Diagnosis and Management of Acute Rhinosinusitis in Children

Transcription

1 Diagnosis and Management of Acute Rhinosinusitis in Children Gualtiero Leo, MD, Francesca Mori, MD, Cristoforo Incorvaia, MD, Simona Barni, MD, and Elio Novembre, MD Corresponding author Gualtiero Leo, MD Pediatric Allergy and Respiratory Pathophysiology Unit, Vittore Buzzi Children s Hospital, Istituti Clinici di Perfezionamento, Via Castelvetro 32, 20154, Milan, Italy. gualtiero.leo@icp.mi.it Current Allergy and Asthma Reports 2009, 9: Current Medicine Group LLC ISSN Copyright 2009 by Current Medicine Group LLC Rhinosinusitis is a common disease in children that is often overlooked. The clinical symptoms of acute rhinosinusitis are nasal blockage or congestion, nasal discharge or postnasal drip (often mucopurulent), facial pain, headache, and reduction in/loss of smell. Direct vision by nasal fibroendoscopy may aid the diagnosis. Regarding imaging criteria, recent consensus documents state that plain sinus x-rays are of limited utility, and CT remains the technique of choice, particularly in children with complications or very persistent or recurrent infections that are unresponsive to medical management. Antibiotics are the primary form of medical treatment for acute bacterial rhinosinusitis, but they should be used when acute bacterial rhinosinusitis presents as persistent or severe disease. This will minimize the number of children with uncomplicated viral upper respiratory tract infections who are treated with antimicrobials. Topical corticosteroids may reduce nasal edema and improve ostial drainage and ventilation of the sinus. Introduction Sinusitis is defined as an inflammation of one or more of the paranasal sinuses. Recent consensus documents suggest that the term rhinosinusitis is preferred to sinusitis for the following reasons: Rhinitis typically precedes sinusitis Sinusitis without rhinitis is rare The mucosa of the nose and sinuses are contiguous Symptoms of nasal obstruction and nasal discharge are prominent in sinusitis [1 ]. Symptoms indicative of rhinosinusitis are nasal blockage, congestion or stuffiness, nasal discharge or postnasal drip (often mucopurulent), facial pain or pressure, headache, and reduction in/loss of smell. The duration of symptoms defines the clinical form: in acute rhinosinusitis (ARS), complete resolution of symptoms takes place in less than 12 weeks, while in chronic rhinosinusitis, symptoms persist for more than 12 weeks. ARS is considered a common disease, although precise data on its prevalence and incidence are lacking [2]. More data are available on prevalence of chronic rhinosinusitis in the general population. Two surveys conducted via interviews of adults in the United States in the 1990s detected a similar prevalence of about 15% [3,4]. A much lower prevalence about 2% was reported in a study based on physicians diagnoses [5]. The few available data on children are similarly contrasting: an old study found by clinical and radiographic evidence that 30% of children 1 to 6 years of age and 15% of those 6 to 12 years of age had sinusitis [6]. More recently, an MRI survey in an unselected population of children detected signs of sinusitis in 45%, with the number increasing to 50% in the presence of nasal obstruction and to 100% in the presence of purulent secretions [7]. Anatomy and Pathophysiology The paranasal sinuses are air-filled spaces within the bones of the head. There are four pairs of paranasal sinuses that are divided in base to their location and routes of drainage: the ethmoid, maxillary, frontal, and sphenoid sinuses. The ethmoid sinuses consist of a honeycomb of cells lying medial to the orbital structures. They consist of 4 to 17 air cells divided into an anterior and posterior group. The anterior cells open into the middle meatus, and the posterior cells open into the superior meatus [8]. The maxillary sinus lies between the teeth and the orbit on both sides and drains into the middle meatus through a channel [9]. The paired frontal sinuses extend from the region of the anterior ethmoid to the forehead and also drain into the middle meatus [9]. The sphenoid sinuses lie behind and slightly inferior to the posterior ethmoid cells. They drain by separate ostia into the sphenoethmoidal recess on either side of the nasal septum posteriorly [9]. The sinuses develop at different ages during childhood. Development

