Clinical Reviews in Allergy & Immunology

, Volume 57, Issue 2, pp 194–212 | Cite as

Gastrointestinal Manifestations of Hypereosinophilic Syndromes and Mast Cell Disorders: a Comprehensive Review

  • Vivian C. Nanagas
  • Anna KovalszkiEmail author


Hypereosinophilic syndrome and mastocytosis are relatively rare proliferative diseases encountered in the general population. However, allergists frequently consider these disorders in the differential of patients presenting with gastrointestinal, pulmonary, cutaneous, and allergic symptoms. Gastrointestinal symptoms are some of the most frequent and/or debilitating aspects of both disease states and in many cases lead to poor quality of life and functional limitation for the patient. They are the third most common clinical manifestation in hypereosinophilic syndrome and have been found to be the most distressful aspect of the disorder in those with systemic mastocytosis. Both eosinophils and mast cells play integral parts in normal gut physiology, but when and how exactly their effector functionality translates into clinically significant disease remains unclear, and the available literature regarding their pathophysiology remains sparse. Eosinophils and mast cells even, in fact, may not necessarily function in isolation from each other but can participate in bidirectional crosstalk. Both are affected by similar mediators and can also influence one another in a paracrine fashion. Their interactions include both production of soluble mediators for specific eosinophil and mast cell receptors (for example, eosinophil recruitment and activation by mast cells releasing histamine and eotaxin) as well as direct physical contact. The mechanistic relationship between clonal forms of hypereosinophilia and systemic mastocytosis has also been explored. The nature of gastrointestinal symptomatology in the setting of both hypereosinophilic syndrome and mast cell disease is frequently manifold, heterogeneous, and the lack of better targeted therapy makes diagnosis and management challenging, especially when faced with a substantial differential. Currently, the management of these gastrointestinal symptoms relies on the treatment of the overall disease process. In hypereosinophilia patients, systemic corticosteroids are mainstay, although steroid-sparing agents such as hydroxyurea, IFN-α, methotrexate, cyclosporine, imatinib, and mepolizumab have been utilized with varying success. In mastocytosis patients, anti-mediator therapy with antihistamines and mast cell stabilization with cromolyn sodium can be considered treatments of choice, followed by other therapies yet to be thoroughly studied, including the role of the low-histamine diet, corticosteroids, and treatment of associated IBS symptoms. Given that both eosinophils and mast cells may have joint pathophysiologic roles, they have the potential to be a combined target for therapeutic intervention in disease states exhibiting eosinophil or mast cell involvement.


Gastrointestinal Hypereosinophilic syndrome Systemic mastocytosis Mast cell Eosinophil Eosinophilic gastrointestinal diseases 



Hypereosinophilic syndromes


Absolute eosinophilic count


Hypereosinophilia of unknown significance


Eosinophilic granulomatosis with polyangiitis


Eosinophilic gastrointestinal diseases


Hypereosinophilic syndrome (myeloid variant)


Hypereosinophilic syndrome (lymphocytic variant)


Granulocyte-macrophage colony-stimulating factor




Innate lymphoid cells


Tumor necrosis factor


Chemokine ligand


Chemokine receptor


High-affinity immunoglobulin E (IgE) receptor




Vascular endothelial growth factor


Myeloproliferative syndrome


Drug reaction with eosinophilia and systemic symptoms


Autoimmune lymphoproliferative syndrome


Systemic lupus erythematosus


Inflammatory bowel disease


High-power field


Food and Drug Administration


Eosinophilic esophagitis


Irritable bowel syndrome


Stem cell factor


Mucosal vascular addressin cell adhesion molecule 1


Vascular cell adhesion molecule 1


Forkhead box O3


Tumor necrosis factor-related apoptosis-inducing ligand


Corticotropin releasing hormone


Platelet activating factor






Aggressive systemic mastocytosis


Disodium cromoglycate


Monoclonal mast cell activation syndrome


Mast cell activation syndrome


Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols




Mast cells


Allergic effector unit


  1. 1.
    Gotlib J (2017) World Health Organization-defined eosinophilic disorders: 2017 update on diagnosis, risk stratification, and management. Am J Hematol 92(11):1243–1259PubMedGoogle Scholar
  2. 2.
    Chen YY, Khoury P, Ware JM et al (2014) Marked and persistent eosinophilia in the absence of clinical manifestations. J Allergy Clin Immunol 133(4):1195–1202PubMedGoogle Scholar
  3. 3.
    Roufosse FE, Goldman M, Cogan E (2007) Hypereosinophilic syndromes. Orphanet J Rare Dis 2:37PubMedPubMedCentralGoogle Scholar
  4. 4.
    Reiter A, Gotlib J (2017) Myeloid neoplasms with eosinophilia. Blood 129(6):704–714PubMedGoogle Scholar
  5. 5.
    Klion A (2009) Hypereosinophilic syndrome: current approach to diagnosis and treatment. Annu Rev Med 60:293–306PubMedGoogle Scholar
  6. 6.
    Roufosse F, Klion AD, Weller PF (2017) Hypereosinophilic syndromes: clinical manifestations, pathophysiology, and diagnosis. In: Bochner BS (ed) UpToDate. UpToDate Inc., Waltham. Accessed 17 December 2017
  7. 7.
    Rothenberg ME (2004) Eosinophilic gastrointestinal disorders (EGID). J Allergy Clin Immunol 113(1):11–28 quiz 29PubMedGoogle Scholar
  8. 8.
    Klion A, Weller P (2014) Eosinophilia and eosinophil-related disorders. In: Adkinson NB Jr, Burks A, Busse W, Holgate S, Lemanske R, O’Hehir R (eds) Middleton's allergy: principles and practice, vol 2, 8th edn. Saunders, Welwyn Garden City. 1205. PrintGoogle Scholar
  9. 9.
    Weller P, Klion A (2017) Eosinophil biology and causes of eosinophilia. In: Mahoney DH and Bochner BS (eds). UpToDate. UpToDate Inc., Waltham. Accessed 17 December 2017
  10. 10.
    Jawairia M, Shahzad G, Mustacchia P (2012) Eosinophilic gastrointestinal diseases: review and update. ISRN Gastroenterol 2012:463689PubMedPubMedCentralGoogle Scholar
  11. 11.
    Mishra A, Hogan SP, Lee JJ, Foster PS, Rothenberg ME (1999) Fundamental signals that regulate eosinophil homing to the gastrointestinal tract. J Clin Invest 103(12):1719–1727PubMedPubMedCentralGoogle Scholar
  12. 12.
    Abbas AL, Lichtman AH, Pillai S (2018) Allergy. In: Cellular and molecular immunology, 9th edn. Elsevier, Philadelphia, p 437Google Scholar
  13. 13.
    Straumann A, Simon HU (2004) The physiological and pathophysiological roles of eosinophils in the gastrointestinal tract. Allergy 59(1):15–25PubMedGoogle Scholar
  14. 14.
    Weller PF, Spencer LA (2017) Functions of tissue-resident eosinophils. Nat Rev Immunol 17(12):746–760PubMedPubMedCentralGoogle Scholar
  15. 15.
    Ackerman SJ, Bochner BS (2007) Mechanisms of eosinophilia in the pathogenesis of hypereosinophilic disorders. Immunol Allergy Clin N Am 27(3):357–375Google Scholar
  16. 16.
    Yan BM, Shaffer EA (2009) Primary eosinophilic disorders of the gastrointestinal tract. Gut 58(5):721–732PubMedGoogle Scholar
  17. 17.
    Bonis P, Furuta G (2017) Clinical manifestations and diagnosis of eosinophilic esophagitis. In: Talley NJ (ed) UpToDate. UpToDate Inc., Waltham. Accessed 17 December 2017
  18. 18.
