Elevated nil values in TB-IGRA: a potential diagnostic clue for pediatric histiocytic necrotizing lymphadenitis

Histiocytic necrotizing lymphadenitis (HNL) is a benign condition in children that is often misdiagnosed due to its clinical overlap with tuberculosis, rheumatic diseases, and lymphadenitis. The QuantiFERON-TB Gold In-Tube assay (TB-IGRA) is routinely used to rule out tuberculosis, but its Nil value (TB-Nil), which reflects background IFN-γ release, remains underutilized. Many studies suggest that elevated IFN-γ levels may aid in the differential diagnosis of HNL. In this study, we investigate the role of TB-Nil in diagnosing HNL.

To investigate the relationship between TB-Nil values and the diagnosis of HNL, we retrospectively enrolled 48 patients who were diagnosed with HNL at the Women and Children's Medical Center, Guangzhou Medical University, between January 2019 and December 2024 and who had undergone TB-IGRA testing. Clinical data were extracted from the electronic medical record system. TB-Nil values were compared between HNL and other common causes of lymphadenitis, including systemic juvenile idiopathic arthritis (sJIA), Kawasaki disease (KD), and bacterial lymphadenitis (BL). Receiver operating characteristic (ROC) curve analysis was performed to evaluate diagnostic performance.

Among the 48 enrolled patients with suspected HNL, 37 were confirmed by pathological diagnosis and the remaining 11 were diagnosed based on clinical criteria. The median Nil level was significantly elevated in HNL patients [0.82 IU/mL, interquartile range (IQR): 0.36-1.18] compared with patients with systemic juvenile idiopathic arthritis (sJIA, median = 0.07 IU/mL, P < 0.0001), Kawasaki disease (KD, median = 0.09 IU/mL, P < 0.0001) and Bacterial Lymphadenitis (BL, median = 0.09 IU/mL, P < 0.0001). Receiver operating characteristic (ROC) curve analysis revealed favorable diagnostic performance of the Nil index for identifying HNL, with an AUC of 0.8781 (95%CI: 0.8138-0.9424). The optimal cutoff value of TB-Nil was determined as 0.19 IU/mL for distinguishing HNL from the three control diseases (sJIA, KD and BL), corresponding to a sensitivity of 78.38% and a specificity of 91.67%.

The routinely available yet often overlooked Nil value from the TB-IGRA is significantly elevated in pediatric HNL and demonstrates favorable diagnostic accuracy. It may serve as a practical, non-invasive adjunctive biomarker for the early differential diagnosis of HNL from other inflammatory diseases. Prospective multi-center studies are warranted to validate these findings.