Current Treatment Options in Allergy

, Volume 3, Issue 4, pp 384–400 | Cite as

Mast Cell Activation Syndromes

Urticaria and Atopic Dermatitis (M Ferrer-Puga, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Urticaria and Atopic Dermatitis

Opinion statement

Mast cell activation syndromes(MCAS) are disorders associated with mast cell activation (MCA), and include Primary MCAS, Secondary MCAS and Idiopathic MCAS. MCAS are characterized by clinical symptoms of MCA in cutaneous, gastrointestinal, respiratory, cardiovascular, musculoskeletal and neurological organs. Mast cell (MC) mediators such as tryptase in serum, and/or histamine or prostaglandin urinary metabolites are typically elevated at base line or transiently during episodes of MCA, and there is a total or partial response to mast cell mediators controller medications. In primary MCAS an activating point mutation at codon 816 of KIT on MC is present in most cases of Systemic Mastocytosis (SM) and Monoclonal Mast Cell Activation Syndrome (MMCAS) and is absent in secondary and Idiopathic MCAS. MCAS might be the underlying cause of unexplained symptoms when several organ systems are involved, such as the gastrointestinal tract and the skin. It is especially important to be able to recognize the constellation of clinical features because response to anti-MC mediator medications is often excellent. This update on mast cell disorders (MCD) provides an insight into the classification, clinical presentations, diagnosis, treatment and management. We describe associated conditions, such as Hymenoptera Reactions, Familial Tryptasemia, Postural Orthostatic Tachycardia Syndrome and Ehlers-Danlos Syndrome.

Keywords

Mast cell Mast cell activation Tryptase Histamine Allergy Anaphylaxis Antihistamines 

