not every seafood allergy is allergy

Attilio BonerUniversity ofVerona, Italy

[email protected]

Introduction

Classification of Seafood

Seafood Allergy

Adverse Reactions to Foreign Substances in Seafood

Adverse Reactions to Infectious Agents that Contaminate Seafood

Recognition and Management of Seafood Poisoning

Conclusion

Not every seafood “allergy” is allergy !

Bahna SL. Ann Allergy Asthma Immunol. 2016;117(5):458-461.

may present with similar symptoms and often may be misdiagnosed as an allergy.

consumption of seafood adverse reactions

immune-mediated allergic reactions or nonimmunologic adverse



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Introduction


Seafood Allergy




Conclusion



•Seafood is a general term that refers to any edible aquatic animal,which includes thousands of different species.

The 2 commonly consumed groups:

fin fish and shellfish

bony (>95%) and cartilaginous.

mollusks and crustaceans



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Introduction


Seafood Allergy




Conclusion


Stephen JN, CEA 2017;47:300-312

• Reported prevalence ranges from self-reported rates of 5% to challenge-proven rates of 0.1%.

• From current available data, it appears that there are significant regional differences in rates of bony fish allergy, with higher reported rates of bony fish allergy in regions with high consumption.

• Across European cities, approximately 0.2% of the population is reported to be allergic to some type of fish.

• The populations of Portugal, Spain and Scandinavian are likely to be the highest consumers of fish in Europe.

Fish allergy epidemiology: How common is it?

International prevalences of reported food allergies and intolerances: comparisons arising from the European

Community Respiratory Health Survey (ECRHS) 1991-1994. Woods RK, Eur J Clin Nutr. 2001;55:298e304.

European Community Respiratory Health Survey (ECRHS).

17280 adults aged 20-44 y from 15 countries

% adults reporting symptoms with ingestion of

3 –

2 –

1 –

0 -

2.8%

shrimp

2.3%

oyster fish

2.2%

Sharp MF, Clin Rev Allergy Immunol. 2014;46(3):258-71.

Seafood allergy: Demographics and Prevalence

•In Europe, most of the populations based prevalence studies come from Spain, Portugal, and the Scandinavian countries.

•Fish allergy in Norway is almost as common as allergy to egg among children, while fish allergy is more common in children from Finland.

•In Spain fish allergy began predominantly before the second year of life.

•Over one third of sensitized children reported multiple fish allergy, most probably due to the major cross-reactive fish allergen parvalbumin (Gad c 1).

•However, the majority of children demonstrated monosensitivity to one or the other fish species.

•Children usually do not outgrow this type of food allergy.


Seafood allergy: Demographics and Prevalence

•In Europe, most of the populations based prevalence studies come from Spain, Portugal, and the Scandinavian countries.

•Fish allergy in Norway is almost as common as allergy to egg among children, while fish allergy is more common in children from Finland.

•In Spain fish allergy began predominantly before the second year of life.

•Over one third of sensitized children reported multiple fish allergy, most probably due to the major cross-reactive fish allergen parvalbumin (Gad c 1).

•However, the majority of children demonstrated monosensitivity to one or the other fish species.

•Children usually do not outgrow this type of food allergy.

populations with high consumption of anchovy and herringspecies (rich in parvalbumin) might be of increased risk

of developing fish allergy.


•Seafood is 1 of the top 8 allergens attributable to IgE-mediatedreactions and is a common cause of food-induced anaphylaxis.

•Fin fish and shellfish have multiple, different allergens that are distinct from one another. Mourad AA, Bahna SL. Fish-allergic patients may be able to eat fish. Expert Rev Clin Immunol. 2015;11:419e430.

•Cross-reactivity between fin fish and shellfish is exceedingly rare. Woo CK, Bahna SL. Not all shellfish “allergy” is allergy! Clin Transl Allergy.2011;1:3.

≠

Seafood allergy: Allergens


Finfish


*

* 90% of fish allergic patients reacts to this allergen,present also in frogsAllergy. 2004;59:653

Collagen

Seafood Allergens

≠

• The major heat-stable pan-fish allergen,

parvalbumin (PV), has been identified and characterized for numerous fish species.

• There are very few reports of allergic reactions to cartilaginous fish despite widespread consumption.

• PV consists of two distinct protein lineages, α and β.

• The α-lineage of this protein is predominant in muscle tissue of cartilaginous fish (Chondrichthyes), while β-PV is abundant in muscle tissue of bony fish (Osteichthyes).

• The low incidence of allergic reactions to ingested rays and sharks is likely due to the lack of molecular similarity, resulting in reduced immunological cross-reactivity between the two PV lineages.

Stephen JN, CEA 2017;47:300-312

Fish allergens

α

β≠

Quantification of major allergen parvalbumin in 22 species of fish by SDS-PAGE. Kobayashi Y, Food Chem. 2016;194:345-53.

•The allergenicity of fish is considered to correlate with the content of parvalbumin, the major fish allergen.

•In this study application of the Sodium Dodecyl Sulphate - PolyAcrylamideGel Electrophoresis (SDS-PAGE) method to 22 species of fish revealed a marked variation in parvalbumin content among fish.

•The parvalbumin content was found to be higher in dorsal white muscle than in ventral white muscle, in rostral part of white muscle than in caudal part of white muscle and in white muscle than in dark muscle.

Large-sized migratory fish, such as salmon, swordfish and tuna, were commonly very low in both parvalbumin content and IgE reactivity.

+- - --+++ +++[parvalbumin]

Quantification of major allergen parvalbumin in 22 species of fish by SDS-PAGE. Kobayashi Y, Food Chem. 2016;194:345-53.

