Safety of Chitosan as Wine Fining Agent in Shrimp Allergic Patients (SWAP)

Hypersensitivity reactions to wine have been rarely reported in the literature, and they are mainly attributed to grape proteins [1], biogenic amines, salicylates, sulfites or yeast [2,3]. However, wine production traditionally involves fining, during which some ingredients such as tannins are removed by co-precipitation with proteins derived from milk (casein, potassium caseinate), egg (ovalbumin, lysozyme), fish (isinglass) or shrimp (chitosan). These proteins are derived from animal sources which are known to play a role in food allergy. This is an increasingly prevalent health problem in Western countries [4,5] and it may manifest itself as life-threatening anaphylactic shock in the presence of only traces of the allergen. Recently, the safety for wine-fining agents derived from milk, fish and egg was established [6]. However, for chitosan, no studies of its safety as a fining agent in allergic patients were performed until now. Chitosan is used as fining agent by the mead and wine industry because of its electrostatic positive charge. Chitosan is obtained by the deacetylation of Chitin [C8H13NO5N]n , a derivative of glucose, and one of the most common polymers found in nature. It is the main component of the cell walls of some fungi, the exoskeletons of arthropods such as crustaceans and insects, the radulae of mollusks, and the beaks of cephalopods, including squid and octopuses [7].

Seafood plays an important role in human nutrition and health, and Portugal is the European country with the second highest consumption [4]. The prevalence of crustacean allergy seems to vary largely between geographical locations, but it seems common in Portugal [8]. The major shellfish allergen is tropomyosin although other allergens may play an important part in allergenicity. The possibility of allergic reactions attributed to traces of chitosan used as a fining agent in wine has not been ruled out, particularly in shrimp allergic patients to whom small traces of the potential allergen may be enough to trigger anaphylactic reactions. Our aim is, therefore, to establish the safety of wine containing chitosan in patients who are severely allergic to shrimp [9].

Potential Risks Several studies published in the literature have evaluated the safety of skin tests, but mostly using commercial extracts. Prick-tests to native foods, called prick-to-prick tests, have been less extensively studied. The CICBAA1 data, from 1,138 food allergic patients of all ages, cover 34,905 prick-to-prick tests to foods. The risk of systemic reactions was evaluated at 0.008% [10, 11]. The negative predictive accuracy for skin prick testing to foods is uniformly high. A negative skin test confirms the absence of an IgE-mediated reaction with 90 to 95% accuracy [12,13]. Therefore, skin testing is highly useful for excluding IgE-mediated food allergy.

However, when positive, these tests, which evaluate sensitization and not clinical allergy, are not without pitfalls, and their results must be confirmed by an oral challenge to avoid over- and under diagnosis.

The double-blind, placebo-controlled, oral food challenge (DBPCFC) is considered the gold standard for diagnosing food allergy and it is preferred for research purposes [14]. The overall level of risk associated with food challenges has been examined. A retrospective series reviewed 584 OFCs performed in children who were estimated to have a ≤50% risk of reaction. Forty-three percent of the challenges were positive. Thirty-nine percent of the reactions were mild, 33% moderate, and 28% severe. The type and incidence of the different reactions were cutaneous (78%), gastrointestinal (43%), oral (26%), lower respiratory (26%), and upper respiratory (25%). No patients had cardiovascular symptoms [15].

Participants with positive and negative skin tests will proceed to oral challenge, as sensitization does not have a linear correlation with clinical allergy. Although the risk of a positive reaction to oral challenge with finned wine with chitosan is very low (severe seafood allergy is usually mediated by major shellfish allergen tropomyosin, not present in chitosan), for safety purposes the challenges will be performed in an appropriate setting, with CPR support available, medication and a doctor present at all times.

Potential Benefits It will allow for patients with shellfish allergy to be informed if they can safely ingest this wine. Furthermore, it will be needed as a public health measure as this information could be included in the wine labels.

STUDY OBJECTIVES

To investigate the safety of chitosan, as wine fining agent, in patients with severe allergy to shrimp.

Primary Outcome: Result of a DBPCFC with chitosan fined wine.