Allergic Rhinitis and Urticaria

IgE-mediated (Type I) causes — the default mechanism

• Aeroallergens: tree, grass and weed pollens (seasonal); dust mite, cockroach, animal dander and indoor molds (perennial). Sensitization requires prior exposure, so true first-exposure allergic rhinitis does not occur.
• Foods: in children milk, egg, peanut, tree nut, wheat, soy; in adults shellfish and tree nuts. A food-triggered wheal appears within minutes to two hours of ingestion.
• Insect stings (Hymenoptera) and latex — classic acute urticaria/angioedema stems.
• Drugs acting through IgE: beta-lactams are the prototype.

Non-IgE mast cell activation (pseudoallergic) causes

• Direct mast cell degranulators: opioids, vancomycin (rapid infusion → flushing of head and torso), radiocontrast, neuromuscular blockers. No prior sensitization needed.
• Aspirin/NSAIDs: COX-1 inhibition shunts arachidonate toward cysteinyl leukotrienes — exacerbates urticaria and underlies aspirin-exacerbated respiratory disease (asthma, nasal polyps, aspirin sensitivity).
• Autoimmune chronic spontaneous urticaria: functional anti-IgE/anti-FcεRI autoantibodies; associated with autoimmune thyroid disease.
• Physical (inducible) urticarias: dermatographism, cold, delayed pressure, vibratory, solar, cholinergic (heat/exercise-induced small punctate wheals).
• Bradykinin-mediated angioedema without wheals: ACE inhibitors, hereditary C1 inhibitor deficiency — histamine plays no role, an important mechanistic contrast.

Non-modifiable risk factors

• Atopic predisposition: personal or family history of asthma, atopic dermatitis, food allergy; polygenic Th2 skew. The strongest single predictor in a stem.
• Age: allergic rhinitis onset typically in childhood/adolescence; chronic spontaneous urticaria peaks in middle-aged women.
• Female sex for chronic urticaria.

Modifiable risk factors

• Allergen burden in the home (dust mite bedding, carpets, pets, cockroach, damp/mold).
• Tobacco smoke, indoor air pollution and occupational exposures (bakers' flour, animal handlers, latex).
• Drug and NSAID use, alcohol, and physical triggers such as heat and tight clothing.
• Untreated comorbid disease: chronic sinusitis, GERD, obesity, and *Helicobacter*/thyroid autoimmunity in chronic urticaria.

Type I Hypersensitivity Reaction (Immediate Type)

• Sensitization phase: Initial allergen exposure leads to processing by antigen-presenting cells and production of IgE antibodies specific to the allergen; these IgE molecules bind to high-affinity receptors (FcεRI) on mast cells and basophils
• Re-exposure phase: Upon subsequent allergen encounter, cross-linking of IgE-FcεRI complexes triggers rapid degranulation of mast cells and basophils within seconds to minutes

Molecular and Cellular Mechanisms

• Immediate mediator release from preformed granules: histamine (causes pruritus, vasodilation, increased vascular permeability), tryptase, chymase, heparin, and bradykinin
• Late-phase mediators (synthesized de novo): leukotrienes (LTC4, LTD4, LTE4—potent vasoconstrictors and smooth muscle contractants), prostaglandins (PGD2), platelet-activating factor, and chemotactic cytokines (eotaxin, RANTES, IL-8)
• Cytokine production: IL-4 and IL-13 promote Th2 differentiation and maintain chronic allergic inflammation; TNF-α and IL-6 amplify inflammatory responses
• Tissue-specific effects in rhinitis: Increased vascular permeability in nasal mucosa → mucosal edema and congestion; increased mucus secretion from goblet cells; recruitment of eosinophils and additional mast cells perpetuates inflammation
• Tissue-specific effects in urticaria: Mast cell and basophil activation in dermis and superficial subcutis → localized edema (urticaria) or deeper subcutaneous edema (angioedema); increased vascular permeability leads to extravasation of fluid into interstitial space

