THE DIAGNOSIS AND MANAGEMENT OF CHRONIC RHINOSINUSITIS

Michael Puruckherr, M.D., Ryland Byrd, M.D., Tom Roy, M.D. and Guha Krishnaswamy, M.D.

Address all correspondence to:
Guha Krishnaswamy, M.D.
Department of Medicine
East Tennessee State University
Johnson City, TN 37614-0622
Tel: (423) 439-6282
Fax: (423) 439-6387

Key words: Sinusitis, Allergy, immune deficiency, cytokines, antihistamines
Running head: Chronic sinusitis

Funded by NIH grants; AI-43310 and HL-63070, The Rondal Cole Foundation and the Chair of Excellence in Medicine (State of Tennessee grant 20233), Cardiovascular Research Institute, and the Research Development Committee, East Tennessee State University.

INTRODUCTION

Sinusitis is a common health problem that lead to frequent visits to primary care physicians and to ear, nose and throat specialists in the United States and other countries. It contributes to a significant amount of health care expenditure due to direct costs arising from physician visits and antibiotics, as well as indirect costs related to missed days at work and a general loss of productivity due to a decrease in life-quality of those affected (14)(24). The 1996 total direct health care expenditures in the USA attributable to sinusitis were estimated with $ 5.8 billion. Of this number about 58.7% (or $3.5 billion) is probably related to chronic sinusitis alone (17). It is estimated that 13.4 million office visits/year are related to sinusitis and/or its sequelae.
Patients with chronic rhinosinusitis also suffer from a poor quality of life and the disease is often associated with other co-morbid conditions such as asthma, eczema and otitis media. A better understanding of the pathogenesis and etiology of chronic rhinosinusitis is essential in order to develop effective therapies. Recently, there has been an evolving concept of an "one airway disease" as the lower and upper airways, paranasal sinuses and middle ear are related anatomically and functionally. Hence, disease in one portion of the airway is prone to spill over into other parts of the airway. This is extremely important to realize as therapy of the patient with sinusitis may lead to improvements in lung function, for example (20). If gastroesophageal reflux is included, then interactions of the upper and lower airways, and the gastrointestinal tract become clinically relevant. Since the majority of patients with sinusitis also suffer from rhinitis, the term rhinosinusitis may be more appropriate (Figure 1). One fifth of patients with chronic sinusitis also have nasal polyposis and a subset of these patients suffer from the aspirin-sensitivity syndrome often associated with asthma and rhinitis.
There is conflict in the criteria for diagnosis of acute or chronic sinusitis. Patients who have been symptomatic for 3 weeks or less are considered to have acute disease while those having prolonged symptoms lasting longer than 6 weeks or more are referred to as having chronic disease.

CLINICAL PRESENTATION

Patients with sinusitis present with a variety of signs and symptoms. These include purulent discharge anteriorly or posteriorly which are believed to be the one of the most significant findings in the diagnosis of rhinosinusitis. The symptom complex for the clinical evaluation includes major and minor criteria. Major criteria include the above described purulent drainage, headache, facial pain or pressure, nasal congestion/blockage, decreased smelling sensation and fever for acute rhinosinusitis. Minor criteria consist of halitosis, fever (nonacute rhinosinusitis), weakness, dental pain, ear fullness (clicking noises) and pain, cough and in children, irritability (14)(32)(31).
In the case of chronic sinusitis, if two or more of the above mentioned major criteria or one major and two minor criteria are found in the history and exam over a 6-12 week time interval the presence of chronic sinusitis is very likely. Some patients may present with relapsing disease which may include acute rhinosinusitis occurring at least 3-4 times/year and lasting for a minimum of 10 days. Additionally it has been proposed that changes on computerized tomography of the paranasal sinuses which are still present $4 weeks following therapy can be considered chronic (14)(18).

