eMedicine Specialties > Rheumatology > Systemic Rheumatic Disease

Eosinophilia-Myalgia Syndrome

Thomas A Medsger Jr, MD, Gerald P Rodnan Professor of Medicine, Director, Scleroderma Research Program, Department of Medicine, University of Pittsburgh School of Medicine
Mohammed Mubashir Ahmed, MD, Associate Professor, Department of Medicine, Division of Rheumatology, University of Toledo College of Medicine; Eisha Mubashir, MD, Fellow in Rheumatology, Department of Medicine, Fellow, Center of Excellence for Arthritis and Rheumatology, Louisiana State University Health Sciences Center, Shreveport; Shrilekha Sairam, MD, MBBS, Fellow, Department of Internal Medicine, Division of Rheumatology, University of Texas at Galveston; Jeffrey R Lisse, MD, FACP, Professor, Department of Internal Medicine, Chief, Section of Rheumatology, University of Arizona School of Medicine

Updated: Oct 15, 2009

Introduction

Background

In October 1989, the health department in New Mexico was notified of 3 patients with an unexplained acute illness characterized by intense myalgias and peripheral blood eosinophilia. Within weeks, a nationwide outbreak of this disease occurred. The disorder was termed eosinophilia-myalgia syndrome (EMS). In November 1989, for the purpose of nationwide surveillance, the US Centers for Disease Control and Prevention (CDC) defined this syndrome as requiring all of the following criteria: (1) incapacitating myalgias, (2) a blood eosinophil count greater than 1000 cells/µL, and (3) no evidence of infection (eg, trichinosis) or neoplastic conditions that could account for these findings.

Shortly thereafter, two case-control studies initiated by the health departments in New Mexico and Minnesota confirmed a strong association between the use of a specific brand of L-tryptophan and the development of EMS. Analyses of implicated lots of L-tryptophan identified many contaminants. The best-characterized of these is 1,1-ethylidenebis (L-tryptophan) (EBT), a tryptophan dimer. With the recall of L-tryptophan from the market in November 1989, a precipitous fall in the frequency of EMS was observed.

A new approach to constructing a criterion standard for validating diagnostic criteria for a disorder was proposed using EMS as the sample disease.¹ Case reports of patients with and without EMS were reviewed and judged by an external panel of clinical experts, thus providing independent validation of the criterion standard case reports. The proposed criteria included two EMS disease onset patterns (acute and subacute).

Contaminated L-tryptophan may not be the only cause of EMS. According to one estimate, 14% of EMS cases were not related to L-tryptophan. Non–L-tryptophan–related cases were more likely to be associated with peripheral edema, rash, sclerodermalike skin changes, alopecia, neuropathy and lower mean eosinophil count, fewer pulmonary symptoms, and a better prognosis than L-tryptophan cases.

A review of toxic oil syndrome (TOS) cases that affected many thousands of Spanish patients in the early 1980s and were associated with adulterated rapeseed oil reveals that TOS shares many clinical and histopathological features with EMS. Furthermore, recent biochemical data have suggested a link between EMS and TOS. A common toxic metabolite (4-aminophenol) causes the release of dangerous carbonyl species.²

In an unusual experiment, an investigator injected himself subcutaneously with quinolinic acid, an L-tryptophan metabolite, resulting in peripheral blood eosinophilia and dermal and subcutaneous inflammatory lesions resembling those of eosinophilic fasciitis and increased transforming growth factor beta-1 (TGFB1) deposition.³ Because increased serum quinolinic acid concentrations have been recorded in eosinophilic fasciitis, these data support a relationship between EMS and eosinophilic fasciitis. This finding is not surprising considering the similar clinical findings in these two disorders.

