Prevalence data are based on different diagnostic procedures. While the prevalence of sensitization (sensitivity) can be estimated by SPT, RAST, and immunoblot, a clinical relevant sensitization (allergy) is evaluated by convincing history (anamnesis) or food challenge tests (ideally by DBPCFC).
1.1 General Population
Prevalence within the author's selected populations is
listed. Those assigned randomly selected ("unselected") with numbers over
500 may be regarded as representative of the "general population". Inclusion
criteria may involve circumstances not related to atopic predisposition
according to current knowledge.
| Country / Subjects | Allergy / Sensitivity | References |
| Italy, Florence
children of general population |
codfish 0.4-0.5% (calculated by extrapolation) | de Martino et al. 1993 |
| Norway, Oslo
general population |
codfish 0.1% | Aas 1966 |
| Sweden (Göteborg,
Uppsala, Västerbotten)
1397 unselected adults, age 20-44 years (study period 1991-92) |
fish 0.3% (RAST) | Björnsson et al. 1996 |
| UK
16420 randomly selected adults (age >15 years) |
fish 0.5% (interview survey, questionnaire) | Emmett et al. 1999 |
1.2 Subjects with Atopic or Other Diseases
| Country / Subjects | Allergy / Sensitivity | References |
| France
81 cases of food- related anaphylaxis (from 1991-92) |
fish 10.4% | Moneret-Vautrin & Kanny 1995 |
| France
80 cases of food- related anaphylaxis (from 1993-97) |
fish 5% | European Commission 1998 |
| France, Nancy and Toulouse
544 food allergic children |
codfish 6.4% (labial food challenge) | Rance et al. 1999b |
| France, Pierre Benite
a) 580 patients with adverse reactions to food b) 60 cases of anaphylaxis (study period 1984-92) |
a) fish 24% (RAST)
b) fish 13% |
Andre et al. 1994 |
| France, Toulouse
142 food allergic children |
codfish 5.6 % (labial food challenge) | Rance & Dutau 1997 |
| France, Toulouse
378 food allergic children |
codfish 7.1% (food challenge) | Rance et al. 1999a |
| Germany,Bonn
150 children allergic to egg white, milk, codfish, wheat, peanut and/or soybean |
codfish 5.3% (RAST) | Liappis & Starke 1999 |
| Italy, Bari
134 patients with atopic dermatitis |
codfish 5.2 % (case history), 10% (RAST) | Bonifazi et al. 1978 |
| Italy, Florence
food allergic children |
codfish 18 % (SPT, RAST)
of which 66 % had clinical symptoms |
Novembre et al. 1988
Vierucci et al. 1989 |
| Italy, Florence
558 children with atopic diseases |
codfish 4.5% (SPT, RAST) | de Martino et al. 1993 |
| Italy, Florence
54 episodes of food-dependent anaphylaxis in 44 children (age 1 month to 16 years) (from 1994-1996) |
fish 30% | Novembre et al. 1998 |
| Italy, Milan
202 with chronic urticaria and suspected food allergy |
fish 0.5% (DBPCFC) | Pigatto & Valsecchi 2000 |
| Netherlands
131 cases of food- induced anaphylaxis (from 1993-1997) |
fish 3.8%(survey, reported to the TNO Nutrition and Food Research Institute) | European Commission 1998 |
| Norway, Oslo
a) food allergic patients b) fish allergic children |
a) codfish 4.2%
b) codfish 88% |
Aas 1966 |
| Spain, Madrid
355 food allergic children |
fish (cod, tuna) 30% (SPT, RAST) | Crespo et al. 1995 |
| Spain, Pamplona
74 patients with atopic dermatitis |
fish 22% (SPT, RAST, Histamine Release) | Resano et al. 1998 |
| Sweden
55 cases of food- induced anaphylaxis (from 1994-1996) |
fish 1.8%(Hospital Reports) | European Commission 1998 |
| Switzerland, Zurich
