AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Histamine fish poisoning, an entirely preventable condition, is among the most common toxicities related to fish ingestion. Histamine fish poisoning, which had been previously termed scombroid fish poisoning, pseudoallergic fish poisoning, histamine overdose, or mahi-mahi flush, accounts for 5% of all food-borne outbreaks reported to the Centers for Disease Control and Prevention (CDC) and 37% of all seafood-related food-borne illnesses. Histamine fish poisoning presents as a possible allergic reaction after consuming certain fish but is actually caused by ingesting toxins within the fish's tissues.¹

The term scombroid, derived from the Greek word scombros (meaning mackerel or tunny), is the basis for the family name Scombridae, which includes mackerel, tuna, marlin, swordfish, albacore, bonito, skipjack, and almost 100 other species. Because the first fish species implicated in this poisoning were from the suborder Scombroidea, the toxicity was originally termed scombroid toxicity or scombroid fish poisoning. The term histamine fish poisoning is now considered more appropriate because most poisonings relate to nonscombroid fish (eg, mahi-mahi [dolphin fish], amberjack, herring, sardine, anchovy, bluefish).

Pathophysiology

The poisoning directly relates to improper preservation and inadequate refrigeration. Histidine decarboxylase (HDC), found in Escherichia coli and in Proteus and Klebsiella species, converts histidine, present in fish tissue, to histamine. These bacteria also live on fish tissue. Without adequate cooling (eg, leaving fish at room temperature for 12 h), these bacteria multiply, increasing the histidine-to-histamine conversion rate and raising histamine levels from 0.1 mg/100 g in a healthy fish to 100 mg/100 g. Toxic levels are estimated at 20-50 mg/100 g.

Elevated histamine levels in the urine of patients and elevated histamine levels in the tissue of the fish confirm that histamine is the causative agent.² Antihistamines traditionally relieve the symptoms and support histamine as the causative agent.

Some theorize a second agent in fish tissues may play a role because attempts to recreate the symptoms by orally feeding people histamine have failed. Histamine is poorly absorbed in the GI tract, and the liver and intestinal mucosa can deactivate histamines. This second causative agent, possibly saurine (histamine hydrochloride), may enhance the activity of histamine, facilitate its absorption, or prevent its inactivation by histamine N-methyltransferase or diamine oxidase. Others postulate that cadaverine or putrescine may be the second agent.

Frequency

United States

The CDC reported approximately 200 outbreaks of scombroid poisoning involving nearly 1400 people from 1973-87.³ Between 1988-1997, 145 reported outbreaks involved 811 persons in 20 states.³ These numbers are increasing with the promotion of fish as a healthy alternative to meat. Most outbreaks have occurred in Hawaii, Florida, California, Washington, New York, and Connecticut, although outbreaks may occur anywhere that has easy access to fresh fish.

International

The implicated fish live in temperate or tropical waters, making populations on adjacent land areas more likely to experience outbreaks.

Mortality/Morbidity

Mortality has become rare. Patients with comorbid illnesses such as coronary artery disease risk acute coronary syndromes caused by the tachycardia and hypotension associated with severe cases of scombroid poisoning.

Race

All races are equally affected.

Sex

Females and males are equally susceptible to histamine fish poisoning.

Age

Histamine fish poisoning equally affects all ages.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Most patients present within 15-60 minutes of toxin ingestion. The uneven distribution of decay may cause different symptoms among people who ate the same fish.

• The patient may note a sharp metallic, bitter, or peppery taste to the fish and describe its appearance as honeycombed.
• Patients taking isoniazid (INH) or monoamine oxidase inhibitors (MAOIs) may have more significant reactions because of histaminase blockade in the GI tract.
• Symptoms of histamine fish poisoning include the following:
• • Skin flushing, typically on upper half of the body. The flushing may be exacerbated by ultraviolet light.
  • Headache (severe and throbbing)
  • Nausea and vomiting
  • Diarrhea
  • Abdominal cramps or epigastric pain
  • Palpitations
  • Pruritus
  • Dizziness
  • Dry mouth
  • Respiratory distress and chest tightness (rare)

