Учебники / Pediatric Sinusitis and Sinus Surgery Younis 2006

produces mucous stasis in the nasal cavities, especially in young children who are unable to blow their noses. This mucous may become locally infected and produce purulent anterior rhinorrhea. Nasal congestion results in the typical ‘‘adenoid facies’’ with persistent open-mouth-breathing posture. Diagnosis may be confirmed by anterior rhinoscopy of the decongested nose, office endoscopy, or lateral neck radiograph. Similar to the rationale behind adenoidectomy for the treatment of recurrent suppurative otitis media, the adenoid pad may serve as a bacterial reservoir predisposing to rhinosinusitis. There is evidence to suggest that adenoidectomy alone provides symptomatic improvement in 79% of children with CRS (19). We advocate adenoidectomy as an initial surgical intervention prior to endoscopic sinus surgery in children with CRS refractory to medical treatment.

Extraesophageal Reflux (EER)

EER has been shown to play an important role in chronic and acute inflammatory disorders of the airway. Double-lumen pH probe studies confirm that acid from the stomach does, in fact, reach the nasopharynx in children with chronic sinus disease (20,21). Children seldom complain of the classic symptoms of gastroesophageal reflux such as heartburn, indigestion, regurgitation, and sour taste in the mouth, and it is estimated that as many as 50% of individuals have ‘‘silent’’ reflux. The gold standard for the evaluation of reflux disease is double-lumen pH probe monitoring. However, reflux may be assessed by a variety of methods including an upper gastrointestinal series, technetium scintigraphy, bronchoscopy with telescopic visualization, and bronchoalveolar lavage for lipid-laden macrophages. Empiric antireflux therapy may be instituted as well. Bothwell et al. retrospectively reviewed 30 children with CRS refractive to medical therapy (22). All were considered candidates for endoscopic sinus surgery. All 30 were treated for reflux including counseling, H2 mockers, prokinetic agents, and proton pump inhibitors. Two patients required Nissen fundoplication. Although they responded to antireflux therapy, two patients underwent surgery for contact point release. Of the remaining 28 patients, 89% avoided sinus surgery after a two-year follow up.

Anatomic or Structural Abnormalities

Although the presence of a deviated septum, choncha bullosa, paradoxical middle turbinate, uncinate hypoplasia, enlarged infraorbital cells, and others have not been definitively shown to cause rhinosinusitis, they may potentiate an infection or may delay resolution of normal mucous drainage and aeration as a result of impaired mucociliary clearance. Medical management aimed at improving the nasal airway and the sinus drainage pathways include topical nasal steroids and decongestants. However, surgical correction may be necessary.

Humoral Immunity Deficiencies

Impaired primary or secondary humoral immunity must be considered in children with recurrent acute rhinosinusitis and CRS who fail to respond to conservative management or fail to improve, even temporarily. The most common of these include IgG subclass deficiency, IgA deficiency, and common variable deficiency. The indication for immune function testing has not been clearly defined. These children present with multiple upper and lower respiratory tract infections. In addition to rhinosinusitis, they may present with recurrent pneumonia, bronchitis, and otitis media. The diagnosis of immunodeficiency is usually made by serum immunoglobulin quantization.

Cystic Fibrosis

Any child with a history of chronic sinusitis with nasal polyposis must be evaluated for cystic fibrosis. Cystic fibrosis is the most common lifethreatening autosomal recessive disorder in Caucasians with an incidence of 1:3200 newborns in the United States. It is less common in African Americans (1:15,000) and Asian Americans (1:31,000). It presents as a progressive obstructive exocrine insufficiency, which manifests as pulmonary and pancreatic insufficiency. Nasal polyposis and sinusitis are seen in varying degrees of severity in nearly all patients. In addition to the clinical presentation, a sweat chloride concentration greater than 60 mmol/L is diagnostic for cystic fibrosis (23).

