Mast Cell Activation Syndrome Variants

PRIMARY MCAS

Primary MCAS results from a clonal population of mast cells, where a genetic alteration in the cells exists, and may be due to mastocytosis or to monoclonal Mast Cell Activation Syndrome (MMAS). Primary MCAS with mastocytosis can be diagnosed if the patient fulfils criteria for MCAS and fulfills the WHO criteria for mastocytosis. MMAS is a distinct disease characterized by the presence of abnormal mast cells and fulfillment of criteria for MCAS, but where sufficient criteria for a diagnosis of mastocytosis are not identified.1-10

SECONDARY MCAS

Secondary MCAS is diagnosed when mast cell activation occurs as an indirect result of another disease or condition.1-3, 9, 11 Physician awareness of the presence of secondary MCAS will allow for more appropriate mast cell activation-targeted treatments, in addition to primary disease-related medications, to be provided. In addition to the widespread example of IgE-dependent allergy as a cause of secondary MCAS, other diseases that can cause secondary MCAS have been reviewed in the literature.1-3, 11

IDIOPATHIC MCAS

Idiopathic MCAS is proposed as a final diagnosis after proposed MCAS criteria have been fulfilled and a thorough evaluation has excluded the possibility of another known underlying cause for this activation.2, 12 Idiopathic MCAS is therefore nonclonal, with regard to current diagnostic capabilities related to mast cell analyses, and has been presented and discussed in the literature by a variety of mast cell disorder specialists.1-3, 9-13 Review of other causes of MCAS to aid physicians in evaluation for the exclusionary diagnosis of idiopathic MCAS have also been provided.1-3, 10

Additional Considerations for MCAS

It is recognized by researchers that current diagnostic methods for capturing a rise in mast cell mediators after a symptomatic episode are not ideal.12, 14, 15 Some patients who present with typical and recurrent signs and symptoms of mast cell activation do not present with elevated levels of mediators for which we are currently able to test. Non-specialist physicians may most commonly use serum tryptase levels to exclude a mast cell disorder. However, some MCAS specialists have indicated that tryptase rises are not seen as often in patients with certain forms of MCAS, and that other changes in bloodwork and urine tests can sometimes be more reliable.13, 14 Additionally, there is a very narrow window of time (1-2 hours after symptoms begin) during which to obtain a serum tryptase test to indicate mast cell activation,2 such that obtaining laboratory evidence of the event can prove difficult in many circumstances. Some specialists suggest that despite lack of proof of elevated mast cell mediators, a response to mast cell or mast cell mediator blockers should be determined in such patients.12 If a patient responds well to anti-mediator treatment and fulfills the other proposed criteria,2 with the exception of displaying a rise in mediators, then a diagnosis of idiopathic MCAS remains open for consideration, as long as other diagnoses continue to be considered (please see Valent article noted below for more information on differential diagnoses). The patient should be periodically monitored to try to capture a rise in any of the mediators for which commercial testing is both available and recognized as a widely accepted diagnostic standard.12

Even the co-criterion requiring a response to mast cell targeted therapy can be difficult to obtain in some patients. Sometimes multiple mast cell (or mast cell mediator) blocking therapies must be tried before successful symptom resolution is attained.3, 16 Also, it is reported in another study, that only one third of MCAS patients experience a complete resolution with treatment; one third have a major response and another third have a minor response, and a combination of drugs is usually required to achieve control of symptoms.10

 

Please visit the following article for more information on mast cell activation syndromes, including potential causes, symptoms, variants, effects of comorbidities and other possible diagnoses to exclude:

Valent P. Mast cell activation syndromes: definition and classification. Allergy. 2013 Apr;68(4):417-24.

References

  1. Akin C, Valent P, Metcalfe DD. Mast cell activation syndrome: proposed diagnostic criteria. J Allergy Clin Immunol. 2010 Dec;126(6):1099-104 e4. http://www.ncbi.nlm.nih.gov/pubmed/21035176
  2. 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. http://www.ncbi.nlm.nih.gov/pubmed/22041891
  3. Valent P. Mast cell activation syndromes: definition and classification. Allergy. 2013 Apr;68(4):417-24. http://www.ncbi.nlm.nih.gov/pubmed/23409940
  4. Akin C, Scott LM, Kocabas CN, Kushnir-Sukhov N, Brittain E, Noel P, et al. Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with “idiopathic” anaphylaxis. Blood. 2007 Oct 1;110(7):2331-3. http://www.ncbi.nlm.nih.gov/pubmed/17638853
  5. Valent P, Akin C, Escribano L, Fodinger M, Hartmann K, Brockow K, et al. Standards and standardization in mastocytosis: consensus statements on diagnostics, treatment recommendations and response criteria. Eur J Clin Invest. 2007 Jun;37(6):435-53. http://www.ncbi.nlm.nih.gov/pubmed/17537151
  6. Sonneck K, Florian S, Mullauer L, Wimazal F, Fodinger M, Sperr WR, 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(2):158-64. http://www.ncbi.nlm.nih.gov/pubmed/17057414
  7. 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 Pract. 2009 Mar;123(3):680-6. http://www.ncbi.nlm.nih.gov/pubmed/19135713
  8. Alvarez-Twose I, Gonzalez de Olano D, Sanchez-Munoz L, Matito A, Esteban-Lopez 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 Jun;125(6):1269-78 e2. http://www.ncbi.nlm.nih.gov/pubmed/20434205
  9. Akin C, Metcalfe DD. Mastocytosis and mast cell activation syndromes presenting as anaphylaxis. In: Castells MC, editor. Anaphylaxis and hypersensitivity reactions. New York: Humana Press; 2011. p. 245-56. http://dx.doi.org/10.1007/978-1-60327-951-2_15
  10. 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 May;35(5):548-62. http://www.ncbi.nlm.nih.gov/pubmed/23642289
  11. Valent P, Horny HP, Triggiani M, Arock M. Clinical and laboratory parameters of mast cell activation as basis for the formulation of diagnostic criteria. Int Arch Allergy Immunol. 2011;156(2):119-27. http://www.ncbi.nlm.nih.gov/pubmed/21576982
  12. Cardet JC, Castells MC, Hamilton MJ. Immunology and clinical manifestations of non-clonal mast cell activation syndrome. Curr Allergy Asthma Rep. 2013 Feb;13(1):10-8. http://www.ncbi.nlm.nih.gov/pubmed/23212667
  13. 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 Jul;128(1):147-52 e2. http://www.ncbi.nlm.nih.gov/pubmed/21621255
  14. Molderings GJ, Brettner S, Homann J, Afrin LB. Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options. J Hematol Oncol. 2011;4:10. http://www.ncbi.nlm.nih.gov/pubmed/21418662
  15. Afrin LB. Polycythemia from mast cell activation syndrome: lessons learned. Am J Med Sci. 2011 Jul;342(1):44-9. http://www.ncbi.nlm.nih.gov/pubmed/21642812
  16. Afrin LB. Presentation, diagnosis and management of mast cell activation syndrome. In: Murray DB, editor. Mast cells: phenotypic features, biological functions and role in immunity. Hauppauge: Nova Science Publishers, Inc.; 2013. p. 155-232.
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