Histamine (Scombroid Toxicity, Mahi-Mahi Flush) Toxicity


Article Author:
Jeremy Traylor
Ahmad Malik


Article Editor:
Scott Goldstein


Editors In Chief:
Kranthi Sitammagari
Mayank Singhal


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Frank Smeeks
Kristina Soman-Faulkner
Trevor Nezwek
Radia Jamil
Patrick Le
Sobhan Daneshfar
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
6/4/2019 8:19:35 PM

Introduction

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. [1][2][3][4][5][6][7][8]

Etiology

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[5][2][1][3]

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.

Epidemiology

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 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. [5][1][2]

Pathophysiology

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. [5][1][7][9] 

Toxicokinetics

Without treatment, scombroid poisoning resolves within 12 to 48 hours with no long-term sequelae. With treatment, even severe cases improve rapidly within one to three hours from initiation of treatment. [5][1][2][3]

Once H1 or H2 blockers block further histamine release, symptoms abate quickly.

History and Physical

Contaminated fish may both smell and appear fresh, but many report the fish tasting “peppery.” The skin may appear honeycombed when cooked. [5][10][7][9] 

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.

Evaluation

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. [5][1][2][3][4] 

Treatment / Management

Treatment is supportive. Antihistamines are the mainstay of treatment. Steroids, beta-2-adrenergic agonists, ipratropium bromide, and adrenalin may be given for severe cases. Activated charcoal may be given if the patient presents within one hour of fish consumption. [5][1][2][3][4] 

Patients with bronchospasm, airway edema, or distributive shock should be treated as anaphylaxis with epinephrine.

Differential Diagnosis

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. [2][3][4][8][9][5]

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.

Prognosis

Prognosis is very good as most patients have rapid improvement with the administration of H1 and/or H2 anti-histamines (diphenhydramine and/or cimetidine or ranitidine). [4][8][9] 

Even patients with severe features often improve within hours of treatment.

Complications

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. [5][3][4][8][9] 

Consultations

Patients may consult with a toxicologist, especially if unfamiliar with diagnosis and/or treatment of scombroid poisoning.

Deterrence and Patient Education

Patients should be educated on proper storage of fish prior to ingestion, especially since most cases are in recreational fisherman. Patients should also be educated that this does not mean the patient has an allergic response to fish. [5][1][2][3][4] 

Pearls and Other Issues

Patients should be educated that this is a reaction to improper fish storage and not an allergic response to the actual fish. [5][1][2][4][8] 

Enhancing Healthcare Team Outcomes

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 a multidisciplinary 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 adrenalin may be given for severe cases. Activated charcoal may be given if the patient presents within one hour of fish consumption.

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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Histamine (Scombroid Toxicity, Mahi-Mahi Flush) Toxicity - Questions

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A 35-year-old female patient presents to the emergency department shortly after eating raw tuna at a local fine dining establishment. She complains of abdominal cramps, diarrhea, and nausea. Examination reveals bilateral expiratory wheezing, facial flushing, and diffuse urticaria. She has no previous history of fish allergy. Vital signs show temperature 98.6 F, heart rate 105bpm, blood pressure 130/80mmHg, respiratory rate 16/min, oxygen satureation 98% on room air. What is the most appropriate initial step in the management of this patient?



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Which of the following is NOT a true statement concerning histamine (Scombroid) toxicity?



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A patient has just consumed Skipjack fish. The patient complains of a burning-peppery taste in their mouth. Which of the following is least likely?



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Which bacteria is least likely to be involved in histamine toxicity or Scombroid poisoning?



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What bacteria is most often thought to cause the reaction leading to histamine toxicity or scombroid poisoning?



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Which is NOT a treatment for histamine toxicity?



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Which of the following causative agents can manifest in the first minutes of ingestion?



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Histamine (Scombroid Toxicity, Mahi-Mahi Flush) Toxicity - References

References

A case of histamine fish poisoning in a young atopic woman., Wilson BJ,Musto RJ,Ghali WA,, Journal of general internal medicine, 2012 Jul     [PubMed]
A large outbreak of scombroid fish poisoning associated with eating yellowfin tuna (Thunnus albacares) at a military mass catering in Dakar, Senegal., Demoncheaux JP,Michel R,Mazenot C,Duflos G,Iacini C,de Laval F,Saware EM,Renard JC,, Epidemiology and infection, 2012 Jun     [PubMed]
Flushing associated with scombroid fish poisoning., Ferran M,Yébenes M,, Dermatology online journal, 2006 Oct 31     [PubMed]
Something fishy: six patients with an unusual cause of food poisoning!, Hall M,, Emergency medicine (Fremantle, W.A.), 2003 Jun     [PubMed]
Rapid detection of chemical hazards (toxins, dioxins, and PCBs) in seafood., Arvanitoyannis IS,Kotsanopoulos KV,Papadopoulou A,, Critical reviews in food science and nutrition, 2014     [PubMed]
Identification and management of toxicological hazards of street foods in developing countries., Proietti I,Frazzoli C,Mantovani A,, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2014 Jan     [PubMed]
Harmelin Y,Hubiche T,Pharaon M,Del Giudice P, [Three cases of scombroid poisoning]. Annales de dermatologie et de venereologie. 2018 Jan;     [PubMed]
Ridolo E,Martignago I,Senna G,Ricci G, Scombroid syndrome: it seems to be fish allergy but... it isn't. Current opinion in allergy and clinical immunology. 2016 Oct;     [PubMed]
Guergué-Díaz de Cerio O,Barrutia-Borque A,Gardeazabal-García J, Scombroid Poisoning: A Practical Approach. Actas dermo-sifiliograficas. 2016 Sep;     [PubMed]
Colombo FM,Cattaneo P,Confalonieri E,Bernardi C, Histamine food poisonings: A systematic review and meta-analysis. Critical reviews in food science and nutrition. 2018 May 3;     [PubMed]

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