Seafood allergies: Fish and shellfish

INTRODUCTION — Seafood allergy is the most common food allergy in adults and among the six most prevalent food allergies in young children [1,2].

The term "seafood" encompasses the following:

●Vertebrate finned fish, such as salmon, tuna, and cod

●Crustaceans, such as shrimp, prawn, crab, lobster, and crawfish

●Mollusks, such as squid, snails, and bivalves (scallops, clams, oysters, mussels, and others)

The term "shellfish," a subset of seafood, includes crustaceans and mollusks.

Seafood allergies are immunologic responses to proteins in these foods and include immunoglobulin E (IgE) antibody-mediated allergy, as well as other allergic syndromes [1]. They are distinct from adverse reactions due to toxins or infectious contaminants, which are not immune based [3,4]. (See "Overview of shellfish, pufferfish, and other marine toxin poisoning".)

In this topic review, the epidemiology, pathogenesis, clinical features, diagnosis, and management of seafood allergies will be presented. Issues of cross-reactivity among different forms of seafood are also addressed. General discussions of food allergy are presented separately in appropriate topic reviews. (See "Food intolerance and food allergy in adults: An overview".)

EPIDEMIOLOGY

General population — Allergies to seafood are estimated to affect 1 to 3 percent of the population [2,5-11]. Allergy to shellfish is among the leading causes of food allergy in adults and the most common cause of food-allergic emergency department visits [12].

Several large studies have provided estimates of prevalence [5-8,10,13]. One multinational survey of 17,280 adults (aged 20 to 44 years) from 15 countries questioned participants about foods that "nearly always" caused "illness" or "trouble" [7]. Shrimp, oysters, and fish were implicated by 2.3, 2.3, and 2.2 percent, respectively.

Internationally, patterns of seafood consumption likely influence the prevalence of specific fish and shellfish allergies. As examples, allergy to whelk is seen in Korea, where this mollusk is a popular form of seafood, and barnacle allergy has been reported in the Portuguese population [14,15]. A random calling survey in Singapore found a reported rate of shellfish allergy of 7.2 percent in 4- to 6-year-olds and 11.6 percent in 14- to 16-year-olds; applying features of a convincing history reduced these rates to 1.2 percent and 5.2 percent, respectively [16]. However, these rates are higher than similar studies from the United States [5,6,10].

A 2019 United States adult study that utilized a survey administered to United States population representative panelists, applying criteria to identify convincing allergy based on symptoms through self-reporting, found a rate of 2.9 percent shellfish and 0.9 percent finned fish allergy [5]. The same approach for children reported a rate of 1.3 percent for shellfish and 0.6 percent for finned fish allergy [2]. A 2004 American study estimated the prevalence of seafood allergy using a nationwide cross-sectional telephone survey in which a standardized questionnaire was administered to households chosen by random calling [6]. Criteria were established in advance to define seafood allergy by either a convincing history of symptoms (eg, urticaria, angioedema, trouble breathing, oral pruritus, or throat closing) or a diagnosis of allergy by a clinician. A total of 5529 households completed the survey (67.3 percent participation rate), representing a census of 14,948 individuals. Fish or shellfish allergy was reported in 6 percent of households and among individuals as follows: 2.3 percent for any seafood allergy, 2 percent for shellfish, 0.4 percent for fish, and 0.2 percent for both fish and shellfish.

This study also revealed the following findings:

●Prevalence rates in children were significantly lower than those in adults in all categories, as follows: any seafood allergy (0.6 versus 2.8 percent), shellfish (0.5 versus 2.5 percent), and fish (0.2 versus 0.5 percent). Boys were affected more often than girls.

●In adults, the sex trend was reversed, and rates in females were significantly higher than in males for both shellfish allergy (2.6 versus 1.5 percent) and fish allergy (0.6 versus 0.2 percent).

●The highest rates of seafood allergy were reported by African Americans, with shellfish reported as the leading cause. In another study, the high rate of shellfish allergy in African American children (compared with White children) was substantially mediated by a higher rate of sensitization to cockroach and house dust mite, supporting the notion that sensitization to homologous tropomyosin proteins in the environmental allergens may influence shellfish allergy [17].

●The most common reported fish allergies, in order of decreasing frequency, were salmon, tuna, catfish, cod, flounder, halibut, trout, and bass.

●The most common reported shellfish allergies, in order of decreasing frequency, were shrimp, crab, lobster, clam, oyster, and mussel.

PATHOGENESIS — The major allergenic proteins in seafood that are responsible for IgE-mediated reactions have been identified [18]. Persons with seafood allergy may react to these and/or other seafood proteins:

●Parvalbumins are major allergens in fish [18]. Enolases, aldolases, and fish gelatin are also significant allergens [19,20].

