Учебники / Rhinosinusitis - A Guide for Diagnosis and Management 2008

James N. Palmer, MD

Department of Otorhinolaryngology – Head and Neck Surgery, University of Pennsylvania Health System, Philadelphia, PA, USA

Christine Reger, MSN, CRNP

Department of Otorhinolaryngology, University of Pennsylvania, Philadelphia,

PA, USA

Rodney J. Schlosser, MD

Department of Otolaryngology, Medical University of South Carolina, Charleston,

SC, USA

Brent A. Senior, MD

Department of Otorhinolaryngology – Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Edwin Tamashiro, MD

Affiliated Otorhinolaryngologist, Faculty of Medicine of Ribeirao˜ Preto, Department of Ophthalmology, Otorhinolaryngology, Head and Neck Surgery, University of Sao˜ Paulo, Sao˜ Paulo, Brazil

Erica R. Thaler, MD

Department of Otorhinolaryngology – Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA, USA

Lawrence W. C. Tom, MD

Associate Professor, Department of Otorhinolaryngology, Head and Neck Surgery, University of Pennsylvania School of Medicine, The Children’s Hospital

of Philadelphia, Philadelphia, PA, USA

Kevin C. Welch, MD

Department of Otorhinolaryngology – Head and Neck Surgery, University of Pennsylvania Health System, Philadelphia, PA, 19104, USA

Chapter 1

Etiology and Impact of Rhinosinusitis

Walleed Abuzaid and Erica R. Thaler

Definition of Rhinosinusitis

Rhinosinusitis is a broad diagnostic label that encompasses a spectrum of disorders involving concurrent inflammation of the mucosa of the nose and paranasal sinuses [1,2]. The wide range of clinical signs and symptoms associated with rhinosinusitis has complicated the establishment of a working clinical definition. Furthermore, patients with rhinosinusitis may present to a variety of practitioners including internists, family care physicians, pediatricians, allergists, pulmonologists, and otolaryngologists. A standardized definition of rhinosinusitis has been sought to facilitate communication among physicians and to promote uniform reporting of the disease. Such a definition facilitates further elucidation of the pathophysiology of sinusitis, the development of a clinical staging system, and the introduction of new treatments based on robust clinical data [3].

Past attempts at defining rhinosinusitis have been largely symptom based. Approximately 87% of visits for the diagnosis and management of rhinosinusitis are in the primary care setting where nasal endoscopy and computed tomography (CT) imaging are not routinely used for diagnosis. Consequently, a variety of national and international consensus meetings have developed symptom-based definitions for the initial diagnosis of rhinosinusitis [3–5]. For example, in 1997, the Task Force for Rhinosinusitis of the American Academy of Otolaryngology identified a range of major and minor factors (Table 1.1), as well as the duration of symptoms, to diagnose and classify rhinosinusitis (Table 1.2) [3]. Nasal endoscopy and imaging modalities such as CT were not considered necessary to confirm the diagnosis. This scheme and other similar symptom-based diagnostic systems conform to standard practice in the primary care setting [5].

Recent studies have demonstrated that symptom-based definitions for rhinosinusitis are imperfect in predicting whether a patient truly has disease. Approximately 73% of chronic rhinosinusitis patients diagnosed using a symptom-based

E.R. Thaler

Department of Otorhinolaryngology – Head and Neck Surgery, University of Pennsylvania,

Philadelphia, PA, USA

e-mail: Erica.Thaler@uphs.upenn.edu

Table 1.1 Factors associated with adult rhinosinusitis as identified by the Task Force on Rhinosinusitis

Source: Reprinted from Lanza DC, Kennedy DW. Adult rhinosinusitis defined. Otolaryngol Head Neck Surg 1997;117:S1–S7 by kind permission of Elsevier [3].

scheme had no supporting objective endoscopic or CT findings to confirm the diagnosis [6]. There is a significant lack of correlation between symptom score and disease presence as diagnosed on CT, with several of the aforementioned “major” factors not elicited in patients with a positive CT [7,8]. Overall, more than half the patients who meet the criteria for the diagnosis of rhinosinusitis will not have evidence of disease on CT scans [7]. Symptom-based diagnostic instruments have good sensitivity but extremely poor specificity for detecting a positive CT scan [9,10]. This limitation has called into question the reliability of the diagnostic criteria used in symptom-based definitions of rhinosinusitis.