•The allergenicity of fish is considered to correlate with the content of parvalbumin, the major fish allergen.

•In this study application of the Sodium Dodecyl Sulphate - PolyAcrylamideGel Electrophoresis (SDS-PAGE) method to 22 species of fish revealed a marked variation in parvalbumin content among fish.

•The parvalbumin content was found to be higher in dorsal white muscle than in ventral white muscle, in rostral part of white muscle than in caudal part of white muscle and in white muscle than in dark muscle.

Large-sized migratory fish, such as salmon, swordfish and tuna, were commonly very low in both parvalbumin content and IgE reactivity.

+- - --+++ +++[parvalbumin]

prick by prick

Comparison of allergenicity and allergens between fish white and dark muscles. Kobayashi A, Allergy.2006;61(3):357-63.

Heated extracts prepared from both white and dark muscles of 5 species of fish and examined for reactivity with IgE in fish-allergic patients by enzyme-linked immunosorbent assay (ELISA) and for allergens by immunoblotting.

Parvalbumin contents in both white and dark muscles determined by ELISA using antiserum against mackerel parvalbumin.

IgE reactivity of the pooled patient serum and 3 patient sera to the heated extracts

from white and dark muscles of: sardine (1), yellowtail (2), horse mackerel (3), red sea bream (4) and Pacific mackerel (5).

Comparison of allergenicity and allergens between fish white and dark muscles. Kobayashi A, Allergy.2006;61(3):357-63.

Heated extracts prepared from both white and dark muscles of 5 species of fish and examined for reactivity with IgE in fish-allergic patients by enzyme-linked immunosorbent assay (ELISA) and for allergens by immunoblotting.

Parvalbumin contents in both white and dark muscles determined by ELISA using antiserum against mackerel parvalbumin.

IgE reactivity of the pooled patient serum and 3 patient sera to the heated extracts

from white and dark muscles of: sardine (1), yellowtail (2), horse mackerel (3), red sea bream (4) and Pacific mackerel (5).

The fish dark muscle is less allergenic than

the white muscle, because the same allergen molecule (parvalbumin) is

contained at much lower levels in the

dark muscle than in the white muscle.

Important variations in parvalbumin content in common fish species: a factor possibly contributing to variable allergenicity. Kuehn A, Int Arch Allergy Immunol 2010;153:359

Fish muscle extracts were separated by SDS-PAGE and parvalbumincontent was estimated by densitometric band quantification.

parvalbumin content ranged from:

<0.05 mg for tuna, 0.3-0.7 mg for mackerel, 1-2.5 mg for salmon, trout and cod >2.5 mg per gram raw muscle for

carp, herring, anchovy and redfish

Variability in parvalbumin content is likely to contribute to the variation in clinical

reactivity to different fish species.

Important variations in parvalbumin content in common fish species: a factor possibly contributing to variable allergenicity. Kuehn A, Int Arch Allergy Immunol 2010;153:359

Fish muscle extracts were separated by SDS-PAGE and parvalbumincontent was estimated by densitometric band quantification.

Variability in parvalbumin content is likely to contribute to the variation in clinical

reactivity to different fish species.

if a subjects isallergic to tunna it isunlekely that he willbe able to tollerate

other fisheswhile if he is allergic

to other fishes(sarde, acciughe) he

may tollerate tunna ?

parvalbumin content ranged from:

<0.05 mg for tuna, 0.3-0.7 mg for mackerel, 1-2.5 mg for salmon, trout and cod >2.5 mg per gram raw muscle for

carp, herring, anchovy and redfish

Missing parvalbumin: implications in diagnostic testing fortuna allergy. Lim DL, J Allergy Clin Immunol 2005;115:874–875.

Dissection of Thunnus tonggol(Bleeker) for evaluation ofparvalbumin.

The fish was skinned and torso sectioned transverselyinto 6 portions (left).

Three of these sections, the (1) rostral, (2) mid, and(3) caudal portions, were further divided into 3 parts,dorsal (D) and ventral (V) white muscle and middle red meat (right).Parvalbumin was found

in the white muscle of tuna and was absent in the red

(+) (-) (+)

Allergy to fish parvalbumins: studies on the cross-reactivity of allergens from 9 commonly consumed fish.

Van Do T, J Allergy Clin Immunol 2005;116:1314–1320

To determine the allergenic cross-reactivity between 9 commonly edible fish: cod, salmon, pollack, mackerel, tuna, herring, wolffish, halibut, and flounder

Sera from 10 patients allergic to fish and rabbit antiseraagainst 3 parvalbumins(Gad c 1, Sal s 1, and The c 1)

herring, and wolffish contained the most potent cross-reacting allergens, whereas •halibut, (pesci piatti) •flounder, (platessa, sogliola) •tuna, (tonno) •mackerel (sgombro) were the least allergenic in the current study.

The latter could probably be tolerated by some of the tested patients.

Allergy to fish parvalbumins: studies on the cross-reactivity of allergens from 9 commonly consumed fish.

Van Do T, J Allergy Clin Immunol 2005;116:1314–1320

To determine the allergenic cross-reactivity between 9 commonly edible fish: cod, salmon, pollack, mackerel, tuna, herring, wolffish, halibut, and flounder

Sera from 10 patients allergic to fish and rabbit antiseraagainst 3 parvalbumins(Gad c 1, Sal s 1, and The c 1)

herring, and wolffish contained the most potent cross-reacting allergens, whereas •halibut, (pesci piatti) •flounder, (platessa, sogliola) •tuna, (tonno) •mackerel (sgombro) were the least allergenic in the current study.

