Rhinosinusitis + Nasal Polyps

What x3 treatments would you use for CRSwNP in a 15 year old male?

1. Intranasal saline rinses 

2. Intranasal corticosteroid spray x1-3 months 

3. ± PO prednisone = if refractory Sx or can’t use INCS

   1. 40mg PO OD x 5 days

   2. THEN 20mg PO OD x5 days 

4. Functional Endoscopic Sinus Surgery (FESS) 

5. Biologic Trial (D.O.M) studied… Dupixent off label, approved for 18yo+ with CRSwNP 

6. Consider LTRA if ASA sensitivity

7. ASA Desesnsitization if AERD!! 

DDx for Nasal Polyposis

CRSwNP

AFRS

ABPA

AERD

Cystic Fibrosis 

Primary Ciliary Dyskinesia 

Malignancy

EGPA

CRSwNP - Age of approval for biologics studied.

D.O.M - All 18yo+

Dupilumab (anti-IL4Ralpha) = 18yo+ - MOST STUDIED

• Downregulates IL4 and IL13 signaling

Omalizumab (anti-IgE) = 18yo+

Mepolizumab (antiIL5sol) = 18yo+

Ongoing investigations for … Benralizumab, Tezepelumab, Reslizumab

Name x2 of the most important cytokines involved in CRSwNP

IL5

IL13

Eotaxin 1-3

MCP-4

IL4

Recruitment and proliferation of eosinophils, promoting enhanced tissue eosinophilia, versus CRSsNP (without NP)

In which type of CRS is TGFbeta increased?

CRSsNP - secondary to nasal obstruction and hypoxia, with neutrophil accumulation and secondary fibrosis. 

CRSsNP:

• increased TGFbeta, IL4, GMCSF, PGE2, LTC4, LTD4, LTE4, LTB4, Lipoxin A4

CRSwNP: 

• increased eosinophil cationic protein, IL5, IgE, eotaxin, RANTES (CCL5), LTC4, LTD4, LTE4, LTB4, Lipoxin A4

• decreased PGE2*** 

Explain the barrier hypothesis in chronic rhinosinusitis

Mechanical / Innate immune barrier defects broadly present in CRS (both wNP and sNP), resulting in …

• an abnormal microbiome

• increased exposure to foreign materials and an excessive compensatory innate and adaptive immune process

WITH NP - bacterial film on mucosal surfaces

• Increased TSLP, IL32, Increased DC activation, Increased IL4, IL5, IL13 for increased B cell and local Eosinophil activation 

• Increased macrophages, IgE 

• Decreased TGFbeta** 

WITHOUT NP - colonization of bacterial fungi 

• increased DC activation, 

• Increased Th1 response, Neutrophil and B cell recruitment 

• Increased TGFbeta** 

Most common bacterial causes of chronic rhinosinusitis

Staph aureus 

Anaerobic bacteria with chronic biofilms and impaired mucociliary clearance (e.g. Prevotella, Fusobacterium) 

Pseudomonas 

Enterobacter

List x4 Clinical Features of chronic rhinosinusitis

PODS*

• Sinus/Facial Pain or Pressure

• Nasal Obstruction and Congestion

• Mucopurulent Discharge

• Loss of Smell / Anosmia / Hyposmia

List x2 associated RED FLAGS that would concern for complication in CRS, that would prompt urgent CT sinus imaging

Proptosis or Periorbital Cellulitis

Abnormal EOM

Vision change

Facial Swelling

Cranial Neuropathy (Bells Palsy)

Severe headache 

Neck stiffness

Altered mental status 

Not improving on antibiotics or recurrent history

List x4 treatment GOALS in CRS

Reduce symptom burden 

Improve QoL 

Reduce exacerbation frequency + intensity 

Prevent complications

Patient with Acute Bacterial Rhinosinusitis (ABRS). This is their first episode. They are able to go to work and to sleep.

1. What first-line antibiotic is indicated for ABRS? 

2. List x2 adjunct therapies?

1. Amoxicillin = first line 5-10 days 

   1. If penicillin allergy - macrolide (azithro) or septra (TMP/SMX) 

   2. Consider Amoxi-Clav IF immunocompromised, or if higher risk of resistance (<15% and increasing)

2. Adjunct Therapies:

   1. Nasal saline rinses

   2. Intranasal corticosteroid 

   3. Antihistamine 

   4. Analgesics / Antipyretics

Most common causes of ABRS?

Strep pneumoniae

H. influenzae (non-typeable, non-encapsulated*)

Moraxella catarrhalis

Confirmatory Tests for Primary Ciliary Dyskinesia

Nasal brushing to assess ciliary motion and ultrastructure by HSVA (high speed video microscopy analysis) and/or TEM (transemission electron microscopy). 

Genetic testing for biallelic or X-linked pathogenic variant to known PCD gene(s) 

What’s the histopathology of nasal polyposis?

Allergic nasal polyps:

• edema

• goblet cell hyperplasia

• thickening of the basement membrane

• numerous leukocytes

• predominantly eosinophilia^^

VS in Cystic Fibrosis have neutrophilia^ with low eosinophils

Chronic Rhinosinusitis (they tell you the diagnosis has been made). 22 year old Syrian man in terrible living conditions (basement, water damage, rodents, cockroaches). 

