Traditional treatment of Chronic Rhinosinusitis - an update

Management of Acute Rhinosinusitis

 

Andrew J. Victores, MD

Masayoshi Takashima, MD

 

Bobby R. Alford Department of Otolaryngology–Head and Neck Surgery, Baylor College of Medicine, Houston, Texas, USA

 

Corresponding author: Masayoshi Takashima, MD

 

6501 Fannin St., Suite NB302

Houston, Texas 77030

Phone: (713) 798-5906

Email: takashim@bcm.edu

 

INTRODUCTION

Rhinosinusitis is a significant healthcare problem that is highly prevalent, affecting approximately 16% of the adult population in the United States annually.1-3 The costs associated with the disease are substantial, including direct costs of management and indirect costs of lost productivity.1 Rhinosinusitis accounts for the fifth most common diagnosis for antibiotic prescription.1

Historically, inflammation of the sinuses has been referred to as sinusitis. In recent years, the term sinusitis has largely been replaced by rhinosinusitis.4 This change came about largely to stress the close relationship between the nose and paranasal sinuses. Most multidisciplinary societies support the concept that nasal mucosal inflammation, or rhinitis, often precedes and almost always accompanies sinus mucosal inflammation.2,5-7 Some limited objective data has been obtained to provide support for this concept. Gwaltney et al used computed tomography (CT) imaging to demonstrate nasal cavity changes in patients with acute rhinosinusitis (ARS).8 Other studies have shown histologic evidence of inflammatory changes in the nasal mucosa in patients with rhinosinusitis.9,10

Sinusitis is categorized by duration of sinonasal inflammation. Sinonasal inflammation with sudden onset of symptoms lasting up to 4 weeks is considered acute rhinosinusitis (ARS).6 Key diagnostic symptoms include purulent nasal drainage, nasal congestion, and facial pain or pressure. One of the challenges in the diagnosis of ARS is differentiating viral from bacterial etiologies. This distinction is important as viral causes of ARS will largely resolve spontaneously whereas bacterial episodes may benefit from antibiotics. The most recent Clinical Practice Guideline from the American Academy of Otolarynology-Head and Neck Surgery suggests a diagnosis of bacterial ARS be considered when symptoms persist longer than 10 days or worsen after a period of initial improvement.6

Some patients have recurrent episodes of ARS. Recurrent acute rhinosinusitis (RARS) is defined by the presence of four or more episodes of acute bacterial rhinosinusitis (ABRS) without signs or symptoms of rhinosinusitis between episodes.6 These patients do not have rhinosinusitis symptoms between episodes. Chronic rhinosinusitis (CRS) is diagnosed if symptoms are persistent for more than 12 weeks.6 CRS is further delineated by the presence or absence of nasal polyposis.

 

PATHOPHYSIOLOGY

The sinonasal tract acts to trap and expel foreign material as well as mount an immune response to these agents. Sinonasal inflammation in ARS begins as a response to foreign antigens, including viruses, bacteria, fungus, and allergens. Unfortunately, this inflammation can lead to sinus obstruction and ARS.

The primary cause of ARS is thought to be viruses. Many patients with the common cold were found to have involvement of the sinuses.8 Inoculation with rhinovirus frequently causes symptoms associated with ARS.11 Impaired sinonasal function from viral infection has also been thought to predispose patients to bacterial infection. However, most viral ARS episodes resolve without proceeding to bacterial rhinosinusitis with only about 0.5% to 2.2% becoming bacterial ARS.12

Bacteria frequently found in patients with acute bacterial rhinosinusitis include Streptococcus pneumonia, Haemophilus influenza, and Moraxella catarrhalis.13 Some studies have also implicated Staphlococcus aureus as a major pathogen.14 In complications that arise from acute sinusitis, polymicrobial isolates are often found with respiratory pathogens or oral flora implicated as sources of the infection.15,16

Anatomic variations can be a predisposing factor in ARS. Variations of anatomy associated with rhinosinusitis include structural abnormalities, increased pneumatization, and supplementary sinus openings.17 Although the evidence is limited, the anatomic abnormalities most associated with ARS include concha bullosa, large infraorbital ethmoid cells, accessory sinus ostia, and ethmoid infundibulum stenosis (Fig. 1).18-20

Environmental irritants, such as allergens and cigarette smoke, may predispose patients to ARS. Many patients with rhinosinusitis suffer from allergic rhinitis.21 Retrospective studies found that at least half of patients presenting with rhinosinusitis also have positive allergy skin test responses.22 Diagnosis and treatment of allergies may aid the management of sinus disease. Sinus function can also be harmed by smoke exposure. Smoking has been linked to a number of upper airway diseases in both children and adults. With regard to the sinuses, studies have linked smoking with altered flora colonization of the sinuses to harbor more potential pathogens.23 Mucociliary clearance also appears to be impaired by smoking.24  