ETIOLOGIES OF CHRONIC RHINOSINUSITIS

TABLE 1 lists the various etiologies that could lead to chronic bacterial rhinosinusitis. Several of these conditions are discussed in further detail below.
The majority of patients with chronic sinusitis have associated rhinitis, either of allergic or infectious origin. On the other hand there is a significant proportion with vasomotor rhinitis, drug induced rhinosinusitis, nonallergic rhinitis with eosinophilia syndrome (NARES), structural rhinitis, neutrophilic rhinosinusitis and some with nasal polyposis, as stated earlier. The term vasomotor rhinosinusitis is used for conditions caused by irritants like air pollutants, smoke or odors, often due to occupational related exposure. In contrast to allergic rhinosinusitis patients with vasomotor rhinosinusitis lack the conjunctival involvement usually found in allergic rhinosinusitis. Rhinitis medicamentosa reflects a condition where repetitive use of nasal decongestants (e.g. oxymetazoline, xylometazoline, etc.) can cause a chronic, progressive and medication-dependant rhinitis. In NARES (nonallergic rhinitis with eosinophilia syndrome) the nasal secretions contain eosinophils as seen in allergic rhinitis but the patient does not suffer from any allergies. This is a steroid-responsive illness and may precede the development of asthma or aspirin sensitivity. Structural rhinitis is usually caused by significant septal deviation or deformities (e.g. after trauma) and can be uni- or bilateral (30). Patients which are sensitive to aspirin and often also to other NSAIDs suffer from severe rhinosinusitis which is frequently accompanied by development of nasal polyps. There is some data to suggest a role for leukotrienes and inflammatory cytokines in eosinophil recruitment and mast cell activation in the aspirin-sensitive syndromes (13)(12).

PATHOGENESIS

The four paired paranasal sinuses (maxillary, ethmoid, frontal and the sphenoid) drain into the nasal cavity. While the frontal, maxillary and anterior ethmoid drain through the osteomeatal complex in the middle turbinate, the posterior ethmoid sinuses and the sphenoids drain via the superior turbinate through the sphenoethmoidal recess. For the maxillary sinus the mucociliary activity must drain against gravity. Messerklinger suggested that recurrent sinusitis is often due to a focus of infection that has remained in a stenotic cleft of the lateral wall (19). These findings let to the understanding that for normal sinus function the patency of the so called "Osteomeatal complex" is critical. Several authors described opacification of the middle meatus and also inflammation in the dependent sinuses in patients with chronic rhinosinusitis (16). The role of allergy, immune deficiency, viral infection and anatomical or structural disease would be to induce osteal obstruction leading to stasis of secretion, secondary infection, inflammatory cytokine synthesis and leukocyte recruitment. This further propagates the inflammatory process, resulting in a vicious cycle, leading to chronicity if untreated or obstruction is unrelieved. A patient with allergic rhinitis can develop sinusitis due to various mechanisms as shown in Figure 2. Increased mucus production, impaired mucociliary clearance and tissue edema can occur with both allergic rhinitis and with sinusitis. This could lead to airway obstruction, stasis and secondary infection, leading to infectious sinusitis. If the patient has other complications, such as structural disease (deviated septum, adenoidal enlargement and nasal polyps or concha bullosa), immune deficiency disease (such as immunoglobulin G or A deficiency), other abnormalities of ventilation such as cystic fibrosis or ciliary dysmotility or viral infectious illness such as coryza which can acutely impair clearance mechanisms, further predispositions to sinusitis are created. Inflammatory response can lead to tissue edema and remodeling, leading to airway obstruction, secondary infection, elaboration of inflammatory cytokines and leukocyte recruitment. This ultimately culminates in infectious sinusitis with all its attendant sequelae.
Mucosal edema, osteal blockage, increased and accumulating viscous mucous secretions or/and decreased mucociliary activity can cause acute, chronic or acute exacerbation of chronic sinusitis (10). Decreased patency or even complete blockage of the sinus ostia decreases gas exchange resulting in hypoxia and hypercapnia. This causes neutrophil activation (increased chemotaxis and degranulation) which leads to more inflammation and also lowers the pH resulting in ciliary dysfunction by lowering ciliary beat frequency. Other causes includes foreign bodies which are in adults often iatrogenic (eg., naso-tracheal or naso-gastric tubes) which produce osteal blockage directly or by inducing mucosal swelling. Infected nasal secretions might also drain back into the sinuses (1). The significance of sinonasal anatomical variations as a cause of chronic rhinosinusitis is controversial. For example Danese et al., found only an association between chronic or recurrent sinusitis in patients with ipsilateral ridges or spurs, unusual deflections of uncinate process and contralateral septal watch glass like deviation but no correlations for other variants like concha bullosa, Haller (infraorbital ethmoidal) cells or accessory maxillary ostium (7). An additional but less recognized factor leading to chronic rhinosinusitis is mucus recirculation. This may occur in a patient who has an accessory sinus ostium of the maxillary sinus where the mucus drains out the usual anatomical way into the middle meatus and then reenters the maxillary sinus through the accessory ostium which is usually located inferior to the osteomeatal complex. Interestingly, nose blowing by propelling nasal secretions into the middle meatus and the maxillary sinus might cause acute sinusitis or recurrent exacerbation of chronic sinusitis and may also worsen chronic sinusitis (9).