Abbreviations

CM

Cutaneous mastocytosis

EDS

Ehlers-Danlos syndrome

HV

Hymenoptera venom

IMCAS

Idiopathic mast cell activation syndrome

MC

Mast cell

MCA

Mast cell activation

MCAS

Mast cell activation syndromes

MCT

Mast Cell T

MCTc

Mast cell TC

MMAS

Monoclonal mast cell activation syndrome

POTS

Postural tachycardia syndrome

SM

Systemic mastocytosis

VIT

Venom immunotherapy

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Metcalfe DD. Mast cells and mastocytosis. Blood. 2008;112(4):946–56.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Galli SJ, Grimbaldeston M, Tsai M. Immunomodulatory mast cells: negative, as well as positive, regulators of immunity. Nat Rev Immunol. 2008;8(6):478–86.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Frieri M. Mastocytosis. In: Challenging cases in allergy and immunology. New York: Humana Press; 2009. p. 201–12.Google Scholar
  4. 4.
    Brown JM, Wilson TM, Metcalfe DD. The mast cell and allergic diseases: role in pathogenesis and implications for therapy. Clin Exp Allergy J Br Soc Allergy Clin Immunol. 2008;38(1):4–18.Google Scholar
  5. 5.•
    Hamilton MJ, Hornick JL, Akin C, Castells MC, Greenberger NJ. Mast cell activation syndrome: a newly recognized disorder with systemic clinical manifestations. J Allergy Clin Immunol. 2011;128(1):147–52.e2. First clinical cohort of patients with noon-clonal mast cell activation syndrome demonstrating the value of urinary mast cell mediators and the response to treatment with mast cell medications.Google Scholar
  6. 6.
    Wang S-H, Dong L, Luo J-Y, Gong J, Li L, Lu X-L, et al. Decreased expression of serotonin in the jejunum and increased numbers of mast cells in the terminal ileum in patients with irritable bowel syndrome. World J Gastroenterol. 2007;13(45):6041–7.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Park JH, Rhee P-L, Kim HS, Lee JH, Kim Y-H, Kim JJ, et al. Mucosal mast cell counts correlate with visceral hypersensitivity in patients with diarrhea predominant irritable bowel syndrome. J Gastroenterol Hepatol. 2006;21(1 Pt 1):71–8.CrossRefPubMedGoogle Scholar
  8. 8.
    O’Sullivan M, Clayton N, Breslin NP, Harman I, Bountra C, McLaren A, et al. Increased mast cells in the irritable bowel syndrome. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2000;12(5):449–57.CrossRefGoogle Scholar
  9. 9.
    Weston AP, Biddle WL, Bhatia PS, Miner PB. Terminal ileal mucosal mast cells in irritable bowel syndrome. Dig Dis Sci. 1993;38(9):1590–5.CrossRefPubMedGoogle Scholar
  10. 10.
    Buhner S, Li Q, Vignali S, Barbara G, De Giorgio R, Stanghellini V, et al. Activation of human enteric neurons by supernatants of colonic biopsy specimens from patients with irritable bowel syndrome. Gastroenterology. 2009;137(4):1425–34.CrossRefPubMedGoogle Scholar
  11. 11.
    He S-H. Key role of mast cells and their major secretory products in inflammatory bowel disease. World J Gastroenterol. 2004;10(3):309–18.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Nakajima S, Bamba N, Hattori T. Histological aspects and role of mast cells in Helicobacter pylori-infected gastritis. Aliment Pharmacol Ther. 2004;20 Suppl 1:165–70.CrossRefPubMedGoogle Scholar
  13. 13.
    Pothoulakis C, Lamont JT. Microbes and microbial toxins: paradigms for microbial-mucosal interactions II. The integrated response of the intestine to Clostridium difficile toxins. Am J Physiol Gastrointest Liver Physiol. 2001;280(2):G178–83.PubMedGoogle Scholar
  14. 14.
    Barbara G, Stanghellini V, De Giorgio R, Corinaldesi R. Functional gastrointestinal disorders and mast cells: implications for therapy. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2006;18(1):6–17.CrossRefGoogle Scholar
  15. 15.
