Allergic Rhinitis

ALLERGIC RHINITIS

ESSENTIALS OF DIAGNOSIS

1. Characterized by sneezing, itching, rhinorrhea, and congestion.
2. May be seasonal, perennial, or both.
3. Can be associated with other chronic conditions, including asthma, otitis media with effusion (OME), rhinosinusitis, and nasal polyposis.
4. Typical symptoms of sneezing, rhinorrhea, and nasal congestion can be associated with viral, bacterial, allergic, and nonallergic etiologies
5. Can have multiple triggers, both inhaled and in­gested.

General Considerations
Allergy is a clinical manifestation of an adverse immune response after repeated contact with usually harmless substances such as pollens, mold spores, animal dander, dust mites, foods, and stinging insects. Allergic rhinitis is an inflammation of the nasal mucous membranes caused by an IgE-mediated reaction to one or more allergens. The prevalence of allergic rhinitis can vary considerably among age groups and locales.

Allergic rhinitis is one of the most common allergic diseases in the United States, affecting between 20% and 25% of the population (approximately 40 million people). Allergic rhinitis may have its onset at any age, but the incidence of onset is greatest in adolescence, with a decreasing incidence with advancing age. Its peak prevalence is during the third and fourth decades (Figure 1).

Figure 1. Prevalence of allergic rhinitis by age group.

The economic costs of allergic rhinitis, both direct and indirect, are considerable. The largest portion of the direct costs is the expenditure for both prescription and nonprescription medications (approximately 4 bil­lion dollars annually). The largest indirect costs are from both the allergy itself and also from the negative side effects of allergy medication (primarily over-the-counter antihistamines).

Although allergic rhinitis is not life threatening, its symptomatic effects are considerable, resulting in a sig­nificantly diminished quality of life for many sufferers. A number of quality of life studies have shown that in almost every facet of daily life, including social and physical functionality, energy and fatigue levels, and a lack of sleep and mental health, patients with allergic rhinitis have a significant loss of the quality of life com­pared with nonallergic individuals. In fact, patients with allergic rhinitis have been shown to have a lower quality of life than many asthmatics. In addition, aller­gic rhinitis may contribute to sleep disorders, fatigue, and—of particular importance with children—learn­ing problems.

Pathogenesis
The allergic response is mediated primarily by a type I hypersensitivity reaction. This response involves the excess production of IgE antibodies and is termed an atopic reaction. In addition to allergic rhinitis, most cases of asthma and atopic dermatitis are considered to have an atopic cause.

In patients with an atopic disposition (a genetic trait), an allergic reaction begins with sensitization to a specific allergen (in allergic rhinitis, these are usually airborne), which induces IgE-antibody production. This occurs through a T-cell, B-cell, and plasma cell cascade. On subsequent exposure, the specific antigen attaches to two specific IgE antibodies attached to the surface of mast cells, which are prevalent in the submu-cosa of the respiratory and gastrointestinal tracts, the subconjunctiva of the eye, and the subcutaneous layer of the skin. Consequently, this IgE-mediated reaction causes degranulation of the mast cell, which then pro­vokes an inflammatory response with the release of mediators such as histamine, leukotrienes, cytokines, prostaglandins, and platelet-activating factor. This is referred to as the early-phase or humeral reaction and occurs within 10–15 minutes of allergen exposure; the release of histamine causes the symptoms of sneezing, rhinorrhea, itching, vascular permeability, vasodilata-tion, and glandular secretion.

The release of cytokines and leukotrienes subsequently causes an influx of inflammatory cells (mainly eosinophils) into the affected area (chemotaxis). This inflammatory response is called the late-phase or cellular reaction, which can begin 4–6 hours after the initial sensitization and may prolong and enhance the allergic cascade for as long as 48 hours. This response is the main cause of the symptoms of nasal congestion and postnasal drip in allergic rhinitis.
In addition, these mediators produce a hyperreac-tion to both specific allergens and nonspecific irritants such as tobacco smoke and chemical fumes, referred to as the priming effect.

Causes
The development of atopy may be influenced by the following:

1. Genetic susceptibility (ie, family history);
   
2. Environmental factors (eg, dust and mold exposure);
3. Exposure to allergens (eg, pollens, animal dander, and foods);
4. Passive exposure to tobacco smoke (especially in early childhood); and
   
5. Diesel exhaust particles (in urban areas)—among other factors.

In infancy and childhood, food allergens such as milk, eggs, soy, wheat, dust mites, and inhalant allergies such as pet dander are the major causes of allergic rhinitis and the comorbidities of atopic dermatitis, otitis media with effu­sion, and asthma. In older children and adolescents, pol­len allergens become more of a causative factor.

Classification

A. Seasonal Allergic Rhinitis
The symptoms of seasonal allergic rhinitis, as its name implies, occur or are increased during certain seasons, usually depending on the pollination of plants to which the patient is allergic. Trees pollinate in the spring, grasses in the late spring and summer, and weeds in the fall. In addition, molds may cause symptoms in the fall. Characteristic symptoms of seasonal allergies include sneezing, watery rhinorrhea, itching of the nose, eyes, ears, and throat, red and watering eyes, and nasal congestion. Symptoms are usually worse in the morning and are aggravated by dry, windy conditions when higher concen­trations of pollen are distributed over a wider area.

B. Perennial Allergic Rhinitis
The symptoms of perennial allergic rhinitis are usually constant, with little seasonal variation, although they may vary in intensity. Characteristic symptoms are pre­dominantly nasal congestion and blockage, and postna-sal drip. Rhinorrhea and sneezing are less common. Eye symptoms are less common, except with animal aller­gies. Seasonal pollen may cause the exacerbation of any of these symptoms.

Common allergens that cause perennial allergic rhi­nitis are indoor inhalants, predominantly dust mites, animal dander, mold spores, and cockroaches (in inner cities). Certain occupational allergens may also cause perennial allergic rhinitis; these are not usually constant because they depend on workplace exposure.

Food allergens may also contribute to perennial allergic rhinitis. In addition, food allergies are often associated with other symptoms, including gastrointes­tinal problems, urticaria, angioedema, and even ana-phylaxis after food is ingested.

