eMedicine Specialties > Rheumatology > Systemic Rheumatic Disease

Eosinophilia-Myalgia Syndrome: Differential Diagnoses & Workup

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
Coauthor(s): 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
Contributor Information and Disclosures

Updated: Oct 15, 2009

Differential Diagnoses

Churg-Strauss Syndrome
Scleroderma
Eosinophilic Pneumonia
Trichinosis
Hypereosinophilic Syndrome
Hypothyroidism
Polymyalgia Rheumatica

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.

More on Eosinophilia-Myalgia Syndrome

Overview: Eosinophilia-Myalgia Syndrome
Differential Diagnoses & Workup: Eosinophilia-Myalgia Syndrome
Treatment & Medication: Eosinophilia-Myalgia Syndrome
Follow-up: Eosinophilia-Myalgia Syndrome
References
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References

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  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].

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  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].

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  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. 4th 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].

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  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].

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Further Reading

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Keywords

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

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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

 
 
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