Shellfish Allergy

Etiology

Reactions or symptoms due to shellfish consumption may be attributable to various factors. Some reactions are not a true allergy due to infectious agents such as parasites, bacteria, viruses, and parasites.[1] Bacteria implicated with shellfish include Vibrio, Listeria, and Salmonella. Toxin-mediated reactions may also occur and trigger symptoms such as ciguatera or saxitoxin. True allergic reactions may occur to substances in the shellfish (such as tropomyosins), or from a component ingested with the shellfish such as spices or chemical additives.[5][6]

Epidemiology

Fish and shellfish combined are suspected to be responsible for a significant portion of allergic reactions. The actual incidence of shellfish allergies is difficult to identify due to the numerous possible etiologies and under-reporting. Even in cases where a true allergic reaction is identified, it is difficult to determine if there could have been a chemical agent or another additive that could have been the triggering agent. Overall, food allergens are responsible for approximately 30,000 anaphylactic events. Foods as a whole are responsible for around one-third of anaphylaxis cases.[7][8]

Pathophysiology

There are multiple allergens responsible for crustacean allergies. Domoic acid is a strong neurotoxin produced by many diatoms of the genus Pseudo-nitzschia. It acts as a glutamate agonist. The consumption of contaminated shellfish can lead to human exposure.[9] Tropomyosins are one of the better-characterized agents. Tropomyosins can be heat-stable and act through an immunoglobulin E (IgE)-dependent mechanism with antibody binding. Other agents responsible include a substance thought to be similar to arginine kinase, a myosin light chain, and a protein that binds to sarcoplasmic calcium. The agents responsible for mollusk allergies are not well identified.

Toxicokinetics

Although shellfish toxicity is secondary to a nonallergic pathway, it is crucial to consider it when challenging to differentiate cases. As mentioned above, there are multiple potential toxins to be aware of in shellfish toxicity. Saxitoxins are responsible for causing paralytic shellfish poisoning and are secondary to dinoflagellates.[10] The toxin is a voltage-gated sodium channel antagonist, which can result in neurologic symptoms, including paralysis and death from respiratory suppression. In a small case series, the effects began to resolve after 4 hours, with the patient returning to normal after 12 hours.

Neurotoxic shellfish poisoning can also occur and may resemble paralytic shellfish poisoning but is much milder.[11] Symptom onset is within 3 hours and includes gastrointestinal and neurologic symptoms. Symptoms include reversal of hot and cold temperature sensations, paresthesias, aches, nausea, vomiting, and diarrhea. It is also believed to be secondary to a dinoflagellate, specifically due to brevetoxins.[12]

Another disease secondary to shellfish is amnesic shellfish poisoning due to domoic acid. These patients demonstrate gastrointestinal symptoms within 24 hours of ingestion and may develop neurologic symptoms such as confusion, disorientation, or memory loss within 48 hours.[13]

Azaspiracid shellfish poisoning is due to marine toxins that can accumulate in shellfish and trigger severe gastrointestinal symptoms. While the toxin may be secondary to dinoflagellates, its origin is unknown. Symptoms persist for 2 to 3 days, and the substance can induce widespread organ damage.[14]

The mildest toxin-associated illness associated with shellfish ingestion is diarrhetic shellfish poisoning, also associated with biotoxins from dinoflagellates. Symptoms are primarily gastrointestinal but may include fevers, chills, or headaches. Timing is generally between 30 minutes and 6 hours after ingestion.

History and Physical

Asking the patient about recent ingestion or their handling of crustaceans or mollusks can help narrow etiologic agents. Most allergic reactions begin within minutes to a few hours after ingesting the food. The severity of symptoms can vary widely from one individual to another. Mild allergies manifest with pruritus and urticaria, while severe cases can have true anaphylaxis with respiratory compromises such as angioedema or wheezing and hypotension. Other signs and symptoms associated with shellfish allergies are atopic dermatitis (eczema), coughing or sneezing, coryza, circumoral paresthesias, nausea, diarrhea, vomiting, dizziness, and fainting.

