Orthopedic Complications in Former Bacillus Calmette-GuÉrin Osteitis Patients

Pöyhönen, Laura; Pauniaho, Satu‐Liisa; Kröger, Liisa; Korppi, Matti

doi:10.1097/inf.0000000000001081

Cited by 10 publications

(7 citation statements)

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“…Partial dominant IFN‐γR1 deficiency, which belongs to the MSMD, was found in three of six Japanese children with BCG osteitis . All Japanese cases were curable with surgery and antimicrobial treatment, in line with the present cases …”

Section: Discussionsupporting

confidence: 88%

Interferon‐γ and interleukin‐12 production in relation to gene polymorphisms in bacillus Calmette–Guérin osteitis

Korppi¹,

Teräsjärvi

Lauhkonen³

et al. 2019

Pediatrics International

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Background: Interferon-c (IFN-c) and interleukin-12 (IL-12) play a crucial role in the defense against mycobacteria, and in the response to bacillus Calmette-Gu erin (BCG) vaccination. We have previously reported clinical and outcome data of 222 BCG osteitis cases diagnosed in 1960-1988 in Finland. The immunological and genetic reports have been based on 132 blood samples obtained in 2007-2008. Methods: We compared IFNc rs2430561 and rs35314021, IL12A rs568408 and rs2243115, and IL12B rs3212227 single-nucleotide polymorphisms (SNP) between 132 BCG osteitis patients and 99 population-based controls. In addition, stimulated production of IFN-c and IL-12 in cell culture was evaluated in relation to the presence of IFNc and IL12 wild versus variant genotypes, respectively. Results: The distributions of IFNc rs2430561, IFNc rs35314021, IL12A rs568408, IL12A rs2243115 and IL12B rs3212227 SNP did not differ between BCG osteitis patients and Finnish population-based controls. For IFNc rs2430561, IFNc rs35314021 and IL12A rs2243115, the negative result was confirmed by comparing the minor allele frequencies (MAF) in BCG osteitis cases with those in the publicly available genome aggregation database, including data for 3,472 Finnish persons. Instead, for IL12A rs568408 and IL12B rs3212227, the comparison of MAF in BCG osteitis cases with those in population-based and in aggregation-based controls gave conflicting results. The presence of the wild versus variant genotype had no significant association with IL-12 or IFN-c production in BCG-stimulated cell cultures. Conclusion: IFNc gene polymorphisms did not show any association with BCG osteitis after newborn vaccination.

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Section: Discussionsupporting

confidence: 88%

Interferon‐γ and interleukin‐12 production in relation to gene polymorphisms in bacillus Calmette–Guérin osteitis

Korppi¹,

Teräsjärvi

Lauhkonen³

et al. 2019

Pediatrics International

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“…Moreover, patients with confirmed or suspected immunodeficiency could be prone to subsequent atypical infections in the previous BCG osteitis site and also present with multiple lesions 13. A recent study evaluating 160 former Finnish patients diagnosed 19–47 years ago in infancy reported a higher rate of 13.8% to have orthopedic complications, such as leg length discrepancy and chronic pain in the affected limb 14. Therefore, surveillance for serious adverse reactions following BCG vaccination and monitoring their long-term outcomes would be necessary.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium bovisOsteitis Following Immunization with Bacille Calmette-Guérin (BCG) in Korea

