Medical Management of Chronic Sinusitis
Jeffrey D. Suh
Alexander G. Chiu
Chronic rhinosinusitis (CRS) is one of the more prevalent chronic illnesses in the United States, affecting at least 14% of the adult U.S. population (1). According to recent 2007 data from the National Health Interview Survey, rhinosinusitis continues to be one of the top 10 leading diagnoses of office visits in the United States. It has been estimated that over $5.8 billion dollars is spent each year treating patients with sinus complaints, and that one in every five antibiotics prescribed are for patients with sinusitis (2). The socioeconomic impact of rhinosinusitis is even greater when indirect costs from decreased work productivity and missed work days are considered. CRS not only causes symptoms directly related to the nasal cavity and sinuses, but also has a substantial negative health impact on quality of life with respect to mood, bodily pain, energy level, physical functioning, and social functioning (3,4). Medically recalcitrant CRS can be even more debilitating than other serious medical conditions such as angina, congestive heart failure, chronic obstructive pulmonary disease, and chronic back pain, or sciatica (3).
Despite its prevalence and importance, the etiology and pathophysiology of CRS is poorly understood. CRS was believed at one time to arise, somewhat simply, from sinus ostium obstruction leading to mucus stasis and subsequent bacterial infection. CRS is now thought to arise from persistent inflammation of the sinonasal mucosa, and perhaps the underlying bone, due to a number of factors. Perhaps the most appropriate broad classification of predisposing factors for CRS is grouping into environmental factors (e.g., pollution, allergens, viruses, bacteria, and molds), general host factors (genetic, granulomatous disorders, immune deficiency, cystic fibrosis, and ciliary defects), and local host factors (chronic localized inflammation, anatomic obstruction, polyps, and tumors) (5). It is clear that CRS is not one disease, but rather is a spectrum of symptoms and signs that can arise from multiple different etiologies.
Although multifactorial in origin, CRS is characterized by a consistent set of symptoms and clinical signs. Persistent mucosal inflammation and thickened mucus often leads to symptoms of postnasal drainage, nasal congestion, decreased sense of smell, and/or facial pressure. Given the consistency of these symptoms, initial medical management of CRS is focused on treating mucosal inflammation and purulent mucus. Those that fail this medical therapy are often recommended to consider sinus surgery. But with a 5% to 10% failure rate from surgery (4), there is an additional subset of patients who are recalcitrant to conventional medical and surgical therapies, leading to alternative therapies centered on anti-infective and anti-inflammatory nasal irrigations.
DEFINITION AND DIAGNOSIS
Clinicians treating CRS must be familiar with the criteria used to make the diagnosis. CRS is defined as persistent symptomatic inflammation of the nasal and sinus mucosa lasting for more than 12 weeks. The diagnosis of CRS is based primarily on medical history and is supported secondarily by confirmatory physical findings. In 2007, an updated clinical practice guideline by the American Academy of Otolaryngology— Head and Neck Surgery was developed by a multidisciplinary expert panel based on evidence from the literature (6) (Table 39.1). Briefly, the diagnosis of CRS requires that inflammation be documented on physical examination, in addition to persistent symptoms that usually include at least two of the following: nasal obstruction, facial congestion/pressure/fullness, discolored nasal discharge, and hyposmia.
STAGING SYSTEMS
A variety of staging systems have been used to stratify patients with CRS according to objective radiologic and endoscopic findings. Familiarity with these staging systems can allow the otolaryngologist to better document changes
in physical examination. Two commonly used staging systems found in the literature are described briefly in this section. These staging systems can be helpful to document exam changes following initiation of medical or surgical therapies.
in physical examination. Two commonly used staging systems found in the literature are described briefly in this section. These staging systems can be helpful to document exam changes following initiation of medical or surgical therapies.
TABLE 39.1 CLINICAL PRACTICE GUIDELINES, ADULT SINUSITIS (2007) | |||||||||||||||||||||||||||||||||
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Lund-Mackay Staging
The Lund-Mackay staging system is widely used in the radiologic assessment of CRS (7). The scoring system is based on computed tomography (CT) scan findings that are often obtained after an adequate trial of medical treatment. Each sinus is evaluated on cross-sectional imaging and noted to be completely clear, partly opaque, or completely opaque and assigned a simple numeric score (Table 39.2). The sinus groups include the maxillary, frontal, sphenoid, anterior ethmoid, and posterior ethmoid sinuses. The ostiomeatal complex is also scored. A total score of 0 to 24 is possible, and each side can be considered separately (0 to 12).
