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Review
. 2025 Feb;53(1):481-487.
doi: 10.1007/s15010-024-02364-0. Epub 2024 Aug 14.

Disseminated, fatal reactivation of bovine tuberculosis in a patient treated with adalimumab: a case report and review of the literature

Gioele Capoferri  1 , Giovanni Ghielmetti  2 , Bettina Glatz  3 , Markus R Mutke  3 , Alexandar Tzankov  4 , Roger Stephan  2 , Peter M Keller  5 , Niklaus D Labhardt  6   7
Affiliations
Review

Disseminated, fatal reactivation of bovine tuberculosis in a patient treated with adalimumab: a case report and review of the literature

Gioele Capoferri et al. Infection. 2025 Feb.

Abstract

Purpose: Tumor necrosis factor inhibitors (TNFi) are known to increase the risk of tuberculosis (TB) reactivation, though cases involving Mycobacterium bovis are rarely reported.

Case presentation/results: We describe a case of disseminated TB with M. bovis in a 78-year-old woman with a negative Interferon-Gamma-Release Assay (IGRA), taking adalimumab due to rheumatoid polyarthritis, which resulted in a fatal outcome. The atypical clinical and histopathological features were initially interpreted as sarcoidosis. The case occurred in Switzerland, an officially bovine tuberculosis-free country. The whole genome sequence of the patient's cultured M. bovis isolate was identified as belonging to the animal lineage La1.2, the main genotype in continental Europe, but showed significant genetic distance from previously sequenced Swiss cattle strains. In a literature review, four cases of bovine tuberculosis reactivation under TNFi treatment were identified, with pulmonal, oral and intestinal manifestations. Similar to our patient, two cases presented a negative IGRA before TNFi initiation, which later converted to positive upon symptomatic presentation of M. bovis infection.

Conclusion: This case highlights the diagnostic challenges of TB in immunosuppressed patients, the limited sensitivity of IGRA, and the importance of considering TB reactivation even in regions declared free of bovine tuberculosis. Detailed patient histories, including potential exposure to unpasteurized dairy products, are essential for guiding preventive TB treatment before TNFi initiation.

Keywords: Mycobacterium bovis; Adalimumab; Bovine tuberculosis reactivation; Non-necrotizing granulomas; Tumour necrosis factor inhibitors.

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Conflict of interest statement

Declarations. Ethical approval: Informed consent for participation in this case report was obtained from the patient’s close family members by the authors. Informed consent: Informed consent to publish this case report was obtained by the authors from the patient’s close family members. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Radiological and histopathological findings. a PET scan showing disseminated hypodense, intensely hypermetabolic splenic lesions and two focal hypermetabolic areas in segments VIII (arrow) and III (*) of the liver. b Histopathologic findings in a splenic biopsy showing a granulocyte-admixed, vague granulomatous reaction (in-between arrows) with a giant cell (*) without necrosis (100x, hematoxylin and eosin stain). c Histopathologic findings in a liver biopsy showing granulomatous hepatitis with multiple rather small non-necrotizing granulomas (in-between arrows located in portal and lobular areas, consisting of lymphocytes, epithelioid and giant cells (40x, hematoxylin and eosin stain)
Fig. 2
Fig. 2
Maximum-likelihood phylogenetic tree generated with the GTR-CAT substitution model including the whole genome sequence of the M. bovis isolate cultured from a urine sample of a Swiss patient, is presented. A total of 350 sequences representing the currently known 8 lineages of M. bovis are color-coded, and the country of origin of the isolates identified as La1.2 is reported. The tree was rooted using Mycobacterium caprae, and the bar scale represents the number of substitutions per site
See this image and copyright information in PMC

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