Q:

I have seen several patients who report anaphylactic sensitivity to catfish, but not to other finned fish (e.g., codfish, salmon). Is there an allergenic protein that is unique to catfish? I am very reluctant to give my blessings for catfish allergic patients to eat other species of finned fish without a clear understanding the protein involved in these highly unique cases.

A:

Thank you for your recent inquiry.

There is a body of literature on catfish allergy, and some of the literature has dealt with the potential reactivity between catfish and other fish. My own assessment of this literature is that there is clearly potential for cross-reactivity, and unfortunately, although in vitro tests and skin tests are helpful, the only definitive test is an oral challenge.

I have copied below for you, four abstracts of articles which were used to formulate this opinion. However, as you can see, these articles are from the older literature. I am not aware of any more recent studies, and therefore am going to ask Dr. Samuel Lehrer, who is the senior author on two of the articles cited below, for this assistance in responding to your inquiry.

When we hear from Dr. Lehrer, I will forward his response to you.

Thank you again for your inquiry.

Ann Allergy Asthma Immunol 1999;83:517–523.
Fish allergy: is cross-reactivity among fish species relevant? Double-blind placebo-controlled food challenge studies of fish allergic adults
Arthur Helbling, MD*; Robert Haydel, Jr, MD†; Marjorie L McCants§; Jon J Musmand, MD‡;
Jane El-Dahr, MD‡,§; and Samuel B Lehrer, PhD§
Background: Allergic reactions to fish are a common cause of food allergy in many areas of the world where fish is a major source of protein. Although different species of fish may be consumed, possible cross-reactivity has received limited investigation.
Objective: The aim of this study was to assess potential cross-reactivity to different species of fish species using double-blind, placebo-controlled food challenges (DBPCFC) in fish-allergic adults and to compare skin test and RASTreactivity with the challenge response.
Methods: Nine skin prick test and/or RAST-positive adult individuals with histories of an immediate-type reaction following fish ingestion were challenged with different fish species using double-blind, placebo-controlled food challenge.
Results: Of a total of 19 double-blind, placebo-controlled fish challenges performed, 14 challenges (74%) resulted in the induction of objective signs that were consistent with an IgE-mediated response. The most common sign observed was emesis (37%); the most prevalent subjective symptoms reported were compatible with the oral allergy syndrome (84%). Three subjects reacted to at least three fish species and one subject reacted to two fish species tested. In regard to the positive challenges, predictive accuracy of skin prick test and RAST was 84% and 78%, respectively.
Conclusion: Our results indicate that clinically relevant cross-reactivity among various species of fish may exist. Advising fish-allergic subjects to avoid all fish species should be emphasized until a species can be proven safe to eat by provocative challenge.

Ann Allergy Asthma Immunol 1996;77:48–54.
Immunopathogenesis of fish allergy:
identification of fish-allergic adults by skin test and radioallergosorbent test
A Helbling, MD*; M L McCants†; J J Musmand, MD‡; H J Schwartz, MD§; and S B Lehrer, PhD†
Background: As the consumption of fish increases in the United States, the importance of allergic reactions to fish has become clear. Since most previous studies on fish allergy have focused on children reacting mainly to codfish, there is a need to investigate allergic reactions to other fish in adults.
Objective: To identify fish-allergic adults, and to assess cross-reactivity among different species of fish by RAST inhibition.
Methods: Thirty-nine individuals who reported fish allergy were selected for study; 32 (82%) were atopic as defined by two or more positive skin tests to common inhalant allergens and a history of allergic reactions and 33 (85%) experienced allergic symptoms within 30 minutes after ingesting fish. The most frequently reported symptoms were hives (69%), itching (69%), and wheezing/chest tightness (54%). Study subjects were skin tested with fish extracts and their sera assayed for IgE antibodies to different fish species.
Results: Thirty-six (92%) of the subjects tested had a positive skin test to at least one of 17 fish extracts tested; 9/35 (26%) reacted to all 17 extracts. Of the atopic (two or more positive skin tests to common inhalant allergens plus a personal and/or family history of allergy) and nonatopic fish-tolerant controls, 20/26 (77%) reacted by skin test to one or more fish extracts tested; the most prevalent positive reaction was to anchovy (73%). A significant correlation (P .01) was observed between skin test reactivity of fish-allergic subjects to most fish extracts and fish RAST reactions. Radioallergosorbent inhibition testing demonstrated significant cross reactivity among pollack, salmon, trout, and tuna; and between mackerel and anchovy.
Conclusion: These results suggest that fish-allergic subjects may be clinically sensitive to more than one species of fish. Skin test reactivity to fish by itself is not an adequate criterion for the confirmation of clinically relevant fish allergy; consequently, fish-allergic subjects with positive skin tests to several fish species should exercise caution when eating fish until tolerance can be demonstrated by doubleblind, placebo-controlled food challenge, at the patient’s earliest convenience.

