L-tryptophan-associated eosinophilia-myalgia syndrome: Clinical and pathological features of an evolving new disease and current concepts of etiology

The eosinophilia-myalgia syndrome (EMS) is a newly recognized illness that occurred in the United States and in other countries in an epidemic form during 1989. The outbreak was associated with ingestion of the essential amino acid L-tryptophan. The illness appears to be heterogeneous; it has an early phase characterized by myalgia, skin rashes, constitutional symptoms, and marked peripheral blood eosinophilia, followed by a late phase characterized by chronic cutaneous, neuromuscular, pulmonary, and other manifestations. Because EMS has no pathognomonic findings, the diagnosis is based on recognizing the characteristic clinical and laboratory features of the syndrome, supported by the histopathological findings of inflammation and fibrosis of the subcutaneous fascia and the connective tissue structures surrounding skeletal muscle and peripheral nerve fibers. Toxicoepidemiological studies suggest that the epidemic of EMS was caused by a point-source contamination of L-tryptophan preparations. Analysis of L- tryptophan preparations identified a tryptophan-related novel amino acid present only in batches associated with EMS, but extensive studies with animals have thus far failed to establish an etiologic role for this contaminant in EMS. A recently identified second contaminant is chemically similar to analide derivatives isolated from samples of cooking oils that caused the toxic oil epidemic in Spain. Experimental studies suggest a major role for eosinophil and fibroblast activation in the pathogenesis of EMS. This newly recognized illness has focused intense interest on the role of chemical and environmental agents in the pathogenesis of various idiopathic illnesses characterized by inflammation and fibrosis.