[Osteitis as a complication of BCG vaccination].

OBJECTIVES: To investigate the incidence and increasing tendency of osteitis after BCG vaccination and, in addition, its clinical features, diagnostic methods and results of treatment. SUBJECTS: 22 cases of Japanese children who received BCG vaccination between 1998 and 2007 and developed osteitis, and were reported in medical journals or meetings. RESULTS AND DISCUSSION: Incidence was very low, 0.2 per 100,000 vaccinations, and an increasing tendency was not seen after 2005, when the vaccination in Japan was limited to below 6 months after birth. However, it might be necessary to follow for much longer period. About 73% of cases of osteitis were seen from 9 to 18 months after receiving the vaccination. The bones of the extremities were commonly affected. Radiography usually showed the defect and cavity formation of the affected bone and often abscess around the lesion. Definitive diagnosis was made by the detection of BCG from the pus or biopsied materials. Recently, multiplex PCR method have been utilized and proved to be a rapid and reliable diagnostic method. Tuberculin reaction was positive, but QFT was negative in all tested cases; QFT will be available for the differential diagnosis of BCG and tuberculous infection. Only 2 patients had multiple lesions, and they had partial interferon-gamma receptor 1 deficiency. Immunodeficiency might have some relationship to the development of osteitis after BCG vaccination. The treatment using INH and RFP was very effective and the outcome was favorable; most of the patients were cured after 6 to 12 months chemotherapy without any complications. However, there is the possibility of defects occurring in the bone and restriction of the articular movement when the diagnosis and treatment are delayed. CONCLUSION: BCG osteitis, although rare, should be considered as a possible complication of the BCG vaccination, and early diagnosis and treatment of this complication is necessary.

[Severe adverse reactions after vaccination with Japanese BCG vaccine: a review].

Japanese BCG vaccine has been admitted by the quality control of World Health Organization (WHO) as the safest BCG vaccine in the world. Even though, BCG, as a live bacterial vaccine, inevitably causes dissemination beyond vaccination site and regional lymph-nodes to various part of the body under certain special conditions. We tried to review the clinical features and immunological status of the cases in which "severe" adverse reactions had developed after vaccination with Japanese freeze-dried BCG vaccine prepared from BCG substrain Tokyo. "Severe" adverse reaction was arbitrarily defined as the adverse reactions of clinical significance developed beyond vaccination site and regional ipsilateral axillary lymph-nodes. By the extensive search of the literatures, 39 cases were identified since 1951 when vaccination with freeze-dried BCG vaccine became compulsory by the Tuberculosis Prevention Law in Japan. Incidence rate was calculated as 0.0182 cases per 100,000 vaccinations. Clinical manifestations of bone and joint were reported in 27 cases (multiple sites: 15 cases, single site: 12 cases), abnormalities in chest X-ray in 13 cases, skin manifestations in 17 cases, diseases in other sites or organs in 8 cases. Most of the cases had lesions in multiple organs. Among these 39 cases, 13 had been diagnosed to have some types of primary immunodeficiency (5 cases: chronic granulomatous disease (CGD); 4 cases: severe combined immunodeficiency (SCID); 4 cases: IFN-gamma receptor 1 deficiency). Further, unidentified defects in cellular immunity were reported in other 6 cases. Death was reported in 6 cases, but in two cases the causes of death were the infections due to different pathogens, namely, pulmonary abscess due to Staphylococcus sp. and bacteremia due to Pseudomonas aeruginosa, respectively, and in only one case death was evidenced as due to disseminated BCG infection by autopsy. All of 6 death cases had some type of immunodeficiency. Apart from fatal cases, outcome of "severe" adverse events were generally favorable and they were successfully treated by anti-tuberculosis therapy with or without surgical treatment for bone and joint lesions. Because the risk of "severe" adverse reactions is high among those of primary immunodeficiency, so it is advisable to avoid BCG vaccination during the first three months after birth when the detection of immunodeficiency is practically impossible.