The Journal of Allergy and Clinical Immunology
Volume 113, Issue 1 , Pages 11-28 , January 2004

Eosinophilic gastrointestinal disorders (EGID)

  • Marc E Rothenberg, MD, PhD

      Affiliations

    • Corresponding Author InformationReprint requests: Marc E. Rothenberg, MD, PhD, Cincinnati Children's Hospital Medical Center, Division of Allergy and Immunology, Department of Pediatrics, 3333 Burnet Ave, MLC 7028, Cincinnati, OH 45229-3039

Received 10 October 2003 ,Revised 15 October 2003 ,Accepted 20 October 2003.

References 

    References
  1. Moon A, Kleinman RE. Allergic gastroenteropathy in children. Ann Allergy Asthma Immunol. 1995;74:5–12
  2. Saavedra-Delgado AM, Metcalfe DD. Interactions between food antigens and the immune system in the pathogenesis of gastrointestinal diseases. Ann Allergy. 1985;55:694–702
  3. Torpier G, Colombel JF, Mathieu-Chandelier C, et al.  Eosinophilic gastroenteritis: ultrastructural evidence for a selective release of eosinophil major basic protein. Clin Exp Immunol. 1988;74:404–408
  4. Keshavarzian A, Saverymuttu SH, Tai PC, Thompson M, Barter S, Spry CJ. Activated eosinophils in familial eosinophilic gastroenteritis. Gastroenterology. 1985;88:1041–1049
  5. Sherman MP, Cox KL. Neonatal eosinophilic colitis. J Pediatr. 1982;100:587–589
  6. Hill SM, Milla PJ. Colitis caused by food allergy in infants. Arch Dis Child. 1990;65:132–133
  7. Odze RD, Wershil BK, Leichtner AM, Antonioli DA. Allergic colitis in infants. J Pediatr. 1995;126:163–170
  8. Furuta GT. Eosinophils in the esophagus: acid is not the only cause. J Pediatr Gastroenterol Nutr. 1998;26:468–471
  9. Fox VL, Nurko S, Furuta GT. Eosinophilic esophagitis: It's not just kid's stuff. Gastrointest Endosc. 2002;56:260–270
  10. Rothenberg ME, Mishra A, Collins MH, Putnam PE. Pathogenesis and clinical features of eosinophilic esophagitis. J Allergy Clin Immunol. 2001;108:891–894
  11. Walsh RE, Gaginella TS. The eosinophil in inflammatory bowel disease. Scand J Gastronenterol. 1991;26:1217–1224
  12. Sarin SK, Malhotra V, Sen Gupta S, Karol A, Gaur SK, Anand BS. Significance of eosinophil and mast cell counts in rectal mucosa in ulcerative colitis. A prospective controlled study. Dig Dis Sci. 1978;32:363–367
  13. Dvorak AM. Ultrastructural evidence for release of major basic protein-containing crystalline cores of eosinophil granules in vivo: cytotoxic potential in Crohn's disease. J Immunol. 1980;125:460–462
  14. Winter HS, Madara JL, Stafford RJ, Grand RJ, Quinlan JE, Goldman H. Intraepithelial eosinophils: a new diagnostic criterion for reflux esophagitis. Gastroenterology. 1982;83:818–823
  15. Liacouras CA, Wenner WJ, Brown K, Ruchelli E. Primary eosinophilic esophagitis in children: successful treatment with oral corticosteroids. J Pediatr Gastroenterol Nutr. 1998;26:380–385
  16. Brown LF, Goldman H, Antonioli DA. Intraepithelial eosinophils in endoscopic biopsies of adults with reflux esophagitis. Am J Surg Pathol. 1984;8:899–905
  17. Rothenberg ME, Mishra A, Brandt EB, Hogan SP. Gastrointestinal eosinophils. Immunol Rev. 2001;179:139–155
  18. Rothenberg ME, Mishra A, Brandt EB, Hogan SP. Gastrointestinal eosinophils in health and disease. Adv Immunol. 2001;78:291–328
  19. Desreumaux P, Nutten S, Colombel JF. Activated eosinophils in inflammatory bowel disease: do they matter?. Am J Gastroenterol. 1999;94:3396–3398
  20. Nishitani H, Okabayashi M, Satomi M, Shimoyama T, Dohi Y. Infiltration of peroxidase-producing eosinophils into the lamina propria of patients with ulcerative colitis. J Gastroenterol. 1998;33:189–195
  21. Guajardo JR, Plotnick LM, Fende JM, Collins MH, Putnam PE, Rothenberg ME. Eosinophil-associated gastrointestinal disorders: a world-wide-web based registry. J Pediatr. 2002;141:576–581
  22. Khan S, Orenstein SR. Eosinophilic gastroenteritis: epidemiology, diagnosis and management. Paediatr Drugs. 2002;4:563–570
  23. Caldwell JH, Tennerbaum JI, Bronstein HA. Serum IgE to eosinophilic gastroenteritis. N Engl J Med. 1975;292:1388–1390
  24. Cello JP. Eosinophilic gastroenteritis: a complex disease entity. Am J Med. 1979;67:1097–1114