●Tropomyosins, sarcoplasmic calcium-binding protein, and glycogen phosphorylase proteins are major allergens in shrimp and possibly other shellfish [21,22]. Other allergens, including the muscle protein myosin light chain, are prominent allergens in shrimp. Several additional proteins (eg, arginine kinase and hemocyanin) are also present in other arthropods (ie, dust mites, cockroaches), accounting for cross-reactivity between these groups [23,24].

The pathogenesis of non-IgE-mediated seafood allergy is unclear. A syndrome that clinically resembles protein-induced enterocolitis has been described in both children and adults. (See 'Non-IgE-mediated reactions' below.)

CLINICAL FEATURES

IgE-mediated reactions — IgE-mediated allergic reactions are the most commonly described type of allergic reactions to seafood ingestion. These may present as generalized reactions, asthmatic reactions in response to occupational or household exposures, or as food-dependent, exercise-induced anaphylaxis.

IgE-mediated reactions are rapid in onset (usually within minutes to one hour after ingestion), and extra-gastrointestinal manifestations, such as urticaria, angioedema, respiratory symptoms, and laryngeal edema, are common (table 1). These can range in severity from mild to life-threatening anaphylaxis; severe reactions are not uncommon [5,25]. The clinical features of IgE-mediated reactions are discussed in more detail separately. (See "Clinical manifestations of food allergy: An overview".)

Occupational and household exposures involving inhalation of cooking or processing vapors may cause asthma [26,27]. (See "Occupational asthma: Pathogenesis".)

Food-dependent, exercise-induced anaphylaxis to seafood has also been reported. In this condition, the food causes symptoms only if ingestion is followed soon after by exercise or exertion but is tolerated in the absence of exertion. Wheat products and seafood are the two most frequently implicated foods in this disorder [28]. (See "Exercise-induced anaphylaxis: Clinical manifestations, epidemiology, pathogenesis, and diagnosis".)

Severity — IgE-mediated fish and shellfish allergies can vary from mild to severe. In one United States prevalence study, 60 to 70 percent of respondents experienced urticaria/angioedema, and over one-half reported dyspnea or throat tightness [6]. Consistent with this, approximately one-half of reactions prompted evaluation by a clinician or care in an emergency department. Despite the severe symptoms, administration of epinephrine was provided to only 16 percent of individuals treated in medical settings. In a study of adults, 57 percent of fish and shellfish allergies were classified as severe [5]. In a study of children, 48.7 percent of shellfish and 49 percent of those with finned fish allergy reported severe reactions [2]. In a retrospective chart review of 68 children with shrimp allergy from a referral center in Texas, the rate of anaphylaxis (compared with lesser reactions) was 12 percent [29].

Deaths from seafood allergy have been recorded. In a registry of food-induced fatal anaphylaxis comprised primarily of children, 1 of 32 deaths was due to fish [25]. In a United Kingdom registry of fatalities from anaphylaxis, 3 of 33 fatalities to a known food were caused by seafood [30].

Non-IgE-mediated reactions — There are several other reactions to seafood exposure that are not IgE mediated. They include:

●Food protein-induced enterocolitis syndrome (FPIES) in children, a non-IgE-mediated allergic reaction

●An enterocolitis-like reaction in adults

●Contact dermatitis in those with occupational and household skin exposure

Gastrointestinal reactions — In some regions, particularly Spain, fish is a prominent cause of FPIES in infants and young children. FPIES is a non-IgE-mediated form of food allergy that presents with profuse vomiting and/or diarrhea several hours after ingestion of a given food [31,32]. Infants and young children can present with a sepsis-like picture. Skin prick tests to the causative food are typically negative. FPIES in children is presented in more detail separately. (See "Food protein-induced enterocolitis syndrome (FPIES)".)

Seafood may also cause an enterocolitis-like disorder in adults, with delayed onset of nausea, crampy abdominal pain, and protracted vomiting or diarrhea [1,33,34]. One severe case involved hypotension and blood-tinged diarrhea reproduced upon oral challenge [35]. This appears to be primarily reported in response to mollusks. Adults typically present after having experienced this on several occasions, reporting that they had attributed the first one or two reactions to possible food poisoning. Indeed, these reactions clinically mimic diarrhetic shellfish poisoning (DSP), beginning one to six hours after ingestion and resolving within a few hours to three days, depending on severity. (See 'Differential diagnosis' below.)

The etiology of these enterocolitis-like reactions in adults is unclear. Their repeated occurrence in certain individuals suggests either that some persons are more susceptible to toxic components in these foods or that this reaction represents a form of allergy. There are very few studies of the pathogenesis of these reactions, although one study of adults with isolated gastrointestinal symptoms to various types of seafood included six patients who reacted repeatedly to oyster in whom specific IgE was generally undetectable [36]. No formal information about epidemiology, range of severity, or prognosis is available, and there are no data to guide informed recommendations about this type of reaction. (See 'Delayed gastrointestinal reactions' below.)

