What Factors Turn an Ordinary Allergic Reaction into Anaphylaxis?

Why do some allergic reactions produce only relatively mild symptoms while others trigger anaphylaxis and eventual death?

Researchers from Berlin have combed through the literature to identify which factors seem to augment allergic reactions most frequently and transform minor reactions into serious problems. “The phenomenon of augmentation has been well known for a long time, but is still neglected,” wrote the authors of the new research review, which appears in the journal Allergy.

The augmenting factor that comes up most frequently in published research is physical exercise. Studies indicate that exercise can increase the effects of allergies triggered by medicine or, more commonly, food — even if the food is eaten a full 4 hours before or 1 hour after the exercise. Some papers have speculated that exercise, by increasing body temperature and blood flow, increases the influx of allergen from the gut to the rest of the body. Other studies have focused on increased osmolarity and a lowered ph, which may increase basophil activation and stimulate histamine release.

Non-steroidal anti-inflammatory drugs, which are often flagged as an independent trigger of allergic reactions, may also augment reactions triggered by other allergens. For example, the study authors note, “NSAIDs can cause gastrointestinal hyperpermeability, which elevates serum gliadin levels in a dose-dependent manner and may therefore accelerate symptom development in gliadin-sensitized patients with wheat allergies.”

Acute infections have also been shown to augment allergic reactions. Indeed, in addition to case reports that report a link, studies of oral tolerance consistently find that threshold tolerances to known allergens are often lower than normal when patients are fighting infections.

Infections may augment allergic reactions in much the same fashion as exercise, with elevated body temperature and blood flow spreading more of the allergen from the gut. Some gastrointestinal infections may also let larger chunks of allergen pass through the gut and to the rest of the body.

Some research has found that very warm environments or very cool environments may augment allergic reactions, but both links remain uncertain, particularly given the lack of any obvious reason why external temperatures would prove significant.

Alcohol, likewise, plays an uncertain role in allergic reactions. There have been some case studies suggesting that alcohol may have triggered anaphylaxis or — at the very least — helped another allergen trigger anaphylaxis.

There are also plausible rationales to explain such reports, rationales that range from the fact that alcoholics are known to have higher IgE levels than teetotalers to the speculation that alcohol may lower inhibitions about ingesting allergens.

But the authors of the new meta-study note a general lack of papers on the topic and conclude that the matter remains unsettled, much like the matter of whether antacids are a substantial augmenting factor for allergic reactions.

The study authors urge clinicians to consider antacid, exercise and all the rest in mind whenever they attempt to diagnose allergy triggers.

“After anaphylactic reactions always ask for possible augmentation and other risk factors during the recent past,” they wrote. “If augmentation is suspected, oral food challenges should be performed in combination with augmenting factors.”

In cases where patients with allergies seem susceptible to augmenting factors, the study authors say doctors should consider urging them to take antihistamines to counteract the possible effect of such aggravators and, of course, to be mindful of the augmenting factors as well as the actual allergens.