TABLE 39.2 LUND-MACKAY STAGING SYSTEM | ||||||||||||||||||
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Lund-Kennedy Endoscopic Scores
In this staging system, the endoscopic appearance of the nose is examined for the presence of polyps (0, none; 1, confined to middle meatus; 2, beyond middle meatus), discharge (0, none; 1, clear and thin; 2, thick and purulent), and edema, scarring or adhesions, and crusting (for each: 0, absent; 1, mild; 2, severe) (8,9,9a).
MEDICAL MANAGEMENT OF CHRONIC RHINOSINUSITIS
The treatment of CRS is based on a number of factors including the type of rhinosinusitis (acute, chronic, or fungal), concurrent medical comorbidities, symptom severity, and response to previous medical treatments (10). In general, the treatment of CRS is intended to reduce symptoms, improve quality of life, and prevent disease progression or recurrence. More specifically, treatments are aimed at reducing mucosal inflammation, controlling infection, and restoring mucociliary clearance. Medical treatment should be considered the cornerstone of disease treatment for CRS, with sinus surgery reserved for medical failures or for patients with complications.
GENERAL TREATMENT STRATEGIES
CRS has recently been simplified to two subgroups; CRS with nasal polyps (NP) and CRS without NP (9). In the past, these two entities were considered to be a spectrum of a single disease, with NP being considered the end point of the evolution of CRS. Current data suggest that there are distinct differences between patients in the subgroups, and that the groups can have different responses to medical treatment (9,11). This chapter discusses the most common treatment modalities used to treat CRS, and focus on specific recommendations based on the CRS subgroup (CRS with or without polyps) when possible.
STEROIDS
Corticosteroids constitute first-line therapy in the medical management of CRS. Glucocorticoids have wide-ranging effects on the nasal mucosa. Studies of glucocorticoids show that they can suppress many phases of the inflammatory process by inhibiting the release of vasoactive mediators, reducing vasodilation, fluid extravasation, edema, and local deposition of mediators (12). Glucocorticoid-treated NP have demonstrated a down-regulation of proinflammatory cytokines and adhesion molecules that attract and activate eosinophils (13,13a). Studies of asthma and allergic rhinitis (AR) show that glucocorticoids decrease a wide variety of proinflammatory cytokines, chemokines, adhesion molecules, and mediator-synthesizing enzymes such as inducible nitric oxide synthase, cyclooxygenase-2,
and phospholipase-A2 (13,13a,14). Both topical and oral corticosteroids are used frequently for CRS and are discussed in the following two sections.
and phospholipase-A2 (13,13a,14). Both topical and oral corticosteroids are used frequently for CRS and are discussed in the following two sections.
Topical Steroids
A number of studies have demonstrated the efficacy of intranasal steroids in the management of CRS with NP. These sprays are used most commonly in the management of symptoms associated with seasonal and perennial AR (15). Nasal corticosteroids have been shown to inhibit both immediate- and late-phase reactions to antigenic stimulation in patients with AR (16). In general, nasal steroids with low systemic bioavailability (such as mometasone furoate, fluticasone propionate, or furoate) have not been associated with bone growth or adrenal suppression, which was first noted with more systemically bioavailable agents such as beclomethasone dipropionate (17). There is also no clear evidence that the use of nasal corticosteroids correlates with systemic changes in bone mineral biology, cataracts, or glaucoma. Adverse effects such as nasal irritation, epistaxis, and crusting with nasal steroids are rare, occurring in less than 10% of patients (18). Rarely, septal perforations have been reported with nasal steroid spray usage. Therefore, to minimize epistaxis and possible perforation, patients are frequently instructed to direct the nasal spray toward the internal lateral aspect of the nasal cavity and not toward the nasal septum.
Topical steroids are routinely used to treat CRS with eosinophilic inflammation or NP. Guidelines from the 2007 European Position Paper on Rhinosinusitis and Nasal Polyps (19) recommends topical steroids as the firstline medication based on the results of several randomized controlled trials with fluticasone propionate, beclomethasone dipropionate, budesonide or mometasone furoate. Studies have demonstrated that topical corticosteroids are beneficial in the treatment of small to medium-sized polyps, nasal symptoms, and that this effect can be maintained with continued use (20,21,22,23,24). Corticosteroid nasal sprays have also been shown to delay the recurrence of polyps after surgery (24,25). There has also been some recent literature describing the use of budesonide respules (Pulmicort; AstraZeneca, Wilmington, DE) as an adjuvant method of treating eosinophilic or polypoid CRS when the respules are directly applied as a nasal drop or as an additive to nasal irrigation (26,27). In theory, a much higher concentration of corticosteroids can be applied to the sinus mucosa with budesonide respules compared to conventional nasal steroid sprays.
