Allergic Rhinitis Immunotherapy: Immune Modulation with Allergy Shots

Allergic rhinitis is an IgE-mediated type 1 hypersensitivity reaction in nasal mucosa following allergen exposure. ARIA classification: intermittent (<4 days/week or <4 weeks) vs persistent (≥4 days/week or ≥4 weeks); mild vs moderate-severe (QoL impact).

Global burden: 10-30% prevalence worldwide, similar in Turkey (rising in Istanbul and large cities with pollution + industrialisation). Economic burden: workplace presenteeism, school underperformance, comorbid asthma (allergic asthma has 80% allergic rhinitis — "one airway, one disease").

Classic allergens: (1) Pollens — tree (olive, oak, birch, maple — March-May), grass (timothy, ragweed — June-September), weed (mugwort, nettle, thyme — late summer); (2) House-dust mites — Dermatophagoides pteronyssinus + farinae (year-round, commonest indoor); (3) Pet dander — cat (Fel d 1 — high airborne persistence), dog (Can f 1); (4) Cockroach — urban indoor; (5) Moulds — Alternaria (outdoor), Aspergillus (indoor), Cladosporium; (6) Occupational — flour (baker), latex (healthcare), grain dust.

Diagnostic approach: detailed history (symptoms, season, triggers, family allergy, comorbid asthma/eczema), nasal endoscopy (oedematous, pale mucosa, exclude polyps), skin prick test (SPT — clinical gold standard, rapid, multiple allergens same session), specific IgE (blood — ImmunoCAP, when SPT not feasible or confirmation), nasal provocation (special). Total IgE generally not useful — neither confirms nor excludes.

Treatment steps (ARIA guideline): (1) Allergen avoidance — mite avoidance (encasings, hot wash, less carpet, humidity control), pollen seasons closed windows + air purifier, pet removal (hard to apply); (2) Intranasal corticosteroid — first-line medical (mometasone furoate, fluticasone furoate, beclomethasone); (3) Second-generation antihistamine — oral (cetirizine, fexofenadine, loratadine, bilastine) or nasal (azelastine, olopatadine); (4) Combination — antihistamine + intranasal steroid (azelastine/fluticasone combo); (5) Leukotriene receptor antagonist (montelukast) — with asthma; (6) Topical nasal anticholinergic (ipratropium) — refractory rhinorrhoea; (7) Oral corticosteroid — short course in exacerbation (generally not advised); (8) Allergen-specific immunotherapy (AIT) — moderate-severe rhinitis, medication-uncontrolled, marked QoL impact; (9) Biologic — omalizumab (anti-IgE — severe with asthma).

Unique feature of AIT: only disease-modifying therapy. Other medications give symptom control (while in use); AIT modulates immunity, benefit persists after treatment ends (5-10 year benefit observable). Additionally prevents asthma development (early AIT in allergic rhinitis children reduces asthma development risk by 50% — long-term benefit).

WAO (World Allergy Organization) + EAACI (European Academy of Allergy and Clinical Immunology) joint recommendation: moderate-severe allergic rhinitis, inadequate response to medication, 3+ months symptoms, QoL impact, IgE-mediated (clinical + test positive) — AIT clearly indicated.

Turkish Allergy and Clinical Immunology Society (TURKADID) + Turkish ENT Society (TKBB) guidelines similar — AIT requires certified allergy specialist or ENT physician, standard clinic setting (emergency equipment + physician). Related service: our general ENT services.

SCIT — subcutaneous immunotherapy (classic allergy shots) is the highest-evidence AIT route since 1911. Subcutaneous injection on upper arm. Standardised allergen extracts used (in Turkey from manufacturers such as Stallergenes, ALK-Abello, Allergopharma).

Phase 1 — build-up: start low concentration, weekly escalating dose. Classic protocol 12-16 weeks (12-16 injections). Cluster (accelerated): same-day multiple injections reach maintenance in 4-8 weeks. Rush: hospitalised/semi-hospitalised, reach maintenance in days — high systemic reaction risk, not first-line.

Phase 2 — maintenance: once at maintenance dose, monthly injection (4-6 week intervals, by clinical judgement). 3-5 years duration (typically 4). Systemic reaction risk lower at maintenance (body acclimatised).