    Talley NJ, Shorter RG, Phillips SF, Zinsmeister AR (1990) Eosinophilic gastroenteritis: a clinicopathological study of patients with disease of the mucosa, muscle layer, and subserosal tissues. Gut 31(1):54–58PubMedPubMedCentralGoogle Scholar
  19. 19.
    Rothenberg M (2014) Eosinophilic gastrointestinal disorders. In: Adkinson N Jr, Bochner B (eds) Middleton's allergy: principles and practice, vol 2, 8th edn. Saunders, Welwyn Garden City. 1095. PrintGoogle Scholar
  20. 20.
    Lake AM (2000) Food-induced eosinophilic proctocolitis. J Pediatr Gastroenterol Nutr 30(Suppl):S58–S60PubMedGoogle Scholar
  21. 21.
    Alfadda AA, Storr MA, Shaffer EA (2011) Eosinophilic colitis: epidemiology, clinical features, and current management. Therap Adv Gastroenterol 4(5):301–309PubMedPubMedCentralGoogle Scholar
  22. 22.
    Lee J, Dierkhising R, Wu TT, Alexander J, Weiler C (2011) Eosinophilic gastrointestinal disorders (EGID) with peripheral eosinophilia: a retrospective review at Mayo Clinic. Dig Dis Sci 56(11):3254–3261PubMedGoogle Scholar
  23. 23.
    Ogbogu PU, Bochner BS (2009) Butterfield JH, et al. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol 124(6):1319–1325.e1313PubMedPubMedCentralGoogle Scholar
  24. 24.
    Jeon YW, Hong SJ, Kim HJ, Han JP, Kim HK, Ko BM, Park SK, Lee MS (2012) A hypereosinophilic syndrome presenting as eosinophilic colitis. Clin Endosc 45(4):444–447PubMedPubMedCentralGoogle Scholar
  25. 25.
    Park TY, Choi CH, Yang SY, Oh IS, Song ID, Lee HW, Kim HJ, Do JH, Chang SK, Cho AR, Cha YJ (2009) A case of hypereosinophilic syndrome presenting with intractable gastric ulcers. World J Gastroenterol 15(48):6129–6133PubMedPubMedCentralGoogle Scholar
  26. 26.
    Fathi AT, Dec GW, Richter JM et al (2014) Case records of the Massachusetts General Hospital. Case 7-2014—a 27-year-old man with diarrhea, fatigue, and eosinophilia. N Engl J Med 370(9):861–872PubMedGoogle Scholar
  27. 27.
    Kobayashi M, Komatsu N, Kuwayama Y, Bandobashi K, Kubota T, Uemura Y, Taguchi H (2007) Idiopathic hypereosinophilic syndrome presenting acute abdomen. Intern Med 46(10):675–678PubMedGoogle Scholar
  28. 28.
    Bauer S, Schaub N, Kummer H, Wegmann W (1994) Prolonged course of an idiopathic hypereosinophilic syndrome with transition to eosinophilic gastroenteritis. Schweiz Med Wochenschr 124(44):1976–1981PubMedGoogle Scholar
  29. 29.
    Scheurlen M, Mörk H, Weber P (1992) Hypereosinophilic syndrome resembling chronic inflammatory bowel disease with primary sclerosing cholangitis. J Clin Gastroenterol 14(1):59–63PubMedGoogle Scholar
  30. 30.
    Murakami S, Misumi M, Sakata H, Hirayama R, Kubojima Y, Nomura K, Ban S (2004) Churg-Strauss syndrome manifesting as perforation of the small intestine: report of a case. Surg Today 34(9):788–792PubMedGoogle Scholar
  31. 31.
    Sharma MC, Safaya R, Sidhu BS (1996) Perforation of small intestine caused by Churg-Strauss syndrome. J Clin Gastroenterol 23(3):232–235PubMedGoogle Scholar
  32. 32.
    Ichikawa Y, Takeuchi M, Yamada M, Hosoi T, Mabuchi T, Okada A, Tomida H, Suhara H, Koya T, Suzuki H, Okada Y (2012) A case of ischemic colitis induced by hypereosinophilic syndrome. Nihon Shokakibyo Gakkai Zasshi 109(12):2074–2081PubMedGoogle Scholar
  33. 33.
    Cheung AC, Hachem CY, Lai J (2016) Idiopathic hypereosinophilic syndrome presenting with hepatitis and achalasia. Clin J Gastroenterol 9(4):238–242PubMedGoogle Scholar
  34. 34.
    Shatery K, Sayyah A (2011) Idiopathic hypereosinophilic syndrome presenting with liver mass: report of two cases: idiopathic hypereosinophilic syndrome and liver mass. Hepat Mon 11(2):123–125PubMedPubMedCentralGoogle Scholar
  35. 35.
    Watanabe M, Matsui N, Hamada S et al (2004) A rare case of idiopathic hypereosinophilic syndrome involving the oral cavity associated with the esophagus and gastrointestinal tract. Intern Med 43(4):336–339PubMedGoogle Scholar
  36. 36.
