Shellfish is one of the most common food allergen sources in Asia (Table 1), and the leading cause of food allergy in Taiwan (18, 19), Thailand (20), Singapore (21), Vietnam (9, 12) and Hong Kong (22). In a survey in which IgE sensitization and skin prick tests were used to determine food allergy prevalence, shrimp was found to be the most commonly sensitized food allergen source in Hong Kong, China and India (8). Up to 13.1 and 10.3% of the Chinese and Indian populations had shrimp-specific IgE (sIgE) that exceeded 0.70 kUA/L, while over 2% of the Hong Kong population was positive to shrimp by skin prick test. On the other hand, shellfish allergy is less common in East Asia where shellfish only accounted for 3.4% of all reported food allergy cases in Japan (23) and 0.87% of parent-reported shellfish allergy in South Korea (13). The prevalence of shellfish allergy was affected by environmental exposures, dietary habits and cross-sensitization with other arthropods such as dust mite or cockroaches (24, 25).

Fish allergy is less common in Asia than shellfish allergy, but its prevalence is still considerably high (Table 1). Fish allergy affected 1.55–1.60% of Vietnamese, which was second to shellfish as the most common type of food allergen source (9, 12). The prevalence of self-reported fish allergy was 2.29% in Philippines where fish is part of the weaning diet and fish sauce widely used as a condiment (26). In contrary, parent-reported fish allergy affected <1.5% of other Asian populations (11, 13, 22, 26). The rates of IgE sensitization to fish were even lower, when none of the 10,681 subjects in China was positive for fish-specific IgE and only 1.2% of subjects in Hong Kong were sensitized to fish (27). Nevertheless, this study only selected cod as the benchmark for sIgE, when this fish species is not popular in many Asia populations. Thus, results from this study probably underestimated the prevalence of fish allergy in Asia.

Seafood allergy is generally believed to be persistent throughout life despite limited published evidence on its natural history (28). Shellfish allergy had late onset at a median age of 25 years old in Canadians (29), whereas shellfish allergy started much earlier in the Asian population. While shellfish allergy affected 0.1% of children aged 0–5 years in the United states (30), IgE sensitization to shellfish was as high as 10.6% among Singaporean children younger than 3 years of age (31). It was noteworthy that shellfish was the most frequent cause of food allergy in several studies that involved school-age or pre-school Asian children (9, 12, 18–22), which was probably attributed to the early introduction of shellfish in the Asian diet. Another possible reason is that exposure to other arthropods like dust mite or cockroach in tropical or subtropical areas of Asia may increase the shellfish allergy through cross-reactive allergens. Shellfish allergy also tends to persist longer as shellfish was reported to be the leading cause of food-induced anaphylaxis in older children and adults in Singapore (32), Hong Kong (33) and Thailand (34). Nevertheless, a Thai study found that 46% of shrimp-allergic patients were able to tolerate shrimp 10 years later, suggesting that some individuals could outgrow shrimp allergy (35). In addition, Ayuso et al. reported greater epitope recognition for shrimp in children than adults, supporting that shrimp sensitization could decrease with age (36). It remains unclear at this stage whether this is a general observation or is limited to some populations.

Similar to shellfish allergy, it is generally believed that fish allergy persists throughout life although the relevant evidence is limited. One study suggested that 65.5% of fish-sensitized infants maintained their sensitization at school age (37). Another study reported that the prevalence of fish allergy was slightly higher in American adults (0.9%) than children (0.6%) (38). The same study also found that nearly 40% of adults having fish allergy started to suffer from this allergy in adulthood. Similar findings were reported in Philippines (26). Alternatively, a small study reported that sIgE levels and skin prick test positivity of fish-allergic patients diminished over a 9-year period, and some subjects were able to tolerate fish with lower allergenicity such as tuna and swordfish (39). Longitudinal studies are required to elucidate the natural history of fish allergy. It is also noteworthy that allergenicity of different fish species could vary significantly, and it is important to distinguish between fish-allergic patients with partial tolerance and true resolution of their fish allergy.

Insects have become a unique diet in China under the cultural influence of traditional Chinese food and medicine. The consumption of oil-fried, water-boiled or ground silkworm pupa is common in China whereas silkworms have been used as therapeutics in traditional medicine and also commonly consumed after boiling with soybean sauce in Korea. Although insects are not widely consumed in western countries at present, edible insects have gained attention as a novel and sustainable food for protein sources worldwide due to the worry about food scarcity.

However, there is increasing recognition about allergy to insects. From 1980 to 2007, 61 (17%) of 358 reported cases of anaphylaxis were triggered by insects including silkworm pupas, cicada pupas, grasshoppers, locusts and hawkmoth (75). Over 1,000 patients experienced anaphylactic reactions following consumption of silkworm pupa annually in China, and foreign tourists also experienced anaphylactic shock after eating silkworm (76). Considering tropomyosin as a pan-allergen in invertebrates including crustaceans, mollusks, dust mites and cockroaches, shrimp-allergic patients are at risk of insect allergy due to cross-reactivity between allergens. As early as 1996, Leung et al. reported co-sensitization among insects, cockroach, fruit fly and shrimp (77). More recently, Jeong et al. (78) reported among 15 patients diagnosed with silkworm pupa allergy that 11 (73.3%) exhibited sIgE reactivity to shrimp and crab by ImmunoCAP (≥0.35 kUA/L) and 53.3% of patients' sera reacted to silkworm pupa tropomyosin. Kamemura et al. (79) also demonstrated strong positive correlation between shrimp- and cricket-specific IgE responses by the IgE crosslinking-induced luciferase expression (EXiLE) assay. Similarly, Broekman et al. (80) showed that all 15 shrimp-allergic patients were also sensitized to mealworm. There was similar basophil reactivity of these shrimp-allergic patients to all tested insect species including mealworm, cricket, grasshopper and moth. By means of immunoblot and nano LC-MS/MS analyses, insect extracts were found to contain a considerable number of arthropod allergens including tropomyosin, arginine kinase, myosin light chain and triosephosphate isomerase. These allergens probably accounted for cross-reactivity between shrimp and insects. Therefore, some shrimp-allergic subjects may also be allergic to insects.