Chronic Inflammation (Late-Phase Reaction)

• Recruitment of eosinophils, T lymphocytes (particularly Th2 cells), and additional mast cells through chemotactic mediators
• Occurs 6-12 hours after allergen re-exposure in susceptible individuals
• Perpetuates inflammation even after immediate symptoms resolve; explains why some patients have persistent symptoms despite allergen avoidance

Allergic Rhinitis

• Nasal symptoms: Rhinorrhea (watery nasal discharge, not purulent), nasal congestion/obstruction, and sneezing (often paroxysmal—multiple consecutive sneezes); typically bilateral and symmetric
• Associated symptoms: Nasal pruritis (itching of nose and palate—highly characteristic), postnasal drip, loss of taste and smell, and mouth breathing (especially in children)
• Ocular symptoms: Allergic conjunctivitis with itchy, watery, red eyes and shiners (dark discoloration under eyes from venous congestion)
• Temporal patterns distinguish subtypes:
• Seasonal allergic rhinitis peaks during specific seasons (spring = tree/grass pollen; fall = ragweed; year-round in some regions)
• Perennial allergic rhinitis occurs year-round, typically triggered by dust mites, pet dander, cockroach antigens, or mold
• Physical findings: Pale, boggy nasal mucosa with clear secretions; nasal polyps may develop with chronic disease; Dennie-Morgan folds (infraorbital creases) and allergic salute (horizontal crease from chronic nose rubbing) suggest chronic atopy
• Fatigue and sleep disturbance from nasal obstruction; impact on school/work performance and quality of life
• Classic presentation: Young patient with seasonal symptoms, family history of atopy, and itching of nose and palate

Urticaria

• Primary lesion—wheal (hive): Raised, erythematous, pruritic plaques ranging from millimeters to centimeters; evanescent (individual lesions last <24 hours before resolving, though new lesions may appear); well-demarcated borders; may have central pallor
• Distribution: Can appear anywhere on body; often symmetric; may coalesce into larger plaques (giant urticaria)
• Pruritus: Intensely itchy—hallmark symptom; often worse in evening and with warmth; scratching may cause linear lesions (excoriations)
• Associated angioedema: Deeper subcutaneous swelling affecting face (lips, tongue, eyelids), throat, hands, feet, and occasionally GI tract; usually non-pitting edema; can be non-pruritic (unlike urticaria) and may last 24-72 hours
• Acute vs. Chronic urticaria:
• Acute urticaria (<6 weeks duration): Usually identifiable trigger (new medication, food, insect sting, infection); self-limited; resolves with treatment
• Chronic urticaria (>6 weeks): Often idiopathic (no identifiable trigger in ~80%); may represent autoimmune phenomenon with anti-IgE or anti-FcεRI autoantibodies; recurrent episodes over months to years
• Triggers for exacerbation: Heat, cold, pressure, vibration, sunlight, emotional stress, NSAIDs, alcohol
• Systemic symptoms: Usually absent in simple urticaria; fever, arthralgia, or lymphadenopathy suggest urticarial vasculitis (rare but important complication)

Allergic Rhinitis

• Clinical diagnosis: Based on characteristic history and symptoms; no single diagnostic test is required for confirmation in typical cases
• Nasal examination: Direct visualization with anterior rhinoscope or nasal speculum reveals pale, boggy mucosa with clear secretions; helps exclude alternative diagnoses (infectious rhinitis, structural abnormalities)
• Allergy testing (not routinely required but helpful to identify specific triggers):
• Skin prick testing: Most sensitive (>95%) and specific method; rapid (15-20 minutes), inexpensive; contraindicated in severe dermatitis or active urticaria; false negatives with antihistamine use (discontinue 3-5 days prior)
• Serum-specific IgE (RAST, ImmunoCAP): Less sensitive but useful if skin testing unavailable or contraindicated; can test multiple allergens simultaneously
• Intradermal testing: More sensitive but higher risk of systemic reactions; reserved for cases where skin prick testing is negative but suspicion remains high
• Nasal challenge testing: Rarely used clinically; research tool for confirming allergen provocation
• Differential diagnosis considerations:
• Rule out infectious rhinitis (purulent discharge, fever, URI symptoms, unilateral findings)
• Vasomotor rhinitis (triggered by temperature, humidity, irritants—not immune-mediated)
• Medication-induced rhinitis (ACE inhibitors, beta-blockers, NSAIDs, cocaine)
• Structural abnormalities (deviated septum, nasal polyps, turbinate hypertrophy)
• Nonallergic rhinitis with eosinophilia syndrome (NARES)

