Eosinophilia-Myalgia Syndrome Clinical Presentation

The clinical manifestations of eosinophilia-myalgia syndrome (EMS) greatly vary. Typically, there is an abrupt onset of incapacitating myalgia, muscle cramps, dyspnea, peripheral edema, low-grade fever, fatigue, and skin rashes. These acute inflammatory symptoms resolve in 3-6 months, and variable degrees of neuropathy, myopathy, and skin thickening occur. Three to 4 years after the acute illness, patients report persistent chronic fatigue, intermittent myalgias, and muscle cramps, but no new manifestations appear after that time.

• Early features of EMS, observed during the first 3-4 months, include the following:

  • Myalgias: Patients complain of generalized, severe, incapacitating muscle pain that tends to worsen over weeks. The shoulders, back, and legs are affected most often. Relapses after complete resolution are common. Muscle weakness is usually not observed at this early stage. Muscle cramps involving the leg and abdominal muscles occur within weeks and may persist for years. Movement, exercise, or change in position may trigger muscle spasm.
  • Edema: Peripheral edema involving the extremities, facial edema, and periorbital edema occur in more than half of patients, typically 3-4 weeks after disease onset.
  • Arthralgias: Pain in large joints is common, but true arthritis is rare.
  • Alopecia: Nonscarring scalp hair loss is observed frequently during the acute illness and then resolves gradually.
  • Skin rash: Cutaneous manifestations develop approximately 3 weeks after the onset of myalgia and last for an average of 3 months. The types of rash seen in patients with EMS include macules varying from small and purplish to large and brownish, urticaria, mucinous yellow plaques, dermatographism, serpiginous lesions, and erythematous plaques. Severe pruritus is prominent in some patients.
  • Skin thickening: These findings occur in approximately one third of the patients. They resemble those seen in eosinophilic fasciitis, with skin thickening and subcutaneous induration affecting the forearms, arms, and legs. Patches of skin thickening resembling morphea are occasionally observed. In contrast with systemic sclerosis, digital skin thickening and Raynaud phenomenon are rare in patients with EMS.
  • Pulmonary symptoms (eg, nonproductive cough, dyspnea, or both): Pulmonary symptoms are observed commonly and usually appear within 2-3 weeks after the onset of myalgias. These complaints are self-limited in most patients and last less than 3 months.
  • Neurological symptoms (eg, paresthesias, numbness, burning sensations): Approximately one third of patients report these symptoms.
  • Gastrointestinal symptoms (eg, dyspepsia, dysphagia, diarrhea): These problems have been described in some patients with EMS.
• At the end of 1 year, more than half of patients with EMS have persistent chronic symptoms, including the following:

  • Myalgias with remissions and relapses
  • Muscle weakness (based on history)
  • Fatigue often described as "profound" (40% of patients)
  • Spontaneous or activity-induced muscle cramps
  • Joint pain and stiffness
  • Paresthesias, including numbness, tingling, and burning sensations
  • Memory loss, difficulty concentrating
  • Difficulty communicating (eg, word finding and word substitution problems)
  • Sclerodermalike skin changes
  • Dyspnea upon exertion
• No new symptoms have been noted after the first 6 months to 1 year after disease onset.
• Analysis of self-reported answers to questionnaires from 333 patients 4 years after the acute illness shows that most patients continued to have symptoms (as described above) and only 10% reported full recovery.

• Skin rashes: These include macules varying from small and purplish to large and brownish, urticaria, mucinous yellow plaques, dermatographism, serpiginous lesions, and erythematous plaques. Rashes commonly occur over the face, neck, and extremities. Truncal involvement is also seen.
• Sclerodermalike skin changes: These include woody, leathery, dry, thickened skin with a peau d'orange appearance similar to eosinophilic fasciitis. These changes appear later in the disease course (after several months) and tend to persist in most patients.
• Muscle weakness: Definite muscle weakness is not observed initially. However, later in the course of the illness, weakness may be present. Muscle weakness is independent of myalgias.
• Pulmonary findings: Objective pulmonary findings are uncommon. Findings vary from normal to those suggestive of interstitial pneumonitis and pleural effusion. Only a few case reports describe mild pulmonary hypertension.
• Facial and extremity edema
• Hepatomegaly
• Neurological findings: These are consistent with sensory or sensorimotor involvement in a glove-stocking distribution. Ascending motor paralysis, compression neuropathies, facial palsy, and encephalitis have been described.

• No specific etiologic agent has been found for EMS.
• Most individuals identified as having EMS during the acute outbreak consumed L-tryptophan (97%) prior to the development of the syndrome.

  • Patients with EMS were exposed to L-tryptophan for 2 weeks to 9 years, with a median exposure of 6 months. The daily dose varied from 500-11,500 mg, with a median dose of 1250 mg.
  • No correlation was observed between the development of EMS and the duration or dose of L-tryptophan use.
• L-tryptophan is an essential amino acid found in many foods and has been available over the counter since 1974. It has been used for insomnia, depression, premenstrual symptoms, and other complications.
• Studies conducted during the epidemic implicated an L-tryptophan product lot manufactured by Showa Denko, a pharmaceutical company in Japan.

  • Administration of L-tryptophan from this lot induced inflammation of subcutaneous fascia and perimysium in mice.
  • The temporal clustering of the disease and a report of a patient not developing EMS when rechallenged with a different lot of L-tryptophan imply a contaminant in the product lot from Showa Denko as the cause of EMS.
  • Extensive research has failed to identify a precise cause, although a contaminant identified as "Peak E" (1,1,ethylidenebis) is most commonly associated with the development of EMS.
• Consumption of L-tryptophan manufactured by the implicated producer did not always result in disease. In one study, 44% of the persons who used the implicated lot did not develop EMS. Genetic and other host factors are also likely to have played a role in the precipitation of EMS.
• Clinical syndromes indistinguishable from EMS have been identified both in persons consuming other nutritional supplements (eg, 5 hydroxytryptophan, L-lysine, niacin) and in individuals without any history of drug intake.
• The exact cause of TOS is not known.