Aspasia Georgala

Immune checkpoint inhibitors (ICIs) improve survival in multiple malignancies but may induce immune-related adverse events (irAEs), including immune-related bronchiolitis (IRB). Radiologic patterns frequently overlap with infectious diseases, particularly tuberculosis (TB), whose reactivation risk may be increased by ICIs via disruption of granuloma integrity. Differentiation between IRB and TB is challenging, especially in patients from endemic areas. We report the case of a 53-year-old Turkish man with metastatic clear-cell renal cell carcinoma, who underwent right nephrectomy followed by nivolumab plus ipilimumab. Four months after treatment, he developed fatigue, dyspnea, productive cough, and weight loss. Chest CT scan showed centrilobular nodules with a tree-in-bud pattern. QuantiFERON® testing was positive. Bronchoalveolar lavage showed lymphocyte predominance with no infectious or neoplastic cells. Transbronchial biopsy demonstrated non-caseating granulomas. PCR for Mycobacterium tuberculosis was negative, and cultures were pending. Given the overlap between IRB and TB, empirical quadruple anti-TB therapy and inhaled corticosteroids were initiated and immunotherapy was temporarily discontinued. After 2 months, given negative mycobacterial cultures and significant hepatotoxicity, isoniazid was discontinued, rifampicin was carefully reintroduced under close monitoring, and the total anti-TB treatment duration was shortened to 4 months. The patient subsequently showed gradual improvement in respiratory symptoms, biomarkers, and radiologic findings. This case illustrates the challenge of distinguishing IRB from TB in ICI-treated patients. Empirical anti-TB therapy may be warranted in high-risk settings despite absent microbiological confirmation but carries toxicity and complicates oncologic management. Pre-treatment latent TB screening and multidisciplinary decision-making are essential to balance infection control with cancer therapy.

Among the challenges in controlling tuberculosis, a rapid and accurate diagnostic test for the detection ofMycobacterium tuberculosiscomplex (MTBc) and its resistance to first line therapies is crucial. We evaluated the performance of the Xpert MTB/RIF Ultra assay (Xpert Ultra) for the rapid detection ofMTBc and rifampicin resistance (RR) in 1120 pulmonary and 461 extra-pulmonary clinical specimens and compared it with conventional phenotypic techniques. The Xpert Ultra assay detectedMTBc in 223 (14.1%) samples with an overall sensitivity and specificity, using culture as the “gold standard”, of 91.1% (95% CI, 85.6–95.1) and 94.5% (95% CI, 93.1–95.6), respectively. The sensitivity of the Xpert Ultra test for smear-negative extra-pulmonary specimens was high (87.1%), even higher than with smear-negative pulmonary specimens (81.8%). But this enhanced sensitivity came with a low overall specificity of smear-negative extra-pulmonary specimens (66.7%). For 73 patients, 79/1423 (3.4%) negative mycobacterial culture samples were found to be positive with Xpert Ultra. Clinical data was necessary to correctly interpret potential false-positive results, especially trace-positive results. Sensitivity of the Xpert Ultra to detect RR compared to drug susceptibility testing was 100% (95% CI, 29.2–100) and specificity was 99.2% (95% CI, 95.8–100). We concluded that the Xpert Ultra test is able to provide a reliable TB diagnosis within a significantly shorter turnaround time than culture. This is especially true for paucibacillary samples such as smear-negative pulmonary specimens and extra-pulmonary specimens.