2 Diagnosis and Management of Acute Rhinosinusitis in Children I Leo et al. I 233 of the ethmoid and maxillary sinuses begins in the third to fourth gestational month; consequently, they are present at birth. The sphenoid sinuses begin to develop at 3 to 5 years of age; the frontal sinuses appear at age 7 to 8 years but are not completely developed until late adolescence [9]. Each sinus cavity (eg, the nasal cavity) is lined by a pseudostratified columnar ciliated epithelium interspersed with goblet cells [10]. The goblet cells and nasal glands produce mucus that covers the surface of all paranasal sinuses. Particles and bacteria can be caught in this mucus, rendered harmless by enzyme-like lysozyme and lactoferrin, and then transported toward the ostial opening. A pivotal role in the pathogenesis of rhinosinusitis is played by the ostiomeatal complex, a functional unit that comprises the maxillary sinus ostia, anterior ethmoid cells with their ostia, ethmoid infundibulum, hiatus semilunaris, and middle meatus [1 ]. The patency of the ostia is a key element for the ventilation and mucociliary clearance of the paranasal sinuses. Significant obstruction of the ostia creates the ideal conditions for the development of sinusitis that may occur if the orifice is too small for the amount of mucus, if mucus production is increased (eg, during an upper respiratory tract infection), or if ciliary function is impaired [1 ]. Obstruction of sinus ostia may lead to mucus impaction and decreased oxygenation in the sinus cavities, with consequent stasis of secretions and stopping of bacterial export. The aeration of the mucosa is decreased, causing a worsening of ciliary dysfunction. The anaerobic environment provides the conditions for bacterial growth. Stasis of secretions and decreased oxygenation create a vicious cycle that may be difficult to break. If the condition persists, it can result in chronic rhinosinusitis. Microbiology The principal bacteria of ARS are Streptococcus pneumoniae, nontypeable Haemophilus influenzae, and Moraxella catarrhalis [11]. S. pneumoniae is the most prevalent pathogen in children with acute bacterial rhinosinusitis, accounting for 30% to 66% of cases. H. influenzae and M. catarrhalis are recovered from about 20% of cases. Neither Staphylococcus aureus nor respiratory anaerobes are likely to be recovered from children with acute bacterial rhinosinusitis. Respiratory viral isolates include adenovirus, parainfluenza, influenza, and rhinovirus in approximately 10% of patients [12]. In the 30% of children with ARS, aspirates of the maxillary sinus are sterile [13]. Although viruses are uncommonly recovered from sinus aspirates, superinfection by bacteria on mucosa damaged by viral infection (common cold) is the most important cause of ARS. Clinical Symptoms Symptoms indicative of ARS are nasal blockage, congestion or stuffiness, nasal discharge or postnasal drip (often mucopurulent), facial pain or pressure, headache, and reduction in/loss of smell [1 ]. Wald [14 ] suggested that the superinfection of paranasal sinus should be suspected in the following cases: 1. Signs and symptoms of a common cold that persist beyond 10 days (any nasal discharge, daytime cough that worsens at night) 2. A cold that seems more severe than usual (high fever, copious purulent discharge, periorbital edema, and pain) 3. A cold that worsens after several days of improvement (with or without fever). Acute bacterial rhinosinusitis may occur with persistent respiratory symptoms after a cold or when severe symptoms are present [11,15]. Persistent symptoms are those that last more than 10 to 14 days [10]. Signs and symptoms of acute bacterial rhinosinusitis and those of prolonged viral upper respiratory tract infection are very similar. It can be difficult to distinguish sequential episodes of uncomplicated upper respiratory tract viral infections from the onset of acute bacterial rhinosinusitis with persistent symptoms. Uncomplicated viral upper respiratory infections generally last 5 to 7 days but may last longer [16,17]. Although the respiratory symptoms may not completely resolve by the 10th day, they almost always peak in severity and begin to improve by that point. The persistence of respiratory symptoms without evidence of improvement suggests the presence of a secondary bacterial infection. The second mode of clinical presentation of acute bacterial rhinosinusitis