Usefulness of the Nasal Allergen Provocation Test in the Diagnosis of Shellfish Allergy.

BACKGROUND AND OBJECTIVES: Shellfish allergy is a major cause of food allergy and anaphylaxis worldwide. Several allergenic proteins have been described in the last few years, but the only diagnostic tool that still enables discrimination between allergic and nonallergic sensitized persons is the oral food challenge (OFC). The aim of this study was to evaluate the usefulness of the nasal allergen provocation test (NAPT) as a diagnostic tool in shellfish allergy. METHODS: Forty-five patients with confirmed sensitization to shrimp by a positive skin prick test (SPT) result with a commercial shrimp extract were recruited and classified as sensitized-allergic or sensitized-nonallergic based on current tolerance to shrimp intake, the result of an OFC with a freeze-dried cooked shrimp mixture extract, or a recent history of anaphylaxis induced by shrimp ingestion. These patients and 10 controls not sensitized to shrimp underwent NAPT with a freeze-dried cooked shrimp mixture extract. The response was evaluated using acoustic rhinometry and a visual analog scale. RESULTS: Significant differences (P=.001) were found between the sensitized-allergic group (18/20 positive NAPT, 90%) and both the sensitized-nonallergic group (2/18 positive NAPT, 11.1%) and controls (0/10 positive NAPT). NAPT enables differentiation between allergic and nonallergic persons with a sensitivity of 90%, specificity of 89%, positive predictive value of 90%, and negative predictive value of 89%. CONCLUSIONS: Our results indicate that NAPT makes it possible to differentiate between sensitized symptomatic patients and sensitized tolerant patients and could be a valuable diagnostic tool when assessing shrimp allergy.

Shellfish Allergy: Unmet Needs in Diagnosis and Treatment.

Seafood is a major cause of food allergy and anaphylaxis worldwide. Shellfish is included among the "big eight" food groups, which are responsible for more than 90% of all cases of food allergy. Approximately 2.5% of the world's population has experienced an adverse reaction to seafood. Seafood allergy is one of the most frequent and lethal allergies that exist. The several allergenic proteins involved in allergic reactions that have been described in recent years include tropomyosin, arginine kinase, myosin light chain, and sarcoplasmic calcium-binding protein. Despite all the data reported in the last few years, shellfish allergy is still diagnosed and treated as it was 50 years ago. The only effective treatment to prevent allergic reactions to shellfish is avoidance. This review aims to update recently published data on shellfish allergy and to highlight those areas that have yet to be resolved.

Overcoming Shellfish Allergy: How Far Have We Come?

Shellfish allergy caused by undesirable immunological responses upon ingestion of crustaceans and mollusks is a common cause of food allergy, especially in the Asia-Pacific region. While the prevalence of shellfish allergy is increasing, the mainstay of clinical diagnosis for these patients includes extract-based skin prick test and specific IgE measurement while clinical management consists of food avoidance and as-needed use of adrenaline autoinjector should they develop severe allergic reactions. Such a standard of care is unsatisfactory to both patients and healthcare practitioners. There is a pressing need to introduce more specific diagnostic methods, as well as effective and safe therapies for patients with shellfish allergy. Knowledge gained on the identifications and defining the immuno-molecular features of different shellfish allergens over the past two decades have gradually translated into the design of new diagnostic and treatment options for shellfish allergy. In this review, we will discuss the epidemiology, the molecular identification of shellfish allergens, recent progress in various diagnostic methods, as well as current development in immunotherapeutic approaches including the use of unmodified allergens, hypoallergens, immunoregulatory peptides and DNA vaccines for the prevention and treatment of shellfish allergy. The prospect of a "cure "for shellfish allergy is within reach.

A comprehensive analysis of the allergenicity and IgE epitopes of myosinogen allergens in Scylla paramamosain.

