A Case of Granulomatosis With Polyangiitis Complicated With Bronchopleural Fistula

Leyda M. Díaz-Correa, MDRheumatology Fellow

University of Puerto Rico (UPR)Department of Internal Medicine

Division of Rheumatology

Disclosure

• The patient consent to the images presented.

Introduction• Granulomatosis with polyangiitis (GPA) is characterized by upper

and lower respiratory tract involvement.

• Upper respiratory tract (URT) involvement with granulomatous inflammation can affect the nasal cavity, sinuses, trachea, and bronchi.

• Pulmonary manifestations range from asymptomatic lung nodules and fixed pulmonary infiltrates to fulminant alveolar hemorrhage.

• Herein, we present an uncommon pulmonary complication of GPA.

Case Description: History of Present Illness

• 58-year-old woman presented to the emergency room with severe headache around her right eye and nose.

• She had history of chronic sinusitis, nasal deformity, decrease audition, and pulmonary symptoms since one year ago.

• She was diagnosed in the past with pulmonary aspergillosis by bronchoscopy cultures and was treated with voriconazole.

• She had intermittent fever, general malaise, arthralgias, decreased appetite, depressed mood, and weight loss.

• No history of hematuria, hemoptysis, skin rash or joint swelling.

Case Description: Physical ExamVitals T: 36 ˚C, HR: 74/min, BP: 110/73mmHG, RR: 18/min

General Alert, awake and oriented x 3, in mild distress due to pain, chronically ill

HEENT Right eye periorbital swelling, chemosis, and scleromalacia; bilateral sclerae erythema; saddle nose deformity; no oral ulcers

Heart Regular rate and rhythm, no murmurs, no rubs

Lungs Prolonged expiratory phase with wheezing bilaterally, more at left side

Abdomen Bowel sounds present, soft and depressible, non-tender

Extremities No edema, no cyanosis

Neuro No focal neurological deficits

Skin No rash, no ulcers, no purpura, no Raynaud’s, no clubbing

MSK No joint tenderness or swelling, no effusions, full AROM, 5/5 muscle strength upper and lower extremities

Case Description: Physical Exam

Right eye periorbital swelling, chemosis, and scleritis; bilateral purulent secretions

Saddle nose deformity

Case Description: Imaging Studies

• Maxillofacial CT: extensive thickening and sclerosis of the walls of the maxillary sinus, sphenoid sinuses, and ethmoidal air cells. Nodular mucosal enhancement lining the maxillary sinuses and nasal cavity. Perforation of the nasal septum, destruction of the uncinate processes, and destruction of the medial wall of the maxillary sinuses. Asymmetric enlargement of the right lacrimal gland.

• Brain MRI/MRA: No significant stenosis or vessel oclussion.

Chest CT Scan Without Contrast

Bilateral cavitary nodules and left distal mainstem bronchus segmental stenosis, as can be seen in GPA. Gas collection at the left apical pleuroparenchymal interface. A bronchopleural fistula cannot be excluded.

Case Description

• Investigative studies– Bronchoscopy: total collapse of the left main bronchus; cellular

findings suggestive of a granulomatous process; culture negative for mycobacteria or fungi; cytology negative for malignant cells.

– PPD: negative– Ophtalmologic exam: dacryocystitis, conjunctivitis; necrotizing

scleritis of right eye and sclreomalacia– Laboratories:

• ESR: 94 mm/hr• P-ANCA, C-ANCA: negative• Antiproteinase 3: positive • Antimyeloperoxidase: negative• Urinalysis: negative• BUN: 16 mg/dl, Creatinine: 0.60 mg/dl

Nasal mucosa with focal necrosis, mixed inflammatory infiltrate with multinucleated giant cells. H&E X200

Nasal Biopsy

Nasal Biopsy

Area showing necrosis, abundant neutrophils, eosinophils and plasma cells. Several multinucleated giant cells are also present (arrow). H&E X400

Case Description

• Diagnosis: GPA • Treatment– Methylprednisolone IV at 2mg/kg for 7 days, then

continued on Prednisone 1mg/kg for 4 weeks followed by taper

– Cyclophosphamide 2mg/kg PO daily– Trimethoprim /Sulfamethoxazole prophylaxis– Antibiotic therapy for dacryocystitis and

conjunctivitis

Case Description:Follow-up and Outcome

• After six months of treatment, she had marked improvement in sinus and facial symptoms.

Right eye periorbital swelling, chemosis, and scleritis resolved.

Follow Up Chest CT ComparisonChest CT without contrastAxial view before treatment

Chest CT with contrastAxial view after treatment

Interval resolution of the cavitary bilateral pulmonary nodules with residual scars. Persistent left apical gas filled cavity at the pleuroparenchymal interface. Left distal mainstem bronchus stenosis persisted.

Follow Up Chest CT ComparisonChest CT without contrast Sagital view before treatment

Chest CT with contrast Sagital view after treatment

Interval resolution of the cavitary bilateral pulmonary nodules with residual scars. Persistent left apical gas filled cavity at the pleuroparenchymal interface. Left distal mainstem bronchus stenosis persisted.

Discussion

• Only a few cases of bronchopleural fistula in patients with GPA have been reported.

• In this case neither the bronchial stenosis nor the bronchopleural fistula improved after systemic immunosuppression with cyclophosphamide and high dose steroids.

• Pulmonary complications in GPA should be recognized and treated with a multidisciplinary approach.

Discussion

• Literature review of patients with GPA and bronchopleural fistula:

Reference Age Pulmonary Manifestations

Therapy

Koyama S, et al. (2010) 28 y/o Pleural effusion and broncho-pleural fistula

Fistula resolved with immunosuppressive treatment alone.

Tao Y, et al. (1994) 36 y/o URT; empyema and bronchopleural fistula

Fistula formed during immunosuppressive treatment, and herpes zoster infection; thoracotomy was required.

References

1. Holle JU, et al. Rheum Dis Clin North Am. 2010 Aug;36(3):507-26.

2. Koyama S, et al. Sarcoidosis Vasc Diffuse Lung Dis. 2010 Jul;27(1):76-9.

3. Tao Y, et al. Nihon Kyobu Shikkan Gakkai Zasshi. 1994 Nov;32(11):1073-7.

Acknowledgements

• UPR, Department of Internal Medicine, Division of Rheumatology: Luis M. Vilá, MD; Grissel Ríos, MD.

• UPR, Department of Radiology: José Maldonado-Vargas, MD; Nicolle de León-Tellado, MD.

• UPR, Department of Pathology: Román Velez-Rosario, MD; Glorimar Rivera-Colón, MD.