Post-epidemic eosinophilia-myalgia syndrome associated with L-tryptophan

Abstract

Eosinophilia-myalgia syndrome (EMS) is characterized by subacute onset of myalgias and peripheral eosinophilia, followed by chronic neuropathy and skin induration. An epidemic of EMS in 1989 was linked to consumption of L-tryptophan that had originated from a single source. Following the ban by the Food and Drug Administration (FDA) on the sale of L-tryptophan, the incidence of EMS declined rapidly. Moreover, no new cases have been described since the FDA ban was lifted in 2005. We report the clinical, histopathologic, and immunogenetic features of a new case of L-tryptophan-associated EMS, along with evidence of activated transforming growth factor β and interleukin-4 signaling in the lesional skin.

Figure 1. Clinical presentation of EMS

A. Skin induration and edema in the left arm is shown and was also present in both upper and lower extremities with palpably thickened fascia. B. Axial magnetic resonance imaging STIR sequence images of the thigh revealed high signal intensity in the fascia surrounding the anterior and posterior compartment muscles (arrows). C. High resolution computed chest tomography showing ground glass changes and air space opacity in the left lung (arrow).

Figure 2. Tissue inflammation, fibrosis, and eosinophil degranulation

Skin (A) and muscle (B – I) biopsy specimens stained with hematoxylin and eosin (A – F), Gomori trichrome (G), and antibodies to eosinophil derived neurotoxin (EDN) (H) and major basic protein (MBP) (I). A. Skin fibrosis with dermal collagen accumulation and eosinophil infiltration (arrow). B. Fascia and muscle specimen demonstrates dense fibrosis of epidermal fascia (dark arrow) and atrophic muscle fascicles (white arrow). C. Higher power magnification reveals scattered necrotic fibers (arrow). D – G. Inflammatory infiltrate (arrows) in the perimysial connective tissue (D), endomysial connective tissue (E), around intramuscular nerve (F), and around intramuscular blood vessels (G). Eosinophils were only rarely detected. H, I. Immunofluorescence analysis. EDN (H) and MBP (I) staining is present in the perimysial and endomysial connective tissue, as well as around intramuscular blood vessel and nerve (not shown).

Figure 3. Genes differentially expressed in EMS skin biopsy relative to healthy controls

Gene expression was measured in an EMS skin biopsy in triplicate and in three independent sex-, age- and anatomical site-matched normal control skin biopsies. All samples were taken from the left forearm. 343 differentially expressed genes were selected using Significance Analysis of Microarrays (FDR = 0.64%). Select genes are indicated and those discussed in the text are in bolded. The full figure with all gene names is available as supplemental Figure S3.