Mast Cell Disorders and Anaphylaxis

  • Sharzad Alagheband
  • Catherine Cranford
  • Patricia StewartEmail author
Living reference work entry


Mast cells arise from pluripotent stem cells. From the original identification of mast cells in the late 1800s, our understanding of these cells’ normal function and role in pathologic disease has expanded greatly; and the understanding of mastocytosis has led to advances in classification and treatment of these diseases. The term mastocytosis describes a group of disorders characterized by abnormal proliferation of mast cells. Mast cell numbers are increased and pathologically infiltrate various organ systems, resulting in a spectrum of disorders from cutaneous mastocytosis (more common in children) to multiple subvariants of systemic mastocytosis, mast cell leukemia, and mastocytomas. Diagnostic criteria have been modified recently to aid in classifying the type of disease, which allows for better determination of both the prognosis and treatment. While treatment is largely symptomatic, with important focus on the management of anaphylaxis, several promising therapeutic targets and agents have recently been identified which may lead to improved survival in more advanced subtypes of disease. These therapies include several tyrosine kinase inhibitors which combat the activating KIT mutations present in most patients with aggressive mastocytosis.


Mastocytosis Mast cell Diagnostic criteria Tryptase KIT D816V 


  1. Abbas AK, Lichtman AHH, Pillai S. Cellular and molecular immunology E-Book. Philadelphia: Elsevier Health Sciences; 2017.Google Scholar
  2. Akin C. Mast cell activation syndromes. J Allergy Clin Immunol. 2017;140(2):349–55.PubMedCrossRefPubMedCentralGoogle Scholar
  3. Akin C, Valent P. Diagnostic criteria and classification of mastocytosis in 2014. Immunol Allergy Clin N Am. 2014;34(2):207–18.CrossRefGoogle Scholar
  4. Akin C, Valent P, Metcalfe DD. Mast cell activation syndrome: proposed diagnostic criteria. J Allergy Clin Immunol. 2010;126(6):1099–1104.e4.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Alandijani S, Casale TB, Ledford DK, Lockey RF. 3-generational familial tryptasemia with multiple clinical presentations. J Allergy Clin Immunol. 2017;139(2):AB166.CrossRefGoogle Scholar
  6. Alvarez-Twose I, et al. Imatinib in systemic mastocytosis: a phase IV clinical trial in patients lacking exon 17 KIT mutations and review of the literature. Oncotarget. 2016;8(40):68950–63.PubMedPubMedCentralGoogle Scholar
  7. Arber DA, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Arock M, et al. KIT mutation analysis in mast cell neoplasms: recommendations of the European Competence Network on Mastocytosis. Leukemia. 2015;29(6):1223–32.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Ashinoff R, Soter NA, Freedberg IM. Solitary mastocytoma in an adult. J Dermatol Surg Oncol. 1993;19(5):487–8.PubMedCrossRefPubMedCentralGoogle Scholar
  10. Barete S, et al. Systemic mastocytosis and bone involvement in a cohort of 75 patients. Ann Rheum Dis. 2010;69(10):1838–41.PubMedCrossRefPubMedCentralGoogle Scholar
  11. Barete S, et al. Long-term efficacy and safety of cladribine (2-CdA) in adult patients with mastocytosis. Blood. 2015;126(8):1009–16; quiz 1050.PubMedCrossRefPubMedCentralGoogle Scholar
  12. Beaven M. Our perception of the mast cell from Paul Ehrlich to now. Eur. J. Immunol. 2009;39(1):11–25.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Bell MC, Jackson DJ. Prevention of anaphylaxis related to mast cell activation syndrome with omalizumab. Ann Allergy Asthma Immunol. 2012;108(5):383–4.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Biosse-Duplan M, Baroukh B, Dy M, de Vernejoul M-C, Saffar J-L. Histamine promotes osteoclastogenesis through the differential expression of histamine receptors on osteoclasts and osteoblasts. Am J Pathol. 2009;174(4):1426–34.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Bonadonna P, et al. Venom immunotherapy in patients with clonal mast cell disorders: efficacy, safety, and practical considerations. J Allergy Clin Immunol Pract. 2013;1(5):474–8.PubMedCrossRefPubMedCentralGoogle Scholar
