Immuno – Hypersensitivity

Master answer

Anaphylaxis

• acute severe type I hypersensitivity reaction affecting multiple organ systems
• most common triggers:
  • Food, Environmental
  • Drugs: antibiotics, muscle relaxants
  • Iodine contrast
  • Chlorhexidine
  • Latex
• Clinical effects
  • Circulatory collapse: profound vasoplegia  distributive shock
  • Airway obstruction: angioedema, bronchospasm,

Pathophysiology

• Multiple exposures to target allergen
• 1st exposure: allergen presented by T helper cells to B cells → B cells produce specific IgE to target allergen
• Circulating IgE attach to mast cells → sensitization
• Subsequent exposure to allergen → allergen binds specific IgE on mast cells → mast cell degranulation → release of allergenic mediators
• Mediators trigger disseminated vasodilation + ↑ vascular permeability +/- bronchospasm → anaphylaxis
  • Histamine: Localised release → urticaria; Systemic release → H1 + H2 → vasodilation, ↑vascular permeability → ↓MAP
  • Bradykinin: ↑production PGI2, NO → vasodilation, ↑ vascular permeability → ↓MAP
  • Prostaglandins: PGID2 → vasodilation, ↑ vascular permeability, bronchoconstriction, chemotactic for neutrophils + activates eosinophils
  • Leukotrienes: LTE B4: chemotactic agent; LTE D4 + E4: angioedema, clotting/ thrombolysis/ DIC
  • Tryptase: activates complement, coagulation, kallikrein-kinin pathways → ↓ BP, angioedema, clotting/ thrombolysis/ DIC
  • TNF-a: cytokine → propagates anaphylactic reaction
  • NO: vasodilates
  • Serotonin: vasodilation, bronchoconstriction, aplatelet activation
  • Platelet activating factor: acts at PAF Rs

Management of Anaphylaxis

• Oxygen
• IV Fluids
• Adrenaline is the drug of choice, as it treats cardiovascular collapse, bronchospasm, and decreases oedema formation.
  • Stabilises mast cells to prevent degranulation
  • Low doses: Beta agonism at (inotropy and chronotropy) and causing smooth muscle relaxation (including bronchorelaxation).
  • Higher doses: alpha effects and causes vasoconstriction.
  • In adults, 0.3-0.5mg IM Q5-15min
  • In children, 0.01mg/kg IM Q5-15min
• Glucagon may be used in β-blocked patients resistant to adrenaline.
  • In adults, 1-5mg IV over 5 minutes, followed by infusion at 5-15microg/min
  • In children, 20-30mcg/kg up to 1mg over 5 minutes

Adjunctive agents include antihistamines and steroids. They are second line as they do not attenuate cardiovascular collapse, resolve airway obstruction, or have strong evidence behind their use. They include:

• Steroids:
  • Work by binding to the cell nucleus and switching off the transcription of various genes which encode for inflammatory mediators such as cytokines, chemokines, adhesion molecules and arachidonic acid.
  • They also activate anti-inflammatory genes such as MAP (mitogen activated protein) and increase the expression of beta2 receptors.
  • Methylprednisolone, Hydrocortisone or Prednisolone
• Antihistamines:
  • Binds to H1 receptors to block the effects of the histamine released from mast cells-
    • inhibition of vasodilatation
    • increased vascular permeability
    • contraction of non-vascular smooth muscle
  • Diphenhydramine 25-50mg IV (Children: 1mg/kg up to 40mg) up to 200mg in 24/24
• Salbutamol, for bronchodilation
• Other Non-pharmacological management includes early intubation to protect against airway obstruction due to angioedema

Kerr / JC 2019

Answer by JC, Kerr