The latter could probably be tolerated by some of the tested patients.

Anchovies also are richin parvalbumins

• In vitro or SPT cross-reactivity is not always predictive of in vivocross-sensitization and actual clinical allergy.

• Individuals sensitive to cod were also sensitized to salmon, whereas Halibut (pesci piatti), flounder (passera, platessa), tuna and mackerel (sgombro) were found to be the least cross-reactive.

• Allergies to cartilaginous fish are rarely reported, possibly due to their low incidence, despite the fact that they are commonly consumed.

• While cross-reactions to both α- and β-PV were observed, β-PV demonstrated significantly more IgE binding than α-PV.

Patterns of clinical cross-reactivity and tolerance across fish species in fish-allergic individuals

Stephen JN, CEA 2017;47:300-312β-PV > α-PV

β-PV

•Heating fish denatures collagen to form gelatin, which is water soluble and can be easily digested by gastrointestinal enzymes.

•However, collagen in raw fish meat is water insoluble.

•The T-cell epitopes of collagen are likely to be resistant to digestion by proteolytic enzymes; therefore, collagen can potentially induce sensitization.

Fish collagen is an important panallergenin the Japanese Population

Kobayashi Y. Allergy 2016;71:720-723

sashimior sushi

Parvalbumin and intact collagen purified from the muscle and skin.

Sera from 36 patients with immediate hypersensitivity reactions such as urticaria, dyspnoea and anaphylactic shock after ingestion of raw and cooked fish.

Pooled serum from 10 healthy volunteers.



% of Japanese patients with fish allergy and sIgE for

50%

collagen paralbumin

50 –

40 –

30 –

20 –

10 –

00

44%

mackerel

sgombro



Cross-reactivity of Pacific mackerel collagen to heated crude extracts from 22 species of fish by the competitive ELISA inhibition test.

Collagen is another panallergen of fishes

• Absorption of allergen across mucosa can be rapid, and codfish proteins have been identified in the sera of healthy individual within 10 min of consumption.

• The biological activity of the allergens was lost at pH 2.0, but at pH 3.0, the protein patterns and histamine-releasing capacity of the proteins were maintained up to 2 h post-digestion.

• The increased pH was a result of antacid medication leading to incomplete digestion and rapid uptake of the allergens.

+++

+++

Changes in allergenicity related to exposure

Stephen JN, CEA 2017;47:300-312


•Tropomyosin is the major shellfish thermostableallergen and is responsible for cross-reactivity between members of the shellfish family,particularly within the crustacean family.

•Newly described allergens and subtle differences in the structures of tropomyosin among different species of shellfish could account for the discrepancy between in vitro cross-antigenicity and clinical cross-allergenicity in patients who may be sensitized to certain allergens, yet not manifest clinical reactivity on ingestion of these cross-reactive items.


Sensitization pattern of crustacean-allergic individuals can indicate allergy to molluscsVidal C, Allergy 2015;70:1493–1496

31 patients with anaphylaxis to crustaceans (14 with mollusc allergy and 17 with mollusc tolerance).

SPTs, sIgEs and SDS-PAGE immunoblotting.

Patients with mollusc allergy presented more frequently (+) SPTs to molluscsand higher sIgE titles in response to both molluscs and crustaceans.

only

+


Positive likelihood ratios for the identification of mollusc allergy

9 –

8 –

7 –

6 –

5 –

4 –

3 –

2 –

1 –

0

10 –

4.3

11 –

10.9

Shrimp-sIgEof 1.57 kUA/l

rPen a1-sIgEof 4.38 kUA/l

31 patients with anaphylaxis to crustaceans (14 with mollusc allergy and 17 with mollusc tolerance).

SPTs, sIgEs and SDS-PAGE immunoblotting.

rPen a 1 Tropomyosin,

Shrimp


•This study shows that patients with crustacean anaphylaxis and MA and patients with isolated crustacean anaphylaxis (i.e.MT) represent two different populations in clinical and immunological terms.

•According to our results, SPTs or prick by prick tests positive to molluscs (clam, mussel, octopus or squid) indicate a risk of reacting against mollusc ingestion in patients with crustacean anaphylaxis.

•In contrast, patients with SPTs positive to shrimp alone are less likely to develop Mollusc Allergy.

•Likewise, patients with MA showed higher sIgE concentrations to molluscsthan did patients with MT.

•These results are consistent with a role of tropomyosin in Mollusc Allergy.

In vivo diagnosis with purified tropomyosin in mite and shellfish allergic patients

Lopez-Matas MA. Ann Allergy Asthma Immunol 2016;116:538-543

850 patients

Mite allergic patients (M)

Shellfish allergicpatients (S)

Mite- and shellfish allergic patients (MS) MITE

40 –

30 –

20 –

10 –

0

% patients with (+) SPT for tropomyosin

28.6%

2.7%

38.5%

SHELLFISH MITE AND SHELLFISH

PATIENTS ALLERGIC to



850 patients

Mite allergic patients

Shellfish allergicpatients

Mite- and shellfish allergic patients MITE

40 –

30 –

20 –

10 –

0


28.6%

2.7%

38.5%



Tropomyosin does not seem to be a relevant mite

allergen in Spain, which also holds true for otherEuropean countries.

Moreover, in our population, tropomyosin is not a

shellfish major allergen, and it seems evident that other shrimp and shellfish

allergens have to be considered.



850 patients




40 –

30 –

20 –

10 –

0


28.6%

2.7%

38.5%



The group MS had the highest prevalence to

tropomyosin sensitization (38.5%), suggesting

that this value iscorrelated with the

cross-reactivity between mites and shellfish

tropomyosins.