Infections and nonspecific irritants may influence perennial allergic rhinitis. In children with allergies, there may be a higher incidence of respiratory tract infections, which in turn tend to aggravate allergic rhinitis and may lead to the development of complications, especially rhi-nosinusitis and otitis media with effusion. Other irritants such as tobacco smoke, chemical fumes, and air pollutants can also aggravate symptoms.

C. Other Classifications
Recently, other classifications of allergic rhinitis have been introduced. One of these is related to both the temporal incidence and the quality of life. Symptoms are classified as being intermittent (<> 4 d/wk or > 4 weeks’ duration) and by the intensity of the symptoms, with either minimal or moderate to severe changes in the quality of life. In another classification system, symptoms are based accord­ing to the type of symptom (eg, patients who experience sneezing and a runny nose or those who are congested) without a temporal relationship.

Clinical Findings

A. Patient History
The diagnosis of allergic rhinitis should determine whether the patient is atopic and, if so, what the caus­ative allergen is. To determine these, a basic clinical evaluation should be performed, which should consist of a patient history, a physical examination, and confir­matory tests.

A careful history provides important clues for the diagnostician. Genetic factors determine the likelihood of an individual becoming sensitized and producing IgE antibodies (ie, being atopic). A family history of aller­gies, eczema, or asthma increases this possibility. Chil­dren with parents who have allergies have been shown to have a > 50% chance of becoming allergic themselves. If only one parent or a sibling has allergies, this rate is lower but still significant.

A thorough allergy history should determine whether symptom patterns are seasonal or perennial. Symptoms may include clear and watery nasal discharge, nasal con­gestion, postnasal drip, and itching of the nose, throat, and eyes. Persistent symptoms are presumed to be due to exposure to an indoor allergen. Seasonal symptoms or symptoms that are reproducible from an inciting factor, such as cat exposure, are most likely to be allergic. If the use of medication, especially antihistamines (both pre­scription and nonprescription) or intranasal corticoster-oids improves symptoms, allergy is probable. This is not the case with either intranasal or oral decongestants, which affect both allergic and nonallergic symptoms. A history of an anaphylactic reaction following ingestion of a particular food or being stung by an insect usually indi­cates an atopic patient.

Patients should be questioned about the onset, dura­tion, type, progression, and severity of their symptoms. A relationship to the seasons is important, with seasonal symptoms usually indicating a pollen allergy or possibly a mold allergy, but temperate climates can blur these seasonal distinctions. Perennial symptoms usually mean an allergy to dust mites, mold, or animals. An increase in symptoms at night usually suggests an allergy to dust mites or pet dander.
Associated ocular, pharyngeal, and systemic symp­toms, including recurrent rhinosinusitis, ear infections, asthma flare-ups, gastrointestinal symptoms, and skin rashes and hives, are important facts to ascertain in the history taking.
The patient should always be questioned about the impact of the symptoms on the quality of his or her life, because the correct diagnosis and, ultimately, sympto­matic relief from the appropriate treatment will play a large part in the functional impact on the patient’s life.

B. Physical Examination
A physical examination should include inspection of the ears, throat, and nasal passages (including after decongesting with a topical decongestant). Typical findings in the nose in patients with seasonal allergic rhinitis include bluish, pale, boggy turbinates; wet, swollen mucosa; and nasal congestion with nasal obstruction. With perennial allergies, nasal congestion is the predominant sign, but the nasal examination may appear normal. Anatomic abnormalities, such as a devi­ated nasal septum, concha bullosa, and nasal polyps, may be present. It should be determined whether these abnormalities are the main cause or merely contributing factors to the patient’s symptoms. If nasal polyps are suspected, an endoscopic nasal exam is also warranted. Other possible physical findings include conjunctivitis, eczema, and, possibly, asthmatic wheezing.

In children, allergic “shiners” (dark circles under the eyes), facial grimacing, mouth breathing, and the “nasal salute” (constant rubbing of the tip of the nose with the hand) are common physical findings. In addition, in this age group, a concomitant otitis media with effusion is also a possibility.

C. Special Tests

1. Allergy testing—Allergy testing is performed to establish objective evidence of atopic disease. It also can determine the causative allergens responsible, which would then lead to specific therapeutic recommenda­tions. Two major types of testing are available for iden­tifying and quantifying allergen sensitivity: skin testing and in vitro serum assays.
2. Skin testing—Skin testing can be epicutaneous, intradermal, or a combination of both.
   a. Skin prick test—The skin prick test is the most common epicutaneous test used. In general, it is a quick, specific, safe, and economical test. With new multitest systems available, it is an easy and simple office procedure to perform and also allows for unifor­ mity in the testing procedure. When a test result is equivocal, it is often followed by an intradermal test.
   b. Intradermal testing—Intradermal testing, using quantitative 1:5 serial dilutions, is the skin testingmethod of choice for most otolaryngic allergists. This type of testing, termed intradermal dilutional testing (IDT) and formerly known as serial endpoint titration (SET), is an excellent quantifier of allergen sensitivity, and, as such, is of significant benefit in the preparation of safe and cost-efficient immunotherapy treatment. Today, many otolaryngologists use the skin prick multitest as a screening test prior to performing IDT.
   
3. In vitro testing—Allergen-specific serum IgE test­ing is an easy and accurate method for determining the presence of atopic allergy, and with newer in vitro tech­nology available, in vitro testing is at least equivalent to skin testing in efficacy. In vitro assays are safe, specific, cost-effective, and reproducible, and do not require the patient to be free of antihistamines and other medica­tions that may interfere with skin testing. They are also easy and quick and are therefore preferred, especially in children and in anxious patients.
   Although the original in vitro assay, the RAST test (radioallergosorbent test), is no longer performed, its name is still used today to generally describe IgE-spe-cific blood testing. However, not all in vitro assays available today are alike. The newer assays tend to be faster, more reliable, and more efficient than previous tests. The ImmunoCap is an excellent example of this newer technology. Not using a reliable assay may affect the diagnosis of atopy and therefore the prescribing of appropriate therapy (Figure 2).
   In vitro testing can be cost-effective if an initial, appro­priately chosen inhalant screening battery of 10–12 aller­gens consisting of the most prevalent pollens, molds, dust mites, and animals in the local environment is used. In chil­dren, common allergenic foods are substituted or added. No further testing is necessary if this battery is negative. If the screening battery is positive and if no immunotherapy is considered, additional allergy testing can be performed.
   

