Modern Rheumatology

ISSN: 1439-7595 (Print) 1439-7609 (Online) Journal homepage: http://www.tandfonline.com/loi/imor20

Granulomatosis with polyangiitis (Wegener's granulomatosis) diagnosed by transbronchial biopsy from stenotic portion of mainstem bronchus Sho Sendo, Goh Tsuji, Ryosuke Umeda, Yoshihide Ichise, Shunichi Kumagai & Yujiro Suzuki To cite this article: Sho Sendo, Goh Tsuji, Ryosuke Umeda, Yoshihide Ichise, Shunichi Kumagai & Yujiro Suzuki (2015) Granulomatosis with polyangiitis (Wegener's granulomatosis) diagnosed by transbronchial biopsy from stenotic portion of mainstem bronchus, Modern Rheumatology, 25:4, 649-652 To link to this article: http://dx.doi.org/10.3109/14397595.2013.844305

Published online: 18 Oct 2013.

Submit your article to this journal

Article views: 50

View related articles

View Crossmark data

Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=imor20 Download by: [Chinese University of Hong Kong]

Date: 05 November 2015, At: 12:54

http://informahealthcare.com/mor ISSN 1439-7595 (print), 1439-7609 (online) Mod Rheumatol, 2015; 25(4): 649–652 © 2013 Japan College of Rheumatology DOI: 10.3109/14397595.2013.844305

CASE REPORT

Granulomatosis with polyangiitis (Wegener’s granulomatosis) diagnosed by transbronchial biopsy from stenotic portion of mainstem bronchus Sho Sendo1, Goh Tsuji1, Ryosuke Umeda1, Yoshihide Ichise1, Shunichi Kumagai1, and Yujiro Suzuki2

Downloaded by [Chinese University of Hong Kong] at 12:54 05 November 2015

1Center for Rheumatic Diseases, and 2Department of Respiratory Medicine, Shinko Hospital, Kobe, Japan

Abstract

Keywords

This report concerns a case of granulomatosis with polyangiitis (GPA) (Wegener’s granulomatosis (WG)) with bronchus narrowing. Although nasal biopsy had been performed three times, no positive histology for GPA (WG) could be obtained. Flexible bronchoscopy revealed diffuse erythema, edema of the mucosa and stenosis of the right mainstem bronchus. Transbronchial biopsy identified granuloma with giant cells. These findings led to a diagnosis of GPA (WG). This case suggests that biopsy from the bronchus is useful for diagnosis of GPA (WG).

Granuloma, Granulomatosis with polyangiitis, Transbronchial biopsy, Stenosis

Introduction Granulomatosis with polyangiitis (GPA) (Wegener’s granulomatosis (WG)) is an uncommon systemic disease characterized by necrotizing granulomatous vasculitis of the upper and lower respiratory tracts and by glomerulonephritis. In addition, variable degrees of disseminated vasculitis involving both small arteries and veins may occur. We present an exceptional case of GPA (WG) with stenosis of the right mainstem bronchus.

Case report A 63-year-old Japanese male was admitted to our hospital because of nasal pain, headache, low-grade fever and hearing loss. He had a medical history of dyslipidemia and hypersensitivity pneumonitis and a family history of rheumatoid arthritis in his sister. The initial diagnosis of sinusitis and otitis media led to sinus surgery and myringotomy. Histology of a resected nasal polyp showed nonspecific inflammation. Postoperative treatment with antibiotics brought no improvement in the patient’s complaints, and he developed coughing and suffered weight loss of 4 kg in the last 4 weeks of the treatment. The clinical course is shown in Figure 1. The subsequent physical examination revealed tenderness of the nose and forehead, saddle nose deformity and scleritis of both eyes. Results of another physical examination were unremarkable. The complete blood count showed leukocytosis (15,000/μl) and mild thrombocytosis (53.5 ⫻ 103⫺/μl). C-reactive protein was elevated to 12.5 mg/dl and myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) was significantly elevated to 12.8 U/ml (normal upper limit: 3.5 U/ml). Other biochemical tests showed no remarkable changes. The urinary analysis findings were unremarkable, showing no occult blood or proteinuria.

Correspondence to: Sho Sendo, MD, The Center for Rheumatic Diseases, Shinko Hospital, 4-47, Wakinohama-cho,1-chome, Chuo-ku, Kobe City, Hyogo Prefecture 651-0072, Japan. Tel: ⫹ 81-78-261-6799. Fax: ⫹ 81-78261-3004. E-mail: [email protected]

History Received 2 April 2013 Accepted 10 May 2013 Published online 18 October 2013