a) 402 food allergic adults (study period 1978-87) b) 383 food allergic patients (study period 1990-94) |
a) fish 7.2 %
b) fish 9.7% (anamnesis, clinical relevance, diagnostic tests) |
a) Wüthrich 1993
b) Etesamifar & Wüthrich 1998 |
| UK, London
100 patients with food intolerance |
fish/shellfish 22% (repeated challenge) | Lessof et al. 1980 |
| UK, Manchester
90 patients experienced anaphylactic reactions to foods (from 1994-1996) |
fish 2.2% (suspected cause of patients' worst reaction) | Pumphrey & Stanworth 1996 |
| USA, Baltimore, MD
20 fish- sensitive patients with atopic dermatitis |
fish 55% (DBPCFC) | Sampson & Ho 1997 |
| USA, Denver, CO
food allergic children (DBPCFC) a) 74 age of <3 years b) 111 age of 3-19 years |
a) fish 4.1%
b) fish 4.5% (DBPCFC) |
Bock & Atkins 1990 |
| USA, Little Rock, AR
165 patients with atopic dermatitis |
codfish 6.7% (SPT) of which 3/9 were DBPCFC-positive | Burks et al. 1998 |
| USA, Long Beach, CA
137 patients with latex allergy |
fish 1.7 % (convincing history of possible IgE mediated symptoms occurring within 60 minutes of ingestion) | Kim & Hussain 1999 |
| USA, Portland, ME
39 fish sensitive adults |
codfish 31 % (case history), 46 % (SPT), 67 % (RAST)
to all tested 17 fish species 26 % (SPT) |
Helbling et al. 1996 |
1.3 Prevalence of Associated Allergies
| Country / Subjects | Allergy / Sensitivity | References | ||||||||||||||||
| Italy, Florence
20 children with codfish allergy |
|
de Martino et al. 1990 |
2 Outgrowing / Persistence of Codfish
Allergy
| Country / Subjects | Allergy / Sensitivity | References |
| Finland, Oulu
children with atopic dermatitis |
Allergy to fish according to age
groups:
0-1 year in 5.3% 1-3 years in 12% 3-15 years in 9.5% (n=57, 43 and 42) (SPT) |
Hannuksela 1987 |
| France, Nancy and Toulouse
35 children with codfish allergy |
Allergy to codfish according to
age groups:
0-1 year in 0% 1-3 years in 29% 3-6 years in 31% 6-15 years in 40% (SPT and/or RAST, food challenge) |
Rance et al. 1999b |
| Symptoms & Case Reports | References | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| systemic reactions
anaphylaxis (6, 7, 9, 10, 14, 12) symptoms on skin and mucous membranes
gastrointestinal symptoms
respiratory symptoms
other symptoms
|
(1) DeBesche 1937
(2) Aas 1978 (3) Bonifazi et al. 1978 (4) Beck & Knudsen-Nissen 1983 (5) Ferre et al. 1985 (6) Yunginger et al. 1991 (7) Hansen & Bindslev-Jensen 1992 (8) de Martino et al. 1993 (9) Andre et al. 1994 (10) Moneret-Vautrin & Kanny 1995 (11) Casimir et al. 1997 (12) James et al. 1997 (13) Bugajska-Schretter et al. 1998 (14) Lin et al. 1998 (15) Patriarca et al. 1998 (16) Helbling et al. 1999 |
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Percentage of Reactions
(2) codfish allergic children (3) fish sensitive adults (4) fish allergic patients with atopic dermatitis (5) codfish allergic children |
(1) Lessof et al. 1980
(2) de Martino et al. 1993 (3) Helbling et al. 1996 (4) Sampson & Ho 1997 (5) Rance et al. 1999b |
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| Threshold for Elicitation of Symptoms
Amounts of codfish inducing symptoms ranged from 6 mg to 6.7 g (anaphylactic reactions 25-50 g) (DBPCFC, 10 codfish allergic adults) (1) Subjective symptoms at doses of 1 g codfish in 71% and at subsequent doses of 4 g in 29% of patients; objective symptoms at doses of 1 g in 14%, at doses of 4 g in 29%, and at doses of 64 g in 14% of patients (DBPCFC, 7 codfish allergic adults) (2) Amounts of dehydrated fish smaller than 500 mg induced symptoms in 17% of patients (DBPCFC, 12 fish allergic children with atopic dermatitis) (3) |
