Учебники / Rhinosinusitis - A Guide for Diagnosis and Management 2008

concerns associated with systemic effect, such as elevation of blood glucose and suppression of the hypothalamic-pituitary-adrenal axis [28]. Furthermore, effect on growth velocity in children appears to be negligible [29]. Topical corticosteroid administration is most commonly achieved using one of many commercially available intranasal steroid sprays; and none of the currently available products is thought to induce significant systemic hormonal effects at prescribed doses.

The primary effect of intranasal corticosteroids is to reduce obstructive symptoms secondary to mucosal inflammatory disease from underlying chronic rhinitis or allergic rhinitis, but decreases in the size of nasal polyps and prevention of postoperative polyp recurrence have been observed as well [30]. Intranasal corticosteroids have also been shown to reduce epithelial and subepithelial eosinophilia in patients with allergic rhinitis when comparing mucosal biopsies before and after treatment during pollen season [31]. It remains unclear how and to what degree intranasal corticosteroids may modulate these responses in the setting of CRS, particularly because studies have shown that penetration into the sinus cavity using a metereddose spray bottle is poor, even in patients who have had prior surgery [13]. Weighing the risks and benefits, however, intranasal corticosteroids are considered a mainstay of long-term medical therapy in CRS patients with or without nasal polyps.

The technique of administration of intranasal corticosteroids has been explored in the literature [32]. To optimize distribution and reduce complications (such as septal erosion or epistaxis), a cross-handed technique is recommended. Patients are instructed to use the right hand to spray the left nostril and the left hand to spray the right nostril; this maximizes delivery to the inferior turbinate, a key structure in the development of congestive symptoms, and also increases the chance of the medication reaching the middle meatus. Various other administration techniques have been explored, and, in selected cases, patients may benefit from steroid instillation with the vertex in a dependent position, such as the “Mecca” position. This technique augments delivery to the middle meatus, frontal recess, or olfactory cleft and may be useful when the endoscopist observes persistent chronic inflammatory disease in these regions. Other head-dependent positions have been described, such as the Mygind position (Fig. 6.3), where the patient lies supine and hangs the head off the edge of the bed. This method appears to be associated with less discomfort than the Mecca position [33]. Other methods of topical steroid application include nasal irrigation with steroid-containing solutions, nebulized steroids, and catheter-assisted steroid instillation.

Various off-label compounded mixtures have been described for irrigation, including mixtures of budesonide with saline at various concentrations. Nebulized steroids, similar to nebulized antibiotics, are administered via specialized commercially available cannulas. Catheter-assisted instillation involves serial infusions of steroid-containing solution through a cannula placed via a surgical sinusotomy. One study examined subjective and objective outcomes of daily infusion of budesonide in postsurgical patients with both CRS and dust mite allergy. After 3 weeks of therapy, data revealed improved symptom scores as well as decreases in eosinophilia and Th2 cytokines compared to placebo controls [34]. In summary, topical nasal steroids can accomplish significant antiinflammatory effect, while

Fig. 6.3 Mygind’s position

sparing the patient from side effects and the toxicities of systemic steroids. These medications, therefore, have a vital role in the long-term management of the CRS patient, particularly in postsurgical patients. At the very least, patients with CRS should be treated with intranasal corticosteroid sprays on a long-term basis. Patients should also be monitored regularly by an otolaryngologist for development of complications associated with corticosteroid sprays, such as epistaxis and septal erosion.

For the sake of completeness, intranasal steroid injection deserves note. In this procedure, performed by an otolaryngologist under endoscopic visualization, triamcinolone is injected directly into polyps or persistent/recurrent foci of polypoid change. Some studies have demonstrated a possible reduction in the need for further sinus surgery when patients underwent close endoscopic follow-up with serial

injections [35]. Patients should be counseled, however, that blindness is a reported, although remote, risk of this procedure.

Systemic Steroids

The value of systemic steroids in the management of chronic inflammatory respiratory disease is well known, particularly in the treatment of asthma and acute exacerbations of asthma. CRS is often described as “asthma of the nose,” and it therefore follows that systemic steroids may take on a similar role in this disease process. In the management of CRS, systemic steroids are typically administered orally in one of the following clinical scenarios: (1) as part of a regimen of maximal medical therapy before considering a patient a candidate for surgery, (2) for use in the perioperative period to reduce the inflammatory burden intraoperatively and to augment optimal healing postoperatively, (3) during exacerbations of CRS, and

(4) in management of comorbidities such as asthma or other allergic/inflammatory conditions. Occasionally, IV therapy is needed, such as if the patient suffers an asthma exacerbation or is unable to take oral medications.

