Introduction

Rhinosinusitis is one of the most common and prevalent illnesses throughout the world. Both acute and chronic forms of rhinosinusitis (RS) have been described, and affect patients of all ages. By a variety of reports, the incidence of RS is increasing, and the number of patients diagnosed around the world with RS continues to climb.¹ Allergy plays a role in the pathogenesis and expression of symptoms among patients with both acute and chronic RS, although the precise relationship between atopy and the presence of sinus disease can be difficult to define. Due to the heterogeneity seen in acute and chronic RS, consensus panels have been convened to provide clarity to the diagnosis of these common conditions, and to develop guidelines for further research and optimal treatment. This chapter will discuss the various types of RS, diagnostic strategies, and treatment options for both acute and chronic rhinosinusitis.

Prevalence and Burden of Rhinosinusitis

From a variety of sources, it has been noted that RS is increasing in prevalence. In the USA alone it is estimated to affect as many as 31 million patients on an annual basis.² It accounts for billions of dollars in expenditure, with significant increases in direct and indirect costs noted over a several year period.³ In addition, 15% of the US population is symptomatic from sinusitis for a period of at least 3 months annually.⁴

While most adults will experience between two and four acute upper respiratory infections annually, less than 2% of these episodes are due to acute bacterial rhinosinusitis (ABRS).⁵ By calculation, there would therefore be an expected 20000000 cases of ABRS in the USA alone on a yearly basis. RS was estimated to account for 9% of pediatric and 21% of adult prescriptions in the USA annually,⁶ with over $3.5 billion USD spent in 1999 funds for the treatment of ABRS alone.⁷

Two recent studies have examined the burden of chronic rhinosinusitis (CRS) on both patient impact and financial cost. Bhattacharyya followed 322 patients with CRS prospectively over a 1-year period.⁸ During that 1-year period, patients received an average of 2.7 courses of oral antibiotics, and used nasal steroids for over 18 weeks. In addition, patients missed an average of 4.8 days of work related to CRS and had mean medical expenses of US$921. In a second study by Murphy et al, over 200 000 patients in a health maintenance organization (HMO) were surveyed during the 1-year period 1994.⁹ Approximately 10% of patients in the HMO were identified with diagnoses of CRS during this one year. Among this patient group, CRS was responsible for an average of 2.0 office visits and 5.1 pharmacy fills per patient during 1994. Extrapolating to the general US population, this study estimated the overall direct cost of CRS in 1994 to be US$4.3 billion.

In addition to the clear economic burden of both acute and chronic RS, both of these diseases exert significant impact on patient symptoms and quality of life. Gliklich and Metson assessed this impact, and noted that RS is associated with a more negative quality of life than other common medical diseases such as chronic obstructive pulmonary disease and lower back pain.¹⁰

Definition of Rhinosinusitis

The term that is currently accepted by the majority of specialists who manage patients with acute and chronic illnesses affecting the paranasal sinuses is rhinosinusitis. While there is still some debate regarding the use of this term, and while there are individuals who prefer the older term sinusitis, rhinosinusitis is the accepted term agreed to by a consensus group of American medical societies, including the American Academy of Allergy, Asthma and Immunology (AAAAI), the American Academy of Otolaryngic Allergy (AAOA), the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS), the American College of Allergy, Asthma and Immunology (ACAAI), and the American Rhinologic Society (ARS).¹¹ The choice of the term rhinosinusitis implies that the physiological condition of the sinuses correlates closely with the concurrent condition of the nose. Nasal disease, i.e. rhinitis, usually precedes the development of sinus disease, and sinusitis is rare without rhinitis.^1,11,12 Given the contiguity of the nasal and sinus mucosa and the interdependency of the nose and sinuses, the term rhinosinusitis (RS) appears to be a more representative name for this process, and will be used in the current chapter.

In 1996, a task force of the AAO-HNS reviewed the current state of knowledge in RS, and drafted a definition statement based upon this expert panel. They defined RS as “a condition manifested by an inflammatory response involving the following: the mucous membranes (possibly including the neuroepithelium) of the nasal cavity and the paranasal sinuses, fluids within these cavities, and/or underlying bone.”¹ The key message implied from this definition is that RS is primarily an inflammatory disease, not an infectious disease. Infection is only one type of pathophysiological process that can affect the sinuses. In addition, recognizing the close relationship between the nose and sinuses, a conjoint conference involving the American allergy/immunology and otolaryngology communities concluded that “rhinosinusitis may be a more appropriate term than either rhinitis or sinusitis alone.”¹² Similar definitions have been applied by the European allergy and otolaryngology communities.¹³

