Auckland Allergy & Eczema Clinic

Histamine Fish Poisoning

Scombroid Poisoning (Histamine Fish Poisoning) and other Seafood-related Illnesses masquerading as Allergies

A Case Report

Was it herbal, scombrotoxic or both?

This is the third of three cases in the last 12 months presenting to me with symptoms consistent with a seafood allergy, where I suspect Scombroid (Histamine) fish Poisoning was the cause.

WT, is a 46 year-old professional who developed flushing, 'hives', nausea, vomiting, light-headedness and diarrhea about 20 minutes after eating a meal at a popular Ponsonby restaurant. The meal included a seared tuna salad for starter, king fish as mains and wine throughout.

20 minutes into his meal he felt 'sick' and went to the toilet, and was later found by friends slumped over the toilet. He was taken by ambulance to Auckland Public Hospital (as the restaurant staff thought he was 'having a heart attack') where he was resuscitated, observed overnight and discharged with a diagnosis of having an anaphylactic reaction to an unidentified food, most likely seafood.

WT came to see me three weeks later, obviously terrified of having another reaction, as "he had eaten all these foods before and loved seafood".

A skin prick test to several of the fresh food items brought in to me from the restaurant plus specific IgE (RAST-type) blood test to all common seafoods including tuna were all negative.

The only medication / tablet WF was taking at the time of the reactions was 'potent herbal multivitamin' (containing tyrosine and numerous minerals) started one week earlier.

Histamine Fish Poisoning (HFP) or Scombroid Poisoning

Incidence of HFP in New Zealand 

The true incidence is unknown in New Zealand, since HFP is not a notifiable disease.

Based on the Public Health Surveillence Annual reports, the occurrence of Scrombroid (histamine) fish poisoning in New Zealand seems quite low for relatively high 'fish eating' nation. Between January 2002 and July 2004 there were 12 outbreaks of HFP reported to the Auckland Regional Public Health Service (An outbreak is defined as: 2 or more linked cases thought to be linked by a common exposure). In these 12 outbreaks a total of 73 cases were identified. In one outbreak alone, 20 cases were reported. The majority of outbreaks implicated smoked kahawai (Arripis trutta). In my opinion these outbreaks grossly underestimate the prevalence of Scrombroid Fish poisoning in New Zealand, as Histamine (Scrombroid) Poisoning is often misdiagnosed as fish allergy. In my practice I would see 2-3 patients each year referred with suspected fish allergy, which clearly had scrombroid fish poisoning. Because these patients usually present weeks after the incident it is not possible to confirm the diagnosis with food analysis for histamine levels and individual cases will not be included in the Public Health surveillance using the strict definition of an outbreak. Also, mild cases often will never seek medical assistance and individual cases are less likely to be suspected than 'outbreaks'.

HFP can be considered a mild-to-moderate form of 'food poisoning' and it occurs worldwide. Apart from of its frequently mild nature, the incidence of HFP is also underestimated because of lack of mandatory reporting, and misdiagnosis (most often as seafood allergy), plus there is a lack of information by medical personnel who see the patients acutely.

Difficulties with underreporting are a worldwide problem. In USA from 1968 to 1980, 103 incidents of intoxication involving 827 people were reported. For the same period in Japan, where the quality of fish is of utmost importance, 42 incidents involving 4,122 people were recorded. The evaluation of a patient reacting to seafood can be difficult if the adverse reaction to particular seafood was caused by a non-allergic reaction.

A major cause of seafood poisoning is the presence of a toxin in certain fish, which produce some symptoms similar to allergic reactions. Histamine fish poisoning (HFP) is a chemical intoxication that occurs after eating bacterially contaminated (spoiled) fish of the dark meat varieties, such as the families of Scombridae or Scomberesocidae, including:

  • Tuna
  • Kahawai
  • Mackerel
  • Bonito
  • Butterfly kingfish

This has lead to the common usage of the term, "scombroid fish poisoning", to describe this illness. However, certain non-scombroid fish have been reported to cause HFP, & in New Zealand these include:

