Skip to main content

Advertisement

Log in

Mast Cell Activation Syndrome

  • Published:
Clinical Reviews in Allergy & Immunology Aims and scope Submit manuscript

Abstract

Mast cell activation syndrome (MCAS) involves the skin, gastrointestinal, cardiovascular, respiratory, and neurologic systems, classified as primary, secondary, and idiopathic. Earlier criteria for MCAS diagnosis included episodic symptoms with mast cell mediators affecting two or more organ systems with urticaria, angioedema, flushing, nausea, vomiting, diarrhea, abdominal cramping, hypotensive syncope, tachycardia, wheezing, conjunctival injection, pruritus, nasal stuffiness, decrease in frequency, severity, or resolution of symptoms with anti-mediator therapy including H1/H2 receptor antagonists, anti-leukotrienes, or mast cell stabilizers. Laboratory data includes an increased validated urinary or serum markers of MCAS, documentation of an increase of the marker above the patient’s baseline value during symptomatic periods on more than two occasions, or baseline serum tryptase levels that are persistently above 15 ng/mL. Laboratory data also includes an increase of the tryptase level above baseline value on one occasion. Other assays are 24-h urine histamine metabolites, PGD2 or its metabolite, and 11-β-prostaglandin F2 alpha. A recent global classification is a response of clinical symptoms, a substantial transient increase in serum total tryptase or increase in other mast cell-derived mediators, histamine or PGD2 or urinary metabolites, and agents that attenuate production or mast cell mediator activities. “Spectrum of MCAS disorders” has been proposed, highlighting symptoms’ diagnostic tests and treatments.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Kinet J-P (1990) The high affinity receptor for IgE. Curr Opin Immunol 2:499–505

    Article  CAS  Google Scholar 

  2. Cambier JC (1995) Antigen and Fc receptor signaling: the awesome power of the immunoreceptor tyrosine based activation motif (ITAM). J Immunol 155:3281–5

    PubMed  CAS  Google Scholar 

  3. Fukamachi H, Kawakami Y, Takei M et al (1992) Association of protein tyrosine kinase with phospholipase C-γ1 in bone marrow-derived mouse mast cells. Proc Natl Acad Sci U S A 89:9524–8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Bischoff SC, Dahinden CA (1992) c-Kit ligand: a unique potentiator of mediator release by human lung mast cells. J Exp Med 175:237–44

    Article  PubMed  CAS  Google Scholar 

  5. Galli SJ, Tsai M, Wershil BK (1993) The c-kit receptor, stem cell factor, and mast cells. What each is teaching us about the others. Am J Pathol 142(4):965–74

    PubMed  PubMed Central  CAS  Google Scholar 

  6. Galli SJ, Zsebo KM, Geissler EN (1994) The kit ligand, stem cell factor. Adv Immunol 55:1–96

    PubMed  CAS  Google Scholar 

  7. Lukacs NW, Strieter RM, Lincoln PM et al (1996) Stem cell factor (c-kit ligand) influences eosinophil recruitment and histamine levels in allergic airway inflammation. J Immunol 156(10):3945–51

    PubMed  CAS  Google Scholar 

  8. Bingham CO III, Austen KF (2000) Mast-cell responses in the development of asthma. J Allergy Clin Immunol 105(2 Pt 2):S527–34

    Article  PubMed  CAS  Google Scholar 

  9. Iemura A, Tsai M, Ando A et al (1994) The c-kit ligand, stem cell factor, promotes mast cell survival by suppressing apoptosis. Am J Pathol 144(2):321–8

    PubMed  PubMed Central  CAS  Google Scholar 

  10. Horny HP, Sotlar K, Valent P (2012) Evaluation of mast cell activation syndromes: impact of pathology and immunohistology. Int Arch Allergy Immunol 159(1):1–5

    Article  PubMed  CAS  Google Scholar 

  11. Meninger CJ, Yano H, Rottapel R et al (1992) The c-kit receptor ligand functions as a mast cell chemoattractant. Blood 4:958–63

    Google Scholar 

  12. Ito T, Smrž D, Jung MY et al (2012) Stem cell factor programs the mast cell activation phenotype. J Immunol 188(11):5428–37