Figure 2. In vitro testing process.

Differential Diagnosis
The differential diagnoses of allergic rhinitis include the fol­lowing:

1. Infectious rhinitis (acute or chronic);
2. Peren­nial nonallergic rhinitis (eg, vasomotor rhinitis);
3. Pollut­ants and irritants;
4. Hormonal rhinitis (eg, pregnancy or hypothyroidism);
   
5. Medication-induced topical rhinitis (rhinitis medicamentosa);
6. Anatomic deformity (eg, a deviated septum, nasal polyps, or a concha bullosa); and
7. Tumors or foreign bodies.

Treatment
The appropriate management of these common respira­tory diseases differs substantially, particularly when allergy is a contributing component. The treatment of allergic rhinitis must consider the main symptoms, their severity, the patient’s quality of life, the cost of therapy, as well as the allergens involved in order to individualize the patient’s treatment options. In addition, in the treatment of nasal allergies, consideration must be given to both the patient’s desire for rapid long-lasting relief of symptoms without side effects and the relief of any particular idio­syncratic symptoms, such as persistent rhinorrhea.

In general, three options are available for the manage­ment of allergic rhinitis:
(1) avoidance and environmental controls,
(2) pharmacotherapy, and
(3) immunotherapy.

A. Environmental Controls
Even if environmental controls are not complete, reduc­ing the allergic load may significantly decrease symp­toms. Methods of minimizing exposure to pollen are to avoid outdoor activities during relevant pollen seasons (eg, mowing the lawn and gardening), to keep home and car windows closed, and to use air conditioning when possible. To control dust mites, mold, and pet dander, the following practices should be used:
(1) reduce house­hold humidity to below 50%;
(2) wash bed linens in hot water;
(3) remove carpets and pets from the most often used living areas, especially bedrooms;
(4) encase pillows, mattresses, and box springs in hypoallergenic coverings (for dust mite protection); and
(5) in poor and urban set­tings, eliminate cockroaches (Table 1). For airborne allergens (eg, animal dander), air purifiers can be used.

B. Pharmacotherapeutic Measures
When selecting a pharmacologic treatment for allergic rhinitis, consideration must be given to the patient’s underlying condition, the likely pathophysiology, the dominant symptoms, the patient’s age and condition, the coexistence of related airway disorders, the patient’s preference, and the patient’s compliance history. In addition, before initiating any pharmacotherapy, the patient’s use and response to previous treatment should be considered (Table 2).

1. Antihistamines—Antihistamines are frequently used as a first-line therapy; many are available without a prescription. They block H1 receptor sites and pre­vent histamine-induced reactions, including inhibiting increased vascular permeability, smooth muscle con­traction, increased mucus production, and pruritus. Antihistamines also inhibit the “wheal and flare” response of the skin and therefore they affect skin testing unless withdrawn a few days before skin testing. They do not affect in vitro testing. Antihistamines are effective in early-phase reaction and therefore reduce sneezing, rhinorrhea, and itching. They have little effect on nasal congestion, a late-phase phenomenon.
   Nonprescription, first-generation antihistamines can cause sedation and impair performance and have been associated with a higher risk of both automobile and work-related accidents, decreased work performance and productivity, and impaired learning and academic performance. These side effects can be significantly exacerbated by alcohol, sedatives, antidepressants, and hypnotics. Many have anticholinergic effects and cause dry mouth. These include diphenhydramine (eg, Benadryl), hydroxyzine (eg, Atarax), chlorpheniramine, and brompheniramine. The latter two are found in most nonprescription cold remedies.
   Second-generation antihistamines have an antihista-mine activity comparable to that of first-generation antihistamines but have a better safety profile with lit­tle, if any, sedation as they have little affinity for central H1 receptors. They have no anticholinergic activity and are well absorbed, with a rapid onset of action and symptom relief usually within 1 hour. Second-genera­tion antihistamines are typically dosed once daily and are rarely associated with drug tolerance with prolonged use. Those available orally in the United States are fex-ofenadine (eg, Allegra), loratadine (eg, Claritin), deslor-atadine (eg, Clarinex), and cetirizine (eg, Zyrtec). A sec­ond-generation intranasal antihistamine, azelastine (eg, Astelin), is also available.
2. Intranasal corticosteroids—Intranasal corticoster-oids may be the most effective medications for the over­all control of allergic rhinitis symptoms. They relieve sneezing, itching, and rhinorrhea, and also nasal con­gestion. Maximal effect may take from 1 to 2 weeks after the onset of their use. Their effectiveness depends applica­tion. They act on the late-phase reaction and therefore prevent a significant influx of inflammatory cells. The newer formulations (mentioned below) have minimal systemic absorption with no systemic side effects, and they have been approved for use in children. They have no systemic side effects with regard to HPA axis sup­pression and do not affect long-bone growth in chil­dren. In young adults and children, they are considered the drugs of choice in the treatment of allergic rhinitis. Local side effects, such as dryness and epistaxis, can be reduced by careful patient instruction on their use and also the regular, concomitant use of intranasal saline. Commonly available intranasal corticosteroids in the United States include triamcinolone (eg, Nasacort), budesonide (eg, Rhinocort), fluticasone (eg, Flonase), and mometasone (eg, Nasonex).
   Table 1. Environmental control of indoor aeroallergens.
   

   Allergen	Environmental Control
   House dust mites	• Encase mattress, box spring, and pillows in occlusive covers • Wash all bedding in water > 130° F weekly • Dehumidify (<> • Remove reservoirs (especially carpeting)
   Pets	• Remove pet from home or at least from patient’s bedroom • Remove reservoirs (carpeting, stuffed furniture), if feasible • Wash animal frequent

3. Systemic corticosteroids—Systemic corticosteroids may be necessary for severe, intractable symptoms. They can be administered either by intramuscular injection or orally. With the latter, a tapering dose is usually given over 3–7 days. Systemic corticosteroids act on inflammation and significantly reduce all the symptoms of allergic rhinitis. The repeated use of these agents can cause serious side effects, such as HPA axis suppression, as well as other common side effects of steroid use.
   Table 2. Pharmacologic agents in the management of allergic rhinitis.
   