  • Western Australian Salmon
  • Sardines
  • Mahi-mahi (dophin fish)
  • Blue Marlin

Other sources of high histamine (and tyramine)

  • Cheeses
    Scrombroid poisoning can also bee seen in the production of Swiss cheese. Several cases have been reported in New Zealand, with Histamine level up to 187mg/100g. Other cheeses that have been reported in outbreaks include: Gouda, Cheddar, Gruyere, and Cheshire.
  • Soy Products
  • Soy sauces and fermented soybean curd
  • Fermented Meats

Scombrotoxin (Histamine) Formation

Certain bacteria produce the enzyme histidine decarboxylase during growth. This enzyme breaks down free histidine, a naturally occurring chemical that is present in larger quantities in some fish (Scombridae) than in others. This results in the formation of histamine and other amines.

The fish are non-toxic when caught, but develops increase in histamine content (Scombrotoxin) with decomposition as bacterial numbers increase. They may look and smell normal, and cooking does not destroy the histamine. Although the condition is caused by histamine intoxication, its pathogenesis is not fully understood, and other toxins or potentiators like tyramine may be involved.

Scombroid fish poisoning is frequently encountered if dead fish remain in set nets during warm sea temperatures, the fish is improperly refrigerated or when refrigeration is delayed.

Histamine is more commonly the result of high temperature spoilage (>70 ° F [21.1 ° C]), than of long term relatively low temperature spoilage.

Once the enzyme histidine decarboxylase is formed, it can continue to produce histamine in the fish even if the bacteria are not active. The enzyme can be active at refrigeration temperatures. The enzyme is likely to remain stable while the fish is frozen and may be reactivated very rapidly after thawing.

Freezing may inactivate the enzyme-forming bacteria. Cooking can inactivate both the enzyme and bacteria. However, once histamine is formed, it cannot be removed by heat or freezing. 

The symptoms of HFP include:

  • Nausea, vomiting, diarrhoea
  • An oral burning sensation or peppery taste in the mouth
  • Hives, itching, red rash (flushing)
  • Hypotension (light-headedness, dizziness or fainting).

The onset of the symptoms usually occurs within a few minutes after ingestion of the implicated food (incubation period from 5 minutes to an hour) and the duration of symptom ranges from a few hours to 24 h.

Diagnosis of scombroid poisoning

Many physicians are not familiar with scrombroid poisoning.

This illness should be suspected in anyone who develops flushing, hives, sweating, burning peppery taste in the mouth and throat, dizziness, nausea and headache within minutes to 2 hours of eating a scrombroid fish. It is much more likely (compared with fish allergy) in someone who regularly eats fish, without previous allergic reactions.

Confirmation of scrombroid poisoning is a simple histamine analysis of the suspect fish. A routine flurometric procedure can determine milligrams (mg) of histamine per 100 grams of edible fish. Histamine levels in freshly caught fish are less than 1mg/100mg fish, but if the fish is left at room temperature the level can increase up to 100mg histamine/100mg fish within 12 hours. Histamine concentrations above 100mg/100g are typically noted in fish associated with actual illnesses.

Hazardous levels are thought to be (In USA the FDA uses 50mg/kg or more as the poisonous action level for tuna) 200 mg/kg)

The Australia New Zealand Food Standsrds (ANZFS) code allows 100mg/kg histamine as the maximum permitted level.

In New Zealand the ESR labs can do this analysis.

The Public Health Service should be notified of suspected cases and they willtrace the source of the fish and investigate the cause.

Are some people more prone to Histamine food poisoning?

Studies have shown that histamine-intolerant individuals may have a deficiency of the enzyme, diamine oxidase, in the small intestinal mucosa, resulting in decreased breakdown, and increased absorption of histamine in the gastrointestinal tract.

Diamine oxidase levels are known to be about 500-fold elevated in pregnancy.

