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 Table of Contents  
Year : 2021  |  Volume : 17  |  Issue : 1  |  Page : 36-39

Statin-induced toxic rhabdomyolysis with hepatocellular jaundice in the elderly

Department of Medicine 5, CMC, Vellore, Tamil Nadu, India

Date of Submission01-Mar-2021
Date of Decision29-May-2021
Date of Acceptance03-Jun-2021
Date of Web Publication17-Aug-2021

Correspondence Address:
Dr. C Jacob Johnson
Department of Medicine, Christian Medical College, Vellore - 632 004, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jiag.jiag_4_21

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Adverse drug reactions (ADRs) are a common cause of hospitalization, increased morbidity and mortality in the elderly. ADRs are difficult to diagnose in the elderly as they often present with nonspecific symptoms such as fatigue, falls, cognitive decline, and constipation. Statins are generally well-tolerated drugs used in the secondary prevention of coronary artery disease. We report a 75-year-old lady who developed jaundice and became bedbound due to statin-induced hepatitis and acute rhabdomyolysis causing proximal myopathy following initiation of atorvastatin 40 mg for the management of coronary artery disease. She had rapid clinical improvement with discontinuation of statin therapy and supportive management. ADR must be considered a part of differential diagnosis in elderly patients during the evaluation of illnesses. In the elderly initiated on statins, it is essential to differentiate benign muscle pain from severe muscle injury with biochemical abnormalities. Prompt discontinuation of statins will lead to rapid improvement and prevent further worsening.

Keywords: Hepatitis, rhabdomyolysis, statin

How to cite this article:
Johnson C J, Gunasekaran K, Jambugulam M, Iyadurai R. Statin-induced toxic rhabdomyolysis with hepatocellular jaundice in the elderly. J Indian Acad Geriatr 2021;17:36-9

How to cite this URL:
Johnson C J, Gunasekaran K, Jambugulam M, Iyadurai R. Statin-induced toxic rhabdomyolysis with hepatocellular jaundice in the elderly. J Indian Acad Geriatr [serial online] 2021 [cited 2023 Feb 8];17:36-9. Available from: http://www.jiag.com/text.asp?2021/17/1/36/323942

  Introduction Top

Statins are drugs that inhibit the enzyme, 3-hydroxy-3- methylglutaryl-CoA reductase (HMGCR); currently, they have been established as the standard of care for secondary prevention of coronary artery disease.[1] Adverse drug reactions (ADRs) with statins are more common, especially in the very frail elderly, this is probably due to the reduced muscle mass, age-related reduction in the hepatic and renal function.

A well-recognized ADR of statins is myotoxicity. Creatine phosphokinase (CPK) elevations > 10 times the upper limit of normal occur in 1/1000 to 1/10, 000 per patient-year among adults who use a statin. This can present as myositis, myopathy, or as rhabdomyolysis (SR). SR is the most severe form of toxicity, it can present with markedly elevated creatine kinase, disseminated intravascular coagulation, acute renal failure, and death. The mechanism of statin-related myopathy (SRM) is poorly understood.[2]

Risk factors for developing SRM include old age >80 years, female gender, Asian descent, coexisting diabetes, hypothyroidism, and polypharmacy. One of these is a common single-nucleotide polymorphism in the SLCO1B1 gene.[3]

We report the case of an elderly patient with SR and hepatotoxicity and discuss the clinical features, pathogenesis, and management of such a patient.

  Case Report Top

A 75-year-old lady Ms N homemaker from Andhra Pradesh had developed sudden-onset severe retrosternal anginal pain and underwent emergency coronary angiography with angioplasty. Post-procedure she was initiated on aspirin, beta-blockers, angiotensin-converting inhibitors, and high-dose atorvastatin 40 mg for secondary prophylaxis. A week after this episode, she started developing gradually progressive predominantly proximal weakness associated with high colored urine and deep yellowish discoloration of the sclera and palms. Symptoms had progressed over 1 month; when she presented to us, she had become completely bedbound and could not swallow liquids or solid food. She did not have any sensory symptoms, no bladder, and bowel incontinence, but was bedbound.