   Class	Mechanism of Action
   Antihistamines	Antagonize the H1 receptor–mediated effects of histamine
   Decongestants	Act predominantly on α-adrenergic recep­tors of the mucosa of the respiratory tract
   Intranasal and oral corticosteroids	Exert a wide range of effects on multiple cell types and mediators
   Mast cell stabilizers	Inhibit the release of mediators from mast cells
   Anticholinergic agents	Antagonize the action of acetylcholine at muscarinic receptors
   Leukotriene modifiers	Antagonize the action of leukotriene re­ceptors or inhibit 5-lipoxygenase and the formation of leukotrienes

   
   
4. Decongestants—Decongestants act on α-adrener-gic receptors of the nasal mucosa, producing vasocon-striction and thus reducing turbinate congestion. They improve nasal patency but do not relieve rhinorrhea, pruritus, and sneezing. These preparations are found mostly in nonprescription cold medicines and should be used with care in patients with cardiac problems and hypertension. Intranasal decongestants (eg, oxymetazoline) can cause rebound nasal congestion and cause dependency if used for more than 3–4 days (rhinitis medicamentosa).
5. Intranasal anticholinergics—These agents tend to control only rhinorrhea and have no other effects on allergy symptoms. One of the most commonly used intranasal anticholinergics is ipratropium bromide (eg, Atrovent). These agents can be combined with other allergic medications to control rhinorrhea in perennial allergic rhinitis.
6. Intranasal cromolyn—Intranasal cromolyn (eg, Nasalcrom) must be used before the onset of symptoms to be effective. This medication must be used through­out the entire exposure; it is considered to be very safe. The recommended dosage is four times daily.
7. Leukotriene inhibitors—Montelukast “Singulair” is a newer medication for the treatment of allergic rhi­nitis. To date, clinical studies have shown its efficacy to be greater than that of placebo, but less effective than antihistamines and intranasal steroids in the treatment of allergic rhinitis (Table 2).
   

C. Immunotherapy
Immunotherapy attempts to increase the threshold level of the appearance of symptoms after aeroallergen expo­sure. The exact mechanism of how immunotherapy works is still unclear; it may be the production of so-called “blocking” antibodies, as well as regulation of the immune cascade that causes allergic reactions.

Indications for immunotherapy include long-term pharmacotherapy for prolonged periods of time, the inadequacy or intolerability of drug therapy, and signif­icant allergen sensitivities. Before beginning immuno-therapy, the physician must first confirm the atopic diagnosis by testing IgE specific to the offending aller­gen (or allergens).

Most immunotherapy administered in the United States today is through a gradual increase in the dose of the antigen(s) given until either a mild systemic symptom or a large local reaction at the subcutaneous injection site occurs (optimal dose therapy). In some centers, sublingual immunotherapy is the method of choice. This is more common in Europe and tends to be easy and safe to administer at home by the patients themselves.

There is no adequate test available to indicate to the patient how long immunotherapy must be continued. Therefore, a clinical response with a reduction in symp­toms dictates the duration of specific treatment. A mini­mum of 2–3 years is usually given to avoid a rapid recur­rence of symptoms in uncomplicated allergic rhinitis.

D. Other Treatment Considerations
The first aspect of treating patients who have not responded well to therapeutic measures, including immunotherapy, is determining to what degree thera­peutic compliance has occurred. The next steps are to adjust drug dosages, try one or two other agents, and consider combination therapy. In addition, the physi­cian should determine whether allergy exposure has increased and should also review the environmental control measures. Finally, it may be necessary to recon­sider the diagnosis and reevaluate the patient.

Table 4. Pharmacotherapies for allergic rhinitis.

Agent	Inflammation	Congestion	Rhinorrhea	Sneezing	Nasal Itch	Ocular Symptoms
Antihistamines 1st generation 2nd generation	±	-	+ +	+ +	+ +	+ +
Topical antihistamines	±	±	+	+	+	±
Decongestants	-	+	-	-	-	-
Intranasal steroids	+	+	+	+	±	±
Oral steroids	+	+	+	+	±	+
Intranasal cromolyn	±	±	±	±	±	±

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Sinusitis

Acute & Chronic Sinusitis
Ashish R. Shah, MD, Frank N. Salamone, MD, & Thomas A. Tami, MD
from Current Diagnosis and Treatment in Otolaryngology - Head and Neck Surgery.2008

ESSENTIALS OF DIAGNOSIS
• Suspect acute bacterial rhinosinusitis with an upper respiratory infection that does not resolve in 10 days or worsens after 5–7 days with symptoms that may include facial pain/pressure, nasal obstruction, and discolored nasal discharge.
• In chronic rhinosinusitis, nasal endoscopy and/or CT scan may be necessary to make the diagnosis because symptoms do not correlate well with findings.

General Considerations

Rhinosinusitis is by far the most common disease of the paranasal sinuses, affecting about 14%, or 31 million adults annually. The costs of chronic rhinosinusitis alone are estimated at over $4 billion per year. The appropriate and cost-effective treatment of rhinosinusitis is therefore critical.
Rhinosinusitis is broadly defined as a group of disorders characterized by inflammation of the nose and paranasal sinuses. Classification by the duration of an inflammatory episode includes acute (up to 4 weeks), subacute (4–12 weeks), and chronic (> 12 weeks). Additional categories include recurrent acute rhinosinusitis (≥ four episodes per year without evidence of chronic rhinosinusitis) and acute exacerbations of rhinosinusitis. Chronic rhinosinusitis may be subclassified as chronic rhinosinusitis with or without nasal polyps and with eosinophilic or noneosinophilic histologic features.