Disorders of Ciliary Motility

Primary ciliary dyskinesia is an autosomal recessive condition characterized by chronic sinusitis, bronchiectasis, and infertility. Situs inversus occurs in 50% of cases (Kartagener syndrome). It has an estimated incidence of one in 20,000 live births. The clinical phenotype is caused by defective ciliary function associated with a range of ultrastructural abnormalities including absent dynein arms, absent radial spokes, and disturbed ciliary orientation (normal is the 9 þ 2 microtubule orientation) (24). The molecular and genetic basis is unknown. The saccharin test, which measures the time taken for a pellet of saccharin placed on the inferior turbinate to be tasted (normal <30 min), is very difficult to perform properly in children (25). Confirmation of the diagnosis ideally requires nasal brushings or biopsy which is available only at specialized centers.

Environmental Exposures

Attendance at day care facilities is associated with a higher incidence of URIs and otitis media. The National Institute of Child Health and Human Development (NICHD) Early Child Care Research Network reported that children in large-group care during the preschool years were about twice as

likely to have a respiratory tract illness and approximately 1.5 times as likely to have a reported ear infection (26). Secondary or passive exposure to cigarette smoke is known to cause increased rates of otitis media and URIs in children. There is growing evidence that secondary smoke exposure may be an important factor in the development of acute rhinosinusitis and CRS as well as chronic rhinitis in children (27).

TREATMENT OVERVIEW

Antimicrobial therapy remains the primary focus in the medical treatment of acute rhinosinusitis. In 1986, Wald et al. conducted a randomized trial comparing the effectiveness of amoxicillin and amoxicillin-clavulanate therapy compared to placebo in the treatment of children with clinical and radiographic diagnosis of ABRS (28). On the third day of treatment, 83% of children receiving antibiotics were cured or improved compared to 51% of the children in the placebo group. On the tenth day of treatment, 79% of children receiving antibiotics were cured or improved compared to 60% of children receiving placebo. They demonstrated approximately 50 to 60% of children will improve gradually without the use of antimicrobials; however, the recovery of an additional 20 to 30% is delayed substantially compared with children who receive appropriate antibiotics.

In contrast, Garbutt et al. challenged the notion that antibiotics are beneficial in children diagnosed with acute rhinosinusitis in 2001 (29). Children with a clinical diagnosis of acute rhinosinusitis were randomized to receive standard dose amoxicillin, amoxicillin-clavulanate, and placebo. Day 14 improvement rates were 79%, 81%, and 79%, respectively. There were no differences in the observed outcome measures of timing or frequency of recovery.

In 1997, the Agency for Healthcare Policy and Research (AHCPR) contracted an expert panel to prepare an evidence-based review of the world’s literature related to the diagnosis and treatment of uncomplicated, commu- nity-based rhinosinusitis (30). They conducted a meta-analysis reviewing over 9000 articles from the literature. Their key findings were that clinical criteriabased diagnosis is the most cost-effective, while sinus radiograms are not cost-effective in the initial management strategy. Antibiotics were found to reduce the incidence of clinical failures by one-half in comparison to no treatment (30).

Currently, the American Academy of Pediatrics Subcommittee on Management of Sinusitis and Committee on Quality Improvement as well as the Sinus and Allergy Health Partnership (SAHP) recommend the use of antibiotics in the treatment of acute sinusitis after completing a review of the literature and conducting a consensus poll of its respective members (4,6). In 2002, Morris and Leach conducted a meta-analysis of available randomized, controlled trials which compared antibiotics versus placebo or standard therapy (nasal irrigations) (31). The evidence contained within this

review supports the notion that antibiotics increase rates of clinical cure or improvement in children with rhinosinusitis. This was based upon the results of six small, randomized, controlled trials incorporating a total of 562 children.

Although antibiotics remain the primary treatment of rhinosinusitis in children, unnecessary antibiotic-prescribing practices may be contributing to increasing rates of antibiotic resistance. Antibiotics prescribed for a viral illness may do nothing more than result in gastrointestinal side effects and hold the potential for serious side effects including allergy, systemic toxicity, and anaphylaxis. The axiom that antibiotics will do no harm is unjustified since the overuse of antibiotics is the principle cause of progressive antibiotic resistance. The overwhelming cost of prescription medications also adds merit to the argument for judicious prescribing practices.

