2.  Definitions
 Clinical characteristics (Symptoms of CRS)
 Classification
 Histopathology and pathomechanism
 Comorbidities and associated conditions
 Diagnosis
 Treatment

3.  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

4.  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

5.  Minor symptoms:
• Headache
• Fever
• Halitosis
• Fatigue
• Dental pain
• Cough
• Ear pain/pressure/fullness
Middleton’s Allergy,principal & practice. Seventh edition.

6. 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 documentation
Rhinoscopic examination OR
Radiograph (sinus CT scan preferred)
Bilateral nasal polyps in AFRS criteria
middle meatus Positive fungal stain or
culture of allergic mucin
AND
IgE-mediated fungal
allergy
J Allergy Clin Immunol 2010;125:S103-15

7.  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

8.  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

9.  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

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

11.  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

12.  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

13.  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

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

15.  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

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

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

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

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

20.  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 CRScNP
Immunol Allergy Clin N Am 29 (2009) 657–668

21.  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

22.  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

23.  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

24. Immunol Allergy Clin N Am 29 (2009) 689–703

25. Immunol Allergy Clin N Am 29 (2009) 689–703

26.  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
Immunol Allergy Clin N Am 29 (2009) 689–703

27.  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
Immunol Allergy Clin N Am 29 (2009) 689–703

28. Immunol Allergy Clin N Am 29 (2009) 689–703

29. Immunol Allergy Clin N Am 29 (2009) 689–703

30. Immunol Allergy Clin N Am 29 (2009) 689–703

31. Immunol Allergy Clin N Am 29 (2009) 689–703

32.  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 drainage
Immunol Allergy Clin N Am 29 (2009) 719–732

33.  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

34.  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

35.  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

36.  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

37.  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 sinus
J Allergy Clin Immunol 2010;125:S103-15

38.  Pathogenesis remain largely unknown
 Disease heterogeneity
 Diagnosis
› Hx 4 major symptoms
› Nasal endoscope , sinus CT
› comorbidity
 Treatment
› Intranasal steroid
› Antibiotics ( if exacerbate )
› FESS