Paranasal Sinus Anatomy & Physiology
The paranasal sinuses are mucosa-lined structures physically contiguous with the nasal cavity. Proposed functions include (1) acting as resonating chambers for the voice, (2) providing protection to the brain from trauma, (3) moisturizing and humidifying ambient air, and (4) lightening the weight of the facial skeleton. However, there is no convincing evidence for any of these theories.
Knowledge of paranasal sinus anatomy is critical to understanding the pathophysiology, the possible complications, and the surgical treatments of sinusitis (Figure 1). Anteriorly, the nasal cavity opens to the outside environment through the skin-lined nasal vestibule. Moving posteriorly, the prominent inferior turbinate can be seen projecting medially from the lateral nasal wall. The nasolacrimal duct empties into the inferior meatus lateral to the inferior turbinate. Superior to the inferior turbinate, the middle turbinate hangs from its attachment to the skull base. Medial to the middle turbinate, the ethmoid bulla can be identified. Anterior and inferior to the bulla, the trough-shaped ethmoid infundibulum serves as the drainage conduit for the anterior ethmoid cells, the maxillary sinus, and the frontal sinus. The hiatus semilunaris is the crescent-shaped opening of the infundibulum into the nose.
The ostiomeatal complex, which includes those ostia that drain into the middle meatus, is an anatomically constricted region that is prone to blockage, especially in the presence of structural anomalies such as Haller cells and concha bullosa. In addition, the ostia themselves are small. The functional diameter of the maxillary sinus ostia is usually only 2–4 mm and the ostia of the ethmoid air cells are even smaller.

Figure 1. Lateral wall of the nasal cavity. (Reproduced, with permission, from Levin HL, Clemente MP. Sinus Surgery: Endoscopic and Microscopic Approaches. Thieme Medical Publishers, 2005.)

Posterior and superior to the middle turbinate lie the superior and, in some people, the supreme turbinates. The sphenoid sinus and the posterior ethmoid cells drain into the sphenoethmoidal recess posterior and medial to the attachment of the superior turbinate.
The relationship of the paranasal sinuses to the brain and the orbits is of critical importance. Superiorly and medially, the cribriform plate of the ethmoid bone serves as the roof of the nasal cavity and the floor of the anterior cranial fossa. More laterally, the ethmoid air cells are separated from the anterior cranial fossa by the fovea ethmoidalis, which is part of the frontal bone. The paper-thin lamina papyracea of the lateral ethmoid bone separates the ethmoid sinuses from the orbit and can serve as a route of the spread of infection from the sinuses to the periorbita.
The nose and paranasal sinuses are lined with pseudo-stratified columnar, ciliated epithelium with goblet and seromucous cells. Normal sinonasal mucociliary clearance is predicated on (1) ostial patency, (2) ciliary function, and (3) mucus consistency. Impairment of any of these factors at the osteomeatal complex may result in mucus stasis, which under the proper conditions induces bacterial growth. Furthermore, cilia have a tendency to propel mucus toward the natural ostia of a sinus, which explains why surgical openings made into a sinus at places other than the natural ostia (eg, in the inferior meatus) are ineffective at draining the sinus (Figure 2)

Figure 2. Acute maxillary sinusitis. The left maxillary sinus is completely opacified and the ostium is occluded.

Pathogenesis & Clinical Features
A. Acute Bacterial Rhinosinusitis

Acute bacterial rhinosinusitis typically begins as a viral upper respiratory infection that persists longer than 10 days. In some cases, a secondary acute bacterial rhinosinusitis may result from ostial blockage owing to mucosal edema and possible ciliary damage. The end result is mucus stasis and the creation of an environment suitable for bacterial proliferation. The most common organisms responsible for acute sinusitis include Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The diagnosis of acute bacterial rhinosinusitis can be made when a viral upper respiratory infection does not resolve within 10 days or worsens after 5–7 days. Symptoms suggestive of the diagnosis are listed in Table 1. Severe symptoms may imply impending complication, and the patient certainly should not wait 5–7 days before receiving further evaluation and treatment.

Table 1. Major and minor factors in the diagnosis of acute sinusitis.
Major Factors
Facial pain or pressure
Facial congestion or fullness
Nasal obstruction or blockage
Nasal discharge, purulence, or discolored postnasal drainage
Hyposmia or anosmia
Purulence in nasal cavity
Fever (in acute rhinosinusitis only)
Minor Factors
Headache
Fever (in chronic sinusitis)
Halitosis
Fatigue
Dental pain
Cough
Ear pain, pressure, or fullness

B. Chronic Rhinosinusitis
The pathophysiology of chronic rhinosinusitis remains incompletely understood, but it is clear that a number of systemic, local, and environmental factors play important predisposing roles. The presence or absence of nasal polyps may represent different pathophysiologic mechanisms. Nasal polyps are smooth, edematous lobulated masses that usually arise from the middle meatus or sphenoethmoid recess and represent a noninfectious and most often eosinophilic inflammatory reaction. Eosinophilic chronic rhinosinusitis represents a spectrum of diseases that may have diverse causes, including both allergic and nonallergic and including allergic fungal rhinosinusitis (AFRS), eosinophilic mucin rhinosinusitis, aspirin-exacerbated respiratory disease (nasal polyps, asthma, and ASA sensitivity), and eosinophilic granuloma. Chronic rhinosinusitis with or without nasal polyps and with noneosinophilic features are thought to be the result of impaired mucociliary clearance, abnormal sinus ventilation, or immune deficiency. Chronic rhinosinusitis with noneosinophilic nasal polyps includes antral choanal polyp, cystic fibrosis, ciliary dyskinesias, and bacterial infection. Chronic rhinosinusitis without nasal polyps may be related to many disorders including immunodeficiency, autoimmune/granulomatous diseases, allergic rhinitis, anatomic irregularities, and scarring.
Although the most common symptoms of chronic rhinosinusitis are nasal discharge, nasal obstruction, facial congestion, and facial pain/pressure, patients with chronic rhinosinusitis with nasal polyps more often have hyposmia and less pain/pressure complaints than those who do not have nasal polyps. Also, patients with chronic rhinosinusitis without nasal polyps may be more likely to have bacterial infection and may be more likely to improve with medical therapies.
The role of bacteria in the pathogenesis of chronic rhinosinusitis is controversial, although antibiotics are frequently prescribed. The most common organisms isolated in chronic rhinosinusitis subjects include Staphylococcus aureus, anaerobes, and gram-negative enterics such as Pseudomonas aeruginosa. Recent avenues of investigation about the relationship of bacteria to chronic rhinosinusitis include the roles of bacterial superantigens, biofilms, and osteitis (Figure 3)

Figure 3. Proposed subclassification of chronic rhinosinusitis. NP, nasal polyps; GERD, gastroesophageal reflux disease; AFRS, allergic fungal rhinosinusitis; ASA, acetylsalicylic acid. (Reproduced, with permission, from Meltzer EO, Hamilos DL, Hadley JA et al. Rhinosensitivity: establishing definitions for clinical research and patient care. Otolaryngol Head Neck Surg. 2004;1315:51.)