In 2003, the Sinus and Allergy Health Partnership (SAHP), a conjoint society made up of representatives from the AAOA, the AAO-HNS, and the ARS, also met to consider the knowledge base around RS, and drafted a similar definition to that offered in 1996. The SAHP defined RS as “a group of disorders characterized by inflammation of the mucosa of the nose and the paranasal sinuses.”¹⁴ The 2004 consensus panel decided to “endorse and adopt” this definition for framing future research strategies and diagnostic and treatment methodologies.¹¹ The members of this panel recognized that inflammatory processes simultaneously affect the nose and sinuses, and that the term rhinosinusitis best describes this concurrent process.

Classification of Rhinosinusitis

It is clear that RS represents a spectrum of diseases rather than a single pathological entity. There are numerous potential sources of inflammation that can target the mucosa of the nose and paranasal sinuses. In addition to the various types of pathophysiological mechanisms that appear to be active in RS, the temporal sequence of symptoms and the degree of chronicity of the process are important factors in determining the nature of the RS and the best method of approaching its treatment.

▪ RS: 1997 Consensus

In the 1997 system, the diagnosis of RS was based purely on patient symptoms. These symptoms were broken down into major and minor factors that were associated with the presence of RS. These major and minor factors are noted in Box 4.1. It is important to note that headache or facial pain are not sufficient symptoms for the diagnosis of RS in the absence of other major or minor factors, primarily nasal in origin. These criteria are useful in assisting the clinician in the consideration of the diagnosis of acute or chronic RS, but do not require the presence of confirmatory findings on either physical examination or radiological imaging to apply a diagnosis. This lack of confirmation was felt to be a weakness in the 1997 document.

BOX 4.1 Factors associated with a diagnosis of rhinosinusitis.

(Adapted from Lanza DC, Kennedy DW. Adult rhinosinusitis defined. Otolaryngol Head Neck Surg 1997;117:S1–S7)

Major factors

Facial pain/pressure^a

Facial congestion/fullness

Nasal obstruction/blockage

Nasal discharge/purulence/discolored postnasal drainage

Hyposmia/anosmia

Purulence in nasal cavity on examination

Fever (acute RS only)^b

Minor factors

Headache

Fever (all nonacute)

Halitosis

Fatigue

Dental pain

Cough

Ear pain/pressure/fullness

^a Facial pain/pressure alone does not constitute a suggestive history for rhinosinusitis in the absence of another major nasal symptom or sign.

^b Fever in acute sinusitis alone does not constitute a strongly suggestive history for acute rhinosinusitis in the absence of another major nasal symptom or sign.

The 1997 task force also described the temporal course of RS and divided RS further into five categories, three primary categories: acute rhinosinusitis, recurrent acute rhinosinusitis, and chronic rhinosinusitis; and two derivative categories: subacute rhinosinusitis and acute exacerbations of chronic rhinosinusitis. The three primary groupings are often used to delineate the time course of RS in individual patients and to assist in the development of appropriate treatment modalities (Figure 4.1).

Figure 4.1 Temporal course of rhinosinusitis: acute, recurrent acute, and chronic.

(Adapted with permission from Lanza DC, Kennedy DW. Adult rhinosinusitis defined. Otolaryngol Head Neck Surg 1997;117:S1–S7.)

Acute Rhinosinusitis

Acute rhinosinusitis (ARS) is a very common condition, and generally has a sudden onset of symptoms, often following a viral upper respiratory infection. It is defined as lasting from 1 day to 4 weeks. It is important to distinguish between a viral upper respiratory infection, which is very common, and an acute bacterial rhinosinusitis. The most robust method of distinguishing these two conditions is the temporal course of the illness. Viral symptoms generally peak within 3 or 4 days of onset and then decline in severity. By contrast, acute bacterial RS generally worsens after 5 days and persists longer than 10 days.¹⁵ In addition, certain physical signs are suggestive of a diagnosis of acute bacterial RS. Facial erythema or swelling are associated with bacterial disease, although they are uncommon. Maxillary tooth pain is correlated well with the presence of bacterial disease, and when accompanied with fever often confirms the presence of acute bacterial RS.¹⁶

Recurrent Acute Rhinosinusitis

Many patients may experience episodes of acute bacterial RS that last 7–10 days and respond rapidly to treatment, yet seem to have frequent recurrent episodes with a similar pattern. Between symptomatic episodes, these patients may be clear of any symptoms of nasal or sinus disease. The frequent recurrent nature of these episodes suggests a separate categorization of disease, which has been called recurrent acute RS. While there are not strict criteria for the diagnosis of this process, some authors have suggested that patients should experience at least four episodes of acute RS within a year, and that intervening periods without symptoms should be at least 8 weeks.^1,17 It is not clear whether recurrent acute RS is a distinct pathophysiological entity, reflecting a unique underlying process, or if it simply reflects random variation in the frequency of disease.

