Food Allergy & Intolerance – Ctomprehensive Bullet-Point Notes

General Definitions and Conceptual Framework

  • Adverse food reactions divide into:
    • Allergy / hypersensitivity: immune-mediated (generally against a food protein or a small molecule – hapten – once it is bound to a larger carrier protein).
    • Intolerance: non-immune; result of the way the organism processes the food/component (e.g., enzymatic deficits, pharmacologic effects, mal-absorption).
  • Determinants that label a food as “friend” or “foe” for each individual:
    • Genetic background (HLA profile, other polymorphisms).
    • Integrity of the intestinal barrier (tight-junction competence).
    • Composition of the gut microbiota.
    • Environmental / physiological stressors.
    • Psychological factors.

Immunologic Basis of Food Allergy

  • Exposure to an allergen → Antigen-presenting cells (APC) (dendritic cell, macrophage) process & present peptides on MHC-II.
    • Costimulation via B7–CD28 required to activate a naïve CD4⁺ T-cell.
  • Activated T-helper cells (Th2-skewed) release cytokines (IL-4, IL-5, IL-13, IFN-γ, etc.) that:
    • Promote B-cell isotype switch from IgM to IgE (via CD40–CD40L interaction).
    • Drive clonal expansion and differentiation into plasma cells → massive IgE production.
  • Sensitisation phase: Allergen-specific IgE binds to high-affinity FcεRI receptors on mast cells & basophils.
  • Re-exposure (effector phase): Cross-linking of surface-bound IgE→ degranulation → release of:
    • Primary mediators:
    • Histamine – vasodilatation & ↑ vascular permeability.
    • Heparin – anticoagulant, reinforces inflammation.
    • Chemotactic factors – recruit eosinophils & neutrophils.
    • Secondary mediators (newly synthesised):
    • Leucotrienes – potent, sustained bronchoconstriction & vascular leak.
    • Prostaglandin D₂ – smooth-muscle contraction, inhibits platelet aggregation.
    • PAF (platelet-activating factor) – powerful chemo-attractant, increases permeability.

Classification of Allergic Reactions (time-course & mechanism)

  • IgE-mediated (immediate, “Type I”): onset minutes–1 h1\text{ h}, may trigger systemic anaphylaxis, acute urticaria, angio-edema, oral allergy syndrome, asthma/rhinitis.
  • Mixed (IgE + cellular) reactions: onset >2 h2\text{ h}, chronic or recurrent; e.g., eosinophilic oesophagitis/gastroenteritis.
  • Cell-mediated (non-IgE; delayed): T-cell driven; e.g., contact dermatitis, dermatitis herpetiformis, celiac disease.

Anaphylaxis (life-threatening culmination)

  • Clinical triad:
    • Cutaneous: generalised urticaria, angio-oedema.
    • Respiratory: bronchospasm, throat/tongue swelling → airway obstruction.
    • Cardiovascular: hypotension, loss of consciousness.
  • Immediate IM epinephrine is cornerstone therapy.

Main Food Allergens (“Big-8” + official list of 14 EU allergens)

  • Big-8: milk, egg, fish, shellfish, wheat (gluten cereals), soy, peanuts, tree nuts.
  • EU 14 list adds: celery, mustard, sesame, lupin, molluscs, sulphur dioxide/sulphites (>10 mg⋅kg−110\,\text{mg·kg}^{-1}).

Specific Allergy: Cow’s Milk Protein Allergy (CMPA)

  • Trigger proteins: caseins, β-lactoglobulin, α-lactalbumin.
  • Pathway identical to classic IgE mechanism described above; may also involve non-IgE mechanisms (proctocolitis, enteropathy).
  • Symptoms: diarrhoea, eczema, failure to thrive, wheeze, irritability.

Pathophysiology of Food Intolerances

  • Core definition: digestive/absorptive defect without immune activation.
  • Most common forms:
    • Lactose intolerance – lactase (β-galactosidase) deficiency → undigested lactose fermented in colon → hydrogen, CO₂, organic acids → bloating, cramps, diarrhoea.
    • Sucrose–isomaltase & maltase deficiency – rare, causes osmotic diarrhoea in infants.
    • Galactosaemia – inherited enzyme block (galactose-1-phosphate uridyl-transferase), toxic metabolite accumulation.
    • Fructose malabsorption – GLUT-5 transporter capacity exceeded or absent.
  • Other non-enzymatic causes:
    • Irritable bowel syndrome (IBS).
    • Sensitivity to food additives (e.g., sulphites inducing asthma).
    • Psychogenic / stress-related responses.