  25. Scudamore HH, Phillips SF, Swedlund HA, Gleich GJ. Food allergy manifested by eosinophilia, elevated immunoglobulin E level, and protein-losing enteropathy: The syndrome of allergic gastroenteropathy. J Allergy Clin Immunol. 1982;70:129–136
  26. Furuta GT, Ackerman SJ, Wershil BK. The role of the eosinophil in gastrointestinal diseases. Curr Opin Gastroenterol. 1995;11:541–547
  27. Iacono G, Carroccio A, Cavataiio F, et al.  Gastroesophageal reflux and cows milk allergy in infants: a prospective study. J Allergy Clin Immunol. 1996;97:822–827
  28. Sampson HA. Food Allergy. JAMA. 1997;278:1888–1894
  29. Walsh SV, Antonioli DA, Goldman H, et al.  Allergic esophagitis in children: a clinicopathological entity. Am J Surg Pathol. 1999;23:390–396
  30. Spergel JM, Beausoleil JL, Mascarenhas M, Liacouras CA. The use of skin prick tests and patch tests to identify causative foods in eosinophilic esophagitis. J Allergy Clin Immunol. 2002;109:363–368
  31. Kelly KJ, Lazenby AJ, Rowe PC, Yardley JH, Perman JA, Sampson HA. Eosinophilic esophagitis attributed to gastroesophageal reflux: improvement with an amino acid-based formula. Gastroenterology. 1995;109:1503–1512
  32. Oyaizu N, Uemura Y, Izumi H, Morii S, Nishi M, Hioki K. Eosinophilic gastroenteritis: Immunohistochemical evidence for IgE mast cell-mediated allergy. Acta Pathol Jpn. 1985;35:759–766
  33. Bischoff SC. Mucosa allergy: role of mast cells and eosinophil granulocytes in the gut. Baillieres Clin Gastroenterol. 1996;10:443–459
  34. Sampson HA. Food allergy. Part 1: immunopathogenesis and clinical disorders. J Allergy Clin Immunol. 1999;103:717–728
  35. Bates B. ‘Explosion’ of eosinophilic esophagitis in children. Pediatr News. 2000;34:4
  36. Weller PF. The idiopathic hypereosinophilic syndrome. Blood. 1994;83:2759–2779
  37. Assa'ad AH, Spicer RL, Nelson DP, Zimmermann N, Rothenberg ME. Hypereosinophilic syndromes. Chem Immunol. 2000;76:208–229
  38. Roufosse F, Cogan E, Goldman M. The hypereosinophilic syndrome revisited. Annu Rev Med. 2003;54:169–184
  39. Cools J, DeAngelo DJ, Gotlib J, et al.  A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med. 2003;348:1201–1214
  40. Kulessa H, Frampton J, Graf T. GATA-1 reprograms avian myelomonocytic cell lines into eosinophils, thromboblasts, and eryth-roblasts. Genes Dev. 1995;9:1250–1262
  41. Yu C, Cantor AB, Yang H, et al.  Targeted deletion of a high-affinity GATA-binding site in the GATA-1 promoter leads to selective loss of the eosinophil lineage in vivo. J Exp Med. 2002;195:1387–1395
  42. Hirasawa R, Shimizu R, Takahashi S, et al.  Essential and instructive roles of GATA factors in eosinophil development. J Exp Med. 2002;195:1379–1386
  43. Wardlaw AJ. Molecular basis for selective eosinophil trafficking in asthma: a multistep paradigm. J Allergy Clin Immunol. 1999;104:917–926
  44. Rothenberg ME. Eosinophilia. N Engl J Med. 1998;338:1592–1600
  45. Dent LA, Strath M, Mellor AL, Sanderson CJ. Eosinophilia in transgenic mice expressing interleukin 5. J Exp Med. 1990;172:1425–1431
  46. Foster PS, Hogan SP, Ramsay AJ, Matthaei KI, Young IG. Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J Exp Med. 1996;183:195–201
  47. Lee NA, McGarry MP, Larson KA, Horton MA, Kristensen AB, Lee JJ. Expression of IL-5 in thymocytes/T cells leads to the development of a massive eosinophilia, extramedullary eosinophilopoiesis, and unique histopathologies. J Immunol. 1997;158:1332–1344
  48. Mishra A, Hogan SP, Lee JJ, Foster PS, Rothenberg ME. Fundamental signals regulate eosinophil homing to the gastrointestinal tract. J Clin Invest. 1999;103:1719–1727
  49. Mishra A, Hogan SP, Brandt EB, Rothenberg ME. An etiological role for aeroallergens and eosinophils in experimental esophagitis. J Clin Invest. 2001;107:83–90
  50. Rothenberg ME. Eotaxin. An essential mediator of eosinophil trafficking into mucosa tissues. Am J Respir Cell Mol Biol. 1999;21:291–295
  51. Silberstein DS. Eosinophil function in health and disease. Crit Rev Oncol Hematol. 1995;19:47–77
  52. Bochner BS, Schleimer RP. Mast cells, basophils, and eosinophils: distinct but overlapping pathways for recruitment. Immunol Rev. 2001;179:5–15