Patients with fibromyalgia syndrome (FMS) and related disorders disproportionately ingested over-the-counter L-tryptophan–containing products, but it is unknown if these individuals were predisposed to EMS. In one study, peripheral blood mononuclear cells (PBMC) from 6 of 7 patients with EMS and other functional somatic syndromes, when incubated with peak E, produced type II (profibrotic) cytokines (compared with 3 of 24 controls).⁴

Pathophysiology

The pathogenesis of EMS remains unknown. The 3 major pathological findings observed in persons with EMS include (1) capillary endothelial cell hyperplasia, with evidence of swelling and necrosis; (2) an inflammatory cell infiltration, including monocytes, histiocytes, lymphocytes, macrophages, and plasma cells, and, occasionally, eosinophils in nerve, muscle, and surrounding connective tissue (eg, the subdermal fascial layer [fasciitis]); and (3) increased fibrosis, mostly in the fascia but also occasionally in skin.

Levels of the cytokines interleukin (IL)–2, IL-4, IL-5, interferon gamma, and granulocyte-monocyte colony stimulating factor (GMCSF) are increased in the serum of some patients with EMS. Serum soluble IL-2 receptor (sIL-2R) levels were elevated in 7 patients with EMS compared with controls. Injection of EBT in rodents caused inflammation in the dermis, fascia, and perimysium. In addition, EBT stimulates fibroblast proliferation and collagen synthesis in vitro, but eosinophilia does not develop in EBT-treated animals. The precise role of this contaminant in the pathogenesis of EMS remains uncertain.

It may be unnecessary to implicate L-tryptophan impurities in the development of EMS. Excessive oral ingestion of tryptophan supplement inhibits histamine degradation by increasing formation of formate and indolyl metabolites, several of which block the degradation of histamine, thereby potentiating its effects. Increased histamine activity is known to induce peripheral blood eosinophilia and myalgia.⁵ Furthermore, patients with hypothalamic-pituitary-adrenal axis dysregulation who do not have EMS also manifest greatly increased sensitivity to ingested tryptophan and histamine. Histamine disequilibrium appears to be a final common pathway for syndromes characterized by eosinophilia with myalgia.

Frequency

United States

By July 1991, 1543 EMS cases in the United States had been reported to the CDC.⁶ However, estimates indicate that 5,000-10,000 people actually had this disease.

International

EMS also occurred in other parts of the world, including the United Kingdom, France, Israel, Japan (12 patients), western Germany (69 patients), and Canada (10 patients). Cohort studies performed during the epidemic estimated that the attack rate of EMS among users of L-tryptophan was 0.5%-9%, depending on the product lot of the L-tryptophan ingested. Since the epidemic of 1989-1991, only a few new cases have been reported.

Mortality/Morbidity

• By July 1991, 31 deaths were attributed to EMS. The mortality rate ranged from 2% in national surveillance data to 6% in some cohorts. Most deaths were the result of neurogenic complications such as ascending polyneuropathy, cardiopulmonary disease, or superimposed infection.
• Of the patients with an acute presentation of EMS, 34% required hospitalization for incapacitating myalgia, muscle cramps, or pulmonary involvement.

Race

• Of the patients reported to have EMS, 97% were white.

Sex

• Eighty-four percent of patients were female.

Age

• EMS occurred most commonly in people aged 35-60 years (age range 17-81 years, mean 49 years).

Clinical

History

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.

Physical

• 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.

Causes

• 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.

Differential Diagnoses

Other Problems to Be Considered

Malignancy
Toxic oil syndrome

Workup

Laboratory Studies

• Because the presenting symptoms and physical findings in eosinophilia-myalgia syndrome (EMS) vary significantly, the workup is mainly directed toward identifying other possible causes of the patient's findings. Laboratory tests are essential in differentiating EMS from other causes of myalgia, weakness, and eosinophilia.
• The presence of peripheral blood eosinophilia is an essential element in the diagnosis of EMS based on the CDC surveillance criteria. This finding may be missed because eosinophilia occurs early in the course of the disease and may later disappear spontaneously.
  • Even though the CDC criteria require an eosinophil count of at least 1000 cells/µL for diagnosis, the counts observed in EMS patients are most frequently higher.
  • Eosinophil counts of 10,000-30,000 cells/µL are not unusual, and the bone marrow shows hyperplasia of eosinophil precursor cells.
• Laboratory findings commonly observed in patients with EMS include the following:
  • Leukocytosis elevations may range from mild to moderate.
  • Abnormal LFT results are common, and mild-to-moderate elevation of transaminase levels is observed in approximately 40% of patients. Frank liver failure has not been described.
  • An elevated creatine kinase level is uncommon, affection only approximately 10% of patients with EMS. Levels that are below normal are more common. Elevated aldolase levels are common and occur in approximately half of patients.
  • Mild-to-moderate elevation of the erythrocyte sedimentation rate (ESR) is observed in one third of patients. ESRs greater than 50 mm/h are infrequent.
  • Antinuclear antibodies with a speckled pattern in low titer are observed in approximately half of patients. The significance of this finding is uncertain.

