is localized to the respiratory system while hives and eczema are localized to the skin. In addition to reacting to oral consumption, skin and asthma reactions can be triggered by inhalation or contact if there are skin abrasions or cuts. After the chemical mediators of the acute response subside, late-phase responses can often occur due to the migration of other white blood cells such as neutrophils, lymphocytes, eosinophils, and macrophages to the initial reaction sites. This is usually seen 2–24 hours after the original reaction. Cytokines from mast cells may also play a role in the persistence of long-term effects. Late-phase responses seen in asthma are slightly different from those seen in other allergic responses, although they are still caused by release of mediators from eosinophils. In addition to IgE-mediated responses, fish allergy can manifest as atopic dermatitis, especially in infants and young children. Some will display both, so that a child could react to an oral food challenge with allergic symptoms, followed a day or two later with a flare up of atopic dermatitis and/or gastrointestinal symptoms, including allergic eosinophilic esophagitis. Fish allergenic proteins The protein parvalbumin has been identified as the major allergen causing fish allergy (but not shellfish allergy, which is caused by tropomyosin). Parvalbumin is resistant to heat and enzymatic digestion, so cooking does not diminish its allergenic potency, nor do digestive enzymes. Bony fishes manifest β-parvalbumin whereas cartilaginous fishes such as sharks and rays manifest α-parvalbumin; allergenicity to bony fishes has a low cross-reactivity to cartilaginous fishes. In addition to β-parvalbumin, fish enolase, aldolase and collagen can also trigger allergic reactions. Fish collagen is widely used in the food industry in foods such as gummy candies, jelly beans or marshmallows. It may also be marketed as a dietary supplement ingredient or as an inactive ingredient in pharmaceutical products. Standardized skin tests that incorporate parvalbumin for fish sensitivity will miss collagen allergy. People may be allergic to parvalbumin, collagen, or both. Non-allergic intolerance Scombroid food poisoning, also referred to as scrombroid, is a reaction from consuming fish that mimics an allergic reaction. It is caused by high concentrations of histamine, synthesized by bacteria in spoiled fish. Histamine is the main natural chemical responsible for true allergic reactions, hence the confusion with fish allergy. Scombroid symptoms onset is typically 10–30 minutes after consumption, and may include flushed skin, headache, itchiness, blurred vision, abdominal cramps and diarrhea. Fish