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. 

• Fatigue

  Their clinical picture was indistinguishable from that of the so-called Chronic Fatigue Syndrome. A chronic fatigue may occur after diverse triggering agents and its represents the peculiar clinical evolution of these four paediatric cases of EMS. [ncbi.nlm.nih.gov]

  […] oral preparations of l- tryptophan ; long-term sequelae include scleroderma and progressive neuropathy. e·o·sin·o·phil·i·a-·my·al·gi·a syn·drome (EMS), a probable autoimmune disorder precipitated by contaminated l -tryptophan tablets; characterized by fatigue [medical-dictionary.thefreedictionary.com]

  Marked fatigue. Skin rashes - including macules, papules and urticarial-type lesions. There can be associated pruritus. Skin involvement - occurs in 60%. [patient.info]

• Fever

  […] l- tryptophan ; long-term sequelae include scleroderma and progressive neuropathy. e·o·sin·o·phil·i·a-·my·al·gi·a syn·drome (EMS), a probable autoimmune disorder precipitated by contaminated l -tryptophan tablets; characterized by fatigue, low-grade fever [medical-dictionary.thefreedictionary.com]

  Eight patients who became ill while taking tryptophan had myalgia, fatigue, rash, fever, edema, alopecia, arthralgias, diminished joint motion, skin tightening, muscle cramping, and distal paresthesias. [ncbi.nlm.nih.gov]

  Fever and myalgia responded to steroids and painkillers. The patient went back to Nigeria after 3 weeks or so. [arthritis-india.com]

  It is characterized by flu -like symptoms that can include muscle spasms and pain, fever and fatigue, as well as shaking, edema, hair loss, and a high eosinophilia count. [wisegeek.com]

  included fever, rash, conjunctivitis, hepatitis and myocarditis. [pharmaceutical-journal.com]

• Weight Loss

  loss, an axonal polyneuropathy, and perivascular lymphoid infiltrates simulating a lymphoma. [ncbi.nlm.nih.gov]

  In the early phase of the disease, most patients have muscle aches; cough; dyspnea; macules, papules, or urticarial skin lesions; intense pruritus; constitutional symptoms, such as fatigue, fever, and weight loss; and persistent, incapacitating myalgias [emedicine.com]

  Some other symptoms of eosinophilia which are usually rare include enlargement of the lymph node, weight loss, sweating at night, other rashes in the skin & sometimes a patient will feel numb with tingling because of nerve damage. [signssymptoms.org]

  Systemic symptoms - fever, weight loss or gain. Marked fatigue. Skin rashes - including macules, papules and urticarial-type lesions. There can be associated pruritus. Skin involvement - occurs in 60%. [patient.info]

• Falling

  Abstract The L-tryptophan eosinophilia myalgia syndrome (L-TRP-EMS), an inflammatory syndrome characterized by eosinophilia, myalgias, perimyositis, fasciitis and neuropathies, occurred in epidemic proportions in the United States in the summer and fall [jpet.aspetjournals.org]

  A total of 1,478 cases of the disorder, including 21 deaths, have been reported to the Centers for Disease Control since the outbreak was detected last fall. [nytimes.com]

  In the summer and fall of 1989, an epidemic outbreak of eosinophilia-myalgia syndrome (EMS) occurred in the United States. This illness is associated with the use of dietary supplements containing L-tryptophan. [web.archive.org]

  Taking L-tryptophan might decrease the amount of time it takes to fall asleep and improve mood in healthy people with sleep problems. [rxlist.com]

  At bedtime, the time it takes to fall asleep after lights out is termed the sleep latency (SL) and normally is 43 ). [doi.org]

• Acutely Ill Patient

  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. [symptoma.com]

  Alopecia: Non-scarring scalp hair loss is observed frequently during the acute illness and gradually resolves. [emedicine.medscape.com]

• Rhinitis

  Patients with similar symptoms who have negative skin tests and a normal serum IgE are said to have nonspecific rhinitis. [btb.termiumplus.gc.ca]

  In our patient, fever, weight loss, and polyneuropathy occurred after an initial presentation of bronchial asthma, allergic rhinitis, and eosinophilia, which fulfilled the diagnostic criteria for EGPA. [karger.com]

