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Tuberculosis and Bacillus Calmette-Guérin Disease in Patients with Chronic Granulomatous Disease: an Experience from a Tertiary Care Center in North India

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Abstract

Chronic granulomatous disease (CGD) is a phagocytic defect characterized by recurrent bacterial and fungal infections. We report clinical profile of patients with CGD and mycobacterial infections in a cohort from North India. A review of clinical and laboratory records was carried out for patients with CGD registered at our center between 1990 and 2021. Of the 99 patients with CGD, 22 had mycobacterial infections—Mycobacterium tuberculosis and M. bovis-BCG in 11 each. Among the children with M. bovis-BCG infection, 6 had localized and 5 had disseminated BCG disease. Median age at onset of symptoms and diagnosis of BCG disease was 5 months and 15 months, respectively. While disseminated forms of BCG were noted only in CYBB defect, none of the patients with NCF1 defect developed complications due to BCG vaccine. A recurring radiological feature was left axillary lymph node calcification, which was present in around 50% of CGD patients with BCG infections. Of 11 patients with tuberculosis, pulmonary, pleuro-pulmonary, abdominal, and disseminated forms were present in 6, 1, 2, and 2, respectively. Median age at onset of symptoms and diagnosis of tuberculosis was 129 months and 130 months, respectively. Molecular defects were identified in CYBB (5), NCF1 (4), and CYBA (1). Incidence of tuberculosis and BCG-related complications in patients with CGD is higher than the normal population. Screening for CGD is warranted in any patient with adverse reactions to BCG vaccination, calcification of left axillary lymph node, and persistent, recurrent or disseminated forms of tuberculosis.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We acknowledge the support from faculty and residents of the pediatric subspecialities in the Department of Pediatrics, Advanced Pediatric Centre, PGIMER, Chandigarh, and other departments of PGIMER, Chandigarh, that helped in the diagnosis and clinical management of the cases. We thank the junior residents of Department of Pediatrics who have assisted in the clinical management. We also thank faculty members, research fellows, and laboratory technicians of the Pediatric Immunology laboratory, Allergy Immunology Unit, Advanced Pediatrics Centre, PGIMER, Chandigarh, who have assisted in the laboratory experiments.

Funding

Dr. Pandiarajan Vignesh received funding from the Indian Council of Medical Research for the project entitled, “Evaluation of immunogenetic risk factors in children with serious forms of mycobacterial infections” (Id: 2020-9482).

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Authors and Affiliations

  1. Allergy Immunology Unit, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Pandiarajan Vignesh, Archan Sil, Ridhima Aggarwal, Wrik Laha, Sanjib Mondal, Manpreet Dhaliwal, Saniya Sharma, Ankur Kumar Jindal, Deepti Suri & Amit Rawat

  2. Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Rakesh Kumar Pilania & Surjit Singh

  3. TB and Serology Division, Department of Medical Microbiology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Sunil Sethi

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Contributions

PV, AS, and RA were involved in conceptualization of the study design. AS, SM, and RA were involved in data collection and computation of data in excel sheet. MD, SS1, and AR helped in processing and interpretation of immunological tests. WL, SM, AS, RA, RKP, AKJ, and DS were actively involved in diagnosis and management of different cases. SS2 supervised the tests related to mycobacterial infections and interpreted the results of those tests. AS, PV, and RA wrote the manuscript. PV, AR, and SS edited the manuscript. PV and AR supervised the entire manuscript preparation.

Corresponding authors

Correspondence to Pandiarajan Vignesh or Amit Rawat.

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Competing Interests

The authors declare no competing interests.

Ethics

This study was performed in line with the principles of the Declaration of Helsinki. The Departmental Review Board of the Advanced Pediatrics Centre approved this manuscript (No. 18-23, dt. 18.03.2023).

Consent to Participate

Informed consent was obtained from the parents of the child included in this report.

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All authors have given final consent for publication. Parents consented for publication of the clinical details of their child in an academic journal.

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Pandiarajan Vignesh and Archan Sil are joint first authors.

Supplementary Information

Supplementary Figure 1:

BCG-vaccination site abscess formation in a child with chronic granulomatous disease. (PNG 2129 kb)

High resolution image (TIF 640 kb)

Supplementary Figure 2:

Chest radiograph showing bilateral pulmonary infiltrates (left panel). Computed tomography images of chest showing patchy areas of mosaic attenuation with ill-defined ground glass opacities are seen in bilateral lungs (right panel). (PNG 4184 kb)

High resolution image (TIF 1066 kb)

Supplementary Figure 3:

Flow chart for screening of CGD in patients with mycobacterial infections. (PNG 2372 kb)

High resolution image (TIF 700 kb)

ESM 4

(DOCX 21 kb)

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Vignesh, P., Sil, A., Aggarwal, R. et al. Tuberculosis and Bacillus Calmette-Guérin Disease in Patients with Chronic Granulomatous Disease: an Experience from a Tertiary Care Center in North India. J Clin Immunol 43, 2049–2061 (2023). https://doi.org/10.1007/s10875-023-01581-w

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