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Mastocytosis and Mast Cell Activation Syndromes Presenting as Anaphylaxis

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Anaphylaxis and Hypersensitivity Reactions

Abstract

Anaphylaxis results from mast cell degranulation induced by allergen-specific IgE as well as various non-IgE-mediated mechanisms. It has been recently demonstrated that intrinsic abnormalities in mast cells, such as presence of activating D816V c-kit mutation, may influence susceptibility to anaphylaxis, especially in patients with “idiopathic” or hymenoptera-induced anaphylaxis. However, despite an improved understanding of the role of clonal mast cell disease in susceptibility to anaphylaxis, the basis of an apparent increase in susceptibility in the majority of patients remains poorly understood. In this chapter, we will review the potential mechanisms of mast cell activation as well as the range of symptoms and the differential diagnosis of patients suspected of having a disease caused by mast cell activation. In addition, we offer a global classification for disorders involving mast cells.

This work was in part supported by the Division of Intramural Research of the NIH/NIAID.

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References

  1. Williams CM, Galli SJ. The diverse potential effector and immunoregulatory roles of mast cells in allergic disease. J Allergy Clin Immunol. 2000;105:847.

    Article  PubMed  CAS  Google Scholar 

  2. Bachelet I, Levi-Schaffer F, Mekori YA. Mast cells: not only in allergy. Immunol Allergy Clin North. 2006;26:407.

    Article  Google Scholar 

  3. Kitamura Y, Oboki K, Ito A. Molecular mechanisms of mast cell development. Immunol Allergy Clin North Am. 2006;26:387.

    Article  PubMed  Google Scholar 

  4. Galli SJ, Maurer M, Lantz CS. Mast cells as sentinels of innate immunity. Curr Opin Immunol. 1999;11:53.

    Article  PubMed  CAS  Google Scholar 

  5. Okayama Y, Kirshenbaum AS, Metcalfe DD. Expression of a functional high-affinity IgG receptor, Fc gamma RI, on human mast cells: Up-regulation by IFN-gamma. J Immunol. 2000;164:4332.

    PubMed  CAS  Google Scholar 

  6. Kiener HP, Baghestanian M, Dominkus M, et al. Expression of the C5a receptor (CD88) on synovial mast cells in patients with rheumatoid arthritis. Arthritis Rheum. 1998;41:233.

    Article  PubMed  CAS  Google Scholar 

  7. el-Lati SG, Dahinden CA, Church MK. Complement peptides C3a- and C5a-induced mediator release from dissociated human skin mast cells. J Invest Dermatol. 1994;102:803.

    Article  PubMed  CAS  Google Scholar 

  8. Fureder W, Agis H, Willheim M, et al. Differential expression of complement receptors on human basophils and mast cells. Evidence for mast cell heterogeneity and CD88/C5aR expression on skin mast cells. J Immunol. 1995;155:3152.

    PubMed  CAS  Google Scholar 

  9. Kulka M, Alexopoulou L, Flavell RA, Metcalfe DD. Activation of mast cells by double-stranded RNA: evidence for activation through Toll-like receptor 3. J Allergy Clin Immunol. 2004;114:174.

    Article  PubMed  CAS  Google Scholar 

  10. Hermens JM, Ebertz JM, Hanifin JM, Hirshman CA. Comparison of histamine release in human skin mast cells induced by morphine, fentanyl, and oxymorphone. Anesthesiology. 1985;62:124.

    Article  PubMed  CAS  Google Scholar 

  11. Spicuzza L, Di Maria G, Polosa R. Adenosine in the airways: implications and applications. Eur J Pharmacol. 2006;533:77.

    Article  PubMed  CAS  Google Scholar 

  12. Galli SJ, Tsai M, Wershil BK, et al. Regulation of mouse and human mast cell development, survival and function by stem cell factor, the ligand for the c-kit receptor. Int Arch Allergy Immunol. 1995;107:51.

    Article  PubMed  CAS  Google Scholar 

  13. Xia HZ, Du Z, Craig S, et al. Effect of recombinant human IL-4 on tryptase, chymase, and Fc epsilon receptor type I expression in recombinant human stem cell factor- dependent fetal liver-derived human mast cells. J Immunol. 1997; 159:2911.

