Mast cell activation syndrome (MCAS) is a challenging specialized condition that allergists-immunologists treat in the outpatient setting. Despite the wide prevalence of the disease, clinicians may feel overwhelmed to provide consistent compassionate care for these patients for a multitude of reasons. Patients uniformly describe feeling unheard during a clinical encounter and thereby often end up seeing multiple physicians and specialists which further complicates their medical care. As such, it is important to characterize patients with MCAS accurately, which includes the assessment of coexistent mimicking or confounding conditions to achieve best medical care outcomes.
Hereditary alpha-tryptasemia (HαT) is a common autosomal dominant genetic trait that results from increased copy numbers of the TPSAB1 gene encoding α-tryptase. Studies have shown that increased relative α-tryptase expression can modify mast-cell-mediated reactions and contribute to increased severity of anaphylaxis. HαT is an independent risk modifier for reaction severity in patients with Hymenoptera venom allergy and systemic mastocytosis. Additionally, there is emerging evidence that HαT and α-tryptase expression more generally are also associated with increased risk of severe reactions to other allergens. Tryptase genotyping may be a promising biomarker for risk stratification of IgE-mediated allergic reaction severity in the future.
Allergy to venoms of stinging insects (bees, yellow jackets, hornets, wasps, and stinging ants) causes large local reactions or systemic reactions, including anaphylaxis. Diagnostic evaluation includes skin testing and/or serum venom-specific IgE and basal serum tryptase (to identify underlying mast cell disorders). Patients with sting anaphylaxis should be prescribed epinephrine and venom immunotherapy which prevents allergic reactions in up to 98% of patients. Most patients may safely discontinue venom immunotherapy after 5 years, although high-risk patients need to continue indefinitely. Further research is needed to improve the predictive value of diagnostic testing and the safety and efficacy of treatment.
Anaphylaxis can be caused by several different mechanisms. Novel therapies on the horizon target these numerous pathways, including tyrosine kinase inhibitors, recombinant allergen-specific blocking antibodies, and monoclonals targeting KIT or inhibitory receptors. This article discusses potential new therapies for both the prevention and treatment of anaphylaxis that are currently in clinical development.
