Allergic Rhinitis

An immunoglobulin E mediated inflammatory disorder of the nasal mucosa triggered by aeroallergen exposure, characterised by sneezing, rhinorrhoea, nasal itch and obstruction. It affects 10 to 30 percent of adults and up to 40 percent of children, and its importance in an ENT context lies in its role as a driver of rhinosinusitis, otitis media with effusion, adenotonsillar hypertrophy and poorly controlled asthma.

Pathophysiology

Sensitisation occurs when allergen presented by dendritic cells drives a T helper 2 response with interleukin 4 and 13, causing B cell class switching to allergen specific immunoglobulin E, which binds to mast cells and basophils.

• Early phase response, within minutes: allergen crosslinks surface immunoglobulin E, causing mast cell degranulation with release of preformed histamine, tryptase and newly synthesised leukotrienes and prostaglandins. Histamine acting on H1 receptors on sensory nerve endings produces itch and sneezing through a cholinergic reflex, and vascular effects produce rhinorrhoea and congestion. This phase responds to antihistamines.
• Late phase response, 4 to 12 hours later: interleukin 5 driven eosinophil recruitment with basophils, T cells and neutrophils, producing sustained obstruction and mucosal hyperreactivity. This phase is the source of chronic nasal blockage and responds to corticosteroid rather than antihistamine, which is why patients whose dominant symptom is congestion report antihistamines as ineffective.
• Priming: repeated exposure lowers the threshold for response, so late season symptoms occur at lower pollen counts than early season symptoms.

Classification

By duration:

• Intermittent: symptoms fewer than 4 days per week, or for less than 4 consecutive weeks.
• Persistent: symptoms 4 or more days per week and for more than 4 consecutive weeks.

By severity:

• Mild: no impairment of sleep, daily activities, sport, work or school, and symptoms not troublesome.
• Moderate to severe: one or more of these impaired.

Common allergens: tree, grass and weed pollens for seasonal disease; house dust mite, animal dander, cockroach and moulds for perennial disease; and occupational allergens including flour, latex and laboratory animals.

The united airway: allergic rhinitis and asthma are manifestations of one disease process in a continuous airway. Between 20 and 50 percent of patients with allergic rhinitis have asthma, and 80 percent or more of asthmatics have rhinitis. Treating the nose improves asthma control and reduces asthma related emergency attendance.

• Sneezing, often in paroxysms and characteristically on waking or on exposure.
• Clear watery rhinorrhoea.
• Nasal itch, which is the symptom most specific for an allergic mechanism, along with itching of the palate, eyes, ears and throat.
• Nasal obstruction, which is the symptom most commonly reported as dominant and most resistant to antihistamines.
• Postnasal drip, throat clearing and cough.
• Allergic conjunctivitis with itchy, watery, red eyes, present in up to 70 percent.
• Reduced smell, which is usually partial and fluctuating. Complete anosmia is unusual and suggests polyps.
• Fatigue, poor concentration, irritability and impaired school and work performance, which are substantially underestimated and result partly from disrupted sleep and partly from the inflammation itself.
• Snoring and sleep disordered breathing, particularly in children.

Physical signs

• Pale, boggy, bluish grey oedematous inferior turbinates with clear secretions.
• Allergic shiners: infraorbital darkening from venous congestion.
• Dennie Morgan lines, that is infraorbital creases.
• Transverse nasal crease from the allergic salute, an upward rubbing of the nose with the palm.
• Mouth breathing, and in long standing childhood disease the elongated facies, high arched palate, dental malocclusion and retrognathia of the adenoid facies.
• Cobblestoning of the posterior pharyngeal wall.
• Conjunctival injection, chemosis and papillae.
• Examine for eczema and auscultate the chest, since atopic comorbidity is the rule.

Clinical, supported by demonstration of specific immunoglobulin E where confirmation of the allergen changes management.