(1) Hansen & Bindslev-Jensen 1992
(2) Helbling et al. 1999 (3) Sicherer et al. 2000 |
4 Diagnostic Features of Codfish Allergy
| Parameters / Subjects | Outcome | References | |||||||||
| Onset of Symptoms, Male:Female Ratio, IgE-level
a) 68 codfish allergic children b) 533 children allergic to other inhalant and/or food allergens |
Onset of asthma significantly lower in codfish
allergic children (P <0.001):
a) 32 months, b) 41 months Significant higher male:femal ratio in codfish allergic children: a) 3.53, b) 1.78 and 0.68 in children allergic to inhalants and foods Significant higher specific serum IgE in codfish allergic children (P <0.001, RAST): a) 14.27 +/- 3.87 kU/L b) 8.12 +/- 4.06 kU/L |
de Martino et al. 1993 | |||||||||
| SPT and IgE
codfish allergic adults |
Significant correlation between SPT and RAST (P<0.0005) | Helbling et al. 1996 | |||||||||
| SPT, IgE and Clinical Relevance
20 codfish allergic patients |
SPT and RAST were found to be reliable for the diagnosis of allergy to codfish | Aas 1978 | |||||||||
| SPT, IgE, Histamine Release and DBPCFC
10 codfish allergic adults |
For identification of DBPCFC-positive subjects, skin prick test and RAST proved to be the most sensitive tests (7/7) (specificity of all tests 90-97 %) | Hansen & Bindslev-Jensen 1992 | |||||||||
| a) RAST and DBPCFC
b) Histamine Release (HR) and DBPCFC 8 codfish allergic adults |
a) RAST with commercial extracts and fresh food:
sensitivity 100% specificity 87-100% b) HR with commercial extracts and fresh food: sensitivity 83% specificity 100% |
Hansen et al. 1996 | |||||||||
| a) RAST and DBPCFC
b) SPT and DBPCFC food-allergic children with atopic dermatitis |
a) predictive values of fish specific IgE > 0.35 kU/L
positive predictive value 49% (95% for IgE > 20 kU/L) negative predictive value 97% b) predictive values of SPT ( > 3 mm) positive predictive value 77% negative predictive value 80% |
Sampson & Ho 1997 | |||||||||
| RAST, SPT and DBPCFC
a) 7 codfish sensitized adults (SPT, history) b) 9 fish allergic adults (tested fish species: catfish, codfish, and snapper) |
a) RAST positivity in 71%
|
Helbling et al. 1999 |
| Treatment* | Outcome | References |
| Elimination Diet
7 children (8-48 months of age) sensitized to fish (RAST, SPT), all children tolerated fish at the beginning of elimination diet |
Instituting fish-free diet based on positive skin test
to fish and associated atopic dermatitis in 5 (plus asthma in one). Effects
of elimination diet after 1-96 months (mean 36 months):
Improvement of atopic dermatitis in 2 patients. Accidental exposure to fish inducing severe symptoms during elimination diet after 24-111 months (mean 70 months): after ingestion in 3 patients (7 occasions), after inhalation in 4 patients (7 occasions), and after skin contact in 4 patients (7 occasions). SPT and RAST remained unchanged or increased after elimination diet. |
Larramendi et al. 1992 |
| Immunotherapy
1 fish/codfish allergic child |
Uncooked codfish odors and accidentally eaten pieces of codfish were tolerated after therapy (immunotherapy administered by daily subcutaneous injections following the schedule for insect venom allergy using codfish extracts) | Casimir et al. 1997 |
