The neuromuscular pathology of the Eosinophilia-Myalgia syndrome.

The Eosinophilia-Myalgia Syndrome (EMS) is a recently reorganized disorder in patients ingesting pharmacologic doses of L-tryptophan. We studied the lesions of skeletal muscle, peripheral nerve and skin in 12 cases of EMS. Perimyositis was severe in four, moderate in two, mild in three and absent in three cases. The lesions contained many eosinophils, T-helper cells, mast cells and activated macrophages. Type 2 myofiber atrophy was present in five cases and in one, this was the only pathologic finding. Severe epineurial inflammation was seen in the three sural nerve biopsies. Indirect evidence for peripheral neurologic involvement in three other cases consisted of inflammation surrounding intramuscular nerve twigs (two cases) and neurogenic atrophy (one case). Phlebitis accompanied the connective tissue inflammation in five cases and endarteritis in one. Fasciitis was present in three of four skin biopsies and dermal fibrosis in one.

L-tryptophan-associated eosinophilic perimyositis, neuritis, and fasciitis. A clinicopathologic and laboratory study of 25 patients.

We have described the spectrum and prevalence of the clinical and laboratory manifestations of a multisystem disorder associated with the ingestion of L-tryptophan. At least 3 subsets of clinical disease have been identified: 1) a neuromuscular disorder which may present with myalgias and mild weakness and then progress to quadriparesis related to an axonal neuropathy and interstitial myositis (perimyositis), 2) a syndrome of eosinophilic fasciitis with characteristic cutaneous induration, and 3) the Löffler syndrome consisting of pulmonary infiltrates with eosinophilia. Corticosteroids may be useful for patients with the Löffler syndrome and offer only a modest benefit in the majority of patients with neuromuscular disease. The clinical course appears to be chronic, and the long-term sequelae of this disorder are unknown. The etiologic agent remains undetermined; however, studies are in progress to examine the mechanism of eosinophilia, appropriate therapeutic intervention, and the long-term outcome of the affected individuals.

Glial transforming growth factor (TGF)-beta isotypes in multiple sclerosis: differential glial expression of TGF-beta 1, 2 and 3 isotypes in multiple sclerosis.

We studied glial transforming growth factor (TGF)-beta isotype expression in 14 cases of multiple sclerosis. Acute active lesions exhibited selective TGF-beta 2 immunoreactivity of lesion encircling ramified microglia. In contrast, astrocytes within chronic active white matter lesions expressed all three isotypes. Chronic active lesions which extended into cortex exhibited selective cortical astrocyte TGF-beta 2 expression. This isotype was also selectively expressed by astrocytes in apparently normal white matter. A similar pattern of glial TGF-beta expression was seen in the pathological control, progressive multifocal leukoencephalopathy. The results suggest that TGF-beta cytokines are locally expressed in demyelination and that the beta 2 isotype may be uniquely regulated.

L-tryptophan-associated eosinophilia-myalgia syndrome: perspective of a new illness.

The current knowledge of the eosinophilia-myalgia syndrome as an evolving new disease entity is reviewed in the context of previously described eosinophilic disorders. The acute and chronic manifestations parallel the findings of the toxic oil syndrome of Spain and include scleroderma-like skin disease, neuropathy, and myopathy.

Paraganglioma of the cauda equina: case report with magnetic resonance imaging description.

The case of a 35-year-old white man with a cauda equina syndrome is presented. Magnetic resonance imaging confirmed the diagnosis, and radiation treatment successfully treated the condition.

Cutaneous manifestations of the L-tryptophan-associated eosinophilia-myalgia syndrome: a spectrum of sclerodermatous skin disease.

The natural history of the clinical and pathologic features of skin disease was reviewed prospectively in 30 patients with the L-tryptophan-associated eosinophilia-myalgia syndrome. Overall, cutaneous manifestations developed in 26 patients (87%). Early lesions were nonspecific and characterized predominantly by an erythematous macular eruption on the trunk and extremities. The most characteristic abnormality noted was the spectrum of sclerodermatous disease in 15 patients (50%) often after a subacute stage of peripheral or truncal edema. Clinical and/or biopsy evidence of eosinophilic fasciitis was seen in nine patients (30%). Findings consistent with diffuse, limited, or localized scleroderma were subsequently observed in nine patients (33%). Small mucinous papules, similar to those seen in scleromyxedema, were found in five patients (17%). Alopecia, frequently a late sequela, developed in 11 (37%). Common histologic features included papillary dermal fibrosis, dermal and fascial infiltrates consisting of mononuclear cells and eosinophils, deposition of glycosaminoglycans in the dermis, and, in some patients, numerous mast cells.

Experimental immunization with Borrelia burgdorferi induces development of antibodies to gangliosides.

Patients with neuroborreliosis produce antibodies, mostly of the immunoglobulin M (IgM) class, to gangliosides, particularly to those with Gal(beta 1-3)GalNac terminal sequences. Lewis rats were immunized with a nonpathogenic strain of Borrelia burgdorferi and with a chloroform-methanol extract (nonprotein) of this organism (CM) to determine whether antibodies to B. burgdorferi also recognized gangliosides. Rats were also immunized with asialo-GM1 to determine whether the elicited antibodies recognized antigens in B. burgdorferi. Rats immunized with B. burgdorferi produced low levels of IgM antibodies that cross-reacted with asialo-GM1 and GM1. Rats immunized with CM had marked IgM reactivity to asialo-GM1 and GM1. Immunization with asialo-GM1 resulted in antibodies that cross-reacted with B. burgdorferi antigens. Although antibodies to B. burgdorferi were of both the IgM and IgG classes, those to CM and to asialo-GM1 and GM1 were predominantly in the IgM fraction. Reactivity of the IgM antibodies decreased after adsorption with the heterologous and the homologous antigens, indicating bidirectional cross-reactivity between CM, asialo-GM1, and GM1 and that immunization with one produces antibodies to the other. There was no in vivo deposition of Ig in peripheral nerves, nor was there nerve pathology as a result of immunizations, but IgM antibodies to asialo-GM1 and CM recognized homologous antigens in the nodes of Ranvier of peripheral nerves from nonimmunized rats. This immunization model suggests that antibodies to gangliosides in Lyme disease have a microbial origin and are potentially relevant in pathogenesis.

Eosinophilic neuritis, perimyositis, and vasculitis associated with ingestion of L-tryptophan.

Four cases are described of a clinical syndrome which developed in the setting of L-tryptophan ingestion. The major manifestations consisted of myalgias, neuropathy, weakness, and profound eosinophilia. Pathologically a vasculitis involving predominantly small veins was observed along with a mixed cellular infiltrate in the perimysium and epineurium. Clusters of eosinophils were characteristically noted in the tissue specimens. The clinical course appears to be chronic although further longterm followup will be required. One patient pursued a relentless downhill course with progressive neurologic impairment and death. Although the mechanism of tissue injury in these individuals is speculative, the possible association of this widely used nonprescription medication with this syndrome should be recognized.