    Muir A, Surrey L, Kriegermeier A, Shaikhkalil A, Piccoli DA (2016) Severe eosinophilic gastroenteritis in a Crohn's disease patient treated with infliximab and adalimumab. Am J Gastroenterol 111(3):437–438PubMedGoogle Scholar
  37. 37.
    Click B, Anderson AM, Koutroubakis IE, Rivers CR, Babichenko D, Machicado JD, Hartman DJ, Hashash JG, Dunn MA, Schwartz M, Swoger J, Barrie III A, Wenzel SE, Regueiro M, Binion DG (2017) Peripheral eosinophilia in patients with inflammatory bowel disease defines an aggressive disease phenotype. Am J Gastroenterol 112(12):1849–1858PubMedGoogle Scholar
  38. 38.
    Zuo L, Rothenberg ME (2007) Gastrointestinal eosinophilia. Immunol Allergy Clin N Am 27(3):443–455Google Scholar
  39. 39.
    Riggle KM, Wahbeh G, Williams EM, Riehle KJ (2015) Perforated duodenal ulcer: an unusual manifestation of allergic eosinophilic gastroenteritis. World J Gastroenterol 21(44):12709–12712PubMedPubMedCentralGoogle Scholar
  40. 40.
    Curtis C, Ogbogu PU (2015) Evaluation and differential diagnosis of persistent marked eosinophilia. Immunol Allergy Clin N Am 35(3):387–402Google Scholar
  41. 41.
    Crane MM, Chang CM, Kobayashi MG, Weller PF (2010) Incidence of myeloproliferative hypereosinophilic syndrome in the United States and an estimate of all hypereosinophilic syndrome incidence. J Allergy Clin Immunol 126(1):179–181PubMedPubMedCentralGoogle Scholar
  42. 42.
    Podjasek JC, Butterfield JH (2013) Mortality in hypereosinophilic syndrome: 19 years of experience at Mayo Clinic with a review of the literature. Leuk Res 37(4):392–395PubMedGoogle Scholar
  43. 43.
    Lefebvre C, Bletry O, Degoulet P, Guillevin L, Bentata-Pessayre M, le Thi Huong du, Godeau P (1989) Prognostic factors of hypereosinophilic syndrome. Study of 40 cases. Ann Med Interne (Paris) 140(4):253–257Google Scholar
  44. 44.
    Tavil B, Aytaç S, Unal S, Kuskonmaz B, Gumruk F, Cetin M (2016) Hypereosinophilic syndrome: Hacettepe experience. J Pediatr Hematol Oncol 38(7):539–543PubMedGoogle Scholar
  45. 45.
    Vaklavas C, Tefferi A, Butterfield J, Ketterling R, Verstovsek S, Kantarjian H, Pardanani A (2007) Idiopathic' eosinophilia with an occult T-cell clone: prevalence and clinical course. Leuk Res 31(5):691–694PubMedGoogle Scholar
  46. 46.
    Klion AD, Noel P, Akin C, Law MA, Gilliland DG, Cools J, Metcalfe DD, Nutman TB (2003) 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 101(12):4660–4666PubMedGoogle Scholar
  47. 47.
    Roufosse F (2015) Management of hypereosinophilic syndromes. Immunol Allergy Clin N Am 35(3):561–575Google Scholar
  48. 48.
    Chusid MJ, Dale DC, West BC, Wolff SM (1975) The hypereosinophilic syndrome: analysis of fourteen cases with review of the literature. Medicine (Baltimore) 54(1):1–27Google Scholar
  49. 49.
    Kovalszki A, Weller PF (2016) Eosinophilia. Prim Care 43(4):607–617PubMedPubMedCentralGoogle Scholar
  50. 50.
    Kovalszki A, Weller PF (2014) Eosinophilia in mast cell disease. Immunol Allergy Clin N Am 34(2):357–364Google Scholar
  51. 51.
    Pochineni V, Lal D, Hasnayen S, Restrepo E (2015) Fatal strongyloides hyperinfection syndrome in an immunocompromised patient. Am J Case Rep 16:603–605PubMedPubMedCentralGoogle Scholar
  52. 52.
    Villarreal O, Villarreal JJ, Domingo JA (1999) Progressive eosinophilia and elevated IgE in enterobiasis. Allergy 54(6):646–648PubMedGoogle Scholar
  53. 53.
    Nanagas V, Montejo J (2017) Hypereosinophilia with systemic symptoms due to pinworm. Ann Allergy Asthma Immunol 119(5):S70Google Scholar
  54. 54.
    Ermens AA, Vlasveld LT, Lindemans J (2003) Significance of elevated cobalamin (vitamin B12) levels in blood. Clin Biochem 36(8):585–590PubMedGoogle Scholar
  55. 55.
    Zittoun J, Farcet JP, Marquet J, Sultan C, Zittoun R (1984) Cobalamin (vitamin B12) and B12 binding proteins in hypereosinophilic syndromes and secondary eosinophilia. Blood 63(4):779–783PubMedGoogle Scholar
  56. 56.
    Dulohery MM, Patel RR, Schneider F, Ryu JH (2011) Lung involvement in hypereosinophilic syndromes. Respir Med 105(1):114–121PubMedGoogle Scholar
