Учебники / Rhinosinusitis - A Guide for Diagnosis and Management 2008

mechanisms may be involved (e.g., nonallergic rhinitis). Since AR is usually first seen in childhood, it is important in all individuals suspected of having AR to determine the age at which they first had symptoms. As AR is frequently not the initial allergic illness experienced by patients, it is also important to inquire whether individuals had any episodes of other atopic illnesses in childhood, such as perioral or perianal eczema, atopic dermatitis, or asthma. In addition, atopic children may also have experienced frequent episodes of otitis media or RS, which may help with determining the likelihood of an individual having an allergic component to their present symptoms.

Since AR has a genetic predisposition, family history is also relevant in assessing the patient. If one or both parents of the patient have AR, the likelihood of the patient having AR increases significantly. The absence of a family history, however, does not preclude the diagnosis of AR.

Assessment of seasonality is an important component of the patient history because many patients with AR have a strong seasonal pattern to the onset and resolution of their symptoms. In patients with SAR, symptoms will closely track pollen counts for relevant antigens, and the presence of clear seasonal relationships strongly suggests a diagnosis of SAR. The absence of seasonal variation does not exclude the presence of AR, however, as patients with PAR often have relatively consistent symptoms throughout the year. Seasonal variability in patients with PAR is also common, as many patients with PAR also have concurrent SAR.

In addition to seasonal variability, patients are often able to describe discrete triggers that will bring about the rapid development of symptoms. It is important, therefore, to inquire about specific triggers of which the patient is aware. Patients often notice symptoms worsening with marked exposure to antigens, as is often seen with allergy to cat dander, dust mites, and ragweed or grass pollen. The absence of patient awareness of discrete triggers does not exclude allergic sensitivities to those antigens, however, as patients often accommodate to the presence of antigens within their environments.

Physical Examination

It is important to examine not only the nose among patients with AR but to evaluate the head and neck for comorbid signs as well. An inspection of the face often suggests signs of AR among both children and adults. Patients with AR often have puffiness of the eyelids or the cheeks, as well as darkening of the skin under the eyes, referred to as “allergic shiners.” These findings are seen secondary to nasal congestion and inflammation. Fine lines may be noted in the lids, referred to as “Dennie’s lines,” which are secondary to spasms of the eyelid musculature. In addition, injection or redness of the conjunctivae may also be seen.

In patients with AR, the nasal examination often shows signs of acute or chronic inflammation. The mucosa in the nose of a patient with AR is often pale, gray to bluish-white, and is frequently boggy and edematous. In contrast, patients with nonallergic or infectious rhinitis often have an inflamed, hyperemic, and

angry-appearing nasal mucosa. The inferior turbinates are often swollen in the patient with AR, and this edema will usually decrease rapidly with administration of a vasoconstricting drug such as oxymetazoline. The nose should also be examined for other signs of nasal pathology, including purulent discharge, which would be common in acute and chronic RS, and nasal polyps, which are commonly seen in patients with chronic RS. Examination of the nose can be conducted using an otoscope, but more thorough examination of the posterior portion of the nasal cavity often requires an endoscopic examination.

In addition, patients with AR often have changes in their pharyngeal mucosa secondary to the increased immune responsiveness of the mucosa. It is common to see “cobblestoning” in the posterior pharyngeal wall among patients with AR. This smoothly irregular surface seen in the posterior oropharynx is caused by the presence of numerous lymphoid follicles in the pharyngeal submucosa. Examination of the skin for signs of atopic dermatitis or eczema can also confirm the presence of allergic findings that often accompany AR. In addition, auscultation of the lungs is important as many patients with AR have concurrent asthma as part of their spectrum of disease.

Allergy Testing

When a patient with symptoms of rhinitis is suspected of being allergic, and when the clinician wishes to confirm a diagnosis of allergy, testing can be conducted using one of several methods (Table 8.2). Because allergy is an important contributor to the expression of symptoms in patients with RS, it is reasonable to consider allergy testing in all patients with recurrent episodes of acute RS and in many, if not all, patients with chronic RS. Confirmation of the presence of allergies in these populations can significantly alter treatment and testing should be utilized as a component of the diagnostic process in patients with problematic RS.

Screening Tests

Screening tests can be used as an initial approach to detect the presence of allergic hypersensitivity. The results should be interpreted as suggestive of the presence of

Table 8.2 Common tests used for diagnosis of allergy

allergy rather than conclusive [11]. Screens can be useful, however, since they can often be done quickly using routine methods available to both primary care physicians and specialists.

One commonly used screening test is total IgE. Through venipuncture, a blood sample can be collected for global assessment of IgE in the patient’s serum. When the concentration of total IgE is elevated (usually above 100 g/mL), this finding is considered suggestive of the presence of allergy. Significant elevations usually correlate with clinically relevant allergy, while total IgE levels within the normal range do not rule out the presence of allergic disease or elevated levels specific to individual antigens. Total IgE levels should therefore be considered suggestive rather than diagnostic of the presence of allergy [12].

