A patient reporting facial flushing, urticaria, abdominal pain, diarrhea, headache, and palpitations within 20-30 minutes of eating fish would lead most emergency physicians to diagnose a classic seafood allergy. Other symptoms might include flushing of the neck and torso, nausea, vomiting, dry mouth, and occasionally wheezing. The symptoms are ameliorated or resolve with basic treatment for an acute allergic reaction, and everyone is convinced that the patient has a fish allergy and should avoid the offending agent in the future.
This is a common scenario, but many such cases are not actually allergic reactions, and are caused by excess histamine in the fish, otherwise known as scombroid poisoning. Scombroid poisoning is the most common cause of ichythyrotoxicosis in the world, but scombroid poisoning, unlike a true allergy caused by an IgE-mediated reaction, is simply due to the deterioration of histidine resulting in excess levels of histamine in poorly stored fish.
Histamine (Scombroid) Fish Poisoning: A Comprehensive Review
Feng C, et al.
Clinic Rev Allerg Immunol
This review discusses the cause, clinical symptoms, treatment, and implications of scombroid poisoning. Scombroid fish include mackerel, bonito, albacore, skipjack, sardines, bluefish, and occasionally salmon, but the majority of scombroid cases are attributed to tuna and mahi mahi. The disease has only been reported in the United States since 1968, but has been reported in homes, restaurants, cafeterias, schools, army barracks, and at medical conferences.
The toxicity is due to a variety of bacteria converting histidine, commonly found in fish, to the toxin, histamine. The process is caused by inadequate storage, particularly inadequate freezing. About 80 percent of fish consumed in the United States is imported from other countries, and one can see how this could occur. Ensuring safety standards, particularly avoiding seafood storage in warm environments, is key to prevention.
The symptoms of histamine poisoning are similar to those of an allergic reaction, and often the process is misdiagnosed as a straightforward IgE-mediated allergy. It has been estimated that scombroid poisoning may cause up to 40 percent of seafood-associated outbreaks that are incorrectly diagnosed as classic allergic reactions.
U.S. fish consumption has markedly increased since the 1980s; average seafood consumption per person is more than 16 pounds a year, and histamine fish poisoning is paralleling the rise in consumption. It often occurs in outbreaks where a number of individuals are affected by the same source. Scombroid poisoning has been reported throughout the world, and the process is annoying, but no deaths have been reported in the United States. Histamine poisoning is usually mild, has a short duration, and is self-limited. Symptoms usually occur within 20-30 minutes of eating histamine-contaminated fish, are ameliorated by antihistamines, or resolve spontaneously within six to eight hours. The symptoms most commonly seen include urticaria, flushing, headache, nausea, vomiting, and lightheadedness. Hypotension, bronchospasm, throat swelling, and respiratory distress may occasionally accompany this process.
This is a relatively new toxicity: Histamine was not proven to be the culprit of scombroid poisoning until 1991. It was previously thought that orally ingested histamine could not be absorbed in sufficient amounts to cause symptoms.
Bacteria that normally reside in fish contain an enzyme, histidine decarboxylase, which converts benign histidine to histamine. A variety of bacteria have histidine decarboxylase activity. The exact type and composition of these bacteria vary according to geographic location, fish feeding habits, water temperature, and the handling process. Once the histamine has been formed, it is resistant to cooking, smoking, freezing, canning, and subsequent refrigeration; none of these can prevent histamine fish poisoning. The fish will smell or appear fresh, but those with scombroid poisoning might report that it tasted metallic, peppery, spicy, or bubbly.
Fortunately, scombroid poisoning is self-limited and has no long-term complications. It has been reported that individuals taking isoniazid or monoamine oxidase inhibitors, which inhibit histamine metabolism, may be more vulnerable to scombroid poisoning and may have prolonged and severe symptoms. The duration of various scombroid poisoning generally depends upon the amount of contaminated fish that was consumed.
The best way to protect against the production of histamine is to keep the product at a temperature of 0°C (32°F) or lower. Histidine decarboxylase is inactivate and bacteria can't grow at these temperatures. When stored at temperatures above 20°C (68°F), it only takes a few hours for enough histamine to be formed to cause symptoms.
Evaluating a patient for possible histamine fish poisoning begins with a history that includes the type of fish, when it was eaten, and if symptoms have occurred in the past, suggesting true allergy. Importantly, it should be noted that it is rare for fish allergy to develop in adults spontaneously. A true allergy is unlikely if someone has tolerated fish in the past. Spoiled fish does not have a specific appearance or odor that would aid in the diagnosis. Even fish with high histamine levels appears fresh. The best historical clue is ascertaining whether others who consumed the same food become similarly ill.
