What causes a sudden food intolerance or allergic reaction?

What Causes Sudden Food Intolerance or Allergic Reactions?

Food allergies are caused by an immune-mediated response—most commonly IgE antibodies binding to specific food proteins (epitopes) and triggering mast cell degranulation—while food intolerances result from non-immunologic mechanisms including enzyme deficiencies, pharmacologic effects, or toxic properties of foods. 1

Mechanisms of Food Allergy (Immune-Mediated)

IgE-Mediated Reactions

• The primary mechanism involves a two-step process: First, exposure to a food allergen through the gastrointestinal tract or skin leads to production of antigen-specific IgE antibodies that bind to mast cell surfaces. 1
• Upon re-exposure, the allergen cross-links bound IgE on mast cells, triggering degranulation and release of preformed mediators (histamine causing edema, bronchoconstriction, and vascular permeability within minutes), newly formed mediators (leukotrienes and prostaglandins within minutes), and induced cytokines (IL-3, IL-4, IL-5, TNF-α over hours). 1
• Symptoms typically manifest within minutes to 2 hours after ingestion and include cutaneous (hives, angioedema), respiratory (wheezing, laryngeal edema), gastrointestinal (cramping, vomiting), and cardiovascular (hypotension, tachycardia) manifestations. 1, 2

Non-IgE-Mediated Reactions

• T-cell mediated immunity targets certain food proteins through delayed-type hypersensitivity (Type IV), with symptoms appearing hours to days after exposure. 1
• Major non-IgE conditions include food protein-induced enterocolitis syndrome (FPIES), dietary protein intolerance, protein enteropathy, and eosinophilic esophagitis. 1, 2

Mechanisms of Food Intolerance (Non-Immune-Mediated)

Enzymatic Defects

• Lactase deficiency prevents metabolism of lactose, resulting in bloating, flatulence, and diarrhea—this is metabolic, not allergic. 1
• Impaired complex carbohydrate digestion and inhibition of diamine oxidase (which metabolizes histamine) represent other enzymatic causes. 1

Pharmacologic and Toxic Mechanisms

• Vasoactive amines (such as histamine) present naturally in foods can cause direct pharmacologic effects mimicking allergic reactions. 1, 3
• Food additives including sulfates can trigger intolerance reactions through non-immunologic pathways. 1

Risk Factors for Development

Genetic and Environmental Factors

• Genetic predisposition (atopy) combined with environmental exposure determines susceptibility to food allergy development. 1
• Skin barrier dysfunction and delayed introduction of allergenic solids are the two most important modifiable risk factors for early-life food allergy. 1
• Reduced microbiome diversity, fewer siblings, and lack of dog ownership correlate with increased food allergy risk. 1

Epithelial Barrier Disruption

• Multiple environmental exposures damage epithelial barriers: allergens, bacteria, viruses, detergents, household cleaners, cigarette smoke, diesel exhaust, and microplastics all disrupt skin and mucosal surfaces. 1
• Epithelial cell activation releases cytokines (IL-25, IL-33, thymic stromal lymphopoietin) that drive allergic disease development and exacerbation. 1

Common Food Allergens

The "Big Eight" in the United States

• Milk, egg, peanut, tree nuts, soy, wheat, fish, and crustacean shellfish account for approximately 90% of serious allergic reactions. 2
• Age-related patterns: Milk is most common in young children; peanut, tree nuts, fish, and shellfish typically persist lifelong, while milk, egg, soy, and wheat allergies are often outgrown. 2

Adult-Onset Food Allergy: A Special Consideration

Adult-onset food allergy to previously tolerated foods remains poorly understood, but often involves a period of food abstention (either physician-directed or due to dietary changes) before reactions develop—this represents loss of oral tolerance rather than new sensitization. 1

Critical Clinical Distinction

A positive allergy test (skin prick test or specific IgE) without clinical symptoms does NOT constitute food allergy—this represents sensitization only, and the positive predictive value is low (40-60%). 1, 2 Diagnosis requires reproducible clinical symptoms upon exposure, making clinical history paramount. 1

Common Pitfall to Avoid

• Broad panel allergy testing independent of clinical history is not recommended and leads to unnecessary dietary restrictions based on sensitization rather than true allergy. 1
• Cross-reactivity (such as between tree nuts or between birch pollen and certain fruits) requires clinical confirmation, not just positive testing. 1, 2