  16. Borate U, Mehta A, Reddy V, Tsai M, Josephson N, Schnadig I. Treatment of CD30-positive systemic mastocytosis with brentuximab vedotin. Leuk Res. 2016;44:25–31.PubMedCrossRefPubMedCentralGoogle Scholar
  17. Brazzelli V, et al. Narrow-band UVB phototherapy and psoralen-ultraviolet A photochemotherapy in the treatment of cutaneous mastocytosis: a study in 20 patients. Photodermatol Photoimmunol Photomed. 2016;32(5–6):238–46.PubMedCrossRefPubMedCentralGoogle Scholar
  18. Brockow K. Epidemiology, prognosis, and risk factors in mastocytosis. Immunol Allergy Clin N Am. 2014;34(2):283–95.CrossRefGoogle Scholar
  19. Brockow K, Metcalfe DD. Mastocytosis. Chemical Immunology and Allergy. 2010;95:110–24.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Brockow K, et al. Regression of urticaria pigmentosa in adult patients with systemic mastocytosis: correlation with clinical patterns of disease. Arch Dermatol. 2002;138(6):785–90.PubMedCrossRefPubMedCentralGoogle Scholar
  21. Brockow K, Jofer C, Behrendt H, Ring J. Anaphylaxis in patients with mastocytosis: a study on history, clinical features and risk factors in 120 patients. Allergy. 2008;63(2):226–32.PubMedCrossRefPubMedCentralGoogle Scholar
  22. Broesby-Olsen S, et al. Omalizumab prevents anaphylaxis and improves symptoms in systemic mastocytosis: efficacy and safety observations. Allergy. 2017;73(1):230–8.PubMedCrossRefPubMedCentralGoogle Scholar
  23. Butterfield JH. Response of severe systemic mastocytosis to interferon alpha. Br J Dermatol. 1998;138(3):489–95.PubMedCrossRefPubMedCentralGoogle Scholar
  24. Butterfield JH, Kao PC, Klee GG, Yocum MW. Aspirin idiosyncrasy in systemic mast cell disease: a new look at mediator release during aspirin desensitization. Mayo Clin Proc. 1995;70(5):481–7.PubMedCrossRefPubMedCentralGoogle Scholar
  25. Butterfield JH, Tefferi A, Kozuh GF. Successful treatment of systemic mastocytosis with high-dose interferon-alfa: long-term follow-up of a case. Leuk Res. 2005;29(2):131–4.PubMedCrossRefPubMedCentralGoogle Scholar
  26. Carter MC, Robyn JA, Bressler PB, Walker JC, Shapiro GG, Metcalfe DD. Omalizumab for the treatment of unprovoked anaphylaxis in patients with systemic mastocytosis. J Allergy Clin Immunol. 2007;119(6):1550–1.PubMedCrossRefPubMedCentralGoogle Scholar
  27. Carter MC, Metcalfe DD, Komarow HD. Mastocytosis. Immunol Allergy Clin N Am. 2014;34(1):181–96.CrossRefGoogle Scholar
  28. Castells MC, Irani AM, Schwartz LB. Evaluation of human peripheral blood leukocytes for mast cell tryptase. J Immunol. 1987;138(7):2184–9.PubMedPubMedCentralGoogle Scholar
  29. Chandesris M-O, et al. Midostaurin in advanced systemic mastocytosis. N Engl J Med. 2016;374(26):2605–7.PubMedCrossRefPubMedCentralGoogle Scholar
  30. Cohen SS, et al. Epidemiology of systemic mastocytosis in Denmark. Br J Haematol. 2014;166(4):521–8.PubMedCrossRefPubMedCentralGoogle Scholar
  31. Correia O, Duarte AF, Quirino P, Azevedo R, Delgado L. Cutaneous mastocytosis: two pediatric cases treated with topical pimecrolimus. Dermatol Online J. 2010;16(5):8.PubMedPubMedCentralGoogle Scholar
  32. Cruse G, Metcalfe DD, Olivera A. Functional deregulation of KIT: link to mast cell proliferative diseases and other neoplasms. Immunol Allergy Clin N Am. 2014;34(2):219–37.CrossRefGoogle Scholar