| Oral Desentization
a) 2 codfish allergic patients b) 7 fish allergic patients |
A diluted food extract followed by increased pure boiled
codfish was administered following a standardized protocol, after therapy
codfish was tolerated (maintenance dose: 200 g boiled fish / week)
a) treatment successfully completed, length of therapy 3 and 5 months b) treatment successfully completed in 5 cases in 4-10 months |
a) Patriarca et al. 1998
b) Nucera et al. 2000 |
| Proteins / Glycoproteins | Allergen Nomenclature | References |
| Allergen M [12-13 kDa] | Gad c 1* | Elsayed & Bennich 1975 |
| 41-kDa Allergen | Galland et al. 1998 | |
| Allergen: 63 kDa | Mata et al. 1994 | |
| Allergens: 12, 21, 24, 33, 47, 61 kDa | Hemmens et al. 1989 | |
| Allergens: 12, 18, 22, 23, 26, 31, 33, 35, 37, 43, 49, 56, 69, 81, > 97 kDa | Hansen et al. 1996 | |
| Allergens: 12, 15, 20, 25, 30, 35, 66, 80, 100, 200 kDa | Bugajska-Schretter et al. 1998 | |
| Allergens: 12, 18, 41, 60, 67, 80, 104, 130 kDa | Dory et al. 1998 | |
| Allergens: 13, 22, 28, 41, 49, 60 kDa | Galland et al. 1998 |
7.1 Sensitization to Codfish Allergens
| Country / Subjects | Sensitivity to | References |
| Austria, Vienna
28 codfish allergic patients |
12 kDa allergen (Gad c 1) in 100 %
(SDS-PAGE immunoblot) |
Bugajska-Schretter et al. 1998 |
| Denmark, Copenhagen
8 codfish allergic adults |
12-13 kDa allergen in 100 % of DBPCFC- positive patients (SDS-PAGE immunoblot) | Hansen et al. 1996 |
| France, Nantes
12 codfish allergic patients |
12 kDa allergen: relative IgE- binding 50 %
30 and 67 kDa allergens: about 10 % of total IgE binding to crude extract (pooled serum, SDS-PAGE immunoblot) |
Dory et al. 1998 |
| Norway, Bergen (a)
Australia, St. Leonards (b) a) 2 codfish , b) 1 fish allergic patient |
6 allergens recognized by all patients' sera, relative intensity of IgE- binding: 12 kDa >> 21, 24 kDa > 33, 47, 61 kDa (SDS-PAGE immunoblot) | Hemmens et al. 1989 |
| Norway, Bergen
a) 11 codfish allergic patients b) fish allergic patients |
12 kDa allergen (Gad c 1)
(a) ELISA inhibition (b) SDS-PAGE immunoblot |
a) Lindstrøm et al. 1996
b) van Do et al. 1999 |
| Norway, Oslo
codfish allergic patients |
At least 7 IgE- binding precipitates (CRIE) | Aukrust et al. 1978 |
7.2 Allergen M (Gad c 1)
7.3 41-kDa-Allergen
| Extract / Purified Allergens | Methods | References |
| Protein extract | Extraction of raw and cooked fish with PBS-buffer overnight at 4°C, centrifugation, lyophilization | Bernhisel-Broadbent et al. 1992 |
| Muscle and Surimi extract | Extraction of raw codfish and surimi with 2 % sodium chloride solution for 18 h, centrifugation, purification by gelfiltration (Sephacryl S200) | Mata et al. 1994 |
| Muscle extract | Homogenization of raw muscle under liquid nitrogen, dissolved in electrophoresis sample buffer | Bugajska-Schretter et al. 1998 |
| Muscle extract | Fillets of pre- rigor mortis and post- rigor mortis codfish were cut and placed into liquid nitrogen, crushed and homogenized in phosphate- buffer (for sarcoplasmic proteins) or PBS-buffer (for myofibrillar proteins) at 4°C, centrifuged and lyphilized | Dory et al. 1998 |
| Allergen M | Purification of myogen fraction by ion-exchange chromatography (DEAE) and gelfiltration (Sephadex G-75) | Aas & Jepsen 1967
Aas & Elsayed 1969 |
| Allergen M | Purification of myogen fraction by isoelectric fractionation | Elsayed & Aas 1971 |