There is increasing recognition that, at present, the accurate diagnosis of rhinosinusitis is reliant on a combination of symptoms and objective investigations. The recent European Position Paper on Rhinosinusitis recommends that a diagnosis of rhinosinusitis should be based on the following[1]:

•Two or more symptoms, one of which should be either nasal blockage/ obstruction/congestion or nasal discharge:

± Facial pain/pressure

± Reduction or loss of smell

•Additionally, there should be objective signs of disease on nasal endoscopy and/or paranasal CT scan.

Endoscopic signs of polyps; and/or mucopurulent discharge primarily from the middle meatus; and/or edema/mucosal obstruction primarily in the middle meatus

CT evidence of mucosal changes within the ostiomeatal complex and/or sinuses

Epidemiology of Rhinosinusitis

The true incidence and prevalence of rhinosinusitis is unknown as many cases do not present to a medical practitioner [11]. Estimates of the prevalence of acute rhinosinusitis are largely based on CT evidence demonstrating that 90% of patients with colds have concurrent viral or bacterial rhinosinusitis [12]. Each year, children and adults average between six and eight and two to three upper respiratory tract infections, respectively. Therefore, more than 1 billion cases of acute rhinosinusitis occur annually [2]. The difficulty in establishing a standardized definition of rhinosinusitis and resulting diagnostic challenge has made it difficult to estimate the prevalence of chronic rhinosinusitis. Nonetheless, recent data indicate that rhinosinusitis, in all its forms, is one of the most prevalent health care problems in the United States [2]. Among a representative sample of 100,000 U.S. adults who participated in the 2005 National Health Survey, 13.4% of respondents indicated a diagnosis of rhinosinusitis in the preceding year [13]. Based on census data, this percentage translates to approximately 32 million Americans medically diagnosed with rhinosinusitis annually [14].

Etiology of Rhinosinusitis

Multiple factors have been implicated in the development of rhinosinusitis (Table 1.3).

Environmental Factors

Microbial Pathogens in Rhinosinusitis

Acute bacterial rhinosinusitis complicates approximately 0.5% of adult and 5% pediatric cases of viral upper respiratory tract infections [15–17]. The mucosal lining and immune defenses of the nose and paranasal sinuses can be damaged by viral infection (common cold) predisposing to bacterial superinfection, the most important cause of acute rhinosinusitis [1]. The species most commonly implicated

Table 1.3 Potential etiologic factors in the pathogenesis of rhinosinusitis

Fig. 1.1 Sinus culture isolates in (a) adult and (b) pediatric acute bacterial rhinosinusitis.

S. pneumoniae, Streptococcus pneumoniae; H. influenzae, Haemophilus influenzae; Strep. species, Streptococcus species; M. catarrhalis, Moraxella catarrhalis; S. aureus, Staphylococcus aureus; S. pyogenes, Streptococcus pyogenes. (Reprinted from Anon JB, Jacobs MR, Poole MD, et al. Antimicrobial treatment guidelines for acute bacterial rhinosinusitis. Otolaryngol Head Neck Surg 2004;130:1–45 by kind permission of Elsevier [23].)

in acute rhinosinusitis are Streptococcus pneumoniae, Haemophilus influenzae, and

Moraxella catarrhalis [18–22] (Fig. 1.1a,b). This is not surprising because these pathogens reside in the nasopharynx and are, therefore, ideally situated to produce secondary overgrowth following viral infection. Generally, the bacteria that induce acute rhinosinusitis in children are the same as those found in acute otitis media [22]. A smaller proportion of cases are attributed to other Streptococcus species, Staphylococcus aureus, and anaerobic species [18,20,23] (Fig. 1.1a,b). Aerobic gram-negative rods, particularly Pseudomonas aeruginosa, are common in acute rhinosinusitis of nosocomial origin, immunocompromised individuals, and those with cystic fibrosis. Fungal sinusitis is most common in the immunocompromised and diabetic populations [22].

