Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Dermatologic Manifestations of Hypereosinophilic Syndrome

  • Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Jan 26, 2016
 

Background

Hypereosinophilic syndrome (HES) encompasses a wide range of clinical manifestations sharing 3 features defined by Chusid et al[1] : (1) a peripheral eosinophil count of greater than 1.5 X 109/L for longer than 6 months; (2) evidence of organ involvement, thus excluding benign eosinophilia; and (3) an absence of other causes of eosinophilia, such as parasite infestation (most common cause of eosinophilia worldwide), allergy (most common cause of eosinophilia in the United States), malignancy, and collagen-vascular disease.

Also see the Pediatrics article Hypereosinophilic Syndrome and the Hematology article Hypereosinophilic Syndrome.

Next

Pathophysiology

Hypereosinophilic syndrome etiology can involve (1) primitive involvement of myeloid cells, essentially due to the occurrence of an interstitial chromosomal deletion on band 4q12 leading to the creation of the FIP1L1-PDGFRA fusion gene (F/P+ variant), or (2) increased interleukin (IL)–5 production by a clonally expanded T-cell population (lymphocytic variant), most frequently characterized by a CD3- CD4+ phenotype.[2, 3]

Multiple cytokines stimulate eosinophil production, including IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-5.[4] In 3 patients with T-cell lymphomas, eosinophilia has been correlated with increased production of these cytokines by the lymphomas. IL-3 and GM-CSF act on other bone marrow–derived lineages, whereas the stimulatory activity of IL-5 appears to be limited to eosinophils and thus suggests it to be the dominant factor in eosinophil proliferation. At present, the source of IL-5 in hypereosinophilic syndrome has not been definitively determined, but evidence points to increased production by CD4+ T-lymphocyte clones.

However, IL-5 mRNA and protein have been found in eosinophils; therefore, the increase in this cytokine cannot be attributed merely to T cells. Also, because some patients with hypereosinophilic syndrome have concomitant neutrophilia, factors other than IL-5 are likely involved. GM-CSF and IL-3 have been shown to be produced by eosinophils, and GM-CSF production was demonstrated in the T-cell clones from patients with hypereosinophilic syndrome.

Eosinophils in hypereosinophilic syndrome infiltrate multiple organs where they inflict tissue damage through the release of granule proteins, including eosinophil peroxidase, major basic protein, eosinophil-derived neurotoxin, and eosinophil cationic protein. They also release proinflammatory cytokines (ie, interleukin 1 alpha, tumor necrosis factor–alpha, interleukin 6, interleukin 8, IL-3, IL-5, GM-CSF, macrophage inflammatory protein), which attract more eosinophils and other inflammatory cells to the area. Cardiac involvement is the most common cause of mortality in hypereosinophilic syndrome. In the heart, the infiltration by eosinophils results in endomyocardial fibrosis, with subsequent development of congestive heart failure (CHF) and death. This infiltration is necessary for tissue damage to occur because patients with peripheral eosinophilia due to other causes (eg, eosinophilic pneumonia) do not develop pathology similar to hypereosinophilic syndrome.

Fip1-like1-platelet-derived growth factor receptor alpha chain (FIP1L1-PDGFRA) mutation has been described in adult patients with hypereosinophilic syndrome.[5] Specifically, a novel oncogenic mutation (FIP1L1-PDGFRA), which results in a constitutively activated platelet-derived growth factor receptor-alpha (PDGFRA), has been invariably associated with a primary eosinophilic disorder and results in clonal lines of pathologic cells.[6]

Pardanani et al[7] examined both the prevalence and the associated clinicopathologic features of the mutation in FIP1L1-PDGFRA in 89 adults presenting with an absolute eosinophil count of higher than 1.5 X 109/L. Pardanani and his team[7] used a fluorescence in situ hybridization–based strategy to identify FIP1L1-PDGFRA in bone marrow cells. None of 8 patients with reactive eosinophilia demonstrated defects in FIP1L1-PDGFRA, whereas the rate of FIP1L1-PDGFRA in the remaining 81 patients with primary eosinophilia was 14% (11 patients). None (0%) of 57 patients with hypereosinophilic syndrome but 10 (56%) of 19 patients with systemic mast cell disease associated with eosinophilia (SMCD-eos) carried the mutated FIP1L1-PDGFRA. Thus, it seems FIP1L1-PDGFRA is not solely responsible for hypereosinophilic syndrome. However, a 40% partial response rate was observed in 10 hypereosinophilic syndrome cases after treatment with imatinib.

McPherson et al[8] reported a 33-year-old man with recurrent papular skin lesions and marked peripheral eosinophilia whose skin histopathology showed a proliferation of CD30+ T cells consistent with lymphomatoid papulosis and in whom molecular analysis of peripheral blood mononuclear cells demonstrated the presence of the FIP1L1/PDGFRA fusion gene.

Previous
Next

Epidemiology

Frequency

United States

The exact incidence of hypereosinophilic syndrome is hard to determine because it is a diagnosis of exclusion. It is a rare condition, although numerous reports exist in the literature. At the National Institutes of Health (NIH) between 1971 and 1982, 50 cases of hypereosinophilic syndrome were diagnosed and followed up.[9] The disease is rare in children.

International

Hypereosinophilic syndrome is rare, and the exact incidence is uncertain.

Race

No racial predilection is recognized for hypereosinophilic syndrome.

Sex

Male predominance (4-9:1 ratio) has been reported in historic series, but this is likely to reflect the quasi-exclusive male distribution of a sporadic hematopoietic stem cell mutation found in a characterized disease variant.[2]

Age

A study from the NIH[9] of 50 patients reported that the mean age of onset was 33 years. In 70% of patients, the onset of disease occurs between 20-50 years. Although rare, this disease hypereosinophilic syndrome does occur in children.[10] A review in 1987[11] from Wales found 18 published reports of hypereosinophilic syndrome in children younger than 16 years. The incidence seems to decrease in elderly persons. Kim et al reported encephalitis in idiopathic hypereosinophilic syndrome in a 14-year-old girl.[12]

Previous
 
 
Contributor Information and Disclosures
Author

Noah S Scheinfeld, JD, MD, FAAD Assistant Clinical Professor, Department of Dermatology, Weil Cornell Medical College; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Assistant Attending Dermatologist, New York Presbyterian Hospital; Assistant Attending Dermatologist, Lenox Hill Hospital, North Shore-LIJ Health System; Private Practice

Noah S Scheinfeld, JD, MD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Abbvie<br/>Received income in an amount equal to or greater than $250 from: Optigenex<br/>Received salary from Optigenex for employment.

Coauthor(s)

Felix Urman, MD Staff Physician, Department of Dermatology, St Luke’s Roosevelt Hospital Center

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD 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: American Medical Association, Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Phi Beta Kappa

Disclosure: Nothing to disclose.

Jeffrey P Callen, MD Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, American College of Rheumatology

Disclosure: Received income in an amount equal to or greater than $250 from: XOMA; Biogen/IDEC; Novartis; Janssen Biotech, Abbvie, CSL pharma<br/>Received honoraria from UpToDate for author/editor; Received honoraria from JAMA Dermatology for associate editor and intermittent author; Received royalty from Elsevier for book author/editor; Received dividends from trust accounts, but I do not control these accounts, and have directed our managers to divest pharmaceutical stocks as is fiscally prudent from Stock holdings in various trust accounts include some pharmaceutical companies and device makers for i inherited these trust accounts; for: Celgene; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble; Amgen.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

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.

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

  2. Roufosse FE, Goldman M, Cogan E. Hypereosinophilic syndromes. Orphanet J Rare Dis. 2007 Sep 11. 2:37. [Medline].

  3. Gonzalez Delgado P, de la Sen Fernandez ML, Soriano Gomis V, Perez Crespo M, Munoz Ruiz C, Hernandez Niveiro E. Cyclical hypereosinophilia with skin manifestations and a clonal T cell population. J Investig Allergol Clin Immunol. 2008. 18(5):401-3. [Medline].

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

  5. Chung KF, Hew M, Score J, et al. Cough and hypereosinophilia due to FIP1L1-PDGFRA fusion gene with tyrosine kinase activity. Eur Respir J. 2006 Jan. 27(1):230-2. [Medline].

  6. Martinaud C, Souraud JB, Cournac JM, Pons S, Ménard G, de Jaureguiberry JP, et al. [Synchronous detection of T-cell clonality and FIP1L1-PDGFRA fusion gene in a hypereosinophilic syndrome.]. Rev Med Interne. 2010 Jul. [Medline].

  7. Pardanani A, Brockman SR, Paternoster SF, et al. FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia. Blood. 2004 Nov 15. 104(10):3038-45. [Medline].

  8. McPherson T, Cowen EW, McBurney E, Klion AD. Platelet-derived growth factor receptor-alpha-associated hypereosinophilic syndrome and lymphomatoid papulosis. Br J Dermatol. 2006 Oct. 155(4):824-6. [Medline].

  9. Fauci AS, Harley JB, Roberts WC, Ferrans VJ, Gralnick HR, Bjornson BH. NIH conference. The idiopathic hypereosinophilic syndrome. Clinical, pathophysiologic, and therapeutic considerations. Ann Intern Med. 1982 Jul. 97(1):78-92. [Medline].

  10. Farruggia P, D'Angelo P, Acquaviva A, et al. Hypereosinophilic syndrome in childhood: clinical and molecular features of two cases. Pediatr Hematol Oncol. 2009 Apr-May. 26(3):129-35. [Medline].

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

  12. Kim HY, Kim YM, Kim SH, Kim HJ. Encephalitis in idiopathic hypereosinophilic syndrome in childhood. Pediatr Radiol. 2010 Jun. [Medline].

  13. Sundaramurthi VL, Prabhavathy D, Somasundaram SV, Wahab AJ. Hypereosinophilic syndrome: cutaneous involvement as the sole manifestation. Indian J Dermatol. 2011 Jan. 56(1):107-9. [Medline]. [Full Text].

  14. Lim KS, Ko J, Lee SS, Shin B, Choi DC, Lee BJ. A case of idiopathic hypereosinophilic syndrome presenting with acute respiratory distress syndrome. Allergy Asthma Immunol Res. 2014 Jan. 6(1):98-101. [Medline]. [Full Text].

  15. Ramzan M, Chopra Y, Grover AK, Yadav SP. Isolated Bilateral Uveitis in Child With Hypereosinophilic Syndrome. J Pediatr Hematol Oncol. 2014 Jan 1. [Medline].

  16. Law AD, Varma S, Varma N, Khadwal A, Prakash G, Suri V, et al. Eosinophilic vasculitis: time for recognition of a new entity?. Indian J Hematol Blood Transfus. 2014 Sep 30. (Suppl 1):325-30. [Medline].

  17. Leiferman KM, Gleich GJ, Peters MS. Dermatologic manifestations of the hypereosinophilic syndromes. Immunol Allergy Clin North Am. 2007 Aug. 27(3):415-41. [Medline].

  18. Ionescu MA, Murata H, Janin A. Oral mucosa lesions in hypereosinophilic syndrome--an update. Oral Dis. 2008 Mar. 2:115-22. [Medline].

  19. Habibagahi Z, Ali Nazarinia M, Aaflaki E, Ali Ostovan M, Hadi Bagheri M. Systemic lupus erythematosus and hyper-eosinophilic syndrome: an unusual association. West Indian Med J. 2009 Jan. 58(1):69-71. [Medline].

  20. Kanamori M, Suzuki H, Sato I, Ohyama K, Tezuka F, Katakura R. A case of idiopathic hypereosinophilic syndrome with leptomeningeal dissemination and intraventricular mass lesion: an autopsy report. Clin Neuropathol. 2009 May-Jun. 28(3):197-202. [Medline].

  21. Plötz SG, Hüttig B, Aigner B, Merkel C, Brockow K, Akdis C, et al. Clinical overview of cutaneous features in hypereosinophilic syndrome. Curr Allergy Asthma Rep. 2012 Apr. 12(2):85-98. [Medline].

  22. Newton JA, Singh AK, Greaves MW, Spry CJ. Aquagenic pruritus associated with the idiopathic hypereosinophilic syndrome. Br J Dermatol. 1990 Jan. 122(1):103-6. [Medline].

  23. Usui S, Dainichi T, Kitoh A, Miyachi Y, Kabashima K. Janeway Lesions and Splinter Hemorrhages in a Patient With Eosinophilic Endomyocarditis. JAMA Dermatol. 2015 Aug. 151 (8):907-8. [Medline].

  24. Bogenrieder T, Griese DP, Schiffner R, et al. Wells' syndrome associated with idiopathic hypereosinophilic syndrome. Br J Dermatol. 1997 Dec. 137(6):978-82. [Medline].

  25. Takekawa M, Imai K, Adachi M, et al. Hypereosinophilic syndrome accompanied with necrosis of finger tips. Intern Med. 1992 Nov. 31(11):1262-6. [Medline].

  26. Hofmann SC, Technau K, Muller AM, Lubbert M, Bruckner-Tuderman L. Bullous pemphigoid associated with hypereosinophilic syndrome: simultaneous response to imatinib. J Am Acad Dermatol. 2007 May. 56(5 Suppl):S68-72. [Medline].

  27. Kempf W, Kazakov DV, Szep Z, Vanecek T. CD30+ clonal T-cell lymphoid proliferation of the skin in a patient with hypereosinophilic syndrome. J Cutan Pathol. 2014 Nov 25. [Medline].

  28. Brockington IF, Olsen EG. Loffler's endocarditis and Davies endomyocardial fibrosis. Am Heart J. 1973. 85:308.

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

  30. Rauch AE, Amyot KM, Dunn HG, Ng B, Wilner G. Hypereosinophilic syndrome and myocardial infarction in a 15-year-old. Pediatr Pathol Lab Med. 1997 May-Jun. 17(3):469-86. [Medline].

  31. Tan SA, Duggal A. Pericardial involvement as a rare manifestation of hypereosinophilic syndrome. South Med J. 2009 Jul. 102(7):751-3. [Medline].

  32. Fernandez AB, Ahmed S, Duncan B, Firshein S, Kluger J. Cardiac tamponade: a rare complication of idiopathic hypereosinophilic syndrome. J Cardiovasc Med (Hagerstown). 2009 Feb. 10(2):188-91. [Medline].

  33. Merika EE, Lefroy D, Milojkovic D, Wakelin SH. Hypereosinophilic syndrome: an indolent rash with a serious cardiac complication. Clin Exp Dermatol. 2015 Jul 26. [Medline].

  34. Moore PM, Harley JB, Fauci AS. Neurologic dysfunction in the idiopathic hypereosinophilic syndrome. Ann Intern Med. 1985 Jan. 102(1):109-14. [Medline].

  35. Grigoryan M, Geisler SD, St Louis EK, Baumbach GL, Davis PH. Cerebral arteriolar thromboembolism in idiopathic hypereosinophilic syndrome. Arch Neurol. 2009 Apr. 66(4):528-31. [Medline].

  36. Chang WL, Lin HJ, Cheng HH. Hypereosinophilic syndrome with recurrent strokes: a case report. Acta Neurol Taiwan. 2008 Sep. 17(3):184-8. [Medline].

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

  38. Numagami Y, Tomita T, Murakami K, Masaki I, Kubo K, Michiharu N. Sinus thrombosis in idiopathic hypereosinophilic syndrome causing fatal cerebral haemorrhage. J Clin Neurosci. 2008 May. 15(5):585-7. [Medline].

  39. Watanabe M, Matsui N, Hamada S, et al. A rare case of idiopathic hypereosinophilic syndrome involving the oral cavity associated with the esophagus and gastrointestinal tract. Intern Med. 2004 Apr. 43(4):336-9. [Medline].

  40. Darki A, Kodali PP, McPheters JP, Virk H, Patel MR, Jacobs W. Hypereosinophilic syndrome with cardiac involvement in a pregnant patient with multiple sclerosis. Tex Heart Inst J. 2011. 38(2):163-5. [Medline]. [Full Text].

  41. Hui CK. A case of dermatopathic lymphadenopathy associated with hypereosinophilic syndrome. Ann Acad Med Singapore. 2012 Jan. 41(1):35-6. [Medline].

  42. Kahn JE, Bletry O, Guillevin L. Hypereosinophilic syndromes. Best Pract Res Clin Rheumatol. 2008 Oct. 22(5):863-82. [Medline].

  43. Zittoun J, Farcet JP, Marquet J, Sultan C, Zittoun R. Cobalamin (vitamin B12) and B12 binding proteins in hypereosinophilic syndromes and secondary eosinophilia. Blood. 1984 Apr. 63(4):779-83. [Medline].

  44. Rothenberg ME. Molecular diagnostics and treatment of patients with the hypereosinophilic syndrome. Clin Adv Hematol Oncol. 2009 Jan. 7(1):43-4. [Medline].

  45. Adams JC, Dal-Bianco JP, Kumar G, Callahan MJ. Hypereosinophilic syndrome with characteristic left ventricular thrombus demonstrated bycontrast echocardiography. Neth Heart J. 2009 Apr. 4:169-70. [Medline]. [Full Text].

  46. Scheinfeld N. A comprehensive review of imatinib mesylate (Gleevec) for dermatological diseases. J Drugs Dermatol. 2006 Feb. 5(2):117-22. [Medline].

  47. Coutre S, Gotlib J. Targeted treatment of hypereosinophilic syndromes and chronic eosinophilic leukemias with imatinib mesylate. Semin Cancer Biol. 2004 Aug. 14(4):307-15. [Medline].

  48. Kobayashi M, Kubota T, Uemura Y, Taguchi H. A case of hypereosinophilic syndrome presenting with chronic cough successfully treated with imatinib. Respirology. 2009 Mar. 14(2):302-4. [Medline].

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

  50. Wagner LA, Speckart S, Cutter B, Gleich GJ. Treatment of FIP1L1/PDGFRA-negative hypereosinophilic syndrome with alemtuzumab, an anti-CD52 antibody. J Allergy Clin Immunol. 2009 Jun. 123(6):1407-8. [Medline].

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

  52. Quintas-Cardama A, Cortes J. Therapeutic options for patients with clonal and idiopathic hypereosinophia. Expert Opin Investig Drugs. 2008 Jul. 17(7):1039-50. [Medline].

  53. Wechsler ME. Combating the eosinophil with anti-interleukin-5 therapy. N Engl J Med. 2008 Mar 20. 358(12):1293-4. [Medline].

  54. Marshall GM, White L. Effective therapy for a severe case of the idiopathic hypereosinophilic syndrome. Am J Pediatr Hematol Oncol. 1989 Summer. 11(2):178-83. [Medline].

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

  56. Razaq W, Beautyman E. Successful Treatment of Refractory Idiopathic Hypereosinophilic Syndrome With Etoposide. Am J Ther. 2009 Jan 8. [Medline].

  57. Walsh GM. Reslizumab, a humanized anti-IL-5 mAb for the treatment of eosinophil-mediated inflammatory conditions. Curr Opin Mol Ther. 2009 Jun. 11(3):329-36. [Medline].

  58. Donald CE, Kahn MJ. Successful treatment of hypereosinophilic syndrome with cyclosporine. Am J Med Sci. 2009 Jan. 337(1):65-6. [Medline].

  59. Taverna JA, Lerner A, Goldberg L, Werth S, Demierre MF. Infliximab as a therapy for idiopathic hypereosinophilic syndrome. Arch Dermatol. 2007 Sep. 143(9):1110-2. [Medline].

  60. Herrero B, Ruiz de la Fuente J, Aleo E, Carceller F, Lassaletta A, Orellana MR, et al. Spontaneous Resolution of Hypereosinophilic Syndrome in an Infant Without Treatment. J Pediatr Hematol Oncol. 2012 Apr 24. [Medline].

  61. Podjasek JC, Butterfield JH. Mortality in hypereosinophilic syndrome: 19 years of experience at Mayo Clinic with a review of the literature. Leuk Res. 2013 Jan 16. [Medline].

  62. Herrero B, de la Fuente JR, Aleo E, et al. Spontaneous resolution of hypereosinophilic syndrome in an infant without treatment. J Pediatr Hematol Oncol. 2012 Aug. 34(6):450-2. [Medline].

 
Previous
Next
 
Urticarial and erythematous rash.
Petechiae on an erythematous base.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.