    PubMed  CAS  Google Scholar 

  14. Ahn, K, Takai, S, Pawankar, R, et al. Regulation of chymase production in human mast cell progenitors. J Allergy Clin Immunol. 2000;106:321

    Article  PubMed  CAS  Google Scholar 

  15. Castells M. Mast cell mediators in allergic inflammation and mastocytosis. Immunol Allergy Clin North Am. 2006;26:465.

    Article  PubMed  Google Scholar 

  16. Finotto S, Mekori YA, Metcalfe DD. Glucocorticoids decrease tissue mast cell number by reducing the production of the c-kit ligand, stem cell factor, by resident cells: in vitro and in vivo evidence in murine systems. J Clin Invest. 1997;99:1721.

    Article  PubMed  CAS  Google Scholar 

  17. Zhu D, Kepley CL, Zhang K, et al. A chimeric human-cat fusion protein blocks cat-induced allergy. Nat Med. 2005;11:446.

    Article  PubMed  CAS  Google Scholar 

  18. Katz HR, Vivier E, Castells MC, et al. Mouse mast cell gp49B1 contains two immunoreceptor tyrosine-based inhibition motifs and suppresses mast cell activation when coligated with the high-affinity Fc receptor for IgE. Proc Natl Acad Sci USA. 1996;93:10809.

    Article  PubMed  CAS  Google Scholar 

  19. Valent P, Horny H, Escribano L, et al. Diagnostic criteria and classification of mastocytosis: a consensus proposal. Leuk Res. 2001;25:603.

    Article  PubMed  CAS  Google Scholar 

  20. Webb LM, Lieberman P. Anaphylaxis: a review of 601 cases. Ann Allergy Asthma Immunol. 2006;97:39.

    Article  PubMed  Google Scholar 

  21. Valent P, Akin C, Escribano L, et al. Standards and standardization in mastocytosis: Consensus statements on diagnostics, treatment recommendations, and response criteria. Eur J Clin Invest. 2007;37:435.

    Article  PubMed  CAS  Google Scholar 

  22. Metcalfe DD. Differential diagnosis of the patient with unexplained flushing/anaphylaxis. Allergy Asthma Proc. 2000;21:21.

    Article  PubMed  CAS  Google Scholar 

  23. Bradding P, Walls AF, Holgate ST. The role of the mast cell in the pathophysiology of asthma. J Allergy Clin Immunol. 2006;117:1277.

    Article  PubMed  CAS  Google Scholar 

  24. Pumphrey RS. Lessons for management of anaphylaxis from a study of fatal reactions. Clin Exp Allergy. 2000;30:1144.

    Article  PubMed  CAS  Google Scholar 

  25. Sampson HA, Mendelson L, Rosen JP. Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med. 1992;327:380.

    Article  PubMed  CAS  Google Scholar 

  26. Amin HS, Liss GM, Bernstein DI. Evaluation of near-fatal reactions to allergen immunotherapy injections. J Allergy Clin Immunol. 2006;117:169.

    Article  PubMed  Google Scholar 

  27. Parikh SA, Cho SH, Oh CK. Preformed enzymes in mast cell granules and their potential role in allergic rhinitis. Curr Allergy Asthma Rep. 2003;3:266.

    Article  PubMed  Google Scholar 

  28. Akin C, Metcalfe DD. Systemic mastocytosis. Annu Rev Med. 2004;55:419.

    Article  PubMed  CAS  Google Scholar 

  29. Lindstedt KA, Kovanen PT. Mast cells in vulnerable coronary plaques: potential mechanisms linking mast cell activation to plaque erosion and rupture. Curr Opin Lipidol. 2004;15:567.

    Article  PubMed  CAS  Google Scholar 

  30. Jensen RT. Gastrointestinal abnormalities and involvement in systemic mastocytosis. Hematol Oncol Clin North Am. 2000;14:579.

    Article  PubMed  CAS  Google Scholar 

  31. Siegert SI, Diebold J, Ludolph-Hauser D, Lohrs U. Are gastrointestinal mucosal mast cells increased in patients with systemic mastocytosis? Am J Clin Pathol. 2004;122:560.

    Article  PubMed  Google Scholar 

  32. Ferguson J, Thompson RP, Greaves MW. Intestinal mucosal mast cells: enumeration in urticaria pigmentosa and systemic mastocytosis. Br J Dermatol. 1988;119:573.

