Chronic rhinosinusitis

CHRONIC
RHINOSINUSITIS
29 DECEMBER 2017
THANSINEE SAETAE, MD.
PEDIATRIC ALLERGY AND IMMUNOLOGY UNIT
KING CHULALONGKORN MEMORIAL HOSPITAL

SYMPTOMS OF RHINOSINUSITIS
A.T. Peters et al. Ann Allergy Asthma Immunol 2014;113:347-385

Sarbjit S. Saini. Middleton's 8th edition.
DEFINITION CHRONIC RHINOSINUSITIS
• Inflammation of the nose and the paranasal
sinuses characterized by 2 or more symptoms;
• (1 of which should be either the first or the second)
• Nasal blockage/obstruction/congestion
• Nasal discharge (anterior/posterior nasal drip)
• Facial pain/pressure
• Reduction or loss of smell
• And Either Endoscopic signs;1 or more;
• Polyps
• Mucopurulent discharge primarily from middle meatus
• Edema/mucosal obstruction primarily in middle meatus
• And/Or CT changes
• Mucosal changes within the ostiomeatal complex
and/or sinuses
Fokkens WJ et al. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012.
A summary for otorhinolaryngologists. Rhinology 2012;50:1-12.
Chronic rhinosinusitis with and without Nasal polyposis:
> 12 weeks without complete resolution of symptoms

EPIDEMIOLOGY
• Affects about
• 11% of adults in Europe
• 12% of adults in the United States.
• CRS has a significant effect on health-related quality of life and is associated with
substantial health care and productivity costs.
Zhang et al.J Allergy Clin Immunol 2017;140:1230-9.

EPIDEMIOLOGY
• CRS without nasal polyp (CRSsNP)
• A GA2LEN study1 estimated the prevalence of CRS measured by questionnaire at 10.9% of
the population.
• CRS with nasal polyps (CRSwNP)
• The prevalence of CRSwNP in Europe is estimated to be between 2.1% (France) to 4.4%
(Finland) and is 4.2% in the United States.2
1. Hastan D et al.. Allergy 2011;66: 1216-23.
2. Zhang et al.J Allergy Clin Immunol 2017;140:1230-9.

Zhang et al.J Allergy Clin Immunol 2017;140:1230-9.

EPIDEMIOLOGY
• Overall,studies have indicated wide variations in the prevalence of chronic
rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps
(CRSwNP) between Asian and European countries.
• Recent research has demonstrated that inflammatory signatures of CRS vary around the
world, with less eosinophilic and more neutrophilic inflammation found in Asia
compared with Europe and NorthAmerica.
• However,the percentage of type 2 signature disease in patients with CRS is
dramatically increasing (‘‘eosinophilic shift’’) in several Asian countries over the
last 20 years.
Zhang et a. J Allergy Clin Immunol 2017;140:1230-9.

EPIDEMIOLOGY
• Nasal polyps occur more frequently in
• Asthma patients with aspirin sensitivity
• Cystic fibrosis; especially when polyps occur in children and adolescents.
• Other conditions;Churg-Strauss syndrome and Kartagener syndrome (situs inversus).
• CRSwNP and aspirin sensitivity were associated with an increased risk of asthma.
• The incidence of nasal polyps is higher in men than in women and significantly increases
after the age of 40 years.
• A clear relationship between allergy and CRSwNP has not been shown.

DEVELOPMENTAL OF SINUSES
• The paranasal sinuses are cavities that are only partially present at birth
(maxillary and ethmoidal sinuses) but develop in childhood from the ethmoidal
sinuses into otherwise compact bone of the forehead and the sphenoidal region.

SINUS PHYSIOLOGY
• The sinus cavities
• Air,classic, pseudostratified, ciliated columnar epithelia interspersed with goblet cells.
• The cilia sweep mucus toward the ostial opening.
• Obstruction of the ostia
• Mucous impaction à decrease oxygenation à anaerobic condition à purulent
secretions à growth of bacteria
• Decrease air pressure within the sinus cavity à pain and the sensation of pressure
• Sinonasal biofilms
• communities of bacteria and fungus, which anchor to the mucosal surfaces or exist
within the mucus layer.
• evasion of host defenses, decreased susceptibility to antibiotic therapy

