UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Eosinophil biology and causes of eosinophilia

Authors
Peter F Weller, MD, FACP
Amy D Klion, MD
Section Editors
Donald H Mahoney, Jr, MD
Bruce S Bochner, MD
Deputy Editors
Alan G Rosmarin, MD
Anna M Feldweg, MD

INTRODUCTION

Eosinophils are predominantly tissue-dwelling cells whose functions in health are not entirely understood. Eosinophils in the peripheral blood or tissues can increase in a wide array of disease states, ranging in severity from mild to life-threatening, and as a result of several mechanisms. When activated, eosinophils are capable of releasing mediators and substances that can damage tissues and contribute to disease pathology.

Normal eosinophil biology, the mechanisms of eosinophilia, tissue damage by eosinophils, and the major causes of eosinophilia are discussed in this topic review. An approach to the patient with eosinophilia and the diagnosis and management of the hypereosinophilic syndromes are reviewed separately. (See "Approach to the patient with unexplained eosinophilia" and "Hypereosinophilic syndromes: Clinical manifestations, pathophysiology, and diagnosis" and "Hypereosinophilic syndromes: Treatment".)

EOSINOPHIL BIOLOGY

Eosinophils are white blood cells (WBCs) of the granulocytic lineage, which also includes neutrophils and basophils [1]. The true physiologic function(s) of eosinophils remain largely unknown although they are likely involved in host immune response to infection, tissue remodeling, tumor surveillance, and maintenance of other immune cells [2]. Eosinophils develop and differentiate in the bone marrow under the influence of interleukin (IL)-5, IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF) [3].

Normal levels — In peripheral blood, an absolute eosinophil count (determined by multiplying the total WBC count by the percentage of eosinophils) of 0 to 500/microL (<0.5 x 109/L) is typically considered normal. Defining the normal range by percentage of WBC can be problematic because differences in absolute neutrophil counts between ethnic groups can dramatically impact the percent of eosinophilia [4]. Blood eosinophil counts have been reported to vary within the same person at different times of day and on different days, both in individuals with eosinophilic disorders and in healthy volunteers [5-7]. However, results are inconsistent among studies, and the variability in counts is rarely large enough to impact care.

Eosinophils are primarily tissue-dwelling cells; they are several hundred-fold more abundant in tissues than in blood [8]. In healthy individuals, eosinophils can be found in the digestive tract (although not the esophagus), spleen, lymph nodes, thymus, mammary glands, and uterus [2]. Recruitment of eosinophils to these tissues is mediated mainly by eotaxins, a family of chemokines (ie, cytokines that stimulate cell migration) that bind to the eosinophil chemokine receptor CCR3.

                        

