Chronic Rhinosinusitis

Inflammation of the nose and paranasal sinuses lasting 12 weeks or longer, defined by two or more symptoms of which one must be nasal blockage or nasal discharge, plus either facial pain or pressure or reduction of smell, together with objective evidence of inflammation on endoscopy or computed tomography. The objective requirement is essential, since symptom based diagnosis alone misclassifies a large proportion of patients who actually have migraine or rhinitis.

Phenotypes

• Chronic rhinosinusitis without nasal polyps, historically considered predominantly neutrophilic with a mixed inflammatory profile.
• Chronic rhinosinusitis with nasal polyps, historically considered eosinophilic and type 2 driven, though considerable overlap exists.
• The current framework favours endotyping by inflammatory pathway rather than phenotype by polyp status, because the endotype determines response to biologic therapy.

Endotypes

• Type 2 inflammation, characterised by interleukin 4, 5 and 13, eosinophils, mast cells, immunoglobulin E and periostin. It predominates in Western populations with polyps, associates with asthma, aspirin exacerbated respiratory disease and severe disease, and is the target of biologic therapy. Tissue eosinophil counts above 10 per high power field and blood eosinophils above 250 to 300 cells per microlitre are practical markers.
• Non type 2 inflammation with type 1 or type 3 patterns, characterised by interferon gamma, interleukin 17 and neutrophils, more common in Asian populations and in cystic fibrosis, and less responsive to corticosteroids and biologics.

Contributing mechanisms

• Epithelial barrier dysfunction with reduced tight junction integrity and impaired innate defence.
• Impaired mucociliary clearance.
• Biofilm formation on sinus mucosa, which explains culture negativity and poor antibiotic response.
• Staphylococcus aureus superantigen driving polyclonal immunoglobulin E production and local eosinophilia.
• Fungal colonisation with an inflammatory response, in allergic fungal rhinosinusitis.
• Anatomical obstruction of drainage pathways.

Associated conditions requiring identification

Asthma, present in up to 65 percent of patients with polyps; aspirin exacerbated respiratory disease, comprising asthma, polyps and nonsteroidal anti inflammatory drug sensitivity, which affects around 10 percent of polyp patients and predicts recurrence; allergic rhinitis; cystic fibrosis, which should be considered in any child with nasal polyps; primary ciliary dyskinesia; immunodeficiency including common variable immunodeficiency and specific antibody deficiency; eosinophilic granulomatosis with polyangiitis; and granulomatosis with polyangiitis.

• Nasal obstruction, which is usually the dominant and most persistent symptom, and is bilateral in most inflammatory disease.
• Anterior or posterior nasal discharge, mucoid to mucopurulent, with postnasal drip and throat clearing.
• Facial pressure and fullness rather than severe pain. Severe unilateral pain is not typical and demands exclusion of another diagnosis.
• Hyposmia or anosmia, which is more marked and more persistent in polyp disease and which is often the symptom patients find most distressing. Ask about it specifically, since patients frequently do not volunteer it.
• Reduced taste as a consequence of smell loss.
• Cough, worse at night, and sore throat from postnasal secretions.
• Sleep disturbance, fatigue and reduced productivity, which are major contributors to the quality of life impact.
• Ear fullness and Eustachian tube dysfunction.
• Asthma exacerbations, which often improve when the sinus disease is treated.

Red flags demanding urgent investigation

• Strictly unilateral symptoms, which raise the possibility of malignancy, inverted papilloma, fungal ball or foreign body.
• Bloody discharge or recurrent unilateral epistaxis.
• Orbital signs: proptosis, diplopia, visual disturbance, epiphora.
• Facial numbness, particularly in the infraorbital distribution.
• Severe frontal headache and frontal swelling.
• Neurological signs, cerebrospinal fluid rhinorrhoea.
• Crusting with septal perforation and saddle nose, indicating vasculitis or cocaine use.
• Systemic features suggesting vasculitis: haemoptysis, haematuria, mononeuritis multiplex, rash.

Examination

• Anterior rhinoscopy, then rigid or flexible nasal endoscopy after decongestion, which is essential for diagnosis. Assess the middle meatus, polyp grade, mucosal oedema, discharge, crusting, septal deviation and the postnasal space.
• Polyp grading from 0 to 3 per side: 0 none, 1 confined to the middle meatus, 2 below the middle turbinate but not the inferior border, 3 reaching or beyond the inferior border of the inferior turbinate.
• Assess smell formally.
• Examine the chest, and examine for systemic disease features.

