Chronic Rhinosinusitis

Chronic Rhinosinusitis

Boonthorn31 March 2010

Outline

Definitions Clinical characteristics (Symptoms of

CRS) Classification Histopathology and pathomechanism Comorbidities and associated conditions Diagnosis Treatment

Definitions

Rhinosinusitis : inflammation of nose and paranasal sinuses

Acute rhinosinusitis (<4 weeks )› purulent nasal drainage, nasal obstruction,

facial pain-pressure-fullness, or both Subacute rhinosinusitis (4 and 8 weeks ) CRS (> 8 or 12 weeks ,medical Rx )

› inflammatory condition involve paranasal sinuses and nasal passages

J Allergy Clin Immunol 2010;125:S103-15

Symptoms of CRS

4 major symptoms ( 2 , to make Dx )› anterior, posterior, or both mucopurulent

drainage usually opaque white or light yellow

› nasal obstruction or blockage › facial pain, pressure, and/or fullness

83%, dull pain ,upper cheeks, between eyes, or in forehead

› decreased sense of smell


Symptoms of CRS

Minor symptoms: • Headache• Fever• Halitosis• Fatigue• Dental pain• Cough• Ear pain/pressure/fullness

Middleton’s Allergy,principal & practice. Seventh edition.

Definitions of rhinosinusitis based on disease classification

CRSsNP CRScNP AFRS

Symptoms present for >12 weeks

Requires >2 of following symptoms Anterior or posterior mucopurulent drainage Nasal congestion Facial pain/pressure Decreased sense of smell

Objective documentationRhinoscopic examination ORRadiograph (sinus CT scan preferred)

Bilateral nasal polyps in middle meatus

AFRS criteria Positive fungal stain or culture of allergic mucin AND IgE-mediated fungal allergy


Classification( Subtypes of CRS )

CRSsNP (60%)› Facial pain, pressure, and/or fullness › Organism : S.pneumoniae, H.influenzae,

M.catarrhalis, S.aureus,S.coagulase-negative › Glandular hyperplasia and submucosal fibrosis

CRScNP (20-33%)› Hyposmia/anosmia› Nasal polyps are typically bilateral› associated with AERD› predominance of eosinophils, high levels of

histamine, and Th2 cytokines


Classification( Subtypes of CRS )

AFRS › Presence of allergic mucin (thick mucus ,light

tan to brown to dark green, degranulated E)› fungal hyphae in mucin› evidence of IgE-mediated fungal allergy

Sinus surgery usually required usually have nasal polyps and

immunocompetent Pathophysiology :chronic, allergic

inflammation directed against colonizing fungi


Histopathology and pathomechanism

CRS› Basement memb. Thickening, goblet cell

hyperplasia, subepithelial edema, mononuclear cell infiltration

› tissue eosinophilia not hallmark of CRSsNP› 31 untreated CRSsNP, all had <10% E

(overall mean 2%)› 123 untreated nasal polyp , 108 showed

>10% E (overall mean 50%)

Middleton’s Allergy,principal & practice. Seventh edition

mucosa in CRS characterized by basement membrane thickening, goblet cell hyperplasia, subepithelial edema, and mononuclear cell infiltration with few eosinophils


Histopathology and pathomechanism

IL-8 and IL-3 increased in CRS mucosa compared to inferior turbinate samples

typical cytokine pattern of CRS › proinflammatory and neutrophil-associated

cytokines, ( IL-1β, TNF-α, IL-8 ), resulting in increased neutrophil activation

CRS show Th1- Cytokines (IFN-γ) and elevated TGF-β , may lead to increased fibrosis, hallmark of CRSsNP

In contrast to nasal polyps, characterized by Th2 cytokine pattern (IL-5) and low TGF-β

Middleton’s Allergy,principal & practice. Seventh edition

Comorbidities and associated conditions

Allergic rhinitis ( 60% of CRS ,perennial )

Immunodeficiency ( hypogammaglobulinemia 12% of adults with CRSsNP )

GERD Defect in mucociliary clearance ( cystic fibrosis and

primary ciliary dyskinesia )

Viral infection (role of viral infection in CRS is controversial )

Systemic disease (presenting feature of WG or CSS, sarcoidosis )

Anatomical abnormalities ( nasal septal deviation, concha bullosa deformity, paradoxical curvature of middle turbinate )

AERD and Asthma (20% CRS have asthma ,2/3 of asthmatic have evidence of CRS ) J Allergy Clin Immunol 2010;125:S103-15

Diagnosis

Nasal endoscopy › discolored mucus or edema in middle

meatus or sphenoethmoidal recess sinus CT scanning

› sinus ostial narrowing or obstruction› sinus mucosal thickening or opacification,

air-fluid levels Evaluated for allergy

› CRS associated with AR adults (60%) and children (36-60% )



Treatment

Topical corticosteroid nasal sprays › recommended for all forms of CRS› Beneficial effects on nasal and sinus pain

Antihistamines › helpful in allergic rhinitis

Antibiotics › used to treat infection if nasal purulence

present ( acute exacerbation ) Antifungals

› Indicate only in invasive forms of sinus mycosis or immunocompromised host


Cor ticosteroidTreatment in CRS

Immunol Allergy Clin N Am 29 (2009) 657–668

Cor ticosteroidTreatment in CRS


Indication of corticosteroids in management scheme of adult patients with CRSsNP, based on EP3OS consensus


Indication of corticosteroids in management scheme of adult patients with CRScNP, based on EP3OS consensus