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Gilfillan AM, Rivera J (2009) The tyrosine kinase network regulating mast cell activation. J Immunol Rev Immunol Rev 228(1):149–69

    Article  CAS  Google Scholar 

  14. Akin C, Valent P, Metcalfe DD (2010) Mast cell activation syndrome: proposed diagnostic criteria. J Allergy Clin Immunol 126:1099–1104

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Akin C (2014) Mast cell activation disorders. J Allergy Clin Immunol Pract 2:252–57

    Article  PubMed  Google Scholar 

  16. Shibao C, Arzubiaga C, 2nd Roberts LJ et al (2005) Hyperadrenergic postural tachycardia syndrome in mast cell activation disorders. Hypertension 45(3):385–90

    Article  PubMed  CAS  Google Scholar 

  17. Naysan J, Kodsi S, Kristal L (2013) Solitary mastocytoma of the eyelid. J AAPOS 17(4):433–434

    Article  Google Scholar 

  18. Auquit-Auckbur I, Lazar C, Deneuve S et al (2012) Malignant transformation of mastocytoma developed on skin mastocytosis into cutaneous mast cell sarcoma. Am J Surg Pathol 36(5):779–82

    Article  PubMed  Google Scholar 

  19. Falleti J, Borgia L, Lalinga AV et al (2012) Mast cell sarcoma of the scalp: the first sign of undisclosed systemic mastocytosis? Pathol Res Pract 208(11):683–6

    Article  PubMed  Google Scholar 

  20. Frieri M (2009) Mastocytosis. Challenging cases in allergy and immunology Ed: Massoud Mahmoudi Chapter 14. pp201-212. Humana Press

  21. Akin C, Scott LM, Kocabas CN et al (2007) Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with “idiopathic” anaphylaxis. Blood 110:2331–3

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Koterba AP, Akin C (2008) Differences in the clinical presentation of anaphylaxis in patients with indolent systemic mastocytosis (ISM) versus idiopathic anaphylaxis (IA). J Allergy Clin Immunol 121:S68a, abstract

    Article  Google Scholar 

  23. Greenberger P, Lieberman P (2014) Idiopathic anaphylaxis. J Allergy Clin Immunol 2:243–250, In Practice Issue #3

    Article  Google Scholar 

  24. Lieberman P et al (2005) An updated practice parameter EdsIdiopathic anaphylaxis. Diagnosis Manage Anaphylaxis 115(3):S483–S523

    Google Scholar 

  25. Valent P, Akin C, Arock M et al (2012) Definitions, criteria & global classification of MC disorders with special reference to MCAS: a consensus proposal. Int Arch Allergy Immunol 157(3):215–25

  26. Alvarez-Twose I, de González OD, Sánchez-Muñoz L et al (2010) Clinical, biological, and molecular characteristics of clonal mast cell disorders presenting with systemic mast cell activation symptoms. J Allergy Clin Immunol 125(6):1269–1278

    Article  PubMed  CAS  Google Scholar 

  27. Frieri M (2009) Anaphylaxis. Chapter 68, pp721-730. In: Manual of Critical Care, Philadelphia, Pa. American College of Physicians

  28. Matito A, Alvarez-Twose I, Morgado JM et al (2014) Anaphylaxis as a clinical manifestation of clonal mast cell disorders. Curr Allergy Asthma Rep 14(8):450

  29. Hamilton MJ, Hornick JL, Akin C et al (2011) A newly recognized disorder with systemic clinical manifestations. J Allergy Clin Immunol 128(1):147–152

  30. Metcalfe DD (2000) Differential diagnosis of the patient with unexplained flushing/anaphylaxis. Allergy Asthma Proc 21(1):21–24

    Article  PubMed  CAS  Google Scholar 

  31. Lafont E et al (2014) Causes and diffential diagnosis of flush. Rev Med Interne 35(5):303–9

    Article  PubMed  CAS  Google Scholar 

  32. Picard M, Giavina-Bianchi P, Mezzano V et al (2013) Expanding spectrum of mast cell activation disorders: monoclonal and idiopathic mast cell activation syndromes. Clin Ther 35(5):548–62

    Article  PubMed  CAS  Google Scholar 

  33. Pardanani A (2012) Systemic mastocytosis in adults. Update on diagnosis, risk stratification, and management. Am J Hematol 87(4):401–11

