Diagnosis and Treatment of Anaphylaxis in Patients with Mastocytosis

Abstract

Patients with systemic mastocytosis (SM) have an increased risk for the development of severe, life-threatening anaphylactic episodes. Despite prophylactic therapy with anti-mediator-type drugs, a mast cell (MC) activation syndrome (MCAS) may be diagnosed in these patients. In a subset of them, an immunoglobulin (Ig)E-dependent allergy is detected as underlying disease. The severity and frequency of anaphylactic reactions neither correlate with the burden of neoplastic MCs nor with specific IgE levels or the serum tryptase level. However, the ‘event-related’ increase in serum tryptase is usually indicative of a severe reaction. In addition, there is a positive correlation between severe anaphylaxis and the type of allergen in SM. In fact, many of these MCAS patients suffer from bee or wasp venom allergy. Currently recommended standard treatments for anaphylaxis in mastocytosis include the prophylactic use of histamine receptor (HR) antagonists, MC stabilizers, life-long immunotherapy in hymenoptera venom allergic patients, and epinephrine injections for emergency situations. In those who have an excessive burden of MCs (smouldering or aggressive SM) cladribine (2CdA) may be effective and may reduce the frequency of severe life-threatening events, and the same can sometimes be achieved with interferon-alpha (IFNα). In the future, additional treatment options, such as IgE-depletion or administration of tyrosine kinase inhibitors targeting IgE-dependent mediator secretion as well as KIT activation and thus MC expansion, may become standard therapy. Key points 1. Patients with mastocytosis have a high risk of developing severe anaphylaxis, especially when suffering from hymenoptera venom allergy, but sometimes also even in the absence of any known trigger or allergy. 2. Management of anaphylaxis in mastocytosis requires special considerations and special knowledge about potential triggers, disease pathogenesis, and treatment options and should be performed in, or in collaboration with, a specialized center.