Several different risk factors and conditions may predispose to severe life-threatening
anaphylaxis.
Systemic mastocytosis (SM) is one such condition. Although many SM patients are suffering from mild or even no mediator-related symptoms, others have recurrent episodes of severe
anaphylaxis, with clear signs of a
mast cell activation syndrome (MCAS) despite prophylactic
therapy with anti-mediator-type drugs. In several of these patients, an
IgE-dependent
allergy is diagnosed. The severity and frequency of MCAS reactions neither correlate with the burden of neoplastic mast cells nor with the levels of specific
IgE or the basal
tryptase level. However, there is a relationship between severe
anaphylaxis in SM and the type of
allergen. Notably, many of these patients suffer from
hymenoptera venom allergy. Currently recommended
therapies include the prophylactic use of anti-mediator-type drugs, long-term
immunotherapy for
hymenoptera venom allergic patients, and
epinephrine-self-injector treatment for emergency situations. In patients who present with an excess burden of mast cells, such as smouldering SM, cytoreductive
therapy with
cladribine (2CdA) may reduce the frequency of severe events. For the future, additional treatment options, such as
IgE-depletion or the use of
tyrosine kinase inhibitors blocking
IgE-dependent mediator secretion as well as KIT activation, may be useful alternatives.