Chronic rhinosinusitis in children

Chronic rhinosinusitis in childrenAnchalee Senavonge MD.Pediatric Allergy and Immunology departmentChulalongkorn University

Definition

Middletion textbook 8th edition, European position paper 2012

Definition

Diagnosis and Management of Rhinosinusitis: Highlights from the 2015 Practice Parameter

Recurrent ARS: at least 3 episodes of ABRS in 1 yr

Phenotypes of CRS

Ann Allergy Asthma Immunol 117 (2016)

Development of sinuses

• Maxillary sinus-1st , begin pneumatization from birth to 12 mo• Ethmoid: present at birth, reach adult size 12-14 yr• Frontal and sphenoid: later, complete pneumatization at mid

to late adolescence

Diagnosis and management of rhinosinusitis: a practice parameter 2014


Ostiomeatal complex

Sinus physiology• Pseudostratified, ciliated columnar epithelia interspersed with

globlet cells• Obstruction mucous impaction and ↓oxygenation ▫ limited gas exchange ↓ oxygen concentrations anaerobic

condition bacteria growth▫↓ Air pressure causes pain and pressure sensation

• Acute purulent sinusitis- ↑pressure pain due to inflammation of the mucosa and pressure from intra-sinus secretions

• Role of biofilm: “mortar” composed of a bacterially extruded exo-polymeric matrix (protein and nucleic acid)


Microbiology in CRSAdults• Aerobes: Streptococcus species

(21%), H influenzae (16%), P aeruginosa (16%), S aureus (10%), and M catarrhalis (10%).

• Anaerobes: Prevotella species (31%), Streptococci (22%), Fusobacterium(16%).

Children• Alpha-hemolytic streptococcus

(20.8%), H influenzae (19.5%), S pneumoniae (14.0%), S epidermidis (13.0%), and S aureus (9.3%).

• Anaerobes were recovered from 8.0% of all isolates

Bacteriologic findings associated withchronic bacterial maxillary sinusitis in adults. Clin Infect Dis. 2002

Maxillary sinus puncture with endoscopic middle meatal culture in pediatric rhinosinusitis.Am J Rhinol. 2008

Microbiology in CRSNosocomial rhinosinusitis • gram-negative enteric species

(eg, P aeruginosa, Klebsiella pneumoniae, Enterobacter species, Proteus mirabilis, and Serratia marcescens)

• gram-positive cocci (occasionally streptococci and staphylococci)

CRSwNP• Polymicrobial aerobic and

anaerobic flora

Bacteriology of chronic maxillary sinusitis associatedwith nasal polyposis. J Med Microbiol. 2005

Nosocomial sinusitis: a unique subset of sinusitis. Curr Opin Infect Dis. 2005;

Clinical manifestation

History•Persistent cough, prolonged anterior and posterior

nasal drainage, congestion• low-grade fever, irritability, and behavioral difficulties •Headache, especially in the frontal area, is a less

common •Frequent URI or recurrent sinusitis•Additional history should focus on identification of

any potential contributing factors

CRS in children. Pediatr Clin N Am 2013

Physical examination


Approach to CRS



Medical treatment of pediatric chronic rhinosinusitis. Am J Rhinol Allergy 2016

Stepwise evaluation of CRS

CRS Epidemiology and medical management. JACI 2011

Contributing factors in CRS


Approach to CRSCRSsNP CRSwNP

• Anatomical defect/ variation • Trauma, foreign body• Environmental triggers• Allergy • Immunodeficiency • GERD

• Eosinophilic mucin RS (EMRS)• Aspirin intolerance • Allergic fungal RS (AFRS)• Cystic fibrosis• Primary ciliary dyskinesia

Structure defect•Septal deviation, Haller cells, paradoxical curvature

of the middle turbinate, and agger nasi cells▫ predispose to obstruction of the ostiomeatal unit,

development of CRS, or both


Environmental triggers•Pollution: carbon monoxide, nitrous dioxide, sulfur

dioxide• Irritants in air pollution: sulfur dioxide ozone and

formaldehyde (indoor pollutant)•Hay fever• Indoor dampness and mold exposure•Active and secondhand cigarette smoking


Allergic/ nonallergic rhinitis• Congestion interfere drainage, ↑secretionhypoxic and

acidosis leads to mucociliary dysfunction bacteria multiply • CRS 36-60% have AR children, 40-84% in adult • CRS with AR likely to have persistent disease despite FESS• Test: SPT, specific IgE