Chronic Rhinosinusitis

Chronic rhinosinusitis (CRS) is in many ways a distinct pathophysiological process that reflects the chronic inflammatory nature of the disease. It is not simply acute disease that has not resolved or has progressed into chronic disease. From a temporal standpoint, CRS is generally classified as persistent sinonasal symptoms for at least 12 weeks,^11,18 although some systems suggest that 8 weeks may be adequate to classify the disease as CRS.¹⁹ CRS likely has numerous mechanisms involved in its pathogenesis, and is probably best considered as a syndrome rather than a unique pathophysiological entity. Recent classification systems make clear distinctions between CRS with the presence of nasal polyps (CRSwNP) and CRS without the presence of nasal polyps (CRSsNP).^11,13

▪ RS: 2004 Consensus

The 2004 consensus document broadens the criteria necessary for the diagnosis of RS. While the document is designed to promulgate diagnostic criteria for research studies and clinical trials, it is practical to include some element of objective evidence into diagnostic practices when managing the patient with presumed RS. This document sets out specific criteria for the diagnosis of various forms of RS based on patient symptoms, the pattern of those symptoms, and the presence of objective documentation. It describes specific definitions for patient care. These consensus criteria are noted in Table 4.1.

TABLE 4.1 Rhinosinusitis consensus definitions for patient care. (Source: Meltzer EO, Hamilos DL, Hadley JA, et al. Rhinosinusitis: establishing definitions for clinical research and patient care. Otolaryngol Head Neck Surg 2004;131:S1–S62)

The 2004 criteria categorize RS into four distinct categories. These categories each have individual diagnostic criteria and definitions.

Acute (Presumed Bacterial) Rhinosinusitis

ARS is defined as an inflammatory condition of the nose and paranasal sinuses that lasts for up to 4 weeks. The etiology of most upper respiratory illnesses, and therefore of most cases of acute RS, is viral. For that reason, antibiotics are usually unnecessary over the first 10 days of treatment. In severe cases of infection, or in worsening disease after 5–7 days, the likelihood of bacterial infection is significantly increased. Patients with acute bacterial RS, usually will have symptoms present for at least 10 days but less than 28 days. In the absence of accompanying signs of progressive infection (e.g., orbital or facial swelling), most cases of ARS in the early course are viral. Specific criteria for the diagnosis of acute bacterial RS include nasal and facial symptoms confirmed by the presence of findings on physical examination or radiological imaging demonstrating the presence of specific findings of RS.

Chronic Rhinosinusitis without Nasal Polyposis

Chronic rhinosinusitis without nasal polyposis (CRSsNP) involves an inflammatory condition of the nose and paranasal sinuses lasting at least 12 weeks in duration. Symptoms that strongly suggest a diagnosis of CRSsNP include anterior and/or posterior mucopurulent drainage, nasal obstruction, facial pain-pressure-fullness, and hyposmia/anosmia. Objective documentation would include a physical examination of the decongested nose demonstrating the presence of inflammatory changes and the absence of nasal polyps within the nose or middle meatus. CT imaging can also confirm the presence of CRSsNP.

Chronic Rhinosinusitis with Nasal Polyposis

Chronic rhinosinusitis with nasal polyposis (CRSwNP) also involves an inflammatory condition of the nose and paranasal sinuses lasting at least 12 weeks in duration. Symptoms are similar to those seen in CRSsNP, although nasal obstruction and hyposmia/anosmia are often more severe among patients with nasal polyps. Again examination of the decongested nose is necessary to demonstrate both the presence of inflammation and of polyps within the nose. These polyps may be confined to the middle meatus on endoscopic examination. In addition, CT scanning can be useful in demonstrating the presence of chronic changes suggestive of nasal polyps.

