Find information on thousands of medical conditions and prescription drugs.


Rhabdomyolysis is the breakdown of skeletal muscle due to injury, either mechanical, physical or chemical. The principal result of this process is acute renal failure due to accumulation of muscle breakdown products in the bloodstream, several of which are injurous to the kidney. more...

Gastroesophageal reflux...
Rasmussen's encephalitis
Raynaud's phenomenon
Reactive arthritis
Reactive hypoglycemia
Reflex sympathetic...
Regional enteritis
Reiter's Syndrome
Renal agenesis
Renal artery stenosis
Renal calculi
Renal cell carcinoma
Renal cell carcinoma
Renal cell carcinoma
Renal failure
Renal osteodystrophy
Renal tubular acidosis
Repetitive strain injury
Respiratory acidosis
Restless legs syndrome
Retinitis pigmentosa
Retrolental fibroplasia
Retroperitoneal fibrosis
Rett syndrome
Reye's syndrome
Rh disease
Rheumatic fever
Rheumatoid arthritis
Rift Valley fever
Rocky Mountain spotted fever
Romano-Ward syndrome
Roseola infantum
Rubinstein-Taybi syndrome
Rumination disorder

Treatment is with intravenous fluids, and dialysis if necessary.


The injury that leads to rhabdomyolysis can be due to mechanical, physical and chemical causes:

  • mechanical: crush trauma, excessive exertion, intractable convulsions, choreoathetosis, surgery, compression by a tourniquet left for too long, local muscle compression due to comatose states, compartment syndrome, rigidity due to neuroleptic malignant syndrome
  • physical: high fever or hyperthermia, electric current
  • chemical: metabolic disorders, anoxia of the muscle (e.g. Bywaters' syndrome, toxin- and drug-related; various animal toxins, some antibiotics, methylenedioxymethamphetamine (MDMA) better known as ecstasy, statins, alcohol

Drug-induced rhabdomyolysis appears to be increasing in incidencepossibly due to the introduction of increasingly potent drugs into clinical practice. Any drug which directly or indirectly impairs the production or use of adenosine triphosphate (ATP) by skeletal muscle, or increases energy requirements so as to exceed ATP production, can cause rhabdomyolysis (Larbi 1998).


Severe cases of rhabdomyolysis often result in myoglobinuria, a condition where the myoglobin from muscle breakdown spills into the urine, making it dark, or "tea colored" (myoglobin contains heme, like hemoglobin, giving muscle tissue its characteristic red color). This condition can cause serious kidney damage in severe cases. The injured muscle also leaks potassium, leading to hyperkalemia, which may cause fatal disruptions in heart rhythm. In addition, myoglobin is metabolically degraded into potentially toxic substances for the kidneys. Massive skeletal muscle necrosis may further aggravate the situation, by reducing plasma volumes and leading to shock and reduced bloodflow to the kidneys.


The diagnosis is typically made when an abnormal renal function and elevated creatine kinase and potassium levels are observed in a patient. To distinguish the causes, a careful medication history is considered useful. Testing for myoglobin levels in blood and urine is rarely performed due to its cost.

Clinical sequelae

  • Hypovolemia (sequestration of plasma water within injured myocytes)
  • Hyperkalemia (release of cellular potassium into circulation)
  • Metabolic acidosis (release of cellular phosphate and sulfate)
  • Acute renal failure (nephrotoxic effects of liberated myocyte components)
  • Disseminated intravascular coagulation (DIC)
  • Hypocalcemia (low calcium levels due to precipitation with phosphate), followed by hypercalcemia (as renal function recovers)


[List your site here Free!]

Rhabdomyolysis associated with quinacrine therapy in a patient with chronic cutaneous lupus erythematosus
From Journal of Drugs in Dermatology, 3/1/05 by Naomi Creel


We describe a patient who developed rhabdomyolysis 6 weeks after starting combination therapy with hydroxychloroquine and quinacrine for the treatment of chronic cutaneous lupus erythematosus (CCLE). Myopathy due to 4-aminoquinolone antimalarials has been well documented. It is plausible that quinacrine may induce muscle injury in a manner similar to other antimalarials but, to our knowledge, rhabdomyolysis associated with antimalarial therapy has not been reported.


Case Report

A healthy 45-year-old African-American female with a history of chronic cutaneous lupus erythematosus (CCLE) presented for evaluation. She had no symptoms of systemic lupus erythematosus and no other medical problems. In the past she had taken hydroxychloroquine at a dose of 200 mg twice a day for several years. Clinically, the patient had scattered hyperpigmented atrophic plaques on her face and scalp. On her knees she had hyperpigmented patches with focal firm nodules. A biopsy of one of the nodules was consistent with chronic cutaneous lupus erythematosus and dystrophic calcinosis. She had no evidence of heliotrope, Gottron's papules or poikilodermatous patches on her skin. She denied myalgias or weakness. In an attempt to improve control of her active lesions, the patient was started on hydroxychloroquine 200 mg twice a day. Because of lack of complete response, quinacrine 100 mg per day was later added. She was instructed to use a broad-spectrum sunscreen daily. Three weeks after beginning quinacrine, the patient developed a pruritic urticarial eruption on her legs. Quinacrine was discontinued at that time.

