Medical Care

The most important component of eosinophilia-myalgia syndrome (EMS) treatment is to discontinue the use of any product containing L-tryptophan.

The mainstay of pharmacologic treatment is glucocorticoid therapy, which benefits many patients but is not effective for all symptoms of EMS.

Other care depends on the manifestations of the disease. In many cases, it is mostly supportive.

Consultations

Because of the high morbidity associated with EMS, referral to mental health experts should be obtained. Psychotherapy may be helpful in dealing with alterations in mood and behavior secondary to the acquired disabilities. Furthermore, psychological evaluation may provide techniques to use in dealing with compromised function for patients who are affected.

Complications

EMS is a multiorgan disease that affects the lungs, the skin, the gastrointestinal tract, the nervous system, and the blood system. Complications affecting these organs can arise from the disease or from adverse effects of therapy.

In one patient, juxta-articular adiposis dolorosa developed secondary to long-term treatment with high doses of corticosteroids. The condition involved multiple, painful, symmetrically distributed, fatty deposits that were localized to the lower extremities. The condition resolved when the corticosteroid dose was reduced.

Prevention

The principal preventative measure is to avoid the use of products containing L-tryptophan.

The use of a multivitamin or a B-complex vitamin may also provide protection against some of the subacute symptoms in EMS.^[44]

Physical rehabilitation in EMS

For most patients, a physician-directed rehabilitation program is recommended.

The rehabilitation program should be tailored for each individual.

Psychological support in EMS

Many patients experience anxiety and/or depression as a result of EMS.

Psychological distress should be treated with the appropriate psychotherapy and/or medication.