  53. Jose PJ, Griffiths-Johnson DA, Collins PD, et al.  Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation. J Exp Med. 1994;179:881–887
  54. Matthews AN, Friend DS, Zimmermann N, et al.  Eotaxin is required for the baseline level of tissue eosinophils. Proc Natl Acad Sci U S A. 1998;95:6273–6278
  55. Hogan SP, Mishra A, Brandt EB, et al.  A pathological function for eotaxin and eosinophils in eosinophilic gastrointestinal inflammation. Nat Immunol. 2001;2:353–360
  56. Resnick MB, Weller PF. Mechanisms of eosinophil recruitment. Am J Respir Cell Mol Biol. 1993;8:349–355
  57. Bochner BS. Road signs guiding leukocytes along the inflammation superhighway. J Allergy Clin Immunol. 2000;106:817–828
  58. Tachimoto H, Ebisawa M, Bochner BS. Cross-talk between integrins and chemokines that influences eosinophil adhesion and migration. Int Arch Allergy Immunol. 2002;128:18–20
  59. Broide D, Sriramarao P. Eosinophil trafficking to sites of allergic inflammation. Immunol Rev. 2001;179:163–172
  60. Shaw SK, Brenner MB. The beta 7 integrins in mucosal homing and retention. Semin Immunol. 1995;7:335–342
  61. Butcher EC, Williams M, Youngman K, Rott L, Briskin M. Lymphocyte trafficking and regional immunity. Adv Immunol. 1999;72:209–253
  62. Gurish MF, Tao H, Abonia JP, et al.  Intestinal mast cell progenitors require CD49dbeta7 (alpha4beta7 integrin) for tissue-specific homing. J Exp Med. 2001;194:1243–1252
  63. Sandborn WJ, Targan SR. Biologic therapy of inflammatory bowel disease. Gastroenterology. 2002;122:1592–1608
  64. von Andrian UH, Engelhardt B. Alpha4 integrins as therapeutic targets in autoimmune disease. N Engl J Med. 2003;348:68–72
  65. Kitayama J, Fuhlbrigge RC, Puri KD, Springer TA. P-selectin, L-selectin, and alpha 4 integrin have distinct roles in eosinophil tethering and arrest on vascular endothelial cells under physiological flow conditions. J Immunol. 1997;159:3929–3939
  66. Artis D, Humphreys NE, Potten CS, et al.  Beta7 integrin-deficient mice: delayed leukocyte recruitment and attenuated protective immunity in the small intestine during enteric helminthic infection. Eur J Immunol. 2000;30:1656–1664
  67. Ghosh S, Goldin E, Gordon FH, et al.  Natalizumab for active Crohn's disease. N Engl J Med. 2003;348:24–32
  68. Mishra A, Hogan SP, Brandt EB, et al.  Enterocyte expression of the eotaxin and interleukin-5 transgenes induces compartmentalized dysregulation of eosinophil trafficking. J Biol Chem. 2002;277:4406–4412
  69. Rothenberg ME. CD44 a sticky target for asthma. J Clin Invest. 2003;111:1460–1462
  70. Floyd H, Ni J, Cornish AL, et al.  Siglec-8. A novel eosinophil-specific member of the immunoglobulin superfamily. J Biol Chem. 2000;275:861–866
  71. Kikly KK, Bochner BS, Freeman SD, et al.  Identification of SAF-2, a novel siglec expressed on eosinophils, mast cells, and basophils. J Allergy Clin Immunol. 2000;105:1093–1100
  72. Rothenberg ME, Luster AD, Lilly CM, Drazen JM, Leder P. Constitutive and allergen-induced expression of eotaxin mRNA in the guinea pig lung. J Exp Med. 1995;181:1211–1216
  73. Rothenberg ME, Luster AD, Leder P. Murine eotaxin: an eosinophil chemoattractant inducible in endothelial cells and in interleukin 4-induced tumor suppression. Proc Natl Acad Sci U S A. 1995;92:8960–8964
  74. Garcia-Zepeda EA, Rothenberg ME, Ownbey RT, Celestin J, Leder P, Luster AD. Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia. Nat Med. 1996;2:449–456
  75. Ponath PD, Qin SX, Ringler DJ, et al.  Cloning of the human eosinophil chemoattractant, eotaxin expression, receptor binding, and functional properties suggest a mechanism for the selective recruitment of eosinophils. J Clin Invest. 1996;97:604–612
  76. Luster AD, Rothenberg ME. Role of monocyte chemoattractant protein and eotaxin subfamily of chemokines in allergic inflammation. J Leukoc Biol. 1997;62:620–633
  77. Patel VP, Kreider BL, Li Y, et al.  Molecular and functional characterization of two novel human C-C chemokines as inhibitors of two distinct classes of myeloid progenitors. J Exp Med. 1997;185:1163–1172
  78. Forssmann U, Uguccioni M, Loetscher P, et al.  Eotaxin-2, a novel CC chemokine that is selective for the chemokine receptor CCR3, and acts like eotaxin on human eosinophil and basophil leukocytes. J Exp Med. 1997;185:2171–2176
