Eosinophilia–myalgia syndrome

Overview

Eosinophilia–myalgia syndrome (EMS) is a rare, potentially life-threatening condition characterized by high levels of eosinophils (a type of white blood cell) in the blood and severe muscle pain (myalgia). The syndrome emerged in the late 1980s and was initially associated with the use of contaminated L-tryptophan supplements. EMS affects multiple organ systems and can lead to chronic, disabling symptoms or even death if not promptly recognized and treated. Though its exact mechanism is not fully understood, EMS is now considered a multisystem toxic or autoimmune reaction triggered by environmental or pharmaceutical exposures.

Causes

The most well-documented cause of EMS is the consumption of contaminated L-tryptophan supplements, particularly those manufactured by a specific company in the late 1980s. The contamination introduced impurities that triggered the immune system to overproduce eosinophils, leading to systemic inflammation. Other possible contributing factors include:

• Genetic predisposition to immune dysregulation

• Environmental or chemical exposures

• Other dietary supplements or medications (rare and less well-documented)

Since regulatory action restricted L-tryptophan production and distribution, the incidence of EMS has significantly declined.

Symptoms

EMS presents with a wide range of symptoms that may appear suddenly or progress gradually. Common clinical features include:

• Severe, diffuse muscle pain (myalgia)

• Peripheral eosinophilia: Elevated eosinophil count in the blood

• Edema: Swelling, especially in the arms and legs

• Skin changes: Thickening, induration (hardening), or rash

• Neurological symptoms: Tingling, numbness, or weakness due to nerve damage

• Fatigue and weakness

• Fever and general malaise

• Respiratory or cardiovascular involvement in severe cases

In some cases, symptoms may mimic other autoimmune or inflammatory diseases, which can delay diagnosis.

Diagnosis

Diagnosis of eosinophilia–myalgia syndrome is clinical and based on a combination of symptoms, laboratory findings, and exclusion of other disorders. Diagnostic criteria generally include:

• Eosinophilia: Absolute eosinophil count greater than 500 cells/μL

• Severe myalgia: Often debilitating, lasting weeks or longer

• Absence of other known causes: Such as parasitic infection, autoimmune disease, or malignancy

• Muscle biopsy: May show inflammation, eosinophilic infiltration, or fibrosis

• Skin or nerve biopsy: May help confirm systemic involvement

• Review of supplement or medication history: Especially use of L-tryptophan or similar agents

Treatment

Treatment of EMS focuses on reducing inflammation, managing symptoms, and preventing progression. Strategies include:

• Discontinuation of suspected causative agent: Immediate cessation of L-tryptophan or other supplements

• Corticosteroids: Such as prednisone, to suppress immune activity and reduce inflammation

• Immunosuppressants: In severe or steroid-resistant cases (e.g., methotrexate or azathioprine)

• Pain management: Analgesics and physical therapy to relieve muscle pain and improve mobility

• Supportive care: For cardiac, respiratory, or neurological complications if present

• Regular monitoring: Blood counts, muscle function, and organ health

Prognosis

The prognosis of EMS varies depending on the severity of the condition and the timing of diagnosis and treatment. Many patients improve with appropriate therapy, but others may experience chronic muscle pain, weakness, skin changes, or neurological deficits. In severe cases, complications such as pulmonary hypertension, heart failure, or neuropathy can lead to long-term disability or even death. Early recognition, cessation of the causative agent, and aggressive treatment can significantly improve outcomes.