Allergic contact dermatitis — Allergic contact dermatitis can result from occupational skin exposure to seafood (eg, in food handlers or packers) [37,38]. Disruption of the skin barrier has been implicated as a risk factor for the development of this condition in exposed workers.

Age of onset and natural course — In the American prevalence survey reviewed previously, allergy developed in adulthood for 40 and 60 percent of individuals with fish and shellfish allergy, respectively [6]. Fifty-eight percent reported multiple reactions, with two to five episodes being typical [6]. Fifteen to 20 percent of people experienced more than six reactions [6]. In the United States survey of adults published in 2019, 48 percent developed shellfish allergy, and 40 percent developed fish allergy during adulthood [5].

Seafood allergy is considered to be persistent in most cases [39]. In the American telephone-based survey, only 3 to 4 percent of individuals with seafood allergy reported developing tolerance over time [6].

However, loss of fish allergy during childhood or in adulthood has been reported, although the extent to which this occurs is not well studied [40]. In a study evaluating IgE binding to various epitopes of major shrimp allergens, children showed stronger and more diverse IgE binding than adults, implying the allergy may resolve with time [41]. In a study of 58 children with fish allergy whose first reaction was at a median 1.3 years, 22 percent achieved tolerance of all fish tested over 1 to 14 years of follow-up [42]. In this study, tolerance to all fish ranged from 3.5 percent in preschool-age children to 45 percent among adolescents. Recurrence of fish allergy after tolerance has also been reported [43].

DIAGNOSIS — A general discussion of the diagnosis of food allergy is presented elsewhere. A summary of this information, with a focus on those aspects that are most relevant to the diagnosis of seafood allergy, is provided below. (See "History and physical examination in the patient with possible food allergy" and "Diagnostic evaluation of IgE-mediated food allergy".)

With the exception of in vitro immunoassays for specific IgE, other diagnostic allergy procedures, including skin testing and food challenges, should be performed by allergy specialists with training in the management of serious allergic reactions.

IgE-mediated reactions — For suspected IgE-mediated reactions, the history of an immediate reaction consisting of typical allergic symptoms supported by positive tests for specific IgE antibodies is sufficient to establish a diagnosis. Either skin prick tests or in vitro tests for IgE are usually performed initially. (See "History and physical examination in the patient with possible food allergy" and "Diagnostic evaluation of IgE-mediated food allergy".)

The positive predictive value of skin prick testing with commercial seafood extracts and IgE immunoassays has not been compared with clinical reactivity in appropriate populations using oral food challenges. This is true for seafood and for most foods.

However, the negative predictive value of skin prick testing with commercial food extracts is generally high. In our clinic, we have found that negative skin tests with commercial seafood extracts that are in accordance with the clinical history are usually reliable. If there is uncertainty or the clinician has limited experience with a specific commercial extract, the actual food can be used for skin testing instead.

If the history is suggestive of allergy and one or both forms of testing are negative, then it is useful to repeat skin testing using the implicated seafood, prepared in a manner similar to the exposure that caused the reaction (eg, raw if sushi caused the reaction). (See 'Diagnostic pitfalls' below.)

Component-resolved diagnostics (CRD) refers to in vitro testing to determine if a patient's IgE binds to individual proteins within an allergenic food. Some CRD testing for allergenic proteins in seafood is commercially available, although these tests are not able to obviate the need for food challenge. (See "Component testing for animal-derived food allergies", section on 'Shrimp'.)

In each case of diagnosed seafood allergy, possible allergy to cross-reactive fish or shellfish must be addressed. (See 'Cross-reactivity' below and 'Eating other seafood' below.)

If the history and/or IgE test results do not clearly indicate an allergy, then clinician-supervised oral food challenges would be required to exclude the diagnosis. The use of challenges in the diagnosis of food allergy is presented separately. (See "Oral food challenges for diagnosis and management of food allergies".)

Asthma — The diagnosis of suspected occupational asthma due to seafood allergy, which is also IgE mediated, involves skin prick testing, pulmonary function testing, and possible bronchoprovocation challenge. Occupational asthma is discussed in more detail separately. (See "Occupational asthma: Clinical features, evaluation, and diagnosis".)

Other reactions — IgE tests are expected to be negative if the symptoms do not suggest an IgE-mediated reaction, such as delayed gastrointestinal reactions or contact dermatitis.

●The diagnosis can be confirmed by challenge in the case of food protein-induced enterocolitis syndrome (FPIES) in children, although this type of challenge can induce severe symptoms and is uncommonly performed. (See "Food protein-induced enterocolitis syndrome (FPIES)".)

●The diagnosis of enterocolitis in adults would also require challenge, although patients who have experienced these reactions on several occasions may decline, understandably. Diagnosis based on history alone is reasonable in cases of recurrent reactions, as this essentially rules out incidental poisoning or bacterial contamination.

●In cases of contact dermatitis, patch testing with a preparation of the seafood in question may be informative, although such testing is not standardized. (See "Patch testing".)