Unfortunately, there is no uniform algorithm regarding exactly when steroids are indicated and what the appropriate dosage and length of therapy may be. This clinical judgment is based on balancing the risks and benefits in any individual patient. Systemic steroids must be used with caution in patients with gastrointestinal ulcers, diabetes, cataracts, glaucoma, and osteoporosis. Nonetheless, oral steroids are considered an integral component in the management of patients with CRSwNP or AFS and in selected patients with comorbid asthma or allergic conditions [36].

Before considering surgery, patients may be treated with a 2- to 3-week steroid taper in conjunction with a prolonged course of antibiotics, as described previously. Initial doses of steroids may begin at 30 mg prednisone daily for patients with CRSsNP. In contrast, patients with CRSwNP may require tapers that begin in the range of 60 to 80 mg per day. Responses may be significant (Fig. 6.4), and these regimens will avert the need for surgery in a subset of patients. However, it remains unclear why some patients do not respond adequately or experience rapid recurrence of symptoms after therapy is discontinued. Suggested oral steroid regimens are outlined in Table 6.1.

Patients who fail maximal medical therapy, and those with diffuse sinonasal polyposis or AFS, are typically considered candidates for surgery. Oral steroids may be initiated from a few days to several weeks preoperatively and then continued postoperatively until resolution of mucosal inflammatory disease is observed endoscopically. Patients with AFS may anticipate prolonged courses (up to several months) and higher dosages. Exacerbations of CRS can be treated using tapers such as those described in Table 6.1. Some patients require chronic low-dose steroid therapy, such as prednisone 5 mg daily or 10 mg every other day. Dosages utilized in chronic lowdose therapy are often lower than that which induces axis suppression. Furthermore, the exact mechanism of action of chronic low-dose oral steroids is largely unknown.

(a)

(b)

Fig. 6.4 (a) Coronal computed tomography (CT) in a patient with allergic fungal sinusitis (AFS). Note the marked paranasal sinus opacification, more pronounced on the patient’s left side. (b) The patient underwent repeat CT with triplanar reconstruction (for intraoperative navigation) after 4 weeks of oral steroid therapy. Note the significant decrease in sinus opacification, particularly when comparing the coronal projection (upper left panel) to the preoperative image

It should be noted that these dosing schemes may require modification based on the patient’s body mass index and comorbidities. Patients who require long-term therapy or frequent tapers should undergo frequent monitoring of blood sugar, bone density, and ophthalmologic status.

CRS, chronic rhinosinusitis; CRSwNP, CRS with nasal polyps; CRSsNP, CRS without nasal polyps; AFS, allergic fungal sinusitis.

Allergy Management

The exact role of allergic rhinitis in the pathophysiology of CRS remains a matter of some controversy, but incidence of allergic rhinitis does exhibit some correlation with CRS. One review summarized that the prevalence of allergic rhinitis reported in patients with CRS ranges from 25% to 84%, with higher prevalence observed in children and in patients undergoing FESS. This review also suggested that mucosal disease, as measured by CT, is greater in patients with inhalant allergies, and that allergen exposure worsens CRS in most patients with both conditions. Additionally, comorbid allergic rhinitis decreases success rates of FESS [5].

Inhalant allergy induces a Th2 cytokine response, with IgE-mediated histamine release in the early phase and inflammatory cell (e.g., eosinophil) influx in the late phase. In addition to histamine, other preformed mediators, as well as synthesized mediators such as leukotrienes, are also involved. The inflammatory milieu observed in allergic rhinitis leads to intuitive links between this disease and CRS and provides a rationale for incorporating allergy management into the management of CRS. There is no consensus regarding the exact roles of antihistamines or leukotriene inhibitors in therapy for CRS, but long-term use of these medications appears rational in patients with suspected inhalant allergies, and particularly those with positive allergy testing. It should be noted that antihistamines appear to be most beneficial in controlling symptoms of nasal pruritis and rhinorrhea, whereas congestive and obstructive symptoms are more responsive to

intranasal corticosteroids. However, relief of obstructive symptoms appears comparable to intranasal steroid when antihistamine is combined with an oral decongestant [37]. Newer-generation, less-sedating antihistamines (loratidine, desloratidine, fexofenadine, cetirizine) should be prescribed, as older-generation, sedating medications (e.g., diphenhydramine) have been associated with significant impairment of alertness and memory [38].

Mucolytics and oral decongestants are potentially useful for symptomatic relief for acute exacerbations of CRS and, occasionally, as long-term therapy. Care must be taken with oral decongestants secondary to potential cardiovascular sympathomimetic side effects. Additionally, extreme care must be taken with the use of topical decongestant nasal sprays, because prolonged (more than 3 to 5 days) use is associated with rebound vasocongestion, or rhinitis medicamentosa. New frontiers in the medical management of allergic rhinitis include also use of omalizumab (Xolair), an anti-IgE monoclonal antibody administered subcutaneously every 2 to 4 weeks. Although omalizumab has been demonstrated to reduce symptoms of allergic rhinitis and asthma, its role in CRS remains unclear. Cost–benefit analysis is an important component to elucidating this issue.