 

MANAGEMENT OF UNCOMPLICATED ARS

Saline Irrigations

Management of sinus disease frequently includes use of saline irrigations. Studies have shown improvement in symptoms and quality of life as well as decreased medication use.6,25,26 Saline irrigations appear to help patients with rhinosinusitis by improving mucociliary clearance and thinning mucus as well as providing an anti-inflammatory effect.27,28 Both isotonic and hypertonic saline have been used for sinusitis. Limited data suggests that hypertonic saline may be superior to isotonic saline.27,29,30 Two randomized clinical trials have demonstrated significant benefit with use of hypertonic saline irrigations, including improvement in sinus related quality of life, symptoms, and mucociliary clearance.26,31

Intranasal Corticosteroids

Another adjunct of sinusitis management is intranasal corticosteroids. The primary function of intranasal corticosteroids is a local anti-inflammatory effect which can in turn provide some symptomatic relief from ARS. Several randomized controlled studies have been performed evaluating the effects of intranasal corticosteroids in ARS.32,33 These studies have demonstrated reduced daily impact of ARS symptoms with intranasal corticosteroid use. A recent Cochrane review also demonstrated significant improvement of ARS symptoms with intranasal corticosteroid use.34 A modest group of patients may even have complete resolution of symptoms. A number of different formulations of intranasal corticosteroids have been used for sinus complaints. A couple of commonly used formulations include fluticasone propionate 110 μg daily or twice daily or mometasone furoate 200 μg daily or twice daily. The adverse events associated with intranasal corticosteroids are relatively limited given the negligible systemic uptake of the medication. Intranasal corticosteroids have been shown to have no significant effect on glucose levels in diabetic patients.35 There also does not appear to be any effect of intranasal corticosteroids on the hypothalamic-pituitary-adrenal axis.36,37 Even in pregnant patients, many clinicians still recommend continuing to use intranasal corticosteroids.38 This is in stark contrast to oral corticosteroids, which are better known for their potential side effects.

Oral Corticosteroids

Oral corticosteroids serve an important role in the management of nasal polyposis, which can develop in patients with chronic rhinosinusitis. The role of oral corticosteroids in acute rhinosinusitis remains less clear. Few studies have specifically addressed this therapy in acute rhinosinusitis and there is significant variability in the dosage and length of therapy that is utilized.39 In addition, many of these studies are confounded by antibiotic use. A Cochrane review meta-analysis failed to find significant evidence to support systemic corticosteroids as a monotherapy in ARS.40 Although some studies did show a modest benefit with oral coritcosteroid use in combination with oral antibiotics, there was no clear consensus. In addition, short-course oral corticosteroid has been associated with adverse events, including gastrointestinal disturbances and insomnia.41 Given the limited data demonstrating any benefit of use and potential side effect of use, oral corticosteroids are generally not used in uncomplicated ARS.

Oral Antibiotics

Antibiotics have traditionally played a role in the management of acute bacterial rhinosinusitis (ABRS). As previously discussed, the challenge can be in differentiating viral and bacterial etiologies. Current practice guidelines suggest using the time course of symptoms to make this distinction.6

Of note, some recent studies have cast doubt on the role of antibiotics in uncomplicated ARS, even in cases of bacterial infections. Many cases of ABRS will resolve spontaneously without antibiotics. In addition, there are adverse events associated with oral antibiotic use. Several randomized controlled trials have compared antibiotic use with placebo for ABRS.42-45 Antibiotics as a first line treatment for ARS was found to have limit benefit in terms of shortening the recovery period, yet had considerable side effects.43 For this reason, some have suggested a period of watchful waiting for uncomplicated ARS. Some clinicians and patients may find this period difficult due to the potential inconvenience, expense, and delay should watchful waiting fail. For this reason, recent Clinical Practice Guidelines from the AAO-HNSF suggest providing a prescription once the diagnosis of ABRS is made, but asking that the patient not fill the prescription unless symptoms worsen or persist longer than 7 days.6

When antibiotics are deemed appropriate for use, the clinician must then select the appropriate regimen. Most research and consensus guidelines currently recommend amoxicillin with or without clavulanate for 5 to 10 days as first-line therapy for adults with uncomplicated ABRS.6 With regard to dosage selection, higher-dose regimens may be more appropriate, as has been demonstrated with amoxicillin with clavulanate. Studies have found reduced nasopharyngeal carriage of pneumococcus with higher dose of amoxicillin with clavulanate.46 Unfortunately, evidence suggests organisms are becoming increasing resistant to penicillin based antibiotics. In fact, penicillin-resistant pneumococcus was isolated in the middle meati of most adult and pediatric patients (72%).47 Clearly, antibiotic resistance is and will remain a serious concern in the treatment of acute bacterial sinus infections.

