Is the L-tryptophan Metabolite Quinolinic Acid Responsible for Eosinophilic Fasciitis?

The eosinophilia-myalgia syndrome is accompanied by alterations in L-tryptophan metabolism with elevated levels of L-kynurenine and quinolinic acid having been recorded. It has been suggested that this is due to activation of indoleamine 2,3-dioxygenase by interferon-gamma. It is unknown whether these products of tryptophan metabolism play a role in the pathogenesis of this syndrome and the closely related condition of eosinophilic fasciitis. To explore this possibility, the principal author (RN) received a series of subcutaneous injections of quinolinic acid. A total of 1200 mg was administered over a 1-month period. Peripheral blood eosinophil counts were monitored and biopsies taken for H&E and immunohistochemical stains. Over the 1-month period the eosinophil count rose from 0.3x10(9)/l to 0.8x10(9)/l before falling to 0.4x10(9)/l approximately 5 weeks later. H&E sections showed a mixed infiltrate of eosinophils and neutrophils extending through the reticular dermis and septa of the panniculus. No deep fascia was obtained on biopsy. The immunohistochemical stain for transforming growth factor beta 1 showed staining of endothelial cells and dendritic cells. The interleukin-5 stain was negative. Our results suggest that quinolinic acid may play a role in cutaneous eosinophilic disorders.