BACKGROUND: Scylla paramamosain is one of the most common and serious food allergens in Asia. Therefore, research on its prevalence, accurate diagnosis, and IgE-binding pattern of the allergens is crucial. OBJECTIVE: To identify the IgE epitopes of the myosinogen allergens in S. paramamosain using phage peptide library. METHODS: The prevalence of allergy to crabs (AC) and of sensitization was analysed using a questionnaire and a serological assay. BAT was performed by flow cytometry, and its diagnostic performance was evaluated in relation to allergens purified from crab myosinogen. IgE-binding epitopes were identified by phage display using the IgE from patients with AC. Sequence- and structure-based bioinformatics analyses were performed to identify allergenic epitopes. RESULTS: Crab was the most common cause of food allergies in this study. Subjects with AC (n = 30) with clear clinical symptoms were identified by immunoblotting and BAT. All of the myosinogen allergens triggered basophil activation; surface expression of CD63 and CD203c was higher in patients allergic to AK and FLN c than in patients allergic to SCP and TIM. In addition to six conformational epitopes of SCP, six linear epitopes and eight conformational epitopes of AK were identified. Five linear epitopes and three conformational epitopes of TIM, nine linear and ten conformational epitopes of FLN c were also identified, and the sequence VH(I/T) L was appeared in epitopes of both TIM and FLN c. The number of epitopes showed consistency with the value of BAT. CONCLUSIONS AND CLINICAL RELEVANCE: BAT can be used for accurate diagnosis of AC. Identification of particular allergenic motifs could be a valuable tool for prevention, diagnosis, and treatment of food allergies.

Death by anaphylactic shock in an institution: an accident or negligence?

This is a description of a man, institutionalised for learning difficulties, known to have an allergy to seafood. After eating a pie, the patient quickly developed dyspnoea and vomiting. The staff at the institution administered epinephrine and called the emergency services. Despite cardiopulmonary resuscitation, the patient died shortly after being admitted to the emergency department of the University Hospitals of Geneva. In the light of the circumstances of the death and of a discrepancy between the information given to the police by the staff at the institution looking after the patient on the one hand, and the preliminary elements of the investigation on the other hand, it was suspected that there was failure in care of the patient and our institute was asked to carry out an autopsy. Basing on all the investigations carried out, the cause of death was anaphylactic reaction following the ingestion of seafood, contrary to what had been alleged by the staff at the home.

Shellfish allergens: tropomyosin and beyond.

IgE-mediated shellfish allergy constitutes an important cause of food-related adverse reactions. Shellfish are classified into mollusks and crustaceans, the latter belonging to the class of arthropoda. Among crustaceans, shrimps are the most predominant cause of allergic reactions and thus more extensively studied. Several major and minor allergens have been identified and cloned. Among them, invertebrate tropomyosin, arginine kinase, myosin light chain, sarcoplasmic calcium-binding protein, and hemocyanin are the most relevant. This review summarizes our current knowledge about these allergens.

Introduction of various allergenic foods during infancy reduces risk of IgE sensitization at 12 months of age: a birth cohort study.

BackgroundIn this study, we aimed to determine whether introducing various allergenic foods during infancy is associated with IgE sensitization at 12 months of age.MethodsDetailed information on feeding practices regarding six possible allergenic foods (fruits, egg white, egg yolk, fish, shellfish, and peanuts) was obtained by administering age-specific questionnaires to parents of infants at ages 6 and 12 months. Fecal secretory IgA (sIgA), fecal eosinophil cationic protein (ECP), and serum levels of total IgE and IgE specific to 20 foods, and IgE specific to 20 inhalant allergens were also quantified at 12 months of age.ResultsAt 12 months of age, infants with IgE sensitization had been introduced to fewer allergenic food items during infancy (3.2±1.4 vs. 3.7±1.3 items). Compared with infants who were given 0-2 allergenic food items, infants introduced to 3-4 or ≥5 allergenic food items showed a significantly lower risk of IgE sensitization (odds ratios (ORs) 0.62 and 0.61, respectively) and lower total IgE levels. In addition, non-introduction of egg white or egg yolk was significantly related to IgE sensitization (ORs 1.41 and 1.26, respectively).ConclusionIncreasing the diversity of allergenic foods in infancy, including fruits, egg white, egg yolk, fish, shellfish, and peanuts, may protect infants from IgE sensitization at 12 months of age.

Shrimp Allergy: Analysis of Commercially Available Extracts for In Vivo Diagnosis.