Diagnostic pitfalls — There are several additional factors that can make the diagnosis of seafood allergy challenging (table 2). Digestion, various processing methods (heating/canning), and preparation issues (eg, which part of the fish is eaten) may influence the amount of relevant allergen in the final meal, as demonstrated by the following studies:

●Studies suggest that fish preparation methods (eg, boiling versus frying versus eating raw) may impact the allergenicity of fish in different ways [11,44,45]. Also, the impact of these factors can vary among species of fish.

●In 38 children who were allergic to tuna or salmon, 12 reacted to canned forms, but 8 of the remaining 26 were found to tolerate the canned forms [46].

●Digestion can also reduce the potential allergenicity of fish allergen and may result in variable clinical outcomes depending on, for example, stomach acidity [47-49].

●The part of the fish ingested can have different levels of the major allergen, such that dark or red muscle may lack the allergen compared with white muscle [50,51]. It is also possible to be allergic to caviar (fish roe) but not fish [52].

●Skin testing to crustacean seafood (eg, shrimp, lobster, crab, crayfish) may be falsely positive due to sensitization to arthropods (eg, dust mite, cockroach).

Because of these variables, it is important to repeat skin testing using the same seafood prepared in a similar manner to that which caused the reaction whenever a convincing clinical history cannot be readily validated by routine testing. For example, a patient was reported who reacted only to canned forms of tuna [53]. (See 'Allergy to additives in canned fish' below.)

DIFFERENTIAL DIAGNOSIS

Scombroid poisoning — The primary masquerader of IgE-mediated reactions is scombroid fish poisoning [3]. The epidemiology, clinical manifestations, and treatment of scombroid poisoning are reviewed separately. (See "Overview of shellfish, pufferfish, and other marine toxin poisoning".)

Several types of dark meat fish (eg, tuna, bluefish, mackerel, and others) elaborate histamine-like chemicals during spoilage that are produced by bacteria in the fish flesh. Upon ingestion, these chemicals can cause reactions that mimic IgE-mediated allergy, with flushing and urticaria beginning within one hour of eating [4]. Symptoms that help distinguish these reactions from allergy include perioral sensations of tingling and burning, headache, and dizziness (as opposed to presyncope).

Diagnosis — Patients with scombroid poisoning do not have evidence of specific IgE to that type of fish. The absence of specific IgE may be demonstrated by skin prick testing with a different sample of the same type of fish, a commercial extract of that fish, or in vitro assays. Challenge with the seafood in question may be needed for conclusive diagnosis of scombroid poisoning.

Other approaches to diagnosis are possible if the patient saved or can obtain some of the fish that caused the reaction:

●A sample of the culprit fish can be analyzed for histamine content, as discussed separately. (See "Overview of shellfish, pufferfish, and other marine toxin poisoning".)

●A sample of the fish can be pulverized and used in prick-by-prick skin testing and compared with the result with a commercial extract of the same fish. If only the culprit fish sample is positive, then it can be used to test a nonallergic volunteer [54]. If both individuals react positively to the culprit fish, then it can be deduced that histamine-like chemicals in the fish sample are the cause of these nonspecific positive reactions, and the diagnosis is scombroid poisoning.

Other types of seafood poisoning — Other types of seafood poisoning (eg, toxins such as ciguatoxin or contamination such as botulism and others) may result in a variety of neurologic and gastrointestinal symptoms that usually do not resemble IgE-mediated allergic reactions [4]. The various forms of seafood poisoning are presented in detail elsewhere. (See "Ciguatera fish poisoning" and "Overview of shellfish, pufferfish, and other marine toxin poisoning".)

Diarrhetic shellfish poisoning (DSP) causes the delayed onset of nausea, vomiting, and colicky abdominal pain and can mimic enterocolitis. DSP results from the ingestion of mollusks contaminated with okadaic acid produced by dinoflagellates. This disorder generally comes to medical attention because of outbreaks. However, because DSP can be relatively mild and self-limited, it is unclear what proportion of cases is unreported. (See "Overview of shellfish, pufferfish, and other marine toxin poisoning", section on 'Diarrheic shellfish poisoning'.)

Anisakis — Allergy to the fish parasite Anisakis simplex represents another potential diagnostic dilemma [55,56]. Anisakis simplex is a nematode that infects fish worldwide and can cause several health issues in humans. Humans are accidental hosts who can become transiently infected as a result of eating the raw or undercooked flesh of infected fish (typically herring, hake, black plaice, and cod) [55]. Deep freezing and rethawing of fish kills the parasite [57]. Some countries (including the United States) have legislation requiring that any fish intended for raw consumption must be deep frozen for specified time periods (which differ depending on the temperatures used) [57]. However, this may not be strictly enforced [58]. The majority of cases of Anisakis simplex reactions have been reported at the highest rates in Portugal and Norway, with reports from many other areas of the world [56].