is the one with severe symptoms, including a temperature of at least 39 C and purulent nasal discharge present concurrently for at least 3 to 4 consecutive days in a child who seems ill [10]. It is important to try to differentiate children with severe symptoms of acute bacterial rhinosinusitis from those with uncomplicated viral upper respiratory tract infections who are moderately ill. In children with uncomplicated viral infections of the upper respiratory tract, fever may be present early in the illness and usually is accompanied by other constitutional symptoms, such as headache and myalgias. The constitutional symptoms usually resolve in the first 48 hours, and respiratory symptoms then become prominent. In most uncomplicated viral infections, purulent nasal discharge does not appear for several days. Accordingly, the simultaneous presence of high fever and purulent nasal discharge for at least 3 to 4 consecutive days defines the severe presentation of ARS. This more severe manifestation of acute bacterial rhinosinusitis is a less common presentation than that with persistent respiratory symptoms [18]. Acute bacterial rhinosinusitis in children also may present with other symptoms and signs that may or may not be specific. Younger children may present with nonspecific symptoms such as irritability, poor appetite, throat clearing, and malodorous breath. Older children and adolescents may complain of more specific symptoms, such as headache and facial pain often

3 234 I Sinusitis including increased irritability and vomiting that occurs in association with gagging on mucus [9]. Complications Infections of the paranasal sinuses can spread into adjacent structures that are protected by osseous barriers. Consequently, the complications of bacterial sinusitis are related to the anatomy and development of the paranasal sinuses [19 ]. Ethmoiditis is commonly implicated in orbital complications [20] that include preseptal or periorbital cellulitis, orbital cellulitis, subperiosteal abscess, and optic neuritis [21]. The frontal sinus is most commonly implicated in sinogenic intracranial infections [22,23]. Considering sinus development, the prevalence of the type of complications is different among age groups. Intracranial complications are very rare in young children and more often occur in the second and third decades of life [24 26]. In comparison, literature reviews have reported that orbital cellulitis affects much younger children (mean age, 7.4 years) [25]. Moreover, simultaneous intracranial and orbital complications are rare in children; their frequency is greater in children 7 years of age or older [27]. Other complications are septicemia and osteomyelitis. Analysis of the pathogens responsible for the complications of acute bacterial rhinosinusitis revealed a slightly different microbiologic profile. In addition to the typical bacteria, several studies reported Streptococcus milleri, S. aureus, other streptococci, other anaerobic pathogens, and polymicrobial infections as being responsible for the complications associated with bacterial rhinosinusitis [24,25,28,29]. Diagnosis The gold standard for the diagnosis of ARS is direct sinus aspiration, an invasive and painful procedure not routinely recommended for diagnosing acute bacterial rhinosinusitis [10]. The procedure is usually reserved for complicated cases or cases in which treatment requires the isolation of a specific microbe for identification of antibiotic sensitivities [21]. A recent European Position Paper on Rhinosinusitis and Nasal Polyps suggested that the diagnosis of ARS can be based on clinical criteria and confirmed by the following endoscopic signs: mucopurulent discharge primarily from middle and/or edema or mucosal obstruction primarily in the middle meatus [1 ]. Clinical examination Physical examination of a child with a clinical history suggesting sinusitis may help to differentiate sinusitis from an uncomplicated upper respiratory tract infection or allergic rhinitis [15,30]. In fact, the physical examination generally does not contribute substantially to the diagnosis of acute bacterial rhinosinusitis. The examination of the face can show swelling and tenderness overlying an affected area; rarely, when orbital involvement occurs, diplopia or proptosis can be observed [9]. Then, the nasal mucosa and quality of secretions should be assessed, preferably by nasal