Sinusitis-asthma• การสดูสารคัดหลัง่จากไซนัสลงไปในปอด• การกระตุ้นผ่านประสาทสมองคู่ท่ี 10 เกิดreflex

bronchospasm •การหายใจทางปากทำาใหเ้กิดภาวะหลอดลมแหง้และ

กระตุ้นการ สรา้งสารท่ีมฤีทธิท์ำาใหห้ลอดลมตีบโดยตรง• การกระตุ้นผ่านทางเซลล์ชนิดต่างๆ ท่ีเก่ียวกับการอักเสบ

เชน่ ทำาให้ eosinophils เขา้ไปในเยื่อบุของทางเดินหายใจทัง้ในไซนัสและหลอดลมมากขึ้น

เอกสารประกอบการประชุมวชิาการประจ ำา 2559 สมาคมสภาองค์กรโรคหดืแหง่ประเทศไทย

เอกสารประกอบการประชุมวชิาการประจ ำา 2559 สมาคมสภาองค์กรโรคหดืแหง่ประเทศไทย

Immunodeficiency

• “Humoral”• Other: ▫ Ataxia

telangiectasia, WAS, C3 deficiency

Immunodeficiency in chronic sinusitis. Am J Rhinol Allergy 2015Infectious CRS, JACI 2016

Immunodeficiency • Test▫ IgA, IgM, IgG, specific Ab level to polysaccharide vaccine

and tetanus/Diphtheria, flow cytometry, level of complement

▫ IgG subclass not typically recommended

Immunodeficiency in chronic sinusitis. Am J Rhinol Allergy 2015

Immunoglobulin deficiency in patients with CRS: Systematic review of the literature and meta-analysis. JACI2015

Immunodeficiency-Systematic review

Immunodeficiency CRS in children•Shapiro et al •34 of 61 children with refractory sinusitis •decreased IgG3 levels and poor response to

pneumococcal antigen -most common


• 94 children with RARS• Mean age 7.7+_2.6 yr• 6 patients not respond

to other therapy --> received IVIg, 4/6 responded

Clinical characteristics of recurrent acute rhinosinusitis in children. Asian Pac J Allergy Immunol 2015

Immunodeficiency-Siriraj study

CRSwNP

Middletion textbook 8th edition

• Eosinophils staining positive for the anti–eosinophil cationic protein (ECP) antibody EG2: prominent and characteristic finding 80% of polyps

• Lymphocytes and neutrophils: predominant in CF and PCD

Ann Allergy Asthma Immunol 117 (2016)

CRSwNP

Allergic fungal rhinosinusitis (AFRS)• CRSwNP with characteristic eosinophilic mucin

• semisolid nasal crusts that are similar to allergic mucin-peanut butter like

• presence of fungi in the mucin by staining or culture• Most common: Bipolaris, Curvalaria, Aspergillus, Drechslera

species

Diagnosis and management of rhinosinusitis: a practice parameter 2014CRS Epidemiology and medical management. JACI 2011

AFRS

1. Opacified sinus cavities despite extensive medical therapy

2. Characteristic CT hyperdensities within the opacified sinuses, which suggest accumulated allergic mucin

3. Evidence of IgE-mediated allergy

CT scans : opacified nasal cavities and paranasal sinuses ‘‘hyperdensities'' within the opacified sinuses, as well as local and linear areas of increased density within the nasal cavities.


AFRS

Cystic fibrosis• Mutations in CFTR on chromosome 7• ↓Chloride ion secretion result in ▫ ↑secretion viscosity▫ also -dilation of glandular ducts,↑ submucosal gland,↑ surfactant

gene expression• Suspect when▫ CRS in young ages (< 6 yr)with nasal polyps (40%)▫ Pseudomonas aeruginosa, Burholderia capacia colonization▫ chronic lung infection, pancreatic insufficiency

• Test: Gibson-Cooke sweat test or quantitative pilocarpine iontophoresis DNA analysis

Medical treatment of pediatric chronic rhinosinusitis. Am J Rhinol Allergy 2016Diagnosis and management of rhinosinusitis: a practice parameter 2014

Ciliary dysfunction• Primary ciliary dyskinesia (Kartagener syndrome)• rare AR disorder 10 per million• Suspect when▫ recurrent otitis media, CRS, pneumonia wih bronchiectasis ▫ situs inversus, sterile