Urticaria

• Clinical diagnosis: Based on characteristic morphology and transient nature of lesions; visual inspection of a typical wheal is diagnostic
• Careful history: Temporal relationship to potential triggers; timing of onset (seconds to minutes

Immediate stabilisation (urticaria/angioedema only)

• Airway assessment first: stridor, tongue or laryngeal swelling, hypotension, or wheeze means anaphylaxis, not simple urticaria. Give epinephrine 0.3 mg IM into the anterolateral thigh (0.15 mg for young children), repeat every 5–15 minutes as needed — per the AAAAI/ACAAI Anaphylaxis Practice Parameter, epinephrine is first-line and antihistamines are adjunctive only. Never substitute an antihistamine or steroid for epinephrine.
• Withdraw the trigger (stop the offending drug, remove the stinger) and prescribe an epinephrine auto-injector with allergist referral.

First-line therapy — allergic rhinitis

• Intranasal corticosteroid (e.g., fluticasone propionate): most effective single agent for congestion because it suppresses the late-phase eosinophilic infiltrate. The AAO-HNS Allergic Rhinitis Clinical Practice Guideline and the ARIA framework place this first for persistent or moderate–severe disease. Counsel on correct aiming (away from the septum) to limit epistaxis.
• Second-generation oral H1 antihistamine (cetirizine, loratadine, fexofenadine): best for sneezing, rhinorrhea and pruritus; poorly CNS-penetrant, so preferred over first-generation agents.
• Allergen avoidance and saline irrigation as adjuncts.

Escalation — rhinitis

• Intranasal antihistamine (azelastine) added to intranasal steroid; intranasal ipratropium for pure rhinorrhea; leukotriene receptor antagonist (montelukast) mainly when asthma coexists — FDA carries a boxed warning for neuropsychiatric effects.
• Allergen immunotherapy (subcutaneous or sublingual tablet) is the only disease-modifying/definitive option; it induces regulatory T cells and IgG4 blocking antibodies and may prevent progression to asthma.
• Surgery (septoplasty, turbinate reduction, polypectomy) treats structural obstruction, not the allergy itself.

First-line and escalation — urticaria

• Second-generation H1 antihistamine at standard dose, then updosing up to fourfold per the Joint Task Force and international urticaria guidelines; add an H2 blocker or leukotriene antagonist as adjuncts.
• Omalizumab (anti-IgE) for antihistamine-refractory chronic spontaneous urticaria; cyclosporine thereafter.

Contraindicated/avoid

• Oral decongestants and topical oxymetazoline beyond ~3 days (rhinitis medicamentosa); avoid decongestants in uncontrolled hypertension.
• Chronic systemic corticosteroids for urticaria — short bursts only.
• First-generation antihistamines in the elderly (anticholinergic, falls) and intranasal steroid should not be withheld out of fear of adrenal suppression at standard doses.

Emergencies — recognise immediately

• Anaphylaxis: systemic mast cell degranulation causing vasodilation and capillary leak. Signalled by urticaria plus any of stridor, hoarseness, wheeze, vomiting, or hypotension. Treat with IM epinephrine before anything else.
• Laryngeal angioedema: submucosal edema of the supraglottis. Voice change, dysphagia, or tongue swelling is the warning sign; secure the airway early. If wheals are absent and the patient takes an ACE inhibitor or has family history, suspect bradykinin-mediated angioedema, which does not respond to epinephrine, antihistamines or steroids and needs C1-inhibitor concentrate or a bradykinin-pathway agent.
• Urticarial vasculitis: immune-complex (Type III) injury, not simple mast cell activation. Signalled by lesions lasting >24 hours, burning rather than itching, purpura and residual hyperpigmentation, with fever or arthralgia; biopsy shows leukocytoclastic vasculitis.