Evaluation

The evaluation and diagnosis of shellfish allergy in an acute setting are on clinical grounds, as no rapid tests exist to diagnose this entity accurately. Assessing vital signs, focusing on respiratory status and blood pressure, is crucial in distinguishing anaphylaxis from a more benign course. A thorough examination of the oropharynx and auscultation of lung sounds to detect edema or wheezing is essential. Many patients have gastrointestinal symptoms, so a comprehensive abdomen exam is also advised. Close examination of the skin for exanthems or edema should also occur.

Mass spectrometry, liquid chromatography, and enzyme-linked immunosorbent assay (ELISA) methods have been devised for domoic acid.[15] A mouse bioassay, ELISA, and high-performance liquid chromatography can assess Saxitoxin. Lastly, brevetoxin can be checked by an antibody radioimmunoassay (RIA), mouse bioassay, and ELISA.

Treatment / Management

There is no specific treatment for shellfish allergies, but preventing contaminated fish from entering the food supply can be very useful.[16] Intravenous fluids are often given to patients who have been vomiting. Standard allergic reaction therapy includes antihistamines (H1 and H2) and steroids. In anaphylaxis, intramuscular (IM) or intravascular (IV) epinephrine should be given immediately, followed by antihistamines, steroids, and IV fluids. In rare cases, refractory to standard treatment intubation may be necessary to protect the airway. The duration of symptoms and response to treatment is highly variable, and no one agreed-upon observation period exists. In general, benign presentations that respond to standard treatment and improve while in the emergency department can be safely discharged home with oral antihistamines and steroids with clear instructions to return for worsening symptoms. True cases of anaphylaxis require admission for further monitoring and close observation.[17][18][19](B3)

Patients should receive instructions to avoid the offending agent or food after treatment. For example, patients with an allergic reaction triggered by crabs should avoid other crustaceans. Despite avoidance, consideration of a prescription for an epinephrine auto-injector may be wise due to the potential for anaphylactic reactions and cross-reactivity.

Differential Diagnosis

The following are some important differential diagnoses that should be considered while making the diagnosis of shellfish allergy:

• Acute urticaria
• Bacterial gastroenteritis
• Bulimia nervosa
• Celiac disease
• Chronic gastritis
• Constipation
• Diverticulitis
• Dumping syndrome
• Esophageal spasm
• Esophageal stricture

Prognosis

In 2017, the National Poison Data System (NPDS) of the Annual Report of the American Association of Poison Control Centers observed patients with a single exposure to paralytic shellfish poisoning. They reported 3 major outcomes, 20 moderate outcomes, 17 minor outcomes, and no deaths among 109 patients.[20] Although anyone eating shellfish harboring HAB toxins could become ill, patients with some chronic illnesses, such as liver disease, may potentially have a more severe form of toxicity.

Mortality rates from paralytic shellfish poisoning, the most severe of the shellfish poisoning syndromes, range between 1% and 12%. In severe cases, muscle paralysis along with respiratory failure can cause death in 2 to 25 hours. However, the risk of death is decreased if healthcare providers have prompt access to advanced life support.  

Complications

The following 5 distinct shellfish-poisoning syndromes can result from the toxicity:

1. Paralytic shellfish poisoning: Symptoms usually commence within 2 hours of exposure but can begin between 15 minutes and 10 hours after eating contaminated shellfish.[10] At the onset, paresthesias of the perioral area, lips, tongue, and gums are noted. After onset, there is rapid progression to the distal extremities. Other symptoms may include headache, paralysis, ataxia, muscle weakness, and cranial nerve dysfunction.
2. Neurologic shellfish poisoning: The illness associated with neurologic shellfish poisoning is less severe than that with paralytic shellfish poisoning. Patients usually present with gastroenteritis, burning sensation in the rectum, and paresthesias of the face, limbs, and trunk. There may also be myalgias, ataxia, vertigo, and inability to distinguish hot and cold sensations.[11][12]
3. Diarrheal shellfish poisoning: It is associated with stomach and intestinal symptoms that begin between 30 minutes and a few hours after exposure and include severe diarrhea, abdominal cramps, nausea, vomiting, and chills.
4. Amnesic shellfish poisoning: Mostly, diarrhea, vomiting, and abdominal pain appear within 24 hours of consuming toxic shellfish. Headaches, loss of memory, and cognitive decline follow these symptoms.[13]
5. Azaspiracid shellfish poisoning: Consuming contaminated shellfish may result in nausea, vomiting, diarrhea, and stomach cramps.[14]