Physical Examination, Complementary Tests, and Functional Status Assessment

In our patient, the diagnosis of subglottic stenosis occurred in the absence of other features of active disease. Tracheobronchial manifestations of WG may take place after remission has been achieved with appropriate immunosuppressive therapy, and airway disease may proceed to airway scarring and stenosis.¹ In the absence of persistent active inflammation, however, the development of SGS does not necessarily indicate failure of immunosuppressive therapy. As in our patient, published and anecdotal evidence suggests that when airway obstruction is caused by fibrotic scarring rather than by active inflammation, strictures develop independently of other features of WG and are unresponsive to systemic immunosuppressive therapy.² SGS, seen in approximately 8.5% to 23% of patients, is considered the most common central airway manifestation of WG. It may be the initial presenting feature in 1% to 6% of patients.³ Isolated SGS is observed in approximately 50% of patients with strictures; in the other half, strictures occur while patients are receiving systemic immunosuppressive therapy for disease activity involving other sites.⁴

This patient had no stridor on neck auscultation. This finding is consistent with the bronchoscopic classification of moderate airway narrowing based on a stenotic index of 53%. Indeed, stridor is usually a sign of severe laryngeal or tracheal obstruction, signaling more than 70% airway lumen narrowing.^5–7 Anatomically fixed obstruction of moderate degree such as that seen in our patient usually causes symptoms with exertion but not at rest.

The absence of ANCA in our patient was not unexpected. In fact, the presence or absence of ANCA neither confirms nor excludes a diagnosis of systemic vasculitis, and both negative and positive predictive values will be strongly influenced by clinical presentation. Most patients with generalized WG have glomerulonephritis and are ANCA positive (90%), whereas those without renal involvement have a lower incidence of ANCA (70%). Among patients with limited forms of the disease, such as those without significant renal involvement and in whom upper respiratory tract symptoms predominate, only 60% are ANCA positive.⁸

Comorbidities

Lack of cardiac involvement by two-dimensional echocardiography (2D echo) was reassuring because WG disease relapse is often associated with heart involvement, less intensive initial treatment in terms of lower CYC doses, and shorter length of time on prednisone >20 mg/day.⁹ No evidence of renal or hepatic dysfunction was found; if surgical or bronchoscopic interventions were to be provided under general anesthesia, such dysfunction could adversely affect perioperative fluid management, increase risks for bleeding, and cause postoperative changes in neurologic status.

Support System

Our patient was married and had a good social support system. As with other chronic conditions, considerable evidence suggests that vasculitis negatively affects patients’ health-related quality of life (HRQL),¹⁰ which usually includes general health, physical functioning, emotional role limitations, physical role limitations, social functioning, mental health, and energy/vitality. Contrary to cancer, which is often considered a “family affair” with significant psychological and emotional impact on family members,¹¹ results of recent studies show that spouses of patients with ANCA-associated vasculitis (AAV), including WG, scored similarly to national norms. Patients with AAV, however, scored lower than normal on all HRQL subscales with the exception of bodily pain. When age, education, race, illness duration, and disease severity were controlled, no significant sex differences in HRQL were noted for patients or spouses.¹²

Patient Preferences and Expectations

This patient had a very active lifestyle and had clearly expressed a desire for treatment. She was prepared to consider all available therapeutic options, including dilation, laser, surgery, and even airway stent insertion if necessary. She agreed to our request that alternatives be discussed with her husband, so they could participate together in medical decision making. Health care provider investment in patient-centered conversations with family members is usually justified because management of chronic illness is a dyadic process that often involves spouses.¹³

Indications

Symptomatic WG-related subglottic stenosis is often part of the spectrum of a multisystem inflammatory process that warrants administration of immunosuppressive agents. Some patients, however, develop or continue to have symptoms of airway obstruction after clinical remission induced by standard therapeutic regimens. Although airway manipulation during periods of active WG should be minimized, other treatment modalities may be warranted¹⁴ after disease has first been controlled in collaboration with a rheumatologist. A bronchoscopic procedure or open laryngotracheoplasty may be offered to improve dyspnea and restore satisfactory airway lumen patency by mechanical dilation with or without laser.

In patients with tracheal obstruction, dyspnea depends on the degree of airway narrowing, as well as on flow velocity. Airway pressures increase dramatically at rest when well over 70% of the tracheal lumen is obliterated. Our patient’s active lifestyle caused high flow velocity through her stenotic airway. This further increased the pressure drop through the stricture, increasing the work of breathing.¹⁵ Improving airway patency to a lesser (mild) degree of narrowing (<50%) would allow our patient to improve exercise capacity and shortness of breath. In one physiology study, the effect of the normal glottis on airway pressure drop is, in fact, of the same order as that of 50% airway narrowing.¹⁶ Thus when airway narrowing is treated, symptoms and exercise tolerance may be dramatically improved by small changes in airway caliber, and perfect normalization of airway lumen patency may not be necessary.

Contraindications

No contraindications to rigid bronchoscopy were known in this patient. However, although this patient had normal dentition without loose teeth, a crown recently placed on the right upper first premolar could potentially be damaged during rigid intubation. The cervical spine range of motion was normal, but her mouth opening measured only two fingerbreadths. This could also increase the risk for tooth damage during rigid bronchoscopy. A plastic tooth guard, rather than a gauze pad, used to protect the teeth would further diminish mouth opening.

Expected Results

Rigid intubation was planned using a small (9.5 mm)-diameter rigid bronchoscope. The scope would be introduced through the vocal cords under direct visualization so as to ensure a secure airway at all times. Careful attention would be necessary to avoid trauma to the teeth given her limited mouth opening and her recently placed dental crown.

In patients with subglottic strictures, the therapeutic success of rigid bronchoscopic dilation is variable. In one study (follow-up after the first dilation of 25.4 ± 14.1 months), two of nine patients never recurred after the initial dilation, and seven required more than one dilation, with one patient requiring permanent tracheostomy.¹⁷ In another study, three patients required repeated treatment using neodymium-doped yttrium aluminum garnet (Nd:YAG) or carbon dioxide (CO₂) laser–guided resection to control airway narrowing.¹⁴

Team Experience

Experience and expediency might result in reduced complications, a greater chance to restore airway patency, and earlier discharge from the hospital, although studies are needed to support this hypothesis. Prospective and ongoing data analysis for bronchoscopic procedures, both feasible and ongoing, might answer these questions in the future.¹⁸

Risk-Benefit Analysis

The risk of further airway injury, resulting in scarring and consequent recurrence of stenosis, is outweighed by the benefit of improving airway patency to improve this patient’s exercise capacity and quality of life. Recurrence, however, may be related to the disease process or to the bronchoscopic treatment itself.

Therapeutic Alternatives for Restoring Airway Patency

Therapeutic alternatives include systemic, bronchoscopic, and open surgical therapies. If disease severity is judged to be life threatening or to be putting an affected organ at risk for irreversible damage, such as airway or renal disease, glucocorticoids in combination with CYC remain the treatment of choice. In less severe cases, methotrexate is the preferred alternative to CYC. Regardless of the severity of other organ manifestations, severe tracheobronchial disease should initially be treated with a combination of oral glucocorticoids and CYC. For patients with documented tracheobronchial disease, some experts use high-dose inhaled glucocorticoids, such as fluticasone 440 to 880 mg twice daily, which is usually initiated when oral glucocorticoids have been tapered to daily doses less than 30 mg.¹⁹ Because our patient had failed two immunosuppressive drugs (glucocorticoids and methotrexate) and was intolerant to CYC, one might consider her as having refractory disease. A monoclonal anti-CD20 antibody, rituximab, was shown to be successful in inducing remission in patients with refractory but limited WG manifestations, including chronic sinusitis, pulmonary nodules, orbital pseudotumor, and subglottic stenosis.²⁰ Others, however, report systemic therapy–induced cures at all disease locations except the subglottis.²¹

Because isolated airway lesions secondary to scarring may improve only after interventional procedures, the decision to use concomitant immunosuppressive medications depends on clinical and laboratory features that may suggest active disease.³ Overall, only 20% to 26% of subglottic strictures caused by Wegener’s granulomatosis respond to glucocorticoids alone or in combination with another immunosuppressant. The remaining 74% to 80% of patients usually require interventional therapies to improve symptoms. In our patient, without clinical or laboratory evidence of other organ involvement, the isolated SGS was considered a manifestation of the scarring process, and she was offered an interventional procedure.