Histamine toxicity or scombroid poisoning (scombrotoxism, scombroid ichthyotoxicosis, Mahi-Mahi flush) is the principal chemical agent fish food-borne disease found in the United States. The second most common is ciguatera poisoning. It also may occur with contaminated Swiss cheese ingestion. Most commonly, the symptoms of Scombroid toxicity mimic the pathophysiology of histamine release, including face and neck flushing, diarrhea, urticarial rash, and headache closely. Patients can rarely have severe bronchospasm or cardiac effects, usually in those patients with predisposing medical conditions such as asthma or significant cardiac disease. 
Scombroid poisoning results from eating contaminated fish that have been improperly stored after being caught. The primary toxic agent implicated in scombroid poisoning is histidine (normally found in dark fish meat), which breaks down to histamine. In temperatures warmer than 4 C, the fish undergo bacterial overgrowth and subsequently convert histidine to histamine. In properly stored fish, histamine is normally less than 0.1 mg per 100 g, but histamine levels in contaminated fish are at least 20 to 50 mg per 100 g of fish. The responsible bacteria are most commonly Escherichia coli, Vibrio, Proteus, Klebsiella, Clostridium, Salmonella, and Shigella. 
Affected fish do not have a distinct odor or appearance although after cooking the skin may appear honeycombed, which makes detection prior to eating difficult. Occasionally, patients report a “peppery” taste to the fish while eating.
The poisonings occurring after Swiss cheese ingestion have been due to bacterial contamination of the raw milk prior to processing. The pathophysiology of the conversion of histidine to histamine remains the same as in histamine toxicity of fish.
Classically, histamine toxicity is associated with eating the dark meat fish, especially the Scombridae and Scomberosocidae families (tuna, mackerel, bonito, skip-jack), hence the name scombroid poisoning. In first-world countries, scombroid poisoning occurs mostly in recreationally caught fish rather than commercial harvests due to strict regulations of commercial fishing vessels. Non-scombroid species, such as amberjack, bluefish, mahi-mahi, sardine, yellowtail, and herring are also commonly responsible. Rarely, contaminated Swiss cheese may cause a reaction. 
Unlike most food poisoning, scombroid poisoning is not secondary to ingestion of a virus or bacterium, but the source of symptoms is chemical. Histidine exists in multiple different types of fish, especially dark meat fish, and at air temperatures above 4 C (40 F), it is converted to histamine via the enzyme histidine decarboxylase. Enteric bacteria such as Escherichia coli, Vibrio, Proteus, Klebsiella, Clostridium, Salmonella, and Shigella are responsible for this conversion. Normal cooking temperatures do not destroy histamine. Histamine is then ingested and leads to an allergic-like reaction by degranulation of mast cells. This degranulation mechanism is similar to that seen in allergy mediated histamine response. 
Signs and symptoms typically occur within 2 hours of ingesting a fish with Scombroid poisoning and last for about 12 to 48 hours. The most common symptoms are rash, flushing, headache, and diarrhea. Less common symptoms include abdominal cramps, blurred vision, cold-like sensation, dizziness, nausea, sweating, and tachycardia. Severe reactions cause angioedema, tongue swelling, respiratory distress, cardiac arrest, and death. Patients taking isoniazid or monoamine oxidase inhibitors can have much worse reactions because of the histaminase blockade in the gastrointestinal tract.
The diagnosis is made clinically with symptoms of rapid onset symptoms within one hour of a fish meal. These symptoms include flushing, rash, headache, diarrhea, similar symptoms in those who also ate the same fish, and prompt improvement after antihistamine administration. The diagnosis may be confirmed by testing histamine levels in uneaten portions of fish or checking for elevated histamine levels in the urine. 
Patients with bronchospasm, airway edema, or distributive shock should be treated as anaphylaxis with epinephrine.
Allergic reaction: patients presenting as an allergic reaction to fish with no history of fish allergy. The diagnosis of scombroid is especially suspicious with multiple people who ate the same fish presenting with allergic reaction symptoms. 
Myocardial ischemia: Sweating, nausea, chest tightness, difficulty breathing can simulate the clinical presentation of acute MI in adults.
Staphylococcal enterotoxin-induced food poisoning: Staphylococcus aureus causes very similar symptoms with sudden onset nausea, vomiting, and abdominal pain within 2 hours after eating contaminated food. These patients, however, may develop fever, while scombroid patients do not. Also, patients with scombroid typically have flushing or rash, while Staphylococcus food poisoning does not.
Other marine foodborne poisoning culprits include ciguatera, shellfish, pufferfish, but all have a long latent period before the onset of symptoms and do not present with histamine reactions, specifically flushing and an urticarial rash.
Most complications are rare. Patients typically improve rapidly with treatment and do not require any follow-up. Most can be discharged home. Those with severe bronchospasm, evidence of shock, or arrhythmias may warrant observation for up to 24 hours. Most patients, even with severe symptoms, improve rapidly with the administration of antihistamines within hours of treatment and can be discharged home. 
Patients may consult with a toxicologist, especially if unfamiliar with diagnosis and/or treatment of scombroid poisoning.
Scombroid toxicity is very rare in the US and most healthcare workers are not familiar with its presentation and management. The toxicity primarily results in symptoms of excess histamine. The disorder is ideally managed by an interprofessional team that includes an emergency department physician, toxicologist, specialty nurses, internist, and an intensivist. Treatment is supportive with antihistamines used to reverse the symptoms. Steroids, beta-2-adrenergic agonists, ipratropium bromide, and epinephrine may be given for severe cases.
Patients with bronchospasm, airway edema, or distributive shock should be treated as anaphylaxis with epinephrine. The outcomes for most patients are excellent.
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