At admission, she was conscious and oriented to time place and person, her blood pressure was 120/60 mm hg, pulse rate was 92/min, and respiratory rate 14/min. She was icteric, there was no pallor or lymphadenopathy. On examination, she was found to have profound symmetrical lower limb predominant proximal muscle weakness power 1/5 both the hips and knees and 3/5 at the ankles, upper limb shoulder flexion–extension was 1/5, elbow flexion–extension was 2/5, the wrist was 2/5 for flexion–extension, handgrip was weak, and there was hypotonia in the upper and lower limbs with areflexia. There were no cranial nerve deficits, sensory examination was normal, and plantars were bilaterally flexor. We considered the possibility of chronic inflammatory demyelinating polyneuropathy, myasthenia gravis, paraneoplastic myopathy, and inflammatory myopathy.

Investigations done at admission included [Table 1] liver function tests (LFT) – direct bilirubinemia of 8.6 mg/dL, aspartate transaminase of 584 U/L, alanine transaminase of 156 U/L, and alkaline phosphatase of 775 [Table 1]. Viral hepatitis due to A, B, C, and E was excluded. Ultrasonography of the abdomen and side-viewing endoscopy were done to rule out anatomical causes of hepatitis and there were no gallstones or strictures. Evaluation of the myopathy showed that CPK at admission was 14,689 U/L. Our patient had syndrome complex of hepatic and muscle involvement, evaluation had ruled out autoimmune and paraneoplastic causes [Table 2]. We considered drug-induced hepatitis and myopathy. We reviewed her medications and identified statin as the cause of her illness. Her statin myalgia clinical index score (Rosenson et al.) was 8. She had a nasogastric tube inserted, atorvastatin was withheld. During her stay in the ward, her CPK and LFT showed rapid improvement [Figure 1]. She was walking with one person assistance at discharge and came walking unassisted for review 1 month later.
Table 1: Lab investigations showing liver function tests and creatine phosphokinase values

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Table 2: Tests to rule out other causes of myopathy

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Figure 1: Figure depicting days in the hospital and creatine phosphokinase levels Source: Original

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  Discussion Top

SRM is the most common adverse associated with statin use, but SR with profound weakness is quite rare [Table 3]. SRM is most common during the 1st year of treatment with a median time of onset of 1 month, but it can occur anytime between 2 weeks and 2 years. Our patient had SR within 1 month of initiating atorvastatin.
Table 3: Grades of statin-related myopathy

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Symptoms of SRM include fatigue, muscle pain, muscle tenderness, muscle weakness, nocturnal cramping, and tendon pain. SRM has been divided into six grades [Table 3], it is important to establish the diagnosis as it will determine the management, outcome, and the decision to restart statins. Statin-related myalgia is the presence of muscle pain without any laboratory evidence of muscle injury also graded as 2 and 3 SRM. When there is an elevation of CPK, the diagnosis is based on the amount of CPK elevation, and CPK elevation 10–50 times normal is classified as SR. Statins can also trigger inflammatory myositis with HMGCR antibodies. The difference between statin SR and statin-induced inflammatory myositis (SIM) is that SR is self-limiting and the weakness resolves within weeks or months while in SIM the statin has triggered a self-sustained inflammatory myositis which must be treated with immunosuppressants.[4]

SR due to statins is quite rare. A meta-analysis of studies on the effect of statins in coronary artery diseases showed that only 2/8618 participants developed SR, while 550/7198 developed myalgia.[5]

