What is the cause of Kikuchi disease?

Cause of Kikuchi Disease

The cause of Kikuchi disease remains unknown, though it is strongly suspected to be triggered by an autoimmune process or viral infection with an exaggerated T-cell-mediated immune response. 1

Proposed Etiologic Mechanisms

Viral Trigger Hypothesis

• The most widely accepted theory suggests a viral etiology, with the disease representing a hyperactive immune response to viral infection 2
• Specific viral associations have been reported, including:
  • COVID-19 infection (temporal association documented in case reports) 3
  • Epstein-Barr virus (EBV) 1
  • Herpes simplex virus 1
• The self-limited nature of the disease, typical resolution within weeks to months, and low recurrence rate (3-4%) support an infectious trigger rather than a chronic autoimmune condition 1

Autoimmune Mechanism

• An exaggerated T-cell-mediated immune response appears central to pathogenesis, regardless of the initial trigger 1, 2
• Strong association exists with systemic lupus erythematosus (SLE):
  • 9% of European KFD patients develop concomitant SLE 4
  • 28% of East Asian patients develop concomitant SLE 4
• This autoimmune overlap suggests shared immunopathogenic mechanisms 4

Geographic and Demographic Patterns

• Kikuchi disease shows marked geographic predilection, being most commonly reported in Asian populations, particularly Japan where it was first described in 1972 4
• This geographic clustering may suggest either genetic susceptibility factors or regional exposure to specific environmental/infectious triggers 4

Clinical Implications of Unknown Etiology

Diagnostic Approach

• Because no specific causative agent has been identified, diagnosis relies entirely on histopathologic examination of excised lymph nodes showing characteristic histiocytic necrotizing lymphadenitis 1, 3, 5
• The unknown etiology necessitates exclusion of serious mimics including lymphoma, SLE, and specific infections before confirming KFD diagnosis 1

Treatment Limitations

• No specific etiologic treatment exists; management is purely supportive with antipyretics and anti-inflammatory medications 1
• Corticosteroids are reserved for severe cases, though their efficacy is variable and some patients relapse despite multiple courses 1
• The lack of targeted therapy reflects our incomplete understanding of disease causation 1

Follow-up Considerations

• Given the association with SLE development, long-term monitoring is recommended even though the acute disease is self-limited 4
• The 9-28% risk of developing SLE suggests ongoing immune dysregulation may persist beyond clinical resolution 4

Important Caveats

The temporal association with viral infections (particularly COVID-19 in recent reports) does not prove causation, as these may simply unmask underlying immune susceptibility rather than directly causing the disease 3. The consistent finding of T-cell-mediated inflammation across all cases suggests a final common pathway regardless of the initial trigger 1, 2.