One manifestation of Anisakis allergy is a generalized reaction involving urticaria, angioedema, abdominal pain, and/or anaphylaxis, which develops as the live larvae penetrate the gastric mucosa [55,59]. Gastrointestinal symptoms may be minimal or absent, and a delay in the onset of symptoms of between 2 and 24 hours is typical [60,61]. This delay between consumption of raw fish and onset of symptoms can be an important diagnostic clue to the presence of Anisakis allergy.

A major allergenic protein (Ani s 7) in Anisakis species has been identified, although a test for the presence of specific IgE to Ani s 7 is not commercially available [62]. It appears that parasite larvae must be viable to induce the reaction described previously, as neither skin testing with whole body extracts nor oral challenge with lyophilized parasites reproduces symptoms [63-65]. Excretory or secretory proteins produced by the live larvae have been implicated as possible allergens [60,64].

Anisakis allergy likely contributes to occupational respiratory allergy and contact dermatitis in fish processing workers. In one study, sensitization to Anisakis was as common as that to fish [65]. However, it is not clear what other clinical syndromes can be correctly attributed to Anisakis allergy. The optimal approach to skin testing is also uncertain, although prick-by-prick skin testing with live larvae appears to be most consistently positive in patients with urticaria/angioedema or anaphylaxis [60]. In contrast, the diagnosis of acute infection with Anisakis can be confirmed with serologic and gastroenterologic tests and is presented separately. (See "Miscellaneous nematodes".)

Allergy to additives in canned fish — It is possible to encounter patients who react to canned fish but tolerate fresh versions of the same fish [53]. Note that the opposite situation is more often true (see 'Eating only certain forms of the food in question' below). Reactions to canned tuna have been attributed to additives, such as soy or cow's milk proteins (eg, casein) or tartrazine added during processing [66,67].

CROSS-REACTIVITY — Parvalbumins in fish and tropomyosins in shellfish are responsible for the majority of IgE-mediated allergies [18,24,68]. People with seafood allergy may react to these and/or to other seafood proteins. (See 'Pathogenesis' above.)

Because the major allergenic proteins for fish and shellfish are different, individuals are usually allergic to one group or the other, although it is possible to be allergic to both. Allergy to both fish and shellfish was reported by approximately 10 percent of all those with any seafood allergy in the American telephone survey previously discussed [6]. In a retrospective study of a referral population of children with seafood allergy, 21 percent with finned fish allergy reported allergy to shellfish; however, this overlap likely represents co-allergy because rates of hen's egg and peanut allergy were higher [46]. Formal challenge studies with sufficient numbers of people would be required to establish definite estimates.

Among persons with allergy to a fish or shellfish, approximately 30 to 75 percent will react clinically to more than one type of fish or shellfish [69]. Conversely, it is also possible to be allergic to just one specific type of fish or shellfish, such as tropical sole, swordfish, or one type of shrimp [70,71]. Patients in the latter group generally lack IgE antibodies to the major allergenic proteins and are presumed to be sensitized to a species-specific protein. Those with bony finned fish allergy may tolerate cartilaginous fish such as dogfish and ray [42,72,73].

As is the case for many foods that share homologous proteins, sensitization (ie, positive allergy tests) to multiple species is more common than clinical reactivity (ie, the development of actual symptoms on ingestion). A Spanish study evaluated the relevance of sensitization to six regionally important species in 79 children with fish allergy [74]. While all subjects had positive skin tests to multiple species, only 39 percent had clinical reactions. Thus, positive test results alone are not sufficient to determine which related foods will cause symptoms.

Fish — Several studies have demonstrated that fish-allergic subjects often react to more than one type of fish, although this is not universal [18,75]. The following are representative:

●In the American telephone survey presented previously, reported reactions to multiple fish among those with any fish allergy was 67 percent [6]. Among the 58 individuals with fish allergy, 19 reported a reaction to only one type, 5 to two types, 13 to three to nine types, and the remainder were uncertain.

●Ten fish-allergic American children were evaluated with double-blind, placebo-controlled oral food challenges (DBPCFCs) to between four and six different species of fish [76]. All reacted to at least one type, and three children reacted to more than one type.

●In a study of 20 codfish-allergic Italian children, positive skin tests to other fish were documented in 5 to 100 percent for each of nine species tested [77]. For those who ingested the fish to which antibody was detected, the clinical reaction rate per fish based on history ranged from 25 to 100 percent. In these cod-allergic children, eel, bass, sole, and tuna most frequently provoked reactions, while salmon, sardine, and dogfish (a type of shark) were least likely to induce symptoms.

●In a study of 35 individuals aged 5 to 19 years with allergy to cod, salmon, or mackerel, tolerance to at least one of three species was found in 29 percent [78].

●A 2011 study of 95 Australian children found that 93 percent were sensitized to multiple types, and 29 percent reported reactions to more than one type [46].

Caviar (fish egg) is a potential allergen but is distinct (not cross-reactive) from fish muscle [79].