THE ROLE OF ALLERGY IN RHINOSINUSITIS

The prevalence of sinusitis in the United States is almost 15% (37 million persons) and is ranked among the commonest chronic conditions. With improvements in diagnostic capacities, more numbers of patients are being diagnoses with chronic sinusitis in recent years. This has resulted in an increase in the number of surgeries for chronic paranasal sinus disease. Allergic rhinitis is fairly common. In some studies, the total cost to society of allergic rhinitis is estimated at 2.4 billion dollars. This includes not only direct costs associated with physician visits, medications and diagnostic testing but also indirect costs associated with loss of productivity due to days lost at work. When associated costs of caring for asthma and sinusitis are included, the costs involved may exceed $ 10 billion. In total, almost 25-30 million persons may be affected by allergic rhinitis in the U.S. alone (29). Figure 1 shows the relationship between allergy, sinusitis, asthma and reflux. Obviously, all of these disorders may be interactive in a given patient and one needs to individualize approaches to therapy based on the presence of one or more of these processes in a given patient (29). Allergic rhinitis presents in an atopic patient with sneezing, rhinorrhea, nasal congestion, itchy eyes, lacrimation and cough. In some cases, generalized symptoms such as fatigue may be associated complicating features and may be related to the effect of cytokines or impaired sleep in a patient with poorly controlled allergic upper airway disease. Allergic rhinitis can be seasonal or perennial. In the case of the latter, indoor, perennial allergens such as mold, dust mites, cockroach allergen or pet dander can lead to year round symptoms. These allergens especially have been linked to the co-development of asthma. Investigators have shown that aggressive treatment of indoor allergen "burden" by the use of specific filters, mattress and pillow encasings and removal of sources of indoor allergen could lead to improvements in lung function in patients with allergic respiratory disease. Of interest, rhinitis is diagnoses in 28-78% of patients with asthma and asthma is diagnoses in nearly 38% of patients with chronic rhinitis and there is evidence to suggest that allergic rhinosinusitis may present a risk factor for subsequent development of asthma. Moreover, some studies have also shown that antihistamines and aggressive therapy of rhinosinusitis can ameliorate asthma (20). Whether this is an indirect effect due to improvement in rhinitis or due to direct improvements in asthma is unclear.

IMMUNE EVALUATION

The immunological evaluation of a patient with persistent rhinosinusitis is essential as occasionally defects are encountered that could lead to specific therapeutic intervention or immune reconstitution. Table 1 provides a suggested outline for the evaluation of immunological function in a patient with recurrent or chronic rhinosinusitis. Nasal cytology can assist in the detection of eosinophils which would suggest either allergic rhinitis or NARES. Presence of excessive neutrophils in a nasal smear would suggest bacterial rhinosinusitis. Cultures are very essential in the evaluation of bacterial sinusitis since the type of pathogen would determine the nature of immune evaluation. This however may be difficult to pursue as it often involves relatively invasive procedures such as a sinus puncture or antral biopsy. In cases where the sinusitis is poorly responsive to therapy or is progressing, tissue cultures and biopsies are required to exclude fastidious pathogens and fungi where the treatments could be dramatically different. In patients with chronic, recurrent sinusitis, especially if associated with recurring pulmonary infections or infections elsewhere, an immunological evaluation may provide useful information. Defects in humoral immunity are associated with low antibody levels, recurring infections with pyogenic or capsulated pathogens and other complications, including autoimmune disease. Evaluation of these disorders is reviewed in Table 1.