Chronic Rhinosinusitis
-
Upload
chulalongkorn-allergy-and-clinical-immunology-research-group -
Category
Documents
-
view
2.443 -
download
0
Transcript of 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
J Allergy Clin Immunol 2010;125:S103-15
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
J Allergy Clin Immunol 2010;125:S103-15
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
J Allergy Clin Immunol 2010;125:S103-15
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
J Allergy Clin Immunol 2010;125:S103-15
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
Middleton’s Allergy,principal & practice. Seventh edition.
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% )
J Allergy Clin Immunol 2010;125:S103-15
Middleton’s Allergy,principal & practice. Seventh edition.
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
J Allergy Clin Immunol 2010;125:S103-15
Cor ticosteroidTreatment in CRS
Immunol Allergy Clin N Am 29 (2009) 657–668
Cor ticosteroidTreatment in CRS
Immunol Allergy Clin N Am 29 (2009) 657–668
Indication of corticosteroids in management scheme of adult patients with CRSsNP, based on EP3OS consensus
Immunol Allergy Clin N Am 29 (2009) 657–668
Indication of corticosteroids in management scheme of adult patients with CRScNP, based on EP3OS consensus
Immunol Allergy Clin N Am 29 (2009) 657–668
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
Immunol Allergy Clin N Am 29 (2009) 677–688
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
Immunol Allergy Clin N Am 29 (2009) 719–732
Anti – Inflammatory Effects of Macrolides: Applications in CRS
Immunol Allergy Clin N Am 29 (2009) 689–703
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
Immunol Allergy Clin N Am 29 (2009) 689–703
Anti – Inflammatory Effects of Macrolides: Applications in CRS
Immunol Allergy Clin N Am 29 (2009) 689–703
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
Anti – Inflammatory Effects of Macrolides: Applications in CRS
Immunol Allergy Clin N Am 29 (2009) 689–703
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
Anti – Inflammatory Effects of Macrolides: Applications in CRS
Immunol Allergy Clin N Am 29 (2009) 689–703
Anti – Inflammatory Effects of Macrolides: Applications in CRS
Immunol Allergy Clin N Am 29 (2009) 689–703
Clinical Use of Macrolides in CRS
Immunol Allergy Clin N Am 29 (2009) 689–703
Anti – Inflammatory Effects of Macrolides: Applications in CRS
Immunol Allergy Clin N Am 29 (2009) 689–703
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
Immunol Allergy Clin N Am 29 (2009) 719–732
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
J Allergy Clin Immunol 2010;125:S103-15
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
Immunol Allergy Clin N Am 29 (2009) 719–732
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
J Allergy Clin Immunol 2010;125:S103-15
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