In summary, a fish-allergic patient is at high risk for reactions to other fish. There are insufficient data to predict which types of fish are more likely to be tolerated based on the known allergy. In addition, skin testing or in vitro tests alone are often not sufficient to identify which types will cause clinical reaction. Homologous fish and chicken proteins may account for rare co-allergy to both of these foods [80].

Shellfish — It is also common for patients allergic to shellfish to react clinically to more than one type of shellfish. Extensive cross-reactivity among shellfish is explained by the fact that invertebrate tropomyosin is a pan allergen with significant sequence homology throughout many invertebrate species, including crustaceans, mollusks, squid, octopus, parasites, and non-marine insects (such as cockroaches, grasshoppers, and dust mites) [18,81-83]. However, there are clearly other factors that influence cross-reactivity as homology cannot be used to predict an individual patient's sensitivity patterns. Invertebrate tropomyosins demonstrate less homology with vertebrate tropomyosins [84].

Overall, based on limited data, approximately 75 percent with a crustacean allergy react to more than one type, but less than 50 percent react to mollusks [69]. Conversely, those with mollusk allergy are high risk (>70 percent) to react to crustaceans. Among mollusk-allergic patients, approximately 50 percent report reactions to more than one type of mollusk. Between 10 to 15 percent of patients allergic to any shellfish are allergic to both crustaceans and mollusks.

In the few studies examining cross-reactivity among foods within the crustacean or mollusk groups, sensitization was very high, and clinical reactivity was lower although very significant. The following studies provide information on these observations [6,81,85]:

●In the United States pediatric prevalence study, 45 percent with a crustacean shellfish allergy reported a mollusk allergy and 81 percent with a mollusk allergy reported a crustacean allergy [10]. A similar study in adults showed 46 percent with crustacean allergy reported mollusk allergy while 70 percent with mollusk allergy reported crustacean allergy [86].

●In the American telephone survey, 232 people had allergy to shrimp, lobster, and/or crab [6]. Of these, 62 percent indicated allergy to one, 20 percent to two, and 18 percent to all three types. Thus, based on patient-provided history, nearly 40 percent of patients reacted to more than one type of crustacean.

●In a study evaluating nine patients with shrimp anaphylaxis, sera from all patients reacted specifically with the tropomyosins of 13 crustaceans and mollusks [81]. However, patients were not challenged, so the clinical correlation is unclear. In an Italian study of 247 people with shrimp allergy, 48 percent also reported allergy to mollusks [87].

●In the American telephone survey, 67 people reacted to scallops, clams, oysters, or mussels [6]. Of these, 51 percent reacted to just one type of mollusk, 19 percent to two, 8 percent to three, and 22 percent to all four types. In addition, 14 percent (41 persons) of those with shellfish allergy reported an allergy to both crustaceans and mollusks.

Cross-reactivity with nonfood allergens — Invertebrate tropomyosin is also found in several non-marine allergenic organisms, such as dust mites, edible crickets, and cockroaches [88].

In a report of asthma induced by snail consumption in 28 patients, radioallergosorbent test (RAST) inhibition studies indicated that dust mite sensitization was the likely initial event, suggesting that sensitization by the respiratory route may predispose to the development of subsequent allergy upon seafood ingestion [82].

Several studies have implicated cross-reactivity between tropomyosins as responsible for the development of shellfish allergy in patients receiving immunotherapy for dust mite allergy [89-91]. However, this phenomenon has not been adequately documented, and other studies do not support the hypothesis. Myosin light chain in shrimp is homologous to an important allergen in cockroach, although the clinical significance of this is unknown [92].

Copepods are microscopic crustaceans that may be found in unfiltered natural drinking water; however, there are no documented allergic reactions attributed to these organisms.

No cross-reactivity between seafood and radiocontrast — There is no cross-reactivity between seafood allergens and radiocontrast media [93]. This misconception is discussed separately. (See "Patient evaluation prior to oral or iodinated intravenous contrast for computed tomography", section on 'Patients with allergies or asthma'.)

MANAGEMENT — The management of seafood allergy does not differ from that of other food allergies and requires instructions on avoidance and education about treatment of reactions in the event of accidental exposure.

Dietary recommendations

Avoidance — All patients must avoid the specific food that induced symptoms. In addition, general avoidance of all fish or all shellfish may be the safest and most practical strategy for people with severe reactions or reactions to multiple types of seafood. (See "Management of food allergy: Avoidance".)

Counseling about avoidance should include discussions about the following issues:

●Cross-contact – Patients must be counseled about accidental exposure to food allergens via cross-contact (ie, inadvertent exposure to the allergenic food by contamination of "safe" foods with small amounts of the culprit food). With seafood, this typically occurs at seafood counters in grocery stores, restaurants, and as a result of shared equipment (especially fryers). It is safer to buy seafood that is individually packaged and frozen. Reactions due to contact with contaminated saliva through kissing or sharing of utensils have also been reported [94].