  […] in children with functional GI disorders.4,5 This article showed similar results in pediatric patients with functional GI disorders, however, the diagnosis was based on the Rome III criteria, and excluded food allergy, asthma, atropic dermatitis, and rhinitis [jnmjournal.org]

  […] bacterial, fungal, or viral infections myeloid leukemia Hodgkin lymphoma mastocystitis, when too many mast cells collect in the skin, bone marrow, liver, and other organs cancerous tumors eosinophilic granuloma, a benign tumor on the bone allergies rhinitis [medicalnewstoday.com]

  Case report A 22-year-old woman with a history of allergic rhinitis, asthma and repeated upper respiratory tract infections in the previous two years developed progressive asthenia, dizziness and left leg paresthesias. [revportcardiol.org]

• Abdominal Distension

  On D3, the pain worsened and was described by the patient as left thoracolumbar colic, radiating to the periumbilical region and testicles, associated with important abdominal distension. [bjid.org.br]

• Xerostomia

  Among the 28 various head and neck manifestations studied, 70% of EMS patients complained of generalized muscle spasms, 66% xerostomia, 62% dyspnea, and 56% dysphagia. [ncbi.nlm.nih.gov]

• Hypertension

  Three had shortness of breath, and one had pulmonary hypertension. [ncbi.nlm.nih.gov]

  Pulmonary hypertension due to toxic oil syndrome. A clinicopathologic study.. Chest, 95 (1989), pp. 325-31 [15] Rubin LJ.. Primary pulmonary hypertension.. N Engl J Med, 336 (1997), pp. 111-7 [16] Rich S.. Primary pulmonary hypertension. [revespcardiol.org]

• Heart Disease

  […] chambers), pericardial disease, unexplained heart murmurs, valvular heart disease, functional evaluation of heart failure, chest pain study following inconclusive initial examination, functional evaluation of ischemic heart disease, functional evaluation [revespcardiol.org]

  **Includes persons who reported they had ever had coronary heart disease, angina pectoris, myocardial infarction, or any other "heart attack." [cdc.gov]

  Involvement of the heart has been described in the third stage of the disease, as observed in our patient. [revportcardiol.org]

• Palpitations

  […] behavioral changes Decreased cognitive function that include: Memory loss Difficulty concentrating or communicating Rarely, the chronic symptoms may include: Heart abnormalities Inflammation of heart muscle (myocarditis) Irregular heartbeats (arrhythmia) Palpitations [dovemed.com]

  Such symptoms include heart (cardiac) abnormalities including inflammation of the heart muscle (myocarditis), irregular heartbeats (arrhythmias) and palpitations. [rarediseases.org]

• Myalgia

  Eosinophilia-Myalgia Syndrome is a topic covered in the 5-Minute Clinical Consult. [unboundmedicine.com]

  We describe a patient with eosinophilia-myalgia syndrome who developed incapacitating myalgias and peripheral eosinophilia responsive only to high dose corticosteroids. [ncbi.nlm.nih.gov]

  Morb Mort Wkly Rep 38:785–788 Google Scholar --(1990a) Analysis of L-tryptophan for the etiology of eosinophilia-myalgia syndrome, Morb Mort Wkly Rep 39:589–591 Google Scholar --(1990b) Update: analysis of L-tryptophan for the etiology of eosinophilia-myalgia [doi.org]

  […] eosinophilia-myalgia syndrome a sometimes fatal syndrome of severe myalgia associated with marked peripheral eosinophilia, associated with the ingestion of oral preparations of l- tryptophan ; long-term sequelae include scleroderma and progressive neuropathy [medical-dictionary.thefreedictionary.com]

• Arthralgia

  On October 1989, eosinophilia and incapacitating myalgia, together with arthralgia, dyspnea, cough and edema of the extremities, were shown to be associated with L-tryptophan ingestion. [ncbi.nlm.nih.gov]

• Myopathy

  Most studies to date describe an associated peripheral neuropathy or combined myopathy and peripheral neuropathy. This report presents 2 EMS patients with myopathy, confirmed by muscle biopsy in 1 case and electrophysiology in both cases. [ncbi.nlm.nih.gov]

