A Paradoxical Puzzle: Delayed reaction during treatment for disseminated BCG

Abstract

A 74-year-old man with no previous history of tuberculosis presented with malaise, pyrexia (39°C) and 35kg weight loss, 16 months after TURBT for transitional cell carcinoma of the bladder and BCG instillation. He was pancytopaenic (Hb 84, Plt 99, WCC 2.94) and CT imaging showed splenomegaly, small pleural effusions and a sinusoidal lesion which on biopsy was not malignant. He did not have any promiment lymphadenopathy or pulmonary consolidation. Autoimmune and HIV screening were negative (CD4 310 (57%)) and both TTE and TOE showed no vegetations. IGRA/Quantiferon-Gold testing was positive and bone marrow biopsy yielded granuloma but no AFB on histology. Standard quadruple therapy was commenced for suspected disseminated mycobacterial disease. Mycobacterial cultures of early morning urine, blood and bone marrow were all positive and later identified as BCG on whole genome sequencing, sensitive to Rifampicin, Isoniazid, Amikacin and Moxifloxacin with undetermined Ethambutol sensitivity. Fully compliant with treatment, he developed a solid part cystic irregular enhancing 35mmmass encasing his left internal carotid artery seven months into treatment. ϒ-IFN-axis testing showed adequate responses to IL12 and IFN stimulation. Biopsy revealed AFB-positive granulomata leading to additional steroids for a presumed paradoxical reaction as well as treatment intensification with Moxifloxacin and Amikacin whilst awaiting cultures, the latter of which was discontinued following negative culture results and clinical and radiological improvement. Paradoxical reactions occur not infrequently (2-23%) and can present delayed (14-270 days) following initiation of treatment. He gained 25kg and made an uneventful recovery having received 18 months of BCG treatment.