Imaging Studies

• Chest radiographic results vary from normal to acute infiltrates.
• Pleural effusion and diffuse and bibasilar infiltrates are seen in less than one third of patients.
• MRI of the brain has shown subcortical infarcts, focal lesions in the deep white matter, cortical atrophy, ventricular dilatation, and diffuse and periventricular white matter abnormalities.
• MR spectroscopic findings are consistent with widespread inflammatory cerebrovascular disease.

Other Tests

• Pulmonary function testing reveals a slightly decreased diffusion capacity in up to half of patients with EMS but no evidence of restrictive lung disease.
• Electrophysiologic studies demonstrate myopathic and neuropathic changes of varying degrees. Nerve conduction studies show mixed demyelination and a pattern of axonal degeneration.
• Echocardiography typically shows normal left ventricular function and estimated pulmonary artery (PA) pressure less than 30 mm Hg.

Procedures

Biopsy of skin muscle and/or subcutaneous tissue

Histologic Findings

No consistent findings are observed in biopsy specimens from patients with EMS; therefore, histopathologic findings are helpful but not diagnostic.

Muscle biopsy commonly reveals inflammatory infiltrates, frequently perivascular, in the endomysium and perimysium. The inflammatory cells are predominantly lymphocytes and acid phosphatase–reactive histiocytes, with rare eosinophils. In some instances, a microangiopathy is present.⁷ Generalized type II myofiber atrophy and denervation atrophy are common, but myofiber necrosis and degeneration are uncommon.

Skin/fascia biopsy findings generally reveal a normal epidermis. The dermis may be normal or may have perivascular infiltrates of monocytes, eosinophils, and lymphocytes without fibrinoid necrosis. Fasciitis is indistinguishable from eosinophilic fasciitis. Findings vary from extensive infiltrates with lymphoplasmacytoid cells, eosinophils, and monocytes to diffuse fibrosis of connective tissue extending into dermis and epimysium. These findings differ from those in patients with scleroderma, who have more collagen deposition in the dermis.

Nerve biopsy findings show a combination of demyelination and axonal degeneration, with epineural, perineural, and perivascular cellular infiltrates.

Treatment

Medical Care

• Stopping ingestion of L-tryptophan or any other agent that may be the offending factor is key in the treatment of patients with eosinophilia-myalgia syndrome (EMS).
• Because of the protean manifestations of EMS, patients are treated based on their symptoms. No drug is known to alter the course of the disease. High doses of corticosteroids (eg, prednisone up to 60 mg/d) may be helpful in acutely ill patients, but the response is not nearly as dramatic as in patients with pure eosinophilic fasciitis.
• Assistance with activities of daily living in either the inpatient or outpatient setting may be required because the myalgia and muscle cramps can be incapacitating.
• Based on symptoms, patients may need hospital admission for evaluation and treatment.

Consultations

• Depending on the clinical features, consultation with a neurologist, rheumatologist, pulmonologist, or dermatologist may be needed. Consultation with a surgeon may be necessary for muscle, nerve, and fascial biopsies.

Diet

• Any over-the-counter medication or herbal supplement should be avoided until further information is available.

Activity

• Bed rest may be required for the intense muscle pain and cramps that occur during the acute phase of the illness.
• During the chronic phase of the disease, strenuous physical activity may cause muscle pain and cramps and should be avoided if these symptoms occur.