850 patients




40 –

30 –

20 –

10 –

0


28.6%

2.7%

38.5%



we can hypothesize that in group MS the first sensitizer were mites,

and after a period these patients developed allergy to shellfish.

1°2°

Seafood allergy in children: a descriptive study. Turner P, Ann Allerg Asthma Immunol 2011;106:494–501

167 children with a history of definite clinical reaction to seafood and/or positive food challenge

•Over 50% of crustacean-allergic children could tolerate non-crustacean fish.

•Sensitization to other fish species was very common in fish-allergic children, with one third reporting clinical reactions to at least two species;

•16% developed symptoms to fish vapours.

•In children with allergy to tuna and/or salmon, at least 21% were able to tolerate the fish in a canned form.

Seafood allergy in children: a descriptive study. Turner P, Ann Allerg Asthma Immunol 2011;106:494–501

167 children had a history of definite clinical reaction to seafood and/or positive food challenge

•Over 50% of crustacean-allergic children could tolerate non-crustacean fish.

•Sensitization to other fish species was very common in fish-allergic children, with one third reporting clinical reactions to at least two species;

•16% developed symptoms to fish vapours.

•In children with allergy to tuna and/or salmon, at least 21% were able to tolerate the fish in a canned form.

consumption of canned fish was associated

with a reduction in SPT size in most patients,

implying that this may have resulted

in the induction of tolerance

in these patients

Cross-reactivity to fish and chicken meat: a new clinical Syndrome

Kuehn A, Allergy 2016; 71:1772–1781.

Patients with food allergy to fish and chicken meat (n = 29) or chicken meat only (n = 7)

without sensitization to hen’s eggs

•Chicken parvalbumin and two new allergens, aldolaseand enolase, were identified at 12, 40, and 50 kDa, respectively.

•They were recognized by sIgEof 61%, 75%, and 83% of all patient sera which were in the majority of the cases (+) for the fish homologues as well.

Cross-reactivity to fish and chicken meat: a new clinical Syndrome

Kuehn A, Allergy 2016; 71:1772–1781.

We identified 3 new chicken allergens, parvalbumin (Gal d 8), enolase(Gal d 9), and aldolase (Gal d 10) and could show that these allergens, which have homologues in fish, are responsible for the clinical cross-reactivity between fish and chicken meat.

We demonstrated different allergen contents in chicken breast, leg, and wing samples leading to the conclusion that these tissues have a variable allergenicity, not only for patients with food allergy to fish and chicken meat but also for chicken meat-allergic patients without concomitant fish allergy

In cooked or roasted foods, enolase and aldolase were detectable in chicken breast while parvalbumin was detectable in chicken legs and wings.

**

*


•There are multiple types of the major allergens parvalbumin in fish and of tropomyosin in shellfish with no cross-reactivity between fish and shelfish allergens.

•Allergenicity in these species is affected by processing and tends to increase by heating but decrease with canning, gastric acidity, and enzymes.

•The allergenicity of crustaceans appears to be higher than of mollusks, followed by fish,

> >



•Most hypersensitivity reactions to seafood are IgE mediated and are associated with rapid onset of symptoms, including gastrointestinal, cutaneous, respiratory, or multiple organ system symptoms, consistent with anaphylaxis.

•They are generally more severe than the reactions to most other food allergens.

•Sensitization and provocation can occur by ingestion, skin contact, or inhalation.Bahna SL. Adverse food reactions by skin contact. Allergy. 2004;59(suppl 78):66e70.Ramirez DA Jr, Food hypersensitivity by inhalation. Clin Mol Allergy. 2009;7:4.



Seafood allergy: Clinical Features,

•The main clinical manifestations of allergic reactions to fish include vomiting and diarrhea while the most extreme form of reaction is life-threatening anaphylactic shock.

•Patients with fish allergy can however also react to aerosolized proteins generated by cooking or processing of fish resulting in dyspnea, wheezing, tightness of the throat, urticaria, edema, and light headedness.

•raw fish allergens from an open-air fish market and detected allergen concentrations ranging from 2 to 25 ng/m3, very similar to the levels identified in the occupational setting causing allergic sensitization.


•Diagnosis of fin fish or shellfish allergy is primarily based on the type, onset, and course of symptoms, supported by a (+) SPTs results or sIgEagainst the item in question.

•Unless the reaction was life-threatening, confirmation may require an oral food challenge test using the same offending seafood item (and possibly preparation).

•The physician should be aware that the patient may react to only certain species of fin fish or shellfish or when it is prepared in a certain method.

•Some patients may react to certain parts but not another, such as the shell but not the meat, white muscle but not dark muscle, or roe (caviar) but not the fish muscle.Mourad AA, Fish-allergic patients may be able to eat fish. Expert Rev Clin Immunol. 2015;11:419e430.

X

XOK

OK

Seafood allergy: Diagnosis

Diagnostic decision tree on how to proceed from the suspicionof fish-relatedallergicsymptoms,Fish allergy: in review.Sharp MF, Clin Rev Allergy Immunol. 2014;46(3):258-71.

* For cod–fish, a diagnostic level of IgE that can predict clinical reactivity in a US population, with >95 % certainty, was identified as20 KUA/l. It is however questionable if this seemingly high value can be extrapolated to other fish species and other populations as IgE values as low as 1 kU/l could be determinedin patients with anaphylactic reactions to pilchard (sardina) andAnchovy (acciuga)

*

Stephen JN, CEA 2017;47:300-312

• The amount of fish ingested may be important for some individuals with fish allergy.

