Allergic Rhinitis Causes & Mechanisms

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Allergic cascade—what happens when an allergen infiltrates the body?

Allergic cascade and allergic rhinitis

The “allergic cascade” and its role in allergic rhinitis (AR)1

The body’s immune response to allergens includes a series of early- and late-phase reactions—the allergic cascade. There are several allergic mediators involved in this cascade, not just histamines.2

Typically, the allergic cascade follows this pattern2,3:

  1. Sensitization to an allergen
  2. Early-phase response upon re-exposure to an allergen
  3. Late-phase response

When the body is exposed to an allergen:

  • Sensitization involves being exposed to an allergen for the first time2
  • The body produces immunoglobulin E (IgE) designed specifically for that particular allergen, but an allergic reaction does not yet occur2 
  • Re-exposure to an allergen triggers an early-phase response that occurs within minutes to an hour2
  • The IgE of mast cells binds to the allergen, crosslinking the IgE2
  • When enough crosslinking occurs, the mast cells explode with histamine and other inflammatory substances, called mediators, such as cytokines, leukotrienes, prostaglandins, eosinophils, and thromboxanes2,3
  • The late-phase response occurs from 3 to 10 hours after allergen re-exposure2 
  • Immune cells, such as eosinophils, secrete substances that increase inflammation and bring other immune cells into the reaction, perpetuating the inflammatory response2
  • Symptoms can be more severe than those in the early phase2

The end result is the allergic response consisting of a range of symptoms such as rhinorrhea (runny nose), sneezing, congestion, and pruritus (itching)2

  • MOA of antihistamines

    Antihistamines work by binding to the H1 receptor, therefore inhibiting histamine (a mediator of the inflammatory response) from binding to the H1 receptor. This hinders the body’s response when exposed to an allergen, thus preventing symptoms such as wheezing, sneezing, coughing, itchy nose and eyes, runny nose, and shortness of breath.4

  • MOA of decongestants

    Decongestants work by stimulating receptors on blood vessels, causing vasoconstriction and shrinking of the nasal turbinates. Constriction alleviates nasal mucosa inflammation and allows the sinuses to drain, thereby reducing nasal congestion.5

  • MOA of anti-leukotrienes

    Anti-leukotrienes block the action of leukotrienes, which cause tightening of airway muscles and production of excess mucus and fluid, reducing nasal secretions.6

  • MOA of intranasal corticosteroids (INSs)

    INSs, often used as first-line treatment for patients with mild persistent or moderate-to-severe symptoms, work locally in the nasal mucosa to block multiple mediators involved in the allergic cascade, including histamine, cytokines, leukotrienes, chemokines, prostaglandins, and tryptase.3,7-9


    • Act on both early and late phases of the inflammation process, therefore relieving the symptoms they cause
    • Provide relief of nasal congestion and itching, runny nose and sneezing, and itchy, watery eyes

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