What is Eosinophilia-Myalgia Syndrome (EMS) and how is it diagnosed and treated in a patient with elevated eosinophil counts and muscle pain, potentially associated with contaminated tryptophan supplements?

Eosinophilia-Myalgia Syndrome (EMS)

Definition and Historical Context

Eosinophilia-Myalgia Syndrome (EMS) is a severe, potentially fatal disorder characterized by marked eosinophilia (>1,000 cells/mm³) and debilitating myalgia, historically linked to contaminated L-tryptophan supplements. 1, 2 This syndrome emerged as an epidemic in 1989 when contaminated tryptophan products caused widespread illness, leading to recognition of this distinct clinical entity. 1

Clinical Presentation

Cardinal Features

• Severe muscle pain and weakness, particularly affecting proximal upper and lower extremities 1, 3
• Marked eosinophilia exceeding 1,000 cells/mm³ (often >8,000 cells/mm³) 1, 2
• Skin manifestations including edema, induration, morphea-like lesions, and pruritus 3
• Mouth ulcers 1

Additional Manifestations

• Fever and abdominal pain 1
• Dyspnea and cough with pulmonary infiltrates 3
• Ascending polyneuropathy in some cases 3
• Skin rash 1

Laboratory Abnormalities

• Elevated serum aminotransferase and aldolase levels 1
• Elevated serum and urinary eosinophil-granule major basic protein 1
• Elevated eosinophil-derived neurotoxin, indicating eosinophil degranulation 1
• Normal erythrocyte sedimentation rate 3
• Negative antinuclear antibodies and other connective tissue disease markers 3

Pathophysiology

Tissue damage results from eosinophilic infiltration with subsequent release of toxic molecules such as major basic protein. 3 Biopsies demonstrate eosinophilic infiltration of muscle, vagina, liver, and other organs, along with extracellular deposition of eosinophil-granule major basic protein. 1

Diagnostic Criteria

The Centers for Disease Control established diagnostic criteria requiring: 2

• Eosinophil count >1,000 cells/mm³
• Debilitating generalized myalgia
• Absence of infectious or neoplastic causation

Electrodiagnostic Findings

• Myopathic changes on electromyography (EMG) 4
• Single fiber EMG may show abnormalities paralleling clinical course 4
• Some patients demonstrate pure myopathy without neuropathic features 4

Differential Diagnosis

EMS shares features with but remains distinct from: 5

• Eosinophilic fasciitis
• Systemic sclerosis variants
• Polymyalgia rheumatica (though EMS has true weakness, not just pain) 6
• Hypereosinophilic syndrome 6

A critical distinguishing feature is the historical association with L-tryptophan ingestion (typically 1.2-2.4 g daily for 3 weeks to 2.5 years). 1

Treatment Approach

Immediate Management

Discontinue L-tryptophan immediately upon diagnosis. 1

Pharmacologic Treatment Algorithm

First-line therapy: Corticosteroids 5, 3

• Indicated for severely ill patients 3
• Improve general symptoms, arthralgias, arthritis, myalgias, skin changes, eosinophilia, and leukocytosis 5
• Critical caveat: Symptoms frequently recur when corticosteroids are tapered, except for eosinophilia and leukocytosis which may remain controlled 5

Second-line therapy: Low-dose pulse oral methotrexate 5

• Reserved for patients unresponsive to corticosteroids or those with severe/refractory disease 5
• Six of seven patients showed continued improvement after mean follow-up of 4.5 months 5
• Allows tapering or discontinuation of corticosteroids without relapse 5
• Well-tolerated with good drug tolerance 5

Ineffective or minimally effective therapies:

• NSAIDs and analgesics provide only transient or minimal relief 5
• D-penicillamine and colchicine show minimal improvement 5
• Azathioprine demonstrates no response 5

Prognosis and Long-term Outcomes

EMS has a prolonged clinical course with potential for fatal complications. 6, 2 Even with treatment discontinuation and corticosteroid therapy, patients remain symptomatic for months. 1 After 10 months of treatment, patients may continue experiencing muscle cramping and reduced endurance with persistent mild electromyographic abnormalities. 4

Clinical Pitfalls

• Do not rely solely on NSAIDs—they are insufficient for symptom control 5
• Anticipate symptom recurrence when tapering corticosteroids; have methotrexate available as backup 5
• Recognize that normal ESR and negative autoantibodies do not exclude EMS—this is characteristic of the syndrome 3
• Consider EMS in any patient with unexplained eosinophilia and myalgia, even if tryptophan use is remote or denied 1
• Monitor for cardiopulmonary complications including pulmonary infiltrates and respiratory symptoms 3