• Moreover, important pan-fish allergens may vary in concentration between fish.

• The fish ED10 eliciting dose to which 10% of an allergic population would be expected to first clinically react is estimated to be 27 mg.

• Other factors may influence thresholds, such as impaired gastric digestion. Codfish proteins digested in hypo-acidic conditions (pH 3.0) were demonstrated to reduce the tolerance levels between 10 to 30 times as compared to digestion at pH 2.0.

• A decision tree has been suggested to manage fish allergy in a stringent manner that also takes into account adverse parasitic and toxin reactions. Sharp MF, Clinic Rev Allergy Immunol 2014; 46:258–271

Diagnosis of fish allergy


•Management of seafood allergy is to practice strict elimination, which in highly allergic individuals may include avoidance of touching or being close to cooking vapors and having available self-injectable epinephrine.

•Specific immunotherapy or other treatment for seafood allergy is not currently available and will require the development of effective and safe protocols, particularly for highly allergic individuals.

Seafood allergy: Management

Induction of tolerance to different types of fish through desensitization with hake D’Amelio C, PAI 2017;28:96-99

•A 6-year-old female who presented with generalized urticariaafter first eating fish (hake) at the age of 9 months and later at the age of 12 months following the reintroduction of small portions of different types of fish (hake and sole).

•She started suffering facial hives after being exposed to steam generated while cooking tuna at her home since the age of six.

•Taking into account the clinical history, we decided to perform oral immunotherapy (OIT) with the fish hake, a white fish which is frequently consumed in our country.

nasello


[email protected]

Introduction


Seafood Allergy




Conclusion




**

*

Gastric Anisakiasis Images in clinical medicineBaden LR, N Engl J Med 2016;375(7):e11

• A 36-year-old previously healthy woman presented with a 2-day history of severe chest pain and epigastric pain associated with nausea and vomiting.

• The patient reported that she had consumed uncooked salmon approximately 2 hours beforethe chest pain developed.

• Gastroscopy revealed multiple anisakislarvae penetrating into the mucosa in the esophagogastric junction, fundus, upper body, middle body, and antrumof the stomach. 11 larvae were removed with endoscopic forceps, after which the patient’s symptomsresolved

•The disease caused by infection with live Anisakis larvae is called anisakiasis.

•Upon a primary exposure to a helminth, various degrees of inflammatory responses are triggered in the host, characterized by the recruitment of inflammatory effector cells such as neutrophils and eosinophils and changes in blood vessel permeability and blood flow.

•Non-specific inflammation is minimal in most natural host–parasite systems but is often enhanced in zoonotic infections where the host is unnatural or non-permissive, and accordingly, infection with Anisakis species often induces a significant eosinophilic inflammation during a primary infection.

•Anisakiasis usually presents as mild to severe abdominal pain, nausea, vomiting and/or diarrhoea (which in many cases leads to the natural expulsion of the parasite), appendicitis, bleeding, and is in some cases accompanied by allergic reactions, such as hives (urticaria), angioedema, bronchospasm and even anaphylactic shock.

Anisakiasis

Nieuwenhuizen NE, Curr Allergy Asthma Rep. 2014;14:455e461.


Allergy to Anisakis simplex and Anisakiasis

•Live larvae in raw or undercooked seafood ingested by human are usually ejected by vomiting and diarrhea or destroyed by digestion.

•Ingested larvae not killed by one of these processes can attach to mucosa and form granulomas (Anisakiasis).

•Gastrointestinal symptoms, urticaria, dermatitis, asthma and even anaphylaxis may occur. Daschner A, J Allergy Clin Immunol. 2000;105:176e181.Nieuwenhuizen NE, Curr Allergy Asthma Rep. 2014;14:455e461.

Seafood allergy: Anisakis simplex


Allergy to Anisakis simplex and Anisakiasis

•Live larvae in raw or undercooked seafood ingested by human are usually ejected by vomiting and diarrhea or destroyed by digestion.

•Ingested larvae not killed by one of these processes can attach to mucosa and form granulomas (Anisakiasis).

•Gastrointestinal symptoms, urticaria, dermatitis, asthma and even anaphylaxis may occur. Daschner A, J Allergy Clin Immunol. 2000;105:176e181.Nieuwenhuizen NE, Curr Allergy Asthma Rep. 2014;14:455e461.


Diagnosis and treatment are made by endoscopic confirmation and surgical removal of the granulomas.

Prevention of Anisakiasis

•The best means of avoiding infection with live Anisakis is to ensure that all fish meant for consumption is deep-frozen (at −20 °C) for at least 24 hGarcia F et al. Freezing protects against allergy to Anisakis simplex.J Investig Allergol Clin Immunol. 2001;11:49–52.

or that

•fish is cooked for at least 10 min at 60 °C .Audicana MT, Ansotegui IJ, de Corres LF, KennedyMW. Anisakis simplex: dangerous—dead and alive? Trends Parasitol. 2002;18:20–5.



Allergy to Anisakis simplex

•Anisakis simplex is a nematode that infests fish, crustacean and mollusks.

•Various species of seafood can act as intermediate hosts for the larvae, which are approximately 2 cm long in size.

•Certain regions, particularly Japan and Spain (45% of hake nasello in Spain), are notable for high rates of infestation. AAITO-IFIACI Anisakis Consortium. Anisakis hypersensitivity in Italy: prevalenceand clinical features: a multicenter study. Allergy. 2011;66:1563-69.