Complications of allergic rhinitis

• Asthma: shared Th2 inflammation along the united airway; new nocturnal cough or exertional wheeze in a rhinitis patient should prompt spirometry.
• Chronic rhinosinusitis and nasal polyposis: mucosal edema obstructs sinus ostia → impaired drainage; signalled by facial pressure, purulent discharge and anosmia.
• Otitis media with effusion and eustachian tube dysfunction: conductive hearing loss and speech delay in children.
• Sleep-disordered breathing from nasal obstruction → daytime fatigue, poor school performance; chronic mouth breathing contributes to adenoid facies and malocclusion.
• Allergic conjunctivitis and secondary bacterial sinusitis.

Treatment-related complications

• Intranasal corticosteroid: epistaxis and septal irritation from direct mucosal drug impaction; rare septal perforation with poor technique. Candidiasis and growth-velocity effects are far less an issue than with inhaled/oral steroids.
• Rhinitis medicamentosa: topical decongestant tachyphylaxis and rebound vasodilation — rapidly worsening congestion in a patient using an over-the-counter spray daily.
• First-generation antihistamines: H1 blockade in the CNS plus muscarinic antagonism → sedation, urinary retention, blurred vision, delirium in the elderly.
• Oral decongestants: alpha-agonism → hypertension, insomnia, palpitations.
• Systemic corticosteroid bursts: hyperglycemia, mood change, and with repeated courses adrenal suppression and bone loss.
• Allergen immunotherapy and skin testing: risk of systemic reaction — administer only where epinephrine and observation are available.

• **Nasal and palatal itching with paroxysmal sneezing and pale, boggy mucosa** is allergic rhinitis; a purulent unilateral discharge with fever is not. Eosinophils on nasal smear support allergy; neutrophils suggest infection.
• The single best next step in a patient with urticaria plus stridor, hypotension or vomiting is IM epinephrine — not diphenhydramine, not steroids, not an airway film. This is the most common exam trap in this topic.
• Individual wheals lasting under 24 hours and leaving no mark define urticaria. If a lesion persists beyond 24 hours, burns rather than itches, or leaves purpura or hyperpigmentation, think urticarial vasculitis and biopsy.
• Angioedema without wheals and without pruritus = bradykinin, not histamine. ACE inhibitor angioedema and hereditary C1-inhibitor deficiency (low C4 is the screening clue) do not respond to antihistamines, steroids or epinephrine.
• Intranasal corticosteroid is the most effective single agent for allergic rhinitis, especially for congestion, per the AAO-HNS guideline; second-generation antihistamines best relieve sneezing, itching and rhinorrhea. Choose the second-generation agent over diphenhydramine to avoid sedation and anticholinergic effects.
• Allergen immunotherapy is the only disease-modifying therapy and the answer when symptoms persist despite optimal pharmacotherapy or the patient wants to reduce medication dependence.
• Hold antihistamines 3–5 days before skin prick testing, or the test is falsely negative; use serum-specific IgE when skin testing is contraindicated (extensive dermatitis, active urticaria, inability to stop antihistamines).
• The classic association: aspirin-exacerbated respiratory disease — nasal polyps, asthma, and aspirin/NSAID sensitivity from COX-1 inhibition shunting arachidonate to leukotrienes. Also link allergic rhinitis to asthma and atopic dermatitis as the atopic march.
• Common distractor: a patient whose congestion worsened after weeks of over-the-counter oxymetazoline has rhinitis medicamentosa; the answer is to stop the spray and start an intranasal corticosteroid, not to increase the decongestant.