Injection procedure: lateral upper arm (posterior to deltoid), subcutaneous, up to 1 mL. Sterile technique. Pre-injection: symptoms reviewed (URI, asthma control, last-dose local/systemic reaction — dose adjustment), blood pressure + pulse, peak flow (asthmatic). Post-injection: 30-minute clinic observation MANDATORY — systemic reactions (anaphylaxis) typically within 30 minutes.

Dose adjustment: local reaction (>5 cm swelling at site, widespread urticaria — reduce next dose); systemic reaction (dyspnoea, hypotension, generalised urticaria — protocol change, allergist review); intercurrent illness (URI, fever — defer); excessive interval (>4-6 weeks — may need restart).

Multi-allergen mix: SCIT advantage allows multiple allergens in same injection (e.g. pollen + mite, or cat + mite). Each clinically meaningful allergen must be test-positive + history-compatible. Maximum 3-5 allergens per vial recommended (efficacy diluted otherwise).

Systemic reaction — anaphylaxis management: SCIT clinics must have emergency equipment. Epinephrine 0.3-0.5 mg IM (lateral thigh), oxygen, IV fluid, corticosteroid + antihistamine (secondary). Hospitalise. Anaphylaxis risk 0.1-0.6% (especially build-up); fatal very rare (~1/2.5 million injections). Patient keeps adrenaline autoinjector (EpiPen) as backup at home.

Efficacy tracking: 6-12 months significant symptom + medication reduction; 1-2 years marked improvement; 3-5 years optimum. Tools: VAS (visual analogue scale), RQLQ (Rhinoconjunctivitis Quality of Life Questionnaire), medication score. Effective: ≥30% symptom reduction + ≥50% medication reduction.

Non-responder evaluation: ~20% don't see expected benefit. Reasons: wrong allergen choice, adherence issues, comorbid disease (nasal polyps, chronic rhinosinusitis), inadequate maintenance dose, smoking/tobacco, incomplete environmental control (pet still home).

Turkish SCIT practice: allergist or ENT physician sets indication, custom or off-the-shelf extract ordered, injection visits planned. SGK supports certain indications (allergic asthma + allergic rhinitis).

SLIT — sublingual immunotherapy (under-tongue), used in Europe since the 1980s and widely after 2000. Tablet (drops or fast-dissolving) placed under tongue, held 1-2 minutes, then swallowed.

Product forms: (1) Lyophilised tablet (e.g. Grazax — Phleum grass pollen; Acarizax — house-dust mite; Itulazax — birch pollen) — EU licensed, used worldwide; (2) Drops (glycerolated solution) — clinical custom formulation; (3) Multi-allergen drops — less common in Turkey vs SCIT; (4) US FDA-approved tablets (Oralair, Grastek, Ragwitek, Odactra).

Indications: allergic rhinitis (moderate-severe, medication-uncontrolled), allergic conjunctivitis, allergic asthma (mild-moderate, controlled), children >5 + adults. Paediatric adherence is SLIT's special advantage (no fear of injection).

Dose schedule — tablet: first dose under clinic observation (30 minutes — rare systemic reactions). Then daily home tablet (morning). Maintenance — 3 years recommended (Acarizax, Grazax). For pollen allergy 4 months pre-season + whole season + 1 month after (8 month treatment); for mite year-round continuous.

Drops protocol: build-up daily increasing drops (e.g. 1 drop week 1, 2 week 2, 4 week 3...) until maintenance (10-15 drops). Then daily or alternate-day continuation. 3-5 year course.

SLIT side effects: local oral reaction very common (first 1-2 weeks) — tongue/lip itch, mild swelling, oral irritation. Usually subsides within 2-4 weeks. Systemic reactions rare (0.05-0.1%) — anaphylaxis very uncommon. No deaths reported in literature across millions of doses. Hence SLIT is home-applicable (except first dose).

SLIT vs SCIT comparison: (1) Efficacy — similar by meta-analysis; SCIT slightly leads in some studies (especially multi-allergen); (2) Safety — SLIT much safer (rare systemic reactions); (3) Adherence — daily SLIT tablet hard (first-year drop-out 30%); SCIT clinic visit hard; (4) Cost — SLIT tablets expensive; SCIT injection cheap but clinic visits add burden; (5) Indication breadth — SCIT multi-allergen, SLIT typically single; (6) Paediatric — SLIT preferred (no injection fear).