In some patients, first-line therapy will fail and alternative antibiotics will need to be considered. Moreover, many patients are allergic to the first line options. Consideration should be given to choosing an antibiotic with adequate coverage, particularly if a culture was obtained. Second-line drugs include trimethoprim-sulfamethoxazole, doxycycline, and a combination of clindamycin plus a third-generation oral cephalosporin.6 Respiratory fluoroquinolones have also been used extensively, especially for patients with recalcitrant disease. Unfortunately, fluoroquinolones are associated with severe adverse events, including cardiac, musculoskeletal, and peripheral neuropathy. For this reason, they have recently fallen under the scrutiny of Food and Drug Administration (FDA) advisory committees.48 As of 2016, a Boxed Warning was placed on use of fluoroquinolones for the purpose of treating sinusitis due to the risk of disabling and potentially irreversible adverse reactions. This will clearly discourage future use of these antibiotics for sinus disease. Perhaps further studies can refine the patient populations for whom the benefits of fluoroquinolones outweigh the risks. The duration of therapy for second-line therapies is typically similar to first-line regimens, with most recommending 10 days or less of therapy.2,6 Shorter courses are generally recommended due to less risk for side effects and greater patient compliance.2,6

Other Non-Surgical Treatments

Various additional therapies aimed at symptomatic relief have been used for ARS. These include decongestants, antihistamines, ipratropium bromide, and mucolytics. Although these therapies are often used by clinicians, there is relatively limited clinical data to confirm their efficacy. Decongestants act to improve nasal obstruction, one of the primary complaints associated with ARS. Unfortunately, randomized controlled studies have not been able to demonstrate a significant clinical benefit of using decongestants compared to placebo.31,49 Decongestants have relatively limited adverse events associated with their use over a short period of time. Prolonged use, on the other hand, can result in rebound nasal swelling and congestion when weaned from the decongestant, referred to as rhinitis medicametosa. Given the lack of clear clinical efficacy for ARS, but limited side effect profile with short course administration, consensus guidelines are unable to recommend or caution against use of decongestants for ARS.7 Another medication proposed for use in ARS is antihistamines. Although antihistamines are thought to decrease nasal drainage, no significant benefit could be demonstrated from their use with adult ARS in several studies.2,50 Similarly, ipratropium and mucolytics have no definite evidence to support their use in ARS.

 

MANAGEMENT OF TREATMENT FAILURE AND COMPLICATIONS

Most episodes of ARS resolve spontaneously or with non-surgical management. Unfortunately, treatment failure or complications of ARS do occur and can require more intensive management. Failure of ARS treatment is defined by worsening or failure of improvement of symptoms after 7 days from the initial diagnosis.6 The complications of ARS are categorized into orbital, intracranial, and osseous.7,51 Orbital complications of ARS occur about twice as frequently as intracranial complications, with osseous complications the least frequent.52 Osseous complications include osteomyelitis of the frontal or maxillary bones. The most common orbital infection is pre-septal cellulitis, although an overall small portion (9%) of these infections are due to ARS compared to post-septal orbital infections (91%).53 Sinusitis accounts for approximately 10% of intracranial infections.7,54,55 Complications of ARS are more often found in children.56,57 Males appear to be more frequently affected by complications of ARS than females.52,58

Orbital complications of sinusitis can vary in severity. The progression of sinus infection to orbital complications can be understood using the Chandler classification system.59 This classification is composed of a progression of five stages of infection from the sinus to the orbit. The least severe and most common (70-80%) of these is periorbital cellulitis (Chandler class I). In patients with periorbital cellulitis, the inflammatory process is confined to the periorbital space by the orbital septum with lack of orbital involvement. As a result, patients typically develop swollen eyelids without pain or impairment in extraocular movement or vision. When inflammation extends past the orbital septum to involve the orbital contents, the patient is deemed to have orbital cellulitis (Chandler class II). Coalescence of infectious fluid between the lamina papyracea and medial periorbita results in a subperiosteal abscess (Chandler class III). In rare cases, intraconal coalescence of purulence can form an orbital abscess (Chandler class IV). Cavernous sinus thrombosis has traditionally been classified as a late stage orbital infection (Chandler class V) with the hallmark of bilateral ocular symptoms. However, cavernous sinus thrombosis has more recently been thought of as an intracranial infection potentially independent of orbital infection.56

Management of complications of ARS includes the same conservative measures typically utilized in uncomplicated ARS. These include saline irrigations, intranasal corticosteroids, and potentially decongestants. However, additional means are usually required to adequately address the complications of ARS.

