When eating poorly preserved fresh fish causes allergic symptoms... which are not allergic symptoms

This is the story of a 14-year-old boy who developed a rash, hot flashes, and shortness of breath two hours after eating a lightly grilled fresh tuna steak purchased at a nearby fish market. He is neither intolerant nor allergic to fish. His father also ate it, but in smaller quantities.

The young patient was taken to the emergency room after treatment with oral antihistamines failed. Despite taking corticosteroids, his condition worsened: loss of consciousness, hives, wheezing, and a drop in blood pressure. An epinephrine injection, an IV drip, a nebulized bronchodilator, and high-flow oxygen were administered.

Faced with this severe anaphylactic shock, which was refractory to treatment, the child was transferred to a pediatric intensive care unit where he was given medications to increase blood pressure, intravenous corticosteroids, and antihistamines. No longer showing any symptoms, the adolescent left the hospital on the third day.

This child suffered from scombrotoxism, also known as scombroidosis, a food poisoning caused by the presence of histamine in certain fish, mainly red-fleshed species belonging to the Scombridae family (tuna, yellowfin tuna, skipjack tuna or bonito, mackerel, mahi-mahi), hence the name given to this poisoning. It is important to note that other fish families, such as Clupeidae (sardines, herring) or Engraulidae (anchovies), can also cause this type of poisoning.

If the fish is not stored immediately after harvest at a temperature of 0°C or lower, Gram-negative bacteria such as Acinetobacter , Citrobacter, Enterobacter, Escherichia coli, Klebsiella, Morganella morganii, Proteus, Pseudomonas, Salmonella and Serratia , present in the gills and intestinal microbiota, convert histidine into histamine using the enzyme histidine decarboxylase when the flesh temperature exceeds approximately 4.4°C.

Histamine is resistant to cooking, smoking, freezing, and canning. Once ingested, it binds to histamine receptors, triggering allergy-like symptoms. Scombroid poisoning is likely underdiagnosed and often mistaken for a fish allergy. Histamine is formed before fish spoilage is even noticeable.

The histamine level in fresh fish is normally less than 1 mg per 100 g of flesh. Poisoning occurs at much higher concentrations, requiring at least 50 mg/100 g to cause scombrotoxin. To ensure a wide margin of safety, European food regulations set a maximum level of between 10 and 20 mg/100 g for fresh produce. In the United States, the Food and Drug Administration (FDA) limits this level to 5 mg per 100 g of fish. In that country, scombrotoxin accounts for approximately 5% of all reported food poisoning cases.

In recent years, it has been suggested that other compounds may play a role in scombroid poisoning, including cadaverine, putrescine, and cis-urocanic acid. The latter is known to stimulate the degranulation of a class of immune cells, mast cells, which results in the release of histamine and thus increases the total histamine concentration in fish tissues. While histamine arises from the decarboxylation of histidine, cadaverine and putrescine are derived from the amino acids lysine and ornithine, respectively. These compounds are formed rapidly due to the postmortem degradation of fish amino acids.

To avoid bacterial proliferation and histamine production, it is essential to handle fish under strict hygienic conditions, paying particular attention to its storage and thawing at low temperatures (no more than 6°C), without ever interrupting the cold chain.

Immediate cooling after capture is crucial. Maintaining low storage temperatures and respecting the cold chain are essential to limit bacterial growth and prevent poisoning.

In summary, scombrotoxism is a chemical-type food poisoning, characterized by symptoms generally appearing between 10 minutes and 2 hours after eating fish naturally containing high concentrations of histidine. It is therefore crucial to maintain the cold chain until consumption to prevent bacterial proliferation.

After ingestion, histamine binds to specific receptors in the body, causing a series of symptoms very similar to those of an allergic reaction. Scombroid poisoning is probably more common than we think, but it is often overlooked.

It is easy to differentiate an allergy from poisoning when several guests present with the same symptoms simultaneously, because it is unlikely that several people will develop an allergy at the same time. On the other hand, when a single patient is affected, it is generally the anamnesis (clinical history) that allows the distinction to be made.

Symptoms typically include flushing of the face, neck, and upper chest, accompanied by hot flashes, sweating, nausea, vomiting, diarrhea, abdominal cramps, headaches, dizziness, palpitations, a burning sensation in the mouth, and a drop in blood pressure. It is important to remember that any fish with a metallic, peppery, or pungent taste should be discarded immediately.

Symptoms usually occur within 10 to 30 minutes of eating fish. The course is most often mild and resolves spontaneously, usually within 24 hours.

Severe cases remain very rare. A case of prolonged, life-threatening vascular collapse was reported in 2021 by an American team. Fish flesh can contain significant amounts of histamine, generating a clinical picture suggestive of anaphylaxis, as in the case described in the introduction to this post.

This syndrome can sometimes present with symptoms similar to those of an acute coronary syndrome, in other words a myocardial infarction. Indeed, in addition to mild symptoms, some patients present with cardiological signs such as chest pain, hypotension and an abnormal electrocardiogram tracing (ST segment elevation), linked to coronary spasm. These situations are generally benign, but may sometimes require appropriate treatment in the event of a significant drop in blood pressure.

The diagnosis of scombrotoxism is based either on measuring histamine concentrations in the patients' blood or on circulating tryptase concentrations. These compounds, involved in immediate hypersensitivity reactions, are always elevated in cases of allergic reaction, whereas tryptase levels are generally normal in cases of scombrotoxism, which - let us repeat - is not an allergy. These measurements can be performed in routine practice, but the samples must be taken shortly after a meal rich in histamine.