  79. Shinkai A, Yoshisue H, Koike M, et al.  A novel human CC chemokine, eotaxin-3, which is expressed in IL-4- stimulated vascular endothelial cells, exhibits potent activity toward eosinophils. J Immunol. 1999;163:1602–1610
  80. Kitaura M, Suzuki N, Imai T, et al.  Molecular cloning of a novel human CC chemokine (Eotaxin-3) that is a functional ligand of CC chemokine receptor 3. J Biol Chem. 1999;274:27975–27980
  81. Zimmermann N, Hogan SP, Mishra A, et al.  Murine eotaxin-2: a constitutive eosinophil chemokine induced by allergen challenge and IL-4 overexpression. J Immunol. 2000;165:5839–5846
  82. Nomiyama H, Osborne LR, Imai T, et al.  Assignment of the human CC chemokine MPIF-2/eotaxin-2 (SCYA24) to chromosome 7q11.23. Genomics. 1998;49:339–340
  83. Combadiere C, Ahuja SK, Murphy PM. Cloning and functional expression of a human eosinophil CC chemokine receptor. J Biol Chem. 1995;270:16491–16494
  84. Ponath PD, Qin S, Post TW, et al.  Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils. J Exp Med. 1996;183:2437–2448
  85. Daugherty BL, Siciliano SJ, DeMartino JA, Malkowitz L, Sirotina A, Springer MS. Cloning, expression, and characterization of the human eosinophil eotaxin receptor. J Exp Med. 1996;183:2349–2354
  86. Bertrand CP, Ponath PD. CCR3 blockade as a new therapy for asthma. Expert Opin Investig Drugs. 2000;9:43–52
  87. Zimmermann N, Hershey GK, Foster PS, Rothenberg ME. Chemokines in asthma: cooperative interaction between chemokines and IL-13. J Allergy Clin Immunol. 2003;111:227–242
  88. Sallusto F, Mackay CR, Lanzavecchia A. Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells. Science. 1997;277:2005–2007
  89. Uguccioni M, Mackay CR, Ochensberger B, et al.  High expression of the chemokine receptor CCR3 in human blood basophils. Role in activation by eotaxin, MCP-4, and other chemokines. J Clin Invest. 1997;100:1137–1143
  90. Gerber BO, Zanni MP, Uguccioni M, et al.  Functional expression of the eotaxin receptor CCR3 in T lymphocytes co-localizing with eosinophils. Curr Biol. 1997;7:836–843
  91. Stellato C, Brummet ME, Plitt JR, Shahabuddin S, Baroody FM, Liu MC, et al.  Expression of the C-C chemokine receptor CCR3 in human airway epithelial cells. J Immunol. 2001;166:1457–1461
  92. Beaulieu S, Robbiani DF, Du X, et al.  Expression of a functional eotaxin (CC chemokine ligand 11) receptor CCR3 by human dendritic cells. J Immunol. 2002;169:2925–2936
  93. Romagnani P, De Paulis A, Beltrame C, et al.  Tryptase-chymase double-positive human mast cells express the eotaxin receptor CCR3 and are attracted by CCR3-binding chemokines. Am J Pathol. 1999;155:1195–1204
  94. Price KS, Friend DS, Mellor EA, De Jesus N, Watts GF, Boyce JA. CC chemokine receptor 3 mobilizes to the surface of human mast cells and potentiates immunoglobulin E-dependent generation of interleukin 13. Am J Respir Cell Mol Biol. 2003;28:420–427
  95. Mattes J, Yang M, Mahalingam S, et al.  Intrinsic defect in T cell production of interleukin (IL)-13 in the absence of both IL-5 and eotaxin precludes the development of eosinophilia and airways hyperreactivity in experimental asthma. J Exp Med. 2002;195:1433–1444
  96. Hogan SP, Mishra A, Brandt EB, Foster PS, Rothenberg ME. A critical role for eotaxin in experimental oral antigen-induced eosinophilic gastrointestinal allergy. Proc Natl Acad Sci U S A. 2000;97:6681–6686
  97. Gurish MF, Humbles A, Tao H, et al.  CCR3 is required for tissue eosinophilia and larval cytotoxicity after infection with Trichinella spiralis. J Immunol. 2002;168:5730–5736
  98. Ma W, Bryce PJ, Humbles AA, et al.  CCR3 is essential for skin eosinophilia and airway hyperresponsiveness in a murine model of allergic skin inflammation. J Clin Invest. 2002;109:621–628
  99. Humbles AA, Lu B, Friend DS, et al.  The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness. Proc Natl Acad Sci U S A. 2002;99:1479–1484
  100. Lamkhioued B, Renzi PM, Abi-Younes S, et al.  Increased expression of eotaxin in bronchoalveolar lavage and airways of asthmatics contributes to the chemotaxis of eosinophils to the site of inflammation. J Immunol. 1997;159:4593–4601
