'I'm Allergic to Shrimp, but Only When I Dance'

In my early days of practice, I saw a patient who claimed that she could eat all foods, including shrimp, but was allergic to shrimp scampi—a simple dish with limited allergic potential. Besides the obvious crustacean, it consists of sautéed butter and garlic, plus or minus shallots or a bit of wine.

After limited testing was negative, I told her that I could not explain this. Then, as she left the office, she said, "Well, maybe I shouldn't dance after eating shrimp scampi."

Cofactor-Enhanced Anaphylaxis

In allergy, something that triggers or aggravates a reaction is termed a cofactor. The contribution of cofactors to immediate, systemic hypersensitivity reactions has been known for quite some time, and the most recognized type is food-dependent, exercise-induced anaphylaxis (FDEIA).

The first case, published in 1979, was in a long-distance runner many hours after eating shellfish (5-24 hr).^[1] After that, sporadic cases of FDEIA were reported along with other cofactors,^[2] particularly nonsteroidal anti-inflammatory drugs (NSAIDs),^[3] followed by a report of food anaphylaxis triggered by NSAIDs but not exercise.^[4]

In one study of cofactor-enhanced food anaphylaxis, the contributing factors were identified by history as exercise (53%) and alcohol (12%), alone or in combination, and NSAIDS (58%).^[5]

Are Some Cofactors Worse Than Others?

Christensen and colleagues^[6] took it a step further and studied 25 people with purported wheat-dependent, exercise-induced anaphylaxis with various cofactor challenges. They performed titrated double-blind, placebo-controlled food challenges with gluten at rest and then with treadmill exercise, aspirin, and alcohol alone—and then if negative, with a combination of exercise and aspirin.

About half of the study participants reacted at rest. The others required a cofactor to provoke a reaction, all of which were enhanced, lowering the food allergen threshold for eliciting symptoms (by 70% with exercise and 85% with aspirin). Alcohol was found to be the least provocative cofactor.

Not surprisingly, the combination of two cofactors led to the greatest reduction in threshold dose (90%) compared with reactions at rest. The reactions were also more severe. In total, 92% of patients reacted to the food allergen with exercise, 84% with aspirin, and 56% with alcohol. For unclear reasons, three of the 25 participants reacted to single cofactors but not to those in combination, which in my opinion speaks to the difficulty of identifying eliciting cofactors in these patients.

Intercurrent infection is another recognized risk factor that lowers the threshold for reactivity to foods. Other proposed cofactors include ACE inhibitors and acid suppression from proton pump inhibitors (which is theorized to reduce allergen degradation).

The clinician's knowledge of cofactors can help to uncover otherwise unexplained intermittent systemic allergic reactions to foods. The transmission of this information to patients is critical. It may not be the standard of care to advise a patient who passes a food challenge that they may still be sensitive to that food under certain circumstances, but perhaps it should be.

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