  33. de Melo Campos P, et al. Familial systemic mastocytosis with germline KIT K509I mutation is sensitive to treatment with imatinib, dasatinib and PKC412. Leuk Res. 2014;38(10):1245–51.PubMedCrossRefPubMedCentralGoogle Scholar
  34. DeAngelo DJ, et al. Efficacy and safety of midostaurin in patients with advanced systemic mastocytosis: 10-year median follow-up of a phase II trial. Leukemia. 2018;32(2):470–8.PubMedCrossRefGoogle Scholar
  35. Delaporte E, et al. Interferon-α in combination with corticosteroids improves systemic mast cell disease. Br J Dermatol. 1995;132(3):479–82.PubMedCrossRefGoogle Scholar
  36. Dobigny C, Saffar J-L. H1 and H2 histamine receptors modulate osteoclastic resorption by different pathways: evidence obtained by using receptor antagonists in a rat synchronized resorption model. J Cell Physiol. 1997;173(1):10–8.PubMedCrossRefPubMedCentralGoogle Scholar
  37. Doyle LA, Hornick JL. Pathology of extramedullary mastocytosis. Immunol Allergy Clin N Am. 2014;34(2):323–39.CrossRefGoogle Scholar
  38. Ellis JM. Urticaria pigmentosa; a report of a case with autopsy. Arch Pathol. 1949;48(5):426–35.Google Scholar
  39. Escribano L, et al. Immunophenotypic characterization of human bone marrow mast cells. A flow cytometric study of normal and pathological bone marrow samples. Anal Cell Pathol. 1998;16(3):151–9.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Escribano L, Akin C, Castells M, Schwartz LB. Current options in the treatment of mast cell mediator-related symptoms in mastocytosis. Inflamm Allergy Drug Targets. 2006;5(1):61–77.PubMedCrossRefGoogle Scholar
  41. Fabbro D, et al. PKC412 – a protein kinase inhibitor with a broad therapeutic potential. Anticancer Drug Des. 2000;15(1):17–28.PubMedGoogle Scholar
  42. Franklin Adkinson N Jr, et al. Middleton’s allergy E-book: principles and practice. London: Elsevier Health Sciences; 2013.Google Scholar
  43. Garriga MM, Friedman MM, Metcalfe DD. A survey of the number and distribution of mast cells in the skin of patients with mast cell disorders. J Allergy Clin Immunol. 1988;82(3 Pt 1):425–32.PubMedCrossRefPubMedCentralGoogle Scholar
  44. Godt O, Proksch E, Streit V, Christophers E. Short- and long-term effectiveness of oral and bath PUVA therapy in urticaria pigmentosa and systemic mastocytosis. Dermatology. 1997;195(1):35–9.PubMedCrossRefPubMedCentralGoogle Scholar
  45. González de Olano D, et al. Safety and effectiveness of immunotherapy in patients with indolent systemic mastocytosis presenting with Hymenoptera venom anaphylaxis. J Allergy Clin Immunol. 2008;121(2):519–26.PubMedCrossRefPubMedCentralGoogle Scholar
  46. Gotlib J. Tyrosine kinase inhibitors in the treatment of eosinophilic neoplasms and systemic mastocytosis. Hematol Oncol Clin North Am. 2017;31(4):643–61.PubMedCrossRefPubMedCentralGoogle Scholar
  47. Gotlib J, et al. Efficacy and safety of midostaurin in advanced systemic mastocytosis. N Engl J Med. 2016;374(26):2530–41.PubMedCrossRefPubMedCentralGoogle Scholar
  48. Growney JD, et al. Activation mutations of human c-KIT resistant to imatinib mesylate are sensitive to the tyrosine kinase inhibitor PKC412. Blood. 2005;106(2):721–4.PubMedPubMedCentralCrossRefGoogle Scholar
  49. Gülen T, Hägglund H, Dahlén B, Nilsson G. Mastocytosis: the puzzling clinical spectrum and challenging diagnostic aspects of an enigmatic disease. J Intern Med. 2016;279(3):211–28.PubMedCrossRefPubMedCentralGoogle Scholar
  50. Hartmann K, et al. Cutaneous manifestations in patients with mastocytosis: Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology. J Allergy Clin Immunol. 2016;137(1):35–45.PubMedCrossRefPubMedCentralGoogle Scholar
