Isotretinoin revolutionized the treatment of acne1 and has been used successfully in many other skin diseases.2 Its adverse effects, which are fewer at low doses of the drug, have been well described.3 Frequent side effects are muscle pain and elevated serum creatine kinase (CK) concentrations.4,5 However, few publications on an association of this drug and rhabdomyolysis have appeared. We report the case of a patient who developed severe rhabdomyolysis while on a low-dose regimen of isotretinoin.

A 30-year-old man with no remarkable medical history, who was a fourth-year resident physician in dermatology, self-prescribed oral isotretinoin at a dose of 20mg/wk to treat seborrheic dermatitis refractory to topical agents. He did not undergo any laboratory testing prior to starting treatment was not taking any other medications or using street drugs. Three months later he developed myalgia and passed dark-colored urine after a 45-minute session of intense anaerobic exercise. He was afebrile and had no other symptoms. He went to the emergency department, where tests showed a highly elevated serum CK concentration (128084IU/L [reference, 0–195IU/L]) and elevated liver enzymes (aspartate aminotransferase, 860U/L [reference, 0–35]; and alanine aminotransaminase, 223U/L [reference, 0–45U/L]). Renal function, plasma electrolytes, and full blood count results were normal. He was admitted, isotretinoin suspended, and intravenous fluids infused to force diuresis and urine alkalinization. The CK concentration gradually fell and symptoms gradually improved. Renal function never deteriorated, and he was discharged after 8 days. On follow-up he remained asymptomatic; serum CK levels, blood counts, and thyroid function test results also remained normal. He was advised not to resume taking isotretinoin. Six months later he restarted regular aerobic and anaerobic exercise with no future incidents.

Rhabdomyolysis is the breakdown and necrosis of striated muscle tissue, usually after the muscle has been severely damaged.6 Other causes included exposure to drugs and poisons, infection, muscle enzyme deficencies, metabolic myopathies, endocrine disorders, electrolyte disturbances, and central hyperthermia.6 Clinical features include muscle pain and weakness, dark-colored urine, and CK levels 5-fold higher than reference values.6 Complications, among them renal insufficiency, electrolyte imbalances and disseminated intravascular coagulation, can be life-threatening.6 Treatment involves life-support measures and intense hydration to prevent kidney failure.6

Isotretinoin has been used successfully to treat acne and is indicated for many skin diseases, including hidradenitis suppurativa, seborrheic dermatitis, rosacea, folliculitis decalvans, and viral warts, among others.2 Myalgia is a common adverse effect that appears in more than 25% of patients on high-dose regimens (0.7–1.0mg/kg/d), but only rarely must treatment be suspended if it develops.3 Asymptomatic serum CK elevation during isotretinoin therapy, which has been well documented, is considered a benign self-limited event. Only rarely does the concentration increase 5-fold. CK monitoring during therapy is not recommended and changes do not justify interrupting treatment.4,5 However, some authors have reported an association between CK elevation and rhabdomyolysis, particularly after intense physical exercise (Table 1),7,8 and 1 case of fatal rhabdomyolysis related to isotretinoin has been reported.9 It seems reasonable to periodically check CK concentrations in patients on this drug if they practice sports and to warn them to avoid intense exercise. Patients on statins and antipsychotic medications, which are associated with rhabdomyolysis, should also be followed and warned. Moreover, the physician should inquire about muscle and joint pain, urine color, and muscle weakness during medical visits.3

Low-dose isotretinoin therapy has proven effective10 and is associated with a lower rate of side effects, including myalgia, than therapy at higher doses.3 Even so, a case of rhabdomyolysis was described in an adolescent treated with 20mg/d.7

We identified no other toxins, medications, drugs, or endocrine disorders that could explain our patient's symptoms. He has remained asymptomatic since suspending isotretinoin and has been able to resume physical exercise. We therefore think that this drug and intense exercise were responsible for the episode of acute muscle damage.

Isotretinoin is a safe drug that is well tolerated, but strict vigilance is needed when it is prescribed3 even at low doses. Although testing prior to starting therapy would not have prevented the development of rhabdomyolysis in our patient, it could lower the risk of complications such as hepatitis and severe dyslipidemia. We think that patients on this drug should be warned to refrain from intense exercise and that physicians should watch for symptoms suggestive of rhabdomyolysis so that treatment can be started promptly.