Antibiotics are often prescribed empirically for acute rhinosinusitis, although the cause is often viral. Consequently, the resistance of respiratory pathogens to antibiotics has been increasing yearly [1,23–25]. The penicillin resistance rate in S. pneumoniae has increased dramatically from 4% in the 1980s to 37% in 1997. The prevalence of -lactamase producing penicillin-resistant H. influenzae and M. catarrhalis has increased over the past several decades to around 40% and 98%, respectively, in the United States [26]. High levels of resistance to first-line antibiotics including penicillin, erythromycin, co-trimoxazole, and older fluoroquinolones have been demonstrated in sinus cultures from patients with acute rhinosinusitis [26]. The widespread antimicrobial resistance among pathogens that cause rhinosinusitis allows for the persistence of infection and the development of chronic rhinosinusitis.

It has been postulated that chronic rhinosinusitis evolves from acute rhinosinusitis, but this has never been definitively proven [1]. The role of bacteria in the development of chronic rhinosinusitis is controversial. Investigators have isolated both aerobic and anaerobic species from the diseased side and the contralateral, nondiseased side of patients with chronic rhinosinusitis, suggesting that colonization does not directly translate to disease [27]. Several studies have consistently isolated a variety of microbial pathogens from the sinuses of chronic rhinosinusitis patients. The majority of these isolates (86%) are aerobic, although anaerobes are isolated in a minority (8%) of patients. There are several distinct differences in the microbiology of chronic rhinosinusitis when compared to acute disease. The most commonly isolated organisms in chronic rhinosinusitis are Staphylococcus aureus (36%) and coagulase-negative Staphylococcus (20%). Streptococcus pneumoniae (9%) is found far less commonly than in acute bacterial rhinosinusitis [28]. Similarly, Haemophilus influenzae and Moraxella catarrhalis do not appear to be major pathogens in chronic rhinosinusitis [2]. Aerobic organisms may be gradually replaced by anaerobes as disease duration lengthens. This is potentially mediated by antimicrobial agents that select for resistant microbes, as well as changes in the local sinonasal environment including reduced oxygen tension and pH. Polymicrobial colonization is also a common feature of chronic rhinosinusitis [1].

Fungi have also been isolated from the sinus cavities of rhinosinusitis patients, but no evidence has been demonstrated for causality. Although fungal proliferation and invasion by species such as Mucor, Alternaria, Candida, Curvularia, Bipolaris, Sporothrix schenckii, and Pseudallescheria boydii can occur in immunocompromised patients, the inflammatory response cascade triggered by fungi is likely to be a more important factor in the etiology of chronic rhinosinusitis [2]. Consequently, desensitization to fungal antigens has proven to be useful in symptom control among certain patients with rhinosinusitis [2]. However, the use of antifungal agents has inconsistent efficacy in patients with chronic rhinosinusitis [1].

Allergy

The suggested association between atopy and rhinosinusitis is based upon the concept that the mucosa of the nasal airway is in a continuum with that of the paranasal sinuses. Mucosal swelling and edema in the region of the ostiomeatal complex may facilitate obstruction of the sinus ostia, reducing ventilation and permitting negative pressure to develop in the sinus cavities. Oxygen tension within the sinuses is reduced, disrupting ciliary function and thereby impairing mucus drainage; this increases the risk of secondary infection [1,29]. Repeated exposure to allergens further reduces the response threshold of the mucosa to other allergens, pollutants, and irritants, increasing edema and effectively “priming” the mucosa for secondary bacterial infection [29].