The overall goal of therapy for rhinosinusitis is to reestablish the normal sinonasal drainage pathways, eradicate pathogenic organisms, prevent suppurative complications, and improve general well-being. These goals must be considered along with the knowledge that as in otitis media, the majority of cases of acute rhinosinusitis will resolve with or without antibiotics.

MICROBIOLOGY OF ACUTE AND CHRONIC RHINOSINUSITIS

The microbiology of ABRS in children has been shown to be similar to that of adults (32). In 2000, a review of bacterial isolation studies was conducted by the SAHP. In children with ABRS, S. pneumoniae is isolated in approximately 35 to 42% of aspirates, whereas H. influenzae and Moraxella catarrhalis are each isolated in 21 to 28%. Other organisms recovered include Streptococcus pyogenes and anaerobes, both of which account for 3 to 7% (Fig. 1) (6). Culture results of children with subacute bacterial rhinosinusitis show a similar organism profile as that found in ABRS (33).

Bacteriologic studies of children with CRS are less certain than those conducted in children with acute rhinosinusitis. Due to differences in the definition of CRS and variations in methods of collection, a wide variability of pathogenic bacteria has been identified. In 1991, Muntz and Lusk (34) cultured 204 ethmoid bullae in children operated on for CRS. The most common organisms isolated were a-hemolytic Streptococcus (23%), S. aureus

(19%), S. pneumoniae (7%), H. influenzae (7%), and M. catarrhalis (7%). Anaerobes are more frequently encountered in children with CRS than acute rhinosinusitis. This may be explained by the low-oxygen tension of chronically obstructed sinuses resulting in a more favorable growth environment for anaerobes. Although not universally accepted, Brook (35) strongly emphasizes the role of anaerobes in chronic sinusitis in children. In a series of 37 culture-positive pediatric patients, anaerobic species were recovered in 100% of cases. The most commonly isolated anaerobes were Prevotella, Peptostreptococcus, and Bacteriodes. In 1988, Otten and Grote (36) studied

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offending organisms must be considered. Since up to 70% of ABRS cases are caused by either S. pneumoniae or H. influenzae, empiric antibiotic therapy should be directed at these organisms (10). Of these, S. pneumoniae is more likely to result in more severe disease and suppurative complications such as orbital or intracranial extension. Several factors should be considered in the selection of an antibiotic for ABRS. These include severity of disease, rate of progression of the disease, recent antibiotic therapies, and community resistance rates of the suspected pathogen. Other factors that may influence antibiotic selection include medication allergy or intolerance, cost, taste, available preparations, and frequency of dosing. Compliance with therapy is a major factor that will influence treatment success. Available antibiotics for use in children with rhinosinusitis include b-lactams (penicillins and cephalosporins), augmented b-lactams, macrolides (erythromycin, clarithromycin, and azythromycin), lincosamides (clindamycin), and folate inhibitors. Although the fluoroquinolones, particularly the newer respiratory fluoroquinolones, provide excellent coverage for both S. pneumoniae and H. influenzae infections, they are currently not approved for use in children younger than 18 years. Tetracyclines are contraindicated for use in children younger than eight years due to risk of tooth enamel discoloration.

According to the guidelines of the SAHP (Table 3), appropriate therapies for children with mild disease who have not received antibiotics in the past four to six weeks include amoxicillin (45–90 mg/kg/day) with or without clavulanate, cetpodoxime proxetil, and cefuroxime axetil. In patients with significant allergy to penicillins and cephalosporins, doxycyline (>8 years old), azithromycin, clarithromycin, erythromycin, or TMP/ SMX may be used (6). For children who have received a prior antibiotic in the past four to six weeks or have moderate disease, double dose amoxicillin (80–90 mg/kg/day) with or without clavulanate should be used if this agent is selected. Also, clindamycin may be considered if S. pneumoniae is identified as a pathogen. Patients with moderate sinus disease and who have received antibiotics, amoxicillin with clavulanate (80–90 mg/kg/day) would be the first line choice. Combination therapy is an alternative, which would include amoxicillin (80–90 mg/kg/day) or clindamycin for gram-positive coverage, plus cefixime, cepodoxime proxetil, or TMP/SMX for gram-negative coverage.