Celiac Disease (Gluten-Sensitive Enteropathy)

Gluten: structure & source

  • Composite protein in wheat, barley, rye (possible in oats – still debated).
  • Made of gliadins + glutenins (gliadins = key toxic fraction).
  • Provides dough elasticity; constitutes ≈80%\approx80\% of wheat protein.

Multi-step Pathogenesis

  1. Dietary exposure – early introduction, excessive intake, or absence of breastfeeding may favour disease.
  2. Intestinal barrier defect – tight-junctions widened (↑ permeability) → peptides slip through epithelium.
  3. Genetic susceptibility – HLA-DQ2 / HLA-DQ8 haplotypes mandatory but not sufficient.
  4. Adaptive response – lamina propria CD4⁺ T-cells recognise deamidated gliadin → cytokines → IgA/IgG anti-gliadin, anti-transglutaminase (tTG), anti-endomysium antibodies.
  5. Villous atrophy – antibodies + inflammation destroy enterocyte micro-villi.

Clinical Consequences

  • Malabsorption signs: chronic diarrhoea, steatorrhoea, abdominal distension, weight loss, growth retardation, anaemia, osteoporosis, fatigue, irritability.
  • Symptom frequency (infographic, %\% of patients):
    • Diarrhoea 167167 (absolute number reported).
    • Abdominal distension 48%48\%.
    • Growth failure 45%45\%.
    • Poor appetite/fatigue 37%37\%.
    • Vomiting 36%36\%.
    • Irritability 25%25\%.
    • Steatorrhoeic stools 22%22\%.
    • Secondary lactose intolerance 21%21\%.

Diagnosis

  • Serology: IgA anti-tTG, anti-endomysium, anti-gliadin.
  • Confirmatory small-bowel biopsy (Marsh classification) if needed.

Treatment

  • Lifelong strict gluten-free diet – exclude wheat, barley, rye, (oats if sensitive).
  • Nutritional rehabilitation, monitor micronutrients.

Comparative Perspective: Allergy vs Intolerance

  • Immune system involvement: present vs absent.
  • Typical mediators: IgE / T-cells / cytokines vs enzymes, transporters, additives.
  • Onset: seconds–hours vs hours–days (often dose-dependent).
  • Severity: can lead to anaphylaxis / systemic shock vs rarely life-threatening (except inborn errors, e.g., galactosaemia).

Cellular Cast & Molecular Players (Summary)

  • T-lymphocyte subtypes:
    • Cytotoxic (CD8⁺) – kill infected/foreign cells.
    • Helper (CD4⁺) – orchestrate immune response.
    • Regulatory/suppressor – down-modulate response.
    • Memory – fast secondary response.
  • B-lymphocytes – produce immunoglobulins (IgM, IgG, IgE, IgA, IgD).
  • Granulocytes – mast cells, basophils, eosinophils: execute immediate hypersensitivity via mediator release.
  • Macrophages / dendritic cells – APCs.

Ethical & Practical Implications

  • Accurate labelling of the 14 mandatory EU allergens; cross-contamination vigilance in food industry.
  • Dietetic counselling for elimination diets to prevent nutritional deficiencies (e.g., calcium in CMPA, fibre/iron in gluten-free regimes).
  • Education on epinephrine autoinjector use for anaphylaxis preparedness.
  • Psychosocial impact: anxiety, quality-of-life reduction, need for school/workplace accommodation.

Multimedia & Additional Resources Mentioned

  • YouTube videos on allergies/intolerances:
    • https://www.youtube.com/watch?v=QQflpu3pvKs
    • https://www.youtube.com/watch?v=ciY9jX89cZM
  • Infographics by Clínica Universidad de Navarra (2016).
  • Revista Médica Clínica Las Condes 2012;23:446-57.

Key Take-Home Messages

  • Always differentiate immune allergy from enzyme-based intolerance when approaching adverse food reactions.
  • In allergies, IgE binding to mast cells is central; in intolerances, enzyme absence (e.g., lactase) predominates.
  • HLA-DQ2/DQ8 typing + anti-tTG antibodies are diagnostic cornerstones for celiac disease.
  • CMPA illustrates classic Type-I hypersensitivity; management involves elimination and, in some cases, tolerance induction protocols.
  • Anaphylaxis requires immediate recognition and epinephrine administration – time is tissue – time is life.