What is on your DDx?

• CRS with NP

• CRS without NP 

• Allergic fungal rhinosinusitis

• Allergic chronic rhinitis (mold, rodents, cockroaches, dust mites)

• Non allergic chronic rhinitis

• Infectious rhinitis (viral, bacterial, fungal)

• Rhinitis medicamentosa

• NERD

• Anatomical abnormalities (spatial deformity, tumors)

• Granulomatosis with polyangiitis 

• Eosinophilic granulomatosis with polyangiitis

• CF

• PCD

• PID (eg: CVID)

Chronic Rhinosinusitis (they tell you the diagnosis has been made). 22 year old Syrian man in terrible living conditions (basement, water damage, rodents, cockroaches).

What investigations do you order? 

• SPT to common environmental allergens (cockroaches, rodents, mold)

• Spirometry

• Sinus CT-Scan

• +/- ENT for rhinoscopy

• +/- Sweat test, ciliary function tests, CBCD, Ig, vaccines responses, sinus cultures

Chronic Rhinosinusitis (they tell you the diagnosis has been made). 22 year old Syrian man in terrible living conditions (basement, water damage, rodents, cockroaches).

You are given SPT results (+cat, mould, hdm, rodent). What avoidance measures can you take?

• Cat: Removal of pet from the home.

• HDM: Humidity < 50%, wash bedding weekly, dust mites covers pillows, mattresses, and box springs, regular vacuuming with HEPA filters, no bunk beds.

• Rodent: Professional exterminator, rodent traps, habitat modification to remove rodent ingress, food, water and shelter.

• Mold: Humidity < 50%, HEPA filter, dilute bleach, professional removal, cleaning visual molds.

Chronic Rhinosinusitis (they tell you the diagnosis has been made). 22 year old Syrian man in terrible living conditions (basement, water damage, rodents, cockroaches).

The father smokes inside, and the patient’s clothes smell of smoke - how would you address this?

• Directly address that this a factor exacerbating symptoms.

• Encourage smoking cessation, offer to prescribe patches. Refer the father if motivated to stop smoking.

Chronic Rhinosinusitis (they tell you the diagnosis has been made). 22 year old Syrian man in terrible living conditions (basement, water damage, rodents, cockroaches).

The patient can’t afford medications - how would you address this?

• Encourage to enroll in provincial extended medical benefits programs for low income families.

• Provide samples.

• Prescribe generics and the least expensive medications.

• Consult Social worker to support application processes. 

Chronic Rhinosinusitis (they tell you the diagnosis has been made). 22 year old Syrian man in terrible living conditions (basement, water damage, rodents, cockroaches).

You are given SPT results (+cat, mould, hdm, rodent).

The landlord refuses to make any modifications to the apartment - and has told your patient that they can’t get out of the lease early - they have to pay the remaining 10 months or else he will pursue legal action - how would you handle this?

• Social worker.

• Legal aid for low income.

• Landlord and tenant board.

• Provide letter to support this is medically indicated.

Patient with nasal congestion and popping in the ears.

What’s on your DDx? 

• Allergic rhinitis.

• Non allergic rhinitis.

• CRS wihtout NP.

• CRS with NP.

• Rhinitis medicamentosa.

• NERD.

• EGPA.

• GPA.

• Allergic fungal rhinosinusitis.

• Infectious rhinitis (viral, bacterial, fungal).

• PCD.

• CF.

• PID (eg: CVID).

Patient with nasal congestion and popping in the ears. They then tell you that there is also epistaxis and hemoptysis.

What investigations do you order?

• SPT environmental allergens.

• Urine analysis & renal function.

• Albumin

• Liver function

• CBCD.

• CRP, ESR.

• ANCA.

• C3, C4

• RF

• CXR.

• Chest & sinus CT-Scan 

• Full PFT

• Sputum cultures.

• ENT & respirology for multidisciplinary approach and consideration for biopsies.

Patient with nasal congestion and popping in the ears. They then tell you that there is also epistaxis and hemoptysis.

Which ANCA is associated with GPA?

c-ANCA associated with PR3

Patient with nasal congestion and popping in the ears. They then tell you that there is also epistaxis and hemoptysis.

They tell you there is active urinary sediment (RBC casts) and nodular changes on CXR.

How would you make the diagnosis (of GPA)?

• Compatible clinical history (triad nose, lung, kidney).

• Biopsy at site of suspected active disease (nephrology or respirology).

Patient with nasal congestion and popping in the ears. They then tell you that there is also epistaxis and hemoptysis.

They tell you there is active urinary sediment (RBC casts) and nodular changes on CXR.

You make a diagnosis of GPA.

What would your management be?

• Involve nephrology, respirology, ENT & rheumatology in multidisciplinary approach.

• Glucocorticoids + rituximab or cyclophosphamide as induction

• Measure Ig’s pre-rituximab

• Maintenance could be rituximab, methotrexate, azathioprine

• Monitoring of response (in person follow up q2-4 weeks, TA, renal function, urinalysis, CBCD, CRP, ESR, chest imaging).

What if a radiologist contacts you about putting in place a protocol to pre-treat everyone that gets contrast.

What would you tell them?

What safety concerns would you have?

• Thank them for their initiative and interest in optimizing patient care & wish for multidisciplinary work.

• But no.

• Limited clinical evidence that pre-medication is beneficial even for patients with a history of reaction when low or iso-osmolar & non-ionic solution is used.

• Concerns about side effects of corticosteroids & Benadryl, masking early symptoms of anaphylaxis.

• Overall not cost efficient. 

Demonstrate how you would prepare the solution for testing. They provide a vial of YJ venom (100mcg in 10mL).

They have needles, swabs, sharps container and vials of 9mL of diluent.

• Wash your hands

• Identify the vials

• Draw 1 mL of 100 mcg/10 mL solution.

• Add to 9 mL vial (1 mcg/mL).

• Draw 0.05 mL of this new solution.

• Swab every vial before drawing solution.

• Dispose of needles immediately after their use.

ADD 5.5 mL with the powder 600 mcg (~ 600 mcg/6 mL)

CRSwNP: 42 yo adult female with 4 courses abx, purulent discharge 11-12 month, anosmia, sense of taste, AR sensitive to pollens, animals, dust mite. No asthma, no AERD. Using nasal saline rinses and nasal ICS intermittently.

 

Diagnostic criteria for CRS

Must have ≥2 of 4 cardinal symptoms (PODS) for ≥12 weeks:
• Nasal obstruction/congestion
• Nasal discharge (anterior/posterior)
• Facial pain/pressure
• Hyposmia/anosmia

AND objective evidence on nasal endoscopy and/or CT showing mucosal inflammation involving the sinuses or middle meatus

She meets criteria based on chronic purulent discharge, anosmia, and objective findings.

CRSwNP: 42 yo adult female with 4 courses abx, purulent discharge 11-12 month, anosmia, sense of taste, AR sensitive to pollens, animals, dust mite. No asthma, no AERD. Using nasal saline rinses and nasal ICS intermittently.

Investigations - ENT and CT finds polyps in maxillary and ethmoid sinuses with calcification present

Nasal endoscopy: confirms nasal polyps

CT sinuses: shows maxillary + ethmoid polyps and calcifications

• Calcifications may suggest allergic fungal rhinosinusitis (AFRS) or chronic infections.

Additional investigations may include:

• Allergy testing – relevant given AR history

• Baseline immune screen: CBC with diff, immunoglobulins ± IgE, vaccine titers (especially with recurrent bacterial infections)

• Consider fungal stain/culture if AFRS suspected

CRSwNP: 42 yo adult female with 4 courses abx, purulent discharge 11-12 month, anosmia, sense of taste, AR sensitive to pollens, animals, dust mite. No asthma, no AERD. Using nasal saline rinses and nasal ICS intermittently.

Initial management.

First-line therapy for CRSwNP includes

Medical:

• Daily intranasal corticosteroid spray (improve adherence)

• Consider short course of oral corticosteroids for polyp reduction

• Continued saline irrigation

• Reinforce correct technique for nasal steroids and rinses.

Address comorbidities:

• Optimize allergic rhinitis:

  • Avoidance measures

  • intranasal antihistamine ± oral antihistamine

• Consider allergen immunotherapy depending on sensitization and symptoms

CRSwNP: 42 yo adult female with 4 courses abx, purulent discharge 11-12 month, anosmia, sense of taste, AR sensitive to pollens, animals, dust mite. No asthma, no AERD. Using nasal saline rinses and nasal ICS intermittently.

Then told that initial management fails. What to do next.

Escalate to ENT for surgery → Functional Endoscopic Sinus Surgery (FESS) with polypectomy

Also allows:

• Improved access for topical therapy

• Tissue pathology/culture

• Management of calcifications/AFRS findings

Consider PID screen – they tell you is negative.

Consider CF / PCD screen

CRSwNP: 42 yo adult female with 4 courses abx, purulent discharge 11-12 month, anosmia, sense of taste, AR sensitive to pollens, animals, dust mite. No asthma, no AERD. Using nasal saline rinses and nasal ICS intermittently.

Recurrence 2 years after despite abx, steroids, surgery. Pt does not want surgery again. What are options.

Typical for refractory CRSwNP, patient declines repeat FESS.

Other options:

• Biologic therapies

  • Dupilumab (IL-4Rα inhibitor; approved for severe CRSwNP) – best evidence

  • Mepolizumab (IL-5 inhibitor) – if eosinophilic phenotype

  • Omalizumab (anti-IgE) – if significant allergic sensitization

• Adjunctive medical therapies

  • Regular topical steroids ± exhalation-delivery devices

  • Steroid irrigations (e.g., budesonide mixed with saline)

  • Short oral steroid courses for flares

  • Leukotriene receptor antagonist (montelukast) for allergic component

  • Allergen immunotherapy — if allergic rhinitis is contributing

  • If AERD phenotype emerges later → ASA desensitization could be considered
    (not indicated currently with no asthma/N-ERD)