Medication

No standard of care exists for eosinophilia-myalgia syndrome (EMS). Because the initial outbreak was sudden and widespread, only anecdotal reports and a few retrospective studies are available to aid in treatment decisions. Furthermore, the variable presentation of the syndrome and subjective nature of the symptoms complicates interpretation of these studies.

For early manifestations of EMS, patients are treated according to their symptoms, with muscle relaxants, analgesics, diuretics, and vitamins.

In addition, patients are commonly treated with prednisone because inflammation plays a role. However, in general, authors have concluded that treatment with corticosteroids is not beneficial in reducing the severity or duration of symptoms. Long-term steroid therapy has no role.

Chronic symptoms, such as muscle pain, spasm, weakness, neuropathy, and skin thickening, are noninflammatory and are treated symptomatically. Intermittent use of muscle relaxants and analgesics may be required.

Corticosteroids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

Prednisone (Sterapred)

Results in prompt resolution of eosinophilia. Subjective improvement noted in symptoms of dyspnea, myalgia, and edema in most patients.

Dosing

Adult

Acute illness: 20-30 mg PO qd
Severe symptoms/organ involvement: 40-60 mg PO qd; taper over 2-4 weeks as symptoms resolve

Pediatric

Not established

Interactions

Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Contraindications

No absolute contraindication; documented hypersensitivity; severe bacterial, viral, or fungal infection; active peptic ulcer disease; diabetes mellitus

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Abrupt discontinuation may cause adrenal crisis; hyperglycemia, edema, avascular necrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Follow-up

Further Inpatient Care

• Patients who are acutely ill with eosinophilia-myalgia syndrome (EMS) may need hospitalization. A workup may be necessary to help rule out infections and neoplasms, which can mimic EMS.

Further Outpatient Care

• Because symptoms of EMS tend to be prolonged, sometimes persisting for years, intermittent treatment with muscle relaxants and analgesics may be required.
• Persistent muscle pain and spasm can interfere with activities of daily living.
• Prolonged nursing support may be required.

Inpatient & Outpatient Medications

• Treatment is based on symptoms. Persistent pain requires analgesics, occasionally including opiates. Muscle relaxants may be needed for the treatment of muscle spasms. A prolonged course of prednisone is neither effective nor indicated.

Transfer

• Incapacitating myalgias may require transfer to a skilled nursing facility or rehabilitation unit for assistance with activities of daily living.

Deterrence/Prevention

• Active exercise may result in relapse of myalgias in some patients. These patients should refrain from prolonged strenuous activity.
• While case reports exist of patients with EMS tolerating a rechallenge with L-tryptophan from different manufacturers, the substance should be avoided.

Complications

• Serious and life-threatening complications (eg, ascending polyneuropathy, cardiomyopathy, myocarditis, myocardial infarction, encephalopathy, stroke, thrombocytopenia) have been reported, but they occur only rarely.

Prognosis

• Most patients with EMS continue to have some symptoms 3-4 years after the acute presentation. These are likely due to permanent tissue damage that occurred in the acute phase of the disease. In a patient-completed survey, signs of acute inflammation after the first year of disease were reported.⁸
• In one series, only approximately 10% of patients with EMS reported complete recovery.
  • Persistent muscle pain, fatigue, and muscle spasm were the most common residual complaints.
  • Subjective memory loss and word-finding difficulties were also reported in this series. These symptoms were not responsive to any therapeutic intervention.
• Patients who had severe disease at onset with internal organ involvement, neurologic findings, and skin thickening tended to have a worse prognosis.

Patient Education

• Patients should be advised that over-the-counter medications are not subjected to rigorous testing for short- or long-term side effects. Their use could result in as yet unknown adverse health consequences.

Miscellaneous

Medicolegal Pitfalls

• Failure to advise the patient to stop using the offending medication
• Failure to consider other diagnoses (eg, malignancy, infection)

References

1. Hertzman PA, Clauw DJ, Duffy J, Medsger TA Jr, Feinstein AR. Rigorous new approach to constructing a gold standard for validating new diagnostic criteria, as exemplified by the eosinophilia-myalgia syndrome. Arch Intern Med. Oct 22 2001;161(19):2301-6. [Medline].