BACKGROUND AND OBJECTIVE: Skin prick testing (SPT) with commercial extracts is the first step in the diagnosis of shrimp allergy, although its clinical efficiency is unknown. Objective: To analyze the clinical usefulness of all commercial crustacean extracts available for SPT in Italy. METHODS: We performed a multicenter study of 157 shrimp-allergic patients who underwent SPT with 5 commercial crustacean extracts and with house dust mite (HDM) extract. Commercial extracts were analyzed using SDS-PAGE and compared with a freshly prepared in-house shrimp extract. IgE to Pen a 1/Pen m 1, Pen m 2, and Pen m 4 was determined, and immunoblot analysis was performed on a large number of sera. RESULTS: The skin reactions caused by commercial crustacean extracts were extremely heterogeneous, resulting in 32 clinical profiles, with marked differences in protein content and missing proteins at molecular weights corresponding to those of major shrimp allergens. Only strong Pen a 1/Pen m 1 reactors reacted to both HDM and all 5 commercial extracts in SPT. Most patients, including those who were tropomyosin-negative, reacted to HDM. Patients reacted to a large and variable array of proteins, and IgE reactivity was common at high molecular weights (>50 kDa). CONCLUSIONS: The in vivo diagnosis of shrimp allergy must continue to be based on SPT with fresh material. Shrimp-allergic patients frequently react to a number of ill-defined high-molecular-weight allergens, thus leaving currently available materials for component-resolved diagnosis largely insufficient. Mites and crustaceans probably share several allergens other than tropomyosin.

Seafood-Associated Shellfish Allergy: A Comprehensive Review.

Shellfish are diverse, serve as main constituents of seafood, and are extensively consumed globally because of their nutritional values. Consequently, increase in reports of IgE-mediated seafood allergy is particularly food associated to shellfish. Seafood-associated shellfish consists of crustaceans (decapods, stomatopods, barnacles, and euphausiids) and molluskans (gastropods, bivalves, and cephalopods) and its products can start from mild local symptoms and lead to severe systemic anaphylactic reactions through ingestion, inhalation, or contact like most other food allergens. Globally, the most commonly causative shellfish are shrimps, crabs, lobsters, clams, oysters, and mussels. The prevalence of shellfish allergy is estimated to be 0.5-2.5% of the general population but higher in coastal Asian countries where shellfish constitute a large proportion of the diet. Diversity in allergens such as tropomyosin, arginine kinase, myosin light chain, and sarcoplasmic binding protein are from crustaceans whereas tropomyosin, paramyosin, troponin, actine, amylase, and hemoyanin are reported from molluskans shellfish. Tropomyosin is the major allergen and is responsible for cross-reactivity between shellfish and other invertebrates, within crustaceans, within molluskans, between crustaceans vs. molluskans as well as between shellfish and fish. Allergenicity diagnosis requires clinical history, in vivo skin prick testing, in vitro quantification of IgE, immunoCAP, and confirmation by oral challenge testing unless the reactions borne by it are life-threatening. This comprehensive review provides the update and new findings in the area of shellfish allergy including demographic, diversity of allergens, allergenicity, their cross-reactivity, and innovative molecular genetics approaches in diagnosing and managing this life-threatening as well as life-long disease.

Sensitization pattern of crustacean-allergic individuals can indicate allergy to molluscs.

This study investigated the sensitization pattern of crustacean-allergic patients according to tolerance to molluscs. Thirty-one patients with anaphylaxis to crustaceans (14 with mollusc allergy and 17 with mollusc tolerance) were studied using skin prick tests (SPTs), specific IgEs (sIgEs) and SDS-PAGE immunoblotting. IgE-reactive shrimp proteins were identified by proteomic analyses. Patients with mollusc allergy presented more frequently SPTs positive to molluscs and higher sIgE titres in response to both molluscs and crustaceans. Shrimp-sIgE and rPen a1-sIgE values of 1.57 kUA /l and 4.38 kUA /l, respectively, showed positive likelihood ratios of 4.3 and 10.9 for the identification of mollusc allergy. Patients with mollusc allergy reacted more frequently to tropomyosin in immunoblots than did patients without it (93% vs 35%, respectively, P = 0.004). Reactivity to proteins other than tropomyosin (n = 14) was not different between the two groups. Among patients with crustacean anaphylaxis, patients with mollusc allergy and mollusc tolerance show a different pattern of sensitization, something that may help identify them.

Risk factors in pediatric shrimp allergy.

