The presentation of EMS varies from one individual to another. A majority of patients will undergo acute and chronic stages.

Acute 

The onset of EMS is often sudden and progressive. The acute phase of the illness lasts 3 to 6 months. Symptoms include low-grade fever, malaise, pruritic rash, and generalized myalgia. The latter is particularly observed in the back, shoulders, and legs. Also, more than half will develop edema in the periorbital region, face, and extremities. Furthermore, a third of EMS cases exhibit neurologic findings including paresthesia, numbness, and burning. Pulmonary findings such as cough and dyspnea are commonly seen as well but usually resolve within 3 months or less. Likewise, gastrointestinal manifestations such as dysphagia and diarrhea have been reported. Another common sign is alopecia.

Chronic

Most patients will experience long-term complications since EMS can persist for 3 to 4 years after the acute illness. This second stage involves various organs especially the skin. Thickening of skin can progress to eosinophilic fasciitis, particularly on the extremities.

Myalgia, muscle weakness, neuropathy, bladder dysfunction, myopathy, and fatigue frequently occur as well. Moreover, muscle cramping develops early and can last for years with devastating spasms triggerd by physical activity. Finally, if the CNS is affected, patients will experience a behavioral and cognitive decline. 

The workup includes obtaining a thorough history as well determining the patient's medication and supplement intake. Also, a detailed physical exam is necessary to assess the severity of the symptoms. Since other diseases may share similar features, it is paramount to exclude other conditions. Hence, most of the studies are performed to rule out differential diagnoses.

Laboratory studies

Laboratory testing is usually extensive. A complete blood count (CBC) in EMS demonstrates eosinophilia, which is key for the diagnosis per the CDC. This finding is observed early but diminishes over time. Therefore, it may not be present in later stages of the disease. CDC criteria define an eosinophil count of 1000 cells/µL as a positive sign for EMS although it is usually in the 10,000 to 30,000 range. Additionally, leukocytosis and elevated liver functions tests (LFTs) are commonly found as the latter is demonstrated in 40% of patients.

Other laboratory findings include increased erythrocyte sedimentation rate (ESR) and aldolase which is in contrast to creatinine kinase. Moreover, a speckled pattern of antinuclear antibodies is seen, but this is an inexplicable finding.

Imaging

As the clinical presentation varies, so will the chest X-ray, which ranges from normal to revelations such as infiltrates and effusions. Brain MRI may demonstrate various abnormalities such as subcortical infarcts, cortical atrophy, focal lesions and other findings as well.

Other

Pulmonary function tests will help clarify if the presentation is due to underlying lung diseases. Electromyography studies investigate the function of muscles and their innervating nerves.

There is no standard treatment for EMS and therapy is usually supportive and symptomatic. Non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, muscle relaxants, and diuretics can provide relief depending on the clinical manifestations of the patient. A key component in the treatment of EMS is the discontinuation of the source such as L-TRP or other implicated substances (if known). Corticosteroids in doses up to 60mg per day may be effective in the treatment of eosinophilic fasciitis, however, the class of drugs has not demonstrated slowing the progression, duration or severity of EMS.

As presentations vary, treatment and expert consultations will reflect the clinical picture. Neurology, rheumatology, pulmonology, dermatology, and surgical expert advice can guide the management of the patient. Some patients require hospital admission. Also, since this disease could be debilitating, assisted living support may be needed. Patients are encouraged to rest and avoid excessive physical activity as the latter can result in exacerbation of muscle pain and cramping.

Studies report that the mortality rate of EMS ranged from 2% to 6%. There were 31 deaths by July 1991. A majority of the fatal cases stemmed from cardiopulmonary conditions, ascending neuropathy, or superimposed infection. The prognosis is poor in those with affected organs, neurologic manifestations such as ascending polyneuropathy, and fibrotic skin.

Acutely ill patients suffering from debilitating myalgia, pulmonary complications, or muscle cramping required hospitalization. Since the acute phase produces irreversible tissue damage, the clinical sequelae in most patients usually lasted for 3 to 4 years. Furthermore, findings of acute inflammation were observed a year post EMS [10]. Only 10% of patients experienced full recovery while many exhibited persistent symptoms such as fatigue, myalgia, and muscle spasm. Memory loss was also observed.

A majority of affected individuals developed EMS during an outbreak in 1989. A thorough investigation traced the disease to contaminated L-TRP although not all cases were attributed to this substance. According to one study, 44% of individuals who consumed a similar product did not develop EMS. Hence, it is likely that genetic predisposition may have played a role.

L-TRP is an essential amino acid found ubiquitously in food and supplements. Furthermore, this over the counter amino acid is used for various conditions such as premenstrual syndrome, depression, insomnia and others.

In patients with EMS, exposure to L-TRP ranged from 2 weeks to 9 years in which the median exposure was 6 months. Furthermore, the daily doses spanned from 500mg to 11,500mg. The median dose was 1250mg. In conclusion, no duration or dose have been linked to the development of this disease. 

In 1989, EMS was initially observed in 3 individuals in New Mexico. Furthermore, the CDC had received 1543 documented cases in the United States by 1991 [5]. It is likely that significantly higher numbers were affected as the estimates suggested 5,000 to 10,000 individuals. However, the number of reported cases has considerably decreased as just a few have been documented since 1991. The most recent were observed in 2011 [6]. Studies have shown that 0.5%-9% of L-TRP users during the epidemic were affected with EMS. The cases were linked to the amino acid’s product lot.

With regards to demographics, most patients with EMS were white (97%) and female (84%). The ages ranged from 18 to 81 years of age but was more common in the middle age. In addition to the United States, United Kingdom, France, Japan, Israel, Germany and Canada reported occurrences.

There are 3 main observations in EMS 1) hyperplasia of capillary endothelial cells, 2) infiltration of inflammatory cells in various tissues such as nerve, muscle and connective tissue, and 3) fibrosis in fascia and skin. In fact, the latter represents the hallmark characteristics of EMS.

The mechanism of disease is not well established. Investigations have narrowed the L-TRP to the manufacturer Showa Denko K, which is based in Japan. There were 60 contaminants [7] implicated in the pathogenesis of EMS. Furthermore, researchers have suggested that the consumption of contaminated L-TRP in predisposed individuals activates a pathogenic pathway involving acute inflammation, eosinophilia and other mechanisms that cause fibrosis of tissues [8]. Other reports, however, observed the development of EMS in people who have not taken L-TRP, which leads to the belief that other xenobiotics may trigger similar immune reactions. 

Another possible theory stems from the inhibition of histamine metabolism by excessive tryptophan supplement intake. Hence, increased histamine produces eosinophilia as well as myalgia [9].

The precise cause is unknown, but L-TRP from certain manufacturers may be implicated. Substances with this should be avoided as a safety measure. Since muscle cramping and pain is usually debilitating and chronic, patients should avoid prolonged physical activity. Also, some patients will need living assistance due to the resultant morbidity.

Eosinophilia–Myalgia syndrome (EMS) is a potentially life-threatening multisystem disorder characterized by two primary manifestations (as its name suggests). It was initially observed in 1989 during an epidemic outbreak that affected 1,500 people and resulted in 30 fatalities [1]. The multiorgan disease involves muscle, nerve, fascia, and/or skin in the context of eosinophilia and myalgias [2] [3]. The Centers for Disease Control (CDC) surveillance program includes peripheral eosinophilia and myalgias in its definition of EMS [4].

The precise etiology is not known, but investigators linked EMS to L-tryptophan (L-TRP) by a manufacturer in Japan. Many patients had consumed a contaminated form of L-TRP, which is found in supplements. After the outbreak, the supplement was removed from the market in 1990. However, not all cases were associated with this contaminant. It is thought that other factors such as genetic predisposition and environment may play a role in the etiology of EMS. 

The clinical presentation varies from one patient to another. The abrupt and progressive disease has an acute and a chronic phase. Furthermore, most patients will have long-term residual symptoms. Chronic sequelae such as muscle pain, cramping, and neuropathy can be morbid in these patients. Additionally, skin fibrosis is common and is typically the hallmark feature of this illness. 

In addition to a history and physical exam, extensive laboratory tests and other studies are performed to diagnose EMS and eliminate differentials. As for treatment, there is no particular therapy for EMS. Hence, treatment is usually for symptom relief. 

Eosinophilia-Myalgia syndrome (EMS) is a rare disease that can affect the different systems in the body such as muscle, nerves, skin, and lungs. The disease was originally discovered in an outbreak in the United States that took place in 1989. It was traced to a substance called tryptophan, which is found in supplements (it is also found in the body and many foods as well). This particular supplement was contaminated and was taken off the market shortly afterwards. There are other possible causes, however, as some patients were not linked to this substance. 

Patients experience a number of symptoms such as muscle pain and cramping, joint pain, skin rashes, numbness or burning sensation of the hands and legs, swelling of face and hands, fatigue, and shortness of breath. Not all patients will have the same symptoms. Also, most individuals with EMS will have long term effects such as muscle pain and cramping. 

The clinician will do a complete history and detailed exam. Also, many blood tests and possibly imaging (such as chest X-ray and brain MRI) will be performed to arrive at the correct diagnosis.

There is no specific medicine for this disease. Treatment is for symptom relief. Patients with debilitating pain may need help with physical activity at home or even in the hospital setting. Patients should not do strenuous activity since this may worsen the cramps and pain. 

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