Medication

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. 2007 Oct. 20(10):1556-62. [QxMD MEDLINE Link].
Allen JA, Peterson A, Sufit R, Hinchcliff ME, Mahoney JM, Wood TA, et al. Post-epidemic eosinophilia-myalgia syndrome associated with L-tryptophan. Arthritis Rheum. 2011 Nov. 63(11):3633-9. [QxMD MEDLINE Link].
Fernstrom JD. Effects and side effects associated with the non-nutritional use of tryptophan by humans. J Nutr. 2012 Dec. 142(12):2236S-2244S. [QxMD MEDLINE Link].
Lacroix C, Mallaret M, Jonville-Bera AP. Pharmacovigilance and drug-induced rare diseases: Strengths of the French Network of Regional Pharmacovigilance Centres. Therapie. 2020 Apr. 75 (2):207-213. [QxMD MEDLINE Link].
Piera-Velazquez S, Wermuth PJ, Gomez-Reino JJ, Varga J, Jimenez SA. Chemical exposure-induced systemic fibrosing disorders: Novel insights into systemic sclerosis etiology and pathogenesis. Semin Arthritis Rheum. 2020 Dec. 50 (6):1226-1237. [QxMD MEDLINE Link].
Klarskov K, Gagnon H, Racine M, Boudreault PL, Normandin C, Marsault E, et al. Peak AAA fatty acid homolog contaminants present in the dietary supplement l-Tryptophan associated with the onset of eosinophilia-myalgia syndrome. Toxicol Lett. 2018 May 22. 294:193-204. [QxMD MEDLINE Link].
Smith MJ, Garrett RH. A heretofore undisclosed crux of eosinophilia-myalgia syndrome: compromised histamine degradation. Inflamm Res. 2005 Nov. 54(11):435-50. [QxMD MEDLINE Link].
Smith MJ, Garrett RH. Part II. Eosinophilia-Myalgia Syndrome: further correlations between compromised histamine degradation, eosinophilias and myopathies. Inflamm Res. 2007 Mar 14. [QxMD MEDLINE Link].
Rieber N, Belohradsky BH. AHR activation by tryptophan--pathogenic hallmark of Th17-mediated inflammation in eosinophilic fasciitis, eosinophilia-myalgia-syndrome and toxic oil syndrome?. Immunol Lett. 2010 Feb 16. 128(2):154-5. [QxMD MEDLINE Link].
Zhang H, Yu P, Xiang ML, Li XB, Kong WB, Ma JY, et al. Prediction of drug-induced eosinophilia adverse effect by using SVM and naïve Bayesian approaches. Med Biol Eng Comput. 2015 Jun 5. [QxMD MEDLINE Link].
Clara RO, Assmann N, Ramos Moreno AC, Coimbra JB, Nurenberger N, Dettmer-Wilde K, et al. Melanocytes are more responsive to IFN-γ and produce higher amounts of kynurenine than melanoma cells. Biol Chem. 2016 Jan. 397 (1):85-90. [QxMD MEDLINE Link].
Yorucu C, Lau K, Mittar S, Green NH, Raza A, Rehman IU, et al. Raman spectroscopy detects melanoma and the tissue surrounding melanoma using tissue-engineered melanoma models. Appl Spectrosc Rev. 2016 Apr 20. 51 (4):243-257. [QxMD MEDLINE Link].
Ronen N, Livne E, Gross B. Oxidative damage in rat tissue following excessive L-tryptophan and atherogenic diets. Adv Exp Med Biol. 1999. 467:497-505. [QxMD MEDLINE Link].
Silver RM, McKinley K, Smith EA, Quearry B, Harati Y, Sternberg EM, et al. Tryptophan metabolism via the kynurenine pathway in patients with the eosinophilia-myalgia syndrome. Arthritis Rheum. 1992 Sep. 35(9):1097-105. [QxMD MEDLINE Link].
Stahl JL, Cook EB, Pariza MA, Cook ME, Graziano FM. Effect of L-tryptophan supplementation on eosinophils and eotaxin in guinea pigs. Exp Biol Med (Maywood). 2001 Mar. 226(3):177-84. [QxMD MEDLINE Link].
Arnouts PJ, Colemont LJ, Van Outryve MJ, Van Moer EM. L-tryptophan-induced eosinophilia-myalgia syndrome. J Intern Med. 1991 Jul. 230(1):83-6. [QxMD MEDLINE Link].
Back EE, Henning KJ, Kallenbach LR, Brix KA, Gunn RA, Melius JM. Risk factors for developing eosinophilia myalgia syndrome among L-tryptophan users in New York. J Rheumatol. 1993 Apr. 20(4):666-72. [QxMD MEDLINE Link].
Henning KJ, Jean-Baptiste E, Singh T, Hill RH, Friedman SM. Eosinophilia-myalgia syndrome in patients ingesting a single source of L-tryptophan. J Rheumatol. 1993 Feb. 20(2):273-8. [QxMD MEDLINE Link].
Johnson KL, Klarskov K, Benson LM, Williamson BL, Gleich GJ, Naylor S. Presence of peak X and related compounds: the reported contaminant in case related 5-hydroxy-L-tryptophan associated with eosinophilia-myalgia syndrome. J Rheumatol. 1999 Dec. 26(12):2714-7. [QxMD MEDLINE Link].
Kamb ML, Murphy JJ, Jones JL, Caston JC, Nederlof K, Horney LF, et al. Eosinophilia-myalgia syndrome in L-tryptophan-exposed patients. JAMA. 1992 Jan 1. 267(1):77-82. [QxMD MEDLINE Link].
Klarskov K, Johnson KL, Benson LM, Gleich GJ, Naylor S. Eosinophilia-myalgia syndrome case-associated contaminants in commercially available 5-hydroxytryptophan. Adv Exp Med Biol. 1999. 467:461-8. [QxMD MEDLINE Link].
Naylor S, Johnson KL, Williamson BL, Klarskov K, Gleich GJ. Structural characterization of contaminants in commercial preparations of melatonin by on-line HPLC-electrospray ionization-tandem mass spectrometry. Adv Exp Med Biol. 1999. 467:769-77. [QxMD MEDLINE Link].
Kilbourne EM, Philen RM, Kamb ML, Falk H. Tryptophan produced by Showa Denko and epidemic eosinophilia-myalgia syndrome. J Rheumatol Suppl. 1996 Oct. 46:81-8; discussion 89-91. [QxMD MEDLINE Link].