2. Martínez-Cabot A, Messeguer A. Generation of quinoneimine intermediates in the bioactivation of 3-(N-phenylamino)alanine (PAA) by human liver microsomes: a potential link between eosinophilia-myalgia syndrome and toxic oil syndrome. Chem Res Toxicol. Oct 2007;20(10):1556-62. [Medline].

3. Noakes R, Spelman L, Williamson R. Is the L-tryptophan metabolite quinolinic acid responsible for eosinophilic fasciitis?. Clin Exp Med. Jun 2006;6(2):60-4. [Medline].

4. Barth H, Klein R, Berg PA. L-tryptophan contaminant 'peak E' induces the release of IL-5 and IL-10 by peripheral blood mononuclear cells from patients with functional somatic syndromes. Clin Exp Immunol. Nov 2001;126(2):187-92. [Medline].

5. Smith MJ, Garrett RH. A heretofore undisclosed crux of eosinophilia-myalgia syndrome: compromised histamine degradation. Inflamm Res. Nov 2005;54(11):435-50. [Medline].

6. Swygert LA, Maes EF, Sewell LE, et al. Eosinophilia-myalgia syndrome. Results of national surveillance. JAMA. Oct 3 1990;264(13):1698-703. [Medline].

7. Silver RM. Pathophysiology of the eosinophilia-myalgia syndrome. J Rheumatol Suppl. Oct 1996;46:26-36. [Medline]. [Full Text].

8. Pincus T. Eosinophilia-myalgia syndrome: patient status 2-4 years after onset. J Rheumatol Suppl. Oct 1996;46:19-24; discussion 24-5. [Medline].

9. Belongia EA, Gleich GJ. The eosinophilia-myalgia syndrome revisited [editorial]. J Rheumatol. Oct 1996;23(10):1682-5. [Medline].

10. Bulpitt KJ, Verity MA, Clements PJ, Paulus HE. Association of L-tryptophan and an illness resembling eosinophilic fasciitis. Clinical and histopathologic findings in four patients with eosinophilia-myalgia syndrome. Arthritis Rheum. Jul 1990;33(7):918-29. [Medline].

11. Clauw DJ, Flockhart DA, Mullins W, et al. Eosinophilia-myalgia syndrome not associated with the ingestion of nutritional supplements. J Rheumatol. Dec 1994;21(12):2385-7. [Medline].

12. Clauw DJ, Pincus T. The eosinophilia-myalgia syndrome: what we know, what we think we know, and what we need to know. J Rheumatol Suppl. Oct 1996;46:2-6. [Medline].

13. Culpepper RC, Williams RG, Mease PJ, et al. Natural history of the eosinophilia-myalgia syndrome. Ann Intern Med. Sep 15 1991;115(6):437-42. [Medline].

14. Freundlich B. Eosinophilia-myalgia syndrome. In: Kelley WA, Harris ED, Ruddy S, Sledge CB, eds. Textbook of Rheumatology. 4^th ed. Philadelphia, Pa: WB Saunders; 1993:1150-7.

15. Haseler LJ, Sibbitt WL Jr, Sibbitt RR, Hart BL. Neurologic, MR imaging, and MR spectroscopic findings in eosinophilia myalgia syndrome. AJNR Am J Neuroradiol. Oct 1998;19(9):1687-94. [Medline].

16. Hertzman PA. Criteria for the definition of the eosinophilia-myalgia syndrome. J Rheumatol Suppl. Oct 1996;46:7-12. [Medline].

17. Hertzman PA, Falk H, Kilbourne EM, et al. The eosinophilia-myalgia syndrome: the Los Alamos Conference. J Rheumatol. Jun 1991;18(6):867-73. [Medline].

