A fatal case of tuberculous meningitis in a child with juvenile idiopathic arthritis: a diagnostic challenge

Bal, Zümrüt Şahbudak; Yazici, Pınar; Şen, Semra; Eraslan, Cenk; Çavuşoğlu, Cengiz; Karapınar, Bülent; Vardar, Fadıl

doi:10.1590/0037-8682-0410-2016

Cited by 7 publications

(5 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%

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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%

“…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%

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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“…This patient was admitted to ITU and was commenced on anti tuberculous therapy however did not survive. His sputum cultures initially were negative and another sample in week 6 was positive for mycobacterium tuberculosis that was responsive to antituberculous therapy [13].…”

Section: Discussionmentioning

confidence: 99%

Sudden Vision Loss: More than Just an Ophthalmic Diagnosis! A Case Report

Bhakti¹,

Anil²,

Shreeya³

et al. 2023

Res Rev Infect Dis

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“…Of the 18 patients who were alive at presentation, 14 had miliary TB, and 4 had central nervous system involvement, both of which are associated with high levels of morbidity and mortality [25,26]. This predilection for severe TB manifestations in children on anti-TNF-α treatment is further documented by several case reports and small case series [27,28]. Notably, the aforementioned study also showed those children typically require prolonged TB treatment (median duration: 50 weeks), and that the risk of long-term sequelae in this patient population is substantial (observed in 28% of the survivors).…”

Section: Discussionmentioning

confidence: 99%

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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A fatal case of tuberculous meningitis in a child with juvenile idiopathic arthritis: a diagnostic challenge

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

Sudden Vision Loss: More than Just an Ophthalmic Diagnosis! A Case Report

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

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