Ann Allergy Asthma Immunol 1997;78:187–94.
Codfish allergy in adults: IgE cross-reactivity among fish species
Tine K Hansen, MD*; Carsten Bindslev-Jensen, MD, PhD*†; Per Stahl Skov, MD‡§; and
Lars K Poulsen, PhD§
Background: Fish is reported to be one of the most common causes of food allergic reactions. Species specificity and patterns of cross-reactivity are still to be defined.
Objective: To demonstrate the immunologic reactivity of clinically codfishallergic adults to four species of fish: cod, mackerel, herring, and plaice.
Methods: IgE reactivity was measured in eight clinically codfish-allergic adult patients, confirmed by double-blind, placebo-controlled challenges with fresh raw codfish, and in 30 codfish-tolerant control subjects, by means of skin prick test, histamine release test, specific IgE tests, SDS-PAGE, and immunoblotting.
Results: All eight patients had positive skin prick tests to plaice and herring, seven of eight to mackerel, whereas fish-induced histamine release from basophil leukocytes was positive in five, four, and six of six patients, respectively. Elevated specific IgE to the fish species was found in all eight, and reactions among the control subjects using an in-house method, the Maxisorp RAST, with freshly prepared fish extracts, were fewer (n 8) than found with Phadebas RAST (n 12) and Pharmacia CAP System (n 11). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting revealed individual and common antigenic proteins in freshly prepared extracts. Sera from all eight patients recognized a protein in the area of 11 to 14 kD in all fish species. This is believed to be a protein fraction analogous to Gad cI. Inhibition of the codfish Maxisorp RAST was obtained with mackerel, herring, and plaice. No cross-reactivity to shrimp or milk was shown.
Conclusion: This study suggests that serologic cross-reactivity to different fish species in clinically codfish-allergic adults exists, and that cod, mackerel, herring, and plaice share a common antigenic structure.

J Microbiol Immunol Infect. 2001 Dec;34(4):301-4.
Fish allergy in atopic children.
Peng YH, Shyur SD, Chang CL, Lai CL, Chu SH, Wu WC, Wu CY.
Source
Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan, ROC.
Abstract
The prevalence of fish allergy among 11 atopic children with elevated levels of specific immunoglobulin (Ig) E for cod was determined. None of the children had a history of fish allergy. All of the children had asthma and allergic rhinitis and 5 of them had also atopic dermatitis. The children underwent allergy skin tests (codfish, tuna, catfish, salmon, flounder, and bass), specific IgE tests (salmon, trout, tuna, eel, and mackerel), and food challenge tests. Skin tests in cod-specific IgE-positive children were positive for codfish in 4 children, tuna in 2, catfish in 2, salmon in 6, flounder in one, and bass in 2. Three children had elevated specific IgE for salmon, 5 for trout, 8 for tuna, 4 for eel, and 4 for mackerel. Oral fish challenge with 10 g of fish did not result in positive reaction in any of the children. In conclusion, a positive food challenge test provided the only definitive confirmation of fish allergy, whereas positive allergy skin tests or positive specific IgE tests were less reliable. Skin tests and in vitro specific IgE assays were not correlated with clinical symptoms of fish allergy, and the results of these 2 tests did not correlate with each other in this study.

Sincerely,
Phil Lieberman, M.D.

We have received the response from Dr. Sam Lehrer. Thank you again for your inquiry and we hope this response is helpful to you.

Sincerely,
Phil Lieberman, M.D.

Response from Dr. Sam Lehrer:
I agree with your reply. This is generally the advice given. I think fish cross reactivity should be better investigated but at this point I would be cautious. You might look into the European literature since more work was done in Europe than the US, especially the earlier literature on Cod fish might be useful. I would recommend just what you said.

If the patient finds it difficult and desires to test further, and the patients symptoms are not severe one possibility might be to do a challenge in the physicians office, starting with very low doses, can use the dose that triggered the cat fish reactions, start with much less, and then increase 4 fold. This is only if the doctor has facilities to deal with any kind of reaction and also the patient does not have a history of systemic anaphylaxis. Also he may need IRB approval depending on his associations

All the best,
Sam

AAAAI - American Academy of Allergy Asthma & Immunology