Allergic Rhinitis and Immune Response Quiz

Rhinitis: Allergic and Non-Allergic

•  Rhinitis is characterized by one or more nasal symptoms including congestion, rhinorrhea, sneezing, and itching.
•  It is classified as either allergic or non-allergic.
•  Allergic and non-allergic rhinitis can both be present in 44-87% of patients.

Allergic Rhinitis: Objectives

• Understand the difference between allergic and non-allergic rhinitis, including mechanisms and treatments.
• Know how to diagnose and treat rhinitis.
• Know the mediators of allergic rhinitis.
• Understand how immunotherapy alters the immune system (not all mechanisms).
• Know what anti-IgE is and how it can affect allergic diseases.
• Understand the immunology of allergic diseases.
• Know the IgE-mediated conditions.
• Define triggers of allergic rhinitis and how to avoid them.

Allergic Rhinitis: Burden

• Affects 10-30% of adults and up to 40% of children worldwide.
• Worldwide prevalence is increasing.
• Impacts quality of life, leading to reduced work productivity and lost school days.
• Direct costs to individuals and society in the United States are $3-4 billion per year.
• Individuals with allergic rhinitis (AR) spend an average of $650 annually on AR-related medical and pharmacy services.

Allergic Rhinitis: Risk Factors

• Family history of atopic disease
• Serum IgE > 100 IU/mL before age 6
• Higher socioeconomic status
• Exposure to environmental irritants (pollution, tobacco smoke)
• Early life exposure to antibiotics
• Positive skin prick test
• Indoor allergen sensitization (6 months - 2 years old)
• Pollen sensitization (2-7 years old)

Allergic Rhinitis - Pathophysiology

• IgE-mediated reaction to inhaled allergens.
• Allergen interacts with IgE on mast cell surfaces, triggering degranulation.
• Early phase: histamine release causing sneezing, rhinorrhea.
• Late phase: arachidonic acid metabolites causing congestion.
• Food allergy rarely causes isolated nasal symptoms.
• Tissue eosinophils contribute to local inflammation and damage.
• Repeated antigen exposure reduces the amount needed to induce an immediate response (priming).
• Air pollutants also affect priming.

Definition- Rhinitis

• Rhinitis is defined by one or more nasal symptoms: congestion, rhinorrhea, sneezing, or itching.
• Classified as either allergic or non-allergic.
• Differential diagnoses should include chronic rhinosinusitis, nasal polyps, cerebrospinal fluid leaks, and structural nasal abnormalities.

Seasonal Allergic Rhinitis: Patterns of Symptoms

• Spring: trees
• Summer: grasses
• Fall: weeds (especially ragweed)
• Perennial: cockroaches, dust mites, pets, mold

Globally Important Sources of Allergens

• House dust mites
• Grass, tree, and weed pollen
• Pets
• Cockroaches
• Molds

CD4+ T helper cells

• Th1: "Anti-allergy" cell. Stimulates phagocyte-mediated defense against intracellular antigens (IFN-γ).
• Th2: "Allergy-producing" cell. Stimulates IgE, eosinophils, and mast cells in response to extracellular antigens. Downregulates Th1 response (IL-4, IL-5, IL-13).

The Hygiene Hypothesis

• Link between decreased exposure to infections in childhood and increased risk of allergies.
• Older siblings typically have more infections and Th2 stimuli , and so are less likely to develop allergies.
• Children with fewer infections (only child) have less Th2 stimuli and increased risk for allergies.

Factors Favoring Th1 and Th2 Phenotypes

• Th1: Presence of older siblings, early exposure to day care, tuberculosis, measles, or hepatitis A infection, rural environment.
• Th2: Widespread use of antibiotics, Western lifestyle, urban environment, diet, sensitization to house-dust mites and cockroaches.

Atopic Conditions

• Anaphylaxis, allergic rhinosinusitis, allergic conjunctivitis, asthma, atopic dermatitis, urticaria/angioedema, food allergies, drug allergies, stinging insect allergies, latex allergy.

Approach to the Atopic Patient: History

• Onset of symptoms (typically by age 10)
• Character, duration, frequency, and severity of symptoms.
• Temporal nature of symptoms (seasonal or perennial).
• Environmental nature of symptoms (home, school, work).
• Family history (maternal and paternal).

Approach to Patient with Atopy: Physical Exam

• Skin: dermatographism, urticaria, dermatitis
• Eyes: allergic shiners, conjunctival papillae
• Nose: pale/bluish mucosa, clear mucus, creases, polyps
• Lungs: wheeze, increased E/I ratio

Approach to Patient with Atopy: Primary Tests

• Skin tests: demonstrate the presence of specific IgE antibodies to aeroallergens, foods, insect venoms, and PCN. Percutaneous and intradermal testing.
• Patients must be off of antihistamines, tricyclics, and beta-blockers. These tests use controlled (+) and (-) samples to determine results.
• RAST (radioallergosorbent test): measures specific IgE. Expensive, less sensitive than skin tests, and results can differ significantly.

