Chapter 85 : Diagnosis of Rare Eosinophilic and Mast Cell Disorders

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Diagnosis of Rare Eosinophilic and Mast Cell Disorders, Page 1 of 2

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Whereas mild to moderate eosinophilia has been reported in as many as 0.1% of North American outpatients (1) and may be due to seasonal allergies, asthma, or other common conditions, marked eosinophilia (>1,500/mm) is relatively infrequent and should always prompt a diagnostic evaluation. The differential diagnosis of marked eosinophilia is broad and includes secondary causes of eosinophilia (Table 1), such as hypersensitivity reactions, helminth infection, and neoplastic and inflammatory disorders, as well as several disorders for which eosinophilia is thought to be the primary etiology. In many cases, a thorough diagnostic evaluation will reveal a secondary cause of the eosinophilia, and appropriate treatment can be instituted. In other instances, a well-defined, single-organ-restricted, primary eosinophil disorder, such as eosinophilic esophagitis, eosinophilic fasciitis, or eosinophilia cystitis, is identified. Once secondary causes and alternative diagnoses have been excluded, however, a systemic primary eosinophil disorder should be considered.

Citation: Akin C, Prussin C, Klion A. 2016. Diagnosis of Rare Eosinophilic and Mast Cell Disorders, p 825-837. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch85
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1. Brigden M, Graydon C . 1997. Eosinophilia detected by automated blood cell counting in ambulatory North American outpatients. Incidence and clinical significance. Arch Pathol Lab Med 121 : 963 967.[PubMed]
2. Hardy WR, Anderson RE . 1968. The hypereosinophilic syndromes. Ann Intern Med 68 : 1220 1229.[PubMed].[CrossRef]
3. 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 27.[PubMed].[CrossRef]
4. Gleich GJ, Schroeter AL, Marcoux JP, Sachs MI, O'Connell EJ, Kohler PF . 1984. Episodic angioedema associated with eosinophilia. N Engl J Med 310 : 1621 1626.[CrossRef].[PubMed]
5. Chen YK, Khoury P, Ware JM, Holland-Thomas NC, Stoddard JL, Gurprasad S, Waldner AJ, Klion AD . 26 August 2013. Marked and persistent eosinophilia in the absence of clinical manifestations. J Allergy Clin Immunol doi:10.1016/j.jaci.2013.06.037.[CrossRef] http://dx.doi.org/doi:10.1016/j.jaci.2013.06.037
6. Simon HU, Rothenberg ME, Bochner BS, Weller PF, Wardlaw AJ, Wechsler ME, Rosenwasser LJ, Roufosse F, Gleich GJ, Klion AD . 2010. Refining the definition of hypereosinophilic syndrome. J Allergy Clin Immunol 126 : 45 49.[CrossRef].[PubMed]
7. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellström-Lindberg E, Tefferi A, Bloomfield CD . 2009. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114 : 937 951.[CrossRef].[PubMed]
8. Valent P, Klion AD, Horny HP, Roufosse F, Gotlib J, Weller PF, Hellmann A, Metzgeroth G, Leiferman KM, Arock M, Butterfield JH, Sperr WR, Sotlar K, Vandenberghe P, Haferlach T, Simon HU, Reiter A, Gleich GJ . 2012. Contemporary consensus proposal on criteria and classification of eosinophilic disorders and related syndromes. J Allergy Clin Immunol 130 : 607 612.e9.[CrossRef].[PubMed]
9. Weller PF, Bubley GJ . 1994. The idiopathic hypereosinophilic syndrome. Blood 83 : 2759 2779.[PubMed]