Maxillary sinus
Frontal sinus
Ethmoid cells
The osteomeatal complex
has been identified as a key region
for ventilation and drainage of
the maxillary,anterior ethmoidal
cells, and frontal sinuses.
The osteomeatal complex
• maxillary infundibulum
• frontal recess
• ethmoidal bulla
• middle meatusOsteomeatal
complex
Middle meatus
Ethmoidal bulla
Maxillary
infundibulum
Frontal recess

MICROBIOLOGY IN CRS
Children
• Aerobes: Alpha-hemolytic streptococcus
(20.8%), H influenzae (19.5%), S pneumoniae
(14.0%), S epidermidis (13.0%),S aureus (9.3%).
• Anaerobes: 8.0%
Adults
• Aerobes: Streptococcus species (21%), H
influenzae (16%), P aeruginosa (16%), S aureus
(10%), and M catarrhalis (10%)
• Anaerobes: Prevotella species (31%),
Streptococci (22%), Fusobacterium species (16%)
Nosocomial
• Gram-negative enteric species: P aeruginosa,
Klebsiella pneumoniae,Enterobacter species,
Proteus mirabilis and Serratia marcescens
• Gram-positive cocci: streptococci,
staphylococci
CRSwNP
• Polymicrobial aerobic and anaerobic flora

• Various bacteria are involved in acute bacterial rhinosinusitis.
• Cultures of the maxillary sinus samples found bacteria with the following frequencies:
26% grew Streptococcus pneumoniae; 28% Haemophilus influenzae; 6% Moraxella
catarrhalis; and 8% Staphylococcus aureus.
• Cultures of the middle meatus samples found bacteria with the following frequencies:
34% grew Streptococcus pneumoniae; 29% Haemophilus influenzae; 11% Moraxella
catarrhalis and 14% Staphylococcus aureus.
ACUTE BACTERIAL RHINOSINUSITIS

• In chronic maxillary sinusitis, by contrast,anaerobic bacteria alone,or mixed
infections with facultative anaerobes and aerobes are predominant.
• e.g. with S. aureus, coagulase-negative staphylococci,Pseudomonas aeruginosa
• A recent study identified species of the genera Pseudomonas, Citrobacter, Haemophilus,
Propionibacterium, Staphylococcus, and Streptococcus being numerically dominant.
CHRONIC RHINOSINUSITIS WITHOUT POLYPS

• It is unclear, however,whether bacterial infections truly contribute to chronic
sinusitis pathophysiology or may instead just be secondary to the local milieu in
an obstructed sinus that encourages bacterial growth.
• It has been suggested,therefore,that together with the CT-based findings of anterior
ethmoidal cells and obstruction of the ostiomeatal complex, the development of chronic
sinusitis is a two-step process involving infection and then mucosal remodeling
with obstruction.
CHRONIC RHINOSINUSITIS WITHOUT POLYPS

CHRONIC RHINOSINUSITIS WITH POLYPS
Nasal polyps are edematous semitranslucent
masses in the nasal and paranasal cavities,originating
mostly from the mucosal linings of the sinuses
and prolapsing into the nasal cavities.

• The typical history in the development of nasal polyps is a “cold that persisted over
months or years, with nasal obstruction and discharge as the most prominent
symptoms.
• Anosmia is a typical symptom for nasal polyps.
• Nasal polyposis rarely causes pain despite the fact that most of the sinuses are opacified.
• Viral infections frequently cause prolonged episodes of severely obstructed nasal passages
and colored secretions, with subsequent bacterial infection.
• Inhalant allergens do not seem to induce additional complaints or to cause polyps.

Allergic Rhinitis
• Skin prick tests for inhalant allergens reveal no difference between polyps from
atopic and nonatopic subjects in terms of concentrations of IgE or numbers of
eosinophils.
• Local total IgE concentrations are high,most likely owing to local production of S.
aureus enterotoxins (SAEs),which act as superantigens and induce polyclonal
IgE formation.

Asthma
• CRSwNP frequently is found in association with asthma and nonspecific
bronchial hyperresponsiveness.
• The medical or surgical treatment of CRSwNP may have a favorable impact on
the control of asthma.

Aspirin sensitivity
• Samter’s triad is described a symptom triad of aspirin sensitivity, corticosteroid-
dependent asthma,and nasal polyposis.
• Aspirin sensitivity is suspected after a typical respiratory reaction.
• Acute asthma and/or rhinitis attacks are caused by ingestion of aspirin and other
NSAIDs that share the ability to inhibit the enzymes COX -1 and -2.
• At least 15% of patients with an aspirin- provoked asthma and rhinitis attack are
unaware of their aspirin sensitivity.