  51. Hauswirth AW, et al. Response to therapy with interferon alpha-2b and prednisolone in aggressive systemic mastocytosis: report of five cases and review of the literature. Leuk Res. 2004;28(3):249–57.PubMedCrossRefPubMedCentralGoogle Scholar
  52. Heide R, et al. Mastocytosis in children: a protocol for management. Pediatr Dermatol. 2008;25(4):493–500.PubMedCrossRefPubMedCentralGoogle Scholar
  53. Hermans MAW, et al. Management around invasive procedures in mastocytosis: an update. Ann Allergy Asthma Immunol. 2017;119(4):304–9.PubMedCrossRefPubMedCentralGoogle Scholar
  54. Hermine O, et al. Case-control cohort study of patients’ perceptions of disability in mastocytosis. PLoS One. 2008;3(5):e2266.PubMedPubMedCentralCrossRefGoogle Scholar
  55. Hochhaus A, et al. Nilotinib in patients with systemic mastocytosis: analysis of the phase 2, open-label, single-arm nilotinib registration study. J Cancer Res Clin Oncol. 2015;141(11):2047–60.PubMedPubMedCentralCrossRefGoogle Scholar
  56. Horan RF, Sheffer AL, Austen KF. Cromolyn sodium in the management of systemic mastocytosis. J Allergy Clin Immunol. 1990;85(5):852–5.PubMedCrossRefPubMedCentralGoogle Scholar
  57. Horny HP, et al. Diagnostic value of immunostaining for tryptase in patients with mastocytosis. Am J Surg Pathol. 1998;22(9):1132–40.PubMedCrossRefPubMedCentralGoogle Scholar
  58. Horny H-P, Sotlar K, Valent P. Mastocytosis: immunophenotypical features of the transformed mast cells are unique among hematopoietic cells. Immunol Allergy Clin N Am. 2014;34(2):315–21.CrossRefGoogle Scholar
  59. International Agency for Research on Cancer and World Health Organization. WHO classification of tumours of haematopoietic and lymphoid tissues. World Health Organization; Lyon, France. 2008.Google Scholar
  60. Jawhar M, et al. Molecular profiling of myeloid progenitor cells in multi-mutated advanced systemic mastocytosis identifies KIT D816V as a distinct and late event. Leukemia. 2015;29(5):1115–22.PubMedCrossRefPubMedCentralGoogle Scholar
  61. Klaiber N, Kumar S, Irani A-M. Mastocytosis in children. Curr Allergy Asthma Rep. 2017;17(11):80.PubMedCrossRefPubMedCentralGoogle Scholar
  62. Kluin-Nelemans HC, et al. Response to interferon alfa-2b in a patient with systemic mastocytosis. N Engl J Med. 1992;326(9):619–23.PubMedCrossRefPubMedCentralGoogle Scholar
  63. Kovalszki A, Weller PF. Eosinophilia in mast cell disease. Immunol Allergy Clin N Am. 2014;34(2):357–64.CrossRefGoogle Scholar
  64. Krauth M-T, Mirkina I, Herrmann H, Baumgartner C, Kneidinger M, Valent P. Midostaurin (PKC412) inhibits immunoglobulin E-dependent activation and mediator release in human blood basophils and mast cells. Clin Exp Allergy. 2009;39(11):1711–20.PubMedCrossRefPubMedCentralGoogle Scholar
  65. Lange M, Niedoszytko M, Nedoszytko B, Łata J, Trzeciak M, Biernat W. Diffuse cutaneous mastocytosis: analysis of 10 cases and a brief review of the literature. J Eur Acad Dermatol Venereol. 2012;26(12):1565–71.PubMedPubMedCentralGoogle Scholar
  66. Laroche M, Livideanu C, Paul C, Cantagrel A. Interferon alpha and pamidronate in osteoporosis with fracture secondary to mastocytosis. Am J Med. 2011;124(8):776–8.PubMedCrossRefPubMedCentralGoogle Scholar
  67. Lehmann T, et al. Severe osteoporosis due to systemic mast cell disease: successful treatment with interferon alpha-2B. Br J Rheumatol. 1996;35(9):898–900.PubMedCrossRefPubMedCentralGoogle Scholar
  68. Lehner E. II. Beiträge zur Klinik und Histologie der Urticaria pigmentosa. Dermatology. 1926;46(2):87–93.CrossRefGoogle Scholar
  69. Lieberoth S, Thomsen SF. Cutaneous and gastrointestinal symptoms in two patients with systemic mastocytosis successfully treated with omalizumab. Case Rep Med. 2015;2015:903541.PubMedPubMedCentralCrossRefGoogle Scholar