●Food labels – Patients must read all food labels. Legislation has been enacted in the United States mandating that the ingredients labels on food packages plainly identify the presence of nine specified allergenic foods. These nine foods include fish and crustacean shellfish (as well as cow's milk, hen's eggs, tree nuts, peanuts, sesame, wheat, and soybeans) [95]. Mollusks are not included.

●Unexpected and nonfood sources – Seafood components can appear in unexpected foods as well as in nonfood items. As an example, fish gelatin is a food additive derived from fish skin. The use of fish gelatin as a food additive is increasing in parallel with concerns over the risk of bovine spongiform encephalopathy with bovine gelatin [19]. Usual doses of fish gelatin are tolerated by most fish-allergic persons, but anaphylactic reactions have been reported [19,96,97]. Results from one small series suggest that some individuals with fish allergy may tolerate fish oil supplements as well [98]. Medications, various health foods, and cosmetics may have ingredients derived from seafood, and labeling of nonfood items is not strictly regulated.

Fish products can be used as clarifying (or fining) agents in the manufacture of some wines. However, available studies indicate that residual fining agents are unlikely to cause allergic reactions in fish-allergic individuals. (See "Management of food allergy: Avoidance", section on 'Alcoholic beverages'.)

●Aerosolized seafood allergens – Many of the allergenic proteins in seafood are stable and could be vaporized or released in steam during cooking. Although airborne exposures to food allergens are unlikely to cause anaphylaxis, respiratory reactions may occur from being near cooking fish, boiling lobsters, or in fish markets [99].

●Caution with antiulcer treatments – Antiulcer drugs increase gastric pH and may impair digestion of food proteins. In a mouse model, antiulcer drugs were reported to predispose to allergic reactions to caviar caused by unstable allergens that would be normally destroyed by digestion [47]. A human study included four codfish-allergic patients who underwent double-blind, placebo-controlled oral food challenge (DBPCFC) to codfish that was predigested at either pH 2 or pH 3 [100]. The codfish preparation digested at pH 3 produced symptoms in these patients at either a lower dose or after a shorter time interval compared with codfish digested at pH 2, suggesting that antiulcer therapy may place patients at increased risk for reactions to ingested seafood.

Eating other seafood — Seafood is obviously not an essential component of the diet, and the most straightforward approach in managing any food allergy is complete avoidance of the culprit food and all similar foods. This strategy would be logically expected to minimize the chances of accidental exposure of the culprit food through cross-contact.

However, there may be disadvantages to the strategy of avoiding all similar foods. There is some evidence, for example, that removing foods from the diet can increase the risk of becoming allergic to them. This appeared to be the case in a report of seven children with atopic conditions who were sensitized to fish but had no clinical symptoms upon ingestion [101]. The children were placed on fish-elimination diets and followed prospectively. Within the ensuing two to five years, all of the children developed clinical allergy to fish, including two with anaphylaxis. Similar examples of this phenomenon exist for other foods [102]. Possible reasons for the heightened sensitivity include both lack of exposure and the opposite explanation, namely, ongoing low-level exposure (through hidden sources or cross-contact).

Thus, if a patient with allergy to a certain fish or shellfish wishes to continue eating other forms of seafood, the clinician's recommendations must carefully balance the patient's preferences with what is known about cross-reactivity among seafood. The severity of the patient's reaction also influences the decision. (See 'Cross-reactivity' above.)

The following scenarios illustrate some of the issues involved and our management approach. Individual clinicians may decide to adopt different strategies depending on their level of expertise and the resources available (eg, ability to perform oral food challenges).

●For patients who have experienced life-threatening anaphylaxis to a specific shellfish, we advise avoidance of all shellfish, largely because of the higher chance of encountering a cross-reactive tropomyosin in these foods. Similarly, a person who reacted to one finned fish would usually be advised to avoid all finned fish. We typically do not advise patients with serious reactions to shellfish to avoid finned fish (or vice versa), since the major allergens in shellfish and finned fish are different. However, patients must be wary of settings in which cross-contamination is common, such as seafood restaurants. It may be wise to avoid these settings altogether.

●For patients with non-life-threatening reactions, we are more flexible in our approach. If patients are content to avoid all shellfish or finned fish (depending on which group they reacted to), we do not discourage this approach. However, if a patient wishes to continue to include similar seafood in the diet, then a careful evaluation must be performed to determine which specific foods may be safely eaten. As an example, a patient who developed an allergy to codfish that is moderate in severity and has been avoiding all seafood for several months may ask about the safety of eating tuna, which had been a regular component of the patient's diet before the reaction.

In this case, we would first perform skin testing with commercial extracts of tuna. If negative, we would allow the ingestion of tuna because the experience in our clinic suggests that the negative predictive value of skin prick testing for seafoods is generally high.

