A previously healthy 57-year-old gentleman presented with a 3-month history of progressive rhinosinusitis including nasal obstruction with bloody discharge, anosmia, and ageusia. He developed night sweats, a 25-pound weight loss, and a productive cough with blood streaked sputum (producing 5-15 mL of blood per day). There was no associated shortness of breath, chest pain, wheezing, rash, ocular, gastrointestinal, urinary, or neurologic symptoms. Social history revealed a 30 pack-year smoking history and previous exposure to aluminum dust and chemical sealants while working at a sheet metal company. There were no risk factors for tuberculosis infection. Initial antibiotic treatment for pneumonia and sinusitis was prescribed, with no subsequent clinical improvement. Urgent referral to respiratory medicine was requested.
On physical examination in the respiratory clinic, the patient's heart rate was 112 beats per minute, and there was a visible ulcer in the right nare, with bloody crusting. The remainder of the physical exam was unremarkable. Laboratory investigations revealed a reduced hemoglobin of 122 g/L, elevated white blood cell count of 19.1 x 109 L-1, and platelet count of 624 x 109 L-1. Electrolytes, creatinine, and liver enzymes were normal. There was a positive c-Antineutrophil Cytoplasmic Antibody test (c-ANCA) with an elevated anti-PR3 antibody titre (253 CU). The anti-MPO and anti-GBM antibodies were negative. Urinalysis revealed no blood or casts, but was positive for protein (1+).
Fig. 1 presents a computed tomography (CT) scan of the chest at the time of initial presentation which showed multiple bilateral mass-like lesions measuring up to 5cm, some demonstrating central necrosis and cavitation with thick and irregular walls. Some of the lesions were pleural-based with suggestion of chest wall extension and there was no pleural effusion.
An urgent bronchoscopy was arranged and showed friable and bloody mucosa in the upper lobes bilaterally (Fig. 2a and b).
Endobronchial biopsies were taken in the upper lobe airways and sequential washings did not reveal evidence of pulmonary hemorrhage (successively bloody returns from saline bronchoalveolar lavages). Biopsies demonstrated large areas of neutrophilic necrosis (so called "basophilic necrosis"), granulomatous inflammation with multi-nucleated giant cells, mucosal ulceration, and squamous metaplasia (Fig. 3). There was no necrotizing vasculitis in the sample. Staining and cultures were negative for acid fast bacilli and fungus.
Given the constellation of endobronchial tissue with neutrophilic necrosis and granulomatous inflammation, positive c-ANCA, and clinical presentation with sino-pulmonary symptoms, the diagnosis of granulomatosis with polyangiitis (GPA) was made. Glucocorticoid treatment with prednisone 60 mg daily was promptly initiated, and after consultation with rheumatology, oral methotrexate was added.
Twenty days later, the patient returned for follow-up after an episode of sudden onset shortness of breath with right scapular chest pain that radiated anteriorly. An urgent chest radiograph revealed a large right sided loculated pneumothorax with small fluid component (Fig. 4).
A chest tube was inserted immediately, and pleural fluid studies revealed pH of 6.9, glucose level <0.1 mmol/L, and predominant fluid neutrophils of 89%. Pleural fluid cultures were negative for bacterial growth. A chest CT was performed, demonstrating enlargement of two pre-existing pulmonary cavities with air fluid levels, open communication with an adjacent bronchus, and hydropneumothorax (Fig. 5). The remaining pulmonary lesions demonstrated improvement when compared with previous imaging (Fig. 5). The pneumothorax and empyema resolved over time with pleural drainage and broad-spectrum intravenous antibiotic treatment.
Pneumothorax with small pleural effusion from a chest radiograph. Posteroanterior chest radiograph demonstrates a large right pneumothorax with small pleural effusion. There are parenchymal abnormalities in the right upper lobe and left perihilar lesion corresponding to residual lesions seen in previous CT.