    Rivera J, Gilfillan AM. Molecular regulation of mast cell activation. J Allergy Clin Immunol. 2006;117(6):1214–25. quiz 1226.CrossRefPubMedGoogle Scholar
  16. 16.••
    Valent P, Akin C, Arock M, Brockow K, Butterfield JH, Carter MC, et al. Definitions, criteria and global classification of mast cell disorders with special reference to mast cell activation syndromes: a consensus proposal. Int Arch Allergy Immunol. 2012;157(3):215–25. Latest classification with diagnostic criteria for mast cell disorders currently in use.CrossRefPubMedGoogle Scholar
  17. 17.
    Castells M, Austen KF. Mastocytosis: mediator-related signs and symptoms. Int Arch Allergy Immunol. 2002;127(2):147–52.CrossRefPubMedGoogle Scholar
  18. 18.
    Triggiani M, Patella V, Staiano RI, Granata F, Marone G. Allergy and the cardiovascular system. Clin Exp Immunol. 2008;153 Suppl 1:7–11.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Seidel H, Molderings GJ, Oldenburg J, Meis K, Kolck UW, Homann J, et al. Bleeding diathesis in patients with mast cell activation disease. Thromb Haemost. 2011;106(5):987–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Prieto-García A, Zheng D, Adachi R, Xing W, Lane WS, Chung K, et al. Mast cell restricted mouse and human tryptase·heparin complexes hinder thrombin-induced coagulation of plasma and the generation of fibrin by proteolytically destroying fibrinogen. J Biol Chem. 2012;287(11):7834–44.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Schwartz LB. Analysis of MC(T) and MC(TC) mast cells in tissue. Methods Mol Biol (Clifton NJ). 2006;315:53–62.Google Scholar
  22. 22.
    Austen KF. Systemic anaphylaxis in the human being. N Engl J Med. 1974;291(13):661–4.CrossRefPubMedGoogle Scholar
  23. 23.
    Serafin WE, Austen KF. Mediators of immediate hypersensitivity reactions. N Engl J Med. 1987;317(1):30–4.CrossRefPubMedGoogle Scholar
  24. 24.
    Simons FER. Anaphylaxis. J Allergy Clin Immunol. 2010;125(2 Suppl 2):S161–81.CrossRefPubMedGoogle Scholar
  25. 25.
    Webb LM, Lieberman P. Anaphylaxis: a review of 601 cases. Ann Allergy Asthma Immunol Off Publ Am Coll Allergy Asthma Immunol. 2006;97(1):39–43.CrossRefGoogle Scholar
  26. 26.
    Lieberman P. Epidemiology of anaphylaxis. Curr Opin Allergy Clin Immunol. 2008;8(4):316–20.CrossRefPubMedGoogle Scholar
  27. 27.
    Peavy RD, Metcalfe DD. Understanding the mechanisms of anaphylaxis. Curr Opin Allergy Clin Immunol. 2008;8(4):310–5.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Golden DB. What is anaphylaxis? Curr Opin Allergy Clin Immunol. 2007;7(4):331–6.CrossRefPubMedGoogle Scholar
  29. 29.
    Finkelman FD, Boyce JA, Vercelli D, Rothenberg ME. Key advances in mechanisms of asthma, allergy, and immunology in 2009. J Allergy Clin Immunol. 2010;125(2):312–8.CrossRefPubMedGoogle Scholar
  30. 30.
    Metcalfe DD. Differential diagnosis of the patient with unexplained flushing/anaphylaxis. Allergy Asthma Proc Off J Reg State Allergy Soc. 2000;21(1):21–4.CrossRefGoogle Scholar
  31. 31.•
    Alvarez-Twose I, González de Olano D, Sánchez-Muñoz L, Matito A, Esteban-López MI, Vega A, et al. Clinical, biological, and molecular characteristics of clonal mast cell disorders presenting with systemic mast cell activation symptoms. J Allergy Clin Immunol. 2010;125(6):1269–78.e2. The authors describe the symptoms and triggers specially for clonal x non-clonal mast cell disorder with a highly predictive algorithm for the diagnoses of these diseases which does not require a bone marrow biopsy.Google Scholar
  32. 32.
    Donker ML, Bakker NA, Jaspers WJM, Verhage AH. Two patients with osteoporosis: initial presentation of systemic mastocytosis. J Bone Miner Metab. 2008;26(2):199–202.CrossRefPubMedGoogle Scholar
  33. 33.
    Valent P, Akin C, Escribano L, Födinger M, Hartmann K, Brockow K, 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