10. Ogbogu PU, Bochner BS, Butterfield JH, Gleich GJ, Huss-Marp J, Kahn JE, Leiferman KM, Nutman TB, Pfab F, Ring J, Rothenberg ME, Roufosse F, Sajous MH, Sheikh J, Simon D, Simon HU, Stein ML, Wardlaw A, Weller PF, Klion AD . 2009. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol 124 : 1319 1325.e3.[CrossRef].[PubMed]
11. Helbig G, Hus M, Francuz T, Dziaczkowska-Suszek J, Soja A, Kyrcz-Krzemień S . 2014. Characteristics and clinical outcome of patients with hypereosinophilia of undetermined significance. Med Oncol 31 : 815.[CrossRef].[PubMed]
12. Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, Cortes J, Kutok J, Clark J, Galinsky I, Griffin JD, Cross NCP, Tefferi A, Malone J, Alam R, Schrier SL, Schmid J, Rose M, Vandenberghe P, Verhoef G, Boogaerts M, Wlodarska I, Kantarjian H, Marynen P, Coutre SE, Stone R, Gilliland DG . 2003. 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 348 : 1201 1214.[CrossRef].[PubMed]
13. Griffin JH, Leung J, Bruner RJ, Caligiuri MA, Briesewitz R . 2003. Discovery of a fusion kinase in EOL-1 cells and idiopathic hypereosinophilic syndrome. Proc Natl Acad Sci U S A 100 : 7830 7835.[CrossRef].[PubMed]
14. Brugnoni D, Airó P, Rossi G, Bettinardi A, Simon HU, Garza L, Tosoni C, Cattaneo R, Blaser K, Tucci A . 1996. A case of hypereosinophilic syndrome is associated with the expansion of a CD3 [minus] CD4 + T-cell population able to secrete large amounts of interleukin-5. Blood 87 : 1416 1422.
15. Cogan E, Schandené L, Crusiaux A, Cochaux P, Velu T, Goldman M . 1994. Brief report: clonal proliferation of type 2 helper T cells in a man with the hypereosinophilic syndrome. N Engl J Med 330 : 535 538.[CrossRef].[PubMed]
16. Klion AD, Law MA, Riemenschneider W, McMaster ML, Brown MR, Horne M, Karp B, Robinson M, Sachdev V, Tucker E, Turner M, Nutman TB . 2004. Familial eosinophilia: a benign disorder? Blood 103 : 4050 4055.[CrossRef].[PubMed]
17. Rioux JD, Stone VA, Daly MJ, Cargill M, Green T, Nguyen H, Nutman T, Zimmerman PA, Tucker MA, Hudson T, Goldstein AM, Lander E, Lin AY . 1998. Familial eosinophilia maps to the cytokine gene cluster on human chromosomal region 5q31-q33. Am J Hum Genet 63 : 1086 1094.[CrossRef].[PubMed]
18. 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 : 4660 4666.[CrossRef].[PubMed]
19. Bain BJ . 2010. Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1. Haematologica 95 : 696 698.[CrossRef].[PubMed]
20. Elling C, Erben P, Walz C, Frickenhaus M, Schemionek M, Stehling M, Serve H, Cross NC, Hochhaus A, Hofmann WK, Berdel WE, Müller-Tidow C, Reiter A, Koschmieder S . 2011. Novel imatinib-sensitive PDGFRA-activating point mutations in hypereosinophilic syndrome induce growth factor independence and leukemia-like disease. Blood 117 : 2935 2943.[CrossRef].[PubMed]
21. Pardanani A, Ketterling RP, Brockman SR, Flynn HC, Paternoster SF, Shearer BM, Reeder TL, Li CY, Cross NC, Cools J, Gilliland DG, Dewald GW, Tefferi A . 2003. CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy. Blood 102 : 3093 3096.[CrossRef].[PubMed]
22. Robyn J, Noel P, Wlodarska I, Choksi M, O'Neal P, Arthur D, Dunbar C, Nutman T, Klion A . 2004. Imatinib-responsive hypereosinophilia in a patient with B cell ALL. Leuk Lymphoma 45 : 2497 2501.[CrossRef].[PubMed]
23. Irusta PM, DiMaio D . 1998. A single amino acid substitution in a WW-like domain of diverse members of the PDGF receptor subfamily of tyrosine kinases causes constitutive receptor activation. EMBO J 17 : 6912 6923.[CrossRef].[PubMed]
