eMedicine Specialties > Pediatrics: General Medicine > Allergy & Immunology

Hypereosinophilic Syndrome: Differential Diagnoses & Workup

Author: Bruce M Rothschild, MD, Professor of Medicine, The Northeastern Ohio Universities College of Medicine; Director, Arthritis Center of Northeast Ohio; Adjunct Professor, Department of Biomedical Engineering, University of Akron
Contributor Information and Disclosures

Updated: Aug 15, 2008

Differential Diagnoses

Agammaglobulinemia
Pancreatitis and Pancreatic Pseudocyst
Asthma
Pericardial Effusion, Malignant
Behcet Syndrome
Pericarditis, Bacterial
Colitis
Pericarditis, Viral
Hodgkin Disease
Polyarteritis Nodosa
Hookworm Infection
Pulmonary Hypertension, Idiopathic
Human Immunodeficiency Virus Infection
Sjogren Syndrome
Loffler Syndrome
Strongyloidiasis
Lymphadenopathy
Superior Mesenteric Artery Syndrome
Myelodysplasia
Trichinosis
Myelofibrosis
Trypanosomiasis
Myocardial Infarction in Childhood
Ulcerative Colitis
Myocarditis, Nonviral
Vasculitis and Thrombophlebitis
Myocarditis, Viral
Veno-occlusive Hepatic Disease
Neurocysticercosis
Visceral Larva Migrans
Non-Hodgkin Lymphoma
Wegener Granulomatosis
Omenn Syndrome

Other Problems to Be Considered

Allergic reaction
Combined immunodeficiency with eosinophilia
Churg-Strauss syndrome
Drug reaction
Eosinophilic fasciitis
Eosinophilic gastroenteritis
Eosinophilic leukemia
Eosinophilic panniculitis
Eosinophilic pneumonia
Eosinophilic urethritis
Eczema
Hereditary eosinophilia
Malignant disease
Parasitic infection
Pulmonary infiltrate with eosinophilia
Radiation-induced eosinophilia
Sweet syndrome

Workup

Laboratory Studies

  • Hypereosinophilic syndrome is characterized by an eosinophil count of 1500/μ L (usually many more).
  • Evaluate for a 4q12 microdeletion (800 kb) that produces recombination fusion, forming the FIP1L1/PDGFRA gene.4,5 The formation of the FIP1L1/PDGFRA fusion gene results in increased tyrosine kinase activity, rendering poor response to steroids but sensitivity to imatinib.6
  • The erythrocyte sedimentation rate (ESR) is usually elevated but can be normal.
  • Leukocyte alkaline phosphatase levels may be high or low.
  • Hypergammaglobulinemia in the form of extremely high immunoglobulin E (IgE) levels is noted in one third of patients.
  • Immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) levels are only rarely elevated.
  • Rheumatoid factor is only rarely present.
  • Coombs test results may be positive.
  • Results of rapid plasma reagent (RPR) tests are rarely positive.
  • Hematuria, proteinuria, and azotemia may be present.
  • Synovial fluid eosinophilia is prominent.
  • Chromosomal analysis rarely reveals abnormalities. When abnormal chromosomes are present, a workup for eosinophilic leukemia is recommended. Eosinophilic leukemia is an unrelated disorder. The presence of chromosome abnormalities or eosinophil blast cells in the circulating blood or marrow may allow the leukemia to be recognized.
  • A laboratory workup is also indicated to rule out disorders that can mimic the hypereosinophilic syndrome (see Differentials).

Imaging Studies

  • Chest radiography may reveal nonspecific focal or diffuse, interstitial, or alveolar infiltrates.
  • CT scanning may reveal pulmonary nodules with a halo of ground-glass attenuation, as well as nonspecific focal or diffuse, interstitial, or alveolar infiltrates.
  • Ultrasonography findings of the affected liver may be normal.
  • Technetium-99m sulfur colloid scanning may reveal nonhomogenous uptake in the presence of liver disease.

Other Tests

  • Electrocardiography may reveal atrial fibrillation, ST-segment depression, T-wave changes, conduction abnormalities, left atrial atrophy, or left ventricular hypertrophy.
  • Electrocardiography reveals involvement in 90% of patients with hypereosinophilic syndrome.

Procedures

  • Bone marrow biopsy may reveal myelofibrosis.
  • The presence of eosinophil blast cells suggests the alternative diagnosis of eosinophilic leukemia, an unrelated disorder.

