Active Endobronchial Wegener??s Granulomatosis

Abstract

A 47-year-old woman presented with symptoms of cough, streaky hemoptysis, and shortness of breath of 4 weeks' duration. A high-resolution computed tomography of the chest revealed cavitating nodular lesions. Her antinuclear cytoplasmic antibody (cANCA) was positive. She underwent flexible bronchoscopy, which revealed inflammation and ulceration of the arytenoids and epiglottis of the larynx (Fig. 1), along with multiple ulcerative lesions of the tracheal and the left main bronchus (“ulcerative tracheobronchitis”) (Fig. 2). Her transbronchial biopsy revealed necrotizing granulomatosis with capillaritis. This pathologic finding along with the radiologic and laboratory reports led to the diagnosis of Wegener's granulomatosis (WG).FIGURE 1: Inflammation and ulceration of the arytenoids and the epiglottis.FIGURE 2: Ulcerative tracheobronchitis of the posterior wall of the trachea and left main bronchus.DISCUSSION Wegener's granulomatosis is a multisystemic, idiopathic, necrotizing granulomatous vasculitis, which mostly involves the upper and lower airways, lungs, and the kidneys.1-5 Other sites that are also involved are the joints, eyes, skin, and the nervous system.1 When the condition is restricted to the respiratory system without the involvement of the renal system, it is referred as limited Wegener's granulomatosis, which is seen in 25% of patients.1,5,7,8 The lung is the most frequent and sometimes only organ involved. Approximately 85% of patients develop lung development during the course of the disease, and 45% have lung involvement at presentation.6,10,11 Endobronchial involvement occurs in up to 55% of the patients.4,13 Hoffman et al in his series of 158 patients found 73% of the patients had presented with upper airway involvement and 92% during the course of the disease. Lower airway involvement present in 48% of the patients at the time of presentation and 85% during the course of the disease.1 The endobronchial involvement could be in the form of active inflammation and ulceration of the mucosa called “ulcerating tracheobronchitis.” This is the most common presentation seen in up to 55% of the patients along with inflammatory pseudotumor and cobblestoning of the mucosa. The late complications include subglottic stenosis, tracheal stenosis, bronchial stenosis, and tracheobronchomalacia.1,2,4,7,13-16,22,24 There has been anecdotal case reports of main bronchus necrosis with WG.23 The etiology and pathogenesis of endobronchial involvement in WG remains uncertain. Feinberg had proposed the initial fibrinoid degeneration of collagen at sites where there is extensive deposition such as tracheal and nasal cartilage, eliciting a granulomatous immune response.19,20 This could cause inflammation and edema leading to stenosis and later organizing to form fibrotic stenosis or give rise to tracheobronchomalacia. The lower airway symptoms of WG consist of cough being the most common, followed by dyspnea, hemoptysis, chest pain, and stridor.13 The upper airway symptoms consist of sinusitis, rhinitis, otitis, and epistaxis; occasionally, one can get perforation of the nasal septum and saddle nose deformity resulting from destruction of the nasal cartilage.9 The radiologic features vary depending on activity of WG from masses, cavitating nodules, parenchymal bands, septal thickenings, parenchymal opacification, centrilobular nodules, interstitial thickening, and diffuse alveolar shadows in alveolar hemorrhage.1,9 Cavitating nodules and masses are predominantly seen in active diseases. Antineutrophil cytoplasm antibodies (cANCA) have been found positive in 70% to 90% of patients with active WG and has a sensitivity of up to 92%.21,25-27 The renal system involvement presents with abnormal laboratory findings like proteinuria, active urine sediment with microscopic hematuria to red cell casts, and in case of severe glomerulonephritis, it can be seen with decline of renal function as seen by an increase of serum creatinine and decreased creatinine clearance.5 The American College of Rheumatology has published the criteria for diagnosis of WG from other vasculitis condition, which include nasal or oral inflammation, abnormal chest radiograph, urinary sediment, and granulomatous inflammation on biopsy. Any 2 or more criteria present are suggestive of WG and has a sensitivity of 88.2% and specificity of 92%. The most common indications for flexible bronchoscopy include hemoptysis followed by dyspnea on exertion, stridor or wheezing, persistent cough, hoarseness of voice, biopsy of masses, and nodules or new infiltrates on immunosuppressive therapy to rule out opportunistic infections.3,9,13,18 Therapeutic procedures such as removal of pseudotumors by biopsy forceps, laser and electrocautery along with balloon dilatation in tracheal and bronchial stenosis can also be carried out with flexible bronchoscope.12,13,14,17,22 Untreated WG has a poor outcome with a median survival time of 5 months. Glucocorticosteroids have been the mainstay of treatment of WG, and the combination of cyclophosphamide and glucocorticosteroids has been the best in the treatment of WG.9 Recognition of the early spectrum of the endobronchial involvement is essential to ensure early therapy that may prevent irreversible organ damage. Active ulcerating tracheobronchitis in a case of WG which, if not diagnosed or treated, can progress into late endobronchial complication of subglottic stenosis, tracheal, or bronchial stenosis.13,24