Neuromuscular manifestations of L-tryptophan-associated eosinophilia-myalgia syndrome: a histomorphologic analysis of 14 patients.

The recent delineation of a clinical syndrome marked by eosinophilia, myalgia, and scleroderma-like skin changes associated with L-tryptophan use has necessitated the Centers for Disease Control to initiate a health alert. The likely association of L-tryptophan ingestion with a syndrome that mimics eosinophilic fasciitis (Shulman's syndrome) further identifies an environmental agent associated with an inflammatory sclerosing rheumatic disease process. In this report, we present the clinical, morphologic, and enzyme histochemical findings in muscle, skin, and fascia biopsies from 14 cases fulfilling the Center for Disease Control diagnostic criteria for L-tryptophan-associated eosinophilia-myalgia syndrome. The clinical syndrome reveals a high incidence of arthralgia, elbow contracture, and clinical neuropathy. The absence of significant change in creatine kinase or sedimentation rate allows for diagnostic separation from other inflammatory myopathies. Histoenzymatic features in muscle biopsies reveal a preferential epimysial-perimysial noneosinophilic infiltration characterized by acid phosphatase reactive histiocytosis, nonnecrotizing venulitis, perineural inflammation within dermis and perimysium, type II fiber atrophy with superimposed denervation features, and perifascicular alkaline phosphatase reactivity representing early neofibroplasia. The constellation of changes in skin, fascia, and muscle, with the defined clinical syndrome, allows for accurate differentiation from allied syndromes, including eosinophilic polymyositis, scleroderma, idiopathic polymyositis/dermatomyositis, polyarteritis nodosa, and toxic oil syndrome. Accurate differentiation from eosinophilic fasciitis still rests on a history of L-tryptophan ingestion.