C. Fungal Rhinosinusitis
1. Invasive fungal sinusitis—Invasive fungal sinusitis is usually a complication of diabetes or an immunocompromised state; it is characterized by a fulminant, invasive infection. A pathologic examination of the black necrotic debris that is often seen intranasally demonstrates arterial and venous thrombosis due to direct fungal invasion. The treatment consists of (1) debriding all involved structures, including the orbital contents, if necessary; (2) aggressive intravenous antifungal therapy; (3) normalizing the underlying immunocompromised state (usually neutropenia); and (4) stabilizing the diabetes. The typical fungal pathogens are Aspergillus, Mucor, and Rhizopus.
2. Fungal ball—Fungal ball is the development of a noninvasive conglomeration of fungal hyphae into a mass. Aspergillus is the most common pathogen, and chronic rhinosinusitis results from paranasal sinus obstruction. Treatment is complete extirpation of the fungal mass.
3. Allergic fungal rhinosinusitis (AFRS)— Fungus can also stimulate an immune response from the sinonasal mucosa, resulting in allergic fungal sinusitis. Typically, polypoid tissue is seen anterior to a mass consisting of mucin, fungal elements, Charcot-Leyden crystals, and eosinophils. Sinus expansion and bony remodeling are hallmark features of this process. Even though this is not an invasive, infectious process, the treatment is primarily surgical with postoperative topical nasal steroids. Immunotherapy and systemic steroids may be necessary to reduce recurrence. Topical antifungals may also prove to have a role in treatment.

Diagnostic Modalities
A. Physical Examination
A complete head and neck exam with anterior rhinoscopy is essential in all patients suspected of having rhinosinusitis. Findings of mucopurulence, edema, septal deflection, and polyps should be noted. The middle meatus is often well visualized after appropriate decongestion.
B. Endoscopic Evaluation
Rigid or flexible nasal endoscopy may be necessary in the evaluation of rhinosinusitis. Findings to be noted include mucopurulence at the ostiomeatal complex and sphenoethmoid recess, edema, erythema, polyps/polypoid tissue, and crusting. In acute bacterial rhinosinusitis, endoscopy is useful to confirm the diagnosis and to obtain cultures at the middle meatus. Because symptoms do not correlate well with findings in chronic rhinosinusitis, endoscopy and/or imaging is essential to make the appropriate diagnosis and to obtain cultures from the middle meatus. When performed carefully to avoid contamination from the nose, middle meatus cultures correlate well with maxillary sinus aspiration, which is the gold standard. Aerobic, anaerobic, fungal, and acid-fast bacilli cultures should be obtained.
C. Imaging Studies
Computed tomography (CT) scanning is currently the method of choice for sinus imaging. Because a viral upper respiratory infection may cause abnormalities on CT that are indistinguishable from rhinosinusitis, imaging in acute bacterial rhinosinusitis has limited usefulness except when complications are suspected. On the other hand, symptoms of chronic rhinosinusitis do not correlate well with findings. Therefore, CT and/ or nasal endoscopy is necessary to make the diagnosis. In addition to providing excellent visualization of mucosal thickening, air fluid levels, and bony structures, coronal scans give optimal visualization of the osteomeatal complex and are conveniently oriented for the surgeon in terms of surgical planning.
Magnetic resonance imaging (MRI) of the sinuses is much less commonly performed than CT scanning largely because this modality does not image bone well. However, MRI can usually differentiate retained mucus from soft tissue masses based on signal intensity characteristics, which have an identical appearance on CT scans; therefore, MRI can be very helpful in differentiating a sinus completely filled with tumor from one partially filled with retained secretions. MRI is also a helpful modality with suspected orbital or intracranial extension.
D. Laboratory Tests
Laboratory tests are rarely helpful in the evaluation of sinusitis. If there is any question of an immunocompromised state, testing for HIV and IgG levels should be performed. An evaluation for sarcoidosis may be appropriate. Also, scarring in the nasal cavity can be seen in autoimmune conditions, such as Wegener granulomatosis, and therefore cytoplasmic-antineutrophil cytoplasmic antibody (C-ANCA), erythrocyte sedimentation rate (ESR), and antinuclear antibody (ANA) tests should be considered.

Differential Diagnosis
The differential diagnoses of acute and chronic sinusitis are many and include the following: the common cold; temporomandibular joint (TMJ) pain; headache (including migraine); tooth, nasal, and trigeminal pain; and sinus neoplasm. The symptoms of facial pressure and pain, purulent nasal discharge, nasal congestion, hyposmia, tooth pain, and a poor response to nasal decongestants can help differentiate these entities.
A. Viral Rhinitis (Common Cold)
The most difficult point in the diagnosis of sinusitis is differentiating it from the common cold. The presence of purulence on examination of the nasal cavity can assist in the diagnosis. Sinus infection is more likely if symptoms become worse after 5 days or last longer than 10 days. Acute unilateral symptoms are also more consistent with sinusitis. Allergic rhinitis may also cause rhinorrhea and postnasal drip, as seen in sinusitis.
B. Temporomandibular Joint Pain
Because of the complex anatomy of the head and neck, many conditions may mimic sinus symptoms. Temporomandibular joint pain is common and is frequently dull and aching in quality. Palpation for joint tenderness and click is therefore important.
C. Headache and Migraine
Headache, both migraine and tension type, may be confused with sinus pain. Migraine headaches are characterized by throbbing head pain, frequently unilateral, that lasts from 4 to 72 hours. Migraines can occur with or without neurologic symptoms such as visual disturbances or numbness. Noting the presence of an aura, the relatively short duration of symptoms, and the response to migraine medicines such as ergot alkaloids can help differentiate migraine headaches from sinusitis. The bandlike frontal pressure associated with tension headache typically worsens as the day goes on, whereas sinus pain remains relatively constant. Sinus pain is typically not as severe as the symptoms associated with cluster headache.
D. Tooth, Nasal, and Trigeminal Pain
Tooth pain may be a result of sinusitis or may be mistaken for sinus pain. Particularly in children, nasal foreign body may cause sinusitis and should be excluded. Trigeminal neuralgia is uncommon, but it can cause paroxysms of lancinating pain along the distribution of the trigeminal nerve. This sensation is in contrast to the constant dull ache of sinusitis.
E. Sinus Neoplasm
Sinus neoplasm is relatively uncommon, but it is critical to exclude. A history of unilateral nasal obstruction and epistaxis warrants further workup, including CT scan and nasal endoscopy. Changes in vision and cranial nerve deficits, particularly in the distribution of the infraorbital nerve, should also cause suspicion. Radiographically, sinus neoplasm is identified by unilateral findings and bone erosion.

