Aetiopathology..clinical features.. investigations..EPOS 2020

1. Rhinosinusitis
(aetiopathology,
clinical features and
investigations)
DR MAHADEV DEUJA
ENT- HNS
TUTH IOM
2078/4/17
Fokkens W.J., Lund V.J. , Hopkins C., Hellings P.W., Kern R., Reitsma S., et al. European Position Paper on Rhinosinusitis
and Nasal Polyps 2020 Rhinology. 2020 Suppl. 29: 1-464.

2. Roadmap
• Definition
• Classification
• Aetiology
• Pathophysiology
• Clinical features
• Investigation
• Rhinosinusitis in children

3. Rhonosinusitis (clinical definition)
• One of which should be either
• Nasal blockage / obstruction /
congestion
• Nasal discharge (anterior /
posterior nasal drip)
• ± facial pain/pressure
• ± reduction or loss of smell
• One of which should be either
• Nasal blockage / obstruction /
congestion
• Nasal discharge (anterior /
posterior nasal drip)
• ± facial pain/pressure
• ± cough
Inflammation of nose and PNS resulting in Presence of 2
or more symptoms
Children
Adults

4. Rhonosinusitis (clinical definition)
Duration
• Acute
• < 12 weeks
• Sudden onset & complete
resolution of symptoms
• Chronic
• >12 weeks symptoms
• No complete resolution of
symptoms
Severity
• Mild = VAS 0-3
• Moderate=VAS >3-7
• Severe = VAS >7-10
• VAS >5 affects patient QOL
(validated in adult CRS only)

5. Rhonosinusitis (clinical definition)
• One of which should be either
• Nasal blockage / obstruction /
congestion
• Nasal discharge (anterior /
posterior nasal drip)
• ± facial pain/pressure
• ± reduction or loss of smell
• And either
• Endoscopic signs of:
• Nasal polyps
• Mucopurulent discharge
primarily from middle meatus
• Oedema / mucosal obstruction
primarily in middle meatus
Inflammation of nose and PNS resulting in Presence of 2
or more symptoms
Adults

6. Rhonosinusitis (clinical definition)
• One of which should be either
• Nasal blockage / obstruction /
congestion
• Nasal discharge (anterior /
posterior nasal drip)
• ± facial pain/pressure
• ± reduction or loss of smell
• And/ or
• CT changes:
• Mucosal changes within the
ostiomeatal complex
and/or sinuses.
• [Minimal thickening, involving only
1 or 2 walls and not the ostial area
is unlikely to represent
rhinosinusitis]
Inflammation of nose and PNS resulting in Presence of 2
or more symptoms
Adults

7. Other clinical definitions
• Recurrent acute rhinosinusitis (RARS) is defined as ≥ 4
episodes per year with symptom free intervals.
• (ideally ≥1 episode confirmed with endoscopy and/or CT)
• Acute exacerbation of chronic rhinosinusitis (AECRS) is
defined as worsening of symptom intensity with return to
baseline CRS symptom intensity, often after intervention with
corticosteroids and/or antibiotics

9. ARS- divided into
Acute viral rhinosinusitis
Acute post-viral rhinosinusitis
Acute bacterial rhinosinusistis
Epos 2012 Epos 2020
Acute bacterial
Rhinosinusitis
Acute bacterial
Rhinosinusitis
needing
antibiotics

10. Epidemiology of ARS
• Common problem, the precise incidence is difficult to estimate.
• Viral
• 2-5 episodes/yr in adults
• 7-10 episodes/yr in school children
• Post-viral/ABRS : 18% (17-21%) prevalence
• 1-2% of post viral ARS seek primary care.

11. Burden of CRS
• Affecting at least 11% of the population
• With a substantial economic burden to healthcare systems, to
patients and to the economy from loss of productivity in the
workplace.
• Rhinosinusitis is one of the top 10 most costly health conditions to
US employers.
• More than peptic ulcer disease, acute asthma, hay fever.
• Patients with recurrent acute rhinosinusitis have average direct
health care costs of $1,091/year
• (USA 2012).

12. AETIOLOGY
• Genetic/Physiological factors: Cystic fibrosis, Primary ciliary
dyskinesia, Immune disorder, Allergy
• Environmental factors: Infection, Smoking, Irritants.
• Structural factors: Concha bullosa, Septal spur, Paradoxical
middle turbinate, Everted uncinate

13. ACUTE RHINOSINUSITIS
• Precipitated by URTI
• Primary cause : viral infections
• 0.5-2% into bacterial sinusitis.
• Common Viruses:
• Rhinoviruses
• Corona virus.
• Influenza
• Para-influenza
• Adenovirus
• Respiratory syncytial virus
• Enterovirus

14. Predisposing factors to ARS
• If bacteria do become implicated the organisms most commonly
see are
• S. pneumoniae (27%),
• H. influenzae (44%),
• M. catarrhalis (14%)
• Other organisms including S. pyogenes and S. aureus.

15. Predisposing factor for ABRS
• Dental: infections and procedures
• Iatrogenic causes: sinus surgery, nasogastric tubes, nasal packing,
mechanical ventilation
• Immunodeficiency: human immunodeficiency virus infection,
immunoglobulin deficiencies Impaired ciliary motility: smoking, cystic
fibrosis, Kartagener syndrome, immotile cilia syndrome
• Mechanical obstruction: anatomic eg deviated nasal
septum/concha bullosa (RARS), nasal polyps, tumour, trauma,
foreign body, granulomatosis with polyangiitis
• Mucosal oedema: preceding viral upper respiratory infection,
allergic rhinitis, vasomotor rhinitis

16. Pathophysiology of ARS
NASAL
EPITHELUM Primary site of
entry for
respiratory
viruses
Active site of
initial host
responses
against viral
infection

17. Pathophysiology of ARS
Cascade of inflammation initiated
by nasal epithelial cells
Damage by infiltrating cells
Oedema, engorgement, fluid
extravasation, mucous production
and sinus obstruction
Post viral ARS/ ABRS

18. Definition of CRS
• 12 consecutive wks of subjective sinonasal symptoms
• 4 cardinal symptoms: blockage, drainage, smell loss, pressure
or pain
• Objective confirmation of inflammation via endoscopy or CT

19. CRS Phenotypes
• Broad clinical syndrome
• Historically, divided into CRS into 2 phenotypes: CRSwNP and
CRSsNP
• Simplistic, multiple clinical patterns exist

20. Chronic Rhinosinusitis
• Genotype-complex, multiple genes, CFTR; Environmental
factors probably more important
• Endotype-new classification systems
• Phenotype-clinical groupings; basis of most treatment at
present

21. Classification of primary CRS

22. Classification of secondary CRS

23. What is CRS?
• Broad clinical syndrome-not a disease
• 2 basic pathways to CRS:
• OMC blockage
• Primary mucosal inflammation

24. Osteomeatal complex
• Common central pathway of mucociliary clearance
• Anterior ethmoid, maxillary, and frontal sinuses
• The maxillary ostium, ethmoid infundibulum, anterior ethmoid
cells, and the frontal recess
• Focal inflammation or mass obstruction
• Disrupt mucociliary flow in multiple sites “upstream,” potentially
propagating rhinosinusitis.

25. Primary Mucosal inflammation in
CRS
Causes ???

26. Etiology and Pathogenesis of CRS
Environment
• Fungal hypothesis
• Superantigen hypothesis
• Biofilm hypothesis
• Microbiome hypothesis
• Allergy
Host
• Eicosanoid hypothesis
• Immune barrier hypothesis
• EPOS2012
• Lamet al.,2015

28. Nasal and Sinus Mucosa
• Site of Interface with the external environment
• In healthy, this occurs with minimal if any inflammation
• Mucosa serves as an “immune barrier”

29. Mucosal Immunity
Overview

30. Nasal and Sinus Mucosa
• Cross talk between host and environment
• Microbiome
• Defense vs. symbiosis
• Stochastic events such as viral infection at a young age
• Early life exposure protective; Hygiene Hypothesis
• Strachan, BJM, 1989
• Gut/airway axis
• Von Mutius, JACI 2016
• Lynch and Boushey, Curr Opin Allergy Clin Immunol., 2016
• SCFA, other compounds-protective!

31. Early Onset CRS Phenotype?
• Milder, atopic, progression of childhood disease
• CRSsNP typically
• Mild asthma or childhood asthma
Host
Barrier
Penetration
Environment
‘Atopic’CRS
Age25

32. CRS Etiology and Pathogenesis
• Host and Environment interact for 40+ years and then barrier is
penetrated resulting in CRS
• More severe, probably more likely to need surgery
• CRSsNP early 40’s; CRSwNP late 40’s
Host
Barrier
Penetration
Environment
CRS
Age45

33. CRS Etiology and Pathogenesis
• Etiologic factors vary so…..the inflammation not the same in all
CRS patients: ENDOTYPES-mechanistic pathways,
types/patterns
Host
Barrier
Penetration
Environment
CRS
Endotypes
Age45

34. Etiology and Pathogenesis of CRS
Genotype
Epigeneticvariation
Environmental
factors
Endotype(s) Phenotypes

35. Etiology and Pathogenesis of CRS
Endotype
Host
Remodeling
Phenotype
Natural history
outcome
Barrier
penetration
Environment
• Goblet hyperplasia
• Polyp formation
• Epithelial barrer abnormalities
• Greater permiability
Driven by type 2 cytokine………monoclonal antibodies.

36. Sinonasal Immunity
1. Mucus/Cilia
2. TJs
3. HDM and sIgA
4. ILC1, 2 and 3
5. Innate cells
6. Tcells
7. Bcells

37. Innate Lymphocytes Guide Immune
Responses

38. CRS Endotypes
• Type 1 inflammation: IFN-γ
• Type 2 inflammation: IL-4, IL-5, IL-13
• Type 3 inflammation: IL-17
• So we can determine tissue patterns based on markers of Type
1, 2 and 3 inflammation in the tissue

39. CRS Endotype Patterns
• T1
• T2
• T3
• T1,2
• T1,3
• T2,3
• T1,2 and 3
• Non typeable

40. Type 2 Inflammation
• Associated with treatment failure
• Asthma
• Eosinophilia
• Higher rate of polyp formation

41. TYPE 2
Inflammation

42. Type 2 Inflammation and Barrier
• Weakened and Immature epithelial barrier
• Chronic immature EMT state
• Barrier failure

43. Barrier Failure and Type 2 CRS
Jacqi summary of OSM story
Pothoven et al., 2015

44. Hypothetical
progression in
Type 2 CRS
Schleimer, R. Ann. Rev. Path., 12:331, 2017
Barrier Penetration Barrier Failure

45. Type 2 Inflammation and Recurrence
• Chronically weak barrier
• Predisposes to recurrence
• Need steroid maintenance
• Severe cases need a biologic

46. Type 1 and 3 Remodeling: Polyps
Barrier
Penetration
Host and
Environment
Type1and
3CRS
Endotype
Remodeling:
polyps

47. Non-Type 2 Inflammation
• Barrier more intact so recurrence less
• Polyps still fibrin
• Polyps less common
• Because t-PA suppression weaker with T1/3 cytokines and no feed-
forward mechanism because barrier more intact.

50. Systemic causes causing rhinosinusitis/
possible differential diagnosis
Congenital Cystic fibrosis Abnormal sweat test
CFTR gene mutation on chromosome 7
Primary ciliary dyskinesia Abnormal mucociliary clearance and cilia
ultrastructure
Primary immunodeficiencies (CVID,
SCID, hypo/dys-gamaglobulinemias
low/absent antibodies
Infectious/
inflamatory
HIV Positive ELISA for HIV
Sarcoidosis Elevated ACE
CXR sign( hilar lymphadenopathy)
Tuberculosis Acid fasr bacilli
Montoux test positive
Granulomatous with
polyangitis(Wegener’s)
cANCA positive
Eosinophilic grannulomatosis with
polyangitis
pANCA positive

51. Systemic causes causing rhinosinusitis/
possible differential diagnosis
Neoplastic Hematological malignancies Abnormal FBC/bone marrow
Sinonasal malignancies Biopsy positive
Radiological changes
Iatrogenic Atrophic rhinitis Excessive crusting following radical nasal
surgery
Chemotherapy/ immunosupression Relevant drug history
Metabolic Malnutrition Low BMI

52. Diagnostics and Objective Assessments in
CRS
• History & symptoms
• General examination – URT & LRT
• Endoscopy
• Quality of life assessment eg SNOT22, SF36
• Allergy tests eg skin prick, RAST
• Imaging
• Olfaction
• Nasal smears, swabs & biopsy for eosins, IgE, ECP etc
• Nasal challenge eg aspirin
• Mucociliary function
• Nasal airway assessment
• Systemic eg haematology for eosins, IgE, ECP, periostin etc
Primary
Secondary
Tertiary
CARE

53. CLINICAL FEATURES
• Rhinorrhea
• ARS
• Secretion: Aqueous or mucoid (initial viral or allergic presentation)
• As bacteria presence increases  mucopurulent, purulent
• Mucosa destruction  secretion may have signs of bleeding.
• CRS
• Less abundant
• Aqueous
• Mucopurulent
Frequently observed symptoms:

54. CLINICAL FEATURES - Contd
2. Nasal obstruction and congestion
• ARS
• Non-specific symptoms
• CRS
• Less frequent, and when present it is normally associated with other
factors, such as septal deviations, allergic rhinitis

55. CLINICAL FEATURES - Contd
• 3. Facial pain or pressure
• ARS:
• Virus: diffuse, very intense.
• Bacterial : non-pulsatile, worsens when the head moved forward;
referred dental pain which worsens with mastication
• CRS:
• Infrequent symptom
• Not specific to diagnosis

56. CLINICAL FEATURES - Contd
• SITE SPECIFIC PAIN:
• Frontal sinusitis: cross the forehead and temple
• Maxillary sinusitis: over the cheeks, temple, teeth and the hard palate
• Ethmoid sinusitis: between medial canthi of eye, redness +/-
• Sphenoid sinusitis: occipital region and vertex

57. CLINICAL FEATURES - Contd
• 4. Hyposmia or anosmia
• ARS
• By nasal obstruction  hindering the access of odor particles to
olfaction areas
• CRS
• Destruction of olfactory epithelium due to prolonged infection
• Influence of purulent secretions present in nasal cavity (cacosmia)

58. CLINICAL FEATURES - Contd
• Bacterial RS
• Ear fullness: drainage of secretions in the pharyngeal ostium region of
auditory tube.
• Cough (dry or productive): post nasal drip
• Sore throat and hoarseness, discomfort in throat
• Laryngeal, pharyngeal and tracheal irritation

59. Clinical examination
• Paranasal sinuses
• ARS- Tenderness++
• CRS- tenderness -

60. Clinical examination
Anterior rhinoscopy
• May reveal supportive findings
• Nasal inflammation, mucosal oedema and purulent nasal discharge
• Occasionally reveal unsuspected findings- polyps or
anatomical abnormalities.
• Drawbacks: unable to assess the middle meatus and the upper
and posterior regions the nose.

61. 3.Nasal endoscopy
• Allows identification of
• Oedema, pus and/or polyps,
• Assessment of sinus cavities following surgery
• Facilitates postoperative debridement or microbiological sampling
when needed.
• Not required in the clinical diagnosis of ARS in primary care settings.
• Correlates quite well with CT scan of the sinuses in patients with CRS.

62. Objective measures of nasal airflow and
patency
• Evaluation of nasal patency
• May be objectively evaluated with
• Peak nasal inspiratory flowmetry (PNIF),
• Active anterior rhinomanometry (AAR),
• Acoustic rhinometry (AR).

63. Temperature
• Fever Indicates severe illness and the need for more active
treatment.
• Associated with a positive bacteriologic culture, predominantly
S. pneumoniae and H. influenzae.

64. Diagnostic tools
• CT scan
• CRS
• Gold standard imaging modality for rhinologic disease.
• ARS is a clinical diagnosis –
• Not recommended unless the condition persists despite treatment, or a
complication is suspected.

65. CT Scan
• Indications:
• Poorly response to clinical treatment
• Recurrent or chronic cases
• In the presence of complications and
for surgical planning
• Advs: Detailed view, Bony anatomy
• Difficult to make: Presence of
secretions , fibrous scars.
• Not always correlated between CT
and clinical findings with trans
and/or postoperative findings.
Scott-Brown’s Otorhinolaryngology Edition 8

66. Recent advances in CT technology
• Helical (spiral) CT:
• Reduce motion artefacts caused by respiration or other sources of
patient movement.
• Imaging during the optimal window of contrast enhancement for
maximal image contrast.
• Ability to reconstruct axial images at arbitrary intervals.

67. 2.Plain Radiography
• Maxillary sinus: OM view
• Frontal sinus: OF view
• Ethmoidal sinus: lateral oblique view
• Sphenoid sinus: submento-vertical view
• Findings: air-fluid level, mucosal
thickening, opacification.
• Adv: low cost, small radiaton(1.6cGy)
• Drawback: low sensitivity
• No longer indicated in RS.

68. 3. Magnetic resonance imaging (MRI)
• Information about mucosa and other soft tissues
• Superior to CT in showing spreading beyond PNS -into the
orbits and intracranial compartment.
• Used to diagnose and stage tumors
• Can differentiate infectious inflammatory disease by bacteria
and virus from fungal diseases
Dr. Nashmee Ali Rasheed/ Rhinosinusitis/ 2075.04.22

69. Histopathology
• Becoming more important for endotyping, thereby directing
potential therapies, e.g. biologics.
• To confirm diagnosis.
• eCRS requires quantification of the numbers of eosinophils,
• i.e.10 or >/HPF. (EPOS 2020)

70. Microbiology
• Newer culture-independent techniques including genetic
sequencing
• May provide significant insight into CRS pathophysiology.
• This include
• Sequencing of all DNA (metagenomics) or all transcribed RNA
(metatranscriptomics)
• Identification of proteins (metaproteomics) or
metabolites (metabolomics)
• Showing the diversity ,structure, full genetic potential and in situ
activity of the mucosa-associated microbiota.

71. Testing for immune function
• Reserved for
• Recalcitrance CRS to standard treatments (e.g rapid recurrence of
symptoms after stopping antibiotics)
• CRS with LRTI(pneumonia, particularly if recurrent, or bronchiectasis).

72. Cont..
• Serum immunoglobin level
• Suspected of having humoral immunodeficiency
• Measurement of serum-specific antibody titres (usually IgG) in
response to vaccine antigens.
• Immunizing a patient with protein antigens (e.g. tetanus toxoid) and
polysaccharide antigens (e.g. pneumococcus) and assessing pre- and
post-immunization antibody levels.

73. C-reactive protein (CRP)
• An aid to targeting bacterial infection and thus limiting
unnecessary antibiotic use.
• Low or normal CRP
• low likelihood of bacterial infection and are unlikely to benefit from
antibiotics.
• Raised CRP is predictive of a positive bacterial culture on sinus
puncture or lavage
• CRP levels are significantly correlated with changes in CT scans

74. Procalcitonin
• Indicating more severe bacterial infection
• Guide prescribing antibiotic in RTI in the community.

75. ESR
• Raised in ABRS,
• Reflect disease severity
• ESR of >10 predictive of sinus fluid levels or sinus opacity on
CT scans.

76. Other tests
• Mucociliary testing - primary ciliary dyskinesia (PCD)
• Sweat testing - for cystic fibrosis
• Investigations to look for LRT infection
• Peak expiratory flow
• Provocation tests and
• Expired nitric oxide measurement.

77. Warning symptom

78. Complications of ABRS
Orbital Intra-cranial Osseous
Pre-septal cellulitis Subdural empyema Pott’s puffy tumor
(subperiosteal abscess of
frontal sinus)
Orbital cellulitis Meningitis/
encephalitis
Maxillary osteomyelitis (in
infancy)
Subperiosteal abscess Intra-cerebral abscess
Orbital abscess Epidural abscess
Superior sagittal sinus
thrombosis
Cavernous sinus thrombosis

79. Barrier
Penetration
Environment
T1/T3
T2
Asthma
Fibrin Polyps, lessfibrosis
Barrier failure
Bronchiectasis
Intact barrier
Fibrosis, lessfibrin
Polyps
Host
CRS Endotypes

80. Barrier
Penetration
Environment
T1/T3
T2
Biologics
Surgery
Corticosteroids (strong)
Surgery
Corticosteroids
(weak)
Antibiotics
Host
Treatment of CRS Endotypes

81. RHINOSINUSITIS IN CHILDHOOD
• Quality of life of parents/children
• Anatomy:
• Birth only maxillary sinus and 2 or 3 ethmoidal cells.
• Sphenoid sinuses are present at the age of 2 years, even though
some rudimentary structure may be seen in neonates.
• Frontal sinuses start to develop at the age of 6 years.
• At about 7 years, maxillary sinuses reach the height of nasal fossa
floor.

82. RHINOSINUSITIS IN CHILDHOOD - Contd
• Immune immaturity: higher number of episodes of upper airway
infections of viral etiology (6 to 10/ year)
• Clear reduction of prevalence after 6 to 8 yrs: owing to
maturation of immune system.
Dr. Nashmee Ali Rasheed/ Rhinosinusitis/ 2075.04.22

83. RHINOSINUSITIS IN CHILDHOOD - Contd
• Symptoms specific than in adults
• Rhinorrhea : most frequent symptom in all forms of RS (70% to
100%)
• Cough (50% to 95%), dry or productive: worsen at night.
• Nasal obstruction and mouth breathing : highly prevalent,
especially in CRS (70% to 100%)
• Fever, halitosis and lack of appetite.
• Headache and facial pressure: uncommon symptoms.
Dr. Nashmee Ali Rasheed/ Rhinosinusitis/ 2075.04.22

84. RHINOSINUSITIS IN CHILDHOOD -
Aetiology factors
• Allergy
• Immunodeficiency
• laryngopharyngeal reflux,
• Primary ciliary dyskinesia
• Adenoid hyperplasia,
• Parental smoking
• Adenoids and tonsils-
• act as a bacterial reservoir.
Dr. Nashmee Ali Rasheed/ Rhinosinusitis/ 2075.04.22

85. Pathogenesis (Paediatric CRS)
• Environmental factors are as likely as genetic ones to influence
the occurrence of nasal polyps.
• Many markers of inflammation are parallel to adults.
• Inflammatory cytokines present in sinus tissues are more
abundant when concomitant asthma is present.

86. Refrences
• Fokkens W.J., Lund V.J. , Hopkins C., Hellings P.W., Kern R.,
Reitsma S., et al. European Position Paper on
Rhinosinusitis and Nasal Polyps 2020 Rhinology. 2020
Suppl. 29: 1-464.
• Walter Graham Scott-Brown, Watkinson JC, Clarke R. Scott-
Brown’s Otorhinolaryngology Head and Neck
SurgerynVolume 1-8th-edition-pdf

87. Thank you
73