Lithium-Induced Rash

Sir: Lithium has been used as a mood stabilizer for decades and has been approved by the U.S. Food and Drug Administration for acute and maintenance therapy of mania in bipolar disorder. The Physicians' Desk Reference lists generalized pruritus with or without rash as one of the dermatologic side effects of lithium.1 We present an interesting case of maculopapular rash that we believe was induced with lithium. Case report. Ms. A, a 60-year-old woman with a past psychiatric history of bipolar disorder, was brought to the emergency room in 2005 by her family for some odd behaviors. The family described a 2-week history of spending sprees, staying up all night, talking excessively, and making inappropriate phone calls. She called her former employers and was verbally abusive to them, which resulted in a restraining order being issued against her. A thorough medical work-up in the emergency room did not reveal any significant findings. Her past medical history was significant for coronary bypass graft, end stage renal disease requiring dialysis, and gastritis. Her current medications were captopril, omeprazole, atrovastatin, aspirin, spirono-lactone, amiodarone, and cetrizine. She was found to have pressured speech with a circumstantial thought process without any psychosis or cognitive impairment. She was later transferred to the psychiatric floor for stabilization. The patient had a history of bipolar disorder with 4 past psychiatric hospitalizations, the last being 6 years ago. She had been on divalproex and lithium in the past with no adverse effects, but noncompliance has been an ongoing issue in her case. There had been no psychiatric follow-up for the last 5 years. A diagnosis of bipolar disorder, most recent episode manic, was made using the DSM-IV diagnostic criteria, and she was started on lithium 300 mg at bedtime and que-tiapine 25 mg at bedtime on an as-needed basis for sleep. Within a few days a significant symptomatic improvement was noticed. On the sixth day after initiation of lithium, she was found to have a red maculopapular rash about 5 cm × 3 cm in size over the left pretibial area. There were no complaints of itching or any signs of systemic infection. Her lithium level a day before was 0.5 mEq/L. Her lithium was withheld, resulting in a fading of her rash over the next 2 days. Unfortunately, she left the hospital against medical advice and went to the home of her daughter, who convinced us that the patient would follow up with outpatient psychiatry within the next few days. It has been reported that women are at increased risk of cutaneous lesions when treated with lithium, usually within the first year of its initiation.2 In our case, the temporal association of the onset of the rash within a week of the initiation of lithium and its fading within 2 days of its discontinuation points to a causal relationship. Although the exact mechanism is unclear, it has been proposed that inhibition of adenylate cyclase/cyclic AMP systems induced by lithium could be responsible for the cutaneous conditions.2 Other lithium-induced skin conditions include psoriasis, acne, folliculitis, exfoliative dermatitis, seborrheic dermatitis, and herpetiform dermatitis. The prevalence rate of lithium-induced cutaneous reaction has been reported to be 34% in one study2 and 45% in another.3 Further investigation regarding cutaneous lesions associated with lithium therapy is warranted as this distressing side effect could adversely affect the medication compliance.