Physical

The initial physical presentation easily can be mistaken for an allergic reaction if the history of fish ingestion is not obtained. Physical signs include the following:

• Diffuse erythematous rash, well demarcated and typically on the head, neck, and upper trunk
• Conjunctival injection
• Tachycardia
• Bronchospasm
• Hypotension
• Angioedema
• Urticaria

Causes

Histamine fish poisoning occurs despite cooking, smoking, or canning the fish. Toxin production occurs when inadequate refrigeration allows bacteria-containing histidine decarboxylase to act. This converts histidine in the fish tissues to histamine. Because bacterial decay of the fish is uneven, symptoms may depend on the amount eaten or the specific part of the fish consumed.

• Proper refrigeration and transport prevents histamine fish poisoning. Chill fish immediately; the goal is to achieve an internal temperature of 50°F (10°C) within 6 hours of the fish's death.
• Affected fish do not appear ill. After preparation, the fish may have a honeycombed appearance or taste peppery. Instruct patients to immediately cease eating the fish if they notice these signs.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

• Toxicity, Shellfish
• Scombroid fish poisoning
• Chinese restaurant syndrome
• With alcohol ingestion
• • Chloral hydrate interaction (Mickey Finn)
  • Tyramine and MAOI interaction
  • Disulfiram-type reaction
  • Ethanol flush
• Without alcohol ingestion - Niacin flush

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• No standard laboratory tests help diagnose histamine fish poisoning.
• If proof is required for epidemiological reasons, a portion of undigested fish may be tested for histamine levels.
• An affected patient has high urinary levels of histamine and N-methylhistidine.

Imaging Studies

• A patient with respiratory complaints may require chest radiography to exclude foreign body aspiration or other respiratory pathology.

Other Tests

• A patient with cardiac complaints may need an ECG to exclude other causes of palpitations or chest tightness.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Most cases of histamine fish poisoning are self-limited; duration is less than 6 hours.

• If the ingestion was recent (ie, <1 h) and the patient can adequately protect his or her airway, consider gastric decontamination. In most instances, illness severity can be well controlled with antihistamines. Complications can occur with ipecac or gastric lavage.
• General management includes intravenous (IV) antihistamines (ie, histamine 1 blockers [H1 blockers] and histamine 2 blockers [H2 blockers]) and, occasionally, steroids.
• Treat bronchospasm with oxygen and beta-adrenergic agents.
• Treat hypotension with IV fluids and, rarely, pressors.
• Physicians often assume patients have an acute allergic reaction and administer epinephrine, which rapidly resolves symptoms.

Consultations

• Most cases require no consultation for medical management.
• Consultation may be requested from the local health department to help confirm diagnosis.
• Contact the local poison control center or toxicology service for information on histamine fish poisoning.

Diet

Patients may express concern about future allergic reactions to fish and seafood. Reassure patients that improper fish handling and storage caused their illness, not an allergic reaction.

Activity

The patient may return to normal activity as tolerated.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Most cases of histamine fish poisoning require symptomatic treatment with antihistamines. Some refractory cases may require use of adrenergic agents.

Drug Category: Antihistamines

These agents are used to reverse symptoms of the causative agent (ie, histamine). Initiate treatment with H1 blockers. H2 blockers may be added for synergistic effects.

Drug Name	Hydroxyzine (Vistaril, Atarax)
Description	Used to manage histamine-mediated pruritus; an alternative to diphenhydramine. Antagonizes H1 receptors in periphery. May suppress histamine activity in subcortical region of CNS.
Adult Dose	25-50 mg PO/IM q6-8h
Pediatric Dose	<6 years: 50 mg/d PO/IM divided tid/qid >6 years: 100 mg/d PO/IM divided tid/qid
Contraindications	Documented hypersensitivity
Interactions	Potentiates effects of CNS depressants (eg, narcotics, barbiturates, ethanol)
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	May exacerbate angle-closure glaucoma, hyperthyroidism, peptic ulcer, or urinary tract obstruction; do not administer SC, intraarterial, or IV because thrombosis and digital gangrene can occur; may cause drowsiness

