Upper airway manifestations of granulomatosis with polyangiitis

Clinical presentation

Diagnosis of GPA in patients younger than 20 years is associated with the development of subglottic stenosis.^23,30 The GPA patient with subglottic stenosis may or may not have other active systemic symptoms. The efficacy of systemic therapy often does not correlate with the degree of subglottic stenosis. Importantly, when systemic disease enters remission, the subglottic stenosis may remain due to residual scarring of the subglottis.³¹

Patients with subglottic stenosis may present with hoarseness, cough, wheeze, stridor, or dyspnea on exertion.^27,32 The stridor and wheeze may be confused with the wheeze of asthma, often leading to misdiagnosis.¹⁷

Subglottic stenosis likely begins at a small degree and increases gradually, allowing the patient to adjust his or her breathing pattern until a critical stenotic airway area is reached. Typically, and dependent on their pulmonary health, patients are asymptomatic until about 75% airway stenosis (60% in children).^33,34 At this point, symptoms may become evident and correlate with the degree of stenosis, ranging from cough and mild shortness of breath to life-threatening stridor and obstruction. Importantly, as the airway caliber narrows, mucous plugging becomes a greater concern, as it can cause acute stridulous exacerbations and airway obstruction.

A significant proportion of patients with GPA who have subclinical asymptomatic stenosis may not receive laryngeal examination. Patients who have suspicious clinical histories should be referred for evaluation of subglottic stenosis prior to symptom worsening.

Patients with significant (approximately 80%) stenosis can present with respiratory symptoms that may be life-threatening. Because airway management in this setting is substantially more difficult, the goal should be to obtain a diagnosis and perform intervention before this advanced presentation develops.

Pauzner et al described a possible association between GPA tracheal stenosis and pregnancy.³⁵ Women of childbearing age who have GPA should be counseled about this possible association and the need for close follow-up during the partum and postpartum periods.

Treatment is controversial

The treatment of subglottic stenosis of GPA requires multidisciplinary management by the rheumatologist, otolaryngologist, and pulmonologist. Systemic manifestations of disease are managed by immunosuppressive therapy, but up to 80% of patients may require surgical management of subglottic stenosis, and the remaining 20% will respond to systemic medical therapy.^22,23,36,37 Overall, the treatment of this disease is controversial and varies by center. The therapeutic arsenal consists of conventional immunosuppressive therapy, endoscopic dilation, endoscopic or laser excision, and surgical resection of the stenotic segment followed by reconstruction.

Tracheotomy. Historically, tracheotomies were performed in approximately one-half of patients with airway manifestations of GPA when the patient had active disease or when airway patency could not be adequately maintained. Most of these patients were eventually decannulated.^23,25 At present, tracheotomy is performed infrequently and is reserved for patients who have either a severely tenuous airway (with tracheotomy the only safe option available to obtain a secure airway) or who express a preference for tracheotomy. In a recent study by Hoffman et al,³⁸ tracheotomy was avoided in 21 patients through the use of stenosis dilation procedures.

Dilation. Endoscopic subglottic dilation is the currently advocated method of treatment, and has shown promising results. In two studies with a total of 41 GPA patients who were able to avoid tracheotomy and open surgical procedures, 24% underwent decannulation of previously placed tracheotomies and 24% required only one procedure at an average follow-up of 3.4 and 5 years per study. In these studies, the technique of intralesional corticosteroid with mechanical dilation (ILCD) was performed.^31,36,38

Preferred: Dilation plus medical therapy

Because of the inflammatory etiology of this condition, surgical intervention has the risk of potentially worsening the stenosis. However, combining dilation of the stenosis with aggressive local medical treatment to prevent scar formation and cellular proliferation has been shown to be effective and safe. This treatment modality was recently recommended as the preferred therapy based on a number of relatively small clinical trials for subglottic stenosis, without the benefit of large controlled trials.

Our patient population consists of two subsets: (1) those who respond well to ILCD and systemic medical therapy, requiring a minimal number of dilations before no longer needing procedures because of a possible “burn out” of the subglottic disease, and (2) those who continue to have recurrence of stenosis, requiring repeat ILCD. The latter group requires close long-term observation.

To counter the effects of the exaggerated healing reaction of inflammation (early) and proliferation (late) following injury, two medications are applied to the area of repaired stenosis. The stenotic lesion is first injected submucosally with a long-acting corticosteroid suspension such as methylprednisolone. The solution is injected along the submucosal-perichondrial plane. Incisions are made in a star-like fashion, employing sharp metal microlaryngeal blades or, less commonly, the carbon dioxide laser. These incisions release the constricting stenotic ring and break it up, widening the diameter of the airway and simultaneously preserving islands of intact mucous membrane between the incisions. This epithelium is intended to regenerate and resurface the expanded lumen. Progressive serial dilations are performed using semirigid, flexible, smooth dilators or high-pressure balloon dilation. The next stage involves repeated topical applications of mitomycin-C to further inhibit fibrosis and restenosis by inhibiting cellular proliferation of the vigorous injury cycles of these lesions. Application of mitomycin-C to the dilated area of a laryngotracheal stenosis has been associated with a decreased rate of stenosis relapse.³⁹

Our group at Cleveland Clinic has never used laser surgery alone without dilation on the subglottic stenosis caused by GPA. Incidentally, patients treated with laser surgery in other institutions prior to their referral to the Cleveland Clinic have developed complicating secondary stenoses that required more extensive surgical intervention to overcome the severe secondary superimposed damage. In theory, use of the laser may create unnecessary thermal injury that likely worsens local damage. These patients required laryngotracheal reconstructive procedures or had to undergo establishment of permanent tracheotomies.

CONCLUSION

Granulomatosis with polyangiitis is a rare disease that may manifest in multiple areas of the head and neck. Careful attention to diagnosis and management is critical, as these patients tend to have progressive disease with debilitating sequelae. The rheumatologist, otolaryngologist, and internist should identify patients with any constellation of symptoms that may be typical of GPA. A collaborative effort to diagnose, treat, and follow these patients is paramount to successful disease management.