fibroendoscopy, which allows a more complete inspection that includes the vision of the ostiomeatal complex [1 ]. Imaging criteria The value of diagnostic radiologic studies in ARS in children is uncertain. Plain sinus x-rays usually are not helpful in diagnosing rhinosinusitis because of their relatively low specificity [21]. Positive radiographic findings in ARS are complete opacification of the sinus, air fluid levels within the sinus, and thickening (> 4 mm) of the sinus mucosal membrane [10]. In children 2 to 16 years of age with persistent symptoms, history of protracted respiratory symptoms predicted significantly abnormal radiographs in 80% of cases [31]. For children 6 years of age or younger, history predicted abnormal sinus radiographs in 88% of cases [10]. Now, because the peak age for acute bacterial rhinosinusitis is less than 6 years and a positive history very frequently predicts the findings of abnormal sinus radiographs in this age group, radiographs can be safely omitted. In contrast to the general agreement that radiographs are not necessary in children 6 years of age or younger with persistent symptoms, the need for radiographs as a confirmatory test for ARS in children older than 6 years of age with persistent symptoms and for all children with severe symptoms (regardless of age) is controversial [32,33]. The recent European Position Paper on Rhinosinusitis and Nasal Polyps referred to plain sinus x- rays as insensitive and of limited utility due to the number of false-positive and false-negative results [1 ]. CT remains the study of choice for the imaging evaluation of ARS and chronic rhinosinusitis. Compared with plain radiographs, CT scans provide better visualization of the sinus cavity and its contents and permit better assessment of complications involving the orbit and intracranial spaces [34]. However, CT may overdiagnose rhinosinusitis. In one study, almost 100% of young children who underwent CT examination for reasons other than sinus disease and who had an upper respiratory tract infection in the previous 2 weeks demonstrated mucosal abnormalities in their sinuses [10]. CT scans are indicated in children who present with complications of acute bacterial rhinosinusitis or who have very persistent or recurrent infections that are unresponsive to medical management [33]. Moreover, CT scans should be reserved for patients in whom surgery is being considered as a management strategy [10]. MRI is the technique of choice when intracranial complications are suspected [35 ]. Management Antibiotic treatment Acute bacterial rhinosinusitis is often a self-limited infection, with the spontaneous cure rates varying by causative organism: 15% for S. pneumoniae, 50% for H. influenzae, and 50% to 70% for M. catarrhalis [36]. Consequently, several investigators have questioned the need

4 Diagnosis and Management of Acute Rhinosinusitis in Children I Leo et al. I 235 for antibiotics in children with ARS [37]. To promote the judicious use of antibiotics, it is essential that children diagnosed with acute bacterial rhinosinusitis meet the defining clinical presentations of persistent or severe disease as described previously [10]. This will minimize the number of children with uncomplicated viral upper respiratory tract infections who are treated with antimicrobials. Antibiotics are the primary form of medical treatment for acute bacterial rhinosinusitis. The objectives of antimicrobial therapy are achievement of a rapid clinical cure, sterilization of the sinus secretions, prevention of suppurative orbital and intracranial complications, and prevention of chronic sinus disease [38]. Of the most frequently involved bacteria (S. pneumoniae, H. influenzae, and M. catarrhalis), the last two can produce β-lactamase and can thereby be resistant to penicillin and its derivates. The prevalence of penicillinresistant S. pneumoniae has recently increased by 25% to 50%. Factors associated with an increased risk for bacterial resistance include age less than 2 years, attendance in child care, use of antibiotics within the past 3 months, and sinus aspirate culture showing growth of an amoxicillinresistant pathogen [39]. Amoxicillin is recommended as first-line therapy because of its general effectiveness, narrow spectrum of activity, safety, palatability, and low cost. The standard dose of 45 mg/kg twice daily can be increased to 90 mg/kg twice daily in the presence