• Nasal endoscopy demonstrating polyps, mucopurulent discharge from the middle meatus, or mucosal oedema and obstruction in the middle meatus. This is required to satisfy the diagnostic definition.
• Non contrast computed tomography of the sinuses in the coronal, axial and sagittal planes, which confirms mucosal disease, defines the extent, and provides essential anatomical detail before surgery. Score with the Lund Mackay system, allocating 0 for no opacification, 1 for partial and 2 for complete opacification of each of the maxillary, anterior ethmoid, posterior ethmoid, sphenoid and frontal sinuses, plus 0 or 2 for the osteomeatal complex, giving a maximum of 24. A score of 4 or more is generally regarded as abnormal.
• Critical anatomical features to identify on the preoperative scan: the depth and asymmetry of the olfactory fossa using the Keros classification, where Keros type III with a depth of 8 to 16 mm carries the highest risk of skull base injury; dehiscence of the lamina papyracea; the position and dehiscence of the internal carotid artery and optic nerve in the sphenoid, particularly with an Onodi cell; the anterior ethmoidal artery position and whether it hangs free in the ethmoid cavity; and the frontal recess anatomy.
• Magnetic resonance imaging where malignancy, fungal disease, an encephalocele or intracranial extension is suspected. It distinguishes retained secretions from soft tissue, which computed tomography cannot.
• Objective smell testing, using a validated instrument, which quantifies a symptom patients report unreliably.
• Endoscopically guided middle meatal culture in treatment failure and in immunocompromised patients.
• Skin prick testing or specific immunoglobulin E for aeroallergens.
• Blood eosinophil count and total immunoglobulin E, which contribute to endotyping and to biologic eligibility.
• Sweat chloride testing and cystic fibrosis genetics in children with polyps and in adults with bronchiectasis or male infertility.
• Nasal nitric oxide screening and ciliary brush biopsy for primary ciliary dyskinesia, with nasal nitric oxide characteristically very low.
• Immunoglobulin G, A and M with subclasses, and specific antibody responses to pneumococcal and tetanus vaccination, in recurrent disease.
• Antineutrophil cytoplasmic antibody, urinalysis and renal function where vasculitis is suspected, with biopsy where indicated.
• Aspirin challenge under supervision where aspirin exacerbated respiratory disease is suspected and desensitisation is contemplated.
• Symptom scoring with the Sino Nasal Outcome Test 22, which quantifies disease burden and tracks response. A score above 20 indicates significant impact and a change of 8.9 points is the minimal clinically important difference.

Differential diagnosis

• Migraine and midfacial segment pain, which account for a large proportion of referrals for facial pain with a normal endoscopy and scan. These do not respond to sinus surgery, and operating on them produces persistent pain and a dissatisfied patient.
• Allergic and non allergic rhinitis without sinus involvement.
• Sinonasal malignancy and inverted papilloma, in unilateral disease.
• Fungal ball, in unilateral opacification with calcification.
• Cerebrospinal fluid rhinorrhoea, in unilateral clear watery discharge.
• Granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis.

Treatment is medical first, with surgery reserved for failure of appropriate medical therapy, and with long term maintenance therapy essential in every case, since surgery does not cure the underlying inflammation.

Foundation therapy for all patients

• Nasal saline irrigation with large volume, low pressure isotonic or hypertonic solution, 240 mL per nostril once or twice daily. It improves symptoms, mechanically removes crusts and inflammatory mediators, and improves the penetration of subsequent topical steroid. Instruct patients to use boiled and cooled or distilled water, since tap water carries a small risk of amoebic infection.
• Intranasal corticosteroid, used continuously and long term: mometasone furoate 100 to 200 micrograms per nostril once or twice daily; fluticasone propionate 100 micrograms per nostril twice daily; or fluticasone furoate 55 micrograms per nostril once daily. Emphasise that benefit takes weeks and that intermittent use fails.
• Corticosteroid delivered by irrigation gives far better sinus distribution than a spray, particularly after surgery. Budesonide respules 0.5 mg in 240 mL of saline irrigation once or twice daily is widely used, with careful counselling about systemic absorption in prolonged use.
• Smoking cessation, which is non negotiable, since smoking worsens outcomes and increases surgical failure.
• Treat coexisting allergic rhinitis and asthma optimally.

Chronic rhinosinusitis without polyps, additional therapy

• Long term low dose macrolide, exploiting anti inflammatory rather than antibacterial effects: clarithromycin 250 mg daily or azithromycin 250 mg three times weekly for 12 weeks. Most useful in patients with normal or low immunoglobulin E and non type 2 disease. Obtain an electrocardiogram before starting where there is cardiac risk, given QT prolongation, and review interactions with statins, warfarin and calcium channel blockers.
• Culture directed antibiotics for acute exacerbations, using co amoxiclav 625 mg three times daily or a culture directed agent for 7 to 14 days.
• Short courses of oral corticosteroid have less evidence in the absence of polyps and are used sparingly.

