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Background: Shellfish allergy is an important cause of food allergy and anaphylaxis worldwide. Several allergenic proteins have been described in the last few years, but the only diagnostic tool that allows discrimination between allergic and non-allergic sensitized subjects is still the oral food challenge (OFC). Objective: The aim of this study was to evaluate the usefulness of nasal allergen provocation test (NAPT) as a diagnostic tool in the diagnosis of shellfish allergy. Methods: Forty-five subjects with confirmed sensitization to shrimp by a positive skin prick test (SPT) to a commercial shrimp extract were recruited and classified as Sensitized-Allergic or non-Allergic based on current tolerance to shrimp intake, the result of an OFC with a freeze-dried cooked shrimp mixture extract, or recent history of anaphylaxis from shrimp ingestion. These subjects and ten controls without shrimp sensitization were subjected to a NAPT with a freeze-dried cooked shrimp mixture extract. The response was evaluated by means of acoustic rhinometry (AcRh) and visual analogue scale scores (VAS). Results: Significant differences (p=.001) were found between the Sensitized-Allergic group (18/20 positive NAPT, 90%) compared to both Sensitized-non-Allergic (2/18 positive NAPT, 11.1%) and Control (0/10 positive NAPT) groups. NAPT allows differentiation between allergic and non-allergic subjects with a S: 90%, E: 89%, PPV: 90% and NPV: 89%. Conclusions: According to the study results NAPT may be a useful diagnostic tool that allows differentiating sensitized symptomatic subjects from sensitized tolerant. It could be a valuable test to consider when conducting a shrimp allergy study.

Cofactors may explain why in some cases food ingestion leads to anaphylaxis while in others elicits a milder reaction or tolerance. With cofactors, reactions become more severe and/or have a lower allergen threshold. Cofactors are present in up to 58% of food anaphylaxis (FAn). Exercise, NSAIDs, and alcohol are the most frequently described, although the underlying mechanisms are poorly known. Several hypotheses have suggested the influence of these cofactors on basophils and mast cells (MCs). Exercise has been suggested to enhance MC activation by increasing plasma osmolarity, redistributing blood flow, and activating adenosine and eicosanoid metabolism. NSAIDs’ cofactor effect has been related with cyclooxygenase inhibition and therefore, prostaglandin E2 (PGE2) production. Indeed, overexpression of adenosine receptor 3 (A3) gene has been described in NSAID-dependent FAn; A3 activation potentiates FcϵRI-induced MC degranulation. Finally, alcohol has been related with an increase of histamine levels by inhibition of diamino oxidase (DAO) and also with and increase of extracellular adenosine by inhibition of its uptake. However, most of these mechanisms have limited evidence, and further studies are urgently needed. In conclusion, the study of the immune-related mechanisms involved in food allergic reactions enhanced by cofactors is of the utmost interest. This knowledge will help to design both tailored treatments and prophylactic strategies that, nowadays, are non-existent.

The controlled drug exposure test (DPT) is currently considered the gold standard for the diagnosis of drug allergy. Drug-induced adverse reactions (ADRs) are a growing reason for consultation in both primary and specialized care. Allergology consultations in Spain are the ones that usually study these ADRs and rule out immunological mechanisms involved in up to 90% of the cases consulted. An adequate approach to these cases has an obvious impact on the costs and efficacy of the treatments required by other specialists, so that if we did not use DPTs, patients would require more expensive, more toxic and less effective treatments in most of the cases. In recent years, a large number of new drugs have been developed and this document is intended to be a practical guide in the management of PDT with the vision of the Spanish Allergology Society. Diagnostic work begins with a detailed history of the patient. Skin tests are only useful for some medications, and in most cases the diagnosis can only be confirmed by DPT. Although there is usually cross-reactivity, DPTs can confirm the diagnosis and also help to find a tolerable alternative drug. The individual management of patients in a programmed way, taking into account both the type of drug to be studied and the patient's comorbidities, usually allows a solution to be found for the majority of patients.