Disseminated Tuberculosis Resulting From Reinfection in a Pediatric Patient Sequentially Treated With Etanercept and Adalimumab

Guerrero-Laleona, Carmelo; Calzada-Hernández, Joan; Bustillo-Alonso, Matilde; Albarova, Jorge Gil; Ildefonso, Marta Medrano-San; Iglesias-Jiménez, Estibaliz; Noguera-Julián, Antoni

doi:10.1097/inf.0000000000001360

Cited by 7 publications

(9 citation statements)

References 11 publications

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“…Our study highlights the great severity of TB disease in children on anti-TNF-α therapy, consistent with previous case reports [10,[13][14][15][16]. All patients captured by our study presented with severe disease.…”

Section: Discussionsupporting

confidence: 91%

“…One case each was reported from healthcare centres in Austria, Croatia, Latvia, Lithuania, Portugal, Switzerland and Ukraine. Two of the cases (case 3 and case 4; Table 1) had previously been detailed elsewhere in case reports [10,11].…”

Section: Resultsmentioning

confidence: 99%

“…To our knowledge, fewer than 20 cases have been described in detail in the peer-reviewed literature so far [10][11][12][13][14][15][16]. Concerningly, several of those cases had a fatal outcome.…”

Section: Introductionmentioning

confidence: 95%

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Tuberculosis Disease in Children and Adolescents on Therapy With Antitumor Necrosis Factor-ɑ Agents: A Collaborative, Multicenter Paediatric Tuberculosis Network European Trials Group (ptbnet) Study

Noguera-Julián

Calzada-Hernández

Brinkmann

et al. 2019

Clinical Infectious Diseases

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Background In adults, anti–tumor necrosis factor-α (TNF-α) therapy is associated with progression of latent tuberculosis (TB) infection (LTBI) to TB disease, but pediatric data are limited. Methods Retrospective multicenter study within the Paediatric Tuberculosis Network European Trials Group, capturing patients <18 years who developed TB disease during anti–TNF-α therapy. Results Sixty-six tertiary healthcare institutions providing care for children with TB participated. Nineteen cases were identified: Crohn’s disease (n = 8; 42%) and juvenile idiopathic arthritis (n = 6; 32%) were the commonest underlying conditions. Immune-based TB screening (tuberculin skin test and/or interferon-γ release assay) was performed in 15 patients before commencing anti–TNF-α therapy but only identified 1 LTBI case; 13 patients were already receiving immunosuppressants at the time of screening. The median interval between starting anti–TNF-α therapy and TB diagnosis was 13.1 (IQR, 7.1–20.3) months. All cases presented with severe disease, predominantly miliary TB (n = 14; 78%). One case was diagnosed postmortem. TB was microbiologically confirmed in 15 cases (79%). The median duration of anti-TB treatment was 50 (IQR, 46–66) weeks. Five of 15 (33%) cases who had completed TB treatment had long-term sequelae. Conclusions LTBI screening is frequently false-negative in this patient population, likely due to immunosuppressants impairing test performance. Therefore, patients with immune-mediated diseases should be screened for LTBI at the point of diagnosis, before commencing immunosuppressive medication. Children on anti–TNF-α therapy are prone to severe TB disease and significant long-term morbidity. Those observations underscore the need for robust LTBI screening programs in this high-risk patient population, even in low-TB-prevalence settings.

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Section: Discussionsupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

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Tuberculosis Disease in Children and Adolescents on Therapy With Antitumor Necrosis Factor-ɑ Agents: A Collaborative, Multicenter Paediatric Tuberculosis Network European Trials Group (ptbnet) Study

Noguera-Julián

Calzada-Hernández

Brinkmann

et al. 2019

Clinical Infectious Diseases

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“…The history revealed that she had recently had contact with a relative with pulmonary TB. Typing of her MTB isolates confirmed complete homology with the strain isolated from her relative, indicating that she had de novo infection rather than reactivation of LTBI [24]. Anti-TNF-α drugs were also started in 9 out of 10 patients with indeterminate QFT-GIT results (ranging from 0 to 1.6 years after assessment), none of whom developed TB disease during follow-up (Supplementary Table 2).…”

Section: Resultsmentioning

confidence: 83%

Dual latent tuberculosis screening with tuberculin skin tests and QuantiFERON-TB assays before TNF-α inhibitor initiation in children in Spain