Allergic Fungal Rhinosinusitis

Allergic fungal rhinosinusitis (AFRS) is classically described as a type of CRS with or without polyposis that is associated in its expression and pathogenesis with an IgE-mediated response to one or more families of fungal organisms. These organisms are present in the sinuses of patients with AFRS, and patients will demonstrate an IgE-mediated hypersensitivity reaction to those fungi, either by in vitro specific IgE testing or through skin tests for relevant fungi. AFRS is not diagnosed in the absence of confirmatory IgE testing, despite the presence of fungi on either culture or histopathology. The diagnosis of AFRS requires the presence of nasal and sinus symptoms for at least 12 weeks, including anterior/posterior mucopurulent drainage, nasal obstruction, and facial pain-pressure-fullness. It also requires a nasal airway examination demonstrating allergic mucin and inflammation, with or without nasal polyps. CT imaging is important to demonstrate the extent of the disease. In addition, physical examination and CT imaging should not demonstrate the presence of changes consistent with invasive fungal sinusitis.

These four conditions share in their pathogenesis the role of acute and chronic inflammatory processes. As will be discussed later in this chapter, various pathological mechanisms and triggers appear to be important in the development of these forms of acute and chronic RS.

Anatomy of the Paranasal Sinuses

The sinuses are paired air-containing cavities present within the bony framework of the face. There are four sets of sinuses on each side of the face: ethmoid, maxillary, frontal, and sphenoid. These chambers connect to the nasal cavity through small ostia and recesses. Normal health of the sinuses depends on their unimpeded ventilation through these ostia, so that airflow can occur into the sinuses and mucus can be cleared from the sinuses into the nose. For that reason, normal configuration and patency of the sinus ostia is a critical factor in the likelihood of the sinuses to become diseased.

The ethmoid and maxillary sinuses can be seen in rudimentary form even in fetal life. The ethmoid and maxillary sinuses are the first sinuses to develop, and are visible on radiographic studies in early childhood. The frontal and sphenoid sinuses, however, do not develop significantly until later childhood, reaching their maximum dimension in adolescence or early adulthood. For that reason, ethmoid sinus disease is seen in young children while frontal and sphenoid sinusitis are noted only much later in life.

Ethmoid Sinuses

The ethmoid bones form the structure for much of the nose and the superior sinuses. They are paired bones bounded in the midline by the perpendicular plate. The superior border of the ethmoid bones is the anterior skull base, and the lateral border is the lamina papyrecea, a thin bony plate that separates the ethmoid sinuses from the orbits. The lamina papyrecea forms a barrier between the ethmoid sinuses and the eyes bilaterally. It is very thin and infection in the ethmoid sinuses can extend into the orbits through this thin bone, resulting in orbital cellulitis or abscess formation.

The anatomy of the ethmoid sinuses is variable. They can be best viewed as a group of discrete cells separated into anatomic regions by a series of bony partitions. These cells can be grouped into two units: the anterior ethmoid cells, which are numerous and smaller in size, and the posterior ethmoid cells, which are less numerous and larger.

The anterior ethmoid cells are contiguous with the nose through an important anatomic region known as the ostiomeatal complex. This area is of primary importance in the normal functioning of the anterior paranasal sinuses. When the ostiomeatal complex is narrowed or occluded, the ethmoid sinuses can easily become diseased, resulting in a higher incidence of acute and chronic rhinosinusitis. The posterior ethmoid sinuses communicate with the nose more posteriorly, and an area known as the sphenoethmoidal recess.

Maxillary Sinuses

The maxillary bones are paired bilaterally and form the mid portion of the anterior face. The nasal cavity opens into the maxillary bone bilaterally at the level of the nostrils. In addition, the orbital processes of the maxillary sinuses make up a portion of the orbital floor.

Contained within the maxillary bones are the maxillary sinuses. These sinuses are the largest of the four sets of sinuses, and are surrounded by bony walls. The maxillary sinus communicates with the nose through an opening in the lateral wall known as the maxillary ostium. The ostium is located on the medial wall of the maxillary sinus, toward its superior border.

Sphenoid Sinuses

Housed within the sphenoid bone in the center of the skull are the paired bilateral sphenoid sinuses. As noted with the posterior ethmoid sinuses, these sinuses also communicate with the nasal cavity bilaterally in the sphenoethmoidal recesses. The ostium of the sphenoid sinus is located in the superior portion of the anterior wall of the sphenoid bone.

Frontal Sinuses

The superior portion of the face is composed of the frontal bone, which forms the contour of the forehead as well as the anterior wall of the cranium. Within this bone the frontal sinuses develop as bilateral pneumatized spaces. The frontal sinuses are of variable size, and are absent in up to 10% of patients. The ostia of the frontal sinuses are found inferiorly, and communicate with the nose through a funnel-shaped channel known as the frontal recess.

