Pathophysiology of Allergic Rhinitis

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 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.

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.

⭐ 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 degranulation → histamine 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).