| 41-kDa Allergen | Isolation from a crude cod extract by ammonium sulfate fractionation, hydroxyapatite chromatography and preparative electrophoresis | Galland et al. 1998 |
| Cross-Reacting Allergens | Subjects / Methods | References |
| Codfish
bass, dentex, eel, sole, and tuna (17 different fish species tested) |
Cross-reacting allergens in cod, bass, dentex, eel, sole, and tuna, inhibition range from 73 - 96 % (RAST inhibition) | de Martino et al. 1990 |
| Codfish
10 different fish species (bass, catfish, flounder, mackerel, perch, salmon, trout, tuna, sardine) |
11 fish allergic patients: 7 patients sensitive to only
1 species, 1 patient to 2 species, and 2 patients to 3 species (oral challenge)
8 patients sensitive to all 10 species in SPT Cross-reactivity did not necessarily correlate with clinical relevance (RAST inhibition) |
Bernhisel-Broadbent et al. 1992 |
| Codfish
salmon |
Inhibition of IgE-binding to salmon by codfish (ELISA inhibition) | Lindstrøm et al. 1996 |
| Codfish
mackerel, herring, and plaice |
Inhibition of IgE- binding to codfish extract by mackerel,
herring, and plaice in 8 codfish allergic patients, no cross-reactivity
to shrimp or milk
(RAST inhibition) |
Hansen et al. 1997 |
| Codfish
catfish, dogfish, snapper (12.5 kDa allergens) |
Inhibition of IgE- binding to 12.5 kDa allergens by codfish extract (immunoblot inhibition) | James et al. 1997 |
| Codfish
tuna, salmon, perch, carp, and eel |
Inhibition of IgE- binding to extracts from tuna, salmon, perch, carp, and eel by codfish ranged from 43 - 97 % in 4 fish allergic patients (RAST inhibition) | Bugajska-Schretter et al. 1998 |
| Codfish
tuna, salmon, perch, carp, and eel (12 kDa) |
Inhibition of IgE- binding to 12 kDa parvalbumins from different species by codfish extract (immunoblot inhibition) | Bugajska-Schretter et al. 1998 |
| Codfish Allergens (12
kDa)
17, 21, 24, and 47 kDa- codfish allergens * |
Gad c 1 (12 kDa) bound IgE was eluted and rebound to 12, 17, 21, 24, and 47 kDa allergens in 1 patient, while in another patient IgE rebound only to 12 kDa allergen (SDS-PAGE immunoblot) | Hemmens et al. 1989 |
| Codfish Allergens
12, 22, 25, 30, 45, 50, 60, 67, 80, 104, and 130 kDa- codfish allergens * |
Exept for the 41, 49, and 55 kDa allergens all IgE- binding proteins from codfish were detected by antiparvalbumin specific antibody (SDS-PAGE immunoblot) | Dory et al. 1998 |
| Codfish (12
kDa)
salmon (Sal s 1) * |
Gad c 1 (12 kDa) and Sal s 1 have some homologous allergenic epitopes (SDS-PAGE immunoblot) | van Do et al. 1999 |
10 Stability of Codfish Allergens
| Treatment | Effects | References |
| Cod myogen fraction (Enzymic
Hydrolysis)
enzymic digestion for a) 48 h, b) < 24 h and c) < 2 h at 37°C (stopped by heating to 80°C, 10 min) |
a) Loss of allergenic activity by treatment with trypsin,
pepsin, subtilisin or pronase, appr. 50% decrease in allergenic activity
by elastase
b) Remaining allergenic activity by pronase treatment c) Remaining allergenic activity by trypsin or pepsin treatment |
Aas & Elsayed 1969 |
| Codfish Allergens (Detergents)
9 household cleaning solutions and 5 chemical detergents mixed with codfish allergen extract, incubation for 20 min at RT |
Guanidine hydrochloride and sodium lauryl sulphate induced
some modifications of allergen patterns;
None of the detergents totally destroyed the allergenic activities, even when used in concentrations up to 10 times than recommended (CIE, CRIE, serum pool of >5 patients) |