Aspirin sensitivity (Cont.)
• The full typical clinical picture of aspirin-exacerbated respiratory disease (AERD)
is characterized by increased blood eosinophil counts,an increase of eosinophils in
the nasal and bronchial mucosa,and elevated cysteinyl-leukotriene
concentrations in the tissue and urine,which further increases after aspirin
exposure.
• Thus far, no validated laboratory test is available to establish the diagnosis, which
must then be based on oral, bronchial,or nasal provocation tests.

Fungal disease
• Fungal sinusitis is currently divided into four primary categories:
• Acute/ fulminant
• Chronic/ indolent
• Fungus ball
• Allergic fungal sinusitis; AFS,
• The most common form and is associated with nasal polyps.
• The fungus ball,also referred to as mycetoma,
• is mostly unilateral,often in association with symptomatic chronic maxillary sinusitis
and little mucosal tissue reaction in an immunocompetent host.
Invasive
Non-Invasive

Fungal disease (Cont.)
• Imaging studies (CT or MRI) may show
heterogeneous opacification, calcification with
increased attenuation in CT, and hypointense signal
characteristics onT2-weighted MRI sequences
secondary to the presence of calcium in the fungal
concretion.
• Within the sinus,creamy or claylike secretions
typically are found.
• A possible dentogenic pathway has to be excluded,
and removal by means of sinus surgery represents the
treatment of choice.

• Fungi associated with allergic fungal rhinosinusitis (AFS) are ubiquitous and predominantly
of the dematiaceous family
• Aspergillus, Rhizopus,Alternaria, Curvularia, Bipolaris specifera, and others.
• AFS mostly develops in atopic young hosts, along with nasal polyps, and immediate
hypersensitivity skin testing specifically for the fungus may yield positive results,with an
elevated serum total IgE and fungus-specific IgG.
• The sinus mucosa shows a characteristic eosinophilic inflammation, with allergic mucin
(seen as peanut butter–like secretions) filling the sinuses.

• Invasive forms
• indolent chronic, slowly destructive disease which is mostly caused by Aspergillus flavus.
• fulminant acute, necrotizing form in immunocompromised hosts (e.g.,AIDS,CD4+
counts less than 50 cells/mL,or neutrophil counts less than 1000 cells/ mL), mostly caused by
Aspergillus fumigatus and often lethal within days of onset because of hematogenous
dissemination despite high-dose intravenous antifungal treatment.

Cystic fibrosis
• Involvement of the nose and sinuses is common in patients with CF.
• Sinusitis is almost always detected in radiologic investigations in patients with CF,
• even if many of these patients have no sinonasal complaints.
• The incidence of CRSwNP in CF varies,ranging from 6% to 48%, and CRSwNP is found in
children of 5 years of age and older.
• A recent study of 211 white adults with CF reported that 37% had CRSwNP.
• 50% of the children between 4 and 16 years of age who present with CRSwNP have CF.

Cystic fibrosis (Cont.)
• Mucosal changes in CF generally affect the
paranasal cavities bilaterally, possibly causing
facial deformities such as hypertelorism in
children.
• Development of the frontal and sphenoid
sinuses may be disturbed,resulting in
hypoplasia or even absence.
• Radiological signs such as the bulging of the
lateral nasal wall and the erosion of the
uncinate process seem to be characteristic of CF.

Cystic fibrosis (Cont.)
• Predominant organisms were Pseudomonas aeruginosa, S. aureus, H. influenzae, and
anaerobes.
• The response to antimicrobial therapy often is suboptimal when compared with that
in persons without CF.
• Sinus surgery should only be performed in case of severe symptoms or before lung
transplantation.
• The development of functional endoscopic sinus surgery has decreased the morbidity of sinus
surgery and reduced the recurrence of nasal polyposis in cystic fibrosis.

