John C. Maize

Department of Dermatology SUNY at Buffalo Buffalo, New York Department of Dermatology Massachusetts General Hospital Boston, Massachusetts

An association between the ingestion tryptophan and a syndrome characterized by scleroderma-like skin abnormalities, fasciitis, and eosinophilia has recently been recognized in the United States. We report the clinical and histopathological findings in nine patients and the results of biochemical analyses of tryptophan metabolism in seven patients with this syndrome. Edema of the extremities, frequently accompanied by pruritus, paresthesia, and myalgia, developed in the nine patients (six women and three men; age range, 30 to 66 years) 1 to 18 months after the start of therapy with tryptophan (1.5 to 3.0 g daily) for insomnia, depression, or obesity. Five patients were taking drugs (benzodiazepines) known to inhibit hypothalamic-pituitary-adrenal function, and one had adrenal insufficiency. All had blood eosinophilia in the acute phase of their illness (mean eosinophil count [+/- SD], 3.62 +/- 2.87 X 10(9) cells per liter). All had histopathological changes in the dermis and subcutaneous tissue typical of scleroderma, and seven patients had eosinophils. The fascia was inflamed and fibrotic, and adjacent skeletal muscle often showed perifascicular inflammation. Tryptophan was discontinued in all patients, and eight received prednisone. The cutaneous symptoms improved, but only two patients had complete resolution of their illness. The patients had plasma levels of tryptophan before and after an oral dose of tryptophan that were similar to those in normal subjects. Plasma levels of L-kynurenine and quinolinic acid, which are metabolites of tryptophan, were significantly higher in four patients with active disease than in three patients studied after eosinophilia had resolved or in five normal subjects (P less than 0.001)--findings consistent with the activation of the enzyme indoleamine-2,3-dioxygenase. This illness resembles eosinophilic fasciitis and probably represents one aspect of the recently reported eosinophilia-myalgia syndrome. The development of the syndrome may result from a confluence of several factors, including the ingestion of tryptophan, exposure to agents that activate indoleamine-2,3-dioxygenase, and possibly, impaired function of the hypothalamic-pituitary-adrenal axis.

Acral lentiginous melanoma is a newly recognized subtype of malignant melanoma that occurs on volar and subungual skin. Histologic examination of 69 primary volar and subungual melanomas revealed 31 (45%) acral lentiginous, 18 (26%) superficial spreading, and two (3%) nodular melanomas. Eighteen biopsies were inadequate for subclassification. Seventy-one percent (49/69) occurred on plantar skin, 10% (7/69) on the palm, and 19% (13/69) on nailbeds. Plantar melanomas occurred most frequently on weight-bearing areas, particularly the heel (45%). Most were level 4 or 5 at the time of diagnosis. The overall five-year survival of patients with plantar melanomas was 43%. The mitotic rate showed an inverse relationship with survival. The ratio of volar skin melanomas to subungual melanomas was 4:1. Ninety-two percent of subungual melanoma occurred on the thumb or great toe. The five-year survival for palmar and subungual melanomas was 19%. Our data confirm that acral lentiginous melanoma is a distinct subtype of melanoma with a unique histologic appearance and behavior, but not all volar and subungual melanomas are the acral lentiginous type.