Type I

• Type I hypersensitivity reactions are referred to as “immediate reactions.”

• Antibody-mediated; include anaphylactic and atopic immune responses

1. IgE is formed as a result of prior sensitization (i.e., previous contact with the antigen) and coats mast cells and basophils.

2. Subsequent encounter with antigen results in an IgE-mediated reaction by preformed IgE antibodies: free antigen binds to two adjacent IgE antibodies (crosslinking) → degranulation of cells

3. Release of histamine and other mediators (e.g., prostaglandin, platelet-activating factor, leukotrienes, heparin, tryptase), leading to:

   • ↑ Smooth muscle contraction → bronchospasm, abdominal cramping

   • Peripheral vasodilation and ↑ vascular permeability → hypovolemia, hypotension

   • Extravasation of capillary blood → erythema

   • Fluid shift into the interstitial space → edema, pulmonary edema

   • Pruritus

4. Mast cell secretion of cytokines and other proinflammatory mediators → eosinophil and neutrophil chemotaxis → late-phase reaction → inflammation and tissue damage

• Description: Individuals with allergies may also react to substances that contain particles that are similar to the main antigen.

• Examples (primary allergen – cross-reactant allergen)

  • Pollen – various foods (e.g., apple, hazelnut, carrot, kiwi, apricots, peaches)

  • Mites – crustaceans

  • Latex – exotic fruits (e.g., banana, avocado, kiwi)

  • Bird dander – egg yolk

  • Cat dander – pork

• Immediate reaction: allergic reaction within minutes of contact with the antigen

• Late-phase reaction: occurs hours after immediate reaction for a duration of 24–72 hours

• Anaphylaxis: pruritus, edema, rash, rhinitis, bronchospasm, and abdominal cramping

• Angioedema: due to mast cell activation in the dermis and/or subcutaneous tissue

• Urticaria (hives)

  • Well-circumscribed, raised, pruritic, and erythematous plaques with a round, oval, or serpiginous shape

  • Up to several centimeters in diameter (wheals)

  • Caused by mast cell activation and degranulation in the superficial dermis → hyperpermeability of microvasculature → edema [10]

  • Differential diagnosis: See “Overview of annular skin lesions.”

• Atopy

  • Genetic predisposition to producing IgE antibodies against certain harmless environmental allergens (e.g., pollen, mites, molds, certain foods)

  • Associated conditions: asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, food allergies

• Allergic conjunctivitis

• Allergic rhinitis

• Allergic asthma

Modalities

• Skin prick test

  • An allergen solution is applied through a skin prick (e.g., of the volar forearm).

  • First-line test for immediate DHRs (safest and easiest) [2]

• Scratch test

  • An allergen is applied to a scratch (∼ 1 cm) on the skin.

  • Comparable to prick test

• Intradermal test

  • Intradermal injection of small amounts of the allergen

  • Can be used to diagnose immediate and nonimmediate HSRs [2][14]

  • More sensitive than skin prick test; higher risk of false positives [12]

  • May lead to anaphylaxis in IgE-mediated HSRs

• Tryptase

  • A relatively specific marker of mast cell activation

  • Elevated levels indicate an increased risk of severe reactions.

• Allergen-specific IgE test (sIgE)

  • Indicated in patients with known allergic triggers and clinical symptoms

  • Preferable to skin testing in patients at high risk of anaphylaxis

  • Quantitatively assessed using enzyme-linked immunosorbent assay (ELISA)

Treatment of type I hypersensitivity reactions depends on the cause of the reaction (see “Hypersensitivity classification” above).

• Drug reactions: Remove the offending drug.

  • Severe reactions: emergency resuscitation; see “Management of anaphylaxis”

  • Moderate reactions (more pronounced urticaria/angioedema, fever, arrhythmia, bronchospasm): antihistamines with or without glucocorticoids

  • Mild reactions (mild urticaria/angioedema, GI symptoms, tremor, palpitations, headache, cough): expectant management with or without antihistamines

  • See “Drug hypersensitivity reactions."

• Emergency self‑management for patients with known allergic reactions

  • Epinephrine autoinjectors, antihistamines, corticosteroids

  • Anaphylaxis emergency action plan

• Urticaria

  • Avoid trigger (if known).

  • H1-receptor blocker (e.g., cetirizine)

  • Glucocorticoids

• Indication

  • Documented IgE-mediated allergy (e.g., allergic rhinitis, allergic asthma, allergy to wasp or bee venom)

  • Significant symptoms and inadequate relief from symptomatic therapy and exposure prophylaxis

  • Significant symptoms despite symptomatic therapy and avoidance of the allergen

• Method

  • Only available for some allergens but can be quite effective

  • Application of specific antigen in subclinical dose (subcutaneous, mucosal)

  • Slow escalation of dose

  • Goal: ↑ production of IgG antibodies instead of excessive IgE production (isotype switching) [17]

  • Duration of treatment: at least 3 years

• Prognosis

  • Success in up to ⅔ of patients

  • Younger patients see comparatively more benefits.

  • Higher success rates in patients with sensitivity to only one allergen (monovalent) as opposed to patients with sensitivity to many allergens (polyvalent)