BCG

Abstract

Various toxicities: 5 case reports In a case report, 5 patients [including 1 female neonate, and 4 males aged 30–82 years; not all exact ages stated] were described, who developed lymphonodal abscess, pneumonia, lacrimal gland abscess, chronic osteomyelitis, persistent fever, miliary pneumonia, urinary tract symptoms, scrotal abscess or cystitis following administration of BCG [Bacillus Calmette-Guerin] for bladder cancer or as a vaccine [not all routes stated; dosages and duration of treatments to reaction onsets not stated]. Case 1: A female neonate received BCG vaccine over the left gluteus muscle at birth. After 48 hours of vaccination, she developed left inguinal abscess along with lymphadenopathy and spontaneous perforation. A lymph node biopsy revealed a granulomatous lymphadenitis along with acid-fast bacilli. Subsequently, the BCG strain was isolated. She was then treated with isoniazid. However, one month later, she presented with a right homers fracture and radiological findings indicating osteolytic regions in the lower limbs, clavicle and right ulna. A diaphysectomy was suggested and rifampicin and ethambutol were added to the treatment regimen. Antibiotic treatment was retained for 4 years. At 8 years of age, she underwent a left pneumonectomy because of recurrent lung infection episodes and bronchoscopic evidence of granulomatous tissue occluding the main left bronchus. Molecular analysis detected an innate interferon-γ receptor R1 defect and an impaired immune response was suspected. At 12 years of age, she developed a lacrimal gland infiltration and a right supraclavicular and left mammary masses. Drainage and incision indicated acidfast bacilli and caseification in the specimen. She was prescribed rifabutin and pain therapy up until admission in April 2017 (at 30 years of age) to the Infectious Diseases Unit in Italy for chronic osteomyelitis involving the right wrist. At admission, she appeared apyretic and suffered of widespread joint pain. An MRI revealed bone expansion, bone marrow oedema, periosteal reaction and lytic areas of the right wrist. A CT scan indicated lytic bone lesions suggesting right homer distal epiphysis and carpus bilaterally. A 8-Fluorine fluodeoxiglucose positron emission tomography with a CT scan (18F-FDG PET/CT) confirmed osteolytic lesions along with high inflammatory activity. Thus, post-BCG vaccination till current presentation, she was diagnosed with lymphonodal abscess, pneumonia, lacrimal gland abscess and chronic osteomyelitis secondary to BCG. She was then continuously treated with rifampicin, isoniazid and ethambutol for 2 months. Additionally, rifampicin and isoniazid were retained for another 4 months till the next visit. Her condition improved and she required no pain therapy. A repeat 18F-FDG PET/CT performed a year later confirmed reduced lesions of high intensity 18F-FDG uptake. Due to a significant history of immune defect, she is still ongoing treatment with rifampicin and isoniazid with a continuous follow-up carried out at the outpatient unit. Case 2: A 72-year-old man, was admitted in April 2019 to the Infectious Diseases Unit in Italy for fever, shivering, anorexia, malaise, irritative symptoms of lower urinary tract infections and severe hypotension leading to syncope. Seven months earlier, he had undergone an excision of the superficial bladder cancer and received a 6-week course of intravesical BCG single dose every week preceded by the first monthly instillation. Last dose of BCG was administered 2 weeks prior to current admission. A BCG disease was suspected due to a significant clinical history. A chest auscultation revealed a reduced sour vesicular murmur. An intradermal Mantoux test reported an induration of 8mm in diameter after 72 hours. A CT scan of the pelvi, abdomen and thorax revealed right pleural effusion, mediastinal lymph nodes enlargement with extensive nodularity in both lungs with a military pattern near to ground glass and consolidative regions in the left upper lobe and right medium lobe. Prostrate reported enlarged, abnormal and colliquative regions in the left lobe. A PCR on urine tested positive for mycobacteria. Thus, he was diagnosed with symptoms associated with urinary tract infection, persistent fever and miliary pneumonia secondary to BCG. He was treated with ethambutol, rifampicin and isoniazid