The role of immunotherapy in long-term management of CRS has been the subject of investigation as well. This issue is of particular importance in patients with allergic rhinitis and CRS who undergo FESS, where data has suggested improved outcomes in those who received immunotherapy, except in the presence of nasal polyps [39]. It is possible this lack of observed benefit is secondary to inherent differences in the pathophysiology of CRSwNP, as other studies have demonstrated a higher incidence of polyps in nonallergic patients [40]. Patients with AFS, in contrast, appear to benefit from postoperative immunotherapy [41]. Overall, immunotherapy should be a strong consideration in CRS patients, with or without polyps, who exhibit significant allergies. However, further outcome data are necessary to quantify the benefit of immunotherapy in CRS and in CRS patients who undergo FESS.

Other Immunomodulatory Considerations

Aspirin Desensitization

Patients with CRS in the setting of polyposis, asthma, and aspirin sensitivity represent a difficult group of patients to manage, both medically and surgically. Studies have revealed more vigorous inflammatory disease as well as poorer treatment outcomes compared to aspirin-tolerant patients [42]. Corticosteroids are often necessary in aspirin-sensitive patients for management of both sinonasal and pulmonary components of the disease. In addition to the multiple treatment options described previously in this chapter, aspirin-sensitive patients should also be considered for aspirin desensitization. Patients are treated with escalating doses of aspirin followed by daily maintenance therapy. Protocols for dose escalation vary widely and may be individualized. Outcome studies have revealed success of aspirin

desensitization in reducing CRS exacerbations, hospitalizations for asthma, and use of systemic steroids [43].

Macrolide Therapy

Recent investigations have suggested that macrolide antibiotics may manifest antiinflammatory effects beyond their antimicrobial properties. Excitement about longterm low-dose macrolide therapy began after Japanese reports of efficacy in treating patients with diffuse panbronchiolitis (a condition phenotypically similar to CF in which Pseudomonas and a variety of other bacteria may be involved) [44]. This therapy has also been evaluated in patients with CF in whom improved pulmonary function testing was demonstrated after 4 weeks of therapy [45].

Recent literature has suggested that this modality decreases symptoms of nasal obstruction and postnasal drip and reduces the quantity and viscosity of nasal secretions [46]. Authors have also reported decreased size of nasal polyps secondary to macrolide treatment [47]. Laboratory analysis has associated macrolides with reduction of proinflammatory cytokines (IL-1, IL-6, IL-8, leukotriene B4), neutrophil recruitment, and fibroblast proliferation [48,49]. In patients with panbronchiolitis or CF, it is possible that macrolides may retard biofilm formation by Pseudomonas and other organisms [50].

Although there is no standardized algorithm for macrolide administration, proposed dosing schemes for adults include clarithromycin 500 mg daily or azithromycin 500 mg every other day, and children may be treated with azithromycin 250 mg every other day [11,45]. Most experts agree that 4 weeks of therapy are necessary before symptomatic relief is realized, but selected patients with recalcitrant CRS may be able to achieve benefits only previously achieved with oral corticosteroids [11]. The practitioner must be familiar with the multiple drug interactions possible with macrolides that may lead to Q-T prolongation. The biochemical mechanism for the immunomodulatory effects of macrolides remains largely unknown.

Summary and Conclusions

CRS is a chronic inflammatory disease of multifactorial etiology. Medical treatment continues to evolve and, unfortunately, a standardized treatment algorithm has not been defined to date. It is likely that bacteria do play some role in the disease process, but not in the manner classically observed in acute infections. Thus, antibiotics are a significant component in the management. Patients should be treated with at least 3 weeks of a culture-directed or broad-spectrum oral antibiotic before consideration of surgery. In addition, antibiotic courses may be required postsurgically for acute exacerbations of CRS, where treatment duration is often longer than that required for isolated acute rhinosinusitis. Patients with CRS often benefit from saline nasal irrigation, particularly postsurgically. Furthermore, additional investigation is necessary to clarify the indications and pharmacokinetics of antibiotic-containing saline irrigations. Topical intranasal steroid sprays are

considered a mainstay in the long-term management of CRS, but the role of oral steroids varies depending on the clinical scenario. Oral steroids are considered an important component in the management of patients with CRSwNP and, in particular, patients with AFS. Management of allergic rhinitis, which includes medical therapy, immunotherapy, and reduction of antigen exposure (via avoidance and nasal irrigation) can have a significant impact on patient symptoms and outcome. Ongoing research into the pathophysiology of CRS is necessary to develop more focused medical therapies.

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