Another commonly used screening method is nasal cytology. As eosinophils are frequently present in significant quantity in the mucus of allergic individuals, a sample of the nasal mucus can be gathered using a small swab or nasal spoon and examined microscopically for the presence of eosinophils. Abundant numbers of eosinophils would be suggestive of allergy, although nasal eosinophils are also elevated among patients with chronic RS as well. The presence of increased eosinophils may therefore be more important in patients with recurrent acute RS than in individuals with chronic RS; elevations in the acute RS population would suggest the presence of allergy as a potential cofactor in the recurrence of the patient’s disease. Results of nasal cytology, however, can be unreliable and should be judged with caution when evaluating the presence of nasal allergy [13].

Confirmatory Tests

In contrast to the use of screening tests, assessment techniques are available to accurately confirm the presence of allergic hypersensitivity and to quantify or estimate the degree of that hypersensitivity. Confirmatory testing for allergy can be conducted using two methods: (1) in vivo testing, in which assessment is conducted through introducing suspected antigens directly into the skin; and (2) in vitro testing, in which serum sampling is done to assess the presence of, and to quantify the amount of, specific IgE antibodies in the systemic circulation.

In vivo testing, also known as skin testing, is the most commonly used method of allergy testing both in the United States and internationally. In all types of skin testing, a small amount of a suspected antigen is introduced into the skin using one of several well-accepted methods. Patients allergic to that antigen will have IgE specific to the antigen bound to the surface of mast cells through prior exposure and sensitization. When the antigen is reintroduced into the skin, it will bind to these IgE antibodies, resulting in cross-linking of adjacent IgE molecules, degranulation of preformed histamine-containing cytoplasmic granules, and release of histamine into the skin. Histamine will bind to cellular receptors in the skin, resulting in localized tissue inflammation. Local inflammation is expressed through a reaction known as wheal and flare, in which transudation and release of plasma into the tissues cause a discrete area of swelling (wheal) and tissue irritation results in local erythema of the skin (flare). This response is very rapid, and is usually noted within 5 to

Fig. 8.4 Skin testing for allergic rhinitis using the intradermal method

following the prior use of prick testing or in a sequential manner using multiple ID tests starting at very dilute concentrations and progressing to more concentrated antigens. The serial use of multiple antigens of increasing concentration is well established and is referred to either as serial endpoint titration (SET) or as intradermal dilutional testing (IDT). Blended testing methods using a combination of prick and ID tests have also been used for many years, and current systems allow more accurate quantification of allergic sensitivity with these techniques with approaches such as modified quantitative testing (MQT) [14].

Because skin testing carries the risk of large local reactions and, rarely, of severe systemic reactions, anaphylaxis, and death, skin testing should be conducted only by clinicians who are trained and experienced in its use. When properly done, however, it is safe and well tolerated.

In vitro allergy testing involves the use of clinical laboratory analysis for the presence of specific IgE antibodies. In this assay, serum drawn from a patient suspected of allergy is evaluated using one of several methods in which both the presence and the amount of specific IgE are assessed to one or more suspected allergens. Serum is incubated with anti-IgE antibodies and complexes are formed with patient IgE antibodies for specific allergens if they are present in the serum. Using

a tagged radioactive or immunoreactive label, these complexes can be quantified and the presence and severity of allergy to each individual antigen can be assessed. Accuracy of results from in vitro testing compare favorably with those obtained through skin testing. The advantage of in vitro testing is that it is simple, rapid, safe, and can be conducted even when patients are on medications that may interfere with skin testing results (e.g., antihistamines). Disadvantages of in vitro testing include higher costs and slightly decreased sensitivity when compared with skin testing [15].

The Association of Allergy and Rhinosinusitis

The majority of information supporting a comorbid link between AR and RS has been gathered from epidemiologic studies conducted over the past 20 years. These data suggest a relationship in the development and expression of symptoms among patients with RS, although a true pathogenetic link has been difficult to establish.

In one classic study, a group of 224 young adults with acute maxillary RS were matched with a group of 103 young adults without RS and evaluated with skin testing for the presence of allergy. Results demonstrated that patients with RS had a numerically higher prevalence of skin-test positivity than did healthy control subjects (45% vs. 33%). These findings suggest that AR may play a role in the development of RS, at least in a subset of sensitive individuals [16].

In another important study, 40 subjects with perennial AR were compared with 30 nonallergic subjects to assess the relative presence of physical and radiologic signs of RS. All subjects had computed tomography (CT) scans of their sinuses to evaluate the presence of findings consistent with RS. Results demonstrated a higher prevalence of RS among patients with perennial AR than among their nonallergic counterparts. These findings again suggest that AR may contribute to the development or persistence of RS in some individuals [17].