24. Vandenberghe P, Wlodarska I, Michaux L, Zachée P, Boogaerts M, Vanstraelen D, Herregods MC, Van Hoof A, Selleslag D, Roufosse F, Maerevoet M, Verhoef G, Cools J, Gilliland DG, Hagemeijer A, Marynen P . 2004. Clinical and molecular features of FIP1L1-PDFGRA (+) chronic eosinophilic leukemias. Leukemia 18 : 734 742.[CrossRef].[PubMed]
25. Pardanani A, Brockman SR, Paternoster SF, Flynn HC, Ketterling RP, Lasho TL, Ho CL, Li CY, Dewald GW, Tefferi A . 2004. FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia. Blood 104 : 3038 3045.[CrossRef].[PubMed]
26. Maric I, Robyn J, Metcalfe DD, Fay MP, Carter M, Wilson T, Fu W, Stoddard J, Scott L, Hartsell M, Kirshenbaum A, Akin C, Nutman TB, Noel P, Klion AD . 2007. KIT D816V-associated systemic mastocytosis with eosinophilia and FIP1L1/PDGFRA-associated chronic eosinophilic leukemia are distinct entities. J Allergy Clin Immunol 120 : 680 687.[CrossRef].[PubMed]
27. Parrillo JE, Fauci AS, Wolff SM . 1978. Therapy of the hypereosinophilic syndrome. Ann Intern Med 89 : 167 172.[PubMed].[CrossRef]
28. Klion AD, Robyn J, Akin C, Noel P, Brown M, Law M, Metcalfe DD, Dunbar C, Nutman TB . 2004. Molecular remission and reversal of myelofibrosis in response to imatinib mesylate treatment in patients with the myeloproliferative variant of hypereosinophilic syndrome. Blood 103 : 473 478.[CrossRef].[PubMed]
29. Gleich GJ, Leiferman KM, Pardanani A, Tefferi A, Butterfield JH . 2002. Treatment of hypereosinophilic syndrome with imatinib mesilate. Lancet 359 : 1577 1578.[CrossRef].[PubMed]
30. Pitini V, Arrigo C, Azzarello D, La Gattuta G, Amata C, Righi M, Coglitore S . 2003. Serum concentration of cardiac Troponin T in patients with hypereosinophilic syndrome treated with imatinib is predictive of adverse outcomes. Blood 102 : 3456 3457. (Author Reply, 102:3457.)[CrossRef].[PubMed]
31. Simon D, Salemi S, Yousefi S, Simon HU . 2008. Primary resistance to imatinib in Fip1-like 1-platelet-derived growth factor receptor alpha-positive eosinophilic leukemia. J Allergy Clin Immunol 121 : 1054 1056.[CrossRef].[PubMed]
32. Lierman E, Michaux L, Beullens E, Pierre P, Marynen P, Cools J, Vandenberghe P . 2009. FIP1L1-PDGFRalpha D842V, a novel panresistant mutant, emerging after treatment of FIP1L1-PDGFRalpha T674I eosinophilic leukemia with single agent sorafenib. Leukemia 23 : 845 851.[CrossRef].[PubMed]
33. Halaburda K, Prejzner W, Szatkowski D, Limon J, Hellmann A . 2006. Allogeneic bone marrow transplantation for hypereosinophilic syndrome: long-term follow-up with eradication of FIP1L1-PDGFRA fusion transcript. Bone Marrow Transplant 38 : 319 320.[CrossRef].[PubMed]
34. Simon HU, Plötz SG, Dummer R, Blaser K . 1999. Abnormal clones of T cells producing interleukin-5 in idiopathic eosinophilia. N Engl J Med 341 : 1112 1120.[CrossRef].[PubMed]
35. Roufosse F, Schandené L, Sibille C, Willard-Gallo K, Kennes B, Efira A, Goldman M, Cogan E . 2000. Clonal Th2 lymphocytes in patients with the idiopathic hypereosinophilic syndrome. Br J Haematol 109 : 540 548.[PubMed].[CrossRef]
36. Roufosse F, Cogan E, Goldman M . 2007. Lymphocytic variant hypereosinophilic syndromes. Immunol Allergy Clin North Am 27 : 389 413.[CrossRef].[PubMed]
37. de Lavareille A, Roufosse F, Schmid-Grendelmeier P, Roumier AS, Schandené L, Cogan E, Simon HU, Goldman M . 2002. High serum thymus and activation-regulated chemokine levels in the lymphocytic variant of the hypereosinophilic syndrome. J Allergy Clin Immunol 110 : 476 479.[PubMed].[CrossRef]