    Article  PubMed  CAS  Google Scholar 

  33. Tetlow LC, Woolley DE. Mast cells, cytokines, and metalloproteinases at the rheumatoid lesion: dual immunolocalisation studies. Ann Rheum Dis. 1995;54:896.

    Article  PubMed  CAS  Google Scholar 

  34. Theoharides TC, Kempuraj D, Sant GR. Mast cell involvement in interstitial cystitis: a review of human and experimental evidence. Urology. 2001;57:47.

    Article  PubMed  CAS  Google Scholar 

  35. Parker RI. Hematologic aspects of mastocytosis: I: Bone marrow pathology in adult and pediatric systemic mast cell disease. J Invest Dermatol. 1991;96:47S.

    Article  Google Scholar 

  36. Akin C. Molecular diagnosis of mast cell disorders: a paper from the 2005 William Beaumont Hospital Symposium on Molecular Pathology. J Mol Diagn. 2006;8:412.

    Article  PubMed  CAS  Google Scholar 

  37. Akin C, Metcalfe DD. Occult bone marrow mastocytosis presenting as recurrent systemic anaphylaxis [abstract]. J Allergy Clin Immunol. 2003;111:S206.

    Article  Google Scholar 

  38. Akin C, Scott LM, Kocabas CN, et al. Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with “idiopathic” anaphylaxis. Blood. 2007;110:2331.

    Article  PubMed  CAS  Google Scholar 

  39. Sonneck K, Florian S, Mullauer L, et al. Diagnostic and subdiagnostic accumulation of mast cells in the bone marrow of patients with anaphylaxis: monoclonal mast cell activation syndrome. Int Arch Allergy Immunol. 2007;142:158.

    Article  PubMed  Google Scholar 

  40. Hungness SI, Singer AM, Akin C. Food-dependent exercise-induced anaphylaxis associated with clonal mast cells carrying an activating c-kit mutation. J Allergy Clin Immunol. 2007;119:S29.

    Article  Google Scholar 

  41. Haeberli G, Bronnimann M, Hunziker T, Muller U. Elevated basal serum tryptase and hymenoptera venom allergy: relation to severity of sting reactions and to safety and efficacy of venom immunotherapy. Clin Exp Allergy. 2003;33:1216.

    Article  PubMed  CAS  Google Scholar 

  42. Ludolph-Hauser D, Rueff F, Fries C, et al. Constitutively raised serum concentrations of mast-cell tryptase and severe anaphylactic reactions to Hymenoptera stings. Lancet. 2001;357:361.

    Article  PubMed  CAS  Google Scholar 

  43. Akin C, Valent P, Escribano L. Urticaria pigmentosa and mastocytosis: the role of immunophenotyping in diagnosis and determining response to treatment. Curr Allergy Asthma Rep. 2006;6:282.

    Article  PubMed  CAS  Google Scholar 

  44. Kassab D, Koterba A, Jiang Y, Akin C. Elevated baseline tryptase levels in patients with mast cell activation syndromes without evidence mastocytosis. J Allergy Clin Immunol. 2008;121:S67.

    Article  Google Scholar 

  45. Schwartz LB. Diagnostic value of tryptase in anaphylaxis and mastocytosis. Immunol Allergy Clin North Am. 2006;26:451.

    Article  PubMed  Google Scholar 

  46. Ditto AM, Harris KE, Krasnick J, et al. Idiopathic anaphylaxis: a series of 335 cases. Ann Allergy Asthma Immunol. 1996;77:285.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA

    Cem Akin

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  1. Cem Akin
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  2. Dean D. Metcalfe
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Correspondence to Cem Akin .

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  1. Harvard Medical School, Ambulatory Center, Brigham and Women’s Hospital, Boyleston Street, Route 9 850, Chestnut Hill, 02467, Massachusetts, USA

    Mariana C. Castells

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Akin, C., Metcalfe, D.D. (2011). Mastocytosis and Mast Cell Activation Syndromes Presenting as Anaphylaxis. In: Castells, M. (eds) Anaphylaxis and Hypersensitivity Reactions. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-951-2_15

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  • DOI: https://doi.org/10.1007/978-1-60327-951-2_15

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60327-950-5

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