  70. Lim JL, Stern RS. High levels of ultraviolet B exposure increase the risk of non-melanoma skin cancer in psoralen and ultraviolet A-treated patients. J Invest Dermatol. 2005;124(3):505–13.PubMedCrossRefPubMedCentralGoogle Scholar
  71. Lim AYN, Ostor AJK, Love S, Crisp AJ. Systemic mastocytosis: a rare cause of osteoporosis and its response to bisphosphonate treatment. Ann Rheum Dis. 2005;64(6):965–6.PubMedPubMedCentralCrossRefGoogle Scholar
  72. Lim KH, Pardanani A, Butterfield JH, Li C-Y, Tefferi A. Cytoreductive therapy in 108 adults with systemic mastocytosis: outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine. Am J Hematol. 2009;84(12):790–4.PubMedCrossRefPubMedCentralGoogle Scholar
  73. Lock AD, McNamara CJ, Rustin MHA. Sustained improvement in urticaria pigmentosa and pruritus in a case of indolent systemic mastocytosis treated with cladribine. Clin Exp Dermatol. 2014;40(2):142–5.PubMedCrossRefPubMedCentralGoogle Scholar
  74. Lortholary O, et al. Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study. Lancet. 2017;389(10069):612–20.PubMedPubMedCentralCrossRefGoogle Scholar
  75. Lyons JJ, et al. Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number. Nat Genet. 2016;48(12):1564–9.PubMedPubMedCentralCrossRefGoogle Scholar
  76. Maeda H, et al. Requirement of c-kit for development of intestinal pacemaker system. Development. 1992;116(2):369–75.PubMedPubMedCentralGoogle Scholar
  77. Markey AC, Churchill LJ, MacDonald DM. Human cutaneous mast cells – a study of fixative and staining reactions in normal skin. Br J Dermatol. 1989;120(5):625–31.PubMedCrossRefPubMedCentralGoogle Scholar
  78. Matito A, et al. Management of anesthesia in adult and pediatric mastocytosis: a study of the Spanish Network on Mastocytosis (REMA) based on 726 anesthetic procedures. Int Arch Allergy Immunol. 2015;167(1):47–56.PubMedCrossRefPubMedCentralGoogle Scholar
  79. Matito A, Azaña JM, Torrelo A, Alvarez-Twose I. Cutaneous mastocytosis in adults and children: new classification and prognostic factors. Immunol Allergy Clin N Am. 2018;38(3):351–63.CrossRefGoogle Scholar
  80. Méni C, et al. Paediatric mastocytosis: a systematic review of 1747 cases. Br J Dermatol. 2015;172(3):642–51.PubMedCrossRefPubMedCentralGoogle Scholar
  81. Metcalfe DD. Classification and diagnosis of mastocytosis: current status. J Invest Dermatol. 1991a;96(3):2S–4S.PubMedCrossRefPubMedCentralGoogle Scholar
  82. Metcalfe DD. The liver, spleen, and lymph nodes in mastocytosis. J Invest Dermatol. 1991b;96(3):45S–6S.PubMedCrossRefPubMedCentralGoogle Scholar
  83. Monnier J, et al. Mast cell sarcoma: new cases and literature review. Oncotarget. 2016;7(40):66299–309.PubMedPubMedCentralCrossRefGoogle Scholar
  84. Morgado JMT, et al. Immunophenotyping in systemic mastocytosis diagnosis: ‘CD25 positive’ alone is more informative than the ‘CD25 and/or CD2’ WHO criterion. Mod Pathol. 2012;25(4):516–21.PubMedCrossRefPubMedCentralGoogle Scholar
  85. Moura DS, Georgin-Lavialle S, Gaillard R, Hermine O. Neuropsychological features of adult mastocytosis. Immunol Allergy Clin N Am. 2014;34(2):407–22.CrossRefGoogle Scholar
  86. Naumann N, et al. Incidence and prognostic impact of cytogenetic aberrations in patients with systemic mastocytosis. Genes Chromosom Cancer. 2018;57:252–9.PubMedCrossRefPubMedCentralGoogle Scholar
  87. Nettleship E. RARE CASES OF IRITIS IN CHILDREN NEAR THE AGE OF PUBERTY. WITH REMARKS. Lancet. 1876;107(2733):86–7.CrossRefGoogle Scholar
  88. Nicoloro-SantaBarbara J, Lobel M, Wolfe D. Psychosocial impact of mast cell disorders: pilot investigation of a rare and understudied disease. J Health Psychol. 2017;22(10):1277–88.PubMedCrossRefPubMedCentralGoogle Scholar
  89. Onnes MC, Tanno LK, Elberink JNGO. Mast cell clonal disorders: classification, diagnosis and management. Curr Treat Options Allergy. 2016;3(4):453–64.PubMedPubMedCentralCrossRefGoogle Scholar