38. Kakinuma T, Sugaya M, Nakamura K, Kaneko F, Wakugawa M, Matsushima K, Tamaki K . 2003. Thymus and activation-regulated chemokine (TARC/CCL17) in mycosis fungoides: serum TARC levels reflect the disease activity of mycosis fungoides. J Am Acad Dermatol 48 : 23 30.[CrossRef].[PubMed]
39. Katoh S, Matsumoto N, Matsumoto K, Tokojima M, Ashitani J, Nakamura-Uchiyama F, Matsushima K, Matsukura S, Nawa Y . 2004. A possible role of TARC in antigen-specific Th2-dominant responses in patients with Paragonimiasis westermani. Int Arch Allergy Immunol 134 : 248 252.[CrossRef].[PubMed]
40. Shimada Y, Takehara K, Sato S . 2004. Both Th2 and Th1 chemokines (TARC/CCL17, MDC/CCL22, and Mig/CXCL9) are elevated in sera from patients with atopic dermatitis. J Dermatol Sci 34 : 201 208.[CrossRef].[PubMed]
41. Musto P, Perla G, Minervini MM, Carella AM, Coco FL, Catalano G . 2004. Imatinib-mesylate for all patients with hypereosinophilic syndrome? Leuk Res 28 : 773 774.[CrossRef].[PubMed]
42. Schandené L, Roufosse F, de Lavareille A, Stordeur P, Efira A, Kennès B, Cogan E, Goldman M . 2000. Interferon alpha prevents spontaneous apoptosis of clonal Th2 cells associated with chronic hypereosinophilia. Blood 96 : 4285 4292.[PubMed]
43. 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 : 828 835.e3.[CrossRef].[PubMed]
44. Gleich GJ, Schroeter AL, Marcoux JP, Sachs MI, O'Connell EJ, Kohler PF . 1984. Episodic angioedema associated with eosinophilia. N Engl J Med 310 : 1621 1626.[CrossRef].[PubMed]
45. Morgan SJ, Prince HM, Westerman DA, McCormack C, Glaspole I . 2003. Clonal T-helper lymphocytes and elevated IL-5 levels in episodic angioedema and eosinophilia (Gleich's syndrome). Leuk Lymphoma 44 : 1623 1625.[CrossRef].[PubMed]
46. Lin AY, Nutman TB, Kaslow D, Mulvihill JJ, Fontaine L, White BJ, Knutsen T, Theil KS, Raghuprasad PK, Goldstein AM, Tucker MA . 1998. Familial eosinophilia: clinical and laboratory results on a U.S. kindred. Am J Med Genet 76 : 229 237.[PubMed].[CrossRef]
47. Rioux JD, Stone VA, Daly MJ, Cargill M, Green T, Nguyen H, Nutman T, Zimmerman PA, Tucker MA, Hudson T, Goldstein AM, Lander E, Lin AY . 1998. Familial eosinophilia maps to the cytokine gene cluster on human chromosomal region 5q31-q33. Am J Hum Genet 63 : 1086 1094.[CrossRef].[PubMed]
48. Klion AD, Law MA, Riemenschneider W, McMaster ML, Brown MR, Horne M, Karp B, Robinson M, Sachdev V, Tucker E, Turner M, Nutman TB . 2004. Familial eosinophilia: a benign disorder? Blood 103 : 4050 4055.[CrossRef].[PubMed]
49. Abonia JP, Rothenberg ME . 2012. Eosinophilic esophagitis: rapidly advancing insights. Annu Rev Med 63 : 421 434.[CrossRef].[PubMed]
50. Rothenberg ME . 2004. Eosinophilic gastrointestinal disorders (EGID). J Allergy Clin Immunol 113 : 11 29.[CrossRef].[PubMed]
51. Attwood SE, Smyrk TC, Demeester TR, Jones JB . 1993. Esophageal eosinophilia with dysphagia. A distinct clinicopathologic syndrome. Dig Dis Sci 38 : 109 116.[PubMed].[CrossRef]
52. Vashi R, Hirano I . 2013. Diet therapy for eosinophilic esophagitis: when, why and how. Curr Opin Gastroenterol 29 : 407 415.[CrossRef].[PubMed]
53. Gonsalves N, Doerfler B, Yang GY, Hirano I . 2009. A prospective clinical trial of six food elimination diets or elemental diet in the treatment of adults with eosinophilic gastroenteritis. Gastroenterology 136 : A280.