Chronic rhinosinusitis with polyps, additional therapy

• Oral corticosteroid: prednisolone 0.5 mg/kg daily, typically 25 to 50 mg, for 5 to 10 days, or a tapering course over 2 to 3 weeks. This reliably shrinks polyps and restores smell, but the effect lasts weeks to a few months. Limit courses to no more than two per year given the cumulative risks of avascular necrosis, osteoporosis, diabetes, cataract, glaucoma, hypertension and mood disturbance. Repeated courses are an indication to escalate to surgery or biologic therapy rather than to continue prescribing steroid.
• Aspirin desensitisation in aspirin exacerbated respiratory disease, with maintenance aspirin 650 mg twice daily or lower maintenance doses, which reduces polyp recurrence and improves asthma control. It requires supervised challenge in a specialist unit and is contraindicated in peptic ulceration and bleeding disorders.
• Leukotriene receptor antagonists such as montelukast 10 mg daily have modest benefit, principally in aspirin exacerbated disease. Counsel about neuropsychiatric adverse effects.

Biologic therapy for severe type 2 disease

Indicated for severe chronic rhinosinusitis with nasal polyps, usually after surgery or where surgery is contraindicated, in patients with evidence of type 2 inflammation, need for systemic steroid or contraindication to it, significantly impaired quality of life, smell loss and comorbid asthma.

• Dupilumab, an interleukin 4 receptor alpha antagonist, 300 mg subcutaneously every 2 weeks. It produces the largest improvements in polyp score, obstruction and smell, and treats coexisting asthma and atopic dermatitis. Monitor for transient blood eosinophilia and conjunctivitis.
• Omalizumab, an anti immunoglobulin E antibody, dosed according to weight and total immunoglobulin E, every 2 to 4 weeks.
• Mepolizumab, an anti interleukin 5 antibody, 100 mg subcutaneously every 4 weeks.
• Assess response at 4 to 6 months against defined criteria including polyp size, smell, symptom score, steroid requirement and asthma control, and discontinue if there is no meaningful response.

Surgery

Indications: failure of an adequate trial of appropriate medical therapy, generally 8 to 12 weeks of topical steroid and saline with a course of oral steroid or antibiotic as appropriate; complications; mucocele; fungal ball; suspicion of neoplasm requiring biopsy; and to create access for topical therapy in severe polyp disease.

• Functional endoscopic sinus surgery aims to restore ventilation and mucociliary drainage while preserving mucosa. The extent is tailored, from uncinectomy and maxillary antrostomy to complete ethmoidectomy, sphenoidotomy and frontal recess surgery.
• Extended approaches for severe polyp disease, including the endoscopic modified Lothrop or Draf III procedure for frontal disease, and reboot or full house surgery removing diseased mucosa, which reduce recurrence in severe eosinophilic disease at the cost of greater crusting.
• Image guidance navigation for revision surgery, distorted anatomy, frontal and sphenoid disease, and skull base or orbital proximity.
• Address the septum and turbinates where they obstruct access or airflow.

Operative complications to anticipate and consent for

• Orbital: injury to the lamina papyracea with orbital fat prolapse, medial rectus injury causing diplopia, and retrobulbar haematoma from anterior ethmoidal artery injury. Retrobulbar haematoma with proptosis, a tense orbit, a fixed dilated pupil and rising intraocular pressure requires immediate lateral canthotomy and cantholysis at the bedside, orbital massage and decompression, and urgent ophthalmology involvement. Delay of more than 60 to 90 minutes risks permanent blindness.
• Optic nerve injury, particularly with an Onodi cell.
• Skull base injury with cerebrospinal fluid leak, most often at the lateral lamella of the cribriform plate, requiring immediate multilayer repair.
• Haemorrhage, including sphenopalatine and anterior ethmoidal artery bleeding, and rarely internal carotid injury in the sphenoid, which requires immediate packing, angiography and endovascular management.
• Adhesions, middle turbinate lateralisation, ostial stenosis and recurrence.
• Anosmia, and empty nose syndrome after excessive turbinate resection.

Postoperative care, which determines the long term outcome

• Saline irrigation from day 1 or 2, high volume, at least twice daily.
• Resume topical corticosteroid at 1 to 2 weeks, ideally as steroid irrigation for better distribution.
• Endoscopic debridement at 1 to 2 weeks and again as required, removing clot, crust and early adhesions.
• Postoperative oral steroid in eosinophilic polyp disease to reduce early recurrence.
• Emphasise repeatedly that surgery does not cure the disease and that lifelong topical treatment is required. Failure to convey this is the commonest cause of recurrence and of patient dissatisfaction.

Follow up

Review with endoscopy at 2 weeks, 6 weeks, 3 months and then at intervals determined by disease severity. Track symptom scores. Recurrence rates in eosinophilic polyp disease approach 40 percent at 5 years, and revision surgery is required in around 20 percent, which should be discussed at the outset.