. 2008 
Proximal muscle weakness upper and lower extremities 2–3/5
20 mg daily
1.5 mg daily
Oh et al. 2012 
Symmetrical proximal muscle weakness
40 mg daily
1 mg (first 3 days); 0.5 mg daily
Medani and Wall 2016 
Muscle weakness 4/5 in all limbs except 5/5 in hip extensor
1.5 mg daily
40 mg daily
0.5–1 mg as required
Advanced age, female sex, presence of comorbidities, and alcohol consumption are further predisposing factors for SAM . Given the high number of prescriptions, clinicians are in need of reliable risk evaluation methods for the identification of vulnerable patients.
More recently, a self-limiting statin-induced primarily toxic necrotizing myopathy can be distinguished from a persisting autoimmune-mediated statin-induced necrotizing myopathy. The latter persists even after cessation of statin therapy and immunosuppressive therapy . In addition, anti-HMG-CoA reductase antibodies can be detected in the serum and muscle of affected patients . Both SAM and immune-mediated necrotizing myopathy (IMNM) show extensive histopathological overlap and might not be distinguished based on biopsy only. In the present case, IMNM was excluded by antibody testing (anti-HMGCR antibody, negative). Neuropathologists should be aware of the possibility of autoimmune-mediated statin-induced necrotizing myopathy and should recommend anti-HMG-CoA reductase antibody testing in all patients with persistent muscle pathology after statin arrest. Clinical monitoring of SAM may include baseline CK levels of patients especially if there are risk factors such as impaired renal function, genetic myopathy in the past medical history, or significant alcohol abuse [9, 10]. Co-medication should be checked for potential interaction with statins, especially if a new medication is prescribed, including herbal cures. Patients with muscle-related symptoms and statin medication should immediately be checked for an increase in CK. Medication should be stopped immediately and CK levels monitored. In case of persistent elevated CK levels after cessation of statin medication other causes of elevated CK levels should be considered and investigated, including anti-HMGCR-associated SAM . Patients should be informed about the risk of developing myopathy and symptoms. Despite the risk of SAM, statin therapy remains a useful and powerful tool in cardiovascular risk reduction and in reducing cardiovascular morbidity and mortality. Our case emphasizes the need for clinicians to be aware of statin-associated necrotizing myopathy even after long-term statin treatment. The presented patient received uneventful simvastatin therapy for a period of 6 years. In addition, we identified colchicine as a potential trigger of SAM in our patient based on its metabolism potentially competing with statin metabolism. Fast recognition of SAM is mandatory to rescue renal function and avoid life-threatening complications. The treatment of choice remains immediate cessation of statin medication and supportive care for renal function. If recognized early enough, the outcome is excellent.
We wish to alert clinicians to the fact that side effects of statins do occur even after a long uneventful statin medication; they should be advised not to exclude that possibility upfront, even if a patient has tolerated the medication for years. In particular, for patients with multiple drugs, clinicians should be aware of possible drug–drug interactions such as colchicine and statins. In cases in which colchicine is indicated, statins not metabolized via the CYP3A4 system should be preferred. Patients with muscle-related symptoms and statin medication should immediately be checked for an increase in CK and levels should be monitored after statin medication is stopped. In cases of persistent elevated CK levels after cessation of statin medication, other causes of elevated CK levels should be considered and investigated, including anti-HMGCR-associated SAM. Further studies are needed to clarify the different pathogeneses of statin-induced myopathies, as well as the optimal management of patients with this severe side effect.
Availability of data and materials
CF histopathological diagnosis and manuscript design. BP treatment of patient, patient investigation, screening laboratory data, and manuscript design. MP treatment of patient and treatment supervision. WM histopathological diagnosis and manuscript draft. SP manuscript draft. LW first-line treatment of patient, initiating manuscript work, and manuscript design. All authors read and approved the final manuscript.
The authors declare that they have no competing interests.
Consent for publication
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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