for 33 days until an increase in LDH, GOT/GPT and GGT levels were observed. His treatment with rifampicin and isoniazid was stopped and ethambutol along with moxifloxacin was continued for 6 months. His condition improved and a thorax CT scan performed in September 2019 showed a significant reduction in size and number of nodularity observed earlier. Case 3: A 69-year-old man presented to the Infectious Diseases Unit in Italy for progressive and painful monolateral scrotal swelling. He had undergone a transurethral resection of a papillary bladder carcinoma two years earlier, followed by a intravesical BCG therapy with six instillations every week. The following year, an additional course of BCG was necessary due to a recurrence suspected with a cistoscopy follow-up. Six weeks later, an irrigation cytology and control cystoscopy showed no bladder carcinoma and normal urine cytology. However, he was prescribed with maintenance dose of intravesical BCG one instillation every 3 weeks for a period of 3 years. Following last instillation, he complained of scrotal swelling a month later. He had a medical history of ulcerative rectocolitis and type 2 diabetes, treated with mesalazine and metformin respectively. He had a high BP and low RR. His left testis had a soft painful mass along with a cutaneous fistula. An ultrasound scan indicated an abscess. Thus, a diagnosis of scrotal abscess secondary to BCG was confirmed and a surgery was suggested. A funiculus spermaticus ligature and left orchiectomy was performed and the specimens were sent for microbiological analysis and histopathology. Histological findings on testis reported a chronic granulomatous disease presenting in the form of caseous necrosis, purulent abscess overlap and giant cells Langhans type. A chest CT showed millimetric nodules and apical fibrosis bilaterally in the right pulmonary lobe. He was initiated on isoniazid, ethambutol and rifampicin due to the history of BCG therapy. Eventually, he was discharged with an instruction to continue antitubercular therapy for 6 months including isoniazid and rifampicin and 2 months of ethambutol therapy. Case 4: A 61-year-old man was admitted to the Infectious Diseases Unit in Italy in September 2019 with a complaint of perineal pain, scanty and frequent urinations, macroscopic haematuria and strangury. His medical history was significant of recurrent polymicrobial urinary tract infections and a transurethral resection of the bladder due to high grade and relapsing urothelial bladder cancer invading the muscle and submucosa. He was then treated with intravesical BCG for a 6-weekly instillation therapy scheduled between January 2019 and February 2019, which was maintained till current admission. An intradermal Mantoux test revealed an induration of 9mm in diameter after 72 hours. A urine analysis showed acid-fast bacilli and a biopsy during cystoscopy indicated a granulomatous chronic cystitis along with giant cells Langhans type. A diagnosis of chronic ulcerative and granoulatous cystitis secondary to BCG were confirmed. Due to these significant findings, he was treated with ethambutol, isoniazid and rifampicin. Two months’ post induction phase, ethambutol was stopped and rifampicin and isoniazid were retained for another 4 months. Thereafter, a good clinical condition was observed. Case 5: An 82-year-old man was admitted to the Infectious Diseases Unit in Italy was subjected to transurethral resection of the bladder and BCG instillation therapy in August 2019 following detection of dysuria and high grade fever. His medical history was significant of poorly differentiated urothelial carcinoma. Upon admission, a Quantiferon TB Gold and tuberculin skin test both tested positive. A urine culture showed ESBL-producing Klebsiella oxytoca for which he was initiated colistin and amikacin. His symptoms showed slight improvement. His dysuria and fever persisted, for which a high-resolution chest CT scan was performed indicating large cavity lesion along with satellite nodules in right upper lobe. Due to his clinical history, laboratory findings and cystitis and fever secondary to BCG, he was initiated on pyrazinamide, ethambutol, isoniazid and rifampicin which resolved fever and dysuria in 12 days. Eventually, he was discharged and a bronchoscopy and urological re-evaluation were advised. A bronchoalveolar lavage 1