  Iatrogenic and toxic myopathies Sieb JP, Gillessen T Muscle & Nerve, 2003, 27, p. 142-156 Eosinophilic myopathic syndromes Pickering MC, Walport MJ Current opinion in rheumatology, 1998, 10, 6, p. 504-510 Clinical improvement of the myopathy in eosinophilia-myalgia [myobase.org]

• Muscle Spasm

  Among the 28 various head and neck manifestations studied, 70% of EMS patients complained of generalized muscle spasms, 66% xerostomia, 62% dyspnea, and 56% dysphagia. [ncbi.nlm.nih.gov]

  Symptoms Myalgias (Uniformly present) Rapid onset with persistent pain Severe and incapacitating pain (limits Activities of Daily Living) Associated with Muscle spasms (esp. calves, Abdomen) Associated with perceived weakness Exacerbated by movement Arthralgias [fpnotebook.com]

  It is characterized by flu -like symptoms that can include muscle spasms and pain, fever and fatigue, as well as shaking, edema, hair loss, and a high eosinophilia count. [wisegeek.com]

  Symptoms of EMS The most difficult symptom of EMS is generalized, severe muscle pain that tends to worsen over weeks and may cause muscle spasms. Symptoms tend to begin suddenly and range from mild to severe. [verywell.com]

  Symptoms of EMS The most common symptom of eosinophilia-myalgia syndrome is generalized, severe muscle pain that tends to worsen over weeks and may cause muscle spasms. Symptoms tend to begin suddenly and range from mild to severe. [verywellhealth.com]

• Muscle Tenderness

  tenderness and cramps, weakness, paresthesias of the extremities, and skin indurations; marked eosinophilia is noted on peripheral blood studies, serum aldolase is increased, and biopsies of peripheral nerve, muscle, skin, and fascia show microangiopathy [medical-dictionary.thefreedictionary.com]

  His examination revealed pigmentation over forehead, muscle tenderness over extremities, swollen and tender wrist joints and pain and crepitus in both knees (suggestive of osteoarthritis). [arthritis-india.com]

  It can cause blood abnormalities and excessive muscle tenderness. It’s not clear whether EMS is caused by an accidental contaminant or by 5-HTP itself. Keep this in mind when deciding whether 5-HTP is right for you. [healthline.com]

  tenderness • No joint tenderness or swelling • Significant proximal muscle weakness in both upper and lower extremities • No focal neurologic abnormalities Case 2: Question • Based on these findings, which of the following diagnoses should be initially [studocu.com]

  tenderness and cramps, weakness, paresthesias of the extremities, and skin indurations. 2, record 2, English, - eosinophilia%2Dmyalgia%20syndrome Record number: 2, Textual support number: 1 OBS The varied symptoms include severe muscle pain and abnormally [btb.termiumplus.gc.ca]

• Alopecia

  Eight patients who became ill while taking tryptophan had myalgia, fatigue, rash, fever, edema, alopecia, arthralgias, diminished joint motion, skin tightening, muscle cramping, and distal paresthesias. [ncbi.nlm.nih.gov]

  Alopecia can occur. Neurological symptoms - can include paraesthesia, burning and numbness. A sensory/sensorimotor neuropathy can occur in a glove and stocking distribution. There may be hyperaesthesia. [patient.info]

• Sweating

  Some other symptoms of eosinophilia which are usually rare include enlargement of the lymph node, weight loss, sweating at night, other rashes in the skin & sometimes a patient will feel numb with tingling because of nerve damage. [signssymptoms.org]

  […] and Manfred Sorg and Karsten Krueger}, journal={Klinische Wochenschrift}, year={1990}, volume={68}, pages={739-742} } SummaryWe present the case of a 35-year-old male patient with severe myalgia and arthralgia in combination with fatigue, nocturnal sweating [semanticscholar.org]

  1990 Klinische Wochenschrift volume 68, pages 739–742 (1990)Cite this article 51 Accesses 8 Citations Metrics details Summary We present the case of a 35-year-old male patient with severe myalgia and arthralgia in combination with fatigue, nocturnal sweating [link.springer.com]

  They lasted 30 to 40 minutes and were accompanied by nausea, sweating, and inability to move out of the bed. My feet felt as if they were caught in a bear trap, and it was the worst pain I would ever felt except for natural childbirth. [sclero.org]

  The symptoms of serotonin syndrome include agitation, delirium, coma, mydriasis, sweating, hyperthermia, tremor, rigidity, and myoclonus ( 36, 37 ). [doi.org]