Despite proven efficacy of intranasal steroids for CRS with NP, benefit for nonpolypoid CRS has been harder to demonstrate (28,29,30,31). A randomized, double-blind, placebo-controlled study on patients with CRS without NP found no significant improvement on endoscopy and symptoms scores with fluticasone propionate for 16 weeks (32). More research is required to support the use of intranasal steroids for CRS without NP.
Systemic Steroids
Oral corticosteroids are commonly used in the treatment of CRS with and without NP for recalcitrant cases or when a rapid, short-term improvement is needed (33,34). However, despite widespread use among both general otolaryngologists and rhinologists, there is a lack of strong evidence with respect to indication, dose and duration (35,36). In 2007, a Cochrane review found only one randomized, controlled trial (37) on oral steroid therapy for CRS with NP (33). The results of this study and others have shown that oral steroids can dramatically reduce polyp size in patients with CRS, reduce nasal obstruction, improve quality of life scores, and decrease inflammatory chemokines and cytokines (37,38,39,40). But without other adjuvant treatments, these benefits are usually short-lived (40). Recent evidence suggests that combination therapy with oral and intranasal corticosteroids can provide long-term reduction in polyp size and improvements in quality of life without significant adverse effects (41).
The most common side effects of oral steroid use include glucose intolerance, hypertension, gastrointestinal bleeding, and altered mood. Adverse effects associated with long-term use of oral steroids include weight gain, glaucoma, cataracts, gastrointestinal complications, adrenal suppression, growth suppression, diabetes mellitus, osteoporosis, and avascular necrosis (most commonly of the hip) (33). These risks must be carefully considered, and patients must be counseled about these side effects prior to initiating long-term therapy.
ANTIBIOTICS
Antibiotics are commonly used in the management of CRS to decrease bacterial load and to treat acute bacterial exacerbations of CRS. There are significant differences in the bacteria present in CRS as compared to acute rhinosinusitis. Antibiotic therapy for CRS has traditionally been aimed at a mixed population of aerobic and anaerobic bacteria. However, despite level 1A evidence of the efficacy of topical steroids in treating rhinosinusitis, no such evidence of antibiotic efficacy in CRS exists and no antibiotic is U.S. Food and Drug Administration (FDA)-approved for the indication of treating CRS. Commonly used agents include amoxicillin-clavulanate, clindamycin, trimethoprim-sulfamethoxazole, or a fluoroquinolone. The optimal duration of therapy has not been studied prospectively, but is typically 3 to 4 weeks long, with longer courses for recalcitrant cases. When treating CRS with antibiotics, it is important that other modalities, such as nasal irrigation and topical or oral corticosteroids, also be included.
The species of bacteria and the incidence of antibiotic resistance vary widely depending on a variety of factors including the chronicity of the disease and the extent of prior antibiotic
therapy. The microbiology of CRS differs from that of acute rhinosinusitis, with a greater incidence of anaerobic bacteria, Staphylococcus aureus, and Pseudomonas aeruginosa, all which must be considered before recommending antibiotics. In a study by Finegold et al. (42) the most common anaerobic bacteria in chronic maxillary sinusitis were Prevotella species, anaerobic streptococci, and Fusobacterium species. The most common aerobic bacteria were Streptococcus species, Haemophilus species, P. aeruginosa, S. aureus, and Moraxella catarrhalis. The microbiology of chronic frontal sinusitis is slightly different, with 21% S. aureus, 21% coagulase-negative staphylococci, 9% Haemophilus influenzae
therapy. The microbiology of CRS differs from that of acute rhinosinusitis, with a greater incidence of anaerobic bacteria, Staphylococcus aureus, and Pseudomonas aeruginosa, all which must be considered before recommending antibiotics. In a study by Finegold et al. (42) the most common anaerobic bacteria in chronic maxillary sinusitis were Prevotella species, anaerobic streptococci, and Fusobacterium species. The most common aerobic bacteria were Streptococcus species, Haemophilus species, P. aeruginosa, S. aureus, and Moraxella catarrhalis. The microbiology of chronic frontal sinusitis is slightly different, with 21% S. aureus, 21% coagulase-negative staphylococci, 9% Haemophilus influenzae
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