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Tue Nov 03 00:00:00 GMT 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Gleich GJ, Klion AD, Lee JJ, Weller PF. The consequences of not having eosinophils. Allergy 2013; 68:829.
  2. Roufosse F, Weller PF. Practical approach to the patient with hypereosinophilia. J Allergy Clin Immunol 2010; 126:39.
  3. Ackerman SJ, Bochner BS. Mechanisms of eosinophilia in the pathogenesis of hypereosinophilic disorders. Immunol Allergy Clin North Am 2007; 27:357.
  4. Hsieh MM, Everhart JE, Byrd-Holt DD, et al. Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences. Ann Intern Med 2007; 146:486.
  5. Spector SL, Tan RA. Is a single blood eosinophil count a reliable marker for "eosinophilic asthma?". J Asthma 2012; 49:807.
  6. Statland BE, Winkel P, Harris SC, et al. Evaluation of biologic sources of variation of leukocyte counts and other hematologic quantities using very precise automated analyzers. Am J Clin Pathol 1978; 69:48.
  7. Sennels HP, Jørgensen HL, Hansen AL, et al. Diurnal variation of hematology parameters in healthy young males: the Bispebjerg study of diurnal variations. Scand J Clin Lab Invest 2011; 71:532.
  8. Weller PF. The immunobiology of eosinophils. N Engl J Med 1991; 324:1110.
  9. Liu Z, Liu Q, Pesce J, et al. Requirements for the development of IL-4-producing T cells during intestinal nematode infections: what it takes to make a Th2 cell in vivo. Immunol Rev 2004; 201:57.
  10. Moore TA, Nutman TB. Eosinophilia in the returning traveler. Infect Dis Clin North Am 1998; 12:503.
  11. Roediger B, Weninger W. Group 2 innate lymphoid cells in the regulation of immune responses. Adv Immunol 2015; 125:111.
  12. Chen YY, Khoury P, Ware JM, et al. Marked and persistent eosinophilia in the absence of clinical manifestations. J Allergy Clin Immunol 2014; 133:1195.
  13. Helbig G, Hus M, Francuz T, et al. Characteristics and clinical outcome of patients with hypereosinophilia of undetermined significance. Med Oncol 2014; 31:815.
  14. Makiya MA, Herrick JA, Khoury P, et al. Development of a suspension array assay in multiplex for the simultaneous measurement of serum levels of four eosinophil granule proteins. J Immunol Methods 2014; 411:11.
  15. Navarro-Román L, Medeiros LJ, Kingma DW, et al. Malignant lymphomas of B-cell lineage with marked tissue eosinophilia. A report of five cases. Am J Surg Pathol 1994; 18:347.
  16. Wilson ME, Weller PF. Eosinophilia. In: Tropical Infectious Diseases: Principles, Pathogens and Practice, 3rd ed, Guerrant RL, Walker DH, Weller PF (Eds), Saunders Elsevier, Philadelphia 2011. p.939.
  17. Ottesen EA, Weller PF. Eosinophilia following treatment of patients with schistosomiasis mansoni and Bancroft's filariasis. J Infect Dis 1979; 139:343.
  18. Reimert CM, Fitzsimmons CM, Joseph S, et al. Eosinophil activity in Schistosoma mansoni infections in vivo and in vitro in relation to plasma cytokine profile pre- and posttreatment with praziquantel. Clin Vaccine Immunol 2006; 13:584.
  19. Sluzevich JC, Sheth AP, Lucky AW. Persistent eosinophilia as a presenting sign of scabies in patients with disorders of keratinization. Arch Dermatol 2007; 143:670.
  20. Roberts LJ, Huffam SE, Walton SF, Currie BJ. Crusted scabies: clinical and immunological findings in seventy-eight patients and a review of the literature. J Infect 2005; 50:375.
  21. Harley WB, Blaser MJ. Disseminated coccidioidomycosis associated with extreme eosinophilia. Clin Infect Dis 1994; 18:627.
  22. Malo J, Luraschi-Monjagatta C, Wolk DM, et al. Update on the diagnosis of pulmonary coccidioidomycosis. Ann Am Thorac Soc 2014; 11:243.
  23. Simons CM, Stratton CW, Kim AS. Peripheral blood eosinophilia as a clue to the diagnosis of an occult Coccidioides infection. Hum Pathol 2011; 42:449.
  24. Kaplan MH, Hall WW, Susin M, et al. Syndrome of severe skin disease, eosinophilia, and dermatopathic lymphadenopathy in patients with HTLV-II complicating human immunodeficiency virus infection. Am J Med 1991; 91:300.
  25. Plumelle Y, Gonin C, Edouard A, et al. Effect of Strongyloides stercoralis infection and eosinophilia on age at onset and prognosis of adult T-cell leukemia. Am J Clin Pathol 1997; 107:81.
  26. Esposito DH, Stich A, Epelboin L, et al. Acute muscular sarcocystosis: an international investigation among ill travelers returning from Tioman Island, Malaysia, 2011-2012. Clin Infect Dis 2014; 59:1401.
  27. Saric M, Kronzon I. Cholesterol embolization syndrome. Curr Opin Cardiol 2011; 26:472.
  28. Kim YJ, Dale JK, Noel P, et al. Eosinophilia is associated with a higher mortality rate among patients with autoimmune lymphoproliferative syndrome. Am J Hematol 2007; 82:615.
  29. Turul T, Tezcan I, Artac H, et al. Clinical heterogeneity can hamper the diagnosis of patients with ZAP70 deficiency. Eur J Pediatr 2009; 168:87.
  30. Klion A. Hypereosinophilic syndrome: current approach to diagnosis and treatment. Annu Rev Med 2009; 60:293.
  31. Adame J, Cohen PR. Eosinophilic panniculitis: diagnostic considerations and evaluation. J Am Acad Dermatol 1996; 34:229.
  32. Glass LA, Zaghloul AB, Solomon AR. Eosinophilic panniculitis associated with chronic recurrent parotitis. Am J Dermatopathol 1989; 11:555.
  33. Kato N. Eosinophilic panniculitis. J Dermatol 1993; 20:185.
  34. Shan SJ, Guo Y. Exenatide-induced eosinophilic sclerosing lipogranuloma at the injection site. Am J Dermatopathol 2014; 36:510.
  35. Batalla A, Rosón E, Posada C, Flórez A. Eosinophilic panniculitis after subcutaneous administration of sodium heparin. Indian J Dermatol Venereol Leprol 2013; 79:849.
  36. Masferrer E, Martin-Ezquerra G, Martínez-Escala E, et al. Eosinophilic panniculitis triggered by intramuscular penicillin and occupational setting. Allergy 2011; 66:436.
  37. Don DM, Ishiyama A, Johnstone AK, et al. Angiolymphoid hyperplasia with eosinophilia and vascular tumors of the head and neck. Am J Otolaryngol 1996; 17:240.
  38. Helander SD, Peters MS, Kuo TT, Su WP. Kimura's disease and angiolymphoid hyperplasia with eosinophilia: new observations from immunohistochemical studies of lymphocyte markers, endothelial antigens, and granulocyte proteins. J Cutan Pathol 1995; 22:319.
  39. Chen H, Thompson LD, Aguilera NS, Abbondanzo SL. Kimura disease: a clinicopathologic study of 21 cases. Am J Surg Pathol 2004; 28:505.
  40. Ma XR, Xin SJ, Ouyang TX, et al. Successful treatment of Kimura's disease with leflunomide and methylprednisolone: a case report. Int J Clin Exp Med 2014; 7:2219.
  41. Ben-Chetrit E, Amir G, Shalit M. Cetirizine: An effective agent in Kimura's disease. Arthritis Rheum 2005; 53:117.
  42. Chang AR, Kim K, Kim HJ, et al. Outcomes of Kimura's disease after radiotherapy or nonradiotherapeutic treatment modalities. Int J Radiat Oncol Biol Phys 2006; 65:1233.
  43. Singh S, Dayal M, Walia R, et al. Intralesional radiofrequency ablation for nodular angiolymphoid hyperplasia on forehead: a minimally invasive approach. Indian J Dermatol Venereol Leprol 2014; 80:419.
  44. Nouchi A, Hickman G, Battistella M, et al. [Treatment of angiolymphoid hyperplasia with eosinophilia (ALHE) using topical tacrolimus: Two cases]. Ann Dermatol Venereol 2015; 142:360.
  45. Rongioletti F, Cecchi F, Pastorino C, Scaparro M. Successful management of refractory angiolymphoid hyperplasia with eosinophilia with thalidomide. J Eur Acad Dermatol Venereol 2016; 30:527.
  46. Aberer W, Konrad K, Wolff K. Wells' syndrome is a distinctive disease entity and not a histologic diagnosis. J Am Acad Dermatol 1988; 18:105.
  47. Caputo R, Marzano AV, Vezzoli P, Lunardon L. Wells syndrome in adults and children: a report of 19 cases. Arch Dermatol 2006; 142:1157.
  48. Beer TW, Langtry JA, Phillips WG, Wojnarowska F. Flame figures in bullous pemphigoid. Dermatology 1994; 188:310.
  49. Falagas ME, Vergidis PI. Narrative review: diseases that masquerade as infectious cellulitis. Ann Intern Med 2005; 142:47.
  50. Sinno H, Lacroix JP, Lee J, et al. Diagnosis and management of eosinophilic cellulitis (Wells' syndrome): A case series and literature review. Can J Plast Surg 2012; 20:91.
  51. Singanayagam A, Lamb L, Makinde JE, et al. Systemic cytokine storm in severe eosinophilic dermatitis. QJM 2015; 108:907.
  52. Ota M, Shimizu T, Hashino S, Shimizu H. Eosinophilic folliculitis in a patient after allogeneic bone marrow transplantation: case report and review of the literature. Am J Hematol 2004; 76:295.
  53. Hernández-Martín Á, Nuño-González A, Colmenero I, Torrelo A. Eosinophilic pustular folliculitis of infancy: a series of 15 cases and review of the literature. J Am Acad Dermatol 2013; 68:150.
  54. Chen KR, Su WP, Pittelkow MR, Leiferman KM. Eosinophilic vasculitis syndrome: recurrent cutaneous eosinophilic necrotizing vasculitis. Semin Dermatol 1995; 14:106.
  55. Li W, Cao W, Song H, et al. Recurrent cutaneous necrotizing eosinophilic vasculitis: a case report and review of the literature. Diagn Pathol 2013; 8:185.
  56. Launay D, Delaporte E, Gillot JM, et al. An unusual cause of vascular purpura: recurrent cutaneous eosinophilic necrotizing vasculitis. Acta Derm Venereol 2000; 80:394.
  57. el-Mofty SK, Swanson PE, Wick MR, Miller AS. Eosinophilic ulcer of the oral mucosa. Report of 38 new cases with immunohistochemical observations. Oral Surg Oral Med Oral Pathol 1993; 75:716.
  58. Damevska K, Gocev G, Nikolovska S. Eosinophilic ulcer of the oral mucosa: report of a case with multiple synchronous lesions. Am J Dermatopathol 2014; 36:594.
  59. Segura S, Pujol RM. Eosinophilic ulcer of the oral mucosa: a distinct entity or a non-specific reactive pattern? Oral Dis 2008; 14:287.
  60. Segura S, Romero D, Mascaró JM Jr, et al. Eosinophilic ulcer of the oral mucosa: another histological simulator of CD30+ lymphoproliferative disorders. Br J Dermatol 2006; 155:460.
  61. McEvoy MT, Peterson EA, Kobza-Black A, et al. Immunohistological comparison of granulated cell proteins in induced immediate urticarial dermographism and delayed pressure urticaria lesions. Br J Dermatol 1995; 133:853.
  62. Noguchi H, Kephart GM, Campbell RJ, et al. Tissue eosinophilia and eosinophil degranulation in orbital pseudotumor. Ophthalmology 1991; 98:928.
  63. Zenarola P, Melillo L, Bisceglia M, et al. NERDS syndrome: an additional case report. Dermatology 1995; 191:133.
  64. Bousquet J, Chanez P, Lacoste JY, et al. Eosinophilic inflammation in asthma. N Engl J Med 1990; 323:1033.
  65. Winter HS, Madara JL, Stafford RJ, et al. Intraepithelial eosinophils: a new diagnostic criterion for reflux esophagitis. Gastroenterology 1982; 83:818.
  66. Brown LF, Goldman H, Antonioli DA. Intraepithelial eosinophils in endoscopic biopsies of adults with reflux esophagitis. Am J Surg Pathol 1984; 8:899.
  67. Karttunen TJ, Niemelä S, Kerola T. Blood leukocyte differential in Helicobacter pylori infection. Dig Dis Sci 1996; 41:1332.
  68. Bischoff SC, Wedemeyer J, Herrmann A, et al. Quantitative assessment of intestinal eosinophils and mast cells in inflammatory bowel disease. Histopathology 1996; 28:1.
  69. Ettinghausen SE. Collagenous colitis, eosinophilic colitis, and neutropenic colitis. Surg Clin North Am 1993; 73:993.
  70. Yamazaki K, Nakadate I, Suzuki K, et al. Eosinophilia in primary biliary cirrhosis. Am J Gastroenterol 1996; 91:516.
  71. Weller PF, Bubley GJ. The idiopathic hypereosinophilic syndrome. Blood 1994; 83:2759.
  72. Dillon JF, Finlayson ND. Idiopathic hypereosinophilic syndrome presenting as intrahepatic cholestatic jaundice. Am J Gastroenterol 1994; 89:1254.
  73. Grauer L, Padilla VM 3rd, Bouza L, Barkin JS. Eosinophilic sclerosing cholangitis associated with hypereosinophilic syndrome. Am J Gastroenterol 1993; 88:1764.
  74. Rosengart TK, Rotterdam H, Ranson JH. Eosinophilic cholangitis: a self-limited cause of extrahepatic biliary obstruction. Am J Gastroenterol 1990; 85:582.
  75. Dabbs DJ. Eosinophilic and lymphoeosinophilic cholecystitis. Am J Surg Pathol 1993; 17:497.
  76. Kendell KR, Day JD, Hruban RH, et al. Intimate association of eosinophils to collagen bundles in eosinophilic myocarditis and ranitidine-induced hypersensitivity myocarditis. Arch Pathol Lab Med 1995; 119:1154.
  77. Spry CJF. A Comprehensive Review and Guide to the Scientific and Medical Literature, Oxford Medical Publications, Oxford 1988.
  78. Monsuez JJ, de Kerviler E, Barboteu M, et al. Non-Hodgkin's lymphoma related eosinophilic endomyocardial disease. Eur Heart J 1994; 15:1423.
  79. Donhuijsen K, Haedicke C, Hattenberger S, et al. Granulocyte-macrophage colony-stimulating factor-related eosinophilia and Loeffler's endocarditis. Blood 1992; 79:2798.
  80. Date A, Jacob M, Johny KV. Eosinophilic leukocytes in diffuse proliferative and exudative glomerulonephritis. Am J Trop Med Hyg 1977; 26:1028.
  81. Liu S, Miller PD, Holmes SA, et al. Eosinophilic prostatitis and prostatic specific antigen. Br J Urol 1992; 69:61.
  82. Lowe D, Fletcher CD, Gower RL. Tumour-associated eosinophilia in the bladder. J Clin Pathol 1984; 37:500.
  83. Nolan CR 3rd, Anger MS, Kelleher SP. Eosinophiluria--a new method of detection and definition of the clinical spectrum. N Engl J Med 1986; 315:1516.
  84. Eltoum IA, Ghalib HW, Sualaiman S, et al. Significance of eosinophiluria in urinary schistosomiasis. A study using Hansel's stain and electron microscopy. Am J Clin Pathol 1989; 92:329.
  85. Mosholt KS, Dahl C, Azawi NH. Eosinophilic cystitis: three cases, and a review over 10 years. BMJ Case Rep 2014; 2014.
  86. Fuller TW, Dangle P, Reese JN, et al. Inflammatory myofibroblastic tumor of the bladder masquerading as eosinophilic cystitis: case report and review of the literature. Urology 2015; 85:921.
  87. Li G, Cai B, Song H, Yang Z. Clinical and radiological character of eosinophilic cystitis. Int J Clin Exp Med 2015; 8:533.
  88. Itano NM, Malek RS. Eosinophilic cystitis in adults. J Urol 2001; 165:805.
  89. Kiliç S, Erguvan R, Ipek D, et al. Eosinophilic cystitis. A rare inflammatory pathology mimicking bladder neoplasms. Urol Int 2003; 71:285.
  90. Lee CC, Leu ML, Kuo HP, Huang CC. Hypereosinophilia in hemodialysis patients. Changgeng Yi Xue Za Zhi 1995; 18:20.
  91. Chan MK, Chow L, Lam SS, Jones B. Peritoneal eosinophilia in patients on continuous ambulatory peritoneal dialysis: a prospective study. Am J Kidney Dis 1988; 11:180.
  92. Patel UO, Fox SR, Moy JN, Korbet SM. Pruritic rash and eosinophilia in a patient receiving peritoneal dialysis. Semin Dial 2011; 24:338.
  93. Forbes TA, Lunn AJ. Montelukast: a novel therapeutic option in eosinophilic peritonitis. Pediatr Nephrol 2014; 29:1279.