Levodopa-induced skin disorders in patients with Parkinson disease: a systematic literature review approach

The use of levodopa for treatment of Parkinson's disease is a well-established clinical practice. Data about the true incidence and severity of cutaneous complications associated with the use of levodopa are largely lacking. Aim of this review was to evaluate the quality of evidence referring to the skin disorders caused by levodopa treatment for Parkinson's disease. Thirty of 1084 studies were included; 8 randomized controlled trials and 22 case reports in a total of 2749 patients. Malignant melanoma was the most frequent oral levodopa-related skin disorder followed by allergic cutaneous reactions, alopecia, vitiligo, skin hyperpigmentation, Laugier-Hunziker syndrome, Henoch-Schonlein syndrome, pseudobullous morphea and scleroderma-like illness. Naranjo scores ranged from 2 to 8. Regarding levodopa clinical trials, the most frequent skin complication was peripheral edema, followed by malignant melanoma. Although evidence is not robust, melanoma is the most frequent and possible fatal levodopa-associated skin disorder, while other skin allergic or immunological reactions are less common and reversible. Although levodopa treatment may induce melanogenesis and promote melanomagenesis, existing evidence does not support an association between levodopa therapy and induction or progression of malignant melanoma. The suggested association with melanoma may reflect the well-documented association of Parkinson's disease with melanoma rather than the exposure to the drug. Nevertheless, until a solid conclusion can be drawn, the use of levodopa in the context of malignant melanoma should be considered with caution. Well-designed prospective studies are needed to determine the cause and effect relationship between levodopa and skin disorders.