Fish

Fish as a Food Allergen in the Human Body

Fish allergy is a serious IgE-mediated food allergy that occurs when the immune system mistakenly identifies certain fish proteins as harmful and triggers an allergic response. Unlike shellfish allergy, which affects crustaceans and mollusks, fish allergy specifically involves finned fish such as salmon, tuna, cod, and halibut.

How Fish Allergy Develops in the Immune System

Sensitization Phase (First Exposure)

• Fish proteins (allergens) enter the body through ingestion, inhalation (cooking vapors), or skin contact.
• Dendritic cells in the gut or respiratory system present these proteins to naïve T-helper (Th2) cells.
• Th2 cells activate B-cells to produce IgE antibodies specific to fish allergens.
• IgE binds to mast cells and basophils, “sensitizing” them for future exposure.

Allergic Reaction Phase (Subsequent Exposure)

• Upon re-exposure, fish allergens bind to IgE-coated mast cells, triggering mast cell degranulation.
• Histamine and inflammatory mediators (e.g., leukotrienes, prostaglandins) are released.
• This results in a rapid immune response causing allergy symptoms.

Major Allergenic Proteins in Fish

Fish allergy is primarily caused by heat-stable muscle proteins that remain allergenic even after cooking.

Allergen Name	Protein Family	Function	Cross-Reactivity	Heat Stability
Parvalbumin (Gad c 1, Sal s 1, Cyp c 1)	Calcium-binding protein	Muscle contraction	High (across all fish species)	Very heat-stable (remains allergenic after cooking)
Collagen (Fish Gelatin, Gad m 3)	Structural protein	Connective tissue	Moderate (found in fish skin and bones)	Heat-stable
Enolase & Aldolase	Enzymes	Metabolism	Moderate (cross-reacts with frog and reptile meats)	Somewhat heat-stable
Vitellogenin	Egg yolk precursor	Found in female fish	Low (specific to fish roe allergy)	Heat-labile

Parvalbumin is the primary allergen in fish allergy and is highly conserved across most fish species, meaning individuals allergic to one type of fish are likely allergic to others (high cross-reactivity).

Symptoms of Fish Allergy

Mild to Moderate Symptoms

• Oral Allergy Symptoms: Tingling, itching, or swelling of the lips, tongue, and throat.
• Skin Reactions: Hives (urticaria), eczema, or redness.
• Gastrointestinal (GI) Issues: Nausea, vomiting, abdominal pain, diarrhea.
• Respiratory Symptoms: Nasal congestion, sneezing, wheezing, difficulty breathing.

Severe Symptoms (Anaphylaxis)

• Swelling of the throat (angioedema), difficulty breathing.
• Drop in blood pressure, dizziness, fainting (anaphylactic shock).
• Severe wheezing or persistent coughing.
• Loss of consciousness (life-threatening reaction).
• Even small amounts of fish can trigger severe reactions in highly allergic individuals, including airborne exposure from fish cooking vapors.

Cross-Reactivity in Fish Allergy

Fish allergy is unique because parvalbumin is highly conserved across fish species, leading to high cross-reactivity.

Cross-Reactive Group	Examples of Fish Species	Cross-Reactivity Risk
White Fish	Cod, Haddock, Pollock, Hake	Very high (same parvalbumin structure)
Oily Fish	Salmon, Tuna, Mackerel, Sardines	High, but tuna and mackerel may be tolerated by some
Flatfish	Halibut, Flounder, Sole	Moderate to high
Exotic Fish	Swordfish, Eel, Shark	Moderate
Fish Roe (Eggs)	Caviar, Tobiko, Masago	Lower risk, but some may react

Fish and shellfish allergies are separate – someone allergic to fish may not be allergic to shrimp, crab, or lobster.

Fish Allergy Diagnosis

Skin Prick Test (SPT)

• A small amount of fish protein is applied to the skin.
• A positive reaction (redness, swelling) indicates sensitivity.

Serum-Specific IgE Test

• Measures IgE antibodies against fish allergens in the blood.
• High IgE levels indicate a stronger allergic response.

Oral Food Challenge (OFC)

• Gold standard test where small amounts of fish are consumed under medical supervision.
• Used when skin and blood tests are inconclusive.

Component-Resolved Diagnostics (CRD)

• Identifies specific allergenic proteins (e.g., Parvalbumin) in fish allergy.
• Helps determine cross-reactivity risk and reaction severity.

Managing Fish Allergy

Strict Avoidance of All Fish

• Avoid all finned fish, including tuna, salmon, cod, and halibut.
• Be aware of fish-based ingredients:
  • Fish sauce (common in Asian cuisine)
  • Worcestershire sauce (may contain anchovies)
  • Caesar dressing (often contains anchovies)
  • Fish stock and broths
  • Surimi (imitation crab meat)
  • Omega-3 fish oil supplements

Cross-Contact Risks

• Shared frying oil (e.g., fries cooked in oil that also fried fish).
• Grills and utensils used for cooking fish.
• Airborne exposure in seafood restaurants (cooking vapors can trigger reactions).

Emergency Treatment

• Epinephrine (EpiPen®) for severe reactions (anaphylaxis).
• Antihistamines (e.g., Benadryl, Zyrtec) for mild reactions.
• Corticosteroids to reduce prolonged allergic inflammation.

Conclusion

• Fish allergy is an IgE-mediated reaction, with Parvalbumin as the primary allergen.
• Symptoms range from mild oral itching to severe anaphylaxis.
• Fish allergy has high cross-reactivity among different fish species.
• Strict avoidance, label reading, and emergency preparedness (EpiPen®) are crucial for managing fish allergy.