• Test: screen-nasal nitric oxide (low in PCD) and the saccharine test, definite-transmission electron microscopy


CRSwNP Clinical clues

Eosinophilic mucin RS

• eosinophilic mucin, co-morbid asthma• CT opacity

AERD • multiple polyps, rapid growth• Samter triad• universal recurrence after surgery

AFRS • often unilateral/limited to 1 or a few sinus cavities• eosinophilic mucin with fungal hyphae and fungal allergy• CT opacity, hyperdensities and bony erosion

CF • <6yr• neutrophilia suggesting the high prevalence of acute

superinfections• Pseudomonas aeruginosa or Burkholderia cepacia• chronic lung infections or pancreatic insufficiency

Kartagener syndrome

Neutrophil, sinus inversus, recurrent otitis media, bronchiectasis

Management of CRS



Management in CRS• Medical

▫ Systemic antibiotic▫ Glucocorticoids▫ Combination systemic

antibiotics and steroid▫ Topical steroid irrigations ▫ Saline irrigations▫ Antihistamines▫ Leukotriene modifiers▫ Antifungal drugs

• Surgical▫ Adenoidectomy▫ FESS▫ Maxillary antral irrigation▫ Balloon sinuplasty

Systemic antibiotics• Controversial- lack of evidence• should use for acute exacerbation • First-line: broad spectum such as Amoxicillin-clavulanic acid• If MRSA suspected: combine Clindamycin, TMP-SMZ• Cystic fibrosis: Fluoroquinone (cover Pseudomonas)• Macrolide: anti-inflammatory effect

CRS in children: what a the treatment options? Immunol Allergy Clin N Am 2009CRS : epidermiology and medical management. JACI 2011

Systemic antibioticsCRSsNP• Short-term (<4 wk)

▫ cefaclor/amoxicillin improve in RARS (56%)

▫ Amoxicillin-clavulanic 67% vs ciprofloxacin 83% (cure rate, 9 days)

• Prolong course▫ Open label adult study-

clindamycin/amox-clav/ doxycycline 6 wk: improve CT at 3, 6 wk

CRSwNP• S aureus colonization 64%

▫ Doxycycline for 20 days – smaller polyps, secretion

▫ Doxycycline –small effect on size at 12 wk (quinolone, amox-clav not)

Oral steroids and doxycycline: approaches to treat nasal polyps. JACI 2010Short-term ATB in nasal polyps and S aureus. Eur Arch Otorhinolaryngol2009

Cefaclor vs amoxicillin in the treatment of sinusitis. Arch Fam Med. 1993Radiographic resolution of CRS after oral antibiotics. Ann AlAsthma Imm2007

Long term systemic Macrolide • Anti inflammatory effect in addition to bacteriostatic

• Erythromycin 500 mg/d 2 wk then 250 mg/d 10 wk combine with nasal irrigation and INCS – improve

• Roxithromycin 150mg/d 12 wk – change from baseline at 12 wk• Azithromycin 500 mg/d 3 d then 200mg/wk 11 wk - no

significant

Evaluation of the medical and surgical treatment of CRS . Laryngoscope. 2004. A dbRCT of macrolide in the treatment of CRS. Laryngoscope. 2006

Lack of efficacy of long-term, low-dose azithromycin in CRS. Allergy 2011

Systemic antibiotics in children• Available data does not justify the use of short-term oral

antibiotics for the treatment of CRS in children (Strength of recommendation: B)

• There might a place for longer-term antibiotics (equivalent to CRS in adults) (Strength of recommendation: D)

• Combination ATB+INCS, no specific recommendation for duration• Short-term show inadequate to relieve symptoms, long –term 3-6

weeks most recommend

European position paper on Rhinosinusitis and nasal polyp 2012

CRS in children: what are the treatment option. Imm Allergy Clin N Am 2009

Systemic antibiotics in children• Lack of good evidence, often treat with same ATB for ARS• Type often depends on local resistance patterns• IV antibiotics- lack of RCT, other intenvention▫ Retrospective study (Don et al) -89% resolution after maxillary sinus

irrigation and adenoidectomy followed by IV ATB 1-4 wk (Cefuroxime>Sulbactam>Ticarcillin clavulanate>Vancomycin)

