Epidemiology

• Relative Prevalence of Scombroid as a Seafood-Related Food-Borne Illness: in the US and Europe, scombroid accounts for 40% of of seafood-related food-borne illness
• Geographic Distribution: scombroid occurs throughout the world
  • In developed countries, scombroid is more commonly associated with with recreational fish catches than commercially-caught fish (due to routine fish inspection by the FDA and US Customs and Border Protection)
  • Fish caught on long lines, improperly refrigerated at sea, and subsequently imported into the US from off the coast of central America were implicated in scombroid cases in the US in the 1990’s
  • Clusters of outbreaks occur related to ingestion of contaminated fish or cheese
  • In Hawaii: scombroid accounts for 31 annual outbreaks per million people

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Etiology

Scombroid Dark Meat Fish

• Albacore
• Bonito
• Mackerel
• Saury
• Skipjack
• Tuna

Non-Scombroid Fish

• Amber Jack
• Anchovy
• Billfish
• Bluefish
• Escolar Fish
• Herring
• Mahi Mahi (Dolphinfish)
• Marlin
• Salmon
• Sardine
• Spearfish (Tetrapturus)
• Swordfish
• Trout
• Yellowtail

Cheeses

• Swiss Cheese

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Physiology

Ingestion of Histamine-Contaminated Fish

• Improper Storage of Caught Fish (Stored Above 40 Degrees F)
  • Improper refrigeration typically occurs at sea after the fish is caught
  • Although typically associated with fresh-caught fish, scombroid may also occur with canned fish (indicating the importance of refrigerating canned fish after opening)
• Spoilage and Contamination by Enteric Bacteria
  • Clostridium Species (see Clostridium, [[Clostridium]])
  • Escherichia Coli (see Escherichia Coli, [[Escherichia Coli]])
  • Halophilic Vibrio Species (see Vibrio, [[Vibrio]])
  • Klebsiella Species (see Klebsiella, [[Klebsiella]])
  • Proteus Species (see Proteus, [[Proteus]])
  • Salmonella Species (see Salmonella, [[Salmonella]])
  • Shigella Species (see Shigella, [[Shigella]])
• Bacterial Conversion of Histidine to Histamine (and Other Biogenic Amines) by Bacterial Histidine Decarboxylase Enzyme
  • The involved dark fish species (as noted above) have the highest content of free histidine in their muscle (white fish typically have lower histidine levels)
  • Histamine and other bioamines are not destroyed by subsequent refrigeration, freezing, canning, or cooking
  • Other biogenic amines are also formed during spoilage and may potentiate the toxicity of histamine: tyramine, putrescine, and cadaverine
• Clinical Symptoms: symptoms are attributable to histamine toxicity

Ingestion of Histamine-Contaminated Swiss Cheese

• Contamination of Raw Milk Prior to Cheese Processing
• Spoilage and Contamination by Enteric Bacteria: as above
• Bacterial Conversion of Histidine to Histamine (and Other Biogenic Amines) by Bacterial Histidine Decarboxylase Enzyme: as above
• Clinical Symptoms: symptoms are attributable to histamine toxicity

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Diagnosis

• Plasma Histamine Level: elevated (generally 2-4x the upper limit of normal) and normalize by 24 hrs
  • Generally not necessary
• Measurement of Histamine Levels in Suspected Fish/Cheese by Local Health Department: confirmatory
  • Level 50-100 mg histamine per 100 g fish -> potentially toxic
  • Level >100 mg histamine per 100 g fish -> diagnostic of poisoning
  • Private companies offer assays that detect elevated histamine levels in fish within an hour

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Clinical Manifestations

General Comments

• Fish Taste
  • Fish appears fresh but tastes “peppery”, “metallic”, “spicy”, or “bubbly”
  • Fish skin can have a honeycombed appearance
• Onset: minutes-hours after ingestion of contaminated fish of cheese
• Drug Modification of Disease Course
  • Anthistamines: may provide some protection against the clinical symptoms of scombroid
  • Isoniazid (INH) (see Isoniazid, [[Isoniazid]]): inhibits histamine metabolism -> may accentuate the clinical symptoms of scombroid

Cardiovascular Manifestations

• Arrhythmias: rarely occur
• Chest Tightness (see Chest Pain, [[Chest Pain]])
• Hypotension (see Hypotension, [[Hypotension]]): may be significant in patients with underlying cardiac disease
• Palpitations (see Palpitations, [[Palpitations]])
• Sinus Tachycardia (see Sinus Tachycardia, [[Sinus Tachycardia]])

Dermatologic Manifestations

• Erythematous/Urticarial Rash of Face/Upper Torso (see Urticaria, [[Urticaria]]): common
• Flushing of Face/Neck (see Flushing, [[Flushing]]): common
  • Typically rapid in onset
  • Associated with feeling of intense warmth
• Peri-Oral Burning/Pruritus/Edema
• Pruritus (see Pruritus, [[Pruritus]])

Gastrointestinal Manifestations

• Crampy Abdominal Pain (see Abdominal Pain, [[Abdominal Pain]])
• Nausea/Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]])
• Diarrhea (see Diarrhea, [[Diarrhea]]): common

Neurologic Manifestations

• Blurred Vision (see Blurred Vision, [[Blurred Vision]])
• Circumoral Parasthesias (see Parasthesias, [[Parasthesias]])
• Dizziness (see Dizziness, [[Dizziness]])
• Headache (see Headache, [[Headache]]): common
• Tremor (see Tremor, [[Tremor]])

Pulmonary Manifestations

• Bronchospasm/Wheezing (see Obstructive Lung Disease, [[Obstructive Lung Disease]]): may be severe in patients with underlying lung disease
• Dyspnea (see Dyspnea, [[Dyspnea]])
• Acute Respiratory Failure (see Respiratory Failure, [[Respiratory Failure]]): rarely occurs

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Treatment

Natural Course

• Time to Resolution: typically resolves within 12-48 hrs (although the duration of clinical symptoms depends on the amount of contaminated food consumed)

Supportive Care

• Fluid Resuscitation: as required
• Mechanical Ventilation (seeGeneral Ventilator Management, [[General Ventilator Management]]): as required for patients with respiratory failure due to obstructing upper airway edema or bronchospasm

Antihistamines

General Comments

• Indications: H1-antihistamines and H2-blockers are generally indicated in patients with significant clinical symptoms

H1 Antihistamines (see H1-Histamine Receptor Antagonists, [[H1-Histamine Receptor Antagonists]])

• Diphenhydramine (Benadryl) (see Diphenhydramine, [[Diphenhydramine]]): usually effective within 30 min

H2 Antihistamines (see H1-Histamine Receptor Antagonists, [[H2-Histamine Receptor Antagonists]])

• Cimetidine (Tagamet) (see Cimetidine, [[Cimetidine]])
• Ranitidine (Zantac) (see Ranitidine, [[Ranitidine]])
• Famotidine (Pepcid) (see Famotidine, [[Famotidine]])

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References

• Biogenic amines in fish, fish products and shellfish: a review. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2011 Nov;28(11):1547-60. doi: 10.1080/19440049.2011.600728. Epub 2011 Aug 11 [MEDLINE]