  57. 57.
    Katre RS, Sunnapwar A, Restrepo CS, Katabathina VS, Mumbower A, Baxi A, Sonavane S (2016) Cardiopulmonary and gastrointestinal manifestations of eosinophil- associated diseases and idiopathic hypereosinophilic syndromes: multimodality imaging approach. Radiographics 36(2):433–451PubMedGoogle Scholar
  58. 58.
    Ko HM, Morotti RA, Yershov O, Chehade M (2014) Eosinophilic gastritis in children: clinicopathological correlation, disease course, and response to therapy. Am J Gastroenterol 109(8):1277–1285PubMedGoogle Scholar
  59. 59.
    Lowichik A, Weinberg AG (1996) A quantitative evaluation of mucosal eosinophils in the pediatric gastrointestinal tract. Mod Pathol 9(2):110–114PubMedGoogle Scholar
  60. 60.
    DeBrosse CW, Case JW, Putnam PE, Collins MH, Rothenberg ME (2006) Quantity and distribution of eosinophils in the gastrointestinal tract of children. Pediatr Dev Pathol 9(3):210–218PubMedGoogle Scholar
  61. 61.
    Lwin T, Melton SD, Genta RM (2011) Eosinophilic gastritis: histopathological characterization and quantification of the normal gastric eosinophil content. Mod Pathol 24(4):556–563PubMedGoogle Scholar
  62. 62.
    Pascal RR, Gramlich TL, Parker KM, Gansler TS (1997) Geographic variations in eosinophil concentration in normal colonic mucosa. Mod Pathol 10(4):363–365PubMedGoogle Scholar
  63. 63.
    Polydorides AD, Banner BF, Hannaway PJ, Yantiss RK (2008) Evaluation of site-specific and seasonal variation in colonic mucosal eosinophils. Hum Pathol 39(6):832–836PubMedGoogle Scholar
  64. 64.
    Klion AD (2009) How I treat hypereosinophilic syndromes. Blood 114(18):3736–3741PubMedPubMedCentralGoogle Scholar
  65. 65.
    Klion AD, Law MA, Riemenschneider W, McMaster M, Brown MR, Horne M, Karp B, Robinson M, Sachdev V, Tucker E, Turner M, Nutman TB (2004) Familial eosinophilia: a benign disorder? Blood 103(11):4050–4055PubMedGoogle Scholar
  66. 66.
    Altman LC, Hill JS, Hairfield WM, Mullarkey MF (1981) Effects of corticosteroids on eosinophil chemotaxis and adherence. J Clin Invest 67(1):28–36PubMedPubMedCentralGoogle Scholar
  67. 67.
    Roufosse F, Klion A, Weller P. Hypereosinophilic syndromes: treatment. In: UpToDate, Bochner BS (eds) UpToDate. UpToDate Inc., Waltham. Accessed 17 December 2017
  68. 68.
    Khoury P, Abiodun AO, Holland-Thomas N, Fay MP, Klion AD (2017) Hypereosinophilic syndrome subtype predicts responsiveness to glucocorticoids. J Allergy Clin Immunol PractGoogle Scholar
  69. 69.
    Vaisben E, Brand R, Kadakh A, Nassar F (2015) The role of empirical albendazole treatment in idiopathic hypereosinophilia—a case series. Can J Infect Dis Med Microbiol 26(6):323–324PubMedPubMedCentralGoogle Scholar
  70. 70.
    Klion AD, Bochner BS, Gleich GJ et al (2006) Approaches to the treatment of hypereosinophilic syndromes: a workshop summary report. J Allergy Clin Immunol 117(6):1292–1302PubMedGoogle Scholar
  71. 71.
    Khoury P, Desmond R, Pabon A, Holland-Thomas N, Ware JM, Arthur DC, Kurlander R, Fay MP, Maric I, Klion AD (2016) Clinical features predict responsiveness to imatinib in platelet-derived growth factor receptor-alpha-negative hypereosinophilic syndrome. Allergy 71(6):803–810PubMedPubMedCentralGoogle Scholar
  72. 72.
    Roufosse F, de Lavareille A, Schandené L, Cogan E, Georgelas A, Wagner L, Xi L, Raffeld M, Goldman M, Gleich GJ, Klion A (2010) Mepolizumab as a corticosteroid-sparing agent in lymphocytic variant hypereosinophilic syndrome. J Allergy Clin Immunol 126(4):828–835.e823PubMedPubMedCentralGoogle Scholar
  73. 73.
    Rothenberg ME, Klion AD, Roufosse FE et al (2008) Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med 358(12):1215–1228PubMedGoogle Scholar
  74. 74.
    Kuang FL, Klion AD (2017) Biologic agents for the treatment of hypereosinophilic syndromes. J Allergy Clin Immunol Pract 5(6):1502–1509PubMedPubMedCentralGoogle Scholar
  75. 75.
    Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G III, O’Gorman MA, Abonia JP, Young J, Henkel T, Wilkins HJ, Liacouras CA (2012) Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol 129(2):456–463 463.e451-453PubMedGoogle Scholar
  76. 76.
    Assa'ad AH, Gupta SK, Collins MH, Thomson M, Heath AT, Smith DA, Perschy TL, Jurgensen CH, Ortega HG, Aceves SS (2011) An antibody against IL-5 reduces numbers of esophageal intraepithelial eosinophils in children with eosinophilic esophagitis. Gastroenterology 141(5):1593–1604PubMedGoogle Scholar
  77. 77.
    Moots RJ, Prouse P, Gumpel JM (1988) Near fatal eosinophilic gastroenteritis responding to oral sodium chromoglycate. Gut 29(9):1282–1285PubMedPubMedCentralGoogle Scholar
  78. 78.
    Suzuki J, Kawasaki Y, Nozawa R, Isome M, Suzuki S, Takahashi A, Suzuki H (2003) Oral disodium cromoglycate and ketotifen for a patient with eosinophilic gastroenteritis, food allergy and protein-losing enteropathy. Asian Pac J Allergy Immunol 21(3):193–197PubMedGoogle Scholar
  79. 79.
    Van Dellen RG, Lewis JC (1994) Oral administration of cromolyn in a patient with protein-losing enteropathy, food allergy, and eosinophilic gastroenteritis. Mayo Clin Proc 69(5):441–444PubMedGoogle Scholar
  80. 80.
    Liacouras CA, Spergel JM, Ruchelli E, Verma R, Mascarenhas M, Semeao E, Flick J, Kelly J, Brown–Whitehorn T, Mamula P, Markowitz JE (2005) Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol 3(12):1198–1206PubMedGoogle Scholar
  81. 81.
    Hua S, Cook D, Walker MM, Talley NJ (2016) Pharmacological treatment of eosinophilic gastrointestinal disorders. Expert Rev Clin Pharmacol 9(9):1195–1209PubMedGoogle Scholar
  82. 82.
    Cianferoni A, Spergel JM (2014) Immunotherapeutic approaches for the treatment of eosinophilic esophagitis. Immunotherapy 6(3):321–331PubMedPubMedCentralGoogle Scholar
  83. 83.
    Imam T, Gupta SK (2016) Topical glucocorticoid vs. diet therapy in eosinophilic esophagitis: the need for better treatment options. Expert Rev Clin Immunol 12(8):797–799PubMedPubMedCentralGoogle Scholar
  84. 84.
    Greenhawt M, Aceves SS, Spergel JM, Rothenberg ME (2013) The management of eosinophilic esophagitis. J Allergy Clin Immunol Pract 1(4):332–340 quiz 341-332PubMedGoogle Scholar
  85. 85.
    Arias A, González-Cervera J, Tenias JM, Lucendo AJ (2014) Efficacy of dietary interventions for inducing histologic remission in patients with eosinophilic esophagitis: a systematic review and meta-analysis. Gastroenterology 146(7):1639–1648PubMedGoogle Scholar
  86. 86.
    Ramsay DB, Stephen S, Borum M, Voltaggio L, Doman DB (2010) Mast cells in gastrointestinal disease. Gastroenterol Hepatol (N Y) 6(12):772–777Google Scholar
  87. 87.
    Doyle LA, Sepehr GJ, Hamilton MJ, Akin C, Castells MC, Hornick JL (2014) A clinicopathologic study of 24 cases of systemic mastocytosis involving the gastrointestinal tract and assessment of mucosal mast cell density in irritable bowel syndrome and asymptomatic patients. Am J Surg Pathol 38(6):832–843PubMedPubMedCentralGoogle Scholar
  88. 88.
    Gilfillan AM, Austin SJ, Metcalfe DD (2011) Mast cell biology: introduction and overview. Adv Exp Med Biol 716:2–12PubMedPubMedCentralGoogle Scholar
  89. 89.
    Bradding P, Saito H (2014) Biology of mast cells and their mediators. In: Adkinson N Jr, Bochner B (eds) Middleton 's allergy: principles and practice, vol 1, 8th edn. Saunders, Welwyn Garden City, pp 228–251Google Scholar
  90. 90.
    Gurish MF, Bryce PJ, Tao H, Kisselgof AB, Thornton EM, Miller HR, Friend DS, Oettgen HC (2004) IgE enhances parasite clearance and regulates mast cell responses in mice infected with Trichinella spiralis. J Immunol 172(2):1139–1145PubMedGoogle Scholar
  91. 91.
    Shin K, Watts GF, Oettgen HC et al (2008) Mouse mast cell tryptase mMCP-6 is a critical link between adaptive and innate immunity in the chronic phase of Trichinella spiralis infection. J Immunol 180(7):4885–4891PubMedPubMedCentralGoogle Scholar
  92. 92.
    Friend DS, Ghildyal N, Gurish MF et al (1998) Reversible expression of tryptases and chymases in the jejunal mast cells of mice infected with Trichinella spiralis. J Immunol 160(11):5537–5545PubMedGoogle Scholar
  93. 93.
    Yu Y, Blokhuis BR, Garssen J, Redegeld FA (2016) Non-IgE mediated mast cell activation. Eur J Pharmacol 778:33–43PubMedGoogle Scholar
  94. 94.
    Aich A, Afrin LB, Gupta K (2015) Mast cell-mediated mechanisms of nociception. Int J Mol Sci 16(12):29069–29092PubMedPubMedCentralGoogle Scholar
  95. 95.
    Gülen T, Akin C (2017) Pharmacotherapy of mast cell disorders. Curr Opin Allergy Clin Immunol 17(4):295–303PubMedGoogle Scholar
  96. 96.
    Akin C, Valent P, Metcalfe DD (2010) Mast cell activation syndrome: proposed diagnostic criteria. J Allergy Clin Immunol 126(6):1099–1104.e1094PubMedPubMedCentralGoogle Scholar
  97. 97.
    Metcalfe DD, Mekori YA (2017) Pathogenesis and pathology of mastocytosis. Annu Rev Pathol 12:487–514PubMedGoogle Scholar
  98. 98.
    Jennings S, Russell N, Jennings B, Slee V, Sterling L, Castells M, Valent P, Akin C (2014) The Mastocytosis Society survey on mast cell disorders: patient experiences and perceptions. J Allergy Clin Immunol Pract 2(1):70–76PubMedGoogle Scholar
  99. 99.
    Jensen RT (2000) Gastrointestinal abnormalities and involvement in systemic mastocytosis. Hematol Oncol Clin North Am 14(3):579–623PubMedGoogle Scholar
  100. 100.
    Sokol H, Georgin-Lavialle S, Canioni D, Barete S, Damaj G, Soucie E, Bruneau J, Chandesris MO, Suarez F, Launay JM, Aouba A, Grandpeix-Guyodo C, Lanternier F, Grosbois B, de Gennes C, Cathébras P, Fain O, Hoyeau-Idrissi N, Dubreuil P, Lortholary O, Beaugerie L, Ranque B, Hermine O (2013) Gastrointestinal manifestations in mastocytosis: a study of 83 patients. J Allergy Clin Immunol 132(4):866–873 e861–863PubMedGoogle Scholar
  101. 101.
    Cherner JA, Jensen RT, Dubois A, O'Dorisio TM, Gardner JD, Metcalfe DD (1988) Gastrointestinal dysfunction in systemic mastocytosis. A prospective study. Gastroenterology 95(3):657–667PubMedGoogle Scholar
  102. 102.
    Behdad A, Owens SR (2013) Systemic mastocytosis involving the gastrointestinal tract: case report and review. Arch Pathol Lab Med. 137(9):1220–1223PubMedGoogle Scholar
  103. 103.
    A Akbar S, Raza S, E Denney J, J Johannesen E, C Doll D (2013) Systemic mastocytosis presenting as acute appendicitis: a case report and review of the literature. Case Rep Oncol 6(1):174–179PubMedPubMedCentralGoogle Scholar
  104. 104.
    Akin C (2017) Mast cell activation syndromes. J Allergy Clin Immunol 140(2):349–355PubMedGoogle Scholar
  105. 105.
    Guilarte M, Santos J, de Torres I, Alonso C, Vicario M, Ramos L, Martinez C, Casellas F, Saperas E, Malagelada JR (2007) Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum. Gut 56(2):203–209PubMedGoogle Scholar
  106. 106.
    Barbara G, Stanghellini V, De Giorgio R et al (2004) Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology 126(3):693–702PubMedGoogle Scholar
  107. 107.
    Wouters MM, Vicario M, Santos J (2016) The role of mast cells in functional GI disorders. Gut 65(1):155–168PubMedGoogle Scholar
  108. 108.
    Vanuytsel T, van Wanrooy S, Vanheel H, Vanormelingen C, Verschueren S, Houben E, Salim Rasoel S, Tόth J, Holvoet L, Farré R, van Oudenhove L, Boeckxstaens G, Verbeke K, Tack J (2014) Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism. Gut 63(8):1293–1299PubMedGoogle Scholar
  109. 109.
    Lee KN, Lee OY (2016) The role of mast cells in irritable bowel syndrome. Gastroenterol Res Pract 2016:2031480PubMedPubMedCentralGoogle Scholar
  110. 110.
    Valent P, Horny HP, Escribano L, Longley BJ, Li CY, Schwartz LB, Marone G, Nuñez R, Akin C, Sotlar K, Sperr WR, Wolff K, Brunning RD, Parwaresch RM, Austen KF, Lennert K, Metcalfe DD, Vardiman JW, Bennett JM (2001) Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res 25(7):603–625PubMedGoogle Scholar
  111. 111.
    Valent P, Akin C, Arock M, Brockow K, Butterfield JH, Carter MC, Castells M, Escribano L, Hartmann K, Lieberman P, Nedoszytko B, Orfao A, Schwartz LB, Sotlar K, Sperr WR, Triggiani M, Valenta R, Horny HP, Metcalfe DD (2012) Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol 157(3):215–225PubMedGoogle Scholar
  112. 112.
    Sethi A, Jain D, Roland BC, Kinzel J, Gibson J, Schrader R, Hanson JA (2015) Performing colonic mast cell counts in patients with chronic diarrhea of unknown etiology has limited diagnostic use. Arch Pathol Lab Med. 139(2):225–232PubMedGoogle Scholar
  113. 113.
    Jakate S, Demeo M, John R, Tobin M, Keshavarzian A (2006) Mastocytic enterocolitis: increased mucosal mast cells in chronic intractable diarrhea. Arch Pathol Lab Med 130(3):362–367PubMedGoogle Scholar
  114. 114.
    Seo H, Park SH, Byeon JS, Woo CG, Hong SM, Chang K, So H, Kwak M, Kim WS, Lee JM, Yang DH, Kim KJ, Ye BD, Myung SJ, Yang SK (2016) Chronic intractable diarrhea caused by gastrointestinal mastocytosis. Intest Res 14(3):280–284PubMedPubMedCentralGoogle Scholar
  115. 115.
    Horan RF, Sheffer AL, Austen KF (1990) Cromolyn sodium in the management of systemic mastocytosis. J Allergy Clin Immunol 85(5):852–855PubMedGoogle Scholar
  116. 116.
    Metcalfe DD (1991) The treatment of mastocytosis: an overview. J Investig Dermatol 96(3 Suppl):55S–56S discussion 56S-59S, 60S-65SPubMedGoogle Scholar
  117. 117.
    Rao SS, Yu S, Fedewa A (2015) Systematic review: dietary fibre and FODMAP-restricted diet in the management of constipation and irritable bowel syndrome. Aliment Pharmacol Ther 41(12):1256–1270PubMedPubMedCentralGoogle Scholar
  118. 118.
    Galdiero MR, Varricchi G, Seaf M, Marone G, Levi-Schaffer F (2017) Bidirectional mast cell-eosinophil interactions in inflammatory disorders and cancer. Front Med (Lausanne) 4:103Google Scholar
  119. 119.
    Landolina N, Gangwar RS, Levi-Schaffer F (2015) Mast cells' integrated actions with eosinophils and fibroblasts in allergic inflammation: implications for therapy. Adv Immunol 125:41–85PubMedGoogle Scholar
  120. 120.
    Minai-Fleminger Y, Elishmereni M, Vita F, Rosa Soranzo M, Mankuta D, Zabucchi G, Levi-Schaffer F (2010) Ultrastructural evidence for human mast cell-eosinophil interactions in vitro. Cell Tissue Res 341(3):405–415PubMedGoogle Scholar
  121. 121.
    Elishmereni M, Alenius HT, Bradding P, Mizrahi S, Shikotra A, Minai-Fleminger Y, Mankuta D, Eliashar R, Zabucchi G, Levi-Schaffer F (2011) Physical interactions between mast cells and eosinophils: a novel mechanism enhancing eosinophil survival in vitro. Allergy 66(3):376–385PubMedGoogle Scholar
  122. 122.
    Elishmereni M, Bachelet I, Nissim Ben-Efraim AH, Mankuta D, Levi-Schaffer F (2013) Interacting mast cells and eosinophils acquire an enhanced activation state in vitro. Allergy 68(2):171–179PubMedGoogle Scholar
  123. 123.
    De Wilde V, Roufosse F, Hermine O (2016) Clonal eosinophil and mast cell diseases: different in the same way? Expert Rev Hematol 9(12):1107–1109PubMedGoogle Scholar
  124. 124.
    Abonia JP, Blanchard C, Butz BB, Rainey HF, Collins MH, Stringer K, Putnam PE, Rothenberg ME (2010) Involvement of mast cells in eosinophilic esophagitis. J Allergy Clin Immunol 126(1):140–149PubMedPubMedCentralGoogle Scholar
  125. 125.
    Otani IM, Anilkumar AA, Newbury RO, Bhagat M, Beppu LY, Dohil R, Broide DH, Aceves SS (2013) Anti-IL-5 therapy reduces mast cell and IL-9 cell numbers in pediatric patients with eosinophilic esophagitis. J Allergy Clin Immunol 131(6):1576–1582PubMedPubMedCentralGoogle Scholar
  126. 126.
    Nin-Asai R, Kono M, Akiyama M (2014) Urticaria pigmentosa complicated with esophageal eosinophilia. J Am Acad Dermatol 71(5):e207–e208PubMedGoogle Scholar
  127. 127.
    Stasikowska-Kanicka O, Danilewicz M, Głowacka A, Wągrowska-Danilewicz M (2012) Mast cells and eosinophils are involved in activation of ulcerative colitis. Adv Med Sci 57(2):230–236PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Allergy and Clinical Immunology, Department of Internal MedicineUniversity of MichiganAnn ArborUSA
  2. 2.Domino’s FarmsAnn ArborUSA

Personalised recommendations