of specific risk factors or resistance. The lower dose can be used for children who are older than 2 years of age, who are not in child care and have not received antimicrobial therapy recently, and whose sinusitis is not severe. If children do not improve within 48 to 72 hours, the diagnosis should be reconsidered, and the antimicrobial agent should be changed if the diagnosis remains sinusitis. Furthermore, the most dramatic differences observed in treated versus untreated patients should occur during the first 72 to 96 hours of treatment [31]. Against β-lactamase producing strains, the combination of amoxicillin/potassium clavulanate (80 90 mg/kg per day of amoxicillin component, with 6.4 mg/kg per day of clavulanate in two divided doses) can inhibit the β-lactamase enzymes, even if diarrhea may occur. Cephalosporins are commonly prescribed to treat ARS and chronic rhinosinusitis. First-generation agents (cephalexin and cefadroxil) have poor effectiveness against H. influenzae infection. Cefaclor, an early second-generation cephalosporin, has poor coverage for all β-lactamase producing M. catarrhalis and some, but not all, H. influenzae strains. In a study, amoxicillin and cefaclor appeared to be of comparable efficacy for the antimicrobial management of ARS in children [40]. Other second-generation cephalosporins (cefuroxime axetil, 30 mg/kg per day, and cefprozil) have good activity against β-lactamase producing agents and can be administered as suspension twice daily. Cefixime, ceftibuten, cefpodoxime axetil, and cefdinir are thirdgeneration cephalosporins that can be given orally once or twice daily. Cefixime and ceftibuten have poor activity against S. pneumoniae and are especially ineffective against penicillin-resistant strains. Neither drug should be used for acute bacterial rhinosinusitis. Cefpodoxime and cefdinir are suitable agents. Other antibiotics used in the past (trimethoprim-sulfamethoxazole and erythromycin-sulfisoxazole) are no longer recommended because of increased pneumococcal resistance. A single dose of ceftriaxone, 50 mg/kg per day intravenously or intramuscularly, can be used in children with vomiting precluding administration of oral antibiotics [10] or in patients who do not respond to a second course of antibiotic treatment [41]. Twenty-four hours later, when the child is clinically improved, an oral antibiotic is substituted to complete the therapy. If the patient is allergic to amoxicillin, cefdinir (14 mg/kg per day in one or two doses), cefuroxime (30 mg/kg per day in two divided doses), or cefpodoxime (10 mg/kg once daily) can be used, but only if the allergic reaction was not a type 1 hypersensitivity reaction. In case of serious allergic reactions, clarithromycin (15 mg/kg per day in two divided doses) or azithromycin (10 mg/kg per day on day 1, then 5 mg/kg per day for 4 days as a single daily dose) can be used in an effort to select an antimicrobial of an entirely different class [10]. If the clinical course suggests that an anaerobic pathogen is more likely, clindamycin or metronidazole can be considered in combination with a broad-spectrum drug [9]. The optimal duration of therapy for patients with acute bacterial rhinosinusitis is not well defined. There are empiric recommendations for 10, 14, 21, and 28 days of treatment. An alternative suggestion has been made that antibiotic therapy should be prolonged 7 days after symptom resolution [11]. Table 1 summarizes the use of antibiotics in treating ARS. Corticosteroid treatment The precipitating factor in ARS appears to be the blockage of the sinus ostium. Topical nasal corticosteroids may reduce nasal edema and improve ostial drainage and ventilation of the sinus. Whether nasal steroid therapy can sufficiently decrease nasal inflammation and improve mucociliary transport to the point at which the ostiomeatal complex becomes competent is unknown. Topical corticosteroids offer the theoretical advantage of a localized therapeutic action in nasal tissues without the occurrence of undesirable systemic effects [42]. A theoretical concern exists regarding the potential spread of infection in acute sinusitis. However, this does not occur when topical corticosteroids are administered concurrently with antibiotics [43]. Barlan et al. [44] found that budesonide may be a useful ancillary treatment to antibiotics in childhood sinusitis and may be effective in reducing the cough and nasal discharge earlier in the course of ARS. Clinical symptoms and signs decreased significantly in both groups (budesonide vs placebo group) compared with baseline (P < 0.01), and significant improvement in the scores of cough and nasal discharge was seen at the end of the second week in the budesonide group when compared with placebo (P < 0.05) [44]. Melt-