There is some evidence for a relationship between allergies and rhinosinusitis. Around 50% to 84% of patients with chronic or recurrent rhinosinusitis had at least one positive skin prick test [30,31]. Sixty percent of the allergic cohort demonstrated significant allergic sensitivity, with 52% positive for multiple allergen sensitivities,

particularly house dust mites [31]. However, the prevalence of allergies in many of these studies may be optimistic because cases were often recruited from allergy or otolaryngology clinics, creating a selection bias [1]. Interestingly, although multiple studies report a higher incidence of positive CT findings in rhinosinusitis patients with the highest degree of sensitivity, other studies indicate that the severity of the allergy does not necessarily correlate with disease severity as assessed on CT scan [31–33]. This suggests that, although allergies may predispose to rhinosinusitis, the eventual development of symptoms is a multifactorial process [31]. Indeed, epidemiologic studies investigating chronic rhinosinusitis reveal no increase in the incidence of disease during pollen season in pollen-sensitized patients, refuting a causative link between allergy and chronic rhinosinusitis [34].

In studies of acute rhinosinusitis, 25% of patients had evidence of allergy after skin testing, nasal smears, and allergy questionnaire versus an allergy prevalence of 16.5% among control cases. Despite this difference, allergic patients did not suffer more acute rhinosinusitis episodes than their nonallergic counterparts, nor did they have significantly different bacteriological or radiologic findings [30].

Overall, the role of allergy in rhinosinusitis remains unclear, which will likely continue to be uncertain until a well-designed prospective study investigating the relationship between allergy and infective rhinosinusitis is conducted. Nevertheless, from a practical standpoint, it is evident that failure to adequately control allergic symptoms reduces the likelihood of successful pharmacologic and surgical intervention [1].

Asthma

Initial evidence for a link between lower and upper respiratory tract disease comes from the observation that asthma and rhinosinusitis coexist in patients at a higher frequency than either condition alone in the general population [35]. The prevalence of asthma in patients with allergic rhinitis is approximately 17% to 38%, considerably higher than the 5% to 8% prevalence of asthma in the general population. The inverse association also holds true, with 60% to 80% of patients with asthma suffering from rhinosinusitis compared to only 10% to 20% of the general population [35,36]. Chronic rhinosinusitis is associated with a 20% prevalence of asthma, approximately fourfold higher than in the general population [37]. Onefifth of patients with chronic rhinosinusitis have coexisting polyposis and, in this subset, the prevalence of asthma is 50% [38]. Furthermore, patients with severe asthma were observed to have more significant sinus disease on CT scan than those with mild asthma [39]. However, these results must be viewed critically since sinus abnormalities detected on imaging in sensitized patients may be a consequence of the underlying allergic state rather than sinus disease [1]. In addition, the true incidence of atopy in the rhinosinusitis population may be lower than estimated in many of these studies. For example, one study indicated that 39% of patients with chronic rhinosinusitis had asthma as well as eosinophilia and elevated IgE, but only 25% of patients had true markers of atopy [40]. Although there does appear to be significant

evidence that asthma and rhinosinusitis are associated, the nature of this relationship and the implications for management have yet to be elucidated.

Pollution

Multiple studies have explored the association between outdoor air pollution and chronic rhinosinusitis. An epidemiologic study from Brazil demonstrated that chronic exposure to urban air pollution was associated with a higher prevalence of rhinosinusitis and upper respiratory tract infections than was diagnosed in children from a rural, pollution-free environment. This effect was correlated with an observed increase in ultrastructural damage to the cilia of the airway epithelium in rats exposed to similar levels of urban pollution [41]. In contrast, a report from Korea found that there was no significant difference in the prevalence of chronic rhinosinusitis between rural and urban areas [42]. Recently, an investigation into the association between air pollution and chronic rhinosinusitis that was conducted in Germany revealed that the spatial distribution of chronic rhinosinusitis correlated with areas in which air pollution exceeded a relatively low threshold [43]. Cigarette smoking has also been associated with a higher prevalence of rhinosinusitis, although further studies have failed to confirm this finding [1]. Environmental factors undoubtedly play a role in the pathophysiology of rhinosinusitis, but confirmatory in vitro histopathological evidence remains scarce.