18. Kilbourne EM, Swygert LA, Philen RM, et al. Interim guidance on the eosinophilia-myalgia syndrome. Ann Intern Med. Jan 15 1990;112(2):85-7. [Medline].

19. Lockshin MD. Which patients with antiphospholipid antibody should be treated and how?. Rheum Dis Clin North Am. Feb 1993;19(1):235-47. [Medline].

20. Margolin L. Non-L-tryptophan related eosinophilia-myalgia syndrome with hypoproteinemia and hypoalbuminemia. J Rheumatol. Mar 2003;30(3):628-9. [Medline].

21. Martin RW, Duffy J, Engel AG, et al. The clinical spectrum of the eosinophilia-myalgia syndrome associated with L-tryptophan ingestion. Clinical features in 20 patients and aspects of pathophysiology. Ann Intern Med. Jul 15 1990;113(2):124-34. [Medline].

22. Philen RM, Posada M. Toxic oil syndrome and eosinophilia-myalgia syndrome: May 8-10, 1991, World Health Organization meeting report. Semin Arthritis Rheum. Oct 1993;23(2):104-24. [Medline].

Keywords

EMS, eosinophilia-myalgia syndrome, toxic oil syndrome, TOS, L-tryptophan, tryptophan, polyneuropathy, cardiopulmonary disease, superimposed infection

Contributor Information and Disclosures

Author

Thomas A Medsger Jr, MD, Gerald P Rodnan Professor of Medicine, Director, Scleroderma Research Program, Department of Medicine, University of Pittsburgh School of Medicine
Thomas A Medsger Jr, MD is a member of the following medical societies: American College of Epidemiology, American College of Rheumatology, American Federation for Medical Research, and Society for Epidemiologic Research
Disclosure: Nothing to disclose.

Coauthor(s)

Mohammed Mubashir Ahmed, MD, Associate Professor, Department of Medicine, Division of Rheumatology, University of Toledo College of Medicine
Mohammed Mubashir Ahmed, MD is a member of the following medical societies: American College of Physicians, American College of Rheumatology, and American Federation for Medical Research
Disclosure: Nothing to disclose.

Eisha Mubashir, MD, Fellow in Rheumatology, Department of Medicine, Fellow, Center of Excellence for Arthritis and Rheumatology, Louisiana State University Health Sciences Center, Shreveport
Disclosure: Nothing to disclose.

Shrilekha Sairam, MD, MBBS, Fellow, Department of Internal Medicine, Division of Rheumatology, University of Texas at Galveston
Disclosure: Nothing to disclose.

Jeffrey R Lisse, MD, FACP, Professor, Department of Internal Medicine, Chief, Section of Rheumatology, University of Arizona School of Medicine
Jeffrey R Lisse, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American College of Rheumatology, American Geriatrics Society, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Carlos J Lozada, MD, Director of Rheumatology Fellowship Program, Associate Professor, Department of Medicine, Division of Rheumatology and Immunology, Jackson Memorial Medical Center, University of Miami School of Medicine
Carlos J Lozada, MD is a member of the following medical societies: American College of Physicians and American College of Rheumatology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Lawrence H Brent, MD, Associate Professor of Medicine, Thomas Jefferson University; Chair, Program Director, Department of Medicine, Division of Rheumatology, Albert Einstein Medical Center
Lawrence H Brent, MD is a member of the following medical societies: American Association of Immunologists, American College of Physicians, and American College of Rheumatology
Disclosure: Genentech Honoraria Speaking and teaching; Genentech Grant/research funds Other; Amgen Honoraria Speaking and teaching; Wyeth Honoraria Speaking and teaching; Abbott Immunology Honoraria Speaking and teaching

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Herbert S Diamond, MD, Professor of Medicine, Temple University School of Medicine; Chairman Emeritus, Department of Internal Medicine, Western Pennsylvania Hospital
Herbert S Diamond, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American College of Rheumatology, American Medical Association, and Phi Beta Kappa
Disclosure: medifocus Honoraria Review panel membership; health dialogs Honoraria Consulting; West Penn Allegheny Health System None Board membership

© 1994- by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)