Food Allergy & Hypersensitivity Comprehensive Notes

Classification of Adverse Food Reactions

  • Two broad mechanisms
    • Non-immunologic (Intolerance)
    • Pharmacologic or toxic effects from naturally occurring or added chemicals.
    • Common triggers: caffeine, alcohol, sulfites, sodium glutamate.
    • Example: Histamine fish poisoning—occurs in any person ingesting a large enough dose of spoiled fish.
    • Immunologic (Hypersensitivity / Food Allergy)
    • Requires an immune response to specific food components.
    • Sub-classified into:
      • IgE-mediated reactions.
      • Non-IgE-mediated (cell-mediated, mixed, or other antibody classes).

Phenotypic Approaches to Food Hypersensitivity

  • By exposure pattern
    • Acute / episodic.
    • Chronic / continuous.
  • By mechanism + timing
    • Acute IgE (typical onset ≤30 min\le 30\,\text{min}; not absolute).
    • Delayed IgE (late-phase reactions possible).
    • Acute non-IgE (e.g., Food protein-induced enterocolitis presenting within hours).
    • Delayed non-IgE (may peak ≤3 days\le 3\,\text{days} post-ingestion).

Mechanism-Presentation Matrix (Key Clinical Clusters)

  • Gastrointestinal
    • Oral allergy syndrome (itching, swelling of lips/palate) — usually IgE.
    • Vomiting, diarrhea, abdominal pain — both mechanisms.
    • Anaphylaxis with GI involvement — fulminant IgE.
  • Skin
    • Urticaria, angio-edema — classic IgE.
    • Atopic dermatitis — mixed; strong non-IgE component in infants.
  • Respiratory
    • Throat tightness, rhinoconjunctivitis, asthma — predominantly IgE.
  • Qualitative severity scale (transcript “+” codes): anaphylaxis/urticaria (++++) > GI & skin (+++) > respiratory (++/+++).

Biochemical Characteristics of Food Allergens

  • Typically proteins with molecular mass 18 000!–!36 000 Da18\,000!\text{–}!36\,000\,\text{Da}.
  • Smaller peptides can be allergenic.
  • Allergenicity modified by:
    • Cooking (heat denatures or enhances, e.g., roasted peanut).
    • Digestion (gastric acid/enzymes may destroy or reveal epitopes).
    • Lipids: fats & oils can reduce intestinal absorption of allergens.

Age-Specific Sensitizing Sources

  1. In-utero (maternal circulation).
  2. Breast milk (dietary antigens traverse mammary epithelium).
  3. Infant formulas (cow milk, soy protein).
  4. Solid foods (progressive dietary expansion after ∼6 mo\sim6\,\text{mo}).
  5. Peanut proteins in skin products (topical exposure → cutaneous sensitization).
  6. Pollen-food syndromes (apple/peach/plum/hazelnut ↔ birch tree pollen).
  7. Latex-fruit syndromes (banana, avocado, kiwi cross-react with latex hevein domain).

High-Impact Allergenic Foods

  • Children: cow milk, hen egg, soy, wheat, peanut, fish.
  • Adults: peanut, tree nuts, shellfish, fish.

Cross-Reactivity Probabilities (Shared Allergen Families)

  • Peanut → other legumes: 5%5\%.
  • Walnut → other tree nuts: 37%37\%.
  • Salmon → other fish: 50%50\%.
  • Shrimp → other shellfish: 75%75\% (and peanut-sensitized pts risk tree nut co-sensitization despite botanical distance).
  • Clinical principle: positivity to one allergen increases chance of sensitization to structurally unrelated allergens (e.g., cow-milk-allergic infants acquiring soy IgE).

Food–Phenotype Associations (Selected)

  • Cow milk → chronic diarrhea, pulmonary hemosiderosis (Heiner syndrome).
  • Egg white → infantile atopic dermatitis.
  • Peanuts → systemic anaphylaxis.
  • Fresh fruits (birch-related) → oral allergy syndrome.

Immunologic Concepts: Sensitization vs. Allergy vs. Tolerance

  • Oral tolerance: Regulatory immune responses (Tregs, IL-10) that block clinical symptoms despite antibody production.
  • Sensitization: Detectable IgE or T-cell reactivity without symptoms; far more common than clinical allergy.
  • Allergy: Sensitization plus reproducible symptoms after exposure.
  • IgG antibodies to foods are ubiquitous; diagnostic value = nil.

Epidemiology

  • Self-reported food reactions: 20!–!25%20!\text{–}!25\% of population.
  • Challenge-proven prevalence:
    • Adults: 1!–!2%1!\text{–}!2\%.
    • Infants/children: 6!–!8%6!\text{–}!8\%.
  • Specific examples:
    • Cow-milk allergy in infants: 2.5%2.5\%.
    • Peanut sensitization: ≈1%\approx1\% and rising.

Natural History

  • Spontaneous remission by ≤3 y\le3\,\text{y} in 85%85\% for cow milk, egg, wheat, soy.
  • Peanut: Previously thought permanent; newer data show subset outgrow, yet risk of re-sensitization persists.
  • Tree nut & seafood allergies tend to be lifelong.
  • Non-IgE GI disorders in infants resolve within 1!–!3 y1!\text{–}!3\,\text{y}; toddler/adult forms more persistent.