Almost 100 drugs have been shown to inhibit diamine oxidase, including:

  • Clauvulanic acid found in Augmentin (antibiotics)
  • Doxycyline
  • Isoniazid (antibiotics used to treat tuberculosis)
  • Metoclopropramide (used to treat 'stomach upsets') 
  • Verapamil (used to treat heart conditions) 
  • Promethazine
  • Monoamine oxidase inhibitors (older drugs used to treat depression)
  • Herbal & Nutritional supplements are an area for future research. Do Nutritional supplements with tyrosine (which is converted to tyramine, a very similar amine to histamine) increase the risk of scrombroid poisoning?

Nutrients regulate diamine oxidase release in intestinal mucosa (1). Some studies suggest that Zinc, manganese, Niacin, Vitamin B12 and folic acid may increase histamine levels.

Alcohol is also seen as a histamine liberator, i.e., it can enhance the effect of histamine in sensitive individuals.

Treatment of Scombroid (Histamine) Poisoning

Since symptoms generally only last a few hours and the condition is rarely life threatening, antihistamines are usually the only drugs necessary.

Adrenaline is often given, as the diagnosis of fish anaphylaxis cannot be excluded at the outset.

Prevention of HFP

Studies have shown that toxic histamine levels can be reached within 12 hours or as little as 2 hours if the catch is not placed on ice or refrigerated. The noted species above should receive care in handling, washing, and proper icing, refrigeration or freezing to prevent the bacterial growth and spoilage.

Thoughts on above case

My guess is that the combination of alcohol with a 'potent' herbal / mineral supplement) predisposed the patient to develop scombroid poisoning due to his tuna meal.

Other food-borne diseases associated with seafood

Bacterial Pathogens

  • Salmonella 
  • Clostridium 
  • Listeria 
  • Vibrio cholerae

Parasites sometimes found in raw seafood (Anisakis) 

Anisakis simplex or cod worm is a seafood parasite that can cause 2 major problems in humans:

  • Infection/Infestation (Anisakiasis ) is also known as herring or cod worm disease. It mainly affects the digestive tracts and only affects those who consume raw (sushi) or undercooked parasitized fish. Studies have shown that 5-80% of fish samples are infested by Anisakis (mainly freshwater fish). Deep-freezing or cooking infected fish is necessary to prevent infection. 
  • Allergy to Anisakis is reported to eating or inhaling the Anisakis allergen due to an IgE-mediated allergic reaction (like in true fish allergy or anaphylaxis). In Spain 1 study showed that allergy to Anisakis was more common than fish allergy. Allergy to this parasite should be suspected when allergic-like reactions occur after eating seafood, yet the results of the skin prick tests and RAST (specific IgE blood tests) tests to seafood are negative.

    Deep-freezing at -20 degrees Celsius for more than 48 hours and cooking at temperatures higher than 60 degrees Celsius for 10 minutes is important for protection against infection with live parasites, but may not protect against reactions to their allergens. The sensitised individual may react to cooked, frozen or canned fish. 

Allergic symptoms due to Anisakis include:

  • Hives, Angioedema (swelling of lips, eyelids)
  • Asthma
  • Joint pains (usually associated with hives)
  • Anaphylaxis

Occupational exposure upon inhaling particles of the parasite includes conjunctivitis and asthma.

Viruses that sometimes contaminate raw seafood

  • Hepatitis A virus
  • Rotavirus
  • Norwalk virus group (renamed noroviruses in Aug 2002)

Norwalk virus group (Noroviruses)

In 2003, 73 outbreaks of Norovirus infections involving 1368 cases were reported to the New Zealand Public health Surveillance.

This is commonly known as viral gastroenteritis. It is usually self-limiting, mild, and characterized by nausea, vomiting, diarrhea, and abdominal pain. Headache and low-grade fever may also occur.

The fecal-oral route via contaminated water and foods transmits Norovirus. Shellfish and salad ingredients are the foods most often implicated in Norovirus outbreaks. Ingestion of raw or insufficiently steamed clams or oysters poses a high risk for infection.

