Anaphylaxis is the systemic and most severe presentation of type I
allergy. A number of conditions were identified that modulate the onset of
anaphylaxis such as co- or augmentation factors, which significantly lower the
allergen dose necessary for triggering
anaphylaxis. Next to physical exercise or alcohol consumption, co-administration of nonsteroidal anti-inflammatory drugs (
NSAID) or concomitant
infectious diseases are well-documented cofactors of
anaphylaxis. Registries for
anaphylaxis document a role for cofactors in about 30% of
anaphylactic reactions. Some disease entities such as '
wheat-dependent exercise-induced anaphylaxis' (
WDEIA) are explicitly characterized by elicitation of
anaphylaxis only in the presence of at least one such cofactor. Using
WDEIA as a model disease, studies demonstrated that exercise increases skin prick test reactivity to and bioavailability of the
allergen. Additional data indicate that alcohol consumption and
NSAID administration display similar effects. Modulation of the cellular activation threshold is another mechanism underlying cofactor-induced
anaphylaxis, most likely also functional when
infectious diseases orchestrate elicitation of
anaphylaxis. Cofactors are increasingly accepted to play a fundamental role in eliciting
anaphylaxis. Consequently, to improve patient management modalities, a better understanding of the underlying mechanisms is warranted. This review aims to update clinicians and clinical scientists on recent developments.