Step 1 of 8
Define the Disease Domain
Classify the presentation into one of seven ENT disease domain groups — type-2 rhinology, united airway, aerodigestive, H&N oncology, otologic frontiers, laryngotracheal/airway, orbital/salivary/systemic interfaces.
Biologic therapy in ENT is decided across seven disease-domain groups:
A. Type-2 rhinology — CRSwNP, AERD/N-ERD, allergic fungal rhinosinusitis (AFRS), refractory allergic rhinitis with asthma/CRSwNP overlap.
B. United airway disease — severe asthma with CRSwNP, asthma with allergic rhinitis, asthma with eosinophilic CRS, asthma with EGPA.
C. Aerodigestive disease — eosinophilic esophagitis (EoE) presenting with dysphagia, food sticking, globus, or refractory "laryngopharyngeal reflux".
D. Head and neck oncology — recurrent or metastatic HNSCC, platinum-refractory HNSCC, cetuximab-eligible locoregional disease.
E. Otologic frontiers — eosinophilic otitis media, autoimmune inner-ear disease, genetic SNHL (especially OTOF) and emerging gene-therapy frontiers.
F. Laryngotracheal / airway frontiers — recurrent respiratory papillomatosis (RRP), GPA-related subglottic stenosis, IgG4-related airway disease, relapsing polychondritis, inflammatory subglottic stenosis.
G. Orbital / salivary / systemic ENT interfaces — thyroid eye disease, Sjögren-related salivary disease, IgG4-related salivary/orbital disease, ANCA vasculitis affecting ENT.
The chapter's master flowchart routes from this domain assignment through diagnostic confirmation, conventional-therapy optimisation, severity/eligibility gating, mechanism selection, safety screening, treatment initiation, and 3-6 month reassessment.
- Type-2 rhinology: CRSwNP · AERD/N-ERD · AFRS · refractory AR
- United airway disease: severe asthma ± CRSwNP/AR/eCRS/EGPA
- Aerodigestive disease: eosinophilic esophagitis
- Head & neck oncology: R/M HNSCC · platinum-refractory · cetuximab-eligible
- Otologic frontiers: eosinophilic OM · autoimmune inner-ear · OTOF gene therapy
- Laryngotracheal frontiers: RRP · GPA subglottic stenosis · IgG4-RD · relapsing polychondritis
- Orbital/salivary/systemic: TED · Sjögren · IgG4 salivary/orbital · ANCA vasculitis
Key statistics
ENT disease domains
7 groups · 14 specific entities
Each domain has a domain-specific algorithm; many overlap (e.g. asthma + CRSwNP + AERD).
★ High-yield pearls (chapter-wide)
- Use biologics in ENT only when diagnosis is objective, conventional therapy is optimised, disease is severe/recurrent/steroid-dependent/function-threatening, a biologically plausible target is present, safety screening is complete, and response metrics + stopping rules are predefined.
- The strongest ENT biologic evidence lies in CRSwNP, severe asthma overlap, EoE, EGPA, HNSCC, ANCA vasculitis, thyroid eye disease, and RRP — frontiers (AFRS, eosinophilic OM, IgG4-related disease, autoimmune salivary disease, regenerative otology) are still emerging.
- United-airway disease is the rule, not the exception — most CRSwNP patients have asthma, and most severe-asthma patients have rhinitis; biologic choice should reflect the dominant phenotype across the whole airway.
- Dupilumab anchors smell loss, asthma, eczema, and EoE overlap; omalizumab the IgE-driven allergic phenotype; mepolizumab/benralizumab the eosinophilic phenotype with EGPA overlap; tezepelumab the broad upstream type-2 mixed-phenotype patient.
- Always plan the stop/switch criteria BEFORE starting a biologic — response windows are 16-24 weeks for CRSwNP, 3-6 months for airway/allergy disease, and imaging-cycle defined for oncology.
- Pembrolizumab ± chemotherapy is first-line for recurrent/metastatic HNSCC with PD-L1 CPS ≥1 (KEYNOTE-048); nivolumab is the platinum-refractory option (CheckMate 141); cetuximab + RT improves outcomes vs RT alone in locoregionally advanced disease (Bonner).
- Rituximab is non-inferior to cyclophosphamide for induction in severe ANCA-associated vasculitis (RAVE) — and is the steroid-sparing option of choice in IgG4-related disease and refractory primary Sjögren syndrome.
- Teprotumumab is approved for active moderate-to-severe thyroid eye disease and improves proptosis, clinical activity score, diplopia, and quality of life — hearing must be monitored for ototoxicity.
- Intralesional bevacizumab reduces recurrent respiratory papillomatosis disease burden and surgical frequency — systemic bevacizumab is reserved for severe diffuse or distal pulmonary disease.
- The safety screen is universal: hypersensitivity, helminth exposure (for type-2 biologics), TB/HBV/HCV (for immunosuppressives), pregnancy planning, live-vaccine timing, and perioperative coordination — non-negotiable for every starter.
Evidence base
3 sources- HIGH
Fokkens WJ et al. · Rhinology · 2023International CPG / consensusPMID 36999780
EPOS/EUFOREA 2023 — most practical CRSwNP biologic indication and response framework; anchors the domain-definition step for type-2 rhinology.
- HIGH
Grayson PC et al. · Annals of the Rheumatic Diseases · 2022Classification criteriaPMID 35110334
EGPA classification criteria — operationalises the diagnosis of EGPA at the domain boundary between united-airway disease (asthma + CRS + eosinophilia) and systemic vasculitis.
- HIGH
Khosroshahi A et al. · Arthritis & Rheumatology · 2015International consensusPMID 25809420
International consensus on IgG4-RD diagnosis and treatment — anchors the domain definition for the IgG4-related ENT presentations (salivary, orbital, sinonasal, skull base, laryngotracheal).
Decision tree
The triage screen is the first gate. Classification routes the stable patient to one of the aetiology-keyed pathways below. Cross-cut cards capture the chapter's must-not-miss rules.