However, if there was any clinical suspicion of tuna allergy or if the clinician was uncomfortable proceeding without additional evaluation, skin testing and oral food challenge with fresh tuna should be performed. If skin tests were positive to tuna but the patient still had a strong interest in eating it, we would perform a cautious graded challenge to determine whether there was true clinical reactivity (because false-positive skin tests are not uncommon).

●We allow persons to continue to eat seafood that has not caused symptoms in the recent past and which they have eaten regularly (similar to having just passed an oral food challenge). As an example, a patient with a newly diagnosed allergy to codfish who continued to eat tuna without incident after the reaction can simply continue to do so.

Eating only certain forms of the food in question — Patients who react to fresh tuna and salmon will often tolerate canned versions of these fish, presumably because of modification of allergens during processing [46]. If an individual has reacted to fresh tuna or salmon and is interested in eating the canned form, we suggest prick-by-prick testing and oral food challenge with the canned fish be performed to ensure the patient tolerates it.

Management of reactions

IgE-mediated reactions — Identification of individuals with IgE-mediated seafood allergy is important because these reactions can be severe. As in other forms of food allergy, the severity of symptoms in a given individual may vary dramatically between reactions, and the severity of an initial reaction should not be used to predict the patient's subsequent risk [103]. Accordingly, all individuals diagnosed with IgE-mediated seafood allergy should have an epinephrine autoinjector(s) available at all times [104]. Patients who have experienced anaphylaxis should have a written anaphylaxis action plan. These measures are discussed in detail separately. (See "Anaphylaxis: Emergency treatment".)

Delayed gastrointestinal reactions — The management of children with food protein-induced enterocolitis syndrome (FPIES) caused by fish and other foods is presented in the specific topic review. (See "Food protein-induced enterocolitis syndrome (FPIES)".)

There are no data to guide recommendations about the treatment of delayed gastrointestinal reactions in adults or the frequency with which patients require acute care. There are no reported fatalities from this disorder.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Food allergy".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Food allergy symptoms and diagnosis (Beyond the Basics)" and "Patient education: Food allergen avoidance (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Epidemiology – Allergy to fish or shellfish (crustaceans and mollusks) affects nearly 1 in 50 adults and is a leading cause of food-induced anaphylaxis. Fish is a common cause of food allergy in children, although rates of seafood allergy are lower than in adults. (See 'Introduction' above and 'Epidemiology' above.)

●Immediate and delayed reactions – Manifestations of immunoglobulin E (IgE) mediated seafood allergy include urticaria/angioedema/anaphylaxis, occupational asthma, and food-dependent, exercise-induced anaphylaxis. IgE-mediated seafood allergy can be severe and is usually long lasting. There are also non-IgE-mediated forms of allergy that present with delayed gastrointestinal reactions, although limited data are available about these reactions. (See 'Clinical features' above.)

●Important allergens – Parvalbumins in fish and tropomyosins in shellfish are the proteins that are responsible for the majority of IgE-mediated allergies. (See 'Pathogenesis' above.)

●Diagnosis – Diagnosis of IgE-mediated seafood allergy is based on a careful history supported by skin prick tests or in vitro tests for specific IgE. Positive tests for food-specific IgE may be present to seafood that is clinically tolerated, and a supervised oral food challenge may be necessary for definitive diagnosis. (See 'Diagnosis' above.)

●Diagnostic challenges – Several factors may alter the allergenicity of seafood and complicate diagnosis, including preparation method, changes as a result of digestion, and the specific part of the fish that is consumed (table 2). The differential diagnosis includes allergy to seafood parasites and nonallergic reactions to toxins in seafood. (See 'Diagnostic pitfalls' above and 'Differential diagnosis' above.)

●Cross-reactivity among types of seafood – Rates of clinical cross-reactivity to different types of seafood within a group are high (ie, a person allergic to one fish is likely to react to others). In contrast, a minority (approximately 10 percent) of those allergic to any seafood are allergic to both fish and shellfish, although this observation is based on limited data. Because false positives on skin testing are possible, supervised challenge may be needed to definitely determine if a patient reacts to a specific seafood. (See 'Cross-reactivity' above.)

●Management – Management of seafood allergies includes instructions about avoidance of the specific culprit food, evaluations for reactivity to related foods in patients who wish to continue eating seafood, and education in the proper management of accidental exposures. (See 'Management' above.)

•All patients with IgE-mediated reactions to fish or shellfish should be equipped with epinephrine autoinjectors, regardless of the severity of their initial reactions. (See 'IgE-mediated reactions' above.)

•Patients with life-threatening reactions are generally advised to avoid all related seafood. Some patients will choose to avoid all seafood to minimize the risk of exposure through cross-contact. (See 'Avoidance' above.)

•Among those with less severe reactions, some may wish to continue eating other forms of seafood in the future. In this case, testing and possibly oral challenges are needed to determine which specific foods are tolerated. (See 'Eating other seafood' above.)