Development of a Scleroderma-like Illness during Therapy with L-5-Hydroxytryptophan and Carbidopa

A scleroderma-like illness developed in a patient treated with L-5 hydroxytryptophan (L-5HTP) and carbidopa for intention myoclonus. The patient had high plasma kynurenine levels that remained high when the L-5HTP-carbidopa combination was discontinued. However, levels rose further on drug rechallenge, suggesting that the drug unmasked an abnormality in one of the enzymes that catabolize kynurenine. Plasma kynurenine was also determined to be high in seven of 15 patients with idiopathic scleroderma, but not in eight patients with intention myoclonus treated with L-5HTP and a decarboxylase inhibitor and in whom scleroderma did not develop or in 10 patients with Parkinson's disease treated with L-dopa and carbidopa. Our data and studies in the literature suggest that two factors may be important in the pathogenesis of some scleroderma-like illness: high plasma serotonin and the abnormality associated with elevated kynurenine. (N Engl J Med. 1980; 303:782–7.) SCLERODERMA-LIKE syndromes have been associated with abnormalities of both the kynurenine and 5-hydroxytryptamine (5-HT, or serotonin) pathways of tryptophan metabolism 1 2 3 4 5 (Fig. 1). Scleroderma-like changes have been found in patients with carcinoid syndrome who have elevated blood levels of serotonin, 4 , 6 and in rats and rabbits receiving intradermal or intra-articular injections of serotonin. 3 , 7 Some patients with idiopathic scleroderma have elevated urinary kynurenine. 1 , 2 , 8 This elevation may result from defects in the enzymes that catabolize kynurenine or may be seen in pyridoxine deficiency due to decreased activity of pyridoxal phosphate-dependent enzymes. 1 , 8 Alterations in the pattern of excretion of tryptophan metabolites resembling those seen in . . .