• History establishing the pattern, seasonality, triggers, home and occupational exposures, pets, and the relationship to specific environments. Improvement on holiday away from home suggests a domestic allergen; deterioration at work suggests occupational allergy.
• Anterior rhinoscopy and nasal endoscopy, the latter to exclude polyps, septal deviation, adenoid hypertrophy and other structural disease.
• Skin prick testing, which is the first line confirmatory test: rapid, sensitive and inexpensive. Antihistamines must be stopped 3 to 7 days beforehand, and tricyclic antidepressants for longer. It requires positive and negative controls and should not be performed in patients with severe uncontrolled asthma, extensive eczema or dermographism, or those unable to stop antihistamines.
• Serum allergen specific immunoglobulin E where skin testing is not feasible. It is unaffected by medication and safe in severe disease, but is more expensive and slightly less sensitive.
• Total immunoglobulin E alone is not useful for diagnosis.
• Nasal provocation testing in occupational allergy and in suspected local allergic rhinitis, where systemic testing is negative but nasal specific immunoglobulin E is produced locally. Local allergic rhinitis accounts for a meaningful proportion of patients previously labelled as non allergic.
• Computed tomography of the sinuses only where rhinosinusitis is suspected, not for uncomplicated rhinitis.
• Spirometry with reversibility in any patient with cough, wheeze or exertional breathlessness, since undiagnosed asthma is common in this population.
• Nasal cytology, showing eosinophilia, which is occasionally useful in distinguishing phenotypes.

Differential diagnosis and the discriminating feature

• Non allergic rhinitis with eosinophilia syndrome: perennial symptoms with nasal eosinophilia but negative allergy testing.
• Vasomotor rhinitis: obstruction and rhinorrhoea triggered by temperature change, odours, alcohol and spicy food, without itch or sneezing.
• Rhinitis medicamentosa: rebound obstruction from prolonged topical decongestant use.
• Drug induced rhinitis: from angiotensin converting enzyme inhibitors, beta blockers, alpha blockers, aspirin and nonsteroidal anti inflammatory drugs, and oral contraceptives.
• Hormonal rhinitis of pregnancy and hypothyroidism.
• Chronic rhinosinusitis with or without polyps.
• Cerebrospinal fluid rhinorrhoea, in unilateral clear watery discharge that increases on bending or straining, confirmed by beta 2 transferrin testing.
• Sinonasal malignancy and foreign body, in unilateral disease.
• Granulomatosis with polyangiitis, with crusting and septal perforation.

Stepwise, based on severity and persistence, with allergen avoidance as the foundation and immunotherapy as the only disease modifying option.

Allergen avoidance

• House dust mite: mattress and pillow encasings, hot washing of bedding at 60 degrees Celsius weekly, removal of carpets and soft toys from bedrooms, humidity reduction below 50 percent, and regular high efficiency particulate air vacuuming. Single measures are ineffective; only comprehensive combined strategies produce benefit.
• Pollen: keep windows closed during high count periods, avoid outdoor activity in early morning and evening when counts peak, shower and change clothes after being outdoors, use pollen filters in cars, and wear wraparound sunglasses.
• Pets: removal is the only fully effective measure, and allergen persists in the home for months afterwards. Where removal is refused, exclude the animal from the bedroom, wash it weekly, and use air filtration.
• Occupational allergens: engineering controls, respiratory protection, and where necessary redeployment, since continued exposure after sensitisation leads to occupational asthma.

Pharmacotherapy

Intranasal corticosteroid, the most effective single class for all symptoms including obstruction:

• Mometasone furoate 100 micrograms per nostril once daily in adults, 50 micrograms per nostril once daily in children aged 3 to 11 years.
• Fluticasone furoate 55 micrograms per nostril once daily in adults, 27.5 micrograms per nostril once daily from 2 years.
• Fluticasone propionate 100 micrograms per nostril once daily.
• Budesonide 128 to 256 micrograms daily.
• Onset of action is 6 to 12 hours with maximal effect at 2 weeks, so continuous rather than as needed use is essential and patients must be told this explicitly.
• Start 2 weeks before the expected pollen season in seasonal disease.
• Technique determines efficacy and adverse effects: use the opposite hand to the nostril, aim laterally toward the ipsilateral outer canthus and away from the septum, and do not sniff hard. Septal directed spraying causes epistaxis, crusting and rarely perforation.
• Adverse effects are local: epistaxis in around 5 to 10 percent, crusting and irritation. Growth effects in children with modern low bioavailability preparations at licensed doses are minimal, but monitor height in children on long term treatment, particularly those also using inhaled corticosteroid.