Sinus computed tomography (CT) showed thickening of nasal and sinus mucosa (Figure 2), while chest radiography showed thickening of pleura on the apex of the right lung (Figure 3a). In addition, the chest CT showed significant narrowing of the right mainstem bronchus (Figure 4a) and presence of a macular consolidation on the apex of the right lung (Figure 3b). Three nasal biopsies were performed before the transbronchial biopsy, but their histology showed only nonspecifi c inflammation (Figure 5). However, flexible bronchoscopy revealed diffuse redness, edema of the mucosa and stenosis of the right mainstem bronchus (Figure 6). The abnormal mucosa was biopsied and its histology showed infi ltration of infl ammatory cells and a granuloma with giant cells (Figure 7a,b). There were no signs of malignancy or tuberculosis. Findings of nasal and sinus infl ammation, otitis media, chest CT scan abnormalities, granulomatous infl ammation in the transbronchial bronchus biopsy specimen and elevated MPO-ANCA led to the diagnosis of GPA (WG). Immunosuppressive therapy with cyclophosphamide (100 mg/day) and prednisolone (25 mg (0.5 mg/kg)/day) was initiated. All of the clinical symptoms improved rapidly and the patient was completely asymptomatic within 1 month. Chest CT after 1 month of treatment showed improvement in the right mainstem bronchus stenosis (Figure 4b).

Discussion GPA (WG) is an incurable form of necrotizing granulomatous vasculitis that affects the upper respiratory tract, lungs, kidneys and other organs. The American College of Rheumatology (ACR) 1990 diagnostic criteria include abnormal urinary sediment, abnormal findings on chest radiographs, oral ulcers or nasal discharge and granulomatous inflammation in biopsy specimens. The presence of two or more of these four criteria is associated with a sensitivity of 88.2% and a specificity of 92.0% [1]. The pathological features of GPA (WG) are necrotizing vasculitis involving predominantly small arteries and veins, granuloma consisting of histiocytes and multinucleated giant cells and “geographic” necrosis [2,3]. Since our case met two of the ACR

650

S. Sendo et al.

Mod Rheumatol, 2015; 25(4): 649–652

Downloaded by [Chinese University of Hong Kong] at 12:54 05 November 2015

Figure 1. Clinical course of the case.

Figure 2. Sinus CT shows thickening of nasal and sinus mucosa (sinusitis).

criteria: nasal discharge and granulomatous inflammation in the biopsy specimen, he was diagnosed with GPA (WG). In 2006, Richard Watts et al. presented the classification algorithm for ANCA-associated vasculitis [4], according to which,

Figure 4. a. Chest CT before treatment shows significant narrowing (arrow) of right mainstem bronchus. b. Chest CT after 1 month of treatment shows significant improvement (arrow) in narrowing of right mainstem bronchus.

if histological evidence is not obtainable but surrogate markers for WG are present and PR3 or MPO-ANCA is detected, the patient is classified as GPA (WG). In our case, even if transbronchial biopsy had not been performed, surrogate markers for GPA (WG) (bronchial stenosis, bloody nasal discharge and crusting for over 1 month, chronic sinusitis and otitis media for over 3 months) were present and MPO-ANCA was detected, so that our patient could be classified as GPA (WG). On the other hand, application of the Chapel Hill Consensus Conference (CHCC) criteria involves only strict histological definitions, not surrogate markers or ANCA. For classification of GPA

Figure 3 a. Chest radiography on admission shows thickening of pleura on apex of right lung (arrow). b. Chest CT before treatment shows macular consolidation on apex of right lung.

Figure 5. Histology (hematoxylin–eosin staining: ⫻ 200) of nasal mucosal biopsy shows nonspecific inflammation.

GPA diagnosed by transbronchial biopsy

DOI 10.3109/14397595.2013.844305

651

Downloaded by [Chinese University of Hong Kong] at 12:54 05 November 2015

Figure 6. Findings of flexible bronchoscopy: diffuse flare, edema of the mucosa and stenosis of the right mainstem bronchus.

(WG) according to CHCC criteria, there had to be evidence of granulomatous change in the biopsy specimen. Moreover, MPO-ANCA is not entirely specific for GPA (WG) but is also present in microscopic polyangiitis. We therefore decided to perform transbronchial biopsy, which proved the presence of the pathological features of GPA (WG). The manifestations of GPA (WG) in the respiratory tract include nasal stenosis, nasal cartilage necrosis, subglottic stenosis, tracheal and bronchial stenosis, granulomatous nodules and masses, alveolar infiltrations and cavities [5]. Stenosis of the subglottis and proximal trachea is seen in 16% of GPA (WG) patients during the course of the disease [6]. However, stenosis of the distal trachea and one of the mainstem bronchi is a rare initial manifestation of GPA (WG) [7].