The patient subsequently developed symptoms of muscle pain and severe weakness with general malaise. Laboratory evaluation revealed an elevated BUN and creatinine and an elevated serum creatine kinase (CK) of 39,000 IU/L (normal 24-173 IU/L) consistent with rhabdomyolysis. History was negative for trauma, overexertion, alcohol, or recreational drug use. The patient denied a family history of genetic defects in muscle enzymes and had no evidence of infection. The patient was hospitalized for supportive care and hydroxychloroquine was discontinued. The patient's muscle status improved over several months.


Rhabdomyolysis is a condition defined by acute necrosis of striated muscle. Clinical symptoms include intense muscle swelling and tenderness with markedly elevated serum CK. Elevations of serum CK over 2,000 times normal may occur. (1) Muscular symptoms and serum enzymes usually resolve when the toxic insult is removed. Common precipitating factors of rhabdomyolysis include severe muscle trauma, ischemia, overexertion, toxins, infections, genetic enzyme defects, and medications.

Autoimmune diseases may be associated with myopathy, but are not often associated with rhabdomyolysis (Table 1). Rarely, dermatomyositis may present with rhabdomyolysis. (1)

Dermatomyositis more commonly presents with insidious onset of proximal muscle weakness and enzyme elevation developing over several months. Systemic lupus erythematosus is associated with myopathy in up to 50% of patients with the disease. (2) Lupus myopathy is characterized by proximal muscle weakness and elevated serum CK. Muscle biopsy may show inflammation, vasculitis of small vessels, and type II muscle fiber atrophy. (2)

Several medications used in dermatology can cause myopathies or rhabdomyolysis (Table 2). Hydroxychloroquine and chloroquine are classified as 4-aminoquinolone antimalarials. Myopathy due to these agents was first described in 1963. (3) Subsequent case reports of antimalarial myopathy describe patients with reversible proximal muscle weakness. Symptoms may be associated with neuropathy and cardiomyopathy. Serum CK may be normal or elevated. (3,4) The antimalarials accumulate in lysosomes and interfere with lysosomal functions. Muscle toxicity may result from a disruption in lysosomal storage in which phospholipids, glycogen, and myeloid accumulate in vacuoles. (2) Muscle biopsy specimens typically show vacuolar changes in myocytes and electron microscopy reveals distinct vacuoles known as curvilinear bodies. Quinacrine is an acridine compound that differs from 4-aminoquinolones because of an extra benzene ring in its chemical structure. It was first developed as a synthetic quinine in the 1920s and became the official medication for antimalarial prophylaxis during World War II. From 1943 to 1945, over 4 million allied soldiers took quinacrine. (5) After the war, quinacrine became widely recognized as effective treatment for lupus erythematosus. (6) Later, the combination of quinacrine and hydroxychloroquine was noted to have synergistic effects. (5,7,8) The production of quinacrine tablets in the US ceased in 1992 due to widespread use of other antimalarials. (9) Quinacrine powder is still available in the US and can be made into a capsule by compounding pharmacies.

Quinacrine is effective in combination with hydroxychloroquine for patients with cutaneous lupus erythematosus not responsive to hydroxychloroquine alone. (10) It also has a role as a single agent if hydroxychloroquine is contraindicated due to ocular toxicity or other intolerance, although it is less effective when used alone. Quinacrine, like hydroxychloroquine, has additional beneficial hypoglycemic, anti-platelet, and lipid-lowering effects in patients with systemic lupus erythematosus. It is also helpful as a cortical stimulant in patients with fatigue. (9)

Aplastic anemia is the most serious adverse reaction to quinacrine. Based on data from World War II, this is a rare reaction associated with drug dose and duration of therapy. (6) Some patients develop a lichenoid eruption prior to development of aplastic anemia and stopping the medication at that point may reverse the process. (6) Other more common side effects include gastrointestinal intolerance, headache, or dizziness. Minor cutaneous side effects include yellow skin discoloration, bluish bruise-like marks in the skin, and urticarial, lichenoid, or eczematous eruptions. Quinacrine does not cause ocular toxicity and it does not cross react with chloroquine and hydroxychloroquine. (5)

The myotoxic potential of quinacrine is not well elaborated. In a review of muscle toxins, quinacrine is listed as a myotoxin associated with pain, sensorimotor polyneuropathy, and cardiomyopathy. (11) The related pathologic findings listed are necrosis, fibroblast proliferation, and lymphocytic infiltration. Another review of muscle toxins links quinacrine with destruction of skeletal muscle and associated myoglobinuria. (12) Neither review included clinical descriptions or references to specific cases of myotoxicity. Additional evaluation of patients with myopathy includes muscle biopsy, electron microscopy, and electromyelogram (EMG), which were not performed on our patient.

