Pulmonary disease following intravesical BCG treatment.

Abstract

The potentially toxic nature of intravesical BCG is illustrated by two patients who developed profound systemic illness with fever, rash, basal crackles, and bilateral shadowing on the chest radiograph after treatment.Bacillus Calmette-Guerin (BCG) is an attenuated strain of Mycobacterium bovis that has been used in the treatment A 75 year old man was treated with intravesical BCG (120 mg of BCG in 60 ml of saline) for transitional cell carcinoma of the bladder. After his third monthly treatment he presented with a seven day history of cough and fever and increasing dyspnoea for one day. He was febrile and he had bilateral basal inspiratory crackles and palpable purpuric skin lesions 3-4 mm in diameter over the thorax. A full blood count showed mild leucocytosis. Alkaline phosphatase activities were mildly increased. A chest radiograph showed bilateral interstitial infiltrates. Granulomas were seen on transbronchial lung biopsy. Skin biopsy showed erythema multiforme; neither granulomas nor acid fast bacilli were seen. Intensive care was needed because of hypoxaemic respiratory failure five days after admission to hospital. Isoniazid 300 mg daily, rifampin 600 mg daily, and prednisone 60 mg daily were started on the day of his transfer. On the 14th day an open lung biopsy was performed because of increasing hypoxaemia and progressive radiographic infiltrates. Diffuse alveolar damage (acute and organising) and granulomatous inflammation were noted (figure). No acid fast bacilli were seen and cultures were negative for mycobacteria. Viral studies, blood cultures, and serological tests for atypical organisms gave negative results.

Bone marrow infection with bacillus Calmette-Guérin (BCG) after intravesical immunotherapy

“…Bone marrow involvement during disseminated disease with BCG has been described in only a few cases. Patients showed involvement of the lungs and/or the liver in addition to bone marrow infiltration as part of a septic process [5][6][7][8][10][11][12]. In our patient and a few others dissemination of BCG was probably restricted to the bone marrow, as chest X-rays or computed tomography scans were negative and no signs of hepatitis were present [9,13].…”

“…True infection has been doubted in some cases of BCG disease, as the result of failure to identify the causative pathogen by culture or molecular biological methods, and clinical manifestations were classified as hypersensitivity reactions [5]. However, in many other cases the positive results of culture and the efficacy of anti-mycobacterial treatment suggest active BCG infection [6][7][8][9][10][11][12][13]. A recent study distinguished between early adverse reactions occurring within 3 months after instillation and late reactions occurring after more than a year [4].…”

“…In a series of 2026 treated patients, fewer than 5% experienced focal infections such as granulomatous prostatitis or epididymo-orchitis, or more generalized manifestations such as hepatitis, pneumonitis and sepsis (reviewed in [4]). In the majority of cases non-caseating granulomas have been found, and involvement of the bone marrow in disseminated disease was reported for only very few cases [5][6][7][8][9][10][11][12][13]. We describe a patient who developed fever, weight loss and pancytopenia two years after completion of BCG therapy, with granulomatous infiltration of the bone marrow and isolation of M. bovis-BCG from the urine.…”

Pulmonary tuberculosis due to bacille Calmette-Gu�rin

“…cussion [9,11,13,24]. There are indicators of a persisting antigenic stimulus over prolonged periods in activated granulomas of the bladder wall [14,17].…”

“…The presence of epitheloid cell granulomas of a tuberculoidlike type obtained by transbronchial biopsy or necropsy has been considered as diagnostic for tuberculous pathogenesis, but in no case have mycobacteria been demonstrated by culture [9,13,24]. The pathogenesis of pulmonary infiltrates following BCG immunotherapy is unknown; specific infection or hypersensitivity pneumonitis after BCG are among the possibilities under disAbbreviation ."…”