Nocardia farcinica as a Potential Pathogen Associated With a Clinical Subtype of Kikuchi-Fujimoto Disease

Fever accompanied by disseminated lymphadenopathy presents a significant diagnostic challenge. Our prior clinical observations indicated a high detection rate of Nocardia farcinica (N. farcinica) deoxyribonucleic acid (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 and 18 people with KFD and CD, respectively, were tested by N. farcinica-specific quantitative real-time polymerase chain reaction (qPCR). Clinical and imaging data were reviewed for comparison.

Nocardia farcinica DNA was significantly more prevalent in KFD (51.4%) than in CD (5.6%) (P < .001). Within KFD, positive people were older, had a shorter onset-to-presentation interval, and exhibited more pronounced leukopenia (all P < .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 = .34) and a trend toward 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.