Histologic Findings

  • Activated eosinophil levels are noted in the blood and involved structures; this finding is associated with fibrosis.

More on Hypereosinophilic Syndrome

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

  1. Martinelli G, Rondoni M, Ottaviani E, Paolini S, Baccarani M. Hypereosinophilic syndrome and molecularly targeted therapy. Semin Hematol. 2007;44(Suppl 2):S4-S16.

  2. James J. Pediatric hypereosinophilic syndrome (HES) differs from adult HES. Pediatrics. 2006;118:S49-S50. [Full Text].

  3. Carey JP, Burke AC. Transient hypereosinophilia in the infant of a mother with hypereosinophilic syndrome. Arch Intern Med. Sep 1982;142(9):1754-5. [Medline].

  4. Roche-Lestienne C, Lepers S, Soenen-Cornu V, et al. Molecular characterization of the idiopathic hypereosinophilic syndrome (HES) in 35 French patients with normal conventional cytogenetics. Leukemia. May 2005;19(5):792-8. [Medline].

  5. Schoch C, Reiter A, Bursch S, et al. Chromosome binding analysis, FISH and RT-PCR performed in parallel in hyperesosinophilic syndrome establishes the diagnosis of chronic eosinophilic leukemia in 22% of cases: A study of 40 patients. Blood. 2004;104:2444.

  6. Miyazawa K, Kakazu N, Ohyashiki K. Clinical features of hypereosinophilic syndrome: FIP1L1-PDGFRA fusion gene-positive disease is a distinct clinical entity with myeloproliferative features and a poor response to corticosteroid. Int J Hematol. Jan 2007;85(1):5-10. [Medline].

  7. [Best Evidence] Rothenberg ME, Klion AD, Roufosse FE, et al. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med. Mar 20 2008;358(12):1215-28. [Medline].

  8. Adame J, Cohen PR. Eosinophilic panniculitis: diagnostic considerations and evaluation. J Am Acad Dermatol. Feb 1996;34(2 Pt 1):229-34. [Medline].

  9. Adams HW, Mainz DL. Eosinophilic ascites. A case report and review of the literature. Am J Dig Dis. Jan 1977;22(1):40-2. [Medline].

  10. Alfaham MA, Ferguson SD, Sihra B, Davies J. The idiopathic hypereosinophilic syndrome. Arch Dis Child. Jun 1987;62(6):601-13. [Medline].

  11. Anders HJ, Schattenkirchner M. Destructive joint lesions and bursitis in idiopathic hypereosinophilic syndrome. Rheumatology (Oxford). Feb 1999;38(2):185-6. [Medline].

  12. Bain BJ. Eosinophilic leukaemias and the idiopathic hypereosinophilic syndrome. Br J Haematol. Oct 1996;95(1):2-9. [Medline].

  13. Chusid MJ, Dale DC, West BC, Wolff SM. The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature. Medicine (Baltimore). Jan 1975;54(1):1-27. [Medline].

  14. Cryer PE, Kissane J. Hypereosinophilic syndrome with pulmonary hypertension. 1976;60:239-247.

  15. Davies J, Spry CJ, Sapsford R, et al. Cardiovascular features of 11 patients with eosinophilic endomyocardial disease. Q J Med. Winter 1983;52(205):23-39. [Medline].

  16. Flaum MA, Schooley RT, Fauci AS, Gralnick HR. A clinicopathologic correlation of the idiopathic hypereosinophilic syndrome. I. Hematologic manifestations. Blood. Nov 1981;58(5):1012-20. [Medline].

  17. Kang EY, Shim JJ, Kim JS, Kim KI. Pulmonary involvement of idiopathic hypereosinophilic syndrome: CT findings in five patients. J Comput Assist Tomogr. Jul-Aug 1997;21(4):612-5. [Medline].

  18. Katz HT, Haque SJ, Hsieh FH. Pediatric hypereosinophilic syndrome (HES) differs from adult HES. J Pediatr. Jan 2005;146(1):134-6. [Medline].

  19. Layzer RB, Shearn MA, Satya-Murti S. Eosinophilic polymyositis. Ann Neurol. Jan 1977;1(1):65-71. [Medline].

  20. Lierman E, Folens C, Stover EH, et al. Sorafenib is a potent inhibitor of FIP1L1-PDGFRalpha and the imatinib-resistant FIP1L1-PDGFRalpha T674I mutant. Blood. Aug 15 2006;108(4):1374-6. [Medline].