  90. Pardanani A. Systemic mastocytosis in adults: 2017 update on diagnosis, risk stratification and management. Am J Hematol. 2016;91(11):1146–59.PubMedCrossRefPubMedCentralGoogle Scholar
  91. Pardanani A, et al. Prognostically relevant breakdown of 123 patients with systemic mastocytosis associated with other myeloid malignancies. Blood. 2009;114(18):3769–72.PubMedCrossRefPubMedCentralGoogle Scholar
  92. Pardanani A, Finke C, Abdelrahman RA, Lasho TL, Hanson CA, Tefferi A. Increased circulating IL-2Rα (CD25) predicts poor outcome in both indolent and aggressive forms of mastocytosis: a comprehensive cytokine–phenotype study. Leukemia. 2013;27(6):1430–3.PubMedCrossRefPubMedCentralGoogle Scholar
  93. Parker RI. Hematologic aspects of mastocytosis: I: bone marrow pathology in adult and pediatric systemic mast cell disease. J Invest Dermatol. 1991;96(3):47S–51S.PubMedCrossRefPubMedCentralGoogle Scholar
  94. Parker RI. Hematologic aspects of systemic mastocytosis. Hematol Oncol Clin North Am. 2000;14(3):557–68.PubMedCrossRefPubMedCentralGoogle Scholar
  95. Rose S. Rapid Responses to Avapritinib (BLU-285) in Mastocytosis. Cancer Discov. 2018;8(2):133.Google Scholar
  96. Ribatti D. The development of human mast cells. An historical reappraisal. Exp Cell Res. 2016;342(2):210–5.PubMedCrossRefPubMedCentralGoogle Scholar
  97. Rogers MP, Bloomingdale K, Murawski BJ, Soter NA, Reich P, Austen KF. Mixed organic brain syndrome as a manifestation of systemic mastocytosis. Psychosom Med. 1986;48(6):437–47.PubMedCrossRefPubMedCentralGoogle Scholar
  98. Rossini M, et al. Bone mineral density, bone turnover markers and fractures in patients with indolent systemic mastocytosis. Bone. 2011;49(4):880–5.PubMedCrossRefPubMedCentralGoogle Scholar
  99. Rossini M, et al. Bone involvement and osteoporosis in mastocytosis. Immunol Allergy Clin N Am. 2014;34(2):383–96.CrossRefGoogle Scholar
  100. Rossini M, et al. Prevalence, pathogenesis, and treatment options for mastocytosis-related osteoporosis. Osteoporos Int. 2016;27(8):2411–21.PubMedCrossRefPubMedCentralGoogle Scholar
  101. Rothe MJ, Grant-Kels JM, Makkar HS. Mast cell disorders: kids are not just little people. Clin Dermatol. 2016;34(6):760–6.PubMedCrossRefPubMedCentralGoogle Scholar
  102. Ruëff F, Placzek M, Przybilla B. Mastocytosis and Hymenoptera venom allergy. Curr Opin Allergy Clin Immunol. 2006;6(4):284–8.PubMedCrossRefPubMedCentralGoogle Scholar
  103. Sadashiv S, Bower K, Bower K, Sahovic E, Bunker M, Christou A. Use of octreotide for relief of gastro-intestinal (GI) symptoms in systemic mastocytosis. Hematol Oncol Stem Cell Ther. 2013;6(2):72–5.PubMedCrossRefPubMedCentralGoogle Scholar
  104. Schuch A, Brockow K. Mastocytosis and anaphylaxis. Immunol Allergy Clin N Am. 2017;37(1):153–64.CrossRefGoogle Scholar
  105. Schwaab J, et al. Comprehensive mutational profiling in advanced systemic mastocytosis. Blood. 2013;122(14):2460–6.PubMedCrossRefPubMedCentralGoogle Scholar
  106. Shih AR, Deshpande V, Ferry JA, Zukerberg L. Clinicopathological characteristics of systemic mastocytosis in the intestine. Histopathology. 2016;69(6):1021–7.PubMedCrossRefPubMedCentralGoogle Scholar
  107. Siebenhaar F, Kühn W, Zuberbier T, Maurer M. Successful treatment of cutaneous mastocytosis and Ménière disease with anti-IgE therapy. J Allergy Clin Immunol. 2007;120(1):213–5.PubMedCrossRefPubMedCentralGoogle Scholar
  108. Siebenhaar F, et al. Rupatadine improves quality of life in mastocytosis: a randomized, double-blind, placebo-controlled trial. Allergy. 2013;68(7):949–52.PubMedCrossRefPubMedCentralGoogle Scholar