BACKGROUND: The prevalence of shellfish allergy is ∼1.3% in the United States, with shrimp most commonly reported. Shellfish is one of the top causes of food-induced anaphylactic reactions, yet there are no reported rates of pediatric shrimp anaphylaxis in the literature. In previously reported adults with shrimp allergy, the rate of anaphylaxis to shrimp was 42%. OBJECTIVE: To describe the rate of anaphylaxis among children with shrimp allergy, demographics, clinical presentation, and cross-reactive sensitization. METHODS: Retrospective chart review of children ≤18 years old who presented with shrimp allergy to Texas Children's Hospital Allergy and Immunology Clinic over 11 years. RESULTS: Sixty-eight patients were identified with shrimp allergy (61% male, 39% female), with a median age of diagnosis at 5.6 years (range, 0.96-16.6 years). The rate of anaphylaxis was 12%, and mucocutaneous symptoms were most common (skin symptoms, 70%; urticaria, 58%; and angioedema, 58%). No factors were positively associated with anaphylaxis, whereas patients without anaphylaxis had a significantly higher rate of eczema compared with those with anaphylaxis (p = 0.02). African Americans and Asian Americans were disproportionately affected (p < 0.001). There were low rates of cross-sensitization for other crustaceans and for mollusks (57% and 26%, respectively). CONCLUSION: The rate of anaphylaxis to shrimp was significantly lower in children with shrimp allergy than in adults, and anaphylactic reactions were negatively associated with eczema. Cross-reactivity to other crustaceans and mollusks does not uniformly occur. Prospective studies with double blinded placebo-controlled food challenges are needed to further characterize patients with shrimp allergy.

Stability and potency of raw and boiled shrimp extracts for skin prick test.

BACKGROUND: The difference of stability between raw and boiled shrimp extracts used in prick tests has never been investigated despite its potential consequences in tests development. The aim of this study was to compare the raw and boiled shrimp extracts of two species; Macrobrachium rosenbergii (freshwater shrimp) and Penaeus monodon (seawater shrimp) held at 4 ?C for different periods of time for their stability and potency in vivo by using the skin prick test (SPT) method. METHODS: Raw and boiled M. rosenbergii and P. monodon extracts were prepared and stored at 4 ?C for 1, 7, 14 and 30 days. Thirty patients were pricked with raw and boiled shrimp extracts at all storage times, as well as prick to prick skin test (PTP) to fresh raw and boiled shrimps of both species. The mean wheal diameter (MWD) resulting from prick tests for all shrimp extracts was measured and compared. RESULTS: The shrimp extracts of all storage times yielded positive skin test results in the range of 90% - 100%. Raw P. monodon extracts induced larger wheals than boiled extracts at all storage times. There was no significant difference of MWD between raw and boiled M. rosenbergii extracts on day 1, 7, and 14. Significant correlations between MWD of PTP to fresh shrimps and SPT to all shrimp extracts were observed. All shrimp extracts were sterile at all storage times. CONCLUSIONS: Raw and boiled M. rosenbergii and P. monodon extracts were stable and sterile at 4 ?C for at most 30 days. SPT with these extracts induced more than 10 mm in shrimp allergy patients and the results were comparable with PTP to fresh shrimps.

Shrimp Extract Exacerbates Allergic Immune Responses in Mice: Implications on Clinical Diagnosis of Shellfish Allergy.

Tropomyosin has been identified as the major cross-reactive shellfish allergen, but recent studies showed the presence of other clinically relevant allergens. This study aims at determining the allergic immune responses of mice sensitized with raw and boiled shrimp extracts in comparison to recombinant tropomyosin (rTM). Female Balb/c mice were intragastrically sensitized and challenged with raw, boiled shrimp or rTM. Systemic, cellular and humoral allergic responses were compared, while allergenicity of the extracts was also compared by skin prick test (SPT) and immunoblot on shrimp allergic subjects. We showed that rTM and shrimp extracts induced IgE- and Th2-mediated allergic responses in mice, distinguished by remarkable intestinal inflammation in small intestine across all regimens. Notably, boiled shrimp extract exhibited the highest sensitization rate (73.7% of mice developed positive TM-specific IgE response) when compared with raw extract (47.8%) and rTM (34.8%). Mice sensitized with boiled extract manifested the highest allergen-specific IgE and Th2 cytokine responses than the others. Immunoblot results indicated that tropomyosin remained the major allergen in extract-based sensitization and had stronger allergenicity in a heat-treated form comparing to untreated TM, which was in line with the SPT results that boiled extract induced larger wheal size in patients. Hemocyanin and glycogen phosphorylase were also identified as minor allergens associated with manifestation of shrimp allergy. This study shows that boiled extract enhanced sensitization and Th2 responses in agreement with the higher allergenicity of heat-treated TM. This study thus presents three shrimp allergy murine models suitable for mechanistic and intervention studies, and in vivo evidence implies higher effectiveness of boiled extract for the clinical diagnosis of shellfish allergy.

IgE Mediated Shellfish Allergy in Children-A Review.