An allergist can confirm a true fish allergy by evaluating for specific immunoglobulin IgE via testing and food challenges. It is unlikely that the offending fish can be found or tested, but histamine levels can be measured. Skin prick testing can help diagnose histamine fish poisoning, though obviously it is not available in the ED.
Antihistamines are the mainstay of treatment for scombroid poisoning and fish allergy. H1 blockers such as diphenhydramine are generally effective. H2 blockers, such as cimetidine and ranitidine, are also beneficial and can be added if symptoms persist or are severe. The symptoms should completely resolve a few hours following antihistamine administration. The use of IM epinephrine can be considered in severe cases, or if the patient is hypotensive or wheezing. Methylprednisolone is often incorporated in the treatment, but the value is controversial.
Comment: Up to two percent of individuals in this country are actually allergic to seafood. Seafood allergy is the most common food allergy in adults and one of the most prevalent food allergies in young children. Symptoms after eating seafood would prompt most to conclude that an allergic reaction has occurred. A true allergy is an immunologic response to the proteins in food that is IgE-mediated. Interestingly, the highest rate of seafood allergy occurs in African Americans, with shellfish being reported as a leading cause. Fish and shellfish allergies can vary from mild to severe, and death can occur.
Many fish, especially those with dark meat, such as tuna, mahi mahi, bluefish, and mackerel, will produce histamine at higher temperatures by bacteria normally present in the fish. Interestingly, an individual who has an allergy to a finned fish would not necessarily have an allergy to shellfish because the allergens are different. The specific treatment for allergy and scombroid poisoning is relatively straightforward, and it's best to refer all patients to an allergist. Those with a true allergy should carry an epinephrine pen because true allergy can be life-threatening. Scombroid poisoning does not appear to be life-threatening.
The proper handling of commercial fish is important, but scombroid poisoning can occur from fish caught by individuals. Anglers often eat tuna, mahi mahi, mackerel, or skipjack. Catching a fish in the morning and storing it in the warm environment of a boat for the day can certainly produce enough histamine to cause a reaction. Toxic histamine levels can accumulate within a few hours via bacterial action. A number of bacteria are responsible, including Escherichia coli, Vibrio, Proteus, Klebsiella, Clostridium, Salmonella, and Shigella. Curiously, scombroid poisoning can also occur by eating Swiss cheese; bacteria contaminate the raw milk prior to processing.
Identifying individuals with similar symptoms who ate the same fish is the best way to confirm scombroid poisoning. Characteristically, patients improve promptly with antihistamine administration. Patients with mild symptoms or those who respond immediately can generally be discharged from the ED after a short period of observation. Some clinicians suggest a day or two of an oral antihistamine, such as loratadine or cetirizine. Those with severe symptoms such as airway edema, bronchospasm, or hypotension should be observed for 12-24 hours.
The treatment of true fish allergy and scombroid poisoning are the same in the ED, and referral to an allergist is recommended because labeling a person with a seafood allergy can have significant consequences to his diet. It would be unfortunate if someone were told in the ED that he has a seafood allergy, eschewing all seafood in the future, when it was benign scombroid poisoning.
Symptoms of Scombroid Toxicity
- Cutaneous flushing of the face and neck, uncomfortable feeling of intense warmth
- Erythematous and urticarial rash, often most prominent on the face and upper torso
- Perioral burning, itching, or edema
- Abdominal cramping, nausea, vomiting, and diarrhea
- Chest tightness with shortness of breath
- Peppery or metallic taste to the fish
- Blurry vision
- Hypotension (distributive shock)
- Bronchospasm and respiratory distress (rare)
- Cardiac arrhythmias (rare)
- Occurs when fish are improperly stored in warm temperatures. Only a few hours are required to produce the toxin.
- Histidine normally found in fish is converted to histamine by histidine decarboxylase, an enzyme found in many bacteria normally residing in fish.
- Toxic levels of histamine can accumulate within two or three hours of storage at temperatures 68°F (20°C) or higher.
- Histamine is not broken down by cooking, freezing, or subsequent refrigeration.
- Fish usually appears fresh, but may have a peppery or metallic taste when eaten.
- Symptoms occur within one hour of eating histamine-contaminated fish.
- Most common symptoms are flushing of the head/neck, feeling of warmth, urticarial rash, and headache.
- Hypotension, bronchospasm, and cardiac arrhythmias occur rarely.
- Symptoms are impossible to differentiate clinically from a true allergy. Identifying the same symptoms in other individuals who consumed the same product can confirm scombroid poisoning.
- A seafood/fish allergy does not develop in adults who have not had symptoms in the past.
- Evaluation by an allergist can uncover true fish allergy.
- Treatment consists of H1- and H2-blocking antihistamines, but occasionally epinephrine may be required.
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