    Article  PubMed  CAS  Google Scholar 

  34. Frieri M, Linn N, Schweitzer M, Angadi C et al (1990) Lymphadenopathic mastocytosis with eosinophilia and biclonal gammopathy. J Allergy Clin Immuno 86:l26–132

    Article  Google Scholar 

  35. Gotlib J, Akin C (2012) Mast cells and eosinophils in mastocytosis, chronic eosinophilic leukemia, and non-clonal disorders. Semin Hematol 49(2):128–37

    Article  PubMed  CAS  Google Scholar 

  36. Bai Y, Bandara G, Ching Chan E (2012) Targeting the KIT activating switch control pocket: a novel mechanism to inhibit neoplastic mast cell proliferation and mast cell activation. Leukemia 27(2):278–85

  37. Bax HJ, Keeble AH, Gould HJ (2012) Cytokinergic IgE action in mast cell activation. Frontiers Immunol Inflamm Vol 3:229

    Google Scholar 

  38. Patel R, Celestin J, Frieri M (2012) An unusual case of mast cell activation syndrome. J Allergy Clin Immunol;, abs #475

  39. Afrin LB (2012) Mast cell activation syndrome masquerading as agranulocytosis. Mil Med 177(1):113–7

    Article  PubMed  Google Scholar 

  40. Kritas SK, Saggini A, Varvara G et al (2013) Mast cell involvement in rheumatoid arthritis. J Biol Regul Homeost Agents 27(3):655–60

    PubMed  CAS  Google Scholar 

  41. Frieri M, Agarwal K, Datar A, Trotta P (1994) Increased interleukin-4 production in response to mast cell mediators and human type I collagen in patients with rheumatoid arthritis. Ann Allergy 72:1–8

    Google Scholar 

  42. Afrin LB (2012) Sclerosing mediastinitis and mast cell activation syndrome. Pathol Res Pract 208(3):181–5

    Article  PubMed  Google Scholar 

  43. Hawrylko E, Spertus A, Mele C et al (1991) Increased interleukin-2 production in response to human type I collagen stimulation in patients with systemic sclerosis. Arthritis Rheum 34:580

    Article  PubMed  CAS  Google Scholar 

  44. Frieri M (1992) Systemic sclerosis. The role of the mast cell and cytokines. Ann Allergy 69:385–397

    PubMed  CAS  Google Scholar 

  45. Frieri M (1993) Systemic sclerosis and related antinuclear antibody serologies. Immunopath; 17:#5, IP 93–5, 1–9

  46. Frieri M, Patel R, Celestin J (2013) Mast cell activation syndrome: a review. Curr Allergy Asthma Rep 13(1):27–32

    Article  PubMed  CAS  Google Scholar 

  47. Frieri M, Quershi M (2013) Pediatric mastocytosis. Review of the literature. Ped Allergy Asthma Pulmonol 26(#4):175–180

    Google Scholar 

  48. Cardet JC, Castells MC, Hamilton MJ (2013) Immunology & clinical manifestations of non-clonal MCAS. Curr Allergy Asthma Rep 13(1):10–8

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Jennings S, Russell N, Jennings B et al (2014) The mastocytosis society survey on mast cell disorders: patient experiences and perception. J Allergy Clin Immunol Pract 2:70–6

    Article  PubMed  Google Scholar 

  50. Bell MC, Jackson DJ (2012) Anaphylaxis prevention related to MCAS with omalizumab letters. Ann Allergy Asthma Immunol 108(5):384–384

    Article  CAS  Google Scholar 

  51. Sokol K, Ghazi A, Kelly BC et al (2014) Omalizumab as a desensitizing agent and treatment in mastocytosis. Rev Case Report J Allergy Clin Immunol Prac 2:266–758

    Google Scholar 

  52. Jagdis A, Vadas P (2014) Omalizumab effectively prevents recurrent refractory anaphylaxis in a patient with monoclonal mast cell activation syndrome. Annals Allergy, Asthma Immunol 113(1):115–116

    Article  Google Scholar 

  53. Petra A, Panagiotidou S, Stewart JM et al (2014) Spectrum of mast cell activation disorders. Expert Rev Clin Immunol 10(6):729–39