Treatment
A. Antibiotics
Antibiotic recommendations for acute bacterial rhinosinusitis have evolved based on increasing resistance patterns. Twenty-five percent of S pneumoniae infections are penicillin resistant, and resistance to macrolides and trimethoprim/sulfamethoxazole (TMP/SMX) is common. Thirty percent of H influenzae and almost all strains of M catarrhalis produce β-lactamase. Current guidelines for antibiotic choice in acute bacterial rhinosinusitis are dependent on the severity of the disease and whether the patient has received antibiotics in the past 4–6 weeks. Duration of treatment should be 10– 14 days. With mild disease and no recent antibiotic use,
recommendations include amoxicillin/clavulanate (1.75– 4 g/250 mg/d or 45–90 mg/6.4 mg/kg/d in children), amoxicillin (1.5–4 g/d or 45–90 mg/kg/d in children), or cefpodoxime, cefuroxime, or cefdinir. β-Lactam-allergic adults should receive TMP/SMX, doxycycline, or a macrolide, and β-lactam-allergic children should receive TMP/SMX or a macrolide. Failure rates, however, with these non–β-lactam antibiotics may reach 25%. With recent antibiotic use or in moderate disease, initial drug selection should include a respiratory quinolone, amoxicillin/clavulanate, ceftriaxone, or a combination to provide broad-spectrum coverage in adults and amoxicillin/clavulanate or ceftriaxone in children. β-Lactam-allergic adults should receive a respiratory quinolone or clindamycin and rifampin, whereas β-lactam-allergic children should receive TMP/SMX, a macrolide, or clindamycin.
Failure to respond to treatment within 72 hours should lead to a reevaluation and change of therapies to provide broader coverage. In this circumstance, CT scan, nasal endoscopy, or culture should be considered.
Chronic sinusitis is associated with a different set of pathogens and therefore demands an antibiotic with a spectrum that includes gram-negative organisms, S aureus, and anaerobes. In addition, longer courses of antibiotics, typically 3–6 weeks, are often recommended. Culture-directed therapy is highly recommended (Table 2).
B. Nasal Sprays and Irrigation
Mucosal inflammation and polyposis, which lead to the obstruction of sinus ostia, are critical in the pathogenesis of most chronic rhinosinusitis. Nasal steroid sprays directly address this problem by reducing mucosal inflammation and the size of polyps, thereby limiting postoperative recurrence. Systemic side effects are uncommon (although arguably possible), and therefore nasal steroids are often prescribed for maintenance therapy in those with chronic rhinosinusitis. Nasal saline irrigation is an important component in the treatment of chronic rhinosinusitis. Frequent rinsing prevents the accumulation of nasal crusts and promotes mucociliary clearance. Hyper-tonic saline may increase the rate of clearance in certain cases. Antibiotic irrigations such as gentamicin (80 mg/L) may be considered in refractory cases of chronic rhinosinusitis. Although nasal saline sprays do not have the mechanical débridement effect of saline irrigation, they do help to keep the mucosa moist and to facilitate mucociliary clearance in both acute bacterial rhinosinusitis and chronic rhinosinusitis.
Oxymetazoline hydrochloride spray causes intense vasoconstriction of the nasal mucosa. Rebound swelling may incite a vicious cycle, leading to complete nasal obstruction and subsequent sinus disease. Oxymetazoline spray may be used for very short periods of time (eg, 3 days) for symptomatic relief usually in acute bacterial rhinosinusitis or acute exacerbations of chronic rhinosinusitis.

Table 2. Efficacy of antibiotics in the therapy of sinusitis.

	Acute Sinusitis			Chronic Sinusitis
Oral Antimicrobial	5 pneumoniae	Haemophilus spp.	Moraxella catarrhalis	S aureus	Anaerobes	Enterics
Penicillin/Amoxicillin	+	0	0	0	±	0
Cephalosporins First-generation Second-generation Third-generation	± + ±	0 + +	0 + +	+ + ±	0 0 0	0 ± +
Amoxicillin/Clavulanate	+	+	+	+	+	+
Macrolides	±	±	±	+	0	0
Clindamycin	+	0	0	+	+	0
Imipenem*/meropenem*	+	+	+	+	+	+
Trimethoprim/sulfamethoxazole	-	+	+	±	0	+
Quniolones (older) or aminoglycosides*	±	+	+	±	0	+
Quinolones (newer)	+	+	+	+	±	+

0, no or little (<>±, some activity (30–80%); +, good activity (> 80%). *Available in parenteral form only.