While it may be difficult to describe a causal relationship between AR and RS, several research studies suggest that the presence of AR may affect the severity of symptoms among individuals with RS, as well as impact resistance to medical therapy. Among a sample of 200 consecutive patients who underwent sinus surgery and also had in vitro testing for routine allergens, 80% of individuals demonstrated significantly elevated levels of specific IgE for one or more antigens. As the prevalence of allergy in the general population is estimated at 25% to 30%, this observation would suggest that the presence of allergy may contribute to the development of chronic RS, or at least affect its severity and response to medical therapy [18].

In another study, 50 consecutive patients who underwent sinus surgery had skin testing for inhalant allergy, received CT scans to assess the severity of chronic RS, and completed quality-of-life instruments to evaluate the perceived impact of their disease. Patients with RS reported significant adverse impact on their quality of life. In addition, the presence and severity of allergy on skin testing was significantly associated with decrements in perceived quality of life. Changes on CT scan,

however, did not appear to be associated with quality of life [19]. These findings were confirmed in a similar study, in which allergy was judged to be an independent predictor of the severity of RS and its response to surgical treatment [20].

Other studies have suggested that the severity of disease among patients with chronic RS is associated with the presence of allergy. In one such study, 104 patients undergoing sinus surgery had preoperative and intraoperative assessments that included CT scans, in vitro allergy tests, sinus cultures, tissue and serum eosinophilias, and quality-of-life measurements. Among patients who underwent surgery, the extent of disease on CT scan and the presence of eosinophils in the sinus tissue were associated with elevations of specific IgE on in vitro allergy testing. The authors suggested that this relationship might be more vigorous among patients with extensive disease. They further suggested that both chronic RS and AR appeared to share similar immune mechanisms [21]. Other authors have reported similar relationships between the presence of allergy and the severity of RS [22–24].

Despite epidemiologic evidence linking AR and RS, convincing mechanisms that would account for the observed association between these two diseases have not been developed. It does appear that instillation of an antigen into the nose among allergic patients known to be sensitive to that antigen will reproduce symptoms consistent with RS. In one such study, 37 patients with known chronic RS and AR were challenged with installation of antigen directly into the nose [25]. Among this group of patients, 29 individuals complained of upper respiratory symptoms in the sinuses and ears. Changes were also noted on sinus radiographs among these individuals. The authors of this study argued that antigen exposure in sensitized individuals causes significant changes in the sinonasal mucosa, resulting in localized edema, mucociliary dysfunction, and increased mucous production. While this model could account for symptom exacerbations among allergic individuals with chronic RS, it is unable to explain the initial development of RS among atopic patients.

In a similar study, nasal antigen challenge among a group of patients with known AR demonstrated changes in the sinuses related to the presence of the antigen. In this study, sensitive patients had antigen instilled into one side of the nose, and eosinophils were harvested from both maxillary sinuses. An increase in eosinophils collected by sinus lavage was noted bilaterally. The authors of this study suggested that a direct neurogenic reflex was responsible for these changes within the sinuses, and that inflammation could be found in the sinuses simply by installation of antigen into the nose [26].

This series of studies suggests that the presence of AR appears to be involved as a cofactor in the disease expression of patients with both acute and chronic RS. Although a direct pathogenic relationship may be difficult to establish, evidence demonstrates that patients with both AR and RS appear to have increased symptoms secondary to their RS, can have their symptoms exacerbated by exposure to antigens, and can be more resistant to treatment, both surgical and medical. For that reason, it is important to recognize the presence of allergies among patients with RS and to assure that management strategies are implemented that address the allergic component of these patients’ symptoms.

Treatment of Allergic Rhinitis in the Patient with Rhinosinusitis

Management of the patient with AR involves a coordinated strategy designed to both modify the burden of disease and decrease its symptomatic expression. Optimal management often utilizes a multifaceted approach to therapy and may involve input from several disciplines to maximize outcome. The treatment of AR has generally been conceptualized to include one or more of three important strategies:

(1) allergen avoidance, (2) pharmacotherapy, and (3) antigen-specific immunotherapy (Table 8.3).

Avoidance

Since AR is a disease that is triggered by exposure to antigens to which an individual has been previously sensitized, it is logical to attempt to control the contact that a patient may have with relevant antigen triggers. The ability to exert effective environmental controls in patients with AR is an important therapeutic adjunct that allows specific treatment interventions to be more successful [27].