PREDISPOSING FACTORS TO RHINOSINUSITIS

IMMUNODEFICIENCY
• Evaluate patients for an immune deficiency
if CRS is resistant to usual medical
and/or surgical therapy. (Rec, B)
• Quantitative immunoglobulins
• IgG,IgA and IgM
• Specific antibody responses
• anti tetanus toxoid titer,pneumococcal vaccine
• If necessary,
• T-cell numbers (flow cytometry)
• T-cell function
Highly suspicious in
1. At least 2 serious sinus infections
2. Recurrent otitis media, recurrent lower
respiratory tract infections, bronchiectasis
The most common PIDs are humoral
immune deficiency.
• specific antibody deficiency
• IgA deficiency
• common variable immunodeficiency

IMMUNODEFICIENCY
• A clinical trial of IgG replacement (400 mg/kg per month) for up to 6 months.
• Humoral immune function should be reassessed at 4-6 months after the last infusion.
• Discontinued Immunoglobulin therapy
• Extend period of significant improvement because the susceptibility to infection
• Lack of clinical efficacy.
The use of immunoglobulin replacement in specific antibody
deficiency or IgG subclass deficiencies remains controversial.

PHENOTYPES OF
CHRONIC RHINOSINUSITIS

1. EPITHELIAL PHENOTYPE OF CRS
• The loss of epithelial barrier function plays an essential role in the
pathogenesis of CRS,
• permitting access to the sinus stromal tissue by allergens,bacteria,bacteria-derived antigens.
• Loss of epithelial barrier function reflects numerous inflammatory processes.
• The metaplastic transformation of epithelial cells into goblet cells, a process mediated
especially by IL-13 in the former and driven by numerous mediators but especially ascribed to
amphiregulin and oncostatin M.
Gurrola and Borish. J Allergy Clin Immunol 2017;140:1499-508.

2. NASAL POLYPOSIS
• Current recommendations phenotype CRS based on the presence (chronic
rhinosinusitis with nasal polyps [CRSwNP]) or absence (chronic rhinosinusitis without
nasal polyps [CRSsNP]) of nasal polyps (NPs).
• CRSwNP is more likely to be associated with an eosinophil-mediatedTH2 (IL-4–, IL-
5–, and IL-13–high) cytokine profile.
• CRSsNP was thought to present as a noneosinophilic disease.

• NP status alone can often be inadequate
for defining a TH2-high/IL-5–high state.
2. NASAL POLYPOSIS (CONT.)
Wang et al. J Allergy Clin Immunol 2016;138:1344-53.
• NPs in patients with CRS can be TH2 low in
between 15% and 80% of patients and similarly,
20% to 75% of these subjects did not express a
robust eosinophilia profile.
• In contrast,a significant subset (5% to 40%) of
patients with CRSsNP displayed a TH-
high/eosinophil-high profile.

• This problem of using NPs alone to define immune status becomes apparent when
considering the endotype of cystic fibrosis (CF).
• The phenotype of CF sinus run the spectrum of being paucigranulocytic,neutrophilic,
eosinophilic, or mixed granulocytic.
• The concept that a single genetic endotype can elicit numerous phenotypes could
extend to all presentations of CRS.
2. NASAL POLYPOSIS (CONT.)

3. INFLAMMATORY CELL PROFILE
(NEUTROPHILICAND EOSINOPHILIC CRS)
• NPs can only at best approximate acting as a surrogate for assessing eosinophil
status,
• An alternative approach is to specifically evaluate sinus tissue and quantify
eosinophil expression.
• Using tissue concentrations of eosinophil cationic protein (ECP) as a surrogate
marker for tissue eosinophilia, as with IL-5, although values were significantly greater
in patients with CRSwNP,there was extensive overlap in ECP concentrations
between patients with and without NPs.*
* Tan et al. J Allergy Clin Immunol 2017;139:699-703.e7.

MICROBIOME PHENOTYPES OF CRS
• Multiple studies have now demonstrated that CRS involves dysbiosis of the
microbiome,
• asymmetric diversity rather than overexpression of a predominant species as the culprit.
• Potential harmful changes that occur with antibiotic and anti-inflammatory
treatments.

ENDOTYPING OF
CHRONIC RHINOSINUSITIS

ENDOTYPING OF CRS
• CRS needs to be approached properly as a continuum of inflammatory processes
with high and variable expression of immune and inflammatory markers.
• It might be possible to make clinically available the means of defining the inflammatory
endotype based on microarray-based studies with detailed analyses of individual
• transcriptomic, proteomic,or one of the vast number of other ‘‘omic’’ signatures.