  34. 34.
    González de Olano D, de la Hoz Caballer B, Núñez López R, Sánchez Muñoz L, Cuevas Agustín M, Diéguez MC, et al. Prevalence of allergy and anaphylactic symptoms in 210 adult and pediatric patients with mastocytosis in Spain: a study of the Spanish network on mastocytosis (REMA). Clin Exp Allergy J Br Soc Allergy Clin Immunol. 2007;37(10):1547–55.Google Scholar
  35. 35.
    Bonadonna P, Perbellini O, Passalacqua G, Caruso B, Colarossi S, Dal Fior D, et al. Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levels. J Allergy Clin Immunol. 2009;123(3):680–6.CrossRefPubMedGoogle Scholar
  36. 36.
    Metcalfe DD, Schwartz LB. Assessing anaphylactic risk? Consider mast cell clonality. J Allergy Clin Immunol. 2009;123(3):687–8.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Castells MC, Irani AM, Schwartz LB. Evaluation of human peripheral blood leukocytes for mast cell tryptase. J Immunol (Baltimore, Md: 1950). 1987;138(7):2184–9.Google Scholar
  38. 38.
    Schwartz LB, Sakai K, Bradford TR, Ren S, Zweiman B, Worobec AS, et al. The alpha form of human tryptase is the predominant type present in blood at baseline in normal subjects and is elevated in those with systemic mastocytosis. J Clin Invest. 1995;96(6):2702–10.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Schwartz LB, Irani AM. Serum tryptase and the laboratory diagnosis of systemic mastocytosis. Hematol Oncol Clin N Am. 2000;14(3):641–57.CrossRefGoogle Scholar
  40. 40.
    Divekar R, Butterfield J. Urinary 11β-PGF2α and N-methyl histamine correlate with bone marrow biopsy findings in mast cell disorders. Allergy. 2015;70(10):1230–8.CrossRefPubMedGoogle Scholar
  41. 41.
    Murphy S, Kelly HW. Cromolyn sodium: a review of mechanisms and clinical use in asthma. Drug Intel Clin Pharm. 1987;21(1 Pt 1):22–35.Google Scholar
  42. 42.
    Chin KW, Garriga MM, Metcalfe DD. The histamine content of oriental foods. Food Chem Toxicol Int J Publ Br Ind Biol Res Assoc. 1989;27(5):283–7.CrossRefGoogle Scholar
  43. 43.
    Picard M, Giavina-Bianchi P, Mezzano V, Castells M. Expanding spectrum of mast cell activation disorders: monoclonal and idiopathic mast cell activation syndromes. Clin Ther. 2013;35(5):548–62.CrossRefPubMedGoogle Scholar
  44. 44.
    Castells M, Metcalfe DD, Escribano L. Diagnosis and treatment of cutaneous mastocytosis in children: practical recommendations. Am J Clin Dermatol. 2011;12(4):259–70.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.••
    Hartmann K, Escribano L, Grattan C, Brockow K, Carter MC, Alvarez-Twose I, 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. New classification of cutaneous mast cell disorders with prognostic factors and familiar aggregation.CrossRefPubMedGoogle Scholar
  46. 46.
    Bodemer C, Hermine O, Palmérini F, Yang Y, Grandpeix-Guyodo C, Leventhal PS, et al. Pediatric mastocytosis is a clonal disease associated with D816V and other activating c-KIT mutations. J Investig Dermatol. 2010;130(3):804–15.CrossRefPubMedGoogle Scholar
  47. 47.
    Cardet J-C, Castells MC, Hamilton MJ. Immunology and clinical manifestations of non-clonal mast cell activation syndrome. Curr Allergy Asthma Rep. 2013;13(1):10–8.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Akin C, Valent P, Metcalfe DD. Mast cell activation syndrome: proposed diagnostic criteria. J Allergy Clin Immunol. 2010;126(6):1099–104.e4.Google Scholar
  49. 49.••
    Castells MC, Hornick JL, Akin C. Anaphylaxis after hymenoptera sting: is it venom allergy, a clonal disorder, or both? J Allergy Clin Immunol Pract. 2015;3(3):350–5. Review on hymenoptera anaphylaxis as a clonal mast cell disorder with pathogenic mechanism, treatment and management options.CrossRefPubMedGoogle Scholar
  50. 50.
