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Topical Tretinoin and Neurologic Side Effects
This report describes a surprising association between topical tretinoin and neurotoxicity. A 39-year-old woman presented with complaints of headache, memory loss, and unsteadiness that interfered with simple daily activities. Examination showed truncal ataxia and dysarthria. The patient was suffering from untreated depression and chronic hepatitis C. Her liver enzymes were elevated by 30%, consistent with mild hepatitis, but her EEG was normal. The cause of the neurologic disease was unclear until the patient revealed that she had borrowed a friend's topical tretinoin (0.025%) to treat her own acne about four to six weeks before she visited the neurologist. She had been using large amounts of cream and developed dermatitis on her face. Two weeks after she stopped using the cream, her neurologic problems improved but her acne worsened. When she restarted the cream, the ataxia returned. The ataxia cleared four weeks after she again stopped using the cream, and she remained well for eight months. Her liver tests were unchanged.
The authors speculate that tretinoin was the cause of the neurotoxicity, since vitamin A and synthetic retinoids can cause headache, pseudotumor cerebri, irritability, ataxia, fatigue, depression, and psychosis. Factors that may have put this patient at risk are increased absorption of the retinoid through her inflamed, excoriated skin and increased availability of the retinoid because of reduced production of retinol-binding protein due to liver disease.
Comment: Topical tretinoin has been on the market for 24 years. This isolated report suggests that many susceptibility factors must be present for neurotoxicity to occur. These include high dose, breakdown of the skin barrier, and liver disease. I think it likely that other, unknown co-factors must also be present. Nevertheless, we need to be cautious when using topical retinoids in patients with liver disease and to warn them about possible neurotoxicity.
— NH Shear
Published in Journal Watch Dermatology March 1, 1996
Citation(s):
Bernstein AL; Leventhal-Rochon JL. Neurotoxicity related to the use of topical tretinoin (Retin-A). Ann Intern Med 1996 124 227-228.
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