  109. Siebenhaar F, Akin C, Bindslev-Jensen C, Maurer M, Broesby-Olsen S. Treatment strategies in mastocytosis. Immunol Allergy Clin N Am. 2014;34(2):433–47.CrossRefGoogle Scholar
  110. Simon J, et al. Interest of interferon alpha in systemic mastocytosis. The French experience and review of the literature. Pathol Biol. 2004;52(5):294–9.PubMedCrossRefPubMedCentralGoogle Scholar
  111. Simons FER, et al. World Allergy Organization Anaphylaxis Guidelines: 2013 update of the evidence base. Int Arch Allergy Immunol. 2013;162(3):193–204.PubMedCrossRefPubMedCentralGoogle Scholar
  112. Simons FER, et al. 2015 update of the evidence base: World Allergy Organization anaphylaxis guidelines. World Allergy Organ J. 2015;8(1):32.PubMedPubMedCentralCrossRefGoogle Scholar
  113. Sokol H, et al. Gastrointestinal involvement and manifestations in systemic mastocytosis. Inflamm Bowel Dis. 2010;16(7):1247–53.PubMedCrossRefPubMedCentralGoogle Scholar
  114. Sokol H, et al. Gastrointestinal manifestations in mastocytosis: a study of 83 patients. J Allergy Clin Immunol. 2013;132(4):866–73.e1–3.PubMedCrossRefPubMedCentralGoogle Scholar
  115. Sokol KC, Ghazi A, Kelly BC, Grant JA. Omalizumab as a desensitizing agent and treatment in mastocytosis: a review of the literature and case report. J Allergy Clin Immunol Pract. 2014;2(3):266–70.PubMedCrossRefPubMedCentralGoogle Scholar
  116. Soter NA, Frank Austen K, Wasserman SI. Oral disodium cromoglycate in the treatment of systemic mastocytosis. N Engl J Med. 1979;301(9):465–9.PubMedCrossRefPubMedCentralGoogle Scholar
  117. Sotlar K, et al. CD25 indicates the neoplastic phenotype of mast cells. Am J Surg Pathol. 2004;28(10):1319–25.PubMedCrossRefPubMedCentralGoogle Scholar
  118. Sotlar K, et al. Aberrant expression of CD30 in neoplastic mast cells in high-grade mastocytosis. Mod Pathol. 2011;24(4):585–95.PubMedCrossRefPubMedCentralGoogle Scholar
  119. Sperr WR, et al. Elevated tryptase levels selectively cluster in myeloid neoplasms: a novel diagnostic approach and screen marker in clinical haematology. Eur J Clin Investig. 2009;39(10):914–23.CrossRefGoogle Scholar
  120. Sukrithan VK, Salamon JN, Berulava G, Sibinga NE, Verma A. Systemic mastocytosis presenting as cardiac tamponade with CD25(+) pericardial mast cells. Clin Case Rep. 2016;4(3):279–81.PubMedPubMedCentralCrossRefGoogle Scholar
  121. Theoharides TC, Valent P, Akin C. Mast cells, mastocytosis, and related disorders. N Engl J Med. 2015;373(2):163–72.PubMedCrossRefPubMedCentralGoogle Scholar
  122. Thompson JH. A CASE OF FACTITIOUS URTICARIA. Lancet. 1893;141(3634):924.CrossRefGoogle Scholar
  123. Travis WD, Li CY, Bergstralh EJ, Yam LT, Swee RG. Systemic mast cell disease. Analysis of 58 cases and literature review. Medicine. 1988;67(6):345–68.PubMedCrossRefPubMedCentralGoogle Scholar
  124. Turner PJ, Kemp AS, Rogers M, Mehr S. Refractory symptoms successfully treated with leukotriene inhibition in a child with systemic mastocytosis. Pediatr Dermatol. 2011;29(2):222–3.PubMedCrossRefPubMedCentralGoogle Scholar
  125. Ustun C, et al. Hematopoietic stem-cell transplantation for advanced systemic mastocytosis. J Clin Oncol. 2014;32(29):3264–74.PubMedPubMedCentralCrossRefGoogle Scholar
  126. Uzzaman A, Maric I, Noel P, Kettelhut BV, Metcalfe DD, Carter MC. Pediatric-onset mastocytosis: a long term clinical follow-up and correlation with bone marrow histopathology. Pediatr Blood Cancer. 2009;53(4):629–34.PubMedPubMedCentralCrossRefGoogle Scholar
  127. Valent P. Diagnosis and management of mastocytosis: an emerging challenge in applied hematology. Hematology Am Soc Hematol Educ Program. 2015;2015:98–105.PubMedCrossRefPubMedCentralGoogle Scholar
  128. Valent P, et al. Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res. 2001;25(7):603–25.PubMedCrossRefPubMedCentralGoogle Scholar