Natural toxins that are sometimes found in seafood 

  • Scrombroid
  • Ciguatera poisoning
  • Shellfish toxins- (PSP, DSP, NSP, ASP)
  • Tetrodotoxin (Puffer fish) 

Ciguatera Poisoning

In 2001 two outbreaks of ciguatera poisoning, involving 8 people was reported to the Public health Surveillance in New Zealand. There were outbreaks of ciguatera poisoning in Auckland in 2002 (one outbreak involving 7 cases) and in 2003 (two outbreaks involving 7 cases). In all outbreaks fish imported from the Pacific Islands was implicated.

Reef fish from the tropical and subtropical waters of the West Indies, the Pacific Ocean, and Indian Ocean poses the greatest threat. In the Pacific, the first Tahitian death on the ship Bounty (from Mutiny on the Bounty) was the ship's surgeon after a fish feast. "Old Bacchus died not from drink, as might have been supposed, but eating a poisonous fish"

The most toxic fish causing ciguatera poisoning is the barracuda, and should always be avoided (according to the Centers for Disease Control and Prevention). Other fish, which may contain the toxin, include red snapper, king fish and grouper. This illness is due to the reef fish feeding on toxic algae, which produces a neurotoxin. Worldwide this poisoning causes more human illness than any other seafood toxicity. Annually, an estimated 50,000 cases of ciguatera poisoning occur worldwide, but this poisoning is difficult to track & there id underreporting.

Because the toxin is heat-stable, it is not affected by cooking. Drying, marinating, or smoking either does not affect it.

Symptoms of ciguatera poisoning usually appear within 3 to 5 hours after the toxic fish has been eaten. Symptoms may include:

  • Nausea, vomiting, watery diarrhea
  • Numbness, and tingling of the mouth and extremities
  • In more severe cases, the individual may suffer muscle pains; dizziness and temperature reversal, where hot objects feel cold and cold objects feel hot.

Most people recover within a few days or weeks with supportive treatment, but ongoing disability has been described.

Some victims have a return of symptoms after drinking alcohol.

Treatment of ciguatera poisoning consists mainly of relieving symptoms and treating complications. There is no antidote for ciguatera poisoning.

Toxic shellfish poisoning (PSP, DSP, NSP, ASP)

In 2001, one outbreak of toxic shellfish poisoning involving two people was reported to the Public Health in New Zealand (none in 2002 & 2003).

All shellfish (filter-feeding mollusks) are potentially toxic. The poisoning is caused by a group of toxins elaborated by algae upon which the shellfish feed.

There are four types of clinical types of Shellfish poisoning based on symptoms:

  • Diarrheic Shellfish Poisoning (DSP) – is usually presents with mild gastrointestinal disorder, i.e., nausea, vomiting, diarrhea, and abdominal pain accompanied by fever, chills, and headaches. Usually associated with mussels, oysters, and scallops.
  • Paralytic Shellfish Poisoning (PSP) – presents predominantly with neurological symptoms and include tingling, burning, numbness, drowsiness, incoherent speech, and respiratory paralysis. Usually associated with mussels, clams, cockles, and scallops.
  • Neurotoxic Shellfish Poisoning (NSP) – presents with both gastrointestinal and neurological symptoms. Not usually seen in New Zealand, as this is usually associated with shellfish harvested along the Florida coast.
  • Amnesic Shellfish Poisoning (ASP) – is characterized by gastrointestinal disorders (vomiting, diarrhea, abdominal pain) and neurological problems (confusion, memory loss, disorientation, seizure, coma). Usually associated with mussels. 

Relative Frequency of Toxic Shellfish poisoning

Good statistical data are largely unavailable. Cases are frequently misdiagnosed and infrequently reported. PSP is the most serious from a public health point of view. The PSP toxin can be very potent resulting in high mortality rates.

Tetrodotoxin Toxicity

Poisoning with the neurotoxin tetrodotoxin occurs after ingestion of various species of puffer fish. The flesh of the puffer fish is considered a delicacy in Japan. Government certified chefs, who prepare the flesh free of the toxic liver, gonads, & skin, usually prevent this toxicity. Despite this many cases of tetrodotoxin poisoning is reported each year.


I thank Dr Greg Simmons, Auckland Regional Public health Services for helpful discussions and advice concerning statistics and other Public Health issues for New Zealand