  101. Lilly CM, Nakamura H, Belostotsky OI, et al.  Eotaxin expression after segmental allergen challenge in subjects with atopic asthma. Am J Respir Crit Care Med. 2001;163:1669–1675
  102. Ying S, Meng Q, Zeibecoglou K, et al.  Eosinophil chemotactic chemokines (eotaxin, eotaxin-2, RANTES, monocyte chemoattractant protein-3 (MCP-3), and MCP-4), and C-C chemokine receptor 3 expression in bronchial biopsies from atopic and nonatopic (intrinsic) asthmatics. J Immunol. 1999;163:6321–6329
  103. Ying S, Robinson DS, Meng Q, et al.  C-C chemokines in allergen-induced late-phase cutaneous responses in atopic subjects: association of eotaxin with early 6-hour eosinophils, and of eotaxin-2 and monocyte chemoattractant protein-4 with the later 24-hour tissue eosinophilia, and relationship to basophils and other C-C chemokines (monocyte chemoattractant protein-3 and RANTES). J Immunol. 1999;163:3976–3984
  104. Berkman N, Ohnona S, Chung FK, Breuer R. Eotaxin-3 but not eotaxin gene expression is upregulated in asthmatics 24 hours after allergen challenge. Am J Respir Cell Mol Biol. 2001;24:682–687
  105. Nakamura H, Luster AD, Nakamura T, et al.  Variant eotaxin: its effects on the asthma phenotype. J Allergy Clin Immunol. 2001;108:946–953
  106. Menzies-Gow A, Ying S, Sabroe I, et al.  Eotaxin (CCL11) and eotaxin-2 (CCL24) induce recruitment of eosinophils, basophils, neutrophils, and macrophages as well as features of early- and late-phase allergic reactions following cutaneous injection in human atopic and nonatopic volunteers. J Immunol. 2002;169:2712–2718
  107. Sabroe I, Peck MJ, Van Keulen BJ, et al.  A small molecule antagonist of chemokine receptors CCR1 and CCR3. Potent inhibition of eosinophil function and CCR3-mediated HIV-1 entry. J Biol Chem. 2000;275:25985–25992
  108. Pereira S, Taylor-Clark T, Darby Y, Powell J, Howarth P, Scadding G. Effects of anti-eotaxin monoclonal antibody CAT-213 on allergen-induced rhinitis. J Allergy Clin Immunol. 2003;111(suppl):S268
  109. Salib R, Salagean M, Lau L, et al.  The anti-inflammatory response of anti-eotaxin monoclonal antibody CAT-213 on nasal allergen-induced cell infiltration and activation. J Allergy Clin Immunol. 2003;111(suppl):S347
  110. Kato M, Kephart GM, Talley NJ, et al.  Eosinophil infiltration and degranulation in normal human tissue. Anat Rec. 1998;252:418–425
  111. Butterworth AE. The eosinophil and its role in immunity to helminth infection. Curr Topics Microbiol Immunol. 1977;77:127–168
  112. Butterworth AE. Cell-mediated damage to helminths. Adv Parasitol. 1984;23:143–235
  113. Behm CA, Ovington KS. The role of eosinophils in parasitic helminth infections: insights from genetically modified mice. Parasitol Today. 2000;16:202–209
  114. Lucey DR, Nicholson WA, Weller PF. Mature human eosinophils have the capacity to express HLA-DR. Proc Natl Acad Sci U S A. 1989;86:1348–1351
  115. Tamura N, Ishii N, Nakazawa M, et al.  Requirement of CD80 and CD86 molecules for antigen presentation by eosinophils. Scand J Immunol. 1996;44:229–238
  116. Woerly G, Roger N, Loiseau S, Dombrowicz D, Capron A, Capron M. Expression of CD28 and CD86 by human eosinophils and role in the secretion of type 1 cytokines (Interleukin 2 and interferon gamma). Inhibition by immunoglobulin A complexes. J Exp Med. 1999;190:487–496
  117. Shi HZ, Humbles A, Gerard C, Jin Z, Weller PF. Lymph node trafficking and antigen presentation by endobronchial eosinophils. J Clin Invest. 2000;105:945–953
  118. Pinto A, Aldinucci D, Gloghini A, et al.  The role of eosinophils in the pathobiology of Hodgkin's disease. Ann Oncol. 1997;2:89–96
  119. Pinto A, Aldinucci D, Gloghini A, et al.  Human eosinophils express functional CD30 ligand and stimulate proliferation of a Hodgkin's disease cell line. Blood. 1996;88:3299–3305
  120. Throsby M, Herbelin A, Pleau JM, Dardenne M. CD11c+ eosinophils in the murine thymus: developmental regulation and recruitment upon MHC class I-restricted thymocyte deletion. J Immunol. 2000;165:1965–1975
  121. Gouon-Evans V, Rothenberg ME, Pollard JW. Postnatal mammary gland development requires macrophages and eosinophils. Development. 2000;127:2269–2282