Facial trauma can significantly affect the bony framework of the sinuses and interfere with normal ostial patency. Facial fractures can alter the dimensions of the sinuses and can lead to increased status of mucus due to this ostial occlusion. Long-term effects of trauma can be seen through the development of expansile cystic masses known as mucoceles secondary to rests of epithelium that do not communicate adequately with the nose.

The sinus chambers are lined with a ciliated pseudostratified columnar respiratory-type epithelium. This mucosa is similar histologically to that seen in the nose and the lower respiratory tract (Figure 4.2). This histological similarity is one reason that inflammatory respiratory diseases commonly affect more than one portion of the respiratory tract simultaneously. This epithelium secretes mucus, which is swept from the interior of the sinuses to the ostia and into the nose by fine cilia on the surface of the mucosal cells. This mucus blanket traps particles in the nose and sinuses, and transports these particles posteriorly into the nasopharynx, where they then can be swallowed. Particulate matter that can affect the nasal and sinus mucosa includes bacteria, viruses, irritants, and allergens.

Figure 4.2 Appearance of the normal respiratory epithelium of the nose and paranasal sinuses.

(Reproduced with permission from Minshall E, Ghaffar O, Cameron L, et al. Assessment by nasal biopsy of long-term use of mometasone furoate aqueous nasal spray in the treatment of perennial rhinitis. Otolaryngol Head Neck Surg 1998;118:648–654.)

Physiology of the Sinuses in Health and Disease

In healthy sinuses, mucus is secreted by goblet cells within the epithelium and transported to the ostia of the sinuses for clearance into the nose. This process for the transport of mucus within the nose and sinuses is known as mucociliary clearance. Through active action of the cilia, mucus is easily moved from the periphery of the sinuses toward the ostia. This mucociliary clearance is generally rapid and efficient, and prevents the accumulation of mucus and particulate debris within the sinus chambers. It is essential for normal sinus health and function (Figure 4.3). Mucociliary clearance patterns within the sinuses are genetically directed to maintain the flow of mucus from the sinuses through the sinus ostium and into the nose itself.²⁰

Figure 4.3 The sinuses in health and disease. The left side of the illustration demonstrates the normal state, with ventilated sinuses and freedom from edema and obstruction. The right side of the illustration demonstrates acute rhinosinusitis, with mucosal edema, ostial obstruction, and retention of mucopurulent secretions in the maxillary antrum.

By contrast, when normal mucociliary clearance is inhibited, either through local physiological changes or through anatomic obstruction, the sinuses become diseased. It is clear that ventilation of the sinuses and drainage of mucus out of the sinuses maintains the normal physiology of the sinuses. Disruptions to this normal ventilation and drainage is a central factor in the pathogenesis of acute and chronic rhinosinusitis.²¹ Many factors can adversely influence the clearance of mucus from the sinuses, and thereby result in acute and chronic changes. Mucociliary clearance can be directly affected by ciliostatic agents, such as tobacco smoke and viral infections. Both irritants such as smoke and viral disease disrupt the cilial layer in the sinuses, resulting in cilial loss and impaired cilial motility. With impairment of the normal clearance mechanisms of the sinus mucosa, mucus stasis occurs and bacterial colonization can begin. As bacteria colonize the sinuses, they can proliferate within the mucus layer and can cause localized acute inflammation. This inflammation will cause tissue edema and ostiomeatal narrowing, which can result in additional injury to the mucosa. In addition, any structural obstruction to the ostia or significant decrease in their diameter will further impair mucociliary clearance and lead to increased bacterial growth. In response to the increased presence of bacteria, normal host mechanisms will recruit neutrophils and other inflammatory cells into the sinuses, resulting in increased local inflammation and secondary injury to the mucosa. An illustration of this inflammatory cycle is displayed in Figure 4.4.

Figure 4.4 The cycle of respiratory injury in rhinosinusitis. Numerous interactive factors contribute to the development of acute and chronic sinus disease.

The consequence of this cyclical inflammation is the creation of conditions that support the development of both acute and chronic rhinosinusitis. As also demonstrated in Figure 4.3, in contrast to the normal physiology of the healthy sinuses, in diseased sinuses conditions exist that favor the proliferation of bacteria and the development of symptoms. In diseased sinuses pressure is created from tissue edema, resulting in contact between the mucous membranes of the nose, turbinates, and sinuses. This contact stimulates nerve fibers resulting in localized pain. In addition, bacteria multiply within the chambers of the sinuses, resulting in additional pain as mucosal swelling increases. In addition, fever is common in response to the presence of infection and the host response generated by the infection. It is clear from this model that normal mucociliary clearance is essential in the normal physiological functioning of the sinuses.