Histamine intolerance vs. scombroid fish poisoning
Histamine intolerance
Scombroid fish poisoning
  • Clinical symptoms due to an imbalance between histamine exposure in foods and the histamine degrading capacity of the patient
  • Symptoms usually consistent with physiologic effects of histamine and occur minutes-hours after ingestion of foods/beverages containing high levels of histamine
  • Healthy (non-histamine intolerant) individuals tolerate these same foods without symptoms
  • Etiology unclear, but a genetic deficiency or drug/alcohol-induced inhibition of histamine degrading enzymes may play a role
  • Reported to play a role in some adult patients with AD or chronic urticaria (improvement with histamine-free diet)
  • Symptoms (similar to physiologic effects of histamine) minutes-hours after ingestion of fish containing high levels of "scombrotoxin"
    • Scombrotoxin - a combination of histamine, other biogenic amines, and potentially other unknown mediators that form as a result of bacterial enzymatic decomposition of fish protein due to inadequate cooling
  • Affects any person that ingests an adequate amount of the the affected fish (e.g. cafeteria outbreaks)
  • Fish species often implicated in scombroid fish poisoning:
    • Scombridae fish family: various types of tuna, wahoo, bonito, mackerel
    • Other families: Mahi-mahi, anchovies, herring, marlin, salmon, yellow-tail, swordfish
  • A dose of histamine that would normally be tolerated as orally administered pure histamine may cause symptoms when the equivalent dose is ingested within affected fish, suggesting the importance of mediators other than histamine in scombroid fish poisoning
Anaphylaxis vs. scombroid fish poisoning
  • Many people dining at the same table can be affected by scombroid (anyone ingesting significant amounts of the fish) vs only the individuals with fish allergy
  • Cutaneous symptoms of scombroid are usually somewhat different, consisting of a prolonged flush with only modest or no urticaria
  • In scombroid, plasma and 24-hour urinary histamine metabolite levels will be elevated, but the serum tryptase level remains normal

  • Except in the case of scombroid fish poisoning, most individuals tolerate massive amounts of histamine orally (e.g. 500 mg, either in foods or as pure histamine) due to rapid degradation by intestinal diamine oxidase
  • Histamine not inactivated by cooking or freezing
  • Ingested histidine may be converted to histamine by human enteric bacteria

Histamine Effects

Normal range 0.3-1 ng/mL

Histamine Metabolism

Red box = assay available

Histamine in Foods

  • Hazardous level: >50 mg/Kg or >2 mg/L





Differential diagnosis



  • it may be possible to determine scombroid fish poisoning by testing (fresh prick to prick) with the actual fish meat that caused a reaction
  • Histamine and histamine metabolite assays - usually elevated in both anaphylaxis and scombroid reaction, ± histamine intolerance
  • Tryptase - usually elevated in anaphylaxis but not histamine intolerance/scombroid reactions
  • DAO (diamine oxidase) level/activity assay - usefulness questionable because many symptomatic patients have normal levels

Sciotec (Austria) DAO Rea, DAO_HIT

Elimination diet and challenge


  • Scombroid fish poisoning: H1, H2 antihistamines PRN, avoid ingesting raw fish kept at >40 degrees F for hours-days
  • Histamine intolerance:
    • Histamine-free diet
    • H1, H2 antihistamines PRN acute symptoms ± QD for possible prophylaxis
    • DAO supplements - effectiveness unproven
    • Vitamin B6 and vitamin C - may increase DAO activity
    • Caution with therapies associated with mast cell degranulation: opiates, contrast media, possibly immunotherapy, etc.
      • Unknown whether these patients have an increased risk of severe anaphylactic/anaphylactoid reactions, but avoidance or pre-medication with antihistamines may be considered