MCAS, evaluation and diagnosis

Mast cell activation syndromes include clonal (mastocytosis and monoclonal mast cell activation syndrome MMCAS) and non-clonal mast cell disorders such as idiopathic mast cell activation syndrome MCAS. The diagnosis as defined by the WHO requires the presence of mast cell activation symptoms, elevation of mast cell mediators and response to mast cell mediators blocking medications. MCAS should be considered in patients with both appropriate clinical symptoms and elevation of mediators during acute symptoms (1). Patients may present with chronic symptoms with acute exacerbations or with episodic events including anaphylaxis. There can be a variety of phenotypes and at least 2 organs systems should be involved. (Adapted from AAAAI MCAS Committee Work Group Report)

1) Cardiovascular—hypotension, tachycardia, and syncope or near-syncope
2) Dermatologic—urticaria, pruritus, and flushing and angioedema, particularly of the eyelids, lips, and tongue
3) Respiratory—wheezing, shortness of breath, and inspiratory stridor
4) Gastrointestinal—crampy abdominal pain, diarrhea, nausea, and vomiting.

During events, elevation in specific biologic markers compared with basal levels can include:
1) 24 h urine collection for PGD2 and its metabolites
2) 24 h urine collection of N-Methyl-histamine
3) Serum Tryptase

Finally, the improvement with treatment using inhibitors of mast cell mediators completes the diagnosis and includes anti-H1 and anti-H2 histamine receptors blockers, leukotriene inhibitors, sodium cromolyn and aspirin (prostaglandin blockade). Omalizumab has been used for patients presenting recurrent anaphylaxis with and without urticaria.

The diagnosis of clonal mast cell disorders includes the evaluation of PB KITD816V mutation and if positive a bone marrow biopsy is indicated to rule out mastocytosis. Patients whose baseline tryptase is >8 ng/ml should be evaluated for Hereditary Alpha Tryptasemia with genotyping for TPSAB1 tryptase genes duplication. Positive patients are likely to have other family members affected since HaT is an autosomal dominant trait which typically affects several generations.

Patients with symptoms compatible with mast cell activation with good response to mast cell mediator controller medications and should be evaluated for mast cell mediators at each of the acute events, since the diagnosis of MCAS requires the demonstration of mast cell activation through biomarkers.

For more thorough review of therapeutic approaches, I refer you to TABLE IV. Treatment interventions for MCAS, in The AAAAI Mast Cell Disorders Committee Work Group Report (2)

1. Mast cell activation syndrome: a newly recognized disorder with systemic clinical manifestations Matthew J Hamilton 1, Jason L Hornick, Cem Akin, Mariana C Castells, Norton J Greenberger. J Allergy Clin Immunol 2011 Jul;128(1):147-152.e2. doi: 10.1016/j.jaci.2011.04.037.

2) Weiler CR, Austen KF, Akin C, Barkoff MS, Bernstein JA, Bonadonna P, Butterfield JH, Carter M, Fox CC, Maitland A, Pongdee T, Mustafa SS, Ravi A, Tobin MC, Vliagoftis H, Schwartz LB. AAAAI Mast Cell Disorders Committee Work Group Report: Mast cell activation syndrome (MCAS) diagnosis and management. J Allergy Clin Immunol. 2019 Oct;144(4):883-896.

Very special thanks to Dr Mariana Castells for her assistance in this response.

I hope you find this helpful in the management of your patient.

Respectfully submitted,
Jeffrey G Demain, MD, FAAAAI