•Larvae are susceptible to heating (>60C for 10 minutes) or freezing (-20°C for 48 hours), but some of their allergens are resistant to cooking, freezing, and partially to digestion.




•Anisakis simplex is a nematode that infests fish, crustacean and mollusks.

•Various species of seafood can act as intermediate hosts for the larvae, which are approximately 2 cm long in size.

•Certain regions, particularly Japan and Spain (45% of hake nasello in Spain), are notable for high rates of infestation. AAITO-IFIACI Anisakis Consortium. Anisakis hypersensitivity in Italy: prevalenceand clinical features: a multicenter study. Allergy. 2011;66:1563-69.

•Larvae are susceptible to heating (>60C for 10 minutes) or freezing (-20°C for 48 hours), but some of their allergens are resistant to cooking, freezing, and partially to digestion.


Exposure to proteins from live or deadAnisakis can cause allergic reactions.


•Anisakis infection should be considered in patients highly suspected of having had an adverse reaction to seafood but who have had negative allergy test results to seafood.

•Diagnosis of Anisakis allergy currently relies on clinical symptoms, a history of exposure to seafood and detection of Anisakis-sIgE or a (+) Anisakis SPT in the absence of specific IgE to the fish or seafood itself.

The clinical history may be less clear when patients present with chronic symptoms such as chronic urticaria, contact dermatitis, asthma and rhino-conjunctivitis, particularly if they are atopic.

•Furthermore, detection of sIgE to Anisakis can also be due to immunologic cross-reactivity to other helminths (e.g. Ascaris) or invertebrates such as dust mites, cockroaches and shrimps.




•A better diagnostic test would therefore use component-resolved diagnosis, including all known allergens of Anisakis, particularly those that do not appear to cross-react with those of other species.

•Since particular allergens are associated with reactions to cooked fish, this approach may also aid in dietary advice given to patients.

•Some patients with Anisakis allergy are able to tolerate a diet of frozen or well-cooked fish, but some patients are sensitized to heat-stable allergens and may react even to well-processed fish.

•Garcia F et al. Freezing protects against allergy to Anisakis simplex. J Investig Allergol Clin Immunol. 2001;11:49–52.•Baeza ML et al. Characterization of allergens secreted by Anisakis simplex parasite: clinical relevance in comparison with somatic allergens. Clin Exp Allergy. 2004;34:296–302.•Moneo I et al. Isolation of a heat-resistant allergen from the fish parasite Anisakis simplex. ParasitolRes. 2005;96:285–9.



Characterized allergens of Anisakis simplexNieuwenhuizen NE, Curr Allergy Asthma Rep. 2014;14:455e461.

*

* a Pepsin- and Heat-Resistant Major Allergen ESP = excretory–secretory products

High prevalence of Anisakis simplex hypersensitivity and allergy in Sicily, Italy

Heffler E, Ann Allergy Asthma Immunol 2016;116:146

15.4%

% patients sensitizedto A simplex

20 –

15 –

10 –

5 –

….0

30%of patients

had mono-

sensitizationto

A simplex.

3419 consecutive patients referred to the allergy clinic during a 22 mo-period.

Sensitizationto A simplex by SPT.



Distribution of allergic symptoms in patients allergic to Anisakis simplex.



gastrointestinal

oral allergy syndrome



Distribution of allergic symptoms in patients allergic to Anisakis simplex.



gastrointestinal

oral allergy syndrome

Allergic symptoms from A simplex ingestion in raw or marinated fish

were quite frequent, with symptoms ranging from

oral allergy syndrome to anaphylaxis.


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Introduction


Seafood Allergy




Conclusion



Clostridium botulinum

•Foodborne botulism occurs on ingestion of food contaminated by toxin secreted by Clostridium botulinum.

•The toxin is resistant to freezing but destroyed by boiling for 10 minutes.

•Initial manifestations of botulism are gastrointestinal symptoms, such as nausea, vomiting, and diarrhea.

•Other initial symptoms can include dry mouth, diplopia, blurred vision, and photophobia caused by loss of pupillary light reflex.

•A symmetric descending flaccid paralysis may occur that can potentially lead to ventilatory failure.



Clostridium botulinum

Botulism is more likely to occur with certain preparationscharacteristic of particular cultures and geographic locations, such as

1) the whale meat mukluk in the Alaskan and Canadian Arctic,

2) rakish in Norway,

3) salted gray mullet feseikh in Egypt,

4) salted eviscerated whitefish kapchunka in Israel and New York City,

5) uncooked salmon ashbal in Iran,

6) fermented fish preserved in rice izushi in Japan, and

7) imported vacuum-packed whitefish in Europe.



Staphylococcus aureus

Staphylococcus aureus can contaminate food during handling byan infected person and the food then left at room temperature for some time.

The produced enterotoxin when ingested causes:1) vomiting,2) abdominal cramps, and 3) diarrhea usually within 24 hours of ingestion.




Vibrio vulnificus

•Vibrio vulnificus, a species of Gram-negative, motile, curved, rod-shaped (bacillus), pathogenic bacteria of the genus Vibrio.

•It is present in marine environment as part of the natural flora of warm coastal waters worldwide and has been isolated from a variety of seafood,including fish, shrimp, oysters, and clams.

•Consumption of contaminated raw or undercooked seafood can result in fulminant sepsis with ecchymoses and bullae.Jones MK, Infect Immun. 2009;77:1723e1733.


Vibrio vulnificus

•Illness typically begins within 1 to 3 days but may be delayed for 7 days.

•Although illness is rare, V vulnificus in human is the leading cause of death related to seafood consumption in the United States, particularly in immunocompromised patients or associated liver disease.Jones MK, Infect Immun. 2009;77:1723e1733.