Diagnosis and management of Rhinosinusitis, a practice parameter update.2014

Topical antibiotics• Systematic review -antibiotic nasal irrigations or nebulizations• Both CRS and acute exacerbations of CRS might benefit• Use 3 to 6 weeks• Topical irrigation with 80 mg/L gentamicin or tobramycin can

also be useful• Caution: SNHL 23% in CF +frequent irrigations with

aminoglycosides

Topical antimicrobials in the management of CRS: a systematic review. Am J Rhinol 2008CRS : epidermiology and medical management. JACI 2011

Intranasal steroids• Helpful in all types of CRS• no RCT in children, recent study show modest benefit• suppress mucosal inflammation especially co-morbid with AR,

asthma• CRS can exacerbate asthma INCS reduce• duration coincide with the longer use of antibiotics typically

3-6 wk• Mometasone fuorate 2 yr, Fluticasone propionate 4 yr

CRS in children: what are the treatment option. Imm Allergy Clin N Am 2009CRS in children. Pediatr Clin N Am 2013

Systemic steroid• A brief course of oral glucocorticoids - treatment for NP (‘medical

polypectomy'), AFRS• Children▫ additional effect on cough, CT scan, nasal obstruction▫ consider when INCS fail to relieve mucosal inflammation

• Hamilos. JACI 2011▫ prednisone 20 mg bid x 5 d10 mg bid x5 d 10 mg od x 5 d TCS

• British guidelines▫ prednisolone 0.5 mg/kg for 5-10 days + betamethasone nasal drops

• Hissaria, JACI2006(Adult trial) ▫ prednisone 30 mg od x 4 d with 5 mg↓ q2days IN budesonide 400 mg bid

CRS Epidemiology and medical management. JACI 2011CRS in children: what are the treatment option. Imm Allergy Clin N Am 2009

Systemic steroid in children•No RCT in children• Amoxicillin/clavulanate for 30 days and randomized to

receive methylprednisolone or placebo, average age 8 yr▫1 Mkday for 10 days, 0.75 MKday for 2 days, 0.5 MKday for

2 days, 0.25 MKday for 1 day• CT score +symptom - significant improvements both ATB

alone and ATB+ steroids

Efficacy and tolerability of systemic methylprednisolone in children and adolescents with CRS: dbRCT. JACI2011

Topical steroid irrigations• Aqueous budesonide 5-mg respule + 1 tsp of saline- benefit in CRS▫head down forward-->right lateral supine-->supine position, 1-2

min once daily• Fluticasone propionate 200 mg per nostril - benefit in polyp▫Position: lie on backs with heads hanging down in an inverted

vertical position, 2 min, once daily

• reduced the need for surgery, improved hyposmia, and decreased nasal polyp volume

CRS : epidermiology and medical management. JACI 2011

•Objective=evaluate the efficacy of postoperative topical sinonasal steroid irrigations for CRS▫budesonide (1 mg) or betamethasone (1 mg) in 240 mL

of normal saline solution

• Improve SNOT-22 score, esp high tissue eosinophilia (>10/hpf)

Nasal saline and nasal spray • Adjunctive• saline irrigation and sprays (1-4 times/day) -effective • less effective as monotherapy compared to topical steroid• Effect: reduces postnasal drainage, removes secretions, rinses

away allergens and irritants, and improves mucociliary clearance

• Nasal larvage (at least 200 mL of warmed saline) with squeeze bottles, syringes, and pot

Nasal saline irrigations for the symp-toms of chronic rhinosinusitis. Cochrane Database Syst Rev 2007

Adjunctive therapy• Antihistamine• Decongestant• Mucolytic agents• Antileukotriene ▫ Adjunct to topical glucocorticoids in the treatment of CRSwNP▫more effective in those with concomitant asthma and aspirin

intolerance (AERD)• Antireflux therapy

CRS Epidemiology and medical management. JACI 2011CRS in children. Pediatr Clin N Am 2013

Antifungal• Based on "fungal hypothesis" • Studies showed (1) fungal hyphae colonize in patients with

CRS (2) CRS show a systemic immune hyperresponsiveness to common inhalant fungi, such as Alternaria species

• However, neither topical antifungals (sprays and irrigations) nor systemic terbinafine are beneficial

Diagnosis and management of Rhinosinusitis, a practice parameter update.2014 CRS Epidemiology and medical management. JACI 2011


CRSsNP• Intensive medical therapy: a brief course of systemic

glucocorticoids + a prolonged course of oral antibiotics + 1 or more adjunctive therapies• Typical regimen: oral prednisone 20 mg bid for 5 days 20 mg od

for 5 days plus 3 -4 weeks of oral ATB (Amoxicillin-clavulanate is an excellent choice for most), sinus culture