Collagen was first identified as a fish allergen in a Japanese study (50), and subsequently regarded as a pan-allergen in this population. Half of 36 fish-allergic Japanese patients reacted to collagen extracted from Pacific mackerel, in comparison to only 16 (44%) patients who were positive to parvalbumin (84). In addition, 13 (36%) subjects were mono-sensitized to collagen. Collagen from Pacific mackerel also significantly inhibited IgE binding to heated crude extract of 22 fish species by 87–93%. In contrast, the sensitization rate to collagen was low in European and Australian populations (52, 85). This much higher rate of collagen sensitization together with strong IgE inhibition in Japanese might be explained by their traditional dietary practice of eating raw fish sashimi or sushi. The risk of collagen sensitization was low in cooked fish, while the insoluble intact collagen found in raw fish might be a potent sensitizing allergen due to its resistance to gastric acid digestion (84).

Fish roes are nutritious food commonly consumed in Japan. Salmon roe, also known as salmon caviar, red caviar, rainbow trout roe and ikra, is a common Japanese cuisine. Fish roe is the fifth most common food allergen source in Japan, and it is mandatory in the Japanese food sanitation law to label fish roe as a possible food allergen. In a retrospective study, half of 68 Japanese subjects reacted to salmon roe on oral food challenge (86). Analysis of sera collected from 20 patients with salmon roe allergy found that β'-component (β'-c) was the major allergen (53). Nine (45%) of 21 sera reacted to lipovitellin. Both lipovitellin and β'-c are degradation fragments of vitellogenin which issynthesized in fish liver and carried to oocytes through bloodstream. β'-c was also characterized as a major fish roe allergen in teleostean such as large yellow croaker (Pseudosciaena crocea) that is widely consumed in China (87). In the contrary, fish roe allergy is rare in western countries. When there is popular consumption of fish roes from sturgeon, paddlefish, cod, lumpfish, capelin, herring and salmon worldwide, there were increasing number of cases with fish roe allergy in USA, Portugal, Spain and Finland (88–91).

Over the past decades, we found more reports on the profiling and characterization of allergens from shrimp as a prototype for shellfish. Tropomyosin has long been regarded as a major crustacean allergen. Over 80% of European shellfish-allergic subjects were sensitized to tropomyosin (92, 93). However, our recent study suggested that only slightly over half of subjects with challenge-proven shrimp allergy were sensitized to tropomyosin (94). Such low sensitization rate to tropomyosin was also reported in Thai (34.2%) and Japanese (37%) (95, 96), supporting that tropomyosin might not be the major allergen in Asians. We further demonstrated that Chinese patients were sensitized to multiple shrimp allergens, with troponin C and fatty acid-binding protein being the major allergens (97, 98).

One possible reason for such diversified sensitization profiles in different Asian populations might be due to the consumption practice for non-muscle body parts of shrimp and crab. While western populations mainly consume muscle of shelled shrimps, shrimp is always served head-on and shell-on in East and Southeast Asia when the shell, cephalothorax (containing brain, heart, stomach and bladder), ovaries and hepatopancreas are consumed together with shrimp muscle. The best example is hemocyanin that is found mainly in shrimp cephalothorax but not muscle. In addition, Khanaruksombat et al. (99) reported novel allergens from muscle, shell, hepatopancreas and ovaries of banana shrimp, Fenneropenaeus merguiensis, that is commonly consumed in Thailand. They detected four immunoreactive bands from shell extract and six immunoreactive bands from ovarian extracts at different vitellogenic stages. On top of arginine kinase and sarcoplasmic calcium-binding protein, these investigators identified a novel allergen called glyceraldehyde-3-phosphate dehydrogenase from the shell. Interestingly, different allergens including vitellogenin, ovarian peritrophin 1 precursor, β-actin and 14-3-3 protein were detected at different stages of ovarian development. It is noteworthy that vitellogenin is a female specific protein also found in the hemolymph of most crustacean species, and its degradation fragments lipovitellin and β'-c were defined as major fish roe allergens. This study highlighted the presence of IgE-binding proteins in both shrimp muscle and organs.

Fermented foods such as kimchi and saeujeot, a salted and fermented shrimp product, are popular food items in Korea and some other Asian countries. Saeujeot is ripened primarily by proteolytic enzymes present in shrimp, and this process confers characteristic flavor and aroma in this food item. Although being heat stable, the allergenicity of tropomyosin decreased during fermentation of shrimps. Park et al. (100) demonstrated that tropomyosin could not be detected after 6 days of fermentation at 25°C, 10 days at 15°C and 30 days at 5°C. More importantly, the binding ability of tropomyosin in saeujeot to patient sera decreased gradually during fermentation process. This binding ability decreased further and faster at higher fermentation temperature, which might be caused by the activity of a trypsin-like enzyme that decomposes tropomyosin. Kim et al. (101) further investigated the allergenicity of saeujeot at various temperatures (25, 15, and 5°C) and salt concentrations (25, 15, and 10%). They showed that the binding ability of tropomyosin decreased faster at higher temperature and lower salt concentration. During fermentation, the allergenicity of saeujeot increased initially as tropomyosin dissolves in salt, while it is subsequently decomposed by enzymes.