No guidelines are available for the management of statin-induced muscle disorders. The recommendations available are based on case reports.[6] Currently, the only effective treatment of statin-induced toxic myopathy is the discontinuation of statins. Our patient fitted into the self-limited toxic statin myopathy with the SR group and so statins were withheld. She improved clinically and her CPK settled rapidly to near normal around 10 days after cessation of statins. A simplified approach and management of SRM and statins-induced hepatotoxicity (SIH) is given in [Figure 2].[7]
Figure 2: Flowchart for the management of statin-related myopathy and statins-induced hepatotoxicity. Adapted from statins in the treatment of dyslipidemia in the presence of elevated liver aminotransferase levels: a therapeutic dilemma

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Statins induced hepatotoxicity

Statin-induced liver injury has been described in case reports and appears to be quite rare; a systematic review showed that there were only 40 cases of statin-induced liver derangements reported till 2009.[8] A study by the United States Drug-induced Liver Injury Network showed that most of the patients (68%) with SIH presented with jaundice. The latency to develop SIH varied from 34 days to 10 years.

Statin-induced hepatic injury has varied presentations it can be either cholestatic or hepatocellular. Several researchers reported a cholestatic pattern in association with the liver injury caused by atorvastatin but may vary from a mere cholestatic pattern to frank hepatocytolysis and including the in-between range of mixed pictures.[9] It is difficult to determine whether the idiosyncratic liver injury caused by a statin will recur if another statin is given but must be done with caution and careful monitoring of the patient. Statins should be avoided in patients with decompensated liver disease, acute liver failure, and cholestasis.

Since studies have shown that SIH is rare only of mild-to-moderate severity and resolves spontaneously with the stopping of medication; routine monitoring of LFT is not recommended for patients started on statins.[10]

Conclusions and key learning points

Drug-related adverse events can cause severe illness in older and it needs a high index of suspicion for diagnosis.

Statins can cause SR, it is important to distinguish benign muscle involvement from severe muscle injury.

Both SRM and SIH resolve spontaneously with the withdrawal of the drug.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Lancet T. Statins for millions more? Lancet 2014;383:669.  Back to cited text no. 1
Turner RM, Pirmohamed M. Statin-related myotoxicity: A comprehensive review of pharmacokinetic, pharmacogenomic and muscle components. J Clin Med 2019;9:22.  Back to cited text no. 2
SEARCH Collaborative Group, Link E, Parish S, Armitage J, Bowman L, Heath S, et al. SLCO1B1 variants and statin-induced myopathy—a genomewide study. N Engl J Med 2008;359:789-99.  Back to cited text no. 3
Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, et al. Statin-associated muscle symptoms: Impact on statin therapy–European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J 2015;36:1012–22.  Back to cited text no. 4
Tiniakou E. Statin-associated autoimmune myopathy: Current perspectives. Ther Clin Risk Manag 2020;16:483-92.  Back to cited text no. 5
Iwere RB, Hewitt J. Myopathy in older people receiving statin therapy: A systematic review and meta-analysis. Br J Clin Pharmacol 2015;80:363-71.  Back to cited text no. 6
Calderon RM, Cubeddu LX, Goldberg RB, Schiff ER. Statins in the treatment of dyslipidemia in the presence of elevated liver aminotransferase levels: A therapeutic dilemma. Mayo Clin Proc 2010;85:349-56.  Back to cited text no. 7
Sikka P, Kapoor S, Bindra VK, Sharma M, Vishwakarma P, Saxena KK. Statin intolerance: Now a solved problem. J Postgrad Med 2011;57:321-8.  Back to cited text no. 8
[PUBMED]  [Full text]  
Russo MW, Scobey M, Bonkovsky HL. Drug-induced liver injury associated with statins. Semin Liver Dis 2009;29:412-22.  Back to cited text no. 9
Russo MW, Hoofnagle JH, Gu J, Fontana RJ, Barnhart H, Kleiner DE, et al. Spectrum of statin hepatotoxicity: Experience of the drug-induced liver injury network. Hepatology 2014;60:679-86.  Back to cited text no. 10


  [Figure 1], [Figure 2]

  [Table 1], [Table 2], [Table 3]


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