  122. Hornung D, Dohrn K, Sotlar K, et al.  Localization in tissues and secretion of eotaxin by cells from normal endometrium and endometriosis. J Clin Endocrinol Metab. 2000;85:2604–2608
  123. Salamonsen LA, Lathbury LJ. Endometrial leukocytes and menstruation. Hum Reprod Update. 2000;6:16–27
  124. Zhang J, Lathbury LJ, Salamonsen LA. Expression of the chemokine eotaxin and its receptor, CCR3, in human endometrium. Biol Reprod. 2000;62:404–411
  125. Gleich GJ, Frigas E, Loegering DA, Wassom DL, Steinmuller D. Cytotoxic properties of the eosinophil major basic protein. J Immunol. 1979;123:2925–2927
  126. Gleich GJ. Mechanisms of eosinophil-associated inflammation. J Allergy Clin Immunol. 2000;105:651–663
  127. Slifman NR, Loegering DA, McKean DJ, Gleich GJ. Ribonuclease activity associated with human eosinophil-derived neurotoxin and eosinophil cationic protein. J Immunol. 1986;137:2913–2917
  128. Rosenberg HF, Dyer KD, Tiffany HL, Gonzalez M. Rapid evolution of a unique family of primate ribonuclease genes. Nat Genet. 1995;10:219–223
  129. Young JD, Peterson CG, Venge P, Cohn ZA. Mechanism of membrane damage mediated by human eosinophil cationic protein. Nature. 1986;321:613–616
  130. Jacoby DB, Gleich GJ, Fryer AD. Human eosinophil major basic protein is an endogenous allosteric antagonist at the inhibitory muscarinic M2 receptor. J Clin Invest. 1993;91:1314–1318
  131. Kita H. The eosinophil: a cytokine-producing cell?. J Allergy Clin Immunol. 1996;97:889–892
  132. Gharaee-Kermani M, Phan SH. The role of eosinophils in pulmonary fibrosis. Int J Mol Med. 1998;1:43–53
  133. Phipps S, Ying S, Wangoo A, Ong YE, Levi-Schaffer F, Kay AB. The relationship between allergen-induced tissue eosinophilia and markers of repair and remodeling in human atopic skin. J Immunol. 2002;169:4604–4612
  134. Lacy P, Levi-Schaffer F, Mahmudi-Azer S, et al.  Intracellular localization of interleukin-6 in eosinophils from atopic asthmatics and effects of interferon gamma. Blood. 1998;91:2508–2516
  135. Lewis RA, Austen KF, Soberman RJ. Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases. N Engl J Med. 1990;323:645–655
  136. Talley NJ, Shorter RG, Phillips SF, Zinsmeister AR. Eosinophilic gastroenteritis: a clinicopathological study of patients with disease of the mucosa, muscle layer, and subserosal tissues. Gut. 1990;31:54–58
  137. Tajima K, Katagiri T. Deposits of eosinophil granule proteins in eosinophilic cholecystitis and eosinophilic colitis associated with hypereosinophilic syndrome. Dig Dis Sci. 1996;41:282–288
  138. Desreumaux P, Bloget F, Seguy D, et al.  Interleukin 3, granulocyte-macrophage colony-stimulating factor, and interleukin 5 in eosinophilic gastroenteritis. Gastroenterology. 1996;110:768–774
  139. Klein NC, Hargrove RL, Sleisenger MH, Jeffries GH. Eosinophilic gastroenteritis. Medicine (Baltimore). 1970;49:299–319
  140. Walker NI, Croese J, Clouston AD, Parry M, Loukas A, Prociv P. Eosinophilic enteritis in northeastern Australia. Pathology, association with Ancylostoma caninum, and implications. Am J Surg Pathol. 1995;19:328–337
  141. Al Samman M, Haque S, Long JD. Strongyloidiasis colitis: a case report and review of the literature. J Clin Gastroenterol. 1999;28:77–80
  142. Lee JH, Rhee PL, Kim JJ, et al.  The role of mucosa biopsy in the diagnosis of chronic diarrhea: value of multiple biopsies when colonoscopic finding is normal or nonspecific. Korean J Intern Med. 1997;12:182–187
  143. Anderson RE, Hardy WR. Hypereosinophilia. Ann Intern Med. 1968;69:1331–1332
  144. Chusid MJ, Dale DC, West BC, Wolff SM. The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature. Medicine (Baltimore). 1975;54:1–27
  145. Simon HU, Plotz SG, Dummer R, Blaser K. Abnormal clones of T cells producing interleukin-5 in idiopathic eosinophilia. N Engl J Med. 1999;341:1112–1120
  146. Cortes J, Ault P, Koller C, et al.  Efficacy of imatinib mesylate in the treatment of idiopathic hypereosinophilic syndrome. Blood. 2003;101:4714–4716
  147. Schaller JL, Burkland GA. Case report: rapid and complete control of idiopathic hypereosinophilia with imatinib mesylate. MedGenMed [online]. 2001;3:1; (6pp). Available at http://www.Medscape.com.
