Shellfish Allergy Clinical Trial
Official title:
Safety of Chitosan as Wine Fining Agent in Shrimp Allergic Patients
Chitosan, the main component of the exoskeletons of crustaceans, mollusks and cephalopods,
has been used as a fining agent in wines. However, its safety among patients allergic to
shellfish has never been evaluated.
Adult patients followed at the Allergy and Clinical Immunology Department who have been
diagnosed with anaphylaxis to shrimp will be invited to participate in the study.
Clinical data will be collected to ascertain for eligibility and written information will be
provided. After signing informed consent, included subjects will perform skin prick-to-prick
tests (PTP) with shrimp boiling water condensate and with fined and unfined wines. All will
perform double blind oral challenge with the fined and unfined wines during 1visit day; the
placebo (unfined wine) and active challenge (fined wine with chitosan) will be separated by
2 hours. Challenge protocol will be performed with successive increasing doses administered
in 4 steps at 15-minute intervals for a total of 100 mL. During the challenge signs and
symptoms will be monitored by a trained physician.
Results will be presented as negative or positive (defined by presence of symptoms and signs
of an allergic reaction).
Categorical data will be compared by chi-square test. P<0.05 will be considered
statistically significant.
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.
;
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention