This document provides an overview of chronic rhinosinusitis (CRS), including its classification, diagnosis, factors associated with it, proposed mechanisms, environmental and host factors, theories of etiology and pathogenesis, complications, and treatment. CRS is defined as symptomatic inflammation of the nose and paranasal sinuses lasting over 12 weeks. It is classified into subtypes based on the presence of nasal polyps and type of inflammation. Both infectious and non-infectious factors are thought to play a role in CRS development and pathogenesis.

1. CHRONIC RHINOSINUSITIS
21TH JUNE 2019
BY
DR OLUWAJUWON OLAGUNJU

5. OUTLINE
• INTRODUCTION
• CLASSIFICATION OF RHINOSINUSITIS
• DIAGNOSIS OF CRS
• FACTORS ASSOCIATED WITH CRS
• PROPOSED MECHANISMS
• ENVIRONMENTAL FACTORS

6. • HOST FACTORS
• THEORIES OF ETIOLOGY AND PATHOGENESIS
• COMPLICATIONS OF RHINOSINUSITIS
• TREATMENT OF CRS
• REFERENCES

7. INTRODUCTION
• Acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS) are defined as
symptomatic inflammation of the nose and paranasal sinuses with the
distinction between the two based on the duration of the complaints.

8. • Although ARS is widely considered to be an infectious disorder. CRS, on the
other hand, is typically described more broadly as an inflammatory disorder,
and the importance of specific microbial agents in driving the process
remains controversial.

9. CLASSIFICATION OF RHINOSINUSITIS
• The Rhinosinusitis Task Force (RSTF) in 2007 proposed a clinical
classification system:
(a) Acute rhinosinusitis (ARS): symptoms lasting or less than 4 weeks with
complete resolution
(b) Subacute RS: duration between 4 and 12 weeks

10. • (c) Chronic RS (CRS) (with or without nasal polyps): symptoms lasting or
more than 12 weeks without complete resolution of symptoms
(d) Recurrent ARS: ≥ 4 episodes per year, each lasting ≥ 7-10 days with
complete resolution in between episodes

11. • (e) Acute exacerbation of CRS: sudden worsening of baseline CRS with
return to baseline after treatment

12. • Four cardinal symptoms of CRS
(a) Anterior or posterior purulent nasal discharge
(b) Nasal obstruction
(c) Face pain or pressure
(d) Hyposmia or anosmia

13. DIAGNOSIS OF CRS
• At least two of the cardinal symptoms + one of the following:
(a) Endoscopic evidence of mucosal inflammation: purulent mucus or
edema in middle meatus or ethmoid region
(b) Polyps in nasal cavity or middle meatus
(c) Radiologic evidence of mucosal inflammation

14. • Three subtypes of CRS:
(a) CRS with nasal polyps (20%-33%) (CRSwNP)
Predominantly neutrophilic inflammation
(b) CRS without nasal polyps (60%-65%) (CRSsNP)
Predominantly eosinophilic inflammation; IL-5 and eotaxin
involvement
(c) Allergic fungal rhinosinusitis (8%-12%)

15. FACTORS ASSOCIATED WITH CRS
• Anatomic abnormalities: Septal deviation and spur, turbinate hypertrophy,
middle turbinate concha bullosa, prominent agger nasi cell, Haller cells,
prominent ethmoidal bulla, pneumatization and inversion of uncinate
process.

16. • Ostiomeatal complex compromise: The common drainage pathway for
frontal, anterior ethmoid, and maxillary sinuses; blockage by inflammation or
infection can lead to obstruction of sinus drainage, resulting in sinusitis.

17. • Mucociliary impairment: Ciliary function plays important role in clearance of
sinuses; loss of ciliary function may result from infection, inflammation, or
toxin; Kartagener syndrome (situs inversus, CRS, and bronchiectasis) may be
associated with CRS.
• Asthma: Up to 50% o CRS patients have asthma.

18. • Bacterial infection: Staphylococcus aureus, coagulase-negative
Staphylococcus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus
mirabilis, Enterobacter, Escherichi coli; with chronicity, anaerobes develop
Fusobacterium, Peptostreptococcus, and Prevotella.

19. • Fungal infection: May cause a range of diseases, from noninvasive fungus
balls to invasive pathologies.
• Allergy: A contributing factor to CRS; there is increased prevalence of
allergic rhinitis in patients with CRS.

20. • Staphylococcal superantigen: Exotoxins secreted by certain S. aureus strains;
they activate cells by linking -cell receptors with MHC II surface molecule on
antigen presenting cells (APCs).

21. • Osteitis: Area of increased bone density and thickening may be a marker of
chronic inflammation.
• Biofilms: 3D structures of living bacteria encased in polysaccharide; have
been found on sinus mucosa in CRS patients.

22. • ASA or Samter triad: Nasal polyposis, aspirin (ASA) sensitivity, and asthma;
mediated by production of proinflammatory mediators, mainly leukotrienes.

23. • Granulomatous vasculitis: Churg-Strauss syndrome: CRSwNP, asthma,
peripheral eosinophilia, pulmonary infiltrates, systemic eosinophilic vasculitis,
and peripheral neuropathy (p-ANCA may be positive).

24. PROPOSED MECHANISMS
• In CRS, the etiology and pathogenesis are much less clear, and the majority
of cases are idiopathic. A small subset, however, occur in association with
known genetic disorders (Kartagener syndrome, cystic fibrosis [CF]),

25. • 3 autoimmune disorders (sarcoidosis, Wegener granulomatosis, systemic
lupus erythematosus), or systemic immunodeficiencies (HIV).
• CRS that occurs in these settings is a local manifestation of a systemic
disease and will typically exhibit a more specific histology and clinical course.

26. • Exogenous agents that trigger or exacerbate the sinonasal inflammation in
these cases may be somewhat selective to the underlying systemic disorder as
well (e.g., Staphylococcus and Pseudomonas in CF).

27. • Idiopathic CRS, which comprises the vast majority of CRS cases as
mentioned above, is a clinical syndrome linked by the unifying presence of
sinonasal mucosal inflammation; however, the etiology and pathogenesis of
this inflammation are complex.

28. • The most widely accepted classification system divides CRS into
• CRS without nasal polyps (CRSsNP) and
• CRS with nasal polyps (CRSwNP)
based on nasal endoscopy.

29. • Historically, CRSsNP was thought to be a disorder characterized by
persistent inflammation that resulted from incomplete resolution of acute
infectious rhinosinusitis.

30. • CRSwNP, on the other hand, was seen as a separate noninfectious disorder
of unclear etiology, possibly associated with atopy.

31. • At present, factors that have been associated with the etiology and
pathogenesis of CRS include fungi, resistant bacteria, superantigens,

32. • biofilms, atopy, mucociliary dysfunction, environmental irritants, acquired
sinonasal obstruction (especially of the ostiomeatal complex), osteitis, and
genetic or epigenetic variation of the host.

33. • This list includes both host and environmental factors

34. ENVIRONMENTAL FACTORS
• FUNGI
The role of fungi in the etiology of CRS remains controversial.
Using sensitive techniques, fungi can be detected in the nasal cavity of all
patients—those with CRS and controls—without a clear increase of fungal
biomass in disease.

35. • Nevertheless, the demonstration of fungi, as well as eosinophilic mucin, in all
patients with CRS formed the initial basis of the fungal hypothesis of CRS.

36. • This theory proposed an exaggerated inflammatory response to the common
airborne fungus Alternaria as the underlying cause of both CRSsNP and
CRSwNP, thought to be forms of a single disease varying only in intensity.

37. • BACTERIA
Although the role of bacteria in ARS is well established, involvement in CRS
is less clear. Culture-independent molecular techniques used to detect
bacteria have demonstrated that the nose and sinuses are clearly not sterile,

38. • even in normal patients, and that the microbiome differs in CRS; together,
this suggests a possible role for bacteria in the etiology and pathogenesis of
this disorder. Staphylococcus aureus was found to be the most frequently
described bacterial pathogen in CRS.

39. • Multiple other species have been implicated in biofilm production in CRS
patients as well, including Haemophilus influenzae, Streptococcus pneumoniae,
Pseudomonas aeruginosa, and Moraxella catarrhalis, although P. aeruginosa and S.
aureus appear to convey a worse prognosis

40. • VIRUSES
Evidence that latent or chronic viral infections can be a source of sinonasal
inflammation that mediates CRS is scant. It is possible, however, that viral
infections may predispose to the subsequent development of CRS later in
life.

41. • Although this hypothesis has not been tested in the upper airway, early
childhood viral infections have been linked to the subsequent development
of asthma years later.

42. • Viral infections may also play a role in CRS exacerbations, as they do in
asthma and chronic obstructive pulmonary disorder.

43. • TOXINS AND ALLERGENS
Environmental toxins have been associated with CRS, but no clear causal
relationship has been established. An increased prevalence of CRS has been found
among factory workers and certain craft and related trade workers, although perhaps
the most well-studied environmental toxin in relation to CRS is
cigarette smoke.

44. • Some evidence shows an association between CRS and exposure to cigarette
smoke, and cigarettes may be linked to worsened surgical outcomes.

45. • Toxins are thought to damage the sinonasal epithelial barrier through
production of reactive oxygen and nitrogen species, with cigarettes in
particular being linked to mucociliary dysfunction, biofilm production, and
proinflammatory cytokine induction.

46. HOST FACTORS
• The presence of host sinonasal inflammation defines CRS, and
various components of the underlying immune responses have
been implicated from the standpoint of etiology and pathogenesis.

47. • However, the type of inflammation seen in the tissue is highly variable, and
this may ultimately distinguish CRS endotypes.

48. • As discussed above, CRS is currently divided into two groups based on the
presence or absence of nasal polyps, but other classification systems have
been considered based on cellular infiltrates, cytokine expression, or tissue
remodelling patterns.

49. THEORIES OF ETIOLOGY
AND PATHOGENESIS
• Several theories have been proposed over the last 15 years in an attempt to
explain the etiology and pathogenesis of CRS.
• The first of these was the fungal hypothesis, which attributed all CRS cases to
an excessive host response to Alternaria fungi.

50. • The leukotriene hypothesis proposes that defects in the eicosanoid pathway,
most closely associated with aspirin intolerance, are also key components in
the pathogenesis of other eosinophilic subtypes of CRS.

51. • The staphylococcal superantigen hypothesis proposes that exotoxins liberated by
staphylococcal bacteria foster nasal polyposis via effects on multiple cell
types.

52. • Staphylococcus superantigens are generally thought of as disease modifiers that
mediate pathophysiology rather than discrete etiologic agents.

53. • The immune barrier hypothesis proposes that defects in the mechanical barrier
and/or the innate immune response of the sinonasal epithelium manifests as
CRS.

54. • Increased microbial colonization and accentuated barrier damage lead to
increased stimulation of the immune system with a compensatory adaptive
immune response.

55. • The biofilm hypothesis suggests that biofilms, in particular staphylococcal
biofilms, can serve as etiologic agents that cause CRS. It can be speculated
that a defect in the immune barrier might facilitate formation of biofilms,
which would suggest a role in pathogenesis rather than etiology.

56. COMPLICATIONS OF RHINOSINUSITIS
• Hematogenous spread: retrograde thrombophlebitis through valveless veins
(veins of Breschet)
• Direct spread: through lamina papyracea, osteomyelitis

57. • Mucoceles
(a) Collection of sinus secretions trapped due to obstruction of sinus
outflow tract; expansile process
(b) Mucopyoceles: infected mucocele
(c) Endoscopic marsupialization is treatment

58. • OPHTHALMOLOGIC
• Chandler classification
(a) Preseptal cellulitis: inflammatory edema; no limitation of extraocular movements
(EOM)
(b) Orbital cellulitis: chemosis, impairment of EOM, proptosis, possible visual
impairment