5 236 I Sinusitis Table 1. Antibiotics for the treatment of acute rhinosinusitis in children Antibiotic Dosage, mg/kg per d Doses/d, n Amoxicillin Amoxicillin/potassium clavulanate 80 90/6.4 2 Cefdinir 14 1 or 2 Cefpodoxime 10 1 Ceftriaxone 50 1 Cefuroxime axetil 30 2 Azithromycin 10 mg/kg on day 1, 5 mg/kg on days Clarithromycin 15 2 Clindamycin (Data from the American Academy of Pediatrics [10].) zer et al. [45] evaluated the efficacy of mometasone furoate nasal spray versus amoxicillin and placebo in patients with acute, uncomplicated rhinosinusitis; 981 patients ( 12 years of age) were randomly assigned to mometasone furoate, 200 μg once daily or twice daily for 15 days, or respective placebo. Mometasone furoate nasal spray, 200 μg twice daily, was significantly superior to placebo and amoxicillin at improving major symptom scores [45]. The authors concluded that in patients with acute, uncomplicated rhinosinusitis, mometasone furoate, 200 μg twice daily, produced significant symptom improvement compared with amoxicillin and placebo without predisposing patients to disease-recurrent or bacterial infection. Oral corticosteroid can be added to treat ARS when the patient does not respond to initial therapy and demonstrates nasal polyposis or has marked mucosal edema [1 ]. Other treatment options Adjuvant therapies such as treatment with antihistamines, decongestants (topical or systemic), saline nasal irrigation (hypertonic or normal saline), or mucolytic agents have undergone relatively few systematic investigations. Currently, there are no data to recommend the use of anti-h1 antihistamines in nonallergic children with acute bacterial rhinosinusitis [10]. A double-blind, randomized, controlled trial showed no additive effect of adding decongestant-antihistamine (nasal oxymetazoline and oral syrup containing brompheniramine and phenylpropanolamine) to amoxicillin [46]. Saline nose drops or sprays are popular with pediatricians. Neither has been studied in patients with acute bacterial rhinosinusitis [10]. Moreover, if the saline is isotonic and at body temperature, it can help in eliminating nasal secretions and can decrease nasal edema [10]. Saline also may act as a mild vasoconstrictor of nasal blood vessels [47]. No clinical trials of mucolytics have been reported in nonatopic children or adults with acute bacterial rhinosinusitis [47]. Thus far, even if no studies have specifically established the role of vaccines in preventing ARS, it is reasonable to suggest that severely affected children will benefit from vaccines such as the conjugated pneumococcal vaccine due to reduced infections by this specific bacterium [48]. Conclusions Rhinosinusitis is a very common but overlooked disease in children. Children with acute bacterial rhinosinusitis may present with persistent symptoms of an upper respiratory tract infection or more severe respiratory symptoms than usual. Moreover, younger children may present with subtle or nonspecific symptoms such as irritability, poor appetite, throat clearing, and malodorous breath. The diagnosis of acute bacterial rhinosinusitis in children is based on clinical criteria and endoscopic signs of mucopurulent discharge from the middle meatus and/or edema primarily in the middle meatus. Appropriate antibiotic therapy may achieve a rapid clinical cure and prevent suppurative complications. Disclosure No potential conflicts of interest relevant to this article were reported. References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: Of importance Of major importance 1. Fokkens WJ, Lund VJ, Mullol J: European Position Paper on Rhinosinusitis and Nasal Polyps. Rhinology 2007, 45(Suppl 20): This is the most recent and complete update on the diagnosis and management of rhinosinusitis. 2. National Center for Health Statistics: Health, United States, With Chartbook on Trends in the Health of Americans. Hyattsville, MD: National Center for Health Statistics; Collins JG: Prevalence of selected chronic conditions: United States, Vital Health Stat , Jan:1 89.