Drug Name	Famotidine (Pepcid)
Description	H2 antagonist that, when combined with an H1 type, may be useful in treating allergic reactions that do not respond to H1 antagonists alone.
Adult Dose	20 mg PO/IV q12h
Pediatric Dose	0.5 mg/kg/d PO/IV divided bid; not to exceed 40 mg/d
Contraindications	Documented hypersensitivity
Interactions	Decreases bioavailability of ketoconazole and itraconazole
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	If changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment

Drug Name	Ranitidine (Zantac)
Description	A competitive, reversible inhibitor of histamine at the H2 receptor. H2 antagonist that, when combined with an H1 type, may be useful in treating allergic reactions that do not respond to H1 antagonists alone.
Adult Dose	150 mg PO q12h 50 mg IV/IM q6-8h
Pediatric Dose	4-5 mg/kg/d PO divided q8-12h; not to exceed 300 mg/d 2-4 mg/kg/d IV divided q6-8h; not to exceed 150 mg/d
Contraindications	Documented hypersensitivity
Interactions	>400 mg/d may decrease metabolism of warfarin, thus increasing effect; decreases bioavailability of ketoconazole and itraconazole
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Caution in renal or liver impairment; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment

Drug Name	Cimetidine (Tagamet)
Description	H2 antagonist that, when combined with an H1 type, may be useful in treating allergic reactions that do not respond to H1 antagonists alone.
Adult Dose	300 mg PO/IV/IM q6-8h
Pediatric Dose	<16 years: 20-40 mg/kg/d PO/IV/IM divided q6h (dosage based on limited experience)
Contraindications	Documented hypersensitivity
Interactions	Reduces metabolism of warfarin, phenytoin, propranolol, nifedipine, diazepam, lidocaine, some tricyclic antidepressants, theophylline, and metronidazole; decreases bioavailability of ketoconazole and itraconazole
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Modify doses in renal or hepatic impairment; rapid IV administration may cause hypotension or arrhythmias; CNS toxicity may occur in elderly persons or debilitated patients

Drug Category: Corticosteroids

These agents elicit anti-inflammatory and immunosuppressive properties and cause profound and varied metabolic effects. They modify the body's immune response to certain stimuli.

Drug Category: Beta-adrenergic agonists

These agents relax the bronchial smooth muscle to relieve bronchospasm.

Drug Category: Vasopressors, adrenergic

Sympathomimetic agents produce direct or indirect stimulation of adrenergic receptors and have various actions depending on the specific receptors involved.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Admit only patients with severe comorbidity or those with refractory cases that require respiratory or pressor support.

Further Outpatient Care

• Patients may require a few doses of an H1 blocker after discharge.
• Some patients complain of a persistent headache, which responds frequently to an H2 blocker.

Transfer

• Only patients with severe bronchospasm or hypotension require transfer.

Deterrence/Prevention

• Proper fish handling and storage, specifically refrigeration, prevents illness.
• Avoid consuming fish that appear spoiled.
• Report any suspected case of histamine fish poisoning to the local health department for investigation.

Complications

• Reported complications include severe bronchospasm, angioedema, hypotension, pulmonary edema, and cardiogenic shock.
• No known fatalities have been linked directly to histamine fish poisoning.

Prognosis

• Prognosis is excellent. Most patients rapidly improve and rarely have sequelae.

Patient Education

• Inform the patient of the cause of illness and how to prevent future episodes by properly refrigerating fish.
• When certain of the histamine fish poisoning diagnosis, reassure patients that they are not allergic to seafood.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Do not assume that all patients who have consumed the same fish will exhibit similar symptoms. Symptoms depend on how much and which portions of the affected tissue were consumed because fish tissue does not homogenously deteriorate.

Special Concerns

• The views expressed in this chapter are those of the author and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States government.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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20. Shoff WH, Shepherd SM. Scombroid, ciguatera, and other seafood intoxications. In: Ford's Clinical Toxicology. 2001:959-61.
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Article Last Updated: Feb 8, 2008