59. • (c) Subperiosteal abscess: pus collection between medial periorbita and
bone; chemosis, exophthalmos, EOM impaired, visual impairment
worsening.
(d) Orbital abscess: pus collection in orbital tissue; complete
ophthalmoplegia with severe visual impairment

60. Superior orbital ssure syndrome (CN III, IV, V1, and VI)
Orbital apex syndrome (CN II, III, IV, V1, and VI)
(e) Cavernous sinus thrombosis: bilateral ocular symptoms; worsening of all
previous symptoms

61. • NEUROLOGIC
• Meningitis: severe headache, fever, seizures, altered mental status, and meningismus
• Epidural abscess: pus collection between dura and bone
• Subdural abscess: pus under dura
• Brain abscess: pus within brain parenchyma

62. • BONY
• Osteomyelitis: thrombophlebitic spread via diploic veins
• Pott puffy tumor: subperiosteal abscess ( frontal bone osteomyelitis to
erosion of the anterior bony table)

63. TREATMENT OF CRS
• Controversial due to the spectrum of disease and underlying etiologies
• Many adjunct therapies have limited evidence to support their use:
mucolytics, antihistamines, decongestants, leukotriene modifiers

64. • Medical treatment of CRS without nasal polyps:
(a) Level 1b evidence
Long-term oral antibiotics (>12 weeks), usually macrolide
Topical nasal corticosteroids
Nasal saline irrigation

65. • Medical treatment of CRS with nasal polyps:
(a) Level 1b evidence:
Topical nasal corticosteroids (drops better than sprays)
Systemic corticosteroids: 1 mg/kg initial dose and taper over 10 days
Nasal saline irrigation
Long-term oral antibiotics (>12 weeks), usually macrolide

66. • SURGICAL TREATMENT OF CRS
(a) Endoscopic sinus surgery is reserved or small percentage of patients with
CRS who fail medical management.
(b) Patients with anatomical variants often benefit from surgery to correct
the underlying abnormality, reestablishing sinus drainage.

67. • (c) Massive polyposis rarely responds to medical treatment and surgery will
relieve symptoms and establish drainage as well as allow or use of topical
corticosteroids.
(d) Other indications or surgery include mucocele formation, and suspected
fungal rhinosinusitis.

68. • (e) Continued use of medical therapy post surgery is key to success and is
required or all patients.

69. REFERENCES
• Brietzke SE, Shin JJ, Choi S, et al. Clinical Consensus Statement: pediatric chronic rhinosinusitis.
Otolaryngol Head Neck Surg. 2014;151(4):542-553.
Brown K, Rodriguez K, Brown OE. Congenital mal ormations o the nose. In: Cummings CW, Flint
PW, Harker LA, et al, eds. Cummings Otolaryngology Head & Neck Surgery. 4th ed. Philadelphia,
PA: Elsevier Mosby; 2005.
Chakrabarti A, Denning DW, Ferguson BJ, et al. Fungal rhinosinusitis: a categorization and de nitional
schema addressing current controversies. Laryngoscope. 2009;119(9):1809-1818.
Fokkens W, Lund V, Mullol J. European position paper on rhinosinusitis and nasal polyps. Rhinol
Suppl. 2007;(20):1-136.
Melia L, McGarry GW. Epistaxis: update on management. Curr Opin Otolaryngol Head Neck Surg.
2011;19(1):30-35.

70. • Rosen eld RM et al. Clinical practice guidelines: adult sinusitis. Otolaryngol Head Neck Surg.
2007;137
(3 Suppl):S1-S31.
Chandra R, Chiu A, et al. Understanding Sinonasal Disease: A primer or medical students
and residents. Am J Rhinol Allerg. 2013:27(Suppl):S1-S62.
Walsh WD, Kern RC. Sinonasal anatomy, unction, and evaluation. In: Bailey BJ, Johnson J ,
Newlands SD, et al, eds. Head & Neck Surgery—Otolaryngology. 4th ed. Philadelphia, PA:
Lippincott Williams & Wilkins; 2006.
• Cummings Otolaryngology Head & Neck Surgery. 6th ed

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