Every allergist remembers a patient who is sensitized to a food, usually tolerates it, and who, at some point, will present an anaphylactic reaction to it. The first description of this type dates back to 1979. It concerns a patient sensitized to shellfish, usually tolerant, but who, during exercise, presented an anaphylactic reaction.
The presence of cofactors explains this phenomenon. These cofactors act according to two mechanisms: they modify the sensitization threshold and induce symptoms for a dose of allergen usually tolerated, or they do not modify the reactogenic threshold, but increase the reaction in terms of severity.
Two types of anaphylaxis modulators can be identified. Some, intrinsic factors, depend on the patient: genetic predisposition, comorbidities such as uncontrolled asthma or mast cell diseases, or even biological determinants such as hormonal status or age. The others, extrinsic factors, are generally physical activity, alcohol consumption, medications (beta blockers, ACE inhibitors) and psychological stress.
More common in adults than in children
Cofactors are more often present in adults than in children. Analysis of data from the Allergo-Vigilance Network (2016-2020), covering 792 reports of anaphylaxis, shows that cofactors were present in 18% of children and 60% of adults. For children, the most frequent cofactors were exercise, exposure to temperature extremes, stress, and fatigue. For adults, it was exercise, medication, alcohol. Several cofactors can be counted in the same patient.
The presence of these cofactors increases the severity of the allergic reaction, as shown in a study of sleep deprivation, which increased the severity score of anaphylactic reaction to peanut by 48% (Dua S. et al. 2019).
Concerning the mechanisms of action, 3 cofactors have been particularly studied: alcohol consumption, exercise and taking nonsteroidal anti-inflammatory drugs. The mechanism common to these 3 cofactors seems to be the increase in intestinal absorption of the allergen, by increasing intestinal permeability.
More specifically for alcohol consumption, the inhibition of adenosine reuptake seems to be involved, which could increase the activation of lymphocytes, stimulating the production of IgE. For the impact of exercise, increased tissue trans-glutaminase activity, vascular redistribution and dehydration are suggested.
Finally, at the metabolic level, studies currently tend to show that adenosine and the metabolism of eicosanoids could be involved in the activation of mast cells and basophils during anaphylactic reactions.
For Virginie Doyen, the identification of cofactors allows therapeutic education, to avoid situations involving them, while recognizing that their avoidance can be difficult. It also underlines the need for better knowledge of the mechanisms involved.