•Diagnosis of V vulnificus infection is by microbiologic culture.

•Treatment includes antibiotics (doxycycline plus a cephalosporin) and supportive care.



Norovirus (Norwalk Virus)

•Norovirus infection is the most common cause of acute gastroenteritisin the United States and is generally referred to as the misnomer of stomach flu. Hall AJ, Emerg Infect Dis. 2013;19:1198e1205.

•Symptomatic illness usually occurs after ingestion of contaminated raw food, including seafood.

•After an incubation period of 24 to 48 hours after ingestion nausea, vomiting and watery diarrhea, can occur.

•Resolution of symptoms usually occurs within 1 to 3 days.



Scombroid Poisoning (Histamine Fish Poisoning)

Bacterial contamination from mishandling of fish results in production of heat-resistant toxic substances, including histamine, scombrotoxin, or other vasoactive amines (putrescine and cadaverine).Hungerford JM. Toxicon. 2010;56:231e243.Jantschitsch C, J Am Acad Dermatol. 2011;65:246e247.

High histamine levels are formed by bacterial proliferation on the surface of fish that have been improperly refrigerated.




•The spoiling bacteria (when bacteria breaks down the food, acids and other waste products are created) can be Proteus, Escherichia coli, Salmonella, Morganellamorganii, Enterobacter aerogenes, Raoultella planticola, and Hafnia alvei.

•Histidine decarboxylase in these bacteria acts on histidine in fish muscle and generates histamine, which can then be ingested.

•It has been proposed that a specific scombrotoxin, cis-urocanic acid, produced from histidine decarboxylationmay also directly degranulate mast cells.




•Histamine development is more likely to occur in raw, unfrozen fish.

Because the fish may appear and smell normal, the consumer may not identify a problem before eating the fish.

•Once the bacteria have formed the enzyme histidine decarboxylase, histamine production can continue even if the bacteria are killed.

•Although cooking can inactivate both the enzyme and the bacteria, the toxic factors produced are heat stable and, once formed, are not destroyed by cooking, smoking, or freezing.





•The most commonly susceptible fish are in the Scombridae andScomberesocidae families, which include: tuna, mackerel, blue fish,anchovies, herring.

•Affected fish may acquire a bitter and peppery taste, although this may occur in normally tasting items as well.

Fish can be screened by a histamine detector, and there is a permissible limit of less than 50 mg/kg in the United States and 100 to 200 mg/kg in Europe.

Histamine poisoning associated with eating tuna burgers. Becker K. JAMA. 2001;285:1327-1330.

20 case-patients with 2 of the following symptoms within 2 hours of eating tuna:

rash, facial flushing, vomiting, diarrhea, dyspnea, a tight feeling in the throat, headache, a metallic or peppery taste in the mouth.

All case-patients ate tuna: 18 ate tuna burgers, 2 ate salad containing tuna, and 2 ate filets.

Tuna samples (available from 3 outbreaks) had histamine levels above the FDA regulatory level of 50 ppm (levels were between 213 and 3245 ppm).




In 19 cases, the tuna used to prepare burgers or salads was frozen and

thawed more than once before serving.

Violations of recommended temperature controls were identified in 2 of the 5 restaurants,

accounting for 14 (64%)

cases.






rapid chilling of fish on the fishing vessel and

keeping the temperature of the fish lower than 0°C

throughout storage and distribution is the best

way to prevent histamine formation.

This is lower than the current FDA

recommendation of 5°C




•Tuna can be especially vulnerable to temperature fluctuations because their average body temperature when caught tends to be several degrees warmer than that of other types of fish.

•Belly meat might have an increased susceptibility to bacterial contamination during the evisceration process because of its proximity to the fish gut cavity, where histamine-forming bacteria reside.

•Furthermore, thin pieces of fish, such as the belly meat used for ground tuna and salads, might be more vulnerable to temperature fluctuations than thicker tuna filets.

•Violation of storage and temperature controls are also more likely with tuna used for salads and burgers, because pieces are stored over a longer period than filets and exposed to multiple thawing and refreezing cycles.


Histamine poisoning is a chemical intoxication with a short incubation period, usually ranging from minutes to a few hours after ingestion.

Symptoms include:

•tingling and burning sensations around the mouth, •headache, •facial flushing and sweating, •rash and itching on the upper body, •abdominal cramps, nausea, vomiting, diarrhea, •heart palpitations.

+

+

+


Histamine poisoning is a chemical intoxication with a short incubation period, usually ranging from minutes to a few hours after ingestion.

Symptoms include:

•tingling and burning sensations around the mouth, •headache, •facial flushing and sweating, •rash and itching on the upper body, •abdominal cramps, nausea, vomiting, diarrhea, •heart palpitations.

Symptoms related to histamine poisoning can also be similar to

those of coronary heart disease, increasing the

possibility of an invasive medical intervention if misdiagnosed.


•In most persons, symptoms are self-limiting, although histamine poisoning can be life-threatening in persons with conditions such as asthma and heart disease.

•Some drugs, such as monoamine oxidase inhibitors, can worsen or prolong an attack by inhibiting the breakdown of histamine.

•Antihistamine medication such as diphenhydramineand cimetidine often relieve symptoms.

•However, severe cases of toxicity can require the same aggressive management as acute anaphylaxis.


Pufferfish Poisoning (pesce palla)

•Pufferfish tetrodotoxin can be present in porcupinefish, globefish, blowfish, mola, ocean sunfish, triggerfish.