Shellfish is a leading cause of food allergy and anaphylaxis worldwide. Recent advances in molecular characterization have led to a better understanding of the allergen profile. High sequence homology between shellfish species and between shellfish and house dust mites leads to a high serological cross-reactivity, which does not accurately correlate with clinical cross-reactions. Clinical manifestations are immediate and the predominance of perioral symptoms is a typical feature of shellfish allergy. Diagnosis, as for other food allergies, is based on SPTs and specific IgE, while the gold standard is DBPCFC. Cross-reactivity between shellfish is common and therefore, it is mandatory to avoid all shellfish. New immunotherapeutic strategies based on hypoallergens and other innovative approaches represent the new frontiers for desensitization.

IgE-Mediated Shellfish Allergy in Children.

Shellfish, including various species of mollusks (e.g., mussels, clams, and oysters) and crustaceans (e.g., shrimp, prawn, lobster, and crab), have been a keystone of healthy dietary recommendations due to their valuable protein content. In parallel with their consumption, allergic reactions related to shellfish may be increasing. Adverse reactions to shellfish are classified into different groups: (1) Immunological reactions, including IgE and non-IgE allergic reactions; (2) non-immunological reactions, including toxic reactions and food intolerance. The IgE-mediated reactions occur within about two hours after ingestion of the shellfish and range from urticaria, angioedema, nausea, and vomiting to respiratory signs and symptoms such as bronchospasm, laryngeal oedema, and anaphylaxis. The most common allergenic proteins involved in IgE-mediated allergic reactions to shellfish include tropomyosin, arginine kinase, myosin light chain, sarcoplasmic calcium-binding protein, troponin c, and triosephosphate isomerase. Over the past decades, the knowledge gained on the identification of the molecular features of different shellfish allergens improved the diagnosis and the potential design of allergen immunotherapy for shellfish allergy. Unfortunately, immunotherapeutic studies and some diagnostic tools are still restricted in a research context and need to be validated before being implemented into clinical practice. However, they seem promising for improving management strategies for shellfish allergy. In this review, epidemiology, pathogenesis, clinical features, diagnosis, and management of shellfish allergies in children are presented. The cross-reactivity among different forms of shellfish and immunotherapeutic approaches, including unmodified allergens, hypoallergens, peptide-based, and DNA-based vaccines, are also addressed.

Emerging approaches in the diagnosis and therapy in shellfish allergy.

PURPOSE OF REVIEW: Despite the high prevalence of shellfish allergy, the clinical management of seafood allergy has remained unchanged over decades. Here, we examined the current status in the diagnosis and clinical management of shellfish allergy and highlighted the imminent need for more specific diagnostic methods, as well as effective and safe therapeutic approaches for shellfish allergy. RECENT FINDINGS: With the advancement in the molecular identifications and definition of reactive epitopes of shellfish allergens, new diagnostic designs such as component-resolved diagnosis, basophil activation test (BAT) and the emerging IgE-crosslinking-induced luciferase expression are emerging. Furthermore, various allergen-specific immunotherapy strategies (such as shellfish extracts and allergens, hypoallergens, hypoallergen DNA vaccines, mimotopes and peptide-based therapies) are being explored at preclinical stages whereas limited nonallergen specific immunotherapy approaches are under clinical trials. SUMMARY: With an increasing understanding of the underlying immunological mechanisms and molecular features of shellfish allergy, the future for developing precise diagnostic and therapeutic strategies to better manage shellfish allergy is promising.

An update on shellfish allergy.

PURPOSE OF REVIEW: Shellfish is an important cause of food allergy worldwide, and a major cause of food-triggered anaphylaxis. Despite the wide variety of shellfish, there is considerable serological and clinical cross-reactivity of major shellfish allergens, and accurate diagnosis remains a challenge in the management of shellfish allergy. RECENT FINDINGS: Novel minor allergens have been discovered and characterized, and advances in component resolved diagnostics have provided insights into the prevalence of sensitization and their clinical importance in shellfish allergy. The extensive cross-reactivity between tropomyosin of house-dust mite and crustacean shellfish has been postulated to be the cause of a proposed mite-shellfish oral allergy syndrome. SUMMARY: More studies in food challenge-proven patients are required to establish the true prevalence and natural history of shellfish allergy. Refinement of component resolved diagnostics and testing for minor allergens may be helpful in developing more precise species-specific tests. Further investigation into the role of tropomyosin in house-dust mite and shellfish allergies may provide novel immunotherapeutic approaches for shellfish allergy.