6 Diagnosis and Management of Acute Rhinosinusitis in Children I Leo et al. I Blackwell DL, Collins JG, Coles R: Summary health statistics for US adults: National Health Interview Survey Vital Health Stat , May: Shashy RG, Moore EJ, Weaver A: Prevalence of the chronic sinusitis diagnosis in Olmsted County, Minnesota. Arch Otolaryngol Head Neck Surg 2004, 130: Maresh MM, Washburn A: Paranasal sinuses from birth to late adolescence. Clinical and roentgenographic evidence of infection. Am J Dis Child 1940, 60: Gordts F, Clement PAR, Buisseret T: Prevalence of sinusitis signs in a non-ent population. Otorhinolaryngology 1996, 58: Bolger WE: Anatomy of the paranasal sinuses. In Diseases of the Sinuses: Diagnosis and Management. Edited by Kennedy DW, Bolger WE, Zinreich SJ. Hamilton, Ontario, Canada: Decker; 2001: Slavin RG, Spector SL, Bernstein IL: The diagnosis and management of sinusitis: a practice parameter update. J Allergy Clin Immunol 2005, 116:S13 S American Academy of Pediatrics. Subcommittee on Management of Sinusitis and Committee on Quality Improvement: Clinical practice guideline: management of sinusitis. Pediatrics 2001, 108: Wald ER: Sinusitis. Pediatr Ann 1998, 27: Nash D, Wald E: Sinusitis. Pediatr Rev 2001, 22: Isaacson G: Sinusitis in childhood. Pediatr Otolaryngol 1996, 43: Wald ER: Beginning antibiotics for acute rhinosinusitis and choosing the right treatment. Clin Rev Allergy Immunol 2006, 30: This is a useful guide to antibiotic treatment of ARS. 15. Fireman P: Diagnosis of sinusitis in children: emphasis on the history and physical examination. J Allergy Clin Immunol 1992, 90: Gwaltney JM Jr, Hendley JO, Simon G, et al.: Rhinovirus infection in an industrial population. II. Characteristics of illness and antibody response. JAMA 1967, 202: Gwaltney JM Jr, Buier RM, Rogers JL: The influence of signal variation, bias, noise and effect size on statistical significance in treatment studies of the common cold. Antiviral Res 1996, 29: O Brien KL, Dowell SF, Schwartz B, et al.: Acute sinusitis: principles of judicious use of antimicrobial agents. Pediatrics 1998, 101: Edmondson NE, Parikh SR: Complications of acute bacterial sinusitis in children. Pediatr Ann 2008, 37: This review focuses on how to recognize and manage the most common complications of ARS. 20. Botting AM, McIntosh D, Mahadevan M, et al.: Paediatric pre- and post-septal peri-orbital infections are different diseases: a retrospective review of 262 cases. Int J Pediatr Otorhinolaryngol 2008, 72: Taylor A: Sinusitis. Pediatr Rev 2006, 27: Hakim HE, Malik AC, Aronyk K, et al.: The prevalence of intracranial complications in pediatric frontal sinusitis. Int J Pediatr Otorhinolaryngol 2006, 70: Qurashi H, Zevallos JP: Subdural empyema as a complication of sinusitis in the pediatric population. Int J Pediatr Otorhinolaryngol 2006, 70: Glickstein JS, Chandra RK, Thompson JW: Intracranial complications of pediatric sinusitis. Otolaryngol Head Neck Surg 2006, 134: Nageswaran S, Woods CR, Benjamin DK Jr, et al.: Orbital cellulitis in children. Pediatr Infect Dis J 2006, 25: Goldberg AN, Oroszlan G, Anderson TD: Complications of frontal sinusitis and their management. Otolaryngol Clin North Am 2001, 34: Herrmann BW, Forsen JW Jr: Simultaneous intracranial and orbital complications of acute rhinosinusitis in children. Int J Pediatr