According to the SAHP, the terms mild and moderate disease reflect the symptom complex, the degree of discomfort of the patient, and the time course of the infection. A child, who is otherwise healthy, with 10 days of persistent anterior and posterior rhinorrhea and fatigue is considered to have mild disease. This same patient with worsening symptoms, including fever and maxillary or frontal tenderness that worsens with bending over, is considered to have moderate disease. These definitions are by no means strict; the determination of the severity of disease requires clinical judgment on a case-by-case basis.

Table 3 SAHP Guidelines for Antibiotic Treatment in Children with Mild/ Moderate ABRS

Symptom severity

Abbreviations: SAHP, Sinus and Allergy Health Partnership; ABRS, acute bacterial rhinosinusitis. Source: From Ref. 6

The predicted efficacy of each antibiotic in the treatment of children with ABRS has been calculated by the SAHP: >90% (amoxicillin/clavulanate and high-dose amoxicillin), 80–90% [(cefpodoxime proxetil, cefixime-based upon H. influenzae and M. catarrhalis coverage only), (cefuroxime axetil, clindamycin-based on gram-positive coverage only), azithromycin, clarithromycin, erythromycin, and TMP/SMX], 70–80% (cefprozil), and 60–70% (cefaclor and loracarbef) (6). The predicted efficacy of cefaclor and loracarbef is slightly better than placebo (49.6%) and thus would not be a good choice in the management of ABRS in children.

appropriately with amoxicillin in either standard (45 mg/kg/day) or high (90 mg/kg/day) dose. Amoxicillin is the most suitable choice in the initial management of non-penicillin allergic children due to its proven efficacy, safety profile, low cost, and tolerability. All but highly resistant S. pneumoniae will respond to conventional doses of amoxicillin, but given the safety profile of high-dose amoxicillin and gradually rising resistance rates, there does not seem to be any compelling reason to use standard dose amoxicillin. S. pneumoniae resistance to penicillins has been documented to be as high as 30% (4,6). Double-dose amoxicillin (90 mg/kg/day) will improve coverage of highly resistant strains of S. pneumoniae. In cases of mild, uncomplicated rhinosinusitis and absence of risk factors, approximately 88% of children with ABRS will respond to amoxicillin (6). Risk factors associated with increased rates of resistant S. pneumoniae and H. influenzae include attendance at day care, prior antimicrobial treatment within past four to six weeks, and age less than two years. Although most of these will still respond to high-dose amoxicillin, the physician should also consider treatment with high-dose amoxicillin-clavulanate (80–90 mg/kg/day).

Selection of a b-lactamase resistant drug is indicated if the infection is due to H. influenzae or M. catarrhalis, since 40% and nearly 98%, respectively, are likely to be b-lactamase positive (4,6). In general, M. catarrhalis is expected to be largely a self-limited disease, not necessarily requiring antibiotic therapy, so treatment directed at S. pneumoniae or H. influenzae should be the primary goal. The addition of clavulanic acid results in irreversible binding of b-lactamase and restoration of the activity of amoxicillin. Cefuroxime axetil and Cefpodoxime proxetil have potent activity against most strains of H. influenzae.

First-generation cephalosporins are rarely used in the treatment of bacterial rhinosinusitis due to lower activity against gram-negative organisms. Second-and third-generation cephalosporins have good spectrum of activity against the most common pathogens, and may be considered in patients with allergy to penicillins, although some cross-class reactivity can occur. Although cefuroxime-axetil, cefpodoxime, and cefixime are potent against most strains of H. influenzae, they are not active against penicillinresistant S. pneumoniae. Ceftriaxone has good activity against both H. influenzae and S. pneumoniae. Cefaclor is susceptible to b-lactamase and is a poor choice overall. Clarithromycin and azithromycin may also be used. Penicillin, cephalexin, and tetracycline should not be used because these drugs do not cover the major organisms that cause acute rhinosinusitis (10). An alternative is the combination of erythromycin (30–50 mg/kg/day) and sulfisoxazole (150 mg/kg/day). Sulfisoxazole is added because erythromycin alone does not adequately cover H. influenziae (38).

Treatment durations recommended for uncomplicated acute rhinosinusitis include a 5- to 14-day course depending on the antibiotic, with a