54. Cheng E, Souza RF, Spechler SJ . 2012. Tissue remodeling in eosinophilic esophagitis. Am J Physiol Gastrointest Liver Physiol 303 : G1175 G1187.[CrossRef].[PubMed]
55. Lucendo AJ, Sánchez-Cazalilla M . 2012. Adult versus pediatric eosinophilic esophagitis: important differences and similarities for the clinician to understand. Expert Rev Clin Immunol 8 : 733 745.[CrossRef].[PubMed]
56. Straumann A, Schoepfer AM . 2012. Therapeutic concepts in adult and paediatric eosinophilic oesophagitis. Nat Rev Gastroenterol Hepatol 9 : 697 704.[CrossRef].[PubMed]
57. Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, Burks AW, Chehade M, Collins MH, Dellon ES, Dohil R, Falk GW, Gonsalves N, Gupta SK, Katzka DA, Lucendo AJ, Markowitz JE, Noel RJ, Odze RD, Putnam PE, Richter JE, Romero Y, Ruchelli E, Sampson HA, Schoepfer A, Shaheen NJ, Sicherer SH, Spechler S, Spergel JM, Straumann A, Wershil BK, Rothenberg ME, Aceves SS . 2011. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol 128 : 3 22.[CrossRef].[PubMed]
58. Molina-Infante J, Ferrando-Lamana L, Ripoll C, Hernandez-Alonso M, Mateos JM, Fernandez-Bermejo M, Dueñas C, Fernandez-Gonzalez N, Quintana EM, Gonzalez-Nuñez MA . 2011. Esophageal eosinophilic infiltration responds to proton pump inhibition in most adults. Clin Gastroenterol Hepatol 9 : 110 117.[CrossRef].[PubMed]
59. Dellon ES, Speck O, Woodward K, Gebhart JH, Madanick RD, Levinson S, Fritchie KJ, Woosley JT, Shaheen NJ . 2013. Clinical and endoscopic characteristics do not reliably differentiate PPI-responsive esophageal eosinophilia and eosinophilic esophagitis in patients undergoing upper endoscopy: a prospective cohort study. Am J Gastroenterol 108 : 1854 1860.[CrossRef].[PubMed]
60. Kephart GM, Alexander JA, Arora AS, Romero Y, Smyrk TC, Talley NJ, Kita H . 2010. Marked deposition of eosinophil-derived neurotoxin in adult patients with eosinophilic esophagitis. Am J Gastroenterol 105 : 298 307.[CrossRef].[PubMed]
61. 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 : 210 218.[CrossRef].[PubMed]
62. Lwin T, Melton SD, Genta RM . 2011. Eosinophilic gastritis: histopathological characterization and quantification of the normal gastric eosinophil content. Mod Pathol 24 : 556 563.[CrossRef].[PubMed]
63. Lucendo AJ, Molina-Infante J . 2014. Emerging therapeutic strategies for eosinophilic esophagitis. Curr Treat Options Gastroenterol 12 : 1 17.[CrossRef].[PubMed]
64. Rieder F, Nonevski I, Ma J, Ouyang Z, West G, Protheroe C, Depetris G, Schirbel A, Lapinski J, Goldblum J, Bonfield T, Lopez R, Harnett K, Lee J, Hirano I, Falk G, Biancani P, Fiocchi C . 2014. T-helper 2 cytokines, transforming growth factor beta1, and eosinophil products induce fibrogenesis and alter muscle motility in patients with eosinophilic esophagitis. Gastroenterology 146 : 1266 1277.e9.[CrossRef].[PubMed]
65. Dellon ES, Sheikh A, Speck O, Woodward K, Whitlow AB, Hores JM, Ivanovic M, Chau A, Woosley JT, Madanick RD, Orlando RC, Shaheen NJ . 2012. Viscous topical is more effective than nebulized steroid therapy for patients with eosinophilic esophagitis. Gastroenterology 143 : 321 324.e1.[CrossRef].[PubMed]
66. Dohil R, Newbury RO, Aceves S . 2012. Transient PPI responsive esophageal eosinophilia may be a clinical sub-phenotype of pediatric eosinophilic esophagitis. Dig Dis Sci 57 : 1413 1419.[CrossRef].[PubMed]
67. Metcalfe DD . 2008. Mast cells and mastocytosis. Blood 112 : 946 956.[CrossRef].[PubMed]
68. Akin C . 2006. Molecular diagnosis of mast cell disorders: a paper from the 2005 William Beaumont Hospital Symposium on Molecular Pathology. J Mol Diagn 8 : 412 419.[CrossRef].[PubMed]
69. 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 : 603 625.[PubMed].[CrossRef]
70. Valent P, Akin C, Escribano L, Födinger M, Hartmann K, Brockow K, Castells M, Sperr WR, Kluin-Nelemans HC, Hamdy NA, Lortholary O, Robyn J, van Doormaal J, Sotlar K, Hauswirth AW, Arock M, Hermine O, Hellmann A, Triggiani M, Niedoszytko M, Schwartz LB, Orfao A, Horny HP, Metcalfe DD . 2007. Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria. Eur J Clin Invest 37 : 435 453.[CrossRef].[PubMed]
71. Carter MC, Metcalfe DD . 2002. Paediatric mastocytosis. Arch Dis Child 86 : 315 319.[PubMed].[CrossRef]
72. Hartmann K, Henz BM . 2002. Cutaneous mastocytosis—clinical heterogeneity. Int Arch Allergy Immunol 127 : 143 146.[CrossRef].[PubMed]
73. Brockow K, Jofer C, Behrendt H, Ring J . 2008. Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk factors in 120 patients. Allergy 63 : 226 232.[CrossRef].[PubMed]
74. Greenhawt M, Akin C . 2007. Mastocytosis and allergy. Curr Opin Allergy Clin Immunol 7 : 387 392.[CrossRef].[PubMed]
75. Hahn HP, Hornick JL . 2007. Immunoreactivity for CD25 in gastrointestinal mucosal mast cells is specific for systemic mastocytosis. Am J Surg Pathol 31 : 1669 1676.[CrossRef].[PubMed]
76. Horny HP, Valent P . 2001. Diagnosis of mastocytosis: general histopathological aspects, morphological criteria, and immunohistochemical findings. Leuk Res 25 : 543 551.[PubMed].[CrossRef]
77. Sperr WR, Escribano L, Jordan JH, Schernthaner GH, Kundi M, Horny HP, Valent P . 2001. Morphologic properties of neoplastic mast cells: delineation of stages of maturation and implication for cytological grading of mastocytosis. Leuk Res 25 : 529 536.[PubMed].[CrossRef]
78. Escribano L, Orfao A, Díaz-Agustin B, Villarrubia J, Cerveró C, López A, Marcos MA, Bellas C, Fernández-Cañadas S, Cuevas M, Sánchez A, Velasco JL, Navarro JL, Miguel JF . 1998. Indolent systemic mast cell disease in adults: immunophenotypic characterization of bone marrow mast cells and its diagnostic implications. Blood 91 : 2731 2736.[PubMed]
79. Sotlar K, Horny HP, Simonitsch I, Krokowski M, Aichberger KJ, Mayerhofer M, Printz D, Fritsch G, Valent P . 2004. CD25 indicates the neoplastic phenotype of mast cells: a novel immunohistochemical marker for the diagnosis of systemic mastocytosis (SM) in routinely processed bone marrow biopsy specimens. Am J Surg Pathol 28 : 1319 1325.[PubMed].[CrossRef]
80. Escribano L, Diaz-Agustin B, López A, Núñez López R, García-Montero A, Almeida J, Prados A, Angulo M, Herrero S, Orfao A Spanish Network on Mastocytosis (REMA), Proposals of the Spanish Network on Mastocytosis (REMA) . 2004. Immunophenotypic analysis of mast cells in mastocytosis: when and how to do it. Cytometry B Clin Cytom 58 : 1 8.[CrossRef].[PubMed]
81. Akin C, Valent P, Escribano L . 2006. Urticaria pigmentosa and mastocytosis: the role of immunophenotyping in diagnosis and determining response to treatment. Curr Allergy Asthma Rep 6 : 282 288.[PubMed].[CrossRef]
82. Pardanani A, Kimlinger TK, Reeder TL, Li CY, Tefferi A . 2003. Differential expression of CD2 on neoplastic mast cells in patients with systemic mast cell disease with and without an associated clonal haematological disorder. Br J Haematol 120 : 691 694.[PubMed].[CrossRef]
83. Akin C, Metcalfe DD . 2004. The biology of Kit in disease and the application of pharmacogenetics. J Allergy Clin Immunol 114 : 13 20.[CrossRef].[PubMed]
84. Garcia-Montero AC, Jara-Acevedo M, Teodosio C, Sanchez ML, Nunez R, Prados A, Aldanondo I, Sanchez L, Dominguez M, Botana LM, Sanchez-Jimenez F, Sotlar K, Almeida J, Escribano L, Orfao A . 2006. KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients. Blood 108 : 2366 2372.[CrossRef].[PubMed]
85. Bodemer C, Hermine O, Palmérini F, Yang Y, Grandpeix-Guyodo C, Leventhal PS, Hadj-Rabia S, Nasca L, Georgin-Lavialle S, Cohen-Akenine A, Launay JM, Barete S, Feger F, Arock M, Catteau B, Sans B, Stalder JF, Skowron F, Thomas L, Lorette G, Plantin P, Bordigoni P, Lortholary O, de Prost Y, Moussy A, Sobol H, Dubreuil P . 2010. Pediatric mastocytosis is a clonal disease associated with D816V and other activating c-KIT mutations. J Invest Dermatol 130 : 804 815.[CrossRef].[PubMed]
86. Kristensen T, Vestergaard H, Møller MB . 2011. Improved detection of the KIT D816V mutation in patients with systemic mastocytosis using a quantitative and highly sensitive real-time qPCR assay. J Mol Diagn 13 : 180 188.[CrossRef].[PubMed]
87. Yavuz AS, Lipsky PE, Yavuz S, Metcalfe DD, Akin C . 2002. Evidence for the involvement of a hematopoietic progenitor cell in systemic mastocytosis from single-cell analysis of mutations in the c-kit gene. Blood 100 : 661 665.[CrossRef].[PubMed]
88. Schwartz LB . 2006. Diagnostic value of tryptase in anaphylaxis and mastocytosis. Immunol Allergy Clin North Am 26 : 451 463.[CrossRef].[PubMed]
89. Akin C, Scott LM, Kocabas CN, Kushnir-Sukhov N, Brittain E, Noel P, Metcalfe DD . 2007. Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with “idiopathic” anaphylaxis. Blood 110 : 2331 2333.[CrossRef].[PubMed]
90. Akin C, Fumo G, Yavuz AS, Lipsky PE, Neckers L, Metcalfe DD . 2004. A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib. Blood 103 : 3222 3225.[CrossRef].[PubMed]
91. Teodosio C, García-Montero AC, Jara-Acevedo M, Sánchez-Muñoz L, Alvarez-Twose I, Núñez R, Schwartz LB, Walls AF, Escribano L, Orfao A . 2010. Mast cells from different molecular and prognostic subtypes of systemic mastocytosis display distinct immunophenotypes. J Allergy Clin Immunol 125 : 719 726.e4.[CrossRef].[PubMed]
92. Akin C, Valent P, Metcalfe DD . 2010. Mast cell activation syndrome: proposed diagnostic criteria. J Allergy Clin Immunol 126 : 1099 1104.e4.[CrossRef].[PubMed]
93. Schwaab J, Schnittger S, Sotlar K, Walz C, Fabarius A, Pfirrmann M, Kohlmann A, Grossmann V, Meggendorfer M, Horny HP, Valent P, Jawhar M, Teichmann M, Metzgeroth G, Erben P, Ernst T, Hochhaus A, Haferlach T, Hofmann WK, Cross NC, Reiter A . 2013. Comprehensive mutational profiling in advanced systemic mastocytosis. Blood 122 : 2460 2466.[CrossRef].[PubMed]
94. Sperr WR, Jordan JH, Baghestanian M, Kiener HP, Samorapoompichit P, Semper H, Hauswirth A, Schernthaner GH, Chott A, Natter S, Kraft D, Valenta R, Schwartz LB, Geissler K, Lechner K, Valent P . 2001. Expression of mast cell tryptase by myeloblasts in a group of patients with acute myeloid leukemia. Blood 98 : 2200 2209.[PubMed].[CrossRef]