Several medications used in dermatology may induce rhabdomyolysis or myopathy. It is critical to recognize the myotoxic effects of these medications. Patients with autoimmune disease may have several factors contributing to myopathy, including a disease flare, overlapping autoimmune disease, steroid myopathy, and antimalarial myopathy. Referral for muscle biopsy or EMG is recommended when the etiology is not clear. (2) Quinacrine should be considered along with other antimalarial agents in the differential of a medication-induced myopathy. In this case rhabdomyolysis was attributed to quinacrine, an adverse effect that has not been reported previously.


1. Wortmann RL. Inflammatory diseases of muscle and other myopathies. In: Ruddy S, Harris ED, Sledge CB (eds.), Kelley's Textbook of Rheumatology. 6th Ed. Philadelphia: W.B. Saunders Company; 2001:230-308.

2. Richter JG, Becker A, Ostendorf B, et al. Differential diagnosis of high serum creatine kinase levels in systemic lupus erythematosus. Rheumatol Int. 2003;23:319-323.

3. Richards AJ. Hydroxychloroquine myopathy. J Rheumatol. 1998;25:1642-1643.

4. Stein M, Bell MJ, Ang LC. Hydroxychloroquine neuromyotoxicity. J Rheumatol. 2000;27:2927-2931.

5. Van Beek MJ, Piette, WW. Antimalarials. Dermatol Clin. 2001;19:147-160.

6. Wallace DJ. The use of quinacrine (Atabrine) in rheumatic diseases: a reexamination. Semin Arthritis Rheum. 1989;18:282-296

7. Tye MF, White H, Apel B, et al. Lupus erythematosus treated with a combination of quinacrine, hydroxychloroquine and chloroquine. N Engl J Med. 1959;260:63-66.

8. Toubi E, Rosner I, Rozenbaum M, et al. The benefit of combining hydroxychloroquine with quinacrine in the treatment of SLE patients. Lupus. 2000;9:92-95.

9. Wallace DJ. Is there a role for quinacrine (Atabrine) in the new millennium? Lupus. 2000;9:81-82.

10. Werth V. Current treatment of cutaneous lupus erythematosus. Dermatol Online J. 2001;7:2.

11. Wald JJ. The effects of toxins on muscle. Neurol Clin. 2000;18:695-718.

12. George KK, Pourmand R. Toxic myopathies. Neurol Clin. 1997;15:711-730.

13. Phanish MK, Krishnamurthy S, Bloodworth LL. Colchicineinduced rhabdomyolysis. Am J Med. 2003;115:166-167.

14. Kumar S. Steroid-induced myopathy following a single oral dose of prednisolone. Neurol India. 2003;51:554-556.

15. Mandel S. Steroid myopathy. Insidious cause of muscle weakness. Postgrad Med. 1982;72:207-210.

16. Wolverton SE, ed. Comprehensive Dermatologic Drug Therapy. Philadelphia: W.B. Saunders Company; 2001.

17. Maltz HC, Balog DL, Cheigh JS. Rhabdomyolysis associated with concomitant use of atorvastatin and cyclosporine. Ann Pharmacother. 1999;33:1176-1179.

18. Guttman-Yassky E, Hayek T, Muchnik L, Bergman R. Acute rhabdomyolysis and myoglobinuria associated with isotretinoin treatment. Int J Dermatol. 2003;42:499-500.

19. Trauner MA, Ruben BS. Isotretinoin induced rhabdomyolysis? A case report. Dermatol Online J. 1999;5:2.

20. Carroll GJ, Will RK, Peter JB, Garlepp MJ, Dawkins RL. Penicillamine induced polymyositis and dermatomyositis. J Rheumatol. 1987;14:995-1001.

CPT Naomi Creel MC USA, (a) Victoria Werth MD (b)

a. Department of Dermatology, Walter Reed Army Medical Center, Washington DC

b. Department of Dermatology, University of Pennsylvania and Philadelphia VA Hospital, Philadelphia, PA

Address for Correspondence

Victoria P. Werth, MD

Department of Dermatology

University of Pennsylvania

2 Rhoads Pavilion, 36th and Spruce

Philadelphia, PA 19104

Phone: 215-662-2399 Fax: 215-349-8339


COPYRIGHT 2005 Journal of Drugs in Dermatology, Inc.
COPYRIGHT 2005 Gale Group

Return to Rhabdomyolysis
Home Contact Resources Exchange Links ebay