C. Systemic Steroids, Decongestants, and Other Therapies
Systemic steroids are highly effective at reducing mucosal inflammation and nasal polyp bulk in chronic rhinosinusitis because of their anti-inflammatory effects. However, a thorough discussion with patients regarding the risks of systemic steroid administration is mandatory. A tapered regimen may be given during severe chronic rhinosinusitis flare-ups and in the postoperative period, but their use should be limited and carefully monitored. Systemic decongestants and mucolytic agents such as guaifenesin may provide some symptomatic relief. Given the favorable side effects of these agents, they are often added to the therapeutic regimen. Leukotriene receptor antagonists (montelukast, zafirlukast) and macrolide antibiotics, which have anti-inflammatory effects, may also prove to be useful therapeutics.
D. Allergy Management
For patients with documented allergic disease, ongoing allergy management is beneficial. Environmental controls, topical steroids, and immunotherapy may prevent exacerbations of rhinitis, therefore preventing the progression to sinusitis.
E. Sinus Surgery
Maximal medical therapy, typically defined as 4–6 weeks of appropriate antibiotics, nasal steroids, and generally systemic steroid therapy, is prescribed prior to the consideration of surgical management. Surgical therapy may be necessary if evidence of mucosal disease or ostiomeatal unit obstruction—as determined by either CT scan or endoscopic evaluation—persists in spite of aggressive medical treatment. Patients with clear anatomic abnormalities or sinonasal polyps may be more likely to respond to surgical therapy.
1. Functional endoscopic sinus surgery—
a. Indications—Functional endoscopic sinus surgery is based on several key observations: (1) widely patent antros-tomies in nonanatomic positions may fail to drain sinuses due to the directionality of mucociliary flow; (2) the ostiomeatal unit is anatomically constricted; and (3) the stripping of sinus mucosa leads to delayed healing and the loss of normal ciliary function. Thus, a conservative endoscopic technique has been developed. The keys to the technique are the use of “through-cutting” instruments that preserve sinonasal mucosa and the excellent visualization made possible with modern telescopes. Mucosal polyps can be carefully débrided, the natural ostia enlarged, and the ethmoid sinuses unroofed, which opens them to the nasal cavity. The improvement in symptoms with functional endoscopic sinus surgery may be expected in more than 90% of patients.
b. Relationship with other treatments—Functional endoscopic sinus surgery must be regarded as only one component of a total sinusitis treatment plan that must also include preoperative optimization of medical therapy, meticulous postoperative care, and, finally, long-term maintenance therapy. Any underlying medical conditions, such as diabetes mellitus, immunodeficiency, and atopic disease, must also be addressed if ultimate success in treatment is to be obtained.
c. Complications—The complications of surgical therapy are related to the close anatomic proximity of the paranasal sinuses to the brain and orbits. An intimate knowledge of this anatomy is critical to safely perform this surgery; a definite learning curve is associated with the adoption of this technique. Injury to the medial wall of the orbit may cause the prolapse of orbital fat into the nasal cavity. A violation of the orbital wall, with subsequent hemorrhage and orbital hematoma, may lead to compression of the optic nerve and blindness. Damage to the cribriform plate region may lead to cerebrospinal fluid leak, herniation of cranial contents, meningitis, or intracranial bleeding.
2. Open sinus surgery—In spite of the versatility of endoscopic procedures, open sinus surgery is sometimes needed. An example is the Caldwell-Luc antrostomy in which the maxillary sinus is entered through a sublabial incision. The Caldwell-Luc approach allows biopsy of the sinus contents; also, once the sinus is entered, a drainage window may be made into the nasal cavity.
If surgery is not an option or the disease is refractory to surgical intervention, a trial of intravenous antibiotic therapy may be appropriate.

Complications

A. Orbital Infection
The lamina papyracea of the ethmoid bone forms a large part of the medial wall of the orbit. The orbit, therefore, is separated from the ethmoid sinuses by the paper-thin and often dehiscent lamina. Because of the weakness of this barrier, the spread of infection
to the orbit is the most common complication of acute sinusitis. In addition, the ophthalmic venous system is devoid of valves and communicates with the ethmoid veins, providing a path for infection to enter the orbit. Infection of the orbital structures usually follows a step-wise sequence as described in Table 3.
Inflammatory edema of the lid may be treated in an outpatient setting with oral antibiotics, provided that close follow-up can be achieved. Orbital cellulitis usually responds to intravenous antibiotics, whereas subperiosteal and orbital abscesses require operative drainage and drainage of the offending sinus. Cavernous sinus thrombosis is truly life threatening and is associated with a poor prognosis even with aggressive medical and surgical management. The incidence of all orbital complications is higher in the pediatric population than in adults.

B. Meningitis

Meningitis usually occurs by extension of infection from the ethmoid or sphenoid sinuses. On examination, patients with this complication may have a diminished sensorium or may be obtunded. The typical signs of meningitis, such as Kernig and Brudzinski signs, may be present. If meningitis secondary to sinus infection is suspected, a high-resolution CT scan of the brain with contrast and a sinus CT scan should be obtained. A CT scan of the brain is critical both to rule out mass effect and to delineate any other intracranial complications. Lumbar puncture is diagnostic and provides material for culture. The treatment for meningitis involves intravenous antibiotics and surgical drainage of the sinuses.

Table 3. Orbital complications of sinusitis.
Lid Edema
No limitation of extraocular movements and vision is normal. Infection is anterior to the orbital septum.
Orbital Cellulitis
Infection of the soft tissue posterior to the orbital septum.
Subperiosteal Abscess
Pus collection beneath the periosteum of the lamina papyracea.
Orbital Abscess
Pus collection in the orbit.
Associated with limitation of extraocular movements, exophthalmos, and visual changes.
Cavernous Sinus Thrombosis
Bilateral eve involvement, meningeal signs, and other intracranial complications.

C. Epidural Abscess

An epidural abscess is a collection of purulent material between the bone of the skull and the dura, typically in relation to frontal sinusitis. The further spread of infection, either by direct extension or by hematogenous seeding, may lead to subdural empyema and eventually to brain abscess (Figure 4). Draining both the abscess and the offending sinuses is mandatory, and long-term antibiotics are often necessary. Regardless of the treatment, morbidity and mortality are high, particularly with subdural involvement.

Figure 14–4. Brain abscess due to frontal sinusitis. This contrast-enhanced axial CT scan shows a left frontal brain abscess caused by frontal sinusitis.

D. Cavernous Sinus Thrombosis
Septic emboli may flow posteriorly through the ophthalmic venous system to the cavernous sinus, causing infection, inflammation, and eventually thrombosis of the sinus. Ocular symptoms include chemosis, sluggish pupillary response, ophthalmoplegia, and blindness. These findings are often bilateral. Intravenous antibiotic treatment should be instituted immediately, and, if indicated, the involved sinuses should be surgically drained. The role of anticoagulation to prevent further thrombus formation and systemic steroid therapy is controversial.
E. Pott Puffy Tumor
If infection in the frontal sinus spreads to the marrow of the frontal bone, localized osteomyelitis with bone destruction can result in a doughy swelling of the forehead classically described as Pott puffy tumor. Surgical drainage and débridement must be undertaken.

Prognosis

The prognosis for acute sinusitis is excellent, with an estimated 70% of patients recovering without treatment. Oral antibiotics may decrease the time that a patient is symptomatic. Chronic sinusitis has a more variable course. If an anatomic cause is found and is rectified by surgery, the prognosis is good. More than 90% of patients have improvement with surgical intervention. However, these patients are always prone to relapse; therefore, a vigorous preventive regimen is essential.

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