Diagnostic Gold Standard

  • Proof of causal link requires:
    1. Improvement on elimination diet.
    2. Recurrence of symptoms on food challenge.

Differential Diagnosis Highlights

  • FTT, hypoproteinemia (protein-losing enteropathy).
  • Heiner syndrome (cow-milk-induced pulmonary infiltrates).
  • Enzyme deficiencies (lactase, pancreatic insufficiency).
  • Structural GI disease vs. allergic enteropathy.
  • Chronic eosinophilic gastroenteritis, GERD, psychogenic food aversion, etc.

Structured Evaluation Workflow

  1. History
    • Reaction phenotype, timing, severity, amount ingested.
    • Personal & family atopy history.
  2. Diagnostic tests
    • Begin with least invasive; escalate with severity.
    • Severe unexplained disease → empiric elemental diet then staged re-introduction.

IgE Testing Metrics

  • Measure total IgE plus specific IgE.
    • Absent/very low total IgE makes specific IgE positivity unlikely.
  • Skin prick testing (SPT)
    • Safe from infancy.
    • Negative predictive value > 85%85\%.
    • Intradermal SPT discouraged (false positives).
  • In-vitro CAP / chemiluminescence
    • Quantitative; good across a broad IgE range.
    • Predictive values vary by food & titer.
  • Mediator assays (histamine, tryptase) useful during acute anaphylaxis to confirm mast-cell degranulation.

Non-IgE Diagnostics

  • Atopy patch test (APT)
    • Food applied ∼48 h\sim48\,\text{h} to intact skin → eczematous reaction.
    • Picks up T-cell–mediated allergy (eosinophilic esophagitis, proctocolitis).
  • Eosinophil counts / biopsy
    • Peripheral eosinophilia or mucosal infiltration hints at non-IgE pathogenesis.
  • IgG / IgA anti-gliadin
    • Used for celiac disease, not classic allergy.

Diagnostic Diet Modalities

  • Targeted elimination
    • Remove suspect foods for 4!–!6 wk4!\text{–}!6\,\text{wk} → assess response.
    • Choice guided by history, cross-reactivity, SPT/CAP, phenotype tables.
    • Examples:
    • GERD → trial dairy elimination.
    • Infant eczema → egg, milk, wheat restrictions.
  • Elemental diet
    • Amino-acid–based formulas (infants) or limited tolerated foods (rice, chicken) for 1!–!3 wk1!\text{–}!3\,\text{wk}.
    • Reserved for severe, multisystem disease where triggers unclear.

Food Challenges

  • Indications
    1. Clarify which component of mixed meal causes reaction.
    2. Test if tolerance has developed (negative SPT/CAP).
    3. Verify clinical relevance of low-level IgE positivity.
    4. Prune overly restrictive diets.
  • Formats
    • Open (preferred in children).
    • Single-blind / double-blind placebo-controlled (DBPCFC) for subjective or psychological cases.
  • Safety
    • Hospital setting for prior anaphylaxis.
    • Home challenges acceptable for non-severe chronic symptoms, with ≥3 d\ge3\,\text{d} between foods.

Contra-Indicated / Unvalidated Tests

  • Multiple-food elimination without rationale.
  • Intradermal SPT to foods.
  • Provocation-neutralization (sublingual/intracutaneous).
  • Serum IgG RAST panels.
  • Cytotoxic testing, leukocyte histamine release, lymphocyte proliferation.

Primary Prevention Strategies

  • Encourage exclusive breast-feeding.
  • If supplementing, choose hydrolyzed "hypoallergenic" formulas.
  • Delayed introduction of highly allergenic solids (peanut, egg, chocolate, tree nuts) beyond infancy.
  • (Emerging data now support early peanut introduction in selected infants, but transcript reflects traditional delay model.)

Therapeutic Principles

  • Strict elimination diet
    • Maintain 2!–!3 y2!\text{–}!3\,\text{y} then reassess with SPT/CAP ± challenge.
  • Anaphylaxis management
    • Education on hidden allergens, cross-reactivity.
    • Epinephrine auto-injector (Epi-Pen) prescription + training.
    • Medical alert identification bracelet.
  • Pharmacologic adjuncts
    • H1 antihistamines (symptom suppression).
    • Topical/systemic corticosteroids for dermatitis, asthma.
    • Investigational: Anti-IgE monoclonal antibodies for severe peanut allergy.
  • Immunotherapy
    • Oral / sublingual desensitization under study.
    • Traditional SCIT for foods carries high risk—generally not recommended.

Summary of Key Points

  • Food allergy: multiple immune mechanisms, broad spectrum of symptoms, may be life-threatening.
  • Often over-diagnosed (by history) or under-diagnosed (in silent chronic disease).
  • High prevalence in childhood; requires vigilant primary care screening and timely referral.
  • Accurate diagnosis → effective management, minimizes nutritional compromise & allergic march.

Referral Triggers for Allergy/Immunology

  • Documented or suspected anaphylactic shock.
  • Chronic GI/respiratory/skin symptoms unresponsive to basic care.
  • Persistent atopic dermatitis, FTT, unexplained pulmonary infiltrates.
  • Polysensitized patients, elevated IgE\text{IgE} or eosinophilia.
  • Need for supervised DBPCFC, complex dietary counseling, or biologic therapy.