Dybendal et al. 1990 |
| Codfish Allergens (Heat)
raw and cooked codfish |
Number of protein bands in raw and cooked codfish: 25
and 23, respectively (SDS-PAGE)
Lower intensity of IgE- binding to allergens from cooked codfish (SDS-PAGE immunoblot) |
Bernhisel-Broadbent et al. 1992 |
| Codfish Allergens (Heat)
raw and boiled (6 min, 1 h, 4 h) codfish, mackerel, herring, and plaice |
Except for mackerel all allergens seemed stable in histamine release test, bands >40 kDa were more heat sensitive, allergens detected in all extracts even after 4 h of boiling and in boiling water (2 codfish allergic patients, SDS-PAGE immunoblot) | Hansen et al. 1994 |
| Pizza Toppings (Heat)
uncooked and cooked pizza toppings |
IgE-binding to uncooked pizza topping extract was inhibited by cooked pizza toppings (max. 76%), pollack (max. 59%), cod (max. 30%), and surimi (max. 52%) (30 fish sensitive patients, RAST inhibition) | Helbling et al. 1992 |
| Codfish Allergens (Storage)
a) pre- and post-rigor mortis b) stored commercial codfish (several days) |
a) No difference in IgE- binding patterns
b) Storage might increase relative IgE- binding, additional bands 18, 41, and 80 kDa allergens (RAST inhibition, SDS-PAGE immunoblot) |
Dory et al. 1998 |
| Reported Adverse Reactions | References |
| Food / Food additives
Fatal anaphylactic reaction in fish allergic patient after ingestion of potatoes fried in same oil that has been used for fish (1) Anaphylactic reactions in fish allergic boy after ingestion of different kinds of fish (cod, tuna, salmon, trout, eel...), fish soup, chopsticks contaminated with fish preparations or canned fish (2) |
(1) Yunginger et al. 1988
(2) Lin et al. 1998 |
| Allergens in Codfish Products | Results | References |
| Codfish Allergens
63 kDa allergen in surimi, a Japanese food product containing fish meat that also may contain starch, egg white, and other ingredients |
Surimi extract gave positive reactions in 6 codfish allergic patients (RAST, RAST inhibition, Histamine Release, SDS-PAGE) | (1) Mata et al. 1994 |
| Fish Allergens
Fish allergens in surimi and pizza toppings |
Extracts of surimi, uncooked and cooked pizza toppings gave positive reactions in fish sensitive patients (RAST, RAST inhibition) | (1) Helbling et al. 1992 |
| Anisakis simplex
Anisakis simplex, a parasite of fish and cephalopods |
Specific IgE to A. simplex (> 0.7 kU/l) in 22 patients with urticaria/angio-edema after fish ingestion, of which 8 were diagnosed as having A. simplex allergy (RAST, clinical symptoms) | (1) Del Pozo et al. 1997 |
| Other Allergen Sources | References |
| Dust
Dust samples from fitted-carpets and linoleum floors in schools in Norway contained codfish allergens, higher contents in samples from carpets |
Dybendal et al. 1989a, 1989b |
| Air Samples: Fish Market
Passively aerosolized fish allergens in samples from an open-air fish market: detectable fish allergen content (2-25 ng/m3 ) on 39 of 41 days (air sampling, IgE-ELISA) |
Taylor et al. 2000 |
| Food Allergen | Labelling / Regulation Status | References |
| International Regulations
Fish and fish products |
mandatory labelling of prepackaged food / advisary status (1) | (1) Codex Alimentarius Commission 1999 |
| European Regulations
Fish and fish products |
labelling appropriate / recommendation (1) | (1) Bousquet et al. 1998 |