  21. Parrillo JE, Borer JS, Henry WL, et al. The cardiovascular manifestations of the hypereosinophilic syndrome. Prospective study of 26 patients, with review of the literature. Am J Med. Oct 1979;67(4):572-82. [Medline].

  22. Postovsky S, Daitzchman M, Dale A, Elhasid R, Ben Arush MW. Unusual presentation of mastoid eosinophilic granuloma in a young patient. Pediatr Hematol Oncol. Jun 2001;18(4):283-9. [Medline].

  23. Spark RP, Gleason DM, DeBenedetti CD, Gigax JH. Is eosinophilic ureteritis an entity? 2 case reports and review. J Urol. Jun 1991;145(6):1256-60. [Medline].

  24. Tefferi A. Blood eosinophilia: a new paradigm in disease classification, diagnosis, and treatment. Mayo Clin Proc. Jan 2005;80(1):75-83. [Medline].

  25. van den Hoogenband HM. Skin lesions as the first manifestation of the hypereosinophilic syndrome. Clin Exp Dermatol. May 1982;7(3):267-71. [Medline].

  26. Wardlaw AJ, Moqbel R, Kay AB. Eosinophils: biology and role in disease. Adv Immunol. 1995;60:151-266. [Medline].

  27. Weller PF, Bubley GJ. The idiopathic hypereosinophilic syndrome. Blood. May 15 1994;83(10):2759-79. [Medline].

  28. White WL, Wahner HW, Brown ML, James EM. Sequential liver imaging in the hypereosinophilic syndrome: discordant images with scintigraphy, ultrasound, and computed tomography. Clin Nucl Med. Feb 1981;6(2):75-7. [Medline].

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Further Reading

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Keywords

disseminated eosinophilic collagen disease, endomyocardial disease, eosinophilia, eosinophilic leukocytosis, myeloproliferative, lymphocytic, idiopathic, hypereosinophilic syndrome, endomyocardial fibrosis, platelet-derived growth factor receptor alpha, PDGFRA, secondary endocarditis, anemia, thrombocytopenia, ascites, hepatic thrombosis, Budd-Chiari syndrome, Raynaud phenomenon, thrombotic phenomenon, mastitis, dementia, endomyocardial fibrosis, myocarditis, arrhythmia, congestive heart failure, valvular incompetence, mitral regurgitation

tricuspid regurgitation, aortic valve disease, vesiculobullous rash, papulonodular rash, livido reticularis, angioedema, cellulitis, erythroderma, erythema annulare, subungual petechiae, digital necrosis, multifocal bursitis, pauciarticular arthritis, small-bowel necrosis, sclerosing cholangitis, chronic active hepatitis, enterocolitis, pancreatitis, hepatosplenomegaly, pleuritis, pulmonary hypertension, encephalopathy, pupillotonia, keratoconjunctivitis sicca, episcleritis, retinal vein thrombosis

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Contributor Information and Disclosures

Author

Bruce M Rothschild, MD, Professor of Medicine, The Northeastern Ohio Universities College of Medicine; Director, Arthritis Center of Northeast Ohio; Adjunct Professor, Department of Biomedical Engineering, University of Akron
Bruce M Rothschild, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Rheumatology, American Federation for Clinical Research, American Heart Association, American Society for Clinical Pharmacology and Therapeutics, International Skeletal Society, New York Academy of Sciences, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

James M Oleske, MD, MPH, François-Xavier Bagnoud Professor of Pediatrics, Director, Division of Pulmonary, Allergy, Immunology and Infectious Diseases, Department of Pediatrics, New Jersey Medical School
James M Oleske, MD, MPH is a member of the following medical societies: Academy of Medicine of New Jersey, American Academy of Pediatrics, American Public Health Association, American Society for Microbiology, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society
Disclosure: "no financial interest" None None

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

David J Valacer, MD, Consulting Staff, Hoffman La Roche Pharmaceuticals
David J Valacer, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American Thoracic Society, and New York Academy of Sciences
Disclosure: Nothing to disclose.

CME Editor

David Pallares, MD, Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville
David Pallares, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology
Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD, Associate Professor, Division of Pulmonary Allergy/Immunology and Infectious Diseases, Department of Pediatrics, UMDNJ-New Jersey Medical School
Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Mucosal Immunology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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