To allow effective allergen avoidance, it is first important to identify those allergens that are relevant in the expression of the patient’s symptoms. The most valuable element of the diagnostic workup of the patient with AR is therefore the allergy history, as important triggers to the development of symptoms can often be readily identified. For example, among patients who are allergic to cat dander, it is quite common for them to realize that they become much more symptomatic when in the presence of cats than when away from them. This simple observation can lead to a treatment strategy of cat avoidance that can decrease the burden of exposure and improve patient symptoms. Clinicians should therefore be diligent in conducting a complete allergy history.

Table 8.3 Management options for treatment of allergic rhinitis

Environmental control procedures

Antigen avoidance

Pharmacotherapy

Antihistamines

Oral

Topical

Decongestants

Oral

Topical

Corticosteroids

Oral/parenteral

Topical

Leukotriene modifiers

Mast cell stabilizers

Anticholinergics

Immunotherapy

Subcutaneous

Sublingual

In addition to exploring the patient’s allergy history, other triggers to the exacerbation of symptoms should also be established. Many patients with AR also have nonallergic triggers—such as cigarette smoke and strong odors—and exposure to these triggers can worsen their allergic disease. Decreasing exposure to nonallergic triggers among patients with AR can limit the expression of their disease and their symptoms of AR and RS.

Three basic strategies should be employed in practicing good environmental controls in allergen avoidance:

1.Remove the source of the antigen (if possible)

2.Remove accumulated antigen

3.Prevent the return of the antigen

As it is not equally plausible to effectively reduce exposure to all relevant antigens, selective implementation of these three strategies can result in optimal management.

For example, it may not be possible to remove the source of outdoor pollens such as grass or ragweed antigens during their season. It is often possible, however, to decrease exposure to the outdoor environment and to prevent the accumulation of grass or ragweed pollen inside the home. Keeping windows closed during pollen seasons, using air conditioning to ventilate and cool the air, and employing wholehouse or room filtration devices can modify the inside environment sufficiently to decrease patient exposure and lessen symptoms. In another example, if a patient is allergic to cat dander, it is possible to remove cats from the home, or to at least limit their presence throughout the house. It may take several months to clear cat dander from the home after removal of the animal, but the decline in the burden of antigen in the environment will improve patient symptoms and lessen nasal inflammation.

While effects of managing allergen exposure have not been directly assessed in the treatment of acute and chronic RS, it would be logical to limit contact with sensitized antigens to decrease local inflammation in the nasal and sinus mucosa. As has been demonstrated in experimental models, nasal inhalation of antigens in sensitive individuals will increase sinus mucosal thickening and the presence of eosinophils. Since these processes are relevant in the development of symptoms among patients with RS, it is reasonable to decrease exposure to known allergens. Simple strategies to limit allergen burden can be safely and easily applied.

Pharmacotherapy

The mainstay of therapy for the treatment of AR is the use of medications designed to decrease allergic symptoms, downregulate inflammatory processes in the nose, and improve patient quality of life. Many classes of medications have been used in the treatment of patients with AR, and their efficacy has been well established (for a listing of these medication classes, see Table 8.4). The utility of these agents

+++, marked benefit; ++, substantial benefit; +, some benefit; +/–, questionable benefit; –, no benefit.

in treating concurrent RS has only been established in a smaller subset of these medications. This section reviews the medical management of AR, and special note is made of evidence that directly impacts the treatment of patients with RS.

Antihistamines

The most frequently prescribed class of medications for the management of AR is the antihistamines. These products have been widely used in the treatment of patients with AR since the 1950s, and their use continues to be common today. Antihistamines were developed in the 1940s and came into widespread use shortly thereafter. Antihistamines work primarily as selective antagonists to the histamine-1 (H1) receptor, in which they bind to these surface receptors on target cells, change the confirmation of these receptors, and occupy and deactivate the response of the receptor to the binding of histamine. Antihistamines have a wide range of clinical efficacy, as well as marked variability in their adverse event profile.

The earliest antihistamines in general use included medications such as diphenhydramine, chlorpheniramine, and hydroxyzine. In general, these agents were poorly selective H1 antagonists that exerted relatively poor binding at the H1 receptor and therefore required significant doses to exhibit a clinical effect. While they could demonstrate clinical efficacy at sufficient dose levels, these agents were also highly lipophilic and readily crossed the blood–brain barrier. When bound to central H1 receptors, these earlier (or first-generation) antihistamines uniformly caused significant central nervous system effects, including sedation, somnolence, drowsiness, and cognitive and psychomotor impairment. In addition, because these agents were relatively nonselective, their use was also accompanied by anticholinergic side effects such as blurred vision, dry mouth, and urinary retention. They are also frequently associated with increased mucous tenacity, which can be problematic in a patient with RS in whom mucociliary clearance is an essential goal of therapy.

Newer, or second-generation, antihistamines demonstrate significantly greater receptor selectivity than their older counterparts. As a result, they are usually effective at significantly lower doses and are not associated with the range and severity of adverse effects noted with first-generation agents. The first group of these