Oral Corticosteroids

reserved for refractory cases or when relatively rapid short term improvement is needed

rapid symptomatic improvement, particularly in nasal obstruction and smell

significant polyp size reduction and reduction of imaging ( orally 2 weeks)

clinical effects lesser than intranasal steroids Prednisone 0.5 -1 mg/kg/d with tapered

reduction of 5 - 10 mg every 2 - 3 days over period of 2 - 3 weeks

Short courses are effective and safe in CRScNPImmunol Allergy Clin N Am 29 (2009) 657–668

SPECIAL CONSIDERATIONS AND LIMITS

Corticosteroids in Children with CRS› Data in children are limited› no studies on efficacy of topical corticosteroids in

pediatric CRS› local corticosteroids are effective and safe in

children with rhinitis Corticosteroids in Pregnant CRS

› US FDA classified intranasal steroids as category C, except for budesonide (B, early pregnancy)

› oral corticosteroids during first trimester should be restricted to lifethreatening conditions (oral clefts reported ) Immunol Allergy Clin N Am 29 (2009) 657–668

Does Reduction of Fungal Load Improve Symptoms in CRS?

in vitro data › amphotericin B nasal lavages are

ineffective at 250 mg/mL when used for 6 consecutive weekly (effective in killing fungi )

1 uncontrolled prospective trial and 4 DBPC studies effect of topical amphotericin B nasal lavage and nasal sprays in CRScNP,CRSsNP failed to show benefit


Does Reduction of Fungal Load Improve Symptoms in CRS?

retrospective review of 23 patients from Australia with refractory allergic fungal sinusitis (AFS) and nonallergic fungal sinusitis› Use itraconazole 100 mg twice daily for 6

months › improvement 19 patients› disease-free at 6 months 11 patients

RCT study of patients with eosinophilic fungal disease required to assess the efficacy of antifungal therapies


Anti – Inflammatory Effects of Macrolides: Applications in CRS


pathophysiologic interaction . Macrolides have effects across all 3 interacting processes: ability to modulate neutrophilic immune response, direct activity on bacteria, antibiofilm properties, and changes to mucus rheology and production




Block production of proinflammatory cytokines, eg.IL-8 and (TNF-a)

effects on neutrophil migration and adhesion

changes to mucus secretion and synthesis

nonbacteriostatic/cidal microbial activity



suppress the NO release from pulmonary macrophages after immune complex injury in rats

lower LTB4 and neutrophils (erythromycin)

reduce goblet cell secretion in response to LPS in animal models





Clinical Use of Macrolides in CRS




Medical treatment options for CRS: beyond steroids, antibiotics, and surgery

Topical saline irrigation› improve symptom scores and symptom control in CRS› In unoperated sinuses, effect limited to nasal cavity› In cystic fibrosis , hypertonic more effective than isotonic› other CRS patients benefit from isotonic irrigations

Mucus modifiers› theoretically improving mucociliary transport› Guaifenesin 1200 mg twice daily reduced congestion ,postnasal

drainage› limited data related to CRS management › Anticholinergics› blocks parasympathetic input to mucus glands and reduces

rhinorrhea › may lead to increased thickness of secretions and paradoxically

worsen postnasal drainageImmunol Allergy Clin N Am 29 (2009) 719–732

Medical treatment options for CRS: beyond steroids, antibiotics, and surgery

Leukotriene modulators› Leukotriene receptor antagonist (montelukast)› added to INCS can improve symptom scores in CRS

patients› 5-Lipoxygenase inhibitor (zileuton)› RCT, significant improvement in olfaction in patients

with CRS and concomitant aspirin sensitive asthma Decongestants ( little role in CRS )

› Topical› Systemic

Lifestyle modification› Stop smoking, get adequate sleep, exercise regularly,

avoid pollution


Treatment

CRScNP oral corticosteroids (10-15 days) to

shrink nasal polyps Topical corticosteroid nasal sprays

› recommended to prevent recurrence of nasal polyps, not always effective

Antileukotriene agents › not FDA approved for treatment of nasal

polyps sinus surgery in severe polyposis


Treatment

AERD : might benefit from aspirin desensitization and daily aspirin therapy, no contraindications to aspirin therapy

Desensitization can improve asthma control and prevent continued growth of NPs, but not usually cause NP regression


Treatment

AFRS› Sinus surgery establish diagnosis› remove inspissated mucus› restore sinus patency› Nearly all have nasal polyps› After surgery, oral corticosteroids ,0.5

mg/kg/d, with gradual tapering to control symptoms

› Topical corticosteroid nasal sprays to control inflammation and prevent recurrence of nasal polyps


Indications for sinus surgery

Functional endoscopic sinus surgery (FESS) › procedure of choice for refractory CRS.

indications for FESS › persistence of CRS symptoms despite medical therapy› correction of anatomic deformities believed to be

contributing to persistence of disease› debulking of advanced nasal polyposis

principal goal of FESS› restore patency to ostiomeatal unit

Additional goals of FESS › correction of septal deformities› Removal of severe concha bullosa deformity › restoration of patency to frontal sinusJ Allergy Clin Immunol 2010;125:S103-15

Conclusion

Pathogenesis remain largely unknown Disease heterogeneity Diagnosis

› Hx 4 major symptoms› Nasal endoscope , sinus CT› comorbidity

Treatment› Intranasal steroid› Antibiotics ( if exacerbate )› FESS

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Chronic Rhinosinusitis

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