Oral antihistamines, second generation, for sneezing, itch and rhinorrhoea:

• Cetirizine 10 mg daily in adults, 5 mg daily aged 2 to 6 years.
• Loratadine 10 mg daily.
• Fexofenadine 120 to 180 mg daily, the least sedating.
• Desloratadine 5 mg daily, bilastine 20 mg daily, rupatadine 10 mg daily.
• Avoid first generation antihistamines such as chlorphenamine and promethazine, which cause sedation, impair cognitive and psychomotor performance including driving, disrupt sleep architecture, and have anticholinergic effects. Their continued prescription for allergic rhinitis is inappropriate.
• Antihistamines are relatively poor for nasal obstruction, which is the commonest reason patients report them as ineffective.

Intranasal antihistamines:

• Azelastine 137 micrograms per nostril twice daily, with a faster onset than oral agents at 15 minutes and superior efficacy for obstruction. Bitter taste limits adherence.
• Combination azelastine with fluticasone propionate in a single device is more effective than either alone and is the treatment of choice for moderate to severe disease inadequately controlled by intranasal steroid.

Additional agents:

• Leukotriene receptor antagonist montelukast 10 mg daily in adults, 5 mg in children 6 to 14 years, 4 mg in children 2 to 5 years. Less effective than intranasal corticosteroid, useful where asthma coexists. Counsel about neuropsychiatric adverse effects including nightmares, agitation and mood change.
• Intranasal ipratropium bromide 42 micrograms per nostril two to three times daily for refractory watery rhinorrhoea, which is its specific indication.
• Intranasal chromones such as sodium cromoglicate, which are safe including in pregnancy but require four times daily dosing and are less effective.
• Nasal saline irrigation as an adjunct.
• Topical decongestants for no more than 5 days, to open the nose sufficiently for steroid to penetrate at the start of treatment.
• Oral corticosteroid: prednisolone 20 to 30 mg daily for 5 to 7 days, reserved for severe uncontrolled symptoms or an important event, and no more than once or twice yearly. Depot intramuscular corticosteroid should not be used, given unpredictable prolonged systemic exposure without added benefit.
• Ocular symptoms: topical antihistamine such as olopatadine or ketotifen drops, or sodium cromoglicate.

Allergen immunotherapy

The only treatment that modifies the natural history, with benefit persisting for years after completion and evidence that it prevents new sensitisations and reduces progression from rhinitis to asthma in children.

• Indications: moderate to severe symptoms inadequately controlled by optimal pharmacotherapy, a clear single or dominant allergen with corresponding sensitisation, unacceptable medication adverse effects, and patient preference to avoid long term medication.
• Subcutaneous immunotherapy: weekly build up over 3 to 4 months then monthly maintenance for 3 to 5 years. Must be given in a facility with resuscitation equipment and a 30 minute observation period, given the risk of systemic reactions and anaphylaxis.
• Sublingual immunotherapy as tablets or drops, taken daily at home after a supervised first dose, for 3 years. Safer, with local oral itch and swelling as the main adverse effects, and preferred in most settings for grass pollen, house dust mite and ragweed.
• Absolute contraindications: severe or uncontrolled asthma, which is the principal risk factor for fatal reactions; active autoimmune disease; malignancy; and beta blocker therapy, which impairs the response to adrenaline. Pregnancy is a contraindication to initiation but maintenance may be continued.
• Assess asthma control before every injection, and postpone if peak flow is reduced or the patient is unwell.

Special populations

• Pregnancy: nasal saline and sodium cromoglicate first; budesonide is the intranasal corticosteroid with the longest safety record; loratadine and cetirizine are the preferred oral antihistamines. Avoid oral decongestants, particularly in the first trimester.
• Children: intranasal corticosteroids at licensed paediatric doses with height monitoring, second generation antihistamines, and consideration of immunotherapy given its disease modifying effect. Address adenoid hypertrophy where obstruction is severe.
• Elderly: avoid first generation antihistamines and oral decongestants given anticholinergic burden, falls and cardiovascular risk.
• Athletes: check preparations against anti doping regulations, since oral pseudoephedrine is restricted above certain urinary thresholds.

Follow up

Review at 4 to 6 weeks after initiating therapy, checking adherence and, critically, nasal spray technique, which is the commonest reason for apparent treatment failure. Escalate through the steps rather than abandoning treatment. Reassess for coexisting rhinosinusitis, polyps or structural obstruction in patients who fail to respond to combination therapy.