• Noneosinophilic NPs (</= 3 eosinophils in
10 distinct x400 high-poweredfields)
• Hypereosinophilic NPs (>/=25 eosinophils
in 10 distinct x400 high-poweredfields),
• The majority of patients fell within a
continuum of intermediate expression
without any distinct cutoff
• That would unambiguously separate an
‘‘eosinophilic’’ from a ‘‘noneosinophilic’’
process.
These data argue that any attempt to define a
distinct cutoff distinguishing eosinophilic
from noneosinophilic polyps would be at
best arbitrary.
Steinke et al. J Allergy Clin Immunol Pract 2017;5:1582-8.

ENDOTYPING OF CRS
• The very concept of their being ‘‘distinct’’ endotypes in patients with CRS is
misguided;
• That is, instead of being distinct phenotypes or endotypes defined by the absolute presence
or absence of eosinophils, a given cytokine, or of any other specific marker.
• It remains reasonable to speculate that more robust expression of any of these
markers can serve as an aid for guiding therapeutic decisions.
• None of these markers has proved superior than distinguishing the presence and absence
of NPs.

PATHOPHYSIOLOGY IN CRSSNP
Two main defensive strategies against the infection come into play.
1. Nonspecific phase
• Mucus and its contents: lysozyme and defensins
• VEGF: promote nasal epithelial cell growth and inhibit
apoptosis.
2. Innate and adaptive immune response
• The innate immune system operates through
phagocytosis of the microorganisms by neutrophils,
monocytes,and macrophages.
• The adaptive immunity reacts on antigen presen-
tation through formation of immune products (Th1&Ab).Deficiencies in epithelial immune barrier function and
the production of antimicrobial proteins presumably
may compromise the interaction between the host and
external immune stimuli.

PATHOPHYSIOLOGY IN CRSSNP
• Sinus fluid from surgical patients with
CRSsNP, inflammatory cells are
predominantly neutrophils
• Tissue eosinophilia is not a hallmark
of CRSsNP with major differences in
the pathophysiology of both sinus
diseases.

PATHOPHYSIOLOGY IN CRSWNP
• The highest concentrations of IL-5, which
correspond to eosinophil cationic protein
(ECP) measurements,were found in polyp
tissue in subjects with nonallergic asthma
and aspirin sensitivity.
• Eosinophil recruitment is mediated mainly
by the chemokines RANTES and eotaxins,
in cooperation with IL-5.
Treatment of eosinophil-infiltrated polyp tissue with
neutralizing anti-IL-5 monoclonal antibodies, in vitro
caused eosinophil apoptosis and decreased tissue
eosinophilia.
Treatment with topical glucocorticosteroids decreased the
density of eosinophils and the expression of VCAM-1 in
polyps, as well as the expression of eotaxin and IL-5, resulting
in a marked reduction of tissue eosinophils.

• An analysis of signal transduction factors revealed an upregulation of GATA3
• Upregulation ofTh2 cytokines
• Downregulation of Foxp3
• Downregulation of regulatoryT cells (Tregs)
• Persistent inflammation typical of polyp disease.
• Nasal polyps contain large quantities of B lymphocytes and plasma cells
• Producing IgA, IgG, IgE
• The expression of B cell–activating factor of the TNF family (BAFF) has been shown to be
upregulated
• Autoantibodies;anti-dsDNA, IgG and IgA antibodies.

Role of Staphylococcus aureus Enterotoxins
• S. aureus may form biofilms to serve as a nidus of infection and allow the microbe to
survive antibiotic treatment
• S. aureus may continuously form enterotoxins with superantigenic activity.
• modify the functions of T and B cells, eosinophils,and other inflammatory cells.
• S. aureus constitutively can release classical and enterotoxin gene cluster locus–derived
enterotoxins (i.e., SAEs)
• SAE stimulation may lead to a Th2-polarized eosinophilic inflammation and further
impairment of T regulatory function,as well as multiclonal IgE production.

Role of Staphylococcus aureus Enterotoxins (Cont.)
• IgE antibodies to SAEs were present in polyp tissue and that these were associated
with a more severe local eosinophilic inflammation
• Up to 80% of polyps from these patients,SAE IgE can be found locally.
• The presence of IgE antibodies to Staphylococcal enterotoxins (SE IgE antibodies) and
the increase in local total IgE significantly increases the risk of suffering from
comorbid asthma.
New therapeutic principles may arise from these
findings, including antibiotic therapy and anti-IgE.

Zhang et a. J Allergy Clin Immunol 2017;140:1230-9.

PATHOPHYSIOLOGY IN CRS
• The typical cytokine pattern of CRSsNP disease consists of proinflammatory
and neutrophil-associated cytokines including IL-1β,TNF-α, and IL-8, resulting in
increased neutrophil activation MPO.
• In contrast with CRSwNP, which is characterized by an eosinophil-richTh2-
dominated cytokine pattern with high IL-5 and, low TGF-β concentrations.

PATIENT EVALUATION, DIAGNOSIS,
DIFFERENTIAL DIAGNOSIS

PATIENT EVALUATION IN CRSSNP
• Evaluation
• Character,severity,duration and course of disease
• Comorbid illnesses,underlying pathologic condition
• Earlier management attempts
• Anterior rhinoscopy may show hyperemia and swelling of the inferior turbinates,structural
deformities of the septum,and even purulentsecretions from the sinuses (middle meatus).
• Endoscopy, mostly performed with a rigid scope after nasal decongestion is achieved, is a
rapid and easy method to evaluate the middle nasal meatus and the ostiomeatal complex,
posterior nasal structures,and the nasopharynx.
• In children,fiberoptic rhinoscopy is a convenient alternative to rigid endoscopy and also
permits examination of the pharynx and larynx.

PATIENT EVALUATION
• Standard sinus radiographs
• may be used for the diagnosis of acute frontal or maxillary
sinusitis
• often do not provide additional information over history alone.
• Ultrasound imaging:may be used in pregnant women
• CT define the extent of the disease,anatomic abnormalities,
and changes in the ostiomeatal complex and provides a “map”
for surgery indicate for evaluation of orbital or cerebral
complications of sinusitis,and in the diagnosis of all sinister
pathologic entities such as tumor,meningoceles, or mucoceles.
• MRI:fungal sinusitis and extension of disease into the brain.
Nasal cultures:
• infections resistant to treatment
• immunocompromised hosts
• HIV,CMT recipients,DM, ICU patients

Rhinitis
Eye diseases and problems with accommodation
may cause periorbital pain sensations.
Facial pain and headache:migraine, tension, cluster and
rebound headaches,cranial neuralgia,and atypical facial pain.
Tumor
Unilateral nasal obstruction,possibly with pain or bloody discharge,is always suggestive of a
sinister pathologic entity such as tumors developing in the nasal,paranasal,or nasopharyngeal cavities.

PATIENT EVALUATION IN CRSWNP
• Diagnosis of CRSwNP is made by rigid nasal endoscopy.
• The extent of disease within the sinuses:CT scan with coronal sections
• mucosal structures and the delicate anatomy of the sinuses
• A CT scan is mandatory before sinus surgery is considered and also must be
available during the procedure to inform the surgeon about anatomic variations.
• An MRI scan may be helpful for the diagnosis of fungal disease or tumor or if intra-
cranial extension of disease is suspected.

The endoscopic staging system is based mainly
on the assumption that polyp growth starts from
the middle nasal meatus and then extends toward
the floor of the nose. The radiologic staging system includes all sinuses and the
ostiomeatal complex bilaterally

• Nasal endoscopy needs to be performed to confirm the diagnosis and exclude other
diseases.
• Turbinate hypertrophy, concha bullosa,CRSsNP, adenoid hypertrophy
• Any unilateral obstruction,nose bleeding,or crusting should be intensively
investigated.
• Papillomas,benign or malignant tumors, meningoencephaloceles
• Nasal polyps may represent a part of a systemic disease.
• Asthma, aspirin sensitivity,Churg-Strauss syndrome, inhalant allergies,CF, and other lung
diseases.

• A smell test, SPT for inhalant allergens,and eventually cytologic examination of
nasal secretions for eosinophils, and a blood sample for an eosinophil count may
provide additional information.
• Endoscopically guided microbiology from the middle meatus or biopsy may help
direct the optimal treatment.

SYSTEMIC ANTIBIOTICS
• The benefit of antibiotic treatment is questionable.
• Antibiotics are indicated to treat acute exacerbations.
• Eradication of infection also depends greatly on whether sinus aeration and
adequate mucociliary clearance can be restored.
• The most appropriate patients with CRS for antibiotic treatment are those with
persistent purulent drainage.
• Antibiotics such as macrolides may have anti-inflammatory together with
antibacterial effects.
• A recent evidence- based review recommended against the use of intravenous
antibiotics for uncomplicated CRS.

