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 disease 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 disease. 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 blood work 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.