BCG-associated osteomyelitis R4 鍾寧 2016/1/20

Case introduction (1) 2y9m old girl, previously healthy and normal development child T-L spine deformity was noticed by her parents since half an year ago. She was hit by door on the back about 2 months ago, and her activity was also decreased since 2 months ago. She could walk downstairs and upstairs by herself smoothly before, but recently she“crawl”upstairs. Recent 2 months Come to Ped neuro OPD Growth: BH: 89.1 cm (15-25th%), BW: 11.5 Kg (3-15th%) PE: no significant finding; kyphosis NE: decreased DTR of lower limbs 2015/12/28

Case introduction (2) T-spine X-ray (2015/12/28) T8 vertebrae planae leading to angulated and excessive kyphosis posture.

Spine MRI (2015/12/29) T8-10 spondylodiscitis with a) collapsed T9 vertebral body b) T8 & T10 osteomyelitis c) Paraspinal abscess formation from T5-T11 with anterior and posterior extension d) Intraspinal canal extension with mass effect on spinal cord e) Equivocal myelopathy at the level of T8-10

MRI TB-PCR(+) AFS(+) AFS(+) AFS(+) MRI CT-guide draiage Ciprofloxacin Ethambutol MRI Rifater (RIF/INH/PZA) Rifampin Isoniazid Streptomycin TB-PCR(+) CDC: MTBC/M. bovis BCG AFS(+) AFS(+) AFS(+) CT-guide draiage MRI

CT-guide draiage Ethambutol (total 1 month) Rifampin Isoniazid (INH+RIF 1~1.5 year) Streptomycin (10 days) Moxifloxacin (total 6 months) CT-guide draiage

Spine MRI (2016/01/07) T8-10 spondylodiscitis with a) Collapsed T9 vertebral body b) T8 & T10 osteomyelitis c) Paraspinal abscess formation from T5-T11 with anterior and porterior extension, mild interval decreased size (AP diamter from 16mm to 13.5mm & R-L diameter from 47mm to 46mm) d) Still intraspinal canal extension with mass effect on spinal cord

BCG-associated osteomyelitis

History of BCG The first use of BCG is a liquid vaccine, which was certified by the WHO since 1953. In 1979, BCG was changed to freeze-dried vaccine manufactured from Japan Tokyo 172 strain. In the past 30 years, the BCG vaccine targets are mainly preschool children aged between 1 and 5 years.

The effectiveness of BCG vaccination BCG vaccine can actually protect against tuberculosis meningitis and disseminated disease in infants, effectively decrease infant deaths or complications due to tuberculosis. There was a significant decrease in the children mortality rate of pulmonary and extra-pulmonary tuberculosis under five years old. Children without completing the BCG vaccination had 16 times higher incidence of tuberculosis meningitis than children with BCG vaccination.

Adverse reactions of BCG vaccination The most common are local lymphadenitis or suppurative lymphadenitits, located in axilla area on injection site or near clavicle area. The incidence of suppurative lymphadenitis is between 100 and 1000 people per million doses. BCG vaccine may cause severe adverse reactions, such as BCG osteomyelitis/osteitis and disseminated BCG infection. Disseminated BCG disease is highly related to immunodeficiency. Most of the BCG osteomyelitis/osteitis patients were children < 2 years old and healthy before the onset of the disease According to WHO, the incidence of BCG-related osteomyelitis/osteitis is around 1-700 per million doses. In Taiwan, the incidence is 50 per million based on the surveillance data from 2008 birth cohort.

BCG-associated osteomyelitis Typically presents in children 1-2 years after BCG inoculation If a child presenting chronic symptoms like pain, limping or local swelling of extremities, BCG osteomyelitis may be considered. Lower limbs was the most common involved site, followed by the axial skeleton, upper limbs, and multiple bones. Epiphysis or metaphysis of long bones are mostly involved, usually show as osteolytic lesions. The lesion is slow with poor response to traditional antibiotics

Taiwan experiences (1) Thirty-eight patients with Mycobacterium bovis BCG–associated osteomyelitis/osteitis, were identified during Taiwan’s vaccine injury compensation program during 1989–2012. The laboratory program which was designed to differentiate BCG from other species of the M. tuberculosis complex, was established in 2004. NC Chiu, et al. Mycobacterium bovis BCG–Associated Osteomyelitis/Osteitis, Taiwan. Emerging Infectious Diseases Vol. 21, No. 3, March 2015

Taiwan experiences (2) The detected incidence of BCG osteitis/osteomyelitis increased from 3.68 cases per million vaccinations during 2002–2006 to 30.1 per million during 2008–2012. The average age at inoculation was 16.2 ± 16.6 days. Symptoms or signs began 3–32 months (average 12.4 ± 6.1 months) after BCG vaccination; for 68%, symptoms or signs developed 7–18 months after vaccination. Interval between Mycobacterium bovis BCG inoculation and osteomyelitis/osteitis onset

Taiwan experiences (3) Extremity bones were more commonly involved than axial bones. For 30 (79%) children, extremity bones were involved: 14 right lower limbs, 7 left lower limbs, 6 left upper limbs, and 3 right upper limbs. The tibia was the most common site (9 patients), followed by ankle bones (8 patients), femur (4 patients), radius and thumb (3 patients each), humerus and knee (2 patients each), and ulna (1 patient). In 8 (21%) children, axial bones were involved: 5 sternums, 2 thoracic vertebrae, and 1 right rib. No specific abnormalities were found with regard to blood cell counts and inflammation markers or to chest radiographs. NC Chiu, et al. Mycobacterium bovis BCG–Associated Osteomyelitis/Osteitis, Taiwan. Emerging Infectious Diseases Vol. 21, No. 3, March 2015

Taiwan experiences (4) Thirty-two (84%) children underwent surgery (excision, debridement, open biopsy), 4 children received arthrotomy (3 ankle and knee joint), and 2 children underwent only aspiration biopsy. Two patients had major sequelae, both involving the thoracic spine and causing severe kyphosis. Medical treatment usually yields a good outcome. Extensive debridement should be avoided. NC Chiu, et al. Mycobacterium bovis BCG–Associated Osteomyelitis/Osteitis, Taiwan. Emerging Infectious Diseases Vol. 21, No. 3, March 2015

The surveillance of BCG-related adverse events in Taiwan Since 2007, the laboratory offers the examination for extrapulmonary tuberculosis strain in children <5 years old or pathological specimens which cannot be isolated.

Management Regimen Duration Surgery Combination therapy: Isoniazid and Rifampin as backbone regimens; a third drug is added (such as streptomycin, ethambutol) Pyrazinamide is resistant to BCG M. bovis Duration Intensive phase for 1-3 months (H + R + S or E), followed by consolidation phase (H + R), for a total duration of 6-24 months Surgery Patients at a higher risk for complications usually have lesions on weight bearing joints, growth plates, or vertebrae. Patients receiving diagnostic procedures instead of surgical interventions may avoid major complications.

預防接種受害救濟

Thanks for your lstening!