Geographic variation in the prevalence of Raynaud's phenomenon: a 5 region comparison.

OBJECTIVE: To determine the population based prevalence of Raynaud's phenomenon (RP) in 5 geographic regions: one in South Carolina, USA, and 4 in France; to explore the relationship of RP to the climate; to investigate possible risk factors; and to describe the characteristics of RP+ subjects in the general population. METHODS: The study consisted of 2 phases: a telephone survey of a randomly drawn sample of households, with 10,149 completed interviews; these were followed by a face to face interview and clinical evaluation (n = 1,534), including diagnosis of RP. The same methodology was used in all 5 regions: for recruitment of subjects, criteria for RP, method of RP diagnosis, and for gathering additional information. RESULTS: The prevalence of RP was found to be related to the climate. The relationship between RP and climate was complicated, however, by the fact that many subjects had moved between climate zones. The relationship of RP to a cold climate became more evident after taking the migration patterns into account: the majority of RP+ subjects in the 2 coldest regions had lived all their lives in the same or a similar climate zone; the majority of RP+ subjects in the 2 warmest regions had previously lived in a colder climate. Other factors associated with RP were family history of RP, cardiovascular diseases, older age, a low body mass index, use of vibrating tools, and outings of a day or more. The classical triphasic RP was rarely encountered in the general population and the most frequently observed signs and symptoms during an RP attack were blanching accompanied by numbness. CONCLUSION: In addition to being a triggering factor for RP attacks, cold also appears to be an etiologic factor in the pathogenesis of RP. A subclinical cold injury, more likely to occur in colder climates, may be responsible for the "local fault" that has been implicated in the pathogenesis of RP and, in association with other risk factors, may predispose subjects to develop clinical RP.

Scleroderma, fasciitis, and eosinophilia associated with the ingestion of tryptophan.

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.