Pathophysiology of Allergic Rhinitis

Pathophysiology of Allergic Rhinitis

Pathophysiology of Allergic Rhinitis

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Pathophysiology of Allergic Rhinitis: Overview - Sneezing Storm Intro

Allergic Rhinitis (AR) is an IgE-mediated nasal mucosal inflammation triggered by allergen exposure, manifesting as paroxysmal sneezing, watery rhinorrhea, nasal itching, and congestion.

⭐ The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines classify AR based on duration (Intermittent/Persistent) and severity (Mild/Moderate-Severe), guiding stepwise management.

ARIA Classification:

  • Duration of Symptoms:
    • Intermittent: < 4 days/week OR < 4 consecutive weeks.
    • Persistent: > 4 days/week AND > 4 consecutive weeks.
  • Severity of Symptoms:
    • Mild: Normal sleep; No impairment of daily activities, sport, leisure; No troublesome symptoms.
    • Moderate-Severe: One or more of: Abnormal sleep; Impairment of daily activities, sport, leisure; Troublesome symptoms.

Common Allergens (Indian Context):

  • Pollen (e.g., Parthenium, grasses)
  • House Dust Mites (e.g., Dermatophagoides pteronyssinus, D. farinae)
  • Fungi (e.g., Aspergillus, Alternaria)
  • Animal dander
  • Cockroach allergens

Pathophysiology of Allergic Rhinitis: Key Players & Sensitization - The Allergy Army

  • Key Cells (The Allergy Army):
    • Antigen Presenting Cells (APCs)
    • Th2 lymphocytes
    • B-cells (→ Plasma cells)
    • Mast cells
    • Eosinophils
    • Basophils
  • Key Mediators (The Weapons):
    • IgE
    • Histamine
    • Leukotrienes ($LTC_4, LTD_4, LTE_4$)
    • Prostaglandins ($PGD_2$)
    • Cytokines (IL-4, IL-5, IL-9, IL-13, TNF-α)
    • Chemokines

Sensitization: Priming the Army

⭐ Th2 lymphocytes are pivotal, releasing IL-4 (promotes IgE synthesis by B cells), IL-5 (recruits/activates eosinophils), and IL-13 (↑ IgE, mucus secretion, airway hyperresponsiveness).

Pathophysiology of Allergic Rhinitis: Early and Late Phases

Pathophysiology of Allergic Rhinitis: Early Phase Reaction - Phase 1 Assault

  • Trigger: Allergen re-exposure.
  • Mechanism: Allergen cross-links IgE on sensitized mast cells → Degranulation.
  • Mediators Released:
    • Pre-formed (minutes):
      • Histamine: Sneezing, itching, rhinorrhea, nasal congestion (vasodilation, ↑ vascular permeability).
      • Tryptase, Proteases, Heparin.
    • Newly Synthesized (minutes-hours):
      • Leukotrienes ($LTC_4, LTD_4, LTE_4$): Potent bronchoconstrictors, ↑ vascular permeability, mucus secretion, chemotaxis.
      • Prostaglandin $D_2$ ($PGD_2$).
      • Platelet-Activating Factor (PAF).
  • Clinical: Onset 5-30 minutes; lasts 1-3 hours.

⭐ Histamine, released from mast cell granules during the early phase, is the primary mediator of acute symptoms like sneezing, pruritus, and watery rhinorrhea, acting on H1 receptors.

Phases of Allergic Rhinitis

Pathophysiology of Allergic Rhinitis: Late Phase & Chronic Features - Phase 2 Siege

  • Onset & Duration:
    • Starts: 4-8 hours post-allergen.
    • Peaks: 12-24 hours.
    • Lasts: 24-48 hours or longer.
  • Mechanism:
    • Infiltration & activation of inflammatory cells: Eosinophils, basophils, Th2 cells, neutrophils, monocytes.
    • Driven by chemokines & cytokines from early phase.
  • Key Player: Eosinophils
    • Release: Toxic proteins (Major Basic Protein - MBP, Eosinophil Cationic Protein - ECP), leukotrienes, cytokines.
    • Effects: Epithelial damage, chronic inflammation.
  • Clinical Manifestations:
    • Predominant: Sustained nasal congestion.
    • Systemic: Fatigue, malaise.
    • Local: Nasal hyperreactivity.
  • Nasal Priming: Repeated allergen exposure ↓ reaction threshold. Pathophysiology of Allergic Rhinitis

⭐ The late-phase reaction, characterized by a significant influx of eosinophils, is responsible for persistent symptoms, particularly nasal congestion, and contributes to nasal hyperreactivity.

High‑Yield Points - ⚡ Biggest Takeaways

  • IgE-mediated Type I hypersensitivity is the core mechanism.
  • Sensitization: Allergen exposure → IgE production → IgE coats mast cells.
  • Early Phase (minutes): Re-exposure → mast cell degranulationhistamine release → acute symptoms.
  • Late Phase (4-8 hours): Eosinophil and lymphocyte infiltration → sustained inflammation and congestion.
  • Th2 cells orchestrate via IL-4 (IgE switching), IL-5 (eosinophil recruitment/activation), IL-13 (mucus).
  • Key mediators: Histamine (sneezing, itching, rhinorrhea), Leukotrienes (nasal blockage).

Practice Questions: Pathophysiology of Allergic Rhinitis

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Allergic rhinitis can lead to _____ otitis media

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