Intravesical BCG (bacillus Calmette-Guerin) instillation is a first-line treatment for superficial transitional cell carcinoma of the bladder. A rare but severe complication of BCG immunotherapy is the development of disseminated BCG disease with pulmonary involvement. When it occurs, it manifests as a bilateral intersititial pneumonitis. In the present report, we describe a patient treated with intravesical BCG immunotherapy who presents with subacute interstitial lung disease and noncaseating granulomas in transbronchial biopsy tissue. His radiographic changes improved following antituberculous therapy.
A 72-year-old white male presented with malaise, nonproductive cough, intermittent fevers, occasional chills, and 30 pound weight loss over 2 weeks. He was undergoing BCG instillation for transitional cell carcinoma of the bladder diagnosed a year ago, with his most recent treatment about 3 weeks ago. He reported few episodes of night sweats. He denied dyspnea, wheezing, and hemoptysis. His PMH was significant for adult-onset diabetes, psoriasis, melanoma on the right arm resected 3 years earlier, transitional cell carcinoma of the bladder, glaucoma, kidney stones, hypertension, anxiety, and CAD. He had no prior known lung disease or abnormal CXR. He had a remote history of tobacco use, no history of alcohol or illicit drugs use, and no inhalational exposures. He had no pets or recent travel. Physical exam was unremarkable except for a SpO2 of 91% on room air and multiple patchy areas of psoriasis on his arms, legs and trunk. Laboratory data revealed mild pancytopenia. CT scan of the chest demonstrated innumerable diffuse bilateral tiny (1–2 mm) pulmonary nodules; a thyroid nodule; mild anterior pericardial thickening, and no appreciable lymphadenopathy (see attached films). Two out of 3 sputa cultures subsequently grew MAI. Bronchoscopy was performed with RLL BAL negative for malignant cells, Legionella, fungi, viruses, and AFB. Transbronchial biopsies revealed several small, non-necrotizing granulomas within the alveolar parenchyma (see attached picture) and were negative for malignancy. A GMS stain was negative for fungi. Acid fast bacilli (AFB) stain identified a single organism within a granuloma (see attached picture). Additional immunoperoxidase studies with antibodies directed against S-100, keratin AE1/AE3, and CD68 show no aberrant staining pattern. He was diagnosed with BCG-induced granulomatous lung disease and started on INH 300mg/d and Rifampin 600mg/d with significant clinical and radiographic improvement within 3 months.
Pneumonitis with miliary nodular or interstitial pattern on chest radiography and CT scanning develops in 0.7% of patients with intravesical instillation of BCG. Dyspnea, accompanied by fever and malaise are the presenting symptoms and progression to respiratory failure can occur. Symptoms can present as early as a few hours or as late as several months following the BCG therapy. The key finding in disseminated BCG disease is the formation of noncaseating granulomas in distant organs; however detection of BCG organisms in tissue samples can be difficult. Recommended treatment for disseminated BCG disease includes a combination of antituberculous medications (with the exception of pyrazinamide, to which BCG is typically resistant). The use of corticosteroids as a standard treatment is controversial.
Intravesical instillation of BCG treatment for transitional cell carcinoma of the bladder is occasionally complicated by BCG pneumonitis. Management of BCG-induced granulomatous pneumonitis should include antituberculous therapy.
Polina Inkoulova, No Financial Disclosure Information; No Product/Research Disclosure Information