95. Georgin-Lavialle S, Lhermitte L, Dubreuil P, Chandesris MO, Hermine O, Damaj G . 2013. Mast cell leukemia. Blood 121 : 1285 1295.[CrossRef].[PubMed]
96. Bonadonna P, Perbellini O, Passalacqua G, Caruso B, Colarossi S, Dal Fior D, Castellani L, Bonetto C, Frattini F, Dama A, Martinelli G, Chilosi M, Senna G, Pizzolo G, Zanotti R . 2009. Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levels. J Allergy Clin Immunol 123 : 680 686.[CrossRef].[PubMed]
97. Alvarez-Twose I, González de Olano D, Sánchez-Muñoz L, Matito A, Esteban-López MI, Vega A, Mateo MB, Alonso Díaz de Durana MD, de la Hoz B, Del Pozo Gil MD, Caballero T, Rosado A, Sánchez Matas I, Teodósio C, Jara-Acevedo M, Mollejo M, García-Montero A, Orfao A, Escribano L . 2010. Clinical, biological, and molecular characteristics of clonal mast cell disorders presenting with systemic mast cell activation symptoms. J Allergy Clin Immunol 125 : 1269 1278.e2.[CrossRef].[PubMed]
98. Cardet JC, Akin C, Lee MJ . 2013. Mastocytosis: update on pharmacotherapy and future directions. Expert Opin Pharmacother 14 : 2033 2045.[CrossRef].[PubMed]
99. Valent P, Sperr WR, Akin C . 2010. How I treat patients with advanced systemic mastocytosis. Blood 116 : 5812 5817.[CrossRef].[PubMed]
100. Gromke T, Elmaagacli AH, Ditschkowski M, Hegerfeldt Y, Koldehoff M, Hlinka M, Ottinger H, Trenschel R, Beelen DW . 2013. Delayed graft-versus-mast-cell effect on systemic mastocytosis with associated clonal haematological non-mast cell lineage disease after allogeneic transplantation. Bone Marrow Transplant 48 : 732 733.[CrossRef].[PubMed]
101. Nakamura R, Chakrabarti S, Akin C, Robyn J, Bahceci E, Greene A, Childs R, Dunbar CE, Metcalfe DD, Barrett AJ . 2006. A pilot study of nonmyeloablative allogeneic hematopoietic stem cell transplant for advanced systemic mastocytosis. Bone Marrow Transplant 37 : 353 358.[CrossRef].[PubMed]
102. Ryan RJ, Akin C, Castells M, Wills M, Selig MK, Nielsen GP, Ferry JA, Hornick JL . 2013. Mast cell sarcoma: a rare and potentially under-recognized diagnostic entity with specific therapeutic implications. Mod Pathol 26 : 533 543.[CrossRef].[PubMed]
103. 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 Jan 21. doi:10.1111/all.12843. [Epub ahead of print][CrossRef] http://dx.doi.org/doi:10.1111/all.12843


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Secondary causes of marked eosinophilia

Citation: Akin C, Prussin C, Klion A. 2016. Diagnosis of Rare Eosinophilic and Mast Cell Disorders, p 825-837. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch85
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Evaluation of patients presumed to have HES

Citation: Akin C, Prussin C, Klion A. 2016. Diagnosis of Rare Eosinophilic and Mast Cell Disorders, p 825-837. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch85
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Classification of mastocytosis from reference

Citation: Akin C, Prussin C, Klion A. 2016. Diagnosis of Rare Eosinophilic and Mast Cell Disorders, p 825-837. In Detrick B, Schmitz J, Hamilton R (ed), Manual of Molecular and Clinical Laboratory Immunology, Eighth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555818722.ch85

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