The highest morbidity worldwide from fish poisoning results from the ingestion of spoiled scombroid fish, such as tuna and mackerel, and its cause is not clear. Histamine could be responsible, because spoiled scombroid fish contain large quantities of histamine. Whether histamine is the causative toxin, however, has remained in question. To address this issue, we investigated whether histamine homeostasis is altered in poisoned people.

The urinary excretion of histamine and its metabolite, N-methylhistamine, was measured in three persons who had scombroid-fish poisoning (scombrotoxism) after the ingestion of marlin. We measured 9α, 11β-dihydroxy-15–oxo–2,3,18,19-tetranorprost-5-ene-1,20-dioic acid (PGD-M), the principal metabolite of prostaglandin D₂, a mast-cell secretory product, to assess whether mast cells had been activated to release histamine.

The fish contained high levels of histamine (842 to 2503 μmol per 100 g of tissue). Symptoms of scombrotoxism — flushing and headache — began 10 to 30 minutes after the ingestion of fish. In urine samples collected one to four hours after fish ingestion, the levels of histamine and N-methylhistamine were 9 to 20 times and 15 to 20 times the normal mean, respectively. During the subsequent 24 hours, the levels fell to 4 to 15 times and 4 to 11 times the normal values. Levels of both were normal 14 days later. PGD-M excretion was not increased at any time. Two persons treated with diphenhydramine had prompt amelioration of symptoms.

Scombroid-fish poisoning is associated with urinary excretion of histamine in quantities far exceeding those required to produce toxicity. The histamine is most likely derived from the spoiled fish. These results identify histamine as the toxin responsible for scombroid-fish poisoning. (N Engl J Med 1991; 324:716–20.)