et al. 2019

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BackgroundMycobacterium bovis Bacille Calmette-Guérin (BCG) osteitis, a rare complication of BCG vaccination, has not been well investigated in Korea. This study aimed to evaluate the clinical characteristics of BCG osteitis during the recent 10 years in Korea.MethodsChildren diagnosed with BCG osteitis at the Seoul National University Children's Hospital from January 2007 to March 2018 were included. M. bovis BCG was confirmed by multiplex polymerase chain reaction (PCR) in the affected bone. BCG immunization status and clinical information were reviewed retrospectively.ResultsTwenty-one patients were diagnosed with BCG osteitis and their median symptom onset from BCG vaccination was 13.8 months (range, 6.0–32.5). Sixteen children (76.2%) received Tokyo-172 vaccine by percutaneous multiple puncture method, while four (19.0%) and one (4.8%) received intradermal Tokyo-172 and Danish strain, respectively. Common presenting symptoms were swelling (76.2%), limited movement of the affected site (63.2%), and pain (61.9%) while fever was only accompanied in 19.0%. Femur (33.3%) and the tarsal bones (23.8%) were the most frequently involved sites; and demarcated osteolytic lesions (63.1%) and cortical breakages (42.1%) were observed on plain radiographs. Surgical drainage was performed in 90.5%, and 33.3% of them required repeated surgical interventions due to persistent symptoms. Antituberculosis medications were administered for a median duration of 12 months (range, 12–31). Most patients recovered without evident sequelae.ConclusionHighly suspecting BCG osteitis based on clinical manifestations is important for prompt management. A comprehensive national surveillance system is needed to understand the exact incidence of serious adverse reactions following BCG vaccination and establish safe vaccination policy in Korea.

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“…Interestingly, the study from Thailand reported, in addition to five localised BCG osteitis cases, also three cases with disseminated BCG infection, and two of them had severe combined immunodeficiency and one had Wiskott-Aldrich syndrome. 8 Thus, the systematic review, 2 and the basic and outcome data of the 222 Finnish BCG osteitis patients 3,4,21,25 and the data of the 93 new patients included in the present review [5][6][7][8][9][10] confirm that there are no major immunological problems in the BCG osteitis patients, if the infection is not disseminated, and if multiple or recurrent lesions are not present.…”

Section: Immunologymentioning

confidence: 80%

“…We carried out a posted questionnaire study for those 207 Finnish BCG osteitis patients with address data available when they were 21-49 years old, and 160(72.1%) of them answered. 22,25 Twenty-two (13.8%) reported orthopaedic sequelae which they connected to BCG osteitis in infancy. Most complications were mild and had not needed any treatment, but five (3.1%) reported that surgery was required.…”

Section: Ther Apymentioning

confidence: 99%

The sixty‐year story of Finnish Bacillus Calmette‐Guérin (BCG) osteitis

Korppi¹

2020

Acta Paediatrica

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Aim A review published in 2015 showed that 331 Bacillus Calmette‐Guérin (BCG) osteitis cases were globally reported in 1976‐2012. The 222 Finnish cases from 1960 to 1988 formed two‐thirds of all cases. The present narrative review summarises epidemiological, clinical and immunological findings obtained from this Finnish cohort in relation to data from other countries. Methods Six reports including 93 BCG osteitis cases, which were not included in the 2015 review, were identified from PubMed. Results In all, 424 BCG osteitis cases have been published. Population‐based data were available only from Finland and Taiwan. The BCG osteitis incidence in Finnish infants was 6.4/100 000/year in 1960‐1988 compared to 3.4/100 000/year in Taiwanese infants in 1998‐2012. The incidence in Finland increased to 36.9/100 000 in 1971‐1977, and the vaccinations were temporarily discontinued. Over half of lesions were in lower limbs and nearly all were solitary in both cohorts. The outcomes after surgery and chemotherapy were good. Immunology of BCG osteitis was studied only in the Finnish cohort. There were deviations from population data in polymorphisms of genes regulating Toll‐like receptors 1, 2 and 6, mannose‐binding lectin and interleukin‐17A. Conclusion BCG osteitis after vaccination is rare. Preliminary findings in innate immunity raise a question of genetic background.

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Orthopedic Complications in Former Bacillus Calmette-GuÉrin Osteitis Patients

Abstract: In 160 Finnish former Bacillus Calmette-Guérin osteitis patients, a questionnaire revealed that later in life, 22 (13.8%) had mild orthopedic complications as a consequence of the infection.

Cited by 10 publications

References 10 publications

Interferon‐γ and interleukin‐12 production in relation to gene polymorphisms in bacillus Calmette–Guérin osteitis

Interferon‐γ and interleukin‐12 production in relation to gene polymorphisms in bacillus Calmette–Guérin osteitis

Mycobacterium bovisOsteitis Following Immunization with Bacille Calmette-Guérin (BCG) in Korea

The sixty‐year story of Finnish Bacillus Calmette‐Guérin (BCG) osteitis

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