A Remedy for Hoarseness in a Patient With Granulomatosis With Polyangiitis

Abstract

To the Editor: Granulomatosis with polyangiitis (GPA) is a multisystemic disease characterized by a necrotizing, granulomatous vasculitis that affects primarily the upper and lower respiratory tracts and kidneys. It typically presents as sinusitis, pulmonary infiltrates, and glomerulonephritis.1 Unlike the well-described pulmonary parenchymal involvement, tracheobronchial manifestations are less recognized by physicians. These extraparenchymal pulmonary manifestations include involvement of the oral cavity, larynx, and trachea. Airway involvement is found in 15% to 55% of patients.2–4 Laryngeal involvement is uncommon but if present, may occur either as a presenting feature or a late-stage manifestation of the disease and will occur in approximately 10% to 20% of cases.5–6 The subglottis and upper trachea are most commonly involved, with the most common finding being circumferential scarring and critical narrowing of the airway. Vocal cord involvement has rarely been reported and is usually not a manifestation of the disease. We report a case of GPA with subglottic stenosis and contiguous involvement of the vocal cords. A 31-year-old woman was diagnosed with GPA in 2001 (+PR3-ANCA). Organ involvement included nasal septum, sinuses, joints, hearing loss, orbit, skin, and lung parenchyma. Her longstanding history included multiple relapses and resistance to standard treatment options including prednisone, cyclophosphamide, methotrexate, azathioprine, and rituximab. She presented to us in 2008 stating that she had noticed a nonproductive cough for the past 2 months. During that time, her cough had worsened and began to interfere with her sleep. In addition, she had become more short of breath, being able to climb only 7 stairs at a time before having to stop and rest. On physical examination, wheezing was evident with decreased breath sounds over the right hemithorax. This was worrisome for bronchial airway involvement; a bronchoscopy was performed, which demonstrated a normal appearing larynx. A mild stricture (10%) was found in the subglottic area and a more severe stenosis was found in the bronchus intermedius (95% stenosis), both of which had a benign appearance. The latter was injected with depomedrol, incised using an electrocautery blade followed by balloon dilatation and mitomycin application. Since that time she had several bronchoscopic procedures over the years with therapeutic interventions in the bronchus intermedius to relieve recurrent stenoses. In 2012, she presented with worsening of her symptoms after discontinuing prednisone secondary to headaches, nausea, and vomiting. She noticed worsening shortness of breath and hoarseness of her voice, which resulted in a repeat bronchoscopy. At the level of the larynx, she had good vocal cord motion bilaterally, with no decrease in movement compared with normal. However, the true cords were now observed to be erythematous and edematous, with areas that had the appearance of granulomatous changes (Fig. 1). In the subglottis, there was a narrowing posteriorly of approximately 20%. We did not biopsy the true vocal cords secondary to the risk of affecting her voice long term. However, a biopsy of the tracheal plaque revealed respiratory and metaplastic squamous mucosa with acute and chronic inflammation with fibrosis. These findings were consistent with active Wegener disease. She was given a course of rituximab and high-dose prednisone. Follow-up bronchoscopy 1 month later revealed complete resolution of the changes seen on her vocal cords and she no longer had hoarseness of her voice.FIGURE 1: GPA with contiguous vocal cord involvement.Tracheobronchial GPA includes subglottic, lower tracheal, and bronchial stenosis, tracheal and endobronchial mass lesions, or ulcerative tracheobronchitis, and less commonly tracheobronchial malacia, follicular bronchiolitis, and bronchiolitis obliterans. Vocal cord involvement has rarely been reported with only a few reports in the literature. In one case report, a woman presented with a 4-month history of hoarseness. A granulomatous lesion involving the vocal cords was detected by a laryngoscopy. GPA was confirmed by biopsy and in this case was the first manifestation of isolated laryngeal involvement.7 In our patient, we opted not to biopsy the true vocal cords. We felt that it was a relative contraindication because of the risk of affecting her voice long-term and low diagnostic yield. The largest report of vocal cord involvement in GPA is from a study in 1998, in which the objective was to describe the computed tomography (CT) appearances of tracheal stenosis in GPA. Ten patients with tracheal involvement were assessed with both spiral CT and bronchoscopy. In 3 patients, there was a contiguous involvement of the vocal cords, which were noted to be thickened and deformed, evident on both CT scan and bronchoscopy; 2 further cases with mild vocal cord inflammation were identified only by bronchoscopy.8 Their conclusion was that spiral CT is a noninvasive technique, which can provide accurate assessment of tracheal lesions and can be complementary to bronchoscopy in the evaluation of vocal cord involvement. The evaluation and diagnosis of a patient with suspected tracheobronchial GPA requires a combination of clinical assessment, serologic testing, sinus and chest imaging, pulmonary function tests, bronchoscopy, and tissue biopsy. The diagnosis is established when serologic and histopathologic evidence of vasculitis and granulomatous inflammation are present in a patient with a compatible clinical presentation. In contrast to open-lung biopsy, bronchoscopic tissue sampling of tracheobronchial luminal abnormalities only reveals histologic features of Wegener’s in a minority of cases. The general principles of medical therapy for GPA also apply to patients who have tracheobronchial involvement. Vocal cord involvement is rarely reported and is most likely a manifestation of a late complication of fully developed or previously treated GPA. Biopsies of this region rarely demonstrate vasculitis and therefore should be avoided if there is an established diagnosis. When vocal cord involvement is bronchoscopically visualized, immediate therapy is warranted to avoid a poor outcome. Our patient significantly improved with prompt treatment of rituximab and high-dose prednisone. Sonali Sethi* Michael Machuzak† *Interventional Pulmonary Medicine †Center for Major Airway Disease, Cleveland, Cleveland Clinic, Respiratory Institute, Cleveland, OH