  129. Valent P, Sperr WR, Schwartz LB, Horny H-P. Diagnosis and classification of mast cell proliferative disorders: delineation from immunologic diseases and non-mast cell hematopoietic neoplasms. J Allergy Clin Immunol. 2004;114(1):3–11; quiz 12.PubMedCrossRefPubMedCentralGoogle Scholar
  130. Valent P, et al. Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria. Eur J Clin Investig. 2007;37(6):435–53.CrossRefGoogle Scholar
  131. Valent P, Akin C, Metcalfe DD. Mastocytosis: 2016 updated WHO classification and novel emerging treatment concepts. Blood. 2017a;129(11):1420–7.PubMedPubMedCentralCrossRefGoogle Scholar
  132. Valent P, et al. Advances in the classification and treatment of mastocytosis: current status and outlook toward the future. Cancer Res. 2017b;77(6):1261–70.PubMedPubMedCentralCrossRefGoogle Scholar
  133. Valent P, et al. Midostaurin: a magic bullet that blocks mast cell expansion and activation. Ann Oncol. 2017c;28(10):2367–76.PubMedCrossRefPubMedCentralGoogle Scholar
  134. van den Elzen MT, et al. Effectiveness and safety of antihistamines up to fourfold or higher in treatment of chronic spontaneous urticaria. Clin Transl Allergy. 2017;7(1):4.PubMedPubMedCentralCrossRefGoogle Scholar
  135. van Doormaal JJ, et al. Prevalence of indolent systemic mastocytosis in a Dutch region. J Allergy Clin Immunol. 2013;131(5):1429–1431.e1.PubMedCrossRefPubMedCentralGoogle Scholar
  136. Vega-Ruiz A, et al. Phase II study of imatinib mesylate as therapy for patients with systemic mastocytosis. Leuk Res. 2009;33(11):1481–4.PubMedPubMedCentralCrossRefGoogle Scholar
  137. Veien M, Szlam F, Holden JT, Yamaguchi K, Denson DD, Levy JH. Mechanisms of nonimmunological histamine and tryptase release from human cutaneous mast cells. Anesthesiology. 2000;92(4):1074–81.PubMedCrossRefPubMedCentralGoogle Scholar
  138. Vieira dos Santos R, et al. Topical sodium cromoglicate relieves allergen- and histamine-induced dermal pruritus. Br J Dermatol. 2010;162(3):674–6.PubMedCrossRefPubMedCentralGoogle Scholar
  139. Weiler CR, Butterfield J. Mast cell sarcoma: clinical management. Immunol Allergy Clin N Am. 2014;34(2):423–32.CrossRefGoogle Scholar
  140. Wiechers T, et al. Large maculopapular cutaneous lesions are associated with favorable outcome in childhood-onset mastocytosis. J Allergy Clin Immunol. 2015;136(6):1581–1590.e3.PubMedCrossRefGoogle Scholar
  141. Wolff K, Komar M, Petzelbauer P. Clinical and histopathological aspects of cutaneous mastocytosis. Leuk Res. 2001;25(7):519–28.PubMedCrossRefGoogle Scholar
  142. Zaheer S, LeBoff M, Lewiecki EM. Denosumab for the treatment of osteoporosis. Expert Opin Drug Metab Toxicol. 2015;11(3):461–70.PubMedPubMedCentralCrossRefGoogle Scholar
  143. Zhang LY, et al. A novel K509I mutation of KIT identified in familial mastocytosis-in vitro and in vivo responsiveness to imatinib therapy. Leuk Res. 2006;30(4):373–8.PubMedCrossRefPubMedCentralGoogle Scholar
  144. Zuberbier T, et al. The EAACI/GA2LEN/EDF/WAO guideline for the definition, classification, diagnosis, and management of urticaria: the 2013 revision and update. Allergy. 2014;69(7):868–87.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Sharzad Alagheband
    • 1
  • Catherine Cranford
    • 1
  • Patricia Stewart
    • 1
    Email author
  1. 1.Department of Medicine, Division of Clinical Immunology and AllergyUniversity of Mississippi Medical CenterJacksonUSA

Section editors and affiliations

  • Dennis K. Ledford
    • 1
  1. 1.Division of Allergy & Immunology, Dept. of Internal MedicineUniversity of South Florida Morsani College of Medicine, James A Haley Veterans' Hospital, Asthma and Immunology Associates of Tampa BayTampaUSA

Personalised recommendations