  148. Ault P, Cortes J, Koller C, Kaled ES, Kantarjian H. Response of idiopathic hypereosinophilic syndrome to treatment with imatinib mesylate. Leukoc Res. 2002;26:881–884
  149. Gleich GJ, Leiferman KM, Pardanani A, Tefferi A, Butterfield JH. Treatment of hypereosinophilic syndrome with imatinib mesilate. Lancet. 2002;359:1577–1578
  150. Griffin JH, Leung J, Bruner RJ, Caligiuri MA, Briesewitz R. Discovery of a fusion kinase in EOL-1 cells and idiopathic hypereosinophilic syndrome. Proc Natl Acad Sci U S A. 2003;100:7830–7835
  151. Klion AD, Noel P, Akin C, et al.  Elevated serum tryptase levels identify a subset of patients with a myeloproliferative variant of idiopathic hypereosinophilic syndrome associated with tissue fibrosis, poor prognosis, and imatinib responsiveness. Blood. 2003;101:4660–4666
  152. Klion AD, Robyn JA, Akin C, et al.  Molecular remission and reversal of myelofibrosis in response to imatinib mesylate treatment in patients with the myeloproliferative variant of hypereosinophilic syndrome. Blood. 2003;
  153. Yoshida T, Naganuma T, Niizawa M, Kakizaki Y, Zeniya A, Masamune O. [A case of eosinophilic gastroenteritis accompanied by perimyo-carditis, which was strongly suspected]. Nippon Shokakibyo Gakkai Zasshi. 1995;92:1183–1188
  154. Hussain A, Brown PJ, Thwaites BC, Hastings AG. Eosinophilic endomyocardial disease due to high grade chest wall sarcoma. Thorax. 1994;49:1040–1041
  155. Andy JJ, Ogunowo PO, Akpan NA, Odigwe CO, Ekanem IA, Esin RA. Helminth associated hypereosinophilia and tropical endomyocardial fibrosis (EMF) in Nigeria. Acta Trop. 1998;69:127–140
  156. Ahmad M, Soetikno RM, Ahmed A. The differential diagnosis of eosinophilic esophagitis. J Clin Gastroenterol. 2000;30:242–244
  157. Mishra A, Rothenberg ME. Intratracheal IL–13 induces eosinophilic esophagitis by an IL-5, eotaxin-1, and STAT6-dependent mechanism1. Gastroenterology. 2003;125:1419–1427
  158. Straumann A, Bauer M, Fischer B, Blaser K, Simon HU. Idiopathic eosinophilic esophagitis is associated with a T(H)2-type allergic inflammatory response. J Allergy Clin Immunol. 2001;108:954–961
  159. Mishra A, Hogan SP, Brandt EB, Rothenberg ME. IL-5 promotes eosinophil trafficking to the esophagus. J Immunol. 2002;168:2464–2469
  160. Orenstein SR, Shalaby TM, Di Lorenzo C, Putnam PE, Sigurdsson L, Kocoshis SA. The spectrum of pediatric eosinophilic esophagitis beyond infancy: a clinical series of 30 children. Am J Gastroenterol. 2000;95:1422–1430
  161. Ruchelli E, Wenner W, Voytek T, Brown K, Liacouras C. Severity of esophageal eosinophilia predicts response to conventional gastro-esophageal reflux therapy. Pediatr Dev Pathol. 1999;2:15–18
  162. Attwood SE, Smyrk TC, Demeester TR, Jones JB. Esophageal eosinophilia with dysphagia. A distinct clinicopathologic syndrome. Dig Dis Sci. 1993;38:109–116
  163. Tottrup A, Fredens K, Funch-Jensen P, Aggestrup S, Dahl R. Eosinophil infiltration in primary esophageal achalasia. A possible pathogenic role. Dig Dis Sci. 1989;34:1894–1899
  164. Fox VL, Nurko S, Teitelbaum JE, Badizadegan K, Furuta GT. High-resolution EUS in children with eosinophilic esophagitis. Gastrointest Endosc. 2003;57:30–36
  165. Fox VL. Pediatric endoscopy. Gastrointest Endosc Clin N Am. 2000;10:175–194
  166. Faubion WA, Perrault J, Burgart LJ, Zein NN, Clawson M, Freese DK. Treatment of eosinophilic esophagitis with inhaled cortico-steroids. J Pediatr Gastroenterol Nutr. 1998;27:90–93
  167. Teitelbaum JE, Fox VL, Twarog FJ, et al.  Eosinophilic esophagitis in children: immunopathological analysis and response to fluticasone propionate. Gastroenterology. 2002;122:1216–1225
  168. Grove A, Allam C, McFarlane LC, McPhate G, Jackson CM, Lipworth BJ. A comparison of the systemic bioactivity of inhaled budesonide and fluticasone propionate in normal subjects. Br J Clin Pharmacol. 1994;38:527–532
  169. Katz AJ, Twarog FJ, Zeiger RS, Falchuk ZM. Milk-sensitive and eosinophilic gastroenteropathy: similar clinical features with contrasting mechanisms and clinical course. J Allergy Clin Immunol. 1984;74:72–78