Skin Testing

• Skin tests are a method to diagnose allergies
• Specific allergens are placed on the patient's skin

IgE-dependent Release of Inflammatory Mediators

• IgE binds to mast cell receptors.
• Triggers granule contents release after allergen exposure: histamine, TNF-α, proteases, heparin, etc.
• Release from mast cells results in symptoms of sneezing, nasal congestion, itchy, runny nose, watery eyes, and wheezing.

Allergic Rhinitis: Treatment (1) - Allergen Avoidance

• Dust mites: reduce humidity, wash bedding regularly, encase mattresses and pillows in allergen-proof covers.
• Cockroaches: clean cockroach reservoirs, pest management.
• Furry pets: exclude from utilized rooms, or washing pets, HEPA air filters and vacuuming, etc.
• Mold/fungi: reduce indoor moisture, minimize, good ventilation, dehumidifier

Allergic Rhinitis: Treatment (2)

• Intranasal Corticosteroids
• Intranasal Antihistamines
• Intranasal Anticholinergics
• Oral Antihistamines
• Nasal lavage
• Intranasal cromolyn
• Oral and Topical Decongestants (limited use recommended)

Allergic Rhinitis: Treatment (3) -Allergen-Specific Immunotherapy

• Repeated allergen administration.
• Results in immunologic changes such as regulatory T lymphocytes, shift of immunity to type 1, and eventual IgG reduction.
• Subcutaneous or sublingual tablets are commonly used.
• Risk of anaphylaxis with subcutaneous injections.

Recommendations

• Allergen immunotherapy should be prescribed by an allergy and immunology specialist.

Allergen Immunotherapy and Immune Tolerance

• Shifts immune response from Th2 to Th1.
• Suppresses seasonal rise in specific IgE.
• Increases specific IgG1 and IgG4.
• Increased levels of IgG and IgA in nasal secretions.
• Reduced reactivity and sensitivity of basophils to antigen.
• Decreases mast cells/eosinophils in target organs.
• Decreases early and late allergic responses.
• Maintains symptom improvement after stopping therapy.
• May affect the natural course of allergic disease.
• May prevent asthma development in 40% of children

Non-allergic Rhinitis (NAR): Background

• Chronic inflammation of nasal mucosa without evidence of allergies (no allergic sensitization).
• Often idiopathic (no known cause) or vasomotor rhinitis.
• Predominant symptoms are nasal congestion and rhinorrhea;
• Associated symptoms: facial/ear pain, pressure, sneezing, post-nasal drip, poor sense of smell, throat clearing, and cough.
• Nasal and/or oral pruritus and ocular symptoms less common.

Non-allergic Rhinitis

• 17-52% of adult rhinitis cases.
• 20 million affected Americans.
• Onset is typically adulthood.
• 70% present after 20 years of age. - Female predominance (2:1)
• Symptoms triggered by nonimmunologic stimuli: cold/dry air, irritants, cigarette smoke, cleaning products, or strong odors.

Non-allergic Rhinitis: Diagnosis

• No pathognomonic symptoms.
• Swollen turbinates or reactive upper airway dysfunction may be observed.
• Assessment of irritant triggers. - Non-specific nasal hyper-reactivity to methacholine, histamine, capsaicin, or cold/dry air.
• Allergen skin/serologic testing negative or not correlating with symptoms.
• Commonly neutrophilic, eosinophilic, or paucigranulocytic inflammatory reactions observed.

Non-Allergic Rhinitis with Eosinophilia (NARES)

• Type of inflammatory Non-allergic Rhinitis.
• Nasal secretions contain > 25% eosinophils.
• Approximately 12-25% of NAR cases.
• Increased nasal symptoms and anosmia.
• Responsive to intranasal glucocorticoids.

Gustatory Rhinitis

• Clear rhinorrhea following food ingestion (immediately).
• Hot/spicy foods are common triggers; any food can elicit a response.
• Food stimulates afferent sensory nerves in the oropharynx which then activate parasympathetic efferent nerves in the nasal mucosa that increase nasal secretions and cause congestion.
• Rarely associated with food allergies, unless anaphylaxis is occurring.

Gustatory Rhinitis: Treatment

• Avoid offending foods.
• Initial treatment is intranasal anticholinergic agents (Ipratropium Bromide).
• Using this agent prophylactically (immediately prior to eating) is most effective.
• Combination of intranasal ipratropium bromide & nasal corticosteroid may be more effective than either medication alone.

Rhinitis Medicamentosa

• Rebound nasal congestion caused by overuse of intranasal alpha-adrenergic drugs (oxymetazoline or phenylephrine) or cocaine.
• In the US, these drugs are labeled with a 3-day treatment warning.
• Diagnosis is made via complete history and exam.
• Nasal mucosa is often erythematous, granular, and show punctate bleeding.
• Topical decongestant use cessation is first line of treatment to resolve this condition.

Summary

• Rhinitis can be allergic, non-allergic, or both.
• Non-allergic rhinitis (NAR) isn't caused by IgE & is treated with intranasal steroids.
• Allergic rhinitis (AR) is primed as the allergen season progresses (fewer allergens trigger responses later in the season).
• AR treatment includes antihistamines, nasal steroids, and immunotherapy.