History
The symptoms of eosinophilia-myalgia syndrome (EMS) vary greatly, but onset is typically acute or subacute and over the first 3-4 months most commonly consists of the following [8] :
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Myalgias: Patients complain of generalized, severe, debilitating muscle pain and/or cramps. The shoulders, back, and legs are most commonly affected. Relapses after complete resolution are common. Weakness is an uncommon symptom early in the disease. Muscle cramps involving the leg and abdominal muscles occur early in the disease course and may persist for years
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Edema: Peripheral edema involving the extremities and face occur in more than half of patients, typically 3-4 weeks after disease onset.
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Arthralgias: Pain in large joints is common, but true arthritis is rare.
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Alopecia: Non-scarring scalp hair loss is observed frequently during the acute illness and gradually resolves.
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Rash: 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.
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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.
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Pulmonary symptoms: Nonproductive cough and/or dyspnea usually appear within 2-3 weeks after the onset of myalgias. They are self-limited in most patients.
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Neurological symptoms: These include parasthesias, numbness, or a burning sensations and affect up to one third of EMS patients.
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Gastrointestinal symptoms: Rarely patients will complain of dysphagia, diarrhea, or dyspepsia.
The clinical manifestations of EMS greatly vary. Typically, there is an abrupt onset of incapacitating myalgias, 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 follow. 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. [18]
The acute inflammatory symptoms just listed typically resolve after 3-6 months, but at 1 year patients with EMS can have chronic symptoms that include the following:
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Subjective muscle weakness
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Spontaneous or activity-induced muscle cramps
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Joint pain and stiffness
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Memory loss
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Difficulty concentrating
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Difficulty communicating (eg, word finding and word substitution problems)
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Scleroderma-like skin changes
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Dyspnea on exertion
Only about 10% of patients, out of 333 surveyed 4 years since symptom onset, reported a complete recovery. [19]
Physical
Rashes occur most commonly over the face, neck, and extremities but truncal involvement is also seen. Examination of the skin in patients with eosinophilia-myalgia syndrome (EMS) may reveal the following:
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Macules varying from small and purplish to large and brownish
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Mucinous yellow plaques
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Serpiginous lesions
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Erythematous plaques
Later in the disease course, the skin may appear scleroderma-like with a woody, peau d’orange appearance similar to eosinophilic fasciitis.
Examination of the muscles will rarely reveal objective weakness early in the disease course, although later in the illness this may be present.
Cardiopulmonary and abdominal examinations are generally normal, but hepatomegaly or findings of interstitial pneumonitis and/or a pleural effusion (i.e. pulmonary crackles, dullness to percussion, etc) may be present.
Extremities and facial exam may show edema. Joint examination may reveal tender joints, but synovitis and effusions are absent.
Neurologic findings are typically sensory abnormalities in a stocking-glove distribution, but reports of ascending paralysis, facial palsy, and encephalitis have been reported. [8]
Causes
Although no one cause of EMS has been identified, most patients (97%) with this disease reported consuming L-tryptophan. The median exposure was 6 months, but this ranged from 2 weeks to 9 years. Doses vary from 500-11,500 mg per day, and the median dose patients consumed was 1250 mg. L-tryptophan is commonly used by patients with FMS but also is taken for insomnia, depression, and premenstrual symptoms. One specific impurity identified in L-tryptophan was 1’1’-ethylidenebis[tryptophan] (EBT).
Not every patient who consumed the specific lot of L-tryptophan from Showa Denko, a pharmaceutical company in Japan, developed EMS. There are other genetic and host factors that are required for a patient to develop EMS. [8]
Other causes include other nutritional supplements like niacin, probiotics, L-lysine, or 5 hydroxytryptophan, but patients can develop EMS without a history of drug or supplement use.