Scombroid syndrome is one of the most common causes of food poisoning related to fish consumption. It was first described in 1799 in Great Britain and then mentioned again in the medical literature in the 1950s. Subsequent outbreaks were reported in the United States in 1968, Japan in 1970, and Great Britain in 1976.

But let's return to the clinical case reported by Portuguese doctors. Doctors at the Santo Antonio University Hospital (northern Portugal) suspected scombroid poisoning because their young patient had a severe reaction to an allergen he had previously tolerated and had normal tryptase levels. A rapid investigation led to an accurate diagnosis and appropriate medical treatment.

An accurate diagnosis is essential to locate the source of contamination and implement rapid public health measures.

Following consultation with the Public Health Department, the fish market's hygiene conditions were assessed, and a sample of frozen tuna kept by the family was sent for analysis. The market was found to be compliant with good hygiene practices. However, the tuna contained 1,496 mg of histamine per kg, confirming the diagnosis of scombroid poisoning.

An accurate diagnosis is crucial to identify the source of contamination and take swift action to protect public health. It also helps avoid imposing an overly restrictive and unnecessary diet on the patient. Thus, patients who are not allergic to tuna or other fish will be able to eat them again without any problems, provided they are properly stored.

Three cases of scombrotoxism in Italy are worth recounting. They were reported in 2024 in the journal La Clinica Terapeutica . The first concerned a young woman who, about 35 minutes after her meal, suddenly experienced significant respiratory discomfort, with bronchospasm, tachycardia, headache, diffuse itching, and redness on the face and trunk, accompanied by a marked general malaise. Her father, a medical biologist, quickly interpreted these signs as an allergic reaction and administered corticosteroids, antihistamine treatment, and oxygen. The patient was then taken to the emergency room.

The second case concerns the father, who approximately 30 minutes after accompanying his daughter to the hospital, felt unwell with severe gastric pain, nausea, and diffuse erythema on the trunk and back. A few hours after the relatives were admitted, the son, who had remained asymptomatic in the emergency room waiting room, also felt unwell, with redness on the face and trunk, accompanied by tachycardia and profuse sweating.

In 2000, doctors in Bordeaux reported in the New England Journal of Medicine the case of nine people who developed scombroid poisoning between 10 and 90 minutes after sharing a meal containing cooked tuna. Analysis of the tuna revealed toxic concentrations of histamine in one piece, linked to improper storage (6 kg of ungutted tuna, stored at 8°C and consumed four days after fishing).

Published in the journal Toxicologie Analytique et Clinique in 2023, a study reported the experience of French Poison Control Centers over a decade (from 2012 to 2021 inclusive) regarding this "frequent but often unrecognized poisoning." Cases of scombrotoxism were identified each year. 47% of cases involved individual poisonings and 53% involved collective poisonings. In total, 173 meals involving 543 patients were collected.

Symptoms appeared within 30 minutes of fish consumption in 50% of cases, and within 75 minutes in 89% of cases.

A sign of severity, such as a drop in blood pressure (collapse), was observed in only 3 of the 543 patients. The course of these three patients was marked by rapid improvement after symptomatic treatment, including the administration of adrenaline. All patients recovered quickly without sequelae, which confirms that scombrotoxism, despite a sometimes impressive clinical picture, does not pose any real difficulty in management when correctly diagnosed.

It also appears that there is no real seasonality, with cases of scombrotoxism observed throughout the year. The coastal and southern departments of France are more affected, but the entire territory, including overseas territories, can be the scene of this type of poisoning.

Data on the origin of the fish indicate that "238 patients were poisoned during a meal in a group, 131 were poisoned while eating in a restaurant, 122 had bought their fish in a supermarket, 38 from the fishmonger, for 7 patients the fish came from their own catch, 4 had obtained it from a bakery (tuna sandwich), and 3 had received it by delivery (sushi)."

Contrary to popular belief, the consumption of raw fish (tartare, ceviche, sushi) does not pose a major risk of scombrotoxin toxicity, the authors note. Indeed, in the vast majority of cases observed, the fish was cooked, often grilled, or even simmered for a long time in sauce. These observations also confirm that histamine, which is heat-stable, does not degrade during cooking or freezing.

Drug treatment with antihistamines was initiated for 72 patients (87.8%). Indeed, the treatment of scombroid syndrome is based solely on the rapid administration of antihistamines, either orally, intramuscularly or intravenously, depending on the severity of the symptoms. Only in the presence of more severe clinical manifestations (drop in blood pressure, cardiac complications) are other treatments indicated.

Corticosteroids were administered to 12 patients (14% of cases). Doctors at French poison control centers emphasize that corticosteroids have no place in the treatment of scombrotoxinosis, a poisoning in which histamine comes directly from massive ingestion via contaminated fish, whereas in an allergy, corticosteroids act by preventing the release of histamine produced by the body. "The use of corticosteroids, although ineffective, is not dangerous and often seems to reassure patients and caregivers. The message that corticosteroids are of no benefit in this poisoning seems particularly difficult to convey," acknowledge Xavier Jarrige, Luc de Haro, and their colleagues.

Beyond the question of treatments, it is important to realize that scombroid poisoning represents a major public health concern, especially since, they emphasize, "scombrotoxism remains just as common today as it was at the end of the last century. Work to inform the public and train [health] professionals is therefore more relevant than ever."

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