Swygert LA, Back EE, Auerbach SB, Sewell LE, Falk H. Eosinophilia-myalgia syndrome: mortality data from the US national surveillance system. J Rheumatol. 1993 Oct. 20(10):1711-7. [QxMD MEDLINE Link].
Campagna AC, Blanc PD, Criswell LA, Clarke D, Sack KE, Gold WM, et al. Pulmonary manifestations of the eosinophilia-myalgia syndrome associated with tryptophan ingestion. Chest. 1992 May. 101(5):1274-81. [QxMD MEDLINE Link].
Tazelaar HD, Myers JL, Drage CW, King TE Jr, Aguayo S, Colby TV. Pulmonary disease associated with L-tryptophan-induced eosinophilic myalgia syndrome. Clinical and pathologic features. Chest. 1990 May. 97(5):1032-6. [QxMD MEDLINE Link].
De Schryver-Kecskemeti K, Bennert KW, Cooper GS, Yang P. Gastrointestinal involvement in L-tryptophan (L-Trp) associated eosinophilia-myalgia syndrome (EMS). Dig Dis Sci. 1992 May. 37(5):697-701. [QxMD MEDLINE Link].
Hepburn A, Coady A, Livingstone J, Pandit N. Eosinophilic cholecystitis as a possible late manifestation of the eosinophilia-myalgia syndrome. Clin Rheumatol. 2000. 19(6):470-2. [QxMD MEDLINE Link].
Greenberg AS, Takagi H, Hill RH, Hasan A, Murata H, Falanga V. Delayed onset of skin fibrosis after the ingestion of eosinophilia- myalgia syndrome-associated L-tryptophan. J Am Acad Dermatol. 1996 Aug. 35(2 Pt 1):264-6. [QxMD MEDLINE Link].
Kaufman LD, Seidman RJ, Phillips ME, Gruber BL. Cutaneous manifestations of the L-tryptophan-associated eosinophilia-myalgia syndrome: a spectrum of sclerodermatous skin disease. J Am Acad Dermatol. 1990 Dec. 23(6 Pt 1):1063-9. [QxMD MEDLINE Link].
Ostezan LB, Callen JP. Cutaneous manifestations of selected rheumatologic diseases. Am Fam Physician. 1996 Apr. 53(5):1625-36. [QxMD MEDLINE Link].
Freimer ML, Glass JD, Chaudhry V, Tyor WR, Cornblath DR, Griffin JW, et al. Chronic demyelinating polyneuropathy associated with eosinophilia- myalgia syndrome. J Neurol Neurosurg Psychiatry. 1992 May. 55(5):352-8. [QxMD MEDLINE Link].
Diggle GE. The toxic oil syndrome: 20 years on. Int J Clin Pract. 2001 Jul-Aug. 55(6):371-5. [QxMD MEDLINE Link].
Philen RM, Posada M. Toxic oil syndrome and eosinophilia-myalgia syndrome: May 8-10, 1991, World Health Organization meeting report. Semin Arthritis Rheum. 1993 Oct. 23(2):104-24. [QxMD MEDLINE Link].
Vanhooren HM, Vanoirbeek JA, Xu H, Verbeken E, Nemery B. Strain-dependent acute lung injury after intra-tracheal administration of a 'refined' aniline-denatured rapeseed oil: a murine model of the toxic oil syndrome?. Food Chem Toxicol. 2007 Dec. 45(12):2563-73. [QxMD MEDLINE Link].
Akanay-Diesel S, Richter J, Schneider M, Schulte KW, Reifenberger J, Hanneken S. [Shulman's syndrome (eosinophilic fasciitis)]. Hautarzt. 2009 Apr. 60(4):278-81. [QxMD MEDLINE Link].
Naoui A, Bouslama K, Abdallah M, et al. [Eosinophilic fasciitis (Shulman's disease): a case series of 11 patients]. Rev Med Interne. 2010 Aug. 31(8):535-9. [QxMD MEDLINE Link].
Varga J, Kahari VM. Eosinophilia-myalgia syndrome, eosinophilic fasciitis, and related fibrosing disorders. Curr Opin Rheumatol. 1997 Nov. 9(6):562-70. [QxMD MEDLINE Link].
Mertens JS, Seyger MM, Thurlings RM, Radstake TR, de Jong EM. Morphea and Eosinophilic Fasciitis: An Update. Am J Clin Dermatol. 2017 Mar 16. [QxMD MEDLINE Link].
Pinal-Fernandez I, Selva-O' Callaghan A, Grau JM. Diagnosis and classification of eosinophilic fasciitis. Autoimmun Rev. 2014 Apr-May. 13(4-5):379-82. [QxMD MEDLINE Link].
Firoz BF, Goldberg LH, Landau J, Kaye V, Berman L. Eosinophilic fasciitis secondary to intravenous iron infusions. Dermatol Online J. 2010 May 15. 16(5):5. [QxMD MEDLINE Link].
Mendoza FA, Purohit S, Kenyon L, Jimenez SA. Severe eosinophilic syndrome associated with the use of probiotic supplements: a new entity?. Case Rep Rheumatol. 2012. 2012:934324. [QxMD MEDLINE Link]. [Full Text].
Schirmer JH, Hoyer BF. [Hypereosinophilic syndrome and other rheumatic diseases with hypereosinophilia]. Z Rheumatol. 2019 May. 78 (4):322-332. [QxMD MEDLINE Link].
Hatch DL, Goldman LR. Reduced severity of eosinophilia-myalgia syndrome associated with the consumption of vitamin-containing supplements before illness. Arch Intern Med. 1993 Oct 25. 153(20):2368-73. [QxMD MEDLINE Link].

Media Gallery

Indurated edematous plaques on a patient with hypereosinophilic syndrome.

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Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists, Phi Beta Kappa, Texas Dermatological Society

Disclosure: Nothing to disclose.

Lester F Libow, MD Dermatopathologist, South Texas Dermatopathology Laboratory

Lester F Libow, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, Texas Medical Association

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.

Additional Contributors

Takeji Nishikawa, MD Emeritus Professor, Department of Dermatology, Keio University School of Medicine; Director, Samoncho Dermatology Clinic; Managing Director, The Waksman Foundation of Japan Inc

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, David Arbesfeld, MD, Vinay Arya, MD, and Nicole Quartarolo, MD, to the development and writing of this article.