Upper airway manifestations of granulomatosis with polyangiitis

Treatment

Refractory CRS in GPA is a complex problem for which aggressive surgical intervention is often counterproductive. Unfortunately, traditional medical therapies are also often inadequate to treat progressive sinonasal symptomatology. As the nasal tissue becomes devascularized, loss of normal mucociliary function aggravates the sinus pathology, and clinical symptoms may worsen. Simple antibiotic regimens used to manage uncomplicated sinusitis are often inadequate in these patients. The subsequent progression to frank necrosis in localized regions creates an intranasal foreign body, allowing bacterial colonization, which is often refractory to antibiotics because of the inability of drug tissue penetration into these devascularized nasal structures.^12,17

Medical management must be tailored to be effective in this complex intranasal milieu. Successful treatment requires a multifaceted and often prolonged treatment course. A high index of suspicion should be maintained for Staphylococcus aureus. As a rule, endoscopically obtained cultures should be used to guide antibiotic selection. Several weeks of culture-directed antibiotics followed by topical antibiotic irrigations (eg, mupirocin irrigations) can be useful to reduce the frequency of sinonasal exacerbations.

Frequent saline irrigations using high-volume, high-flow irrigation devices (as opposed to low-volume, low-flow applicators such as nasal spray bottles) can be an excellent adjunct to maintenance therapy and are effective in clearing debris and augmenting mucociliary clearance in affected nasal cavities and those with septal perforations. Occasional in-office endoscopic debridement of large crusts adherent to intranasal structures or the edges of a septal perforation can also help to improve obstructive symptoms.

Surgery for refractory cases. Surgery should be reserved for refractory cases unresponsive to maximal medical efforts or those cases with impending complications (ie, mucoceles). Overall, only 16% of patients with sinonasal GPA required surgical intervention in a large series of 120 patients at our institution. In this series, one-third of all patients had undergone previous functional nasal surgery at an outside institution without resolution of symptoms. Anecdotal evidence suggests that surgery for GPA can contribute to additional scarring and lead to protracted sinonasal symptoms.^10,18

The decision to perform surgery is individualized and based on severity of the disease process, patient expectations, and surgeon expertise. In our experience at Cleveland Clinic, functional endoscopic sinus surgery in the setting of GPA is a surgical challenge, given extensive alteration of the sinonasal anatomy from previous surgery, prior and ongoing inflammation, chronic crusting, and scarring. Consequently, it has been our practice to employ conservative efforts prior to consideration of surgery. A complete surgical cure is exceedingly rare, and the patient should be counseled about the possible need for revision surgery and ongoing nonsurgical therapies. Meticulous postoperative care with weekly postoperative debridement, saline or antibiotic irrigations, and culture-directed antibiotics, is essential during the early postoperative recovery phase.

Management of epiphora. The most common ophthalmologic findings in patients with GPA include chronic epiphora and orbital pseudotumor. With the advent of advanced endoscopic techniques, the otolaryngologist plays a greater role in the surgical management of these ophthalmologic disease entities. In a series reported by Cannady et al,¹⁰ endoscopic dacrocystorhinostomy was performed successfully in seven patients, including one revision.

Nasal reconstruction for saddle-nose deformity: effective in selected patients. The progressive loss of septal support that occurs with the enlarging anterior septal perforation often results in significant collapse of the cartilaginous midvault of the nose. The tip cartilages in turn also begin to lose projection, resulting in a shortened nose with the characteristic saddle-nose deformity. The psychologic impact of this disfiguring facial abnormality is significant. The loss of midvault support also results in worsening nasal obstruction and increases the incidence of anosmia as the superior nasal vault becomes obstructed. For these reasons, patients often seek referral for potential reconstruction.

Despite the potential benefits, the general consensus in the medical community has been that surgical procedures on the nose should be avoided in GPA patients.¹⁷ Most nasal destruction in these patients is the consequence of poor tissue perfusion from the active vasculitis. Poor wound healing, reconstructive graft resorption, and worsening necrosis have been observed in patients who have undergone ill-advised surgical procedures.

These poor outcomes do not, however, preclude the potential for safe and effective surgical intervention. In three small published series, good surgical outcomes were achieved but the procedures were done in very highly selected patients and were modified to address the specific clinical issues seen in GPA patients.^19–21 The critical step in achieving a good outcome is working closely with the patient’s rheumatologist to identify an appropriate clinical window during which the patient’s disease process is in a period of relative remission. The second major factor is to modify the surgical techniques to take into account the very poor vascular framework of the recipient nasal bed.

Management of COM. Because the COM in patients with GPA is frequently secondary to nasopharyngeal disease, systemic control of GPA is the first priority. Systemic control is also the first-line treatment for patients with mixed or sensorineural hearing loss, or with vertigo. For continued or symptomatic middle ear effusions that do not resolve with systemic therapy, placement of a ventilation tube may be considered. In patients with significant hearing loss, hearing amplification devices may be warranted.^15,22 Cochlear implant devices in GPA patients are experimental and may pose undue risks of meningitis.

SUBGLOTTIC STENOSIS AND TRACHEAL MANIFESTATIONS

Subglottic stenosis affects 10% to 20% of patients with GPA.^1,23,24 Because of its potential life-threatening airway complications, patients should be carefully assessed for this disease manifestation. It may be the only manifestation of GPA or may be part of a spectrum of other disease manifestations. Therefore, the work-up for subglottic stenosis of unknown etiology should always include an evaluation for GPA.

Pathophysiology and disease course

The etiology of subglottic stenosis in GPA is not well understood. Theories primarily involve the vulnerability of the subglottic tissues to damage, chronic inflammation, and scarring.²⁵ The combination of vasculitis in the setting of active inflammation may synergistically produce a hyperactive reparative mechanism in GPA patients that leads to cartilaginous fibrotic scarring and stenosis. Wound healing can be divided into the phases of inflammation, proliferation, and remodeling. An imbalance or exaggerated response of any of these levels (and likely all) produces an abnormal healing response.²⁶ Similarly, each of these phases may be targeted to improve the healing process.

Patient evaluation

The presence of subglottic stenosis must be considered in a GPA patient with respiratory symptoms. As part of the routine initial evaluation, an office-based nasopharyngeal/laryngeal endoscopy using a flexible laryngoscope should be performed to assess the presence and severity of luminal airway narrowing. Flexible laryngoscopy reveals a circumferential narrowing of the subglottis. The stenotic tissue may vary from friable with erythematous and inflamed mucosa to a rigid mature fibrotic band, depending on the inflammatory state of the stenosis.^18,27

Subclinical stenosis may be identified with routine endoscopy. An appropriate baseline is needed to follow the progression of disease and to adjust the timing of any potential intervention. The ability to digitally record a patient’s examination allows further tracking of disease and is commonly used in our practices.

Although flexible fiberoptic examination is critical in diagnosis and follow-up, intraoperative direct laryngoscopy using rigid laryngoscopes and telescopes provides the optimum view of the subglottis. In particular, this view provides greater information on the length and degree of the stenosis and allows evaluation of potential stenotic segments in the inferior trachea.

Spiral CT with 3-dimensional reconstruction of the laryngotracheal lumen and virtual bronchoscopy may provide information that complements laryngoscopy. CT may permit assessment of the entire tracheobronchial pathway. Because 15% to 55% of GPA patients have additional bronchial stenotic segments, assessment of the entire airway is important.^28,29