What is the pathophysiological mechanism by which salmon protein induces enterocolitis?

Pathophysiological Mechanism of Salmon Protein-Induced Enterocolitis

Salmon protein causes enterocolitis through a non-IgE-mediated inflammatory response in the gastrointestinal tract, characterized by increased neutrophil activation, cytokine release (particularly TNF-α), and disruption of intestinal mucosal barrier function. 1, 2

Immune Mechanisms

• Cell-mediated response: Unlike typical food allergies, FPIES is primarily non-IgE mediated, involving T-cell activation and inflammatory cytokine release 1
• TNF-α elevation: Research shows increased TNF-α production in peripheral blood mononuclear cells of patients with fish-induced FPIES 3
• Dendritic cell activation: Higher expression of HLA-DR in dendritic cells has been detected in patients with fish FPIES, suggesting antigen presentation plays a key role 3
• Neutrophilia: Acute reactions show increased neutrophil counts (≥1500 neutrophils above baseline), indicating significant inflammatory response 1

Gastrointestinal Effects

• Mucosal inflammation: Salmon protein triggers local inflammation in the intestinal mucosa, leading to:

  • Increased intestinal permeability
  • Fluid shifts into the intestinal lumen
  • Subsequent vomiting and diarrhea occurring 1-4 hours after ingestion 1

• Laboratory findings: During acute reactions, patients may demonstrate:

  • Leukocytosis with left shift
  • Thrombocytosis (reported in 65% of acute FPIES cases)
  • Presence of fecal leukocytes and eosinophils
  • Methemoglobinemia in severe cases 1, 2

Clinical Manifestation Patterns

• Acute presentation: Characterized by repetitive vomiting 1-4 hours after salmon ingestion, often accompanied by:

  • Lethargy
  • Pallor
  • Diarrhea (typically 5-10 hours after ingestion)
  • In severe cases, hypotension and hypothermia 1

• Chronic presentation: Occurs with regular exposure to salmon protein:

  • Progressive vomiting and diarrhea (sometimes with blood)
  • Potential dehydration and metabolic acidosis
  • Poor weight gain or failure to thrive 1

Geographic and Population Factors

• Regional variations: Fish (including salmon) is a common FPIES trigger in Mediterranean countries like Italy and Spain, suggesting potential genetic or dietary factors in susceptibility 2, 4
• Age of onset: Fish-induced FPIES typically presents between 6-12 months of age, with diagnosis often delayed after multiple reactions 5, 3

Diagnostic Considerations

• Negative IgE testing: Skin prick tests and specific IgE to fish are typically negative in salmon FPIES 5, 3
• Oral food challenge: Remains the gold standard for diagnosis, with reactions reproducing the characteristic delayed vomiting and other symptoms 1
• Atopy patch testing: May be positive in some cases (positive in 6 of 16 patients in one study), but has limited diagnostic value 3

Clinical Course and Prognosis

• Persistent allergy: Fish-induced FPIES, including salmon, tends to be more persistent than other forms of FPIES, with many children maintaining reactivity beyond age 6 5, 3
• Limited cross-reactivity: Some patients may tolerate certain fish species while reacting to others, suggesting protein-specific reactions rather than pan-fish sensitivity 5

Understanding this pathophysiology is crucial for proper diagnosis and management of salmon-induced FPIES, as it differs significantly from IgE-mediated fish allergies in both mechanism and presentation.