Anatomic Factors

Mucociliary Impairment

Intact ciliary function is a key defense mechanism against infection of the paranasal sinus and nasal mucosa. Mucociliary flow is compromised by viral rhinosinusitis, which produces increasing ciliary damage during the first week of infection. Regeneration of ciliary function does occur, but initially consists of short and immature cilia that are not as efficient in maintaining mucociliary flow. Consequently, the risk of bacterial superinfection is increased, which, in turn, results in further loss of cilia and compounds the ongoing infection [1,44,45]. As a result, a secondary ciliary dyskinesia develops as a result of chronic rhinosinusitis, permitting persistence of infection. The importance of mucociliary clearance is highlighted in primary ciliary dyskinesia, Kartagener’s syndrome, in patients who frequently present with recurrent and chronic rhinosinusitis. Similarly, patients with cystic fibrosis produce viscous mucous secretions that directly impair ciliary function, predisposing to chronic rhinosinusitis [1].

Anatomic Variations

Anatomic variations of the lateral nasal wall and nasal septum have long been implicated in the etiology of chronic rhinosinusitis. These assertions are based on the

concept that certain anatomic features can disturb nasal physiology by impairing mucous flow and, hence, predisposing to infection [1,46]. For example, nasal deviation can potentially force the middle turbinate laterally, narrowing the middle meatus and compromising airflow and mucous outflow from the paranasal sinuses. This problem could be compounded by a concha bullosa, which further narrows the middle meatus [46]. Obstruction of the associated ostiomeatal complex can lead to ethmoidal and maxillary sinus disease [47].

Considering the relative preponderance of anatomic variation in nasal structures (64.9%–86%), the relationship between anatomy and rhinosinusitis could be highly relevant [48]. Concha bullosa is detected in 13.2% to 50% of healthy individuals and in 33.8% to 72.6% of cases with symptoms of rhinosinusitis [46]. Although there have been reports linking this anatomic variant to rhinosinusitis, there is also evidence that there is no significant difference in the incidence of concha bullosa between healthy and diseased individuals [49]. Another study demonstrated that rhinosinusitis often occurred on the opposite side to the concha bullosa, further arguing against a causal role for this anatomic variant in the disease process [46]. Septal deviation of greater than 3 mm from the midline has been correlated with chronic rhinosinusitis in some studies [50,51]. This finding has also been refuted in the literature [42,52]. The lack of a significant correlation between any anatomic variant as detected on CT and rhinosinusitis has been demonstrated repeatedly [1,48,53]. In the absence of a study that definitively demonstrates obstruction of the ostiomeatal complex by an anatomic variant, a causal role for paranasal anatomy in rhinosinusitis cannot be assumed.

Systemic Disorders and Rhinosinusitis

Immunodeficiency

Immunocompromised states have been associated with an increased risk of rhinosinusitis and, as a result, immunological testing is a critical component of the diagnostic workup of chronic or recurrent rhinosinusitis [1]. Low levels of immunoglobulin (Ig) G, A, and M have been found in 17.9%, 16.7%, and 5.1%, respectively, of patients with refractory rhinosinusitis. Approximately 10% of these cases are a result of common variable immunodeficiency, and a selective IgA deficiency was diagnosed in 6% of cases. Forty percent of the study cohort was anergic, and subsequent assessment of T-lymphocyte function revealed that 54.8% of cases showed an abnormal proliferation response to recall antigens [54]. Ataxia telangiectasia and X-linked agammaglobulinemia have also been associated with rhinosinusitis [1].

With the increasing incidence of acquired immunodeficiency syndrome (AIDS), several investigators have studied the relationship between human immunodeficiency virus (HIV) infection and the risk of rhinosinusitis. The development of suppressed humoral and cellular immunity, impaired mucociliary clearance, and increased levels of IgE in AIDS patients could theoretically increase the risk of rhinosinusitis [1]. Interestingly, rhinosinusitis has not been consistently associated