SYSTEMIC ATB IN CHILDREN
• There is no good evidence in the literature to support the use of
antibiotics for the treatment of CRS in children.
• The same ATB for acute rhinosinusitis
• Amoxicillin (45 or 80 mg/kg daily).
• Amoxicillin-clavulanate à cover B-lactamase organisms,H influenzae
• Alternative choices:quinolones or clindamycin with a 2nd or 3rd generation
cephalosporins

LONG-TERM SYSTEMIC MACROLIDE ANTIBIOTICS
Roxithromycin 150mg/d 12 wk – change from baseline
at 12 wk
Azithromycin 500 mg/d 3 d then 200mg/wk 11 wk
– no significant
Erythromycin 500 mg/d 2 wk then 250 mg/d 10 wk combine
with nasal irrigation and INCS – improve
• Clinical studies showing beneficial effects
are quite limited.
• These studies do not clearly
differentiate effects in CRSsNP or
CRSwNP.

TOPICAL ANTIBIOTICS IN CRS
• The role of topical antibiotics also continues to be an area of controversy.
• not recommend this intervention as either first-line or an appropriate prolonged therapy.
• In the postoperative period the sinus cavities
• delivery of medication to the sinonasal mucosa.
• Consider a 3 to 6 weeks course of topical antibiotics for CRS.
• With or without a nebulizer.
• Mupirocin, gentamicin or tobramycin irrigations
• Sensorineural hearing loss was noted in 23% of patients with CF who had used frequent irrigations.
Gurrola and Borish. J Allergy Clin Immunol 2017;140:1499-508

SYSTEMIC ANTIBIOTICS IN CRSWNP
• Doxycycline (200 mg on the first day followed
by 100 mg once daily for 20 days)
• significant decrease in polyp size beginning at
week 2 and persisting for 12 wks
• significant decrease in nasal secretion of
eosinophil cationic protein
• no significant improvement in nasal peak
inspiratory flow rate
Van Zele et al. J Allergy Clin Immunol. 2010;125: 1069-1076
Schalek P et al. Eur Arch Otorhinolaryngol. 2009;266:1909-1913
• Patients undergoing FESS
• Quinolone, Amoxicillin-clavulanate,
Cotrimoxazole, Placebo * 3 wks.
• No significancebetter results were found in
the antibiotic group
• Doxycycline had a significant but small effect
on polyp size compared with placebo,which was
present for the length of the study (12 weeks).
• Doxycycline showed a significant effect on
postnasal discharge.

STEROID NASAL SPRAYS
• CRSwNP and CRSsNP: Use INS (sprays and aerosols) (StrRec,A)
• reduce symptoms of blockage,rhinorrhea,and occasionally hyposmia
• however,symptoms recur within weeks to months of discontinuation of treatment.
• Children:
• There are no RCTs evaluating the effect of INSs in children with CRS.
• However,proven efficacy and safety of INSs in AR in children makes INSs a
reasonable and safe choice for treatment of CRS.
• Mometasone fuorate 2 yr, Fluticasone propionate 4 yr

TOPICAL STEROID SINUS INSTILLATIONS OR DROPS
• CRSsNP
• benefit from topical steroid irrigations (rinses)
• effects on nasal and sinus pain symptoms,avoid surgery during the treatment
period.
• CRSwNP
• controversy results
• decreased need for sinus surgery (from 78% to 52%)
• also may reduce the incidence of polyp recurrence after surgery.
• may be inadequate for severe bilateral polyps.
Topical steroid instillations and/or drops are not approved by
the FDA in the United States.

SYSTEMIC GLUCOCORTICOIDS
• CRSsNP: short course of oral steroids for treatment of (Rec, C)
• CRSwNP: short-term treatment with oral steroids in because it decreases polyp
size and alleviates symptoms.(StrRec,A)
• medical polypectomy
• repeated applications of oral corticosteroid bursts may lead to systemic side effects.
• beginning with 32 mg of prednisolone and stepwise reducing the dose during a 14 to 20
days oral course
• Children:
• When intranasal steroids fail to relieve mucosal inflammation or nasal polyps.
Wu et al. Immunol Allergy Clin N Am 2009;29:705–717

SALINE IRRIGATION, AH, DECONGESTANTS, LTRA
Saline irrigation (Rec,A)
• Adjunctive treatment
• Improve medication delivery,healing
outcomes,and mucociliary clearance.
• Determination of the optimal composition
and pH of the irrigation.
• The optimal delivery method for saline
irrigation is not clear.
• Antihistamines
• Consider in pt coexistent
• Alpha-adrenergic decongestants
• No beneficial for maintenance
treatment
• Leukotriene modifiers
• adjunct to topical steroid in CRSwNP.
• Montelukast modest symptomatic
benefit
Gurrola and Borish. J Allergy Clin Immunol 2017;140:1499-508