    Horny H-P, Sotlar K, Valent P. Evaluation of mast cell activation syndromes: impact of pathology and immunohistology. Int Arch Allergy Immunol. 2012;159(1):1–5.CrossRefPubMedGoogle Scholar
  51. 51.
    Alvarez-Twose I, Zanotti R, González-de-Olano D, Bonadonna P, Vega A, Matito A, et al. Nonaggressive systemic mastocytosis (SM) without skin lesions associated with insect-induced anaphylaxis shows unique features versus other indolent SM. J Allergy Clin Immunol. 2014;133(2):520–8.CrossRefPubMedGoogle Scholar
  52. 52.
    Bonadonna P, Gonzalez-de-Olano D, Zanotti R, Riccio A, De Ferrari L, Lombardo C, 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.CrossRefPubMedGoogle Scholar
  53. 53.
    Ryan RJH, Akin C, Castells M, Wills M, Selig MK, Nielsen GP, et al. Mast cell sarcoma: a rare and potentially under-recognized diagnostic entity with specific therapeutic implications. Mod Pathol Off J U S Can Acad Pathol Inc. 2013;26(4):533–43.Google Scholar
  54. 54.
    Horny HP, Valent P. Diagnosis of mastocytosis: general histopathological aspects, morphological criteria, and immunohistochemical findings. Leuk Res. 2001;25(7):543–51.CrossRefPubMedGoogle Scholar
  55. 55.
    Costa JJ, Demetri GD, Harrist TJ, Dvorak AM, Hayes DF, Merica EA, et al. Recombinant human stem cell factor (kit ligand) promotes human mast cell and melanocyte hyperplasia and functional activation in vivo. J Exp Med. 1996;183(6):2681–6.CrossRefPubMedGoogle Scholar
  56. 56.
    Jordan J-H, Schernthaner G-H, Fritsche-Polanz R, Sperr WR, Födinger M, Chott A, et al. Stem cell factor-induced bone marrow mast cell hyperplasia mimicking systemic mastocytosis (SM): histopathologic and morphologic evaluation with special reference to recently established SM-criteria. Leuk Lymphoma. 2002;43(3):575–82.CrossRefPubMedGoogle Scholar
  57. 57.
    Pardanani A. Systemic mastocytosis: disease overview, pathogenesis, and treatment. Hematol Oncol Clin N Am. 2012;26(5):1117–28.CrossRefGoogle Scholar
  58. 58.
    Butterfield JH, Weiler CR. Prevention of mast cell activation disorder-associated clinical sequelae of excessive prostaglandin D(2) production. Int Arch Allergy Immunol. 2008;147(4):338–43.CrossRefPubMedGoogle Scholar
  59. 59.
    Frieri M, Alling DW, Metcalfe DD. Comparison of the therapeutic efficacy of cromolyn sodium with that of combined chlorpheniramine and cimetidine in systemic mastocytosis. Results of a double-blind clinical trial. Am J Med. 1985;78(1):9–14.CrossRefPubMedGoogle Scholar
  60. 60.
    González-de-Olano D, Alvarez-Twose I, Vega A, Orfao A, Escribano L. Venom immunotherapy in patients with mastocytosis and hymenoptera venom anaphylaxis. Immunotherapy. 2011;3(5):637–51.CrossRefPubMedGoogle Scholar
  61. 61.
    Alvarez-Twose I, González-de-Olano D, Sánchez-Muñoz L, Matito A, Jara-Acevedo M, Teodosio C, et al. Validation of the REMA score for predicting mast cell clonality and systemic mastocytosis in patients with systemic mast cell activation symptoms. Int Arch Allergy Immunol. 2012;157(3):275–80.CrossRefPubMedGoogle Scholar
  62. 62.
    Bonadonna P, Zanotti R, Müller U. Mastocytosis and insect venom allergy. Curr Opin Allergy Clin Immunol. 2010;10(4):347–53.CrossRefPubMedGoogle Scholar
  63. 63.
    González de Olano D, Alvarez-Twose I, Esteban-López MI, Sánchez-Muñoz L, de Durana MDAD, Vega A, 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.CrossRefPubMedGoogle Scholar
  64. 64.
    Bonadonna P, Zanotti R, Caruso B, Castellani L, Perbellini O, Colarossi S, et al. Allergen specific immunotherapy is safe and effective in patients with systemic mastocytosis and Hymenoptera allergy. J Allergy Clin Immunol. 2008;121(1):256–7.CrossRefPubMedGoogle Scholar
  65. 65.
    Turk J, Oates JA, Roberts LJ. Intervention with epinephrine in hypotension associated with mastocytosis. J Allergy Clin Immunol. 1983;71(2):189–92.CrossRefPubMedGoogle Scholar
  66. 66.
    Akin C. Anaphylaxis and mast cell disease: what is the risk? Curr Allergy Asthma Rep. 2010;10(1):34–8.CrossRefPubMedGoogle Scholar
  67. 67.
    Lieberman P, Nicklas RA, Oppenheimer J, Kemp SF, Lang DM, Bernstein DI, et al. The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol. 2010;126(3):477–80.e1–42.Google Scholar
  68. 68.
    Bonadonna P, Bonifacio M, Lombardo C, Zanotti R. Hymenoptera allergy and mast cell activation syndromes. Curr Allergy Asthma Rep. 2016;16(1):5.CrossRefPubMedGoogle Scholar
  69. 69.
    Sabato V, Van De Vijver E, Hagendorens M, Vrelust I, Reyniers E, Fransen E, et al. Familial hypertryptasemia with associated mast cell activation syndrome. J Allergy Clin Immunol. 2014;134(6):1448–50.e3.Google Scholar
  70. 70.
    Lyons JJ, Sun G, Stone KD, Nelson C, Wisch L, O’Brien M, et al. Mendelian inheritance of elevated serum tryptase associated with atopy and connective tissue abnormalities. J Allergy Clin Immunol. 2014;133(5):1471–4.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Jacob G, Costa F, Shannon JR, Robertson RM, Wathen M, Stein M, et al. The neuropathic postural tachycardia syndrome. N Engl J Med. 2000;343(14):1008–14.CrossRefPubMedGoogle Scholar
  72. 72.
    Shibao C, Arzubiaga C, Roberts LJ, Raj S, Black B, Harris P, et al. Hyperadrenergic postural tachycardia syndrome in mast cell activation disorders. Hypertension. 2005;45(3):385–90.CrossRefPubMedGoogle Scholar
  73. 73.
    Wallman D, Weinberg J, Hohler AD. Ehlers-Danlos Syndrome and Postural Tachycardia Syndrome: a relationship study. J Neurol Sci. 2014;340(1-2):99–102.CrossRefPubMedGoogle Scholar
  74. 74.
    Gazit Y, Nahir AM, Grahame R, Jacob G. Dysautonomia in the joint hypermobility syndrome. Am J Med. 2003;115(1):33–40.CrossRefPubMedGoogle Scholar
  75. 75.
    De Wandele I, Calders P, Peersman W, Rimbaut S, De Backer T, Malfait F, et al. Autonomic symptom burden in the hypermobility type of Ehlers-Danlos syndrome: a comparative study with two other EDS types, fibromyalgia, and healthy controls. Semin Arthritis Rheum. 2014;44(3):353–61.CrossRefPubMedGoogle Scholar
  76. 76.
    De Wandele I, Rombaut L, Leybaert L, Van de Borne P, De Backer T, Malfait F, et al. Dysautonomia and its underlying mechanisms in the hypermobility type of Ehlers-Danlos syndrome. Semin Arthritis Rheum. 2014;44(1):93–100.CrossRefPubMedGoogle Scholar
  77. 77.
    Garland EM, Celedonio JE, Raj SR. Postural tachycardia syndrome: beyond orthostatic intolerance. Curr Neurol Neurosci Rep. 2015;15(9):60.CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Mathias CJ, Low DA, Iodice V, Owens AP, Kirbis M, Grahame R. Postural tachycardia syndrome—current experience and concepts. Nat Rev Neurol. 2012;8(1):22–34.CrossRefGoogle Scholar
  79. 79.
    Sheldon RS, Grubb BP, Olshansky B, Shen W-K, Calkins H, Brignole M, et al. 2015 heart rhythm society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Heart Rhythm Off J Heart Rhythm Soc. 2015;12(6):e41–63.CrossRefGoogle Scholar
  80. 80.•
    Jennings S, Russell N, Jennings B, Slee V, Sterling L, Castells M, et al. The Mastocytosis Society survey on mast cell disorders: patient experiences and perceptions. J Allergy Clin Immunol Pract. 2014;2(1):70–6. Description of diagnoses and symptoms of Mastocytoses base on patient’s perceptions.CrossRefPubMedGoogle Scholar

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© Springer International Publishing AG 2016

Authors and Affiliations

  1. 1.Division of Rheumatology, Immunology and Allergy; Department of MedicineBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  2. 2.Clinical Immunology and Allergy DivisionUniversity of São PauloSão PauloBrazil

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