STEPTRACKERIMMUNOLOGY + PHARMACOLOGY | HYPERSENSITIVITY | HIGH-YIELD REVIEW

Type I Hypersensitivity

Preformed IgE on mast cells meets allergen and triggers degranulation within minutes — from hay fever to anaphylaxis — followed hours later by a cellular late phase.

FOCUS ON
Sensitization: Th2 (IL-4, IL-13) → B cells switch to IgE → IgE binds FcεRI on mast cells/basophils. Re-exposure: allergen cross-links IgE → immediate phase (minutes): histamine, tryptase, heparin → vasodilation, leak, bronchospasm, itch; late phase (hours): leukotrienes (C4, D4, E4), prostaglandin D2, PAF, eosinophils (IL-5) → sustained inflammation. Examples: anaphylaxis (food, bee sting, penicillin), allergic rhinitis, urticaria, allergic asthma, atopic dermatitis, eosinophilic esophagitis. Anaphylaxis → IM epinephrine first; ↑ serum tryptase confirms. Tests: skin-prick, serum specific IgE. Treatment: avoidance, antihistamines, leukotriene blockers, cromolyn, omalizumab, allergen immunotherapy (IgG4 blocking antibodies).
DISORDER
TRIGGER · MECHANISM
CLINICAL PICTURE
MANAGEMENT
Anaphylaxis
Systemic IgE-mediated mast cell release (peanut, shellfish, stings, β-lactams, latex)
Urticaria, angioedema, wheeze, stridor, hypotension, vomiting within minutes
IM epinephrine (thigh) first · then fluids, antihistamines, steroids · tryptase within hours
Anaphylactoid reaction
Direct mast cell activation without IgE (vancomycin, opioids, radiocontrast)
Similar picture; no prior sensitization needed
Slow infusion, premedicate
Allergic rhinitis
Pollen, dust mites, dander
Sneezing, itchy watery eyes, clear rhinorrhea, pale boggy turbinates
Intranasal steroids, antihistamines
Allergic asthma
IgE + Th2 + eosinophils; late phase → airway remodeling
Episodic wheeze, cough; Curschmann spirals, Charcot-Leyden crystals
ICS, LABA, montelukast, omalizumab, anti-IL-5
Urticaria · angioedema
Dermal (hives) or deep dermal mast cell release
Itchy wheals that come and go within 24 h
H1 blockers · non-itchy angioedema without hives → bradykinin (HAE, ACE-I)
Atopic dermatitis
Barrier defect (filaggrin) + Th2
Itchy flexural eczema in children; atopic march to asthma, rhinitis
Emollients, topical steroids, dupilumab
Food allergy · eosinophilic esophagitis
IgE (immediate) · Th2 eosinophilic infiltration
Hives, vomiting · dysphagia, food impaction, rings on endoscopy
Avoidance, PPI, topical steroids
Mast cell mediators — preformed
Histamine (H1: itch, leak, bronchospasm), tryptase, heparin, ECF
Minutes
Tryptase = mast cell specific
Mast cell mediators — newly made
Leukotrienes C4/D4/E4 (bronchoconstriction), LTB4, PGD2, PAF
Hours (late phase)
Montelukast, zileuton
Allergy testing
Skin-prick or intradermal wheal; serum allergen-specific IgE
Stop antihistamines before skin tests
Total IgE ↑ in atopy, parasites, ABPA, hyper-IgE syndrome
Allergen immunotherapy
Gradual dosing → IgG4 "blocking" antibodies, Tregs
Venom, pollen, mite allergy
Risk of anaphylaxis during build-up

Picture it — the four hypersensitivity types

allergenhistaminemast cell + IgETYPE I · minutes
Type IAllergen cross-links IgE on mast cells → histamine and other mediators within minutes.
phagocyteIgG on a fixed cellTYPE II · cell-bound
Type IIIgG or IgM binds antigen fixed on a cell or tissue → complement, phagocytosis or receptor dysfunction.
bloodvessel wallimmune complexes + complementTYPE III · complexes
Type IIISoluble immune complexes deposit in vessel walls and glomeruli → complement and neutrophils cause vasculitis.
Th1macrophageIFN-γT cells, no antibodyTYPE IV · 48–72 h
Type IVSensitized T cells release IFN-γ (or kill directly) → reaction peaks at 48–72 hours, no antibody involved.

Schematic diagrams, not to scale.

Mechanism — two exposures

First exposureTh2 → IL-4 → IgE
→
IgE arms mast cellsFcεRI
Re-exposure: allergen cross-links IgE
→
Degranulation (minutes)Histamine, tryptase
→
Late phase (hours)Leukotrienes, eosinophils

Drugs for type I reactions

DRUG
TARGET
USE
Epinephrine
α1 (BP), β2 (bronchi), β1
Anaphylaxis first line
H1 antihistamines
Histamine receptor
Rhinitis, urticaria
Montelukast
CysLT1 receptor
Asthma, rhinitis
Cromolyn
Mast cell stabilizer
Prevention
Omalizumab
Free IgE
Allergic asthma, urticaria

How it's tested

COMMON CONFUSIONAnaphylaxis (IgE, needs prior exposure) vs anaphylactoid reaction (direct mast cell release, can happen on the first dose) — treatment is the same.
THE TRAPAntihistamines and steroids don't replace epinephrine in anaphylaxis; patients on β-blockers may need glucagon.
YOUR APPROACHMinutes after exposure + skin/airway/circulation → type I → epinephrine → confirm with tryptase → prevent with avoidance or immunotherapy.

If you see… think…

Hives, wheeze and hypotension minutes after peanuts → anaphylaxis (IM epinephrine)
Mast cell–specific marker of anaphylaxis → tryptase
Antibody that arms mast cells → IgE (FcεRI)
Cytokine for IgE class switching → IL-4
Mediators of the late phase → leukotrienes, eosinophils
Flushing on vancomycin without prior exposure → anaphylactoid (direct mast cell)
Anaphylaxis on a β-blocker refractory to epinephrine → glucagon
Anti-IgE monoclonal antibody → omalizumab
Dysphagia, food impaction, esophageal rings in an atopic teen → eosinophilic esophagitis
Filaggrin mutation → atopic dermatitis