Histopathological confirmation of the diagnosis of GPA (WG) should be the gold standard. A biopsy from nasal mucosa is easily performed because of the high rate of involvement in the nasal area and low risks associated with extensive biopsy (samples measuring over 5 mm are generally required). Nevertheless, the histopathological changes are often non-specific and show only signs of acute or chronic inflammation. Biopsies from the nasal region thus frequently fail to establish a diagnosis of GPA (WG) [11,12]. On the other hand, clinical and pathological series have shown that the respiratory tract is a better biopsy site for GPA (WG), and a high diagnostic yield from open lung biopsy or videoassisted thoracic surgery has been established [8]. However, these operations involve certain risks. On the other hand, transbronchial biopsy is associated with fewer risks and can therefore be used for patients with less severe lung disease. Schnabel et al. reported that transbronchial biopsy of alveolar tissue seldom yielded positive results for GPA (WG) patients with mild-to-moderate pulmonary disease unless they were obtained from grossly abnormal lung areas. However, a high rate of positive findings was associated with transbronchial biopsy of ulcerative exophytic or stenotic tracheobronchial lesions [9]. Since airway involvement in GPA (WG) can mimic tracheobronchial tumors such as adenoid cystic carcinoma, tracheal amyloidosis and stenosis from tuberculosis [10], these diseases must be excluded before a diagnosis of GPA (WG) can be established. Although our patient could have been diagnosed with GPA (WG) on the basis of the presence of surrogate markers for GPA (WG) and positive ANCA, transbronchial biopsy made the diagnosis more definitive. Because evidence of granulomatous inflammation (positive findings for GPA (WG)) in these tissues could not be obtained from the three preceding nasal biopsies, we performed transbronchial biopsy from the right mainstem bronchus and proved infiltration of inflammatory cells and presence of granuloma with giant cells. In cases of GPA (WG) with bronchial stenosis, it can thus be effective for establishing a definite diagnosis to try transbronchial biopsy from the tracheobronchial lesion even if no positive findings can be obtained from other tissues.

Acknowledgements We thank Dr. Rieko Ito, Department of pathology, Shinko Hospital and Dr. Arata Motoyama, Department of Radiology, Akashi City Hospital for the generous suggestion of the patients.

Conflict of interest None. Figure 7. a. Histology (hematoxylin–eosin staining: ⫻ 200) of bronchoscopic biopsy specimen from right mainstem bronchus reveals infiltration of inflammatory cells and granuloma with a giant cell (arrow). b. This histology (hematoxylin–eosin staining: ⫻ 400) shows a high power view of the granulomatous inflammation with two giant cell (arrow).

References 1. Leavitt RY, Fauci AS, Bloch DA, Michel BA, Hunder GG, Arend WP, et al. The American College of Rheumatology 1990

652

2.

3. 4.

5.

Downloaded by [Chinese University of Hong Kong] at 12:54 05 November 2015

6.

S. Sendo et al.

criteria for the classification of Wegener’s granulomatosis. Arthritis Rheum. 1990;33(8):1101–7. Mark EJ, Matsubara O, Tan-Liu NS, Fienberg R. The pulmonary biopsy in the early diagnosis of Wegener’s (pathergic) granulomatosis: a study based on 35 open lung biopsies. Hum Pathol.1988;19(9): 1065–71. Devaney KO, Travis WD, Hoffman GS, Leavitt RY, Lebovics RS, Fauci AS. Interpretation of head and neck biopsies in Wegener’s granulomatosis. Am J Surg Pathol.1990;14(6):555–64. Watts R, Lane S, Hanslik T, Hauser T, Hellmich B, Koldingsnes W, et al. Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies. Arthritis Rheum Dis. 2007;66(2): 222–7. Rodrigues AJ, Jacomelli J, Baldow RX, Barbas CV, Figueiredo VR. Laryngeal and tracheobronchial involvement in Wegener’s granulomatosis. Rev Bras Rheumatol. 2012; 52(2):227–35. Hoffman GS, Ker GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, et al. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992;116(6):488–98.

Mod Rheumatol, 2015; 25(4): 649–652

7. Daum TE, Specks U, Colby TV, Edell ES, Brutinel MW, Prakash UB, et al. Tracheobronchial involvement in Wegener’s granulomatosis. Am J Respir Crit Care Med.1995;151(2):522–26. 8. Travis WD, Hoffman GS, Leavitt RY, Pass HI, Fauci AS. Surgical pathology of the lung in Wegener’s granulomatosis. Review of 87 open lung biopsies from 67 patients. Am J Surg Pathol.1991;15(4): 315–33. 9. Schnabel A, Holl-Ulrich K, Dalhoff K, Reuter M, Gross WL. Efficacy of transbronchial biopsy in pulmonary vasculitides. European Respir J.1997;10(12):2738–43. 10. Ananthakrishnan L, Sharma N, Kanne JP. Wegener’s Granulomatosis in the Chest: High-Resolution CT Findings. Am J Roentgenol. 2009;192(3):676–82. 11. Devaney KO, Travis WD, Hoffman G, Leavitt R, Lebovics R, Fauci AS. Interpretation of head and neck biopsies in Wegener’s granulomatosis. A pathologic study of 126 biopsies in 70 patients. Am J Surg Pathol. 1990;14(6):555–64. 12. Gottschlich S, Ambrosch P, Kramkowski D, Laudien M, Buchelt T, Gross WL, et al. Head and neck manifestations of Wegener’s granulomatosis. Rhinology. 2006;44(4):227–33.

Granulomatosis with polyangiitis (Wegener's granulomatosis) diagnosed by transbronchial biopsy from stenotic portion of mainstem bronchus.

This report concerns a case of granulomatosis with polyangiitis (GPA) (Wegener's granulomatosis (WG)) with bronchus narrowing. Although nasal biopsy h...
2MB Sizes 0 Downloads 0 Views