et al. 2022

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Tumor-necrosis-factor-α inhibitors (anti-TNF-α) are associated with an increased risk of tuberculosis (TB) disease, primarily due to reactivation of latent TB infection (LTBI). We assessed the performance of parallel LTBI screening with tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube assays (QFT-GIT) before anti-TNF-α treatment in children with immune-mediated inflammatory disorders in a low TB-burden setting. We conducted a multicenter cohort study involving 17 pediatric tertiary centers in Spain. LTBI was defined as the presence of a positive TST and/or QFT-GIT result without clinical or radiological signs of TB disease. A total of 270 patients (median age:11.0 years) were included, mainly with rheumatological (55.9%) or inflammatory bowel disease (34.8%). Twelve patients (4.4%) were diagnosed with TB infection at screening (LTBI, n = 11; TB disease, n = 1). Concordance between TST and QFT-GIT results was moderate (TST+/QFT-GIT+, n = 4; TST−/QFT-GIT+, n = 3; TST+/QFT-GIT-, n = 5; kappa coefficient: 0.48, 95% CI: 0.36–0.60). Indeterminate QFT-GIT results occurred in 10 patients (3.7%) and were associated with young age and elevated C-reactive protein concentrations. Eleven of 12 patients with TB infection uneventfully completed standard LTBI or TB treatment. During a median follow-up period of 6.4 years, only 2 patients developed TB disease (incidence density: 130 (95% CI: 20–440) per 100,000 person-years), both probable de novo infections.Conclusion: A substantial number of patients were diagnosed with LTBI during screening. The dual strategy identified more cases than either of the tests alone, and test agreement was only moderate. Our data show that in children in a low TB prevalence setting, a dual screening strategy with TST and IGRA before anti-TNF-α treatment is effective. What is Known:• The optimal screening strategy for latent tuberculosis in children with immune-mediated inflammatory disorders remains uncertain.• Children receiving anti-TNF-α drugs are at increased risk of developing severe tuberculosis disease. What is New:• A dual screening strategy, using TST and an IGRA assay, identified more children with latent tuberculosis than either of the tests alone.• Identification and treatment of latent tuberculosis before initiation of anti-TNF-α therapy averted incident tuberculosis cases.

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“…Die Daten legen nahe, dass die bei Erwachsenen beobachteten Risiken der Reaktivierung einer tuberkulösen InfektionunterAnti-TNF-α-Therapiesehrwahrscheinlichauchfür behandelte Kinder und Jugendliche von Bedeutung sind, obwohl hier nur wenige Publikationen vorliegen. ZuKindernundJugendlichenliegeneinzelneFallberichteoder Ergebnisse kleiner Kohortenstudien vor, die auch über schwere und zum Teil letale Verläufe einer Tuberkulose unter einer Anti-TNF-a-Therapie berichteten [22][23][24][25]. Die bisher größte Studie zudemThemaderTNF-α-assoziiertenTuberkulosebeiKindern und Jugendlichen wurde kürzlich von der Paediatric Network European Trials Group (ptbnet), einem Netzwerk von Pädiatern, die in Europa im Bereich der Kindertuberkulose mit dem Fokus auf klinische Forschungsprojekte kooperieren, veröffentlicht [26].…”

Section: Tuberkulose Unter Therapie Mit Tnf-α-inhibitorenunclassified

Tuberkulose bei Kindern und Jugendlichen unter Therapie mit TNF-α-Inhibitoren

Feiterna‐Sperling¹

2022

Kinder- und Jugendmedizin

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ZUSAMMENFASSUNGAufgrund des erhöhten Risikos einer Tuberkulose beim Einsatz von Tumor-Nekrose-Faktor (TNF)-α-Inhibitoren in der Therapie der juvenilen idiopathischen Arthritis und anderer chronisch-entzündlicher Erkrankungen soll bei allen Kindern und Jugendlichen vor Beginn einer Therapie mit TNF-α-Inhibitoren eine Tuberkulose ausgeschlossen werden und ein Screening auf das Vorliegen einer latenten tuberkulösen Infektion erfolgen. Das Screening beinhaltet eine sorgfältige Anamnese, die Durchführung eines Interferon-Gamma-Release-Assays und/oder Tuberkulin-Hauttests sowie eine Röntgen-Thorax-Aufnahme bei einem positiven Testresultat und/oder klinischem Hinweis auf eine Tuberkulose. Eine präventive Therapie der latenten tuberkulösen Infektion soll mit Isoniazid und Rifampicin über 3 Monate oder alternativ mit Isoniazid für 9 Monate durchgeführt werden.

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Disseminated Tuberculosis Resulting From Reinfection in a Pediatric Patient Sequentially Treated With Etanercept and Adalimumab

Cited by 7 publications

References 11 publications

Tuberculosis Disease in Children and Adolescents on Therapy With Antitumor Necrosis Factor-ɑ Agents: A Collaborative, Multicenter Paediatric Tuberculosis Network European Trials Group (ptbnet) Study

Tuberculosis Disease in Children and Adolescents on Therapy With Antitumor Necrosis Factor-ɑ Agents: A Collaborative, Multicenter Paediatric Tuberculosis Network European Trials Group (ptbnet) Study

Dual latent tuberculosis screening with tuberculin skin tests and QuantiFERON-TB assays before TNF-α inhibitor initiation in children in Spain

Tuberkulose bei Kindern und Jugendlichen unter Therapie mit TNF-α-Inhibitoren

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