Ann Thorac Surg 2002;74:1948-1952
© 2002 The Society of Thoracic Surgeons
Original article: general thoracic
Role of thoracic surgery and interventional bronchoscopy in Wegener’s granulomatosis
Martin J. Utzig, MDa,
Johannes Warzelhan, MDa,
Heinz Wertzel, MDa,
Ingrid Berwanger, MDa,
Joachim Hasse, MDa*
a Department of Thoracic Surgery, University Hospital of Freiburg, Freiburg, Germany
Accepted for publication July 9, 2002.
* Address reprint requests to Dr Hasse, Department of Thoracic Surgery, University Hospital of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany
e-mail: hasse{at}ch11.ukl.uni-freiburg.de
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Abstract
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BACKGROUND: Wegener’s granulomatosis (WG) is defined as granulomatous vasculitis affecting small and medium-sized arteries and veins. Histologically, inflammatory changes with infiltration of the endothelium, fibrinoid necrosis, and formation of necrotizing granulomas are found. Pulmonary involvement is one of the cardinal features of WG and occurs in 85% of patients during the course of disease. Surgery is often required for both diagnosis and therapy.
METHODS: Fifteen consecutive patients are presented to illustrate the spectrum of surgical interventions in WG.
RESULTS: In 8 patients open lung biopsy, wedge resection, or segmental resection for hitherto undiagnosed infiltrate revealed WG. Eight patients presented with tracheal stenosis and all 8 underwent repetitive tracheoscopic dilation. Five patients presented with subglottic stenosis without any signs of pulmonary manifestation. All patients underwent tracheoscopic dilation, 3 in conjunction with glucocorticoid injection therapy. After multiple dilations, 1 patient still had destructing ulcerative tracheitis in which total stenting maintained airway patency. One patient received subglottic tracheal resection prior to multiple dilations; another patient, because of expiratory tracheal collapse, underwent stabilization of the membranous part of the trachea and the large bronchi with a polytetrafluoroethylene implant.
CONCLUSIONS: Surgical lung biopsy in numerous patients established the final diagnosis. Thoracic surgery including bronchologic measures such as bouginage and stenting, however, also has a place in the long-term management of WG.
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Introduction
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Wegener’s granulomatosis (WG) is characterized by an aseptic, necrotizing, granulomatous vasculitis of the small to medium-sized vessels [1]. Preferentially, the upper and lower respiratory tract and the kidneys are affected in more than 90% of cases [2–5]. The most common site of upper respiratory tract disease is the paranasal sinuses, presenting with discharge, sinusitis, and facial pain. Nasal involvement includes progressive obstruction leading to chondral destruction and saddle nose deformity. Stenoses of the trachea, in particular in the sublaryngeal position (subglottic stenosis [SGS]) may result from the disease. Dyspnea, cough, and pleuritic chest pain are among the pulmonary symptoms. Chest roentgenograms typically show (cavitated) nodules, infiltrates, and hilar adenopathy.
Renal involvement is usually preceded by pulmonary disease. Renal failure from glomerulonephritis is often the dominant clinical feature. Although renal and pulmonary involvement are the main aspects of WG, the pathology is not limited to the respiratory and urinary tracts. It may affect almost any organ systemically or locally. Systemic symptoms and signs include fever, malaise, headache, weight loss, anorexia, and arthralgia. Further organ involvement affects joints, skin, eye, ear, nervous system, and heart.
In an attempt to differentiate WG from other forms of vasculitis, the American College of Rheumatology published criteria for the classification of WG [6]. These criteria include abnormal urinary sediment, abnormal findings on chest roentgenogram, oral ulcers or nasal discharge, and granulomatous inflammation on biopsy. Additionally, antineutrophil cytoplasmic antibodies (cANCA) are sensitive and specific for WG.
The presence of granulomatous inflammation on biopsy still remains the best single discriminator for diagnosing WG [6]. The most reliable diagnostic yield can be expected from sugical excision of a representative pulmonary lesion. Complications and irreversible damage such as tracheobronchial stenoses and pulmonary necrosis in selected patients may require interventional bronchoscopy or lung resection. We reviewed 15 consecutive patients to illustrate the spectrum of surgery and surgical bronchology in the assessment of WG.
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Patients and methods
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From February 1992 to July 1998, 15 patients with WG underwent surgical interventions (Table 1).
Eight patients were female; age ranged from 29 to 69 years (mean 49 years). As 5 patients required multiple surgical procedures, 37 interventions were performed.
All patients had upper or lower respiratory tract involvement. Ulcerative sinusitis or rhinitis were seen in 13 patients; 3 patients had a destruction of the nasal skeleton and developed severe saddle nose deformity. None of the patients had rapidly progressive glomerulonephritis, but 3 had microhematuria. At the time of initial diagnosis, 8 patients had positive test results for cANCA, and 3 other patients developed positive test results during their clinical course. Immunosuppressive treatment with systemic glucocorticoid agents and methotrexate or cyclophosphamide was commenced as soon as the diagnosis was established.
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Results
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Parenchymal involvement
Pulmonary parenchymal disease was seen in 10 patients, 3 of whom had additional central airway affection. Two patients underwent major resections as surgical therapy for complications of WG refractory to other treatments. A 65-year-old woman with a history of breast cancer had segmental resection for suspected metastasis in the left upper lobe. The histologic diagnosis, however, was WG and subsequent cANCA testing was positive. Four years later, despite medical treatment, she presented with massive hemoptysis from the same lung. At urgent re’-thoracotomy segments 4, 5, and 6 showed gross destruction also involving the left main pulmonary artery (Fig. 1).
Completion pneumonectomy was performed after intrapericardial control of the pulmonary artery centrally to the ligamentum arteriosum. She died 1 year later at the age of 71 from biventricular heart failure associated to aortic valve stenosis, diabetes, varicosis, and episodes of pulmonary embolism without new alterations attributable to WG.
A second patient, a 38-year-old man, developed necrotizing pneumonia, bronchiectasis, and abscess formation as a result of unstentable destruction of the right intermediate bronchus requiring lower bilobectomy. The diagnosis of WG had been established on tracheo-bronchial biopsies 2 years previously, during the course of treatment of subglottic tracheal and peripheral bronchial stenoses and was confirmed by positive cANCA.
Of the remaining 8 patients with pulmonary lesions, 7 had open or video-assisted explorative thoracotomies to assess the etiology. In 1 woman with concomitant subglottic stenosis and positive cANCA, the lesion disappeared under medical treatment. The choice of open versus video-assisted thoracic surgery (VATS) was determined by the radiologic patterns. The VATS technique was used in 2 patients with peripheral, multiple infiltrates. One patient underwent open atypical resection despite former positive nasal biopsy, because the pulmonary lesion had resembled a malignant process.
Tracheobronchial disease
Eight patients had granulomatous stenosis or bronchial wall destruction, including 3 aforementioned cases with involvement of lung parenchyma. Seven patients had SGS at the cricoid level presenting with a firm circular granulomatous rim with a rather smooth surface, whereas in 1 patient the stenosis was due to irregular granulomatous formations extending from about 1 cm below the vocal cords to the supracarinal segment. Despite medical treatment and six consecutive treatments of dilation for progressive obliteration of the tracheal lumen, this patient received staged stenting with two 50-mm telescoped silicone-coated stents of 20 mm diameter (Boston Scientific) that have been in place for 4.5 years (Fig 2).
In 1 patient SGS developed 18 months after the obstruction of the right intermediate bronchus and subsequent lower bilobectomy. One patient had previously been treated for tracheomalacia and expiratory collapse by right thoracotomy and pars membranacea polytetrafluoroethylene (Gore-Tex; W.L. Gore and Assoc, Flagstaff, AZ) of the trachea and main bronchi as described by Herzog and colleagues [9]. Severe SGS developed 3 years later and was treated by repetitive dilations.
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Fig 2. Chest roentgenogram demonstrating a marked tracheal stenosis bridged by two telescoped stents (patient no. 10). The black squares mark the telescoping ends of the stents.
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The treatment of SGS was subglottic segmental resection as described by Herridge and colleagues [2] in 1 female patient with simultaneous progressive destruction of the nasal skeleton. Most recently, 6.5 years later, this patient presented with mild relapse. In all remaining cases with SGS, dilations were applied under general anesthesia with the use of rigid bronchoscopes (Storz, Tuttlingen, Germany) starting with pediatric-sized instruments with an outer diameter of 6 mm, increasing incrementally to an adult size of 11.2 mm. In the last 3 patients of this series with typical SGS, dilation was accompanied by local submucosal injection of 1 mL cristalloid triamcilone-acetate (Volon A cristalloid suspension; Bristol-Myers Squibb, New York). The injection of 1 mL fractioned into four doses was applied clockwise at 90° intervals with a slightly curved long cannula. The exposure of the subglottic area was achieved with a short mediastinoscope (Storz) and ventilation was maintained with high-frequency jet catheter. This treatment was repeated up to four times.
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Comment
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According to the American College of Rheumatology 1990 criteria for the classification of WG, at least two of the following four criteria must be present: purulent nasal discharge with or without oral ulcers; pulmonary nodules, cavities, or infiltrates on chest roentgenogram; abnormal urinary findings typical of glomerulonephritis; and granulomatous inflammation on biopsy (Fig 3) [6].
As emphasized by several research groups [5, 6, 10], the presence of necrotizing granulomas on biopsy is the best single discriminator and remains the gold standard for the diagnosis of WG. As the upper or lower respiratory tract is affected initially in 73% and 45% of patients, respectively [3, 4], biopsy specimens are commonly taken from the nose, sinuses, or trachea. Yet controversy exists over the efficacy and specificity of these biopsies. DelBuono and Flint [11] and Colby and associates [12], for example, found 53% and 71% of nasal biopsies, respectively, as "diagnostic of" or "consistent with" WG. But according to Devaney and colleagues [13], most oronasal biopsy specimens show nonspecific pathologic changes. They found that nasal and sinus biopsies, due to the small amounts of tissue taken, revealed granulomatous inflammation in only up to 42% of all specimens and additional vasculitis and necrosis in only 16%. In contrast, lung tissue samples are larger and provide more prominent vasculature. Therefore, open or video-assisted lung biopsies usually yield a reliable diagnosis. Indeed, according to Travis and coworkers [14], vascular changes are identified in 94% and parenchymal necrosis in 84% of lung specimens. In our series, 7 patients were diagnosed by open or video-assisted thoracotomics as having WG. As 4 patients had had nonspecific biopsies previously, the open or video-assisted techniques proved to be effective tools for diagnosing WG and for ruling out malignancy.
Although parenchymal lung manifestation is common in WG [1, 3, 4], therapeutic surgery is not usual: in our experience, major resections including completion pneumonectomy were required in only 2 patients for late complications.
Patients with WG are at great risk for severe airway obstruction. According to Rosenberg and colleagues [15], reduced FEV1 and mid-expiratory flow rate may be seen in more than 50%. Respiratory complications such as functional obstructive defects and atelectasis are often caused by tracheobronchial stenosis. Subglottic stenosis occurs in 10% to 23% of all patients and in up to half of younger patients [7, 16–18]. According to Langford and colleagues [7], SGSs develop or progress independently of other features of active WG, even while patients receive systemic immunosuppressive therapy. Surgery is common (74% to 80%) [7, 18]. As intralesional glucocorticoid injections have been successfully used to treat SGS of other etiologies [19–22], Langford and colleagues [7] evaluated this intratracheal approach in WG. They found that SGS developed in 43 of 189 patients (23%); 20 of the 43 underwent up to 21 bronchoscopic dilation/injection therapies (median 3, range 1–21). After intratracheal therapy no other surgical procedures were required on any of the 20 patients. In our experience, the incidence of SGS is higher than reported by LANGFORD and colleagues, and SGS can develop under immunosuppressive medication. Of our 15 patients, 8 had tracheal stenosis, all but one of cricoid type. They underwent intratracheal dilation and 3 of them had GC injection therapy. The median number of treatments each patient received was 2.5 (range 1 to 6). Due to tremendous inflammation and destruction of the trachea, in 1 patient further rigid dilation was technically impossible. Thus, to maintain patency, 2 silicone-covered Wall-stents were inserted. All patients gained substantial relief from dyspnea. Thus, rigid bronchoscopy with dilation of the stenotic segment and glucocorticoid injection therapy provided an effective treatment of WG-associated SGS, although repeat treatment might be necessary
Without treatment, WG runs a rapidly fatal course, with a mean survival of 5 months. Standard therapy, established in the early 1970s, includes oral prednisone and cyclophosphamide; more than 90% of patients treated with this regimen will experience marked improvement within 4 to 8 weeks [3, 8, 23]. However, remission is achieved in only 
75%. Moreover, cyclophosphamide has significant side effects including cystitis, interstitial lung disease, bone marrow suppression, chromosome damage, and thus predisposition to neoplasia, in particular lymphoma and bladder cancer. The significant treatment-related morbidity has prompted a search for less toxic regimens. Although azathioprine and methotrexate are less effective for achieving remission, they may be useful in the maintenance of remission [8, 24, 25]. Because in our study in all but 1 patient SGS developed under immunosuppressive therapy, systemic treatment was continued. However, in the absence of other features of active WG, isolated SGS is managed with intratracheal treatment alone and does not require the institution of systemic immunosuppressive therapy [7].
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Abstract
Introduction