Otorhinolaryngol 2004, 68: Ho CF, Huang YC, Wang CJ, et al.: Clinical analysis of computed tomography-staged orbital cellulitis in children. J Microbiol Immunol Infect 2007, 40: Oxford LE, McClay J: Medical and surgical management of subperiosteal orbital abscess secondary to acute sinusitis in children. Int J Pediatr Otorhinolaryngol 2006, 70: Lindbaek M, Hjortdahl P: The clinical diagnosis of acute purulent sinusitis in general practice a review. Br J Gen Pract 2002, 52: Wald ER, Chiponis D, Ledesma-Medina J: Comparative effectiveness of amoxicillin and amoxicillin-clavulanate potassium in acute paranasal sinus infections in children: a double-blind, placebo-controlled trial. Pediatrics 1986, 77: Diament MJ: The diagnosis of sinusitis in infants and children: x-ray, computed tomography, and magnetic resonance imaging. Diagnostic imaging of pediatric sinusitis. J Allergy Clin Immunol 1992, 90: McAlister WH, Kronemer K: Imaging of sinusitis in children. Pediatr Infect Dis J 1999, 18: Chow AW: Acute sinusitis: current status of etiologies, diagnosis, and treatment. Curr Clin Top Infect Dis 2001, 21: Triulzi F, Zirpoli S: Imaging techniques in the diagnosis and management of rhinosinusitis in children. Pediatr Allergy Immunol 2007, 18(Suppl 18): This is a useful review on the diagnostic role of imaging in rhinosinusitis in children. 36. Conrad DA, Jenson HB: Management of acute bacterial rhinosinusitis. Curr Opin Pediatr 2002, 14: Garbutt JM, Goldstein M, Gellman E, et al.: A randomized, placebo-controlled trial of antimicrobial treatment for children with clinically diagnosed acute sinusitis. Pediatrics 2001, 107: Wald ER: Sinusitis in infants and children. Ann Otol Rhinol Laryngol Suppl 1992, 155: Novembre E, Mori F, Pucci N, et al.: Systemic treatment of rhinosinusitis in children. Pediatr Allergy Immunol 2007, 18(Suppl 18): Wald ER, Reilly JS, Casselbrandt M, et al.: Treatment of acute maxillary sinusitis in childhood: a comparative study of amoxicillin and cefaclor. J Pediatr 1984, 104: Anon JB: Acute bacterial rhinosinusitis in pediatric medicine: current issues in diagnosis and management. Paediatr Drugs 2003, 5(Suppl): Sahay JN, Ibrahim NB, Chattergee SS, et al.: Long-term study of flunisolide treatment in perennial rhinitis with special reference to nasal mucosal histology and morphology. Clin Allergy 1980, 10: Druce HM: Adjuncts to medical managements of sinusitis. Otolaryngol Head Neck Surg 1990, 103: Barlan IB, Erkan E, Bakir M, et al.: Intranasal budesonide spray as an adjunct to oral antibiotic therapy for acute sinusitis in children. Ann Allergy Asthma Immunol 1997, 78: Meltzer EO, Bachert C, Staudinger H: Treating acute rhinosinusitis: comparing efficacy and safety of mometasone furoate nasal spray, amoxicillin, and placebo. J Allergy Clin Immunol 2005, 116: McCormick DP, John SD, Swischuk LE, et al.: A double-blind, placebo-controlled trial of decongestantantihistamine for the treatment of sinusitis in children. Clin Pediatr (Phila) 1996, 35: Spector SL, Bernstein IL, Li JT, et al.: Parameters for the diagnosis and management of sinusitis. J Allergy Clin Immunol 1998, 102:S107 S Dagan R, Sikuler-Cohen M, Zamir O, et al.: Effect of a conjugate pneumococcal vaccine on the occurrence of respiratory infections and antibiotic use in day-care centre attendees. Pediatr Infect Dis J 2001, 20: