Hypereosinophilic Syndrome Clinical Presentation

  • Author: Venkata Samavedi, MBBS, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Jan 10, 2012
 

History

Hypereosinophilic syndrome is a heterogeneous disease process; thus, multiple manifestations may occur simultaneously or individually. The presenting symptoms can be sudden and dramatic, which sometimes occur with cardiac, neurologic, or thrombotic complications, but, more often, the onset is insidious.[25] In one case series, 12% of patients with hypereosinophilic syndrome discovered it as an incidental finding.

Virtually any organ system may be involved in hypereosinophilic syndrome, but the heart, central nervous system (CNS), skin, and respiratory tract are commonly involved. Thromboembolic disease is not infrequent. Major symptoms of hypereosinophilic syndrome include the following:

Cardiac symptoms are as follows:

  • The cardiac system is one of the most frequently involved systems, and cardiac complications are a leading cause of mortality.
  • Damage typically occurs in 3 stages: (1) initial acute necrosis early in the disease process that typically has no clinical manifestations but may occasionally be severe enough to cause symptoms; (2) thrombotic phase; and (3) endomyocardial fibrosis. Common symptoms in these phases include chest pain, dyspnea, or orthopnea.

Hematologic symptoms are as follows:

  • Hematologic symptoms are largely nonspecific and may include fatigue, which may be due to the anemia that is occasionally observed with hypereosinophilic syndrome.
  • Left upper quadrant pain may indicate splenomegaly, which occurs in about 40% of patients.
  • Thrombotic episodes occur frequently and often present as neurologic symptoms. The thrombotic events may occur solely due to cardiac disease, or they may be caused by hypercoagulability. The mechanism of hypercoagulability is unknown.

Neurologic symptoms are as follows:

  • Embolic or thrombotic strokes or transient ischemic episodes may occur and are often the initial manifestations of hypereosinophilic syndrome.
  • Some patients with hypereosinophilic syndrome experience an encephalopathy caused by CNS dysfunction.
  • Blurred vision and slurred speech have been reported.
  • Peripheral neuropathies account for about 50% of all neurologic symptoms in hypereosinophilic syndrome. Their etiology is poorly understood, but the symptoms may present as symmetric or asymmetric sensory changes, pure motor deficits, or mixed sensory and motor complaints.

Pulmonary symptoms are as follows:

  • The most benign variant of hypereosinophilic syndrome involves eosinophilic infiltrates in the bases and periphery of the lungs, according to one source.
  • Patients often have recurrent angioedema.
  • A chronic, persistent cough, usually nonproductive, is the most common respiratory symptom reported in hypereosinophilic syndrome.
  • Dyspnea may occur due to CHF or pleural effusions (which are not always secondary to CHF).
  • Less frequently, pulmonary fibrosis occurs after prolonged disease and often accompanies cardiac fibrosis.
  • Bronchospasm and asthmatic symptoms are infrequent.
  • Rhinitis is sometimes a presenting symptom.

Rheumatologic symptoms are as follows:

  • Arthralgias and myalgias are frequent complaints.
  • Raynaud phenomenon occurs but is infrequent.

Dermatologic symptoms are as follows:

  • Skin involvement is common and nonspecific.
  • The most common symptom is pruritus.
  • Dermatographism and angioedema are also frequently present.

Gastrointestinal symptoms are as follows:

  • Diarrhea is a relatively common complaint, occurring in approximately 20% of patients with hypereosinophilic syndrome.
  • Nausea and abdominal pain are also common complaints.
  • Occasionally, small bowel necrosis due to microthrombi can occur.
  • Some patients present with sclerosing cholangitis.

Constitutional symptoms are as follows:

  • Many patients experience fever and night sweats.
  • Some sources identify anorexia and weight loss as common presenting symptoms; however, other sources report that these symptoms do not usually occur unless underlying cardiac disease is present.
Next

Physical

The physical findings of hypereosinophilic syndrome are varied and parallel the clinical history.

Cardiac findings are as follows:

  • Evidence of CHF becomes prominent with advanced hypereosinophilic syndrome and is an ominous sign.
  • Various murmurs may be heard, especially mitral or tricuspid regurgitation.
  • Splinter hemorrhages are often observed with cardiac involvement.
  • Physical findings typical of restrictive heart disease can be expected.

Hematologic findings include splenomegaly in approximately 40% of patients.

Neurologic findings are as follows:

  • Physical findings associated with stroke and transient ischemic attacks can be observed.
  • When peripheral neuropathy is present, findings may be purely sensory, entirely motor, or a combination of both.
  • Deficits are often symmetric.
  • Mononeuritis multiplex and muscle atrophy due to radiculopathy are sometimes encountered.
  • Generalized weakness is observed but is less specific.

Pulmonary findings are as follows:

  • Rales may accompany infiltrates and fibrosis.
  • Findings typical of CHF with effusion may also be encountered.
  • Angioedema is often a prominent feature associated with pulmonary involvement.

Rheumatologic findings are as follows:

  • Large joint effusions can occur.
  • Digital necrosis is rare but sometimes observed with associated Raynaud phenomenon.

Dermatologic findings are as follows:

  • The skin is among the most common organ systems involved in hypereosinophilic syndrome; more than half of all patients have cutaneous involvement. In a minority of reports, skin involvement is the only manifestation of hypereosinophilic syndrome.
  • Most skin eruptions fall into 2 patterns. One pattern is angioedematous or urticarial and associated with a benign prognosis. The other pattern is erythematous, pruritic papules, plaques, and nodules, with or without ulceration.
  • A special form of urticaria is dermatographism, which occurs in up to 75% of affected patients.
  • Other less common cutaneous manifestations include erythroderma, erythema annulare centrifugum, erythema gyratum repens, and mucosal ulcerations.
  • Note the images below.Indurated edematous plaques of hypereosinophilic sIndurated edematous plaques of hypereosinophilic syndrome on a patient's legs. Erythroderma in a patient with hypereosinophilic sErythroderma in a patient with hypereosinophilic syndrome.

Gastrointestinal findings are as follows:

  • Hepatomegaly may occur with chronic active hepatitis due to hypereosinophilic syndrome.
  • Hepatomegaly may also occur with Budd-Chiari syndrome, which may infrequently be a thrombotic complication of hypereosinophilic syndrome.
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Contributor Information and Disclosures
Author

Venkata Samavedi, MBBS, MD  Internist in Houston, TX

Disclosure: Nothing to disclose.

Coauthor(s)

Ronald A Sacher, MB, BCh, MD, FRCPC  Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, and Royal College of Physicians and Surgeons of Canada

Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

Vincent E Herrin, MD  Associate Professor of Medicine, Divisions of Hematology and Oncology, University of Mississippi School of Medicine

Vincent E Herrin, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine and American Society of Hematology

Disclosure: Nothing to disclose.

Joe C Files, MD  Director, Division of Hematology, Associate Chairman, Professor, Department of Internal Medicine, University of Mississippi Medical Center

Joe C Files, MD is a member of the following medical societies: American Association for Cancer Education, American Association for the Advancement of Science, American College of Physicians, American Federation for Medical Research, American Heart Association, American Medical Association, American Society of Human Genetics, Mississippi State Medical Association, New York Academy of Sciences, and Southern Medical Association

Disclosure: Nothing to disclose.

Youwen Zhou, MD, PhD, FRCP(C)  Associate Professor, Department of Dermatology and Skin Science, University of British Columbia; Director, Hyperhidrosis Specialty Clinic, Co-Director, Psoriasis and Phototherapy Centre, Consulting Physician, Department of Dermatology, Vancouver General Hospital, Co-Director, Vitiligo and Pigmentation Clinic, Oncologist Consultant, Skin Tumor Program, BC Cancer Agency

Youwen Zhou, MD, PhD, FRCP(C) is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Paul Schick, MD  Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital

Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Hematology, International Society on Thrombosis and Haemostasis, and New York Academy of Sciences

Disclosure: Nothing to disclose.

Specialty Editor Board

Antoni Ribas, MD  Assistant Professor of Medicine, Division of Hematology-Oncology, University of California at Los Angeles Medical Center

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Troy H Guthrie, Jr, MD  Director of Cancer Institute, Baptist Medical Center

Troy H Guthrie, Jr, MD is a member of the following medical societies: American Federation for Medical Research, American Medical Association, American Society of Hematology, Florida Medical Association, Medical Association of Georgia, and Southern Medical Association

Disclosure: Nothing to disclose.

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD  Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

References

  1. Seifert M, Gerth J, Gajda M, et al. [Eosinophilia - a challenging differential diagnosis] [German]. Med Klin (Munich). Aug 15 2008;103(8):591-7. [Medline].

  2. Galli SJ, Goetzl EJ. Eosinophils, basophils, and mast cells. In: Handin RI, Stossel TP, Lux SE, Stossel TP, eds. Blood: Principles and Practice of Hematology. Baltimore, Md: Lippincott Williams & Wilkins; 1995:621-40.

  3. Klion AD, Bochner BS, Gleich GJ, et al, and The Hypereosinophilic Syndromes Working Group. Approaches to the treatment of hypereosinophilic syndromes: a workshop summary report. J Allergy Clin Immunol. Jun 2006;117(6):1292-302. [Medline].

  4. 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].

  5. Simon HU, Rothenberg ME, Bochner BS, Weller PF, Wardlaw AJ, Wechsler ME, et al. Refining the definition of hypereosinophilic syndrome. J Allergy Clin Immunol. Jul 2010;126(1):45-9. [Medline].

  6. Klion AD. Eosinophilic myeloproliferative disorders. Hematology Am Soc Hematol Educ Program. 2011;2011:257-63. [Medline].

  7. Hardy WR, Anderson RE. The hypereosinophilic syndromes. Ann Intern Med. Jun 1968;68(6):1220-9. [Medline].

  8. Wardlaw AJ, Kay AB. Eosinopenia and eosinophilia. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, eds. Williams Hematology. 5th ed. New York, NY: McGraw- Hill; 1995:844-52.

  9. Tefferi A, Patnaik MM, Pardanani A. Eosinophilia: secondary, clonal and idiopathic. Br J Haematol. Jun 2006;133(5):468-92. [Medline].

  10. Rothenberg ME. Eosinophilia. N Engl J Med. May 28 1998;338(22):1592-600. [Medline].

  11. Gleich GJ, Leiferman KM. The hypereosinophilic syndromes: current concepts and treatments. Br J Haematol. May 2009;145(3):271-85. [Medline].

  12. Helbig G, Wieczorkiewicz A, Dziaczkowska-Suszek J, Majewski M, Kyrcz-Krzemien S. T-cell abnormalities are present at high frequencies in patients with hypereosinophilic syndrome. Haematologica. Sep 2009;94(9):1236-41. [Medline].

  13. Cincin AA, Ozben B, Tanrikulu MA, Baskan O, Agirbasli M. Large apical thrombus in a patient with persistent heart failure and hypereosinophilia: Löffler endocarditis. J Gen Intern Med. Oct 2008;23(10):1713-8. [Medline].

  14. Bain B. The idiopathic hypereosinophilic syndrome and eosinophilic leukemias. Haematologica. Feb 2004;89(2):133-7. [Medline]. [Full Text].

  15. Bain BJ. Eosinophilia--idiopathic or not?. N Engl J Med. Oct 7 1999;341(15):1141-3. [Medline].

  16. Oliver JW, Deol I, Morgan DL, Tonk VS. Chronic eosinophilic leukemia and hypereosinophilic syndromes. Proposal for classification, literature review, and report of a case with a unique chromosomal abnormality. Cancer Genet Cytogenet. Dec 1998;107(2):111-7. [Medline].

  17. Weller PF. The idiopathic hypereosinophilic syndrome. Arch Dermatol. May 1996;132(5):583-5. [Medline].

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

  19. Fauci AS, Harley JB, Roberts WC, et al. NIH conference. The idiopathic hypereosinophilic syndrome. Clinical, pathophysiologic, and therapeutic considerations. Ann Intern Med. Jul 1982;97(1):78-92. [Medline].

  20. Yamada Y, Sanchez-Aguilera A, Brandt EB, et al. FIP1L1/PDGFRalpha synergizes with SCF to induce systemic mastocytosis in a murine model of chronic eosinophilic leukemia/hypereosinophilic syndrome. Blood. Sep 15 2008;112(6):2500-7. [Medline].

  21. Simon HU, Plötz SG, Dummer R, Blaser K. Abnormal clones of T cells producing interleukin-5 in idiopathic eosinophilia. N Engl J Med. Oct 7 1999;341(15):1112-20. [Medline]. [Full Text].

  22. Brugnoni D, Airó P, Rossi G, et al. A case of hypereosinophilic syndrome is associated with the expansion of a CD3-CD4+ T-cell population able to secrete large amounts of interleukin-5. Blood. Feb 15 1996;87(4):1416-22. [Medline]. [Full Text].

  23. Bain BJ. Relationship between idiopathic hypereosinophilic syndrome, eosinophilic leukemia, and systemic mastocytosis. Am J Hematol. Sep 2004;77(1):82-5. [Medline]. [Full Text].

  24. Lefebvre C, Bletry O, Degoulet P, et al. [Prognostic factors of hypereosinophilic syndrome. Study of 40 cases] [French]. Ann Med Interne (Paris). 1989;140(4):253-7. [Medline].

  25. Klion A. Hypereosinophilic syndrome: current approach to diagnosis and treatment. Annu Rev Med. 2009;60:293-306. [Medline].

  26. Adams JC, Dal-Bianco JP, Kumar G, Callahan MJ. Hypereosinophilic syndrome with characteristic left ventricular thrombus demonstrated by contrast echocardiography. Neth Heart J. Apr 2009;17(4):169-70. [Medline].

  27. Parrillo JE, Fauci AS, Wolff SM. Therapy of the hypereosinophilic syndrome. Ann Intern Med. Aug 1978;89(2):167-72. [Medline].

  28. Luciano L, Catalano L, Sarrantonio C, et al. AlphaIFN-induced hematologic and cytogenetic remission in chronic eosinophilic leukemia with t(1;5). Haematologica. Jul 1999;84(7):651-3. [Medline]. [Full Text].

  29. Yamada O, Kitahara K, Imamura K, et al. Clinical and cytogenetic remission induced by interferon-alpha in a patient with chronic eosinophilic leukemia associated with a unique t(3;9;5) translocation. Am J Hematol. Jun 1998;58(2):137-41. [Medline]. [Full Text].

  30. Malbrain ML, Van den Bergh H, Zachée P. Further evidence for the clonal nature of the idiopathic hypereosinophilic syndrome: complete haematological and cytogenetic remission induced by interferon-alpha in a case with a unique chromosomal abnormality. Br J Haematol. Jan 1996;92(1):176-83. [Medline].

  31. Verstovsek S, Tefferi A, Kantarjian H, Manshouri T, Luthra R, Pardanani A, et al. Alemtuzumab therapy for hypereosinophilic syndrome and chronic eosinophilic leukemia. Clin Cancer Res. Jan 1 2009;15(1):368-73. [Medline].

  32. Schwartz LB, Sheikh J, Singh A. Current strategies in the management of hypereosinophilic syndrome, including mepolizumab. Curr Med Res Opin. Aug 2010;26(8):1933-46. [Medline].

  33. Bain BJ. Hypereosinophilia. Curr Opin Hematol. Jan 2000;7(1):21-5. [Medline].

  34. Broustet A, Bernard P, Dachary D, et al. Acute eosinophilic leukemia with a translocation (10p+;11q-). Cancer Genet Cytogenet. Apr 15 1986;21(4):327-33. [Medline].

  35. Felice PV, Sawicki J, Anto J. Endomyocardial disease and eosinophilia. Angiology. Nov 1993;44(11):869-74. [Medline].

  36. Fischkoff SA, Testa JR, Schiffer CA. Acute eosinophilic leukemia with a (10;11) chromosomal translocation. Leukemia. Jun 1988;2(6):394-7. [Medline].

  37. Maubach PA, Bauchinger M, Emmerich B, Rastetter J. Trisomy 7 and 8 in Ph-negative chronic eosinophilic leukemia. Cancer Genet Cytogenet. Jun 1985;17(2):159-64. [Medline].

  38. Salmon-Nguyen F, Busson M, Daniel M, et al. CALM-AF10 fusion gene in leukemias: simple and inversion-associated translocation (10;11). Cancer Genet Cytogenet. Oct 15 2000;122(2):137-40. [Medline].

  39. Schwartz RS. The hypereosinophilic syndrome and the biology of cancer. N Engl J Med. Mar 27 2003;348(13):1199-200. [Medline].

 
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Indurated edematous plaques of hypereosinophilic syndrome on a patient's legs.
Erythroderma in a patient with hypereosinophilic syndrome.
 
 
 
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