• Pruritic Rash

  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. [symptoma.com]

  Clinical resolution was progressively reached after 15 days of corticosteroid therapy, and the patient was discharged within three weeks.20 A young woman has sought care in the emergency room with an extensive pruritic rash, fever, lymphadenomegaly, arthralgia [bjid.org.br]

  Enalapril has been reported to cause a pruritic rash associated with eosinophilia.34 The rash resolved seven days after enalapril was discontinued. [pharmaceutical-journal.com]

• Eczema

  However, hair loss does occur in up to 22% of people with an atopic condition (asthma, allergies, eczema). And this type of hair loss, called alopecia areata, also has been seen in people with eosinophil-related disorders. [verywellhealth.com]

  I was told I might have eczema; however, the doctor, a brilliant allergist, actually said this to me the first time he saw my legs: "I have never seen anything like this rash, and I do not know what it is." That was late August 1989. [sclero.org]

  […] associated with organ dysfunction that is seen with 1 or more of the following: fibrosis (lung, heart, gastrointestinal tract, skin, or others); thrombosis with or without thromboembolism; cutaneous and mucosal erythema, edema/angioedema, ulceration, or eczema [hematologyandoncology.net]

• Tremor

  OBJECTIVE: To describe the development of tremor, myoclonus, and myokymia as chronic sequelae of eosinophilia-myalgia syndrome (EMS). [ncbi.nlm.nih.gov]

  […] characterized by chronic pain in the muscle tissues, similar to fibromyalgia) * Neuropathy (a problem with functioning of the nerves.Symptoms include numbness, weakness, burning pain especially at night and loss of reflexes) * Neurologic pain in joints * Tremor [dailystrength.org]

  Side effects similar for Trp/N and TCAD (tremor, dry mouth, nausea, dizziness in some patients); Trp/N+TCAD mild tremor and dry mouth in most patients. 33 Patients Treatment Effect on plasma Trp Effects/adverse events Reference Depressed (F, M) ( n = [doi.org]

• Seizure

  Studies haven’t been able to support the claims that 5-HTP supplements help with seizure disorders or Parkinson’s disease symptoms. [healthline.com]

  Antibiotics and anti-seizure drugs, as well as antivirals used to treat human immunodeficiency virus (HIV) infection, are most often linked to serious DRESS episodes. [verywellhealth.com]

  Since no approval was sought, the agency initiated seizure actions against two manufacturers of L-tryptophan products. The first case was dismissed because L-tryptophan had accidentally been included on a GRAS list published in 1977. [quackwatch.org]

• Agitation

  The symptoms of serotonin syndrome include agitation, delirium, coma, mydriasis, sweating, hyperthermia, tremor, rigidity, and myoclonus ( 36, 37 ). [doi.org]

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.

• Tryptophan Increased

  L-tryptophan increases a chemical in the brain called serotonin. Meperidine (Demerol) can also increase serotonin in the brain. [rxlist.com]

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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3. Silver RM, Heyes MP, Maize JC, Quearry B, Vionnet-Fuasset M, Sternberg EM. Scleroderma, fasciitis, and eosinophilia associated with the ingestion of tryptophan. New England Journal of Medicine. 1990;322(13):874-81.
4. Centers for Disease Control (CDC). Eosinophilia-myalgia syndrome and L-tryptophan-containing products--New Mexico, Minnesota, Oregon, and New York, 1989. Morbidity and Mortality Weekly Report. 1989;38(46):785-8.
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7. Hill RH Jr, Caudill SP, Philen RM, Bailey SL, Flanders WD, Driskell WJ, Kamb ML, Needham LL, Sampson EJ. Contaminants in L-tryptophan associated with eosinophilia myalgia syndrome. Archives of Environmental Contamination and Toxicology. 1993;25(1):134-42.
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9. Smith MJ, Garrett RH. A heretofore undisclosed crux of eosinophilia-myalgia syndrome: compromised histamine degradation. Inflammatory Resolution. 2005;54(11):435-50.
10. Pincus T. Eosinophilia-myalgia syndrome: patient status 2-4 years after onset. Journal of Rheumatology Supplement. 1996; 46:19-24; discussion 24-5.