•The toxin is produced outside the fish bodies by bacteria andaccumulates in fish liver, gonads, and skin.

•In Japan, fugu (prepared from the flesh of pufferfish) is required to be prepared by chefs trained and certified to be devoid of the potentially poisonous parts.

•Within minutes to hours, individuals develop nausea, dizziness, weakness, paresthesias, loss of reflexes, hypotension, motor paralysis, and respiratory failure.

flesh of pufferfish



Seafood Neurotoxin (paralytic shellfish poisoning)

•Seafood neurotoxins (saxitoxin and its derivatives) are producedby cyanobacteria in fresh water and by dinoflagellates(marine plankton) in seawater.

•Mollusks are more commonly implicated than crustaceans.Pufferfish may be affected as well.

•Florida monitors the neurotoxin concentrations in pufferfishalong its east coast.

•Afflicted persons develop paresthesia and numbness within < 30 minutes of ingestion, first in the mouth and then in the face and neck, followed by drowsiness, motor incoordination, and muscular weakness that may progress to respiratory paralysis.

Florida



Ciguatera Fish Poisoning

•The dinoflagellate Gambierdiscus toxicus in blue-green algae can infect reef fish and produce ciguatoxin, maitotoxin, scaritoxin, and gambieric acid.Lehane L. Ciguatera update. Med J Aust. 2000;172:176e179.

•It is endemic in the Pacific and Caribbean regions.

•Implicated fish include barracuda, amberjack, grouper, snapper,and moray eel.

•In Hong Kong, outbreaks occurred every few years, and the dominant fish switched from snapper to grouper.

Blue green algae may look like algae but

it’s actually bacteria




•The toxins are heat stable and lipid soluble and are more in the fish head, viscera, roe(uova), and skin.

•Within 1 to 4 hours of consuming the affected fish, symptoms develop as gastrointestinal (vomiting, diarrhea, colic), neurologic (paresthesia, numbness, pruritus, myalgia, arthralgia), and cardiovascular (bradycardia, hypotension).

Gastrointestinal symptoms subside within days of rehydration.Cardiovascular symptoms respond to atropine and dopamine.Neurologic symptoms may persist for weeks or months and mayrespond to amitriptyline, nifedipine, gabapentin, or pregabalin.

Brett J, Pregabalin to treat ciguatera fish poisoning. Clin Toxicol (Phila). 2015;53:588.




•The toxins are heat stable and lipid soluble and are more in the fish head, viscera, roe(uova), and skin.

•Within 1 to 4 hours of consuming the affected fish, symptoms develop as gastrointestinal (vomiting, diarrhea, colic), neurologic (paresthesia, numbness, pruritus, myalgia, arthralgia), and cardiovascular (bradycardia, hypotension).

Gastrointestinal symptoms subside within days of rehydration.Cardiovascular symptoms respond to atropine and dopamine.Neurologic symptoms may persist for weeks or months and mayrespond to amitriptyline, nifedipine, gabapentin, or pregabalin.

Brett J, Pregabalin to treat ciguatera fish poisoning. Clin Toxicol (Phila). 2015;53:588.


toxins interfere with the function of nerve endings


Azaspiracid Shellfish Poisoning

•Azaspiracids are polyether marine toxins possibly produced by dinoflagellateand accumulate in various shellfish.

•Eating the affected shellfish causes severe acute gastrointestinal symptoms that persist for 2 to 3 days.



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Introduction


Seafood Allergy




Conclusion



•Seafood poisoning may be underdiagnosed, particularly when mild or when misdiagnosed or self-attributed as an allergy and a proper history is not undertaken to differentiate a likely mechanism of action.

•The presence of similar symptoms in other individuals who shared the same meal, absence of prior reactions to the same seafood, and its subsequent tolerance without symptoms should favor a toxic reaction.

•The level of suspicion for toxic reactions should be higher in regions with seasonal algal bloomsand high levels of biotoxins or toxic algae.



•Except in scombroid poisoning, the toxin in most of these toxic syndromes does not alter the taste or appearance of the seafood item, and it is not inactivated by ordinary cooking.

The most likely toxin will depend on the seafood species






Treatment of these toxic syndromes is mainly supportive,including respiratory support in patients with pending

respiratory failure.





In acute cases, gastric emptying and administration of activated charcoal have been

recommended to prevent furtherabsorption of the toxins.


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Introduction


Seafood Allergy




Conclusion



Reactions to seafood can be allergic in nature to:

1) a known allergen in fin fish or shellfish or

2) can be attributable to something other than seafood protein,

such as contamination by other food allergens,

3) seafood parasite Anisakis simplex,

4) additives,

5) natural rubber latex, or

6) chemical contamination, or

7) seafood-associated toxins by bacterial action.

Not every seafood “allergy” is allergy: Conclusions


Clinicians are advised to take a careful history and not assume allergy as the default mechanism for a reported adverse reaction to a seafood item.

A detailed history should be obtained about;

1) nature and timing of the reaction,

2) type of item involved,

3) whether other members of the dining party also fell ill, and

4) patient’s own history of consuming these items.

These inquiries can help differentiate a likely IgE-mediated reaction from a toxic one. or



Whenever allergy tests are performed and the results are negativefor the suspected seafood item, the physician should consider:

1. Anisakis simplex allergy if the seafood is from a highly infested region.

2. seafood-associated toxins or botulism in individuals with neurologic symptoms or when multiple consumers are affected,

3. if the fish tasted spoiled or is from a typical species, scombroidpoisoning should be considered.


Thank you for your attention to the story my granpatold you!Mia Charlize Powell

not every seafood allergy is allergy

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