• extend up to 6 weeks in patients with colored secretion• Maintenance: TCS, considers long-term macrolide



CRSwNP -management• Initial: brief course of oral glucocorticoids, TCS• Maintenance: ▫TCS▫Mucosal colonization with S aureus 64% CRSwNP (30%

healthy) –Doxycycline begin at week 2 and persist for 12 weeks

▫Antileukotrienes and aspirin desensitization▫Surgery



AFRS- management• Surgery• Systemic steroid: 1 mg/kg prednisone for 10 days, slowly reduced

by 1 to 2.5 mg/wk post-op• after surgery, topical glucocorticoid with budesonide • oral or topical antifungal- no trials, some respond (200 mg twice-

daily oral itraconazole to adults for 3 to 6 months)


Indication for surgery in CRS1. Complete nasal obstruction in CF caused by massive

polyposis or medialization of the lateral nasal wall2. Orbital abscess3. Intracranial complications4. Antrochoanal polyp5. Mucocoeles or mucopyocoeles6. Fungal rhinosinusitis


Adenoidectomy • Remove infection reservoir, biofilms• Meta-analysis in children 9 studies, mean age 5.8 yr-8/9 show

improvement 69.3%• One study (Ramadan) show asthma +young(<7yr) likely to

fail combine with FESS

CRS in children: what are the treatment option. Imm Allergy Clin N Am 2009 Diagnosis and management of Rhinosinusitis, a practice parameter update.2014

Maxillary antral irrigation•Optimize benefit of adenoidectomy•Clear seceretion/infection+ provide culture material•Adenoidectomy alone 61% vs combine 88% (in 32

children with CRS)•Post-op antibiotic- no improvement, not necessary

Diagnosis and management of Rhinosinusitis, a practice parameter update.2014 CRS in children: what are the treatment option. Imm Allergy Clin N Am 2009

Functional endoscopic sinus surgery (FESS)• When adenoidectomy fail-stepwise approach• Mucociliary clearance disorder such as CF, Kartagener

syndrome- offer first option • In children, less widespread due to concerns of hindering

midface growth• Outcomes are excellent 80-100% improve • Second-look: majority not endorsed • Risk (meta-analysis -0.6%) globe, CSF leak, nasolacrimal duct

injury

CRS in children: what are the treatment option. Imm Allergy Clin N Am 2009

•Many advocate a conservative approach to FESS in children, limited to removal of any obvious obstruction (such as polyps and concha bullosa), as well as anterior bulla ethmoidectomy and maxillary antrostomy

Balloon catheter sinuplasty (BCS)•Ballon dilatation of sinus ostia•Alternative to FESS•primarily used for maxillary sinus


Thank you

อาจารย์ comment****

CRSsNP• ICSเป็นหลัก•ATB ถ้ามี acute RS on top amoxicillin 1st line• Long term macrolide 12-15 wk•Adjunctive - ในเด็กมี saline irrigation เรื่อง steroid

ผสมนำ้า มsีtudy เฉพาะใน adult post op (เพราะการผ่าตัด จะเปิดทางให้ steroid เขา้ไปได้)

CRSwNP•Steroid: ICS + oral pred อาจารยใ์หป้ระมาณ 1 อาทิตย์•ATB ถ้ามี acute RS on top•Doxycycline มrีole in adult ถ้า รกัษาอ่ืนๆไมด่ีขึ้นให2้1 วนัเด็กยงัไมม่กีารศึกษาวา่ให้

•Saline irrigations

Surgery •Adenoidectomy: first step เชื่อวา่ adenoid reservior •FESS:2nd ในเด็ก ทำา แค่ maxillary +ethmoid เรยีกวา่

miniFESS (ไมท่ำาfrontal)

อ่ืนๆ•AFRS subset ABPA? เกิดจาก local invasive กระตุ้น IgG

imm cpx• ในเด็ก polyp เปน neutrophilเด่น• อ jet สงสยั incomplete form of CF?• Irrigate must positive pressue, gravity/ hypertonic ยงั

บวกลบ pH ด่าง แบบbuffer มท่ีีใชใ้น USA• การทำา sinus C/S ใช้ swab การเจาะจะทำากรณีTx failure ,

imm def•Macrolide เชื่อวา่ ยบัยัง้ IL8?? TLR

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Chronic rhinosinusitis in children

Health & Medicine