Pathophysiology, diagnosis and management of exercise-induced anaphylaxis

Abstract

Implications for future research are the physiological changes that occur during exercise need deeper consideration to ensure that proposed mechanisms are realistic and actually occur within the time frame and exercise-intensity domain during which the reported FDEIA occurred. These theories must be tested rigorously with sufficiently powered studies if progress is to be made in determining the perplexing pathophysiology of FDEIA.

About the role and underlying mechanisms of cofactors in anaphylaxis

“…To date, the best characterized EIA syndrome which therefore can serve as a model disease is FDEIA following consumption of products containing wheat (25). This most prevalent subform of FDEIA, termed 'wheat-dependent exercise-induced anaphylaxis' (WDEIA), was characterized in detail by Palosuo et al (26).…”

“…Matsuo et al (30) could show significantly increased uptake of gliadin in humans after consumption of wheat followed by adequate physical exertion. One possible underlying mechanism is intestinal barrier dysfunction; however, a high intensity and a long duration of more than 8 h were shown to be necessary to obtain a relevant barrier dysfunction (25). This indicates at least additional other mechanisms of action, because clinical observation shows that the intensity of exercise necessary to trigger FDEIA in humans varies quite tremendously from exercise near exhaustion to very mild.…”

“…These were more marked if patients underwent a defined form of exercise prior to testing (32,33). One explanation for this decreased cellular activation threshold that is discussed is increased plasma osmolality, because intense exercise leads to an increased serum osmolality and changes in pH (25,34,35). However, in vitro studies confirming this hypothesis applied osmolality levels of at least 340 mOsm normally not reached under exercise or even under pathologic conditions, which only slightly exceed physiological values of 280-290 mOsm (25,34,35).…”

“…One explanation for this decreased cellular activation threshold that is discussed is increased plasma osmolality, because intense exercise leads to an increased serum osmolality and changes in pH (25,34,35). However, in vitro studies confirming this hypothesis applied osmolality levels of at least 340 mOsm normally not reached under exercise or even under pathologic conditions, which only slightly exceed physiological values of 280-290 mOsm (25,34,35). Alternative concepts postulate that activation of tissue transglutaminase (tTG) in the intestinal mucosa is able to enhance degranulation on a cellular level and that exercise-induced release of endorphins may enhance MC or basophil activation.…”

“…Like ASA, alcohol relaxes tight junctions in gut epithelium suggesting consecutive increase in intestinal protein absorption (25). Especially for small proteins, an alcohol-dependent increase in the intestinal absorption seems to be an underlying mechanism for anaphylaxis (55,56); however, experimental evidence is still sparse.…”