TREATMENT: CRSWNP WITH AERD
• Avoidance of aspirin and other NSAIDs
• may prevent exacerbations but does
not prevent progression of disease.
• selective COX-2 inhibitors (celecoxib,
rofecoxib) usually are well tolerated.
• Leukotriene receptor antagonists
• evidence for their unique efficacy is lacking.
• Oral and/or topical glucocorticosteroids
• effective but they cause side-effects in long-
term usage.
• Aspirin desensitization
• relapse of risk in case of noncompliance
• does not appear to modify the long-term
course of the asthma or sinus disease.
• gastrointestinal side effects
• long-term studies after surgery are lacking.

TREATMENT: CRSWNP WITH AFS
• Antifungals are indicated only for invasive forms of sinus mycosis or in immuno-
compromised patients.
• Both surgical intervention and the use of systemic and long-term topical
corticosteroids are recommended.
• Total serum IgE can be helpful in the clinical follow-up of these patients,
• an increase in total serum IgE was found to have significant predictive value for the need
of recurrent surgical intervention.

SURGERY
• Removing mucosal disease and the involved bone within the
ethmoid sinuses and sinus ostia under endoscopic visualization
• to restore sinus ventilation and drainage by opening the key areas
and preserve sinus mucosa.
• To reduce symptoms, increase the quality of life, decrease morbidity

FUNCTIONAL ENDOSCOPIC SINUS SURGERY (FESS)
• Standard procedure
• good results in patients resistant to medical treatment.
• Complications
• severe bleeding,orbital trauma,and cerebrospinal fluid leaks
• meningitis or cerebral damage
• Extensive postoperative care and follow-up are required to
preserve the postoperative results and prevent polyp regrowth.

SURGERY IN CHILDREN
Adenoidectomy
• Remove infection reservoir,biofilms
• < 7 years with asthma were more likely to
have failed adenoidectomy à FESS
Maxillary antral irrigation
• clear secretion & infection
• provide culture material
Balloon sinuplasty
• additional benefit to irrigation alone or in
combination with adenoidectomy
FESS
• in case of recurrenceof symptoms.
• Favor in à CF, nasal polyposis,
antrochoanal polyposis, or AFRS
• limited approach to FESS in
children
• removal of any obvious obstruction
• anterior bulla ethmoidectomy and
maxillary antrostomy.
1st step in the management of
refractory to maximal medical
management

FUTURE TREATMENTS OF CRS
Anti-IgE :Consider anti-IgE (omalizumab) for treatment of CRSwNP. (Rec, C)
• Double-blinded, placebo-controlled RCT
• 4 to 8 (subcutaneous) doses of omalizumab (n =16) or placebo (n = 8)
• significant decrease in total nasal endoscopic polyp scores after 16 weeks
• alleviate airway symptoms and QOL scores.
Gevaert et al. J Allergy Clin Immunol 2013;131:110-6.

COMPLICATIONS
• Orbital complications may develop in children and adolescents.
• Penetrating from the ethmoid or the frontal sinus through the thin bone of the orbital
frame.
• The first sign typically is reddish swelling of the medial upper eyelid (cellulitis),which may
develop into a subperiostial abscess,an intraorbital or eyelid abscess,or an orbital
phlegmona.
• Orbital phlegmona
• The patient may require immediate hospitalization for surgical care and intravenous
antibiotic treatment.
• Lead to a thrombosis of the cavernous sinus, with possible intracranial infection and
complete loss of vision.

COMPLICATIONS
• In adults
• Empyema of the frontal sinus may lead to meningitis, an epidural or subdural brain
abscess. à Immediate intervention
• Osteomyelitis of the frontal bone also necessitates surgical intervention and long-term
antibiotic treatment.
• Recurrent episodes of meningitis may arise from bony defects in the frontal skull base or the
sphenoid sinus,and require closure of the defect to prevent future risks.
• Fungal disease, if invasive, can penetrate bony structures and the orbit,cheek, and brain.
• Chronic closure of the frontal,ethmoidal, or sphenoidal sinuses may furthermore lead to
the development of a pyomucocele à surgically drained through the nose.

Chronic rhinosinusitis

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