    Article  PubMed  CAS  Google Scholar 

  54. Brockow K (2014) Epidemiology, prognosis, risk factors in mastocytosis. Immunol Allergy Clin North Am 34(2):283–295

    Article  PubMed  Google Scholar 

  55. Yip HK, Kolesnikoff N, Yu C et al (2014) Mechanisms of vitamin D3 metabolite repression of IgE-dependent mast cell activation. J Allergy Clin Immunol 133(5):1356–64

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Sabato V, Van De Vijver E, Hagendorens M et al (2014) Mast cell activation. Familial hypertryptasemia with associated mast cell activation syndrome. J Allergy Clin Immunol 133:1356–1364

    Article  CAS  Google Scholar 

  57. Wiednig M, Beham-Schmid C, Kranzelbinder B et al (2013) Clonal mast cell proliferation in pruriginous skin in hypereosinophilic syndrome. Dermatology 227(1):67–71

    Article  PubMed  CAS  Google Scholar 

  58. Doyle LA, Sepehr GJ, Hamilton MJ et al (2014) A clinicopathologic study of 24 cases of systemic mastocytosis involving the gastrointestinal tract and assessment of mucosal mast cell density in irritable bowel syndrome and asymptomatic patients. Am J Surg Pathol 38(6):832–43

    Article  PubMed  PubMed Central  Google Scholar 

  59. Hwang S-L, Lu Y, Li X (2014) ERK1/2 antagonize AMPK-dependent regulation of FcεRI-mediated mast cell activation and anaphylaxis. J Allergy Clin Immunol 134:714–21

    Article  PubMed  CAS  Google Scholar 

  60. Schäfer D, Dreßen P, Brettner S et al (2014) Prostaglandin D2-supplemented “functional eicosanoid testing and typing” assay with peripheral blood leukocytes as a new tool in the diagnosis of systemic mast cell activation disease: an explorative diagnostic study. J Transl Med 12(1):213

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Sibilano R, Frossi B, Pucillo CE (2014) Mast cell activation: a complex interplay of positive and negative signaling pathways. Eur J Immunol; Jul 27

  62. Kounis NG, Mazarakis A, Almpanis G et al (2014) The more allergens an atopic patient is exposed to, the easier and quicker anaphylactic shock and Kounis syndrome appear: clinical and therapeutic paradoxes. J Nat Sci Biol Med 5(2):240–4

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Alevizos M, Karagkouni A, Panagiotidou S et al (2014) Stress triggers coronary mast cells leading to cardiac events. Ann Allergy Asthma Immunol 112(4):309–16

    Article  PubMed  CAS  Google Scholar 

  64. Afrin LB (2013) Utility of hydroxyurea in mast cell activation syndrome. Exp Hematol Oncol 2(1):28

    Article  PubMed  PubMed Central  Google Scholar 

  65. Afrin LB (2014) Mast cell activation syndrome as a significant comorbidity in sickle cell disease. Am J Med Sci; Aug 28

  66. Gülen T, Hägglund H, Sander B et al (2014) The presence of mast cell clonality in patients with unexplained anaphylaxis. Clin Exp Allergy 44(9):1179–87

    Article  PubMed  CAS  Google Scholar 

  67. Lu Y, Li X, Park YN, Kwon O et al (2014) Britanin suppresses IgE/Ag-induced mast cell activation by inhibiting the Syk pathway. Biomol Ther (Seoul) 22(3):193–9

    Article  CAS  Google Scholar 

  68. Akin C (2014) Mast cell activation disorders. J Allergy Clin Immunol Pract 2(3):252–7

    Article  PubMed  Google Scholar 

  69. Haenisch B, Fröhlich H, Herms S et al (2014) Evidence for contribution of epigenetic mechanisms in the pathogenesis of systemic mast cell activation disease. Immunogenetics 66(5):287–97

    Article  PubMed  CAS  Google Scholar 

Download references

Ethical Statement

I have no grant support or any conflict of interest for this review.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marianne Frieri.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Frieri, M. Mast Cell Activation Syndrome. Clinic Rev Allerg Immunol 54, 353–365 (2018). https://doi.org/10.1007/s12016-015-8487-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12016-015-8487-6

Keywords

Navigation