Modern developments: (1) Recombinant allergen vaccines — pure protein, safer + specific (clinical development); (2) Hypoallergenic modifications (allergoids) — fewer side effects, allowing higher dose; (3) Adjuvant formulations — TLR agonists, MPL (monophosphoryl lipid A) — enhance response; (4) Intralymphatic immunotherapy (ILIT) — direct lymph node injection, fewer doses in shorter time; (5) Epicutaneous immunotherapy (EPIT) — patch, in research for paediatric food allergy; (6) Peptide immunotherapy — T-cell epitopes, IgE-independent, safety advantage.

Biologic integration: omalizumab (anti-IgE) before or with AIT — reduces systemic reaction risk, enhances AIT efficacy. Severe allergic asthma or high-IgE patients — combinations in clinical research. Dupilumab (anti-IL-4/13) in atopic dermatitis + asthma; not in allergic rhinitis primary but considered in comorbid cases.

COVID-19 and AIT: pandemic increased SCIT clinic visit risk; SLIT home advantage. Continuity matters — interruption risks relapse. Modern recommendation: continue AIT (with telehealth consults), including after vaccines. For the related clinical reference, see sinusitis page.

Typical patient journey: ENT or allergy specialist examination (allergic rhinitis diagnosis) → 1-3 month medical treatment trial (intranasal steroid + antihistamine) → insufficient response or marked QoL impact → allergen testing (SPT or specific IgE) → AIT indication evaluation → SCIT vs SLIT choice (patient preference + suitability + available allergen form) → counselling + consent → start treatment → regular follow-up + outcome assessment → 3-5 years treatment → termination.

Counselling + consent: as AIT is an immune modulation procedure, medical consent is required. Patient must understand: duration (3-5 years — long commitment), injection/tablet frequency, expected benefit (significant improvement 1-2 years; optimal 3-5 years), side effects (local vs systemic, rare anaphylaxis possible), discontinuation risk (relapse), cost, alternatives (continued medical treatment, nasal surgery — turbinate reduction, polyp surgery).

Follow-up intervals: (1) Build-up — weekly (each injection physician/nurse supervised); (2) Maintenance — monthly injection (SCIT) or daily tablet (SLIT) + 3-monthly clinic; (3) Annual review — symptom questionnaire, medication use, side-effect check, dose/route change if needed; (4) End of treatment — closing visit, long-term outcome questionnaire.

Efficacy evidence — meta-analyses: SCIT grass pollen rhinitis — 30-40% symptom reduction + 50%+ medication reduction. SLIT tablets (Grazax, Acarizax) — similar reductions in randomised trials. Asthma prevention: early AIT in children with allergic rhinitis — reduces asthma development risk in following 5-10 years by 50% (PAT — Preventive Allergy Treatment study).

Paediatric AIT: standard from age 5; performed when trigger conditions + allergen panel suitable. Children gain asthma-prevention advantage + long-term (into adult life) benefit. Adherence easier (family motivation).

AIT in pregnancy: NEW initiation NOT recommended (systemic reaction risk + unknown fetal effect). Maintenance can continue if started pre-pregnancy (allergy + obstetrics consult). Postpartum + lactation — AIT can continue.

Elderly (>65) AIT: careful evaluation — comorbidities (cardiovascular, beta-blocker), risk-benefit. Mild-moderate cases sometimes prefer alternatives (continued medical).

Cost-effectiveness: AIT expensive first 3-5 years (treatment + clinic visits); after 5-10 years QoL + reduced medications/visits make it cost-effective (NICE + European economic analyses).

Turkish SGK and AIT: grass pollen, house-dust mite, cat allergy with standardised extracts — AIT under SGK coverage with conditions (allergic asthma + allergic rhinitis indication, allergy specialist report, periodic follow-up). Wider coverage with private health insurance.

Patient motivation and adherence: 3-5 years is a long commitment — patient knowledge + expectation management critical. First 3-6 months may show no obvious effect (inform patient). Ongoing family/social support + regular clinic motivation helpful.

Future: peptide + recombinant + nanotechnology vaccines (safer, shorter), adjuvants (potent Treg induction, fast effect), biologic combinations (anti-IgE + AIT), epicutaneous + intralymphatic innovations, AI-based personalised treatment planning (per patient genetics + immune profile). The next 10-15 years will bring more personalised, shorter, safer AIT. Related reading: our Istanbul ENT services.