The diagnosis of an IgE-mediated permanent food allergy is a life-changing event for patients and their families. The risk of a systemic reaction upon exposure and the possibility of anaphylaxis makes a life-threatening event out of any accidental exposure even when minute amounts of protein are involved or, especially in the case of crustaceans, when aerosolized particles are likely to be inhaled. Furthermore, each systemic episode is an entirely independent event which may turn out more severe than previous ones [1, 2, 11]. Adding to the uncertainty of systemic reactions due to food allergies, there is no diagnostic modality that would predict severity of reaction: skin tests and immunological assays for IgE antibody levels only predict likelihood of reaction and not severity [12]. The unpredictability of each reaction and the possibility of a fatal outcome places a constant burden on affected people who live under the threat of a sudden systemic reaction on practically every encounter, no matter how trivial, with food. Further complicating things, information on ingredients lists of manufactured foods is often misleading or erratic, and personnel involved in the preparation and serving of meals may lack access to relevant information. In light of these facts, long-term continuous control of immune responses to food allergens is a pressing necessity. Allergen-specific immunotherapy is the only disease-modifying modality for food allergy. Its implementation in a feasible, efficient, cost-effective, and safe way is the mainstay of long-term management [13]. With the present report, sublingual immunotherapy is presented, for the first time, as a useful modality in the long-term management of allergy to crustaceans. Administration of sublingual immunotherapy at home three times a day was tolerated by all patients and compliance remained satisfactory during the treatment period. During challenges, no systemic reactions were observed. Subsequent regular exposure to shrimp every other day was also tolerated without problems. Patients who remained asymptomatic during challenge, as well as patients who developed symptoms of localized nature with their first challenge and were placed on a limited-exposure protocol of 15–20 g every other day, have not developed symptoms with subsequent exposures to larger amounts of crustaceans. Consumption of shrimp at standard-serving (3 oz.) was not associated with symptoms on follow-up in either group.

The mechanisms of tolerance induction through sublingual immunotherapy have been extensively studied for long, but several of its long-term aspects are yet to be delineated [14]. Sublingual immunotherapy is user-friendly, inexpensive, free of significant complications, and is characterized by compliance levels superior to those of other forms of immunotherapy for allergens [15].

Regarding the long-term sustained outcome of desensitization, little is known and is mostly derived from experience with other food desensitization protocols. Sublingual immunotherapy for peanut allergy has been shown to result in decreased peanut-specific basophil activation and skin prick reactivity, as well as other parameters of IgE-effected sensitivity [16]. Upon discontinuation of sublingual immunotherapy, however, less than 11% of followed subjects had achieved sustained unresponsiveness [16]. Since sustained-unresponsiveness studies cannot be pursued in a private-practice setting, this issue will have to be addressed by larger-scale research projects. The patients of this cohort have all been advised to continue exposure to shrimp indefinitely at a minimum dose of 20 g every other day. As of the time of writing this report, no adverse events have been reported following regular intake of said amounts or with consumption of usual servings of crustaceans.

A pertinent feature of the present study is the assessment of symptoms and their evaluation in regard to their characterization as systemic or not. The resulting decision to continue with the challenge versus halting it was of major importance for the outcome of the challenges. By consensus, the emergence of a second symptom from a different system calls for an obligatory definition of the reaction at hand as an immune response of systemic nature [2, 10, 11]. In view of the risk for anaphylaxis, such a development would have led to cessation of the challenge and its assessment as a failure. For certain symptoms, however, a departure from the literary application of these criteria practice may be necessary, if these symptoms can be safely attributed to non-immune events, especially anxiety-related responses. In our study, certain symptoms were characterized as localized events even if they occurred along with other localized symptoms from a different system. Specific criteria for such an assessment were applied. Symptoms were termed as localized if: (i) they could be directly and unequivocally ascribed to anxiety, (ii) their severity had no measurable equivalent in objective parameters, (iii) increasing challenge doses led to no worsening of any other symptom and no escalation of the reaction was observed. The highly variable, subjective, and heterogenous nature of malaise, dizziness, nausea/vomiting, abdominal cramps, anxiety, tachycardia, and flushing is to be considered before the clinician in charge of the challenge arrives at the conclusion that mast cell degranulation of systemic magnitude has occurred. Without this modification and careful evaluation of symptoms within their context and timeliness, the rate of falsely-assessed failed food challenges is likely to be over-appreciated to the detriment of the patient’s interest.

A limitation of this study is that the challenges reported were all conducted with shrimp and this experience does not reflect established outcomes regarding other crustaceans, even though on follow up patients reported tolerance to other crustaceans. There is also a certain possibility that the tolerance that is demonstrated here may be limited to the three shrimp species that were exclusively used in the challenges. Furthermore, tropomyosin component testing was not performed and sensitization to Pen a 1 versus other shrimp allergens was not assessed [17]. Cross-reactivity with dust mite antigens was not studied either.

Fifty-three (80%) of the shrimp-allergic patients of the study had a history of a systemic reaction to shrimp, which was confirmed in 17 (25%) by baseline oral challenge. However, among the patients who underwent a post-treatment challenge, 12 patients (68%) had a history of systemic reactions and only 8 patients (44%) also had a positive oral shrimp baseline challenge before initiation of treatment. These discrepancies reflect a relatively higher willingness among patients with a history of localized-nature reactions to undergo a challenge, as well as for providers to order one.

A significant limitation of this study was the lack of pre-treatment baseline oral challenges for shrimp for 49 (75%) subjects. In a prospective study, routine baseline oral challenges would have been the standard of diagnosis. This drawback is inherent to the conditions of this study which was conducted in the setting of a private practice. The safety of the diagnosis of shrimp allergy for 75% subjects was based on the combination of the following positive findings: (i) all patients had been assessed by at least two Board certified Allergists from different practices, all of whom confirmed either the diagnosis of a systemic response, or a risk for a response serious enough to necessitate presription of Epinephrine and specific diet measures; (ii) all patients had positive shrimp skin tests performed by at least two different Allergists; (iii) by the time the post-treatment challenge was attempted, all patients had positive shrimp IgEs on at least 6 different occasions, several months apart, performed by different laboratories. The specificity of these combined data, although not as valid as a baseline oral challenge, was considered satisfactory for the purpose of treatment.