Nocardia farcinica as a potential pathogen associated with a clinical subtype of Kikuchi-Fujimoto disease.

Abstract

Fever accompanied by disseminated lymphadenopathy presents a significant diagnostic challenge. Our prior clinical observations indicated a high detection rate of Nocardia farcinica (N. farcinica) DNA in patients with this presentation. Kikuchi-Fujimoto disease (KFD) is a common cause in young adults with fever and lymphadenopathy, yet its etiological drivers remain largely unknown. This dual-center study aimed to investigate the prevalence of N. farcinica infection in a pathologically confirmed KFD cohort, to analyze its correlation with clinical phenotypes, particularly systemic involvement, in comparison to Castleman disease (CD). Formalin-fixed, paraffin-embedded tissue specimens from 35 KFD and 18 CD patients were tested by N. farcinica-specific qPCR. Clinical and imaging data were reviewed for comparison. N. farcinica DNA was significantly more prevalent in KFD (51.4%) than in CD (5.6%) (P<0.001). Within KFD, positive patients were older, had a shorter onset-to-presentation interval, and exhibited more pronounced leukopenia (all P<0.05). A history of recent trauma (11.1% vs. 0%) and immunosuppression (5.6% vs. 0%) was exclusively documented in the N. farcinica-positive group, albeit in small number. Furthermore, N. farcinica-positive patients showed a higher, though not statistically significant, prevalence of bilateral lymph node involvement (72.2% vs. 52.9%, P=0.34) and a trend towards involvement of more nodal regions compared to negative counterparts. This study demonstrated a potential association between N. farcinica and KFD, suggesting a clinical subtype characterized by older age, shorter onset-to-presentation interval, and significant leukopenia. These findings offer novel etiological insights and suggest potential targeted therapeutic approaches, warranting validation through larger prospective studies.