Intravenous Antibiotics

Intravenous (IV) antibiotics are rarely needed for uncomplicated ARS. On the other hand, they frequently serve a role in the management of complications of ARS. Broad-spectrum coverage should be considered. Cultures taken from purulent drainage should be obtained and used to further direct antibiotics selection. Consideration of local antimicrobial susceptibilities may also need to be factored into the decision. Intravenous antibiotics along with conservative measures can treat the majority of ARS complications without the need for surgical intervention. Surgery is typically reserved for severe complications of ARS or those patients with complications who fail appropriate IV antibiotic therapy.

Surgery

During an episode of ARS, the sinonasal mucosa becomes edematous and hyperemic. The narrowed space and increased susceptibility to bleeding make surgery during this state more difficult. Moreover, nearly all cases of uncomplicated ARS resolve without surgical intervention. For this reason, there is very limited role, if any, for surgery in the management of uncomplicated ARS. Unfortunately, untreated or resistant bacterial species of ARS can develop complications which necessitate surgery. The goals of surgery are to decompress pressure on vital structures in the orbit or intracranially if present, drain any purulent fluid collection, obtain cultures to direct antibiotics, and facilitate future irrigation and drainage by expanding sinonasal access to the site of infection.  

Surgery for orbital complications of ARS depend on the extent and severity of infection. As previously discussed, Chandler et al described a classification for the severity of orbital complications from ARS.59 Clinical and radiographic findings help to distinguish these complications. Most patients present early enough to be managed non-surgically with antibiotics and other conservative measures. However, the formation of subperiosteal abscess or orbital abscess may required endoscopic sinus surgery to open the sinuses, drain the abscess, obtain cultures, and potentially decompress the orbit.

Subperiosteal abscesses usually result from extension of infection from the ethmoid sinuses to the periorbita adjacent to the lamina papyracea bone.60-62 For this reason, subperiosteal abscess formation mostly occurs medial to the orbit. They account for approximately 12-17% of orbital infections.62-65 Management of this complication is controversial, with some advocating for a more conservative approach with IV antibiotics and others encouraging rapid surgical drainage.62,64,66,67 Surgical intervention can usually be performed through a transnasal endoscopic approach with anterior ethmoidectomy and opening of the lamina papyracea bone (Fig. 2).62 This approach is preferable to an external approach due to the lower morbidity and superior cosmesis. 64,66 Endoscopic surgery can be used even when the abscess extends partially superiorly or inferiorly to the orbit.68 Further extension could require an external surgical approach to the orbit. Surgery is not always needed for adequate subperiosteal abscess management. In fact, medical therapy alone maybe sufficient, particularly in younger patients. Patients who are younger than the age of nine appeared more likely to respond to medical therapy than older patients.62,65,69 One possible reason for this difference could be that younger patients more often contain a single bacterial isolate within the subperiosteal abscess as opposed to older patients with polymicrobial isolates.69,70

Unlike subperiosteal abscesses, the presence of an orbital abscess usually necessitates surgical intervention. This is particularly the case if there is lack of improvement with antibiotic management or there is concurrent intracranial infection. The surgical approach required for adequate drainage of the abscess is dependent on positioning within the orbit. Purulent loculation located medially can potentially be addressed with a transnasal endoscopic approach, whereas a location farther from the lamina papyracea can be more challenging to access endoscopically and require and external approach.

Some patients who suffer from orbital complications of ARS also develop intracranial complications. One study found nearly half of patients with intracranial complications of rhinosinusitis had periorbital cellulitis or abscess.71 Fortunately, intracranial complications are relatively rare, only identified in about 3-4% of adults and children admitted with ARS.72,73 Intracranial complications include meningitis and intracranial abscess. Aggressive management must be undertaken if one of these complications occurs. Intravenous antibiotic coverage should be utilized with selection of an agent that crosses the blood-brain barrier. Surgical intervention consists of drainage of the involved sinuses and evacuation of any coexistent abscess. An external approach to intracranial drainage can require a craniotomy or burr hole.

Some patients suffer from recurrent episodes of ARS. Recurrent ARS can significantly impair patient quality of life.74 Management of this disease can be challenging with limited success using antibiotics and intranasal corticosteroids.75,76 Endoscopic sinus surgery has shown promising results, improving quality of life to near normal post-operatively.