  170. Bauer S, Schaub N, Dommann-Scherrer CC, Zimmermann DR, Simon HU, Wegmann W. Long-term outcome of idiopathic hypereosinophilic syndrome transition to eosinophilic gastroenteritis and clonal expansion of T-cells. Eur J Gastroenterol Hepatol. 1996;8:181–185
  171. Jaffe JS, James SP, Mullins GE, Braun-Elwert L, Lubensky I, Metcalfe DD. Evidence for an abnormal profile of interleukin-4 (IL-4), IL-5, and gamma-interferon (gamma-IFN) in peripheral blood T cells from patients with allergic eosinophilic gastroenteritis. J Clin Immunol. 1994;14:299–309
  172. Lake AM. Food-induced eosinophilic proctocolitis. J Pediatr Gastroenterol Nutr. 2000;30(suppl):S58–S60
  173. Dvorak AM, Onderdonk AB, McLeod RS, et al.  Ultrastructural identification of exocytosis of granules from human gut eosinophils in vivo. Int Arch Allergy Immunol. 1993;102:33–45
  174. Brandt EB, Strait RT, Hershko D, et al.  Mast cells are required for experimental oral allergen-induced diarrhea. J Clin Invest. 2003;112:1666–1677
  175. Beyer K, Castro R, Birnbaum A, Benkov K, Pittman N, Sampson HA. Human milk-specific mucosal lymphocytes of the gastrointestinal tract display a TH2 cytokine profile. J Allergy Clin Immunol. 2002;109:707–713
  176. Leung VK, Liew CT, Sung JJ. Fatal strongyloidiasis in a patient with ulcerative colitis after corticosteroid therapy. Am J Gastroenterol. 1997;92:1383–1384
  177. Kelly KJ. Eosinophilic gastroenteritis. J Pediatr Gastroenterol Nutr. 2000;30(suppl):S28–S35
  178. Talley NJ, Kephart GM, McGovern TW, Carpenter HA, Gleich GJ. Deposition of eosinophil granule major basic protein in eosinophilic gastroenteritis and celiac disease. Gastroenterology. 1992;103:137–145
  179. Justinich C, Katz A, Gurbindo C, et al.  Elemental diet improves steroid-dependent eosinophilic gastroenteritis and reverses growth failure. J Pediatr Gastroenterol Nutr. 1996;23:81–85
  180. Guajardo JR, Rothenberg ME. Eosinophilic esophagitis, gastroenteritis, gastroenterocolitis, and colitis. In:  Metcalfe DD,  Sampson HA,  Simon RA editor. Food allergy: adverse reactions to foods and additives. 3rd ed.. Malden (MA): Blackwell Publishing; 2003;p. 217–226
  181. Liu LX, Chi J, Upton MP, Ash LR. Eosinophilic colitis associated with larvae of the pinworm Enterobius vermicularis. Lancet. 1995;346:410–412
  182. Khoshoo V, Schantz P, Craver R, Stern GM, Loukas A, Prociv P. Dog hookworm: a cause of eosinophilic enterocolitis in humans. J Pediatr Gastroenterol Nutr. 1994;19:448–452
  183. Machida HM, Catto Smith AG, Gall DG, Trevenen C, Scott RB. Allergic colitis in infancy: clinical and pathologic aspects. J Pediatr Gastroenterol Nutr. 1994;19:22–26
  184. Chang JW, Wu TC, Wang KS, Huang IF, Huang B, Yu IT. Colon mucosa pathology in infants under three months of age with diarrhea disorders. J Pediatr Gastroenterol Nutr. 2002;35:387–390
  185. Van Sickle GJ, Powell GK, McDonald PJ, Goldblum RM. Milk- and soy protein-induced enterocolitis: evidence for lymphocyte sensitization to specific food proteins. Gastroenterology. 1985;88:1915–1921
  186. Kweon MN, Yamamoto M, Kajiki M, Takahashi I, Kiyono H. Systemically derived large intestinal CD4(+) Th2 cells play a central role in STAT6-mediated allergic diarrhea. J Clin Invest. 2000;106:199–206
  187. Garrett JK, Jameson SC, Thompson B, et al.  Anti–IL-5 (mepolizumab) therapy for hypereosinophilic syndromes. J Allergy Clin Immunol. 2004;113:115–119
  188. Pardanani A, Elliott M, Reeder T, et al.  Imatinib for systemic mast-cell disease. Lancet. 2003;362:535–536

 Series editors: William T. Shearer, MD, PhD, Lanny J. Rosenwasser, MD, and Bruce S. Bochner, MDThis activity is available for CME credit. See page 41A for important information.Supported in part by the Burroughs Wellcome Fund, the Human Frontier Science Program RG 264/99, the International Life Science Institute, National Institutes of Health/National Institutes of Allergy and Infectious Disease R01 AI42242 and AI45898, and the kind support of Martin Schlaff.Disclosure of potential conflict of interest: M. E. Rothenberg has a consultant arrangement with Cambridge Antibody Technology and receives grants/ research support from Burroughs Wellcome.

PII: S0091-6749(03)02531-4

doi: 10.1016/j.jaci.2003.10.047

The Journal of Allergy and Clinical Immunology
Volume 113, Issue 1 , Pages 11-28 , January 2004