SCLERODERMA, FASCIITIS, AND EOSINOPHILIA ASSOCIATED WITH THE INGESTION OF TRYPTOPHAN

被引:271
作者
SILVER, RM
HEYES, MP
MAIZE, JC
QUEARRY, B
VIONNETFUASSET, M
STERNBERG, EM
机构
[1] MED UNIV S CAROLINA,DEPT DERMATOL,CHARLESTON,SC 29425
[2] NIMH,WASHINGTON,DC 20032
[3] NIAMSD,WASHINGTON,DC
关键词
D O I
10.1056/NEJM199003293221302
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
An association between the ingestion of 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×l09 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<0.001) — findings consistent with the activation of the enzyme indoleamine2,3-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. A RECENTLY described condition termed the eosinophilia—myalgia syndrome has been reported in epidemic form in the United States.1 Case–control studies have established an association between the use of products containing the amino acid tryptophan and the development of the syndrome.2 Although its full spectrum has yet to be defined, it is similar in some respects to a previously described chemically induced illness, the toxic-oil syndrome, which occurred in epidemic form in Spain in 1981,3 and the syndrome of eosinophilic fasciitis. We have previously described a scleroderma-like illness in a patient receiving L-5-hydroxytryptophan and carbidopa that was remarkably similar to the… © 1990, Massachusetts Medical Society. All rights reserved.
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页码:874 / 881
页数:8
相关论文
共 35 条
[1]  
AUFFRANC JC, 1985, ANN DERMATOL VENER, V112, P691
[2]   5-HYDROXYTRYPTAMINE . A CYTOSPECIFIC GROWTH STIMULATOR OF CULTURED FIBROBLASTS [J].
BOUCEK, RJ ;
ALVAREZ, TR .
SCIENCE, 1970, 167 (3919) :898-&
[3]   INTERACTION BETWEEN GABAERGIC NEUROTRANSMISSION AND RAT HYPOTHALAMIC CORTICOTROPIN-RELEASING HORMONE-SECRETION INVITRO [J].
CALOGERO, AE ;
GALLUCCI, WT ;
CHROUSOS, GP ;
GOLD, PW .
BRAIN RESEARCH, 1988, 463 (01) :28-36
[4]   EFFECT OF LY53857, A SELECTIVE 5HT2 RECEPTOR ANTAGONIST, ON 5HT-INDUCED INCREASES IN CUTANEOUS VASCULAR-PERMEABILITY IN RATS [J].
COHEN, ML ;
SCHENCK, K .
LIFE SCIENCES, 1989, 44 (14) :957-961
[5]   POTENTIAL NEUROTOXICITY OF TRYPTOPHAN [J].
FREESE, A ;
SCHWARTZ, KJ ;
DURING, M .
ANNALS OF INTERNAL MEDICINE, 1988, 108 (02) :312-313
[6]   FIBROTIC DISORDERS ASSOCIATED WITH METHYSERGIDE THERAPY FOR HEADACHE [J].
GRAHAM, JR ;
SUBY, HI ;
LECOMPTE, PR ;
SADOWSKY, NL .
NEW ENGLAND JOURNAL OF MEDICINE, 1966, 274 (07) :359-&
[7]  
HAYES MP, 1989, BR RES, V491, P173
[8]   QUANTIFICATION OF QUINOLINIC ACID IN RAT-BRAIN, WHOLE-BLOOD, AND PLASMA BY GAS-CHROMATOGRAPHY AND NEGATIVE CHEMICAL IONIZATION MASS-SPECTROMETRY - EFFECTS OF SYSTEMIC L-TRYPTOPHAN ADMINISTRATION ON BRAIN AND BLOOD QUINOLINIC ACID CONCENTRATIONS [J].
HEYES, MP ;
MARKEY, SP .
ANALYTICAL BIOCHEMISTRY, 1988, 174 (01) :349-359
[9]   (O-18)QUINOLINIC ACID - ITS ESTERIFICATION WITHOUT BACK EXCHANGE FOR USE AS INTERNAL STANDARD IN THE QUANTIFICATION OF BRAIN AND CSF QUINOLINIC ACID [J].
HEYES, MP ;
MARKEY, SP .
BIOMEDICAL AND ENVIRONMENTAL MASS SPECTROMETRY, 1988, 15 (05) :291-293
[10]   DETERMINATION OF SERUM KYNURENINE AND HEPATIC TRYPTOPHAN DIOXYGENASE ACTIVITY BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY [J].
HOLMES, EW .
ANALYTICAL BIOCHEMISTRY, 1988, 172 (02) :518-525