What is Kikuchi-Fujimoto disease, a condition primarily affecting young Asian women?

Kikuchi-Fujimoto Disease: Overview

Kikuchi-Fujimoto disease (KFD) is a rare, benign, self-limiting histiocytic necrotizing lymphadenitis that primarily presents with fever and tender cervical lymphadenopathy, most commonly affecting young women of Asian descent, though it occurs across all ethnic groups. 1, 2

Clinical Presentation

Key Features:

• Unilateral cervical lymphadenopathy is the hallmark presentation, though generalized lymphadenopathy occurs in approximately 24% of cases 1, 3
• Fever lasting typically 1 week to 1 month accompanies the lymph node enlargement 1
• Age and demographics: Median age around 25-35 years, with slight variation in sex predilection (some studies show female predominance, others show slight male predominance) 1, 3
• Geographic distribution: While more common in Asian populations, KFD affects all races and has been increasingly recognized in non-Asian populations 2, 4, 5

Laboratory Findings

• Leukopenia is present in approximately 42% of patients and is a characteristic finding 1, 3
• Antinuclear antibody (ANA) positivity may be present in some cases 3

Pathophysiology and Etiology

The exact cause remains unclear, though infectious and autoimmune mechanisms have been implicated, with viral triggers (including Epstein-Barr virus) suspected in pathogenesis 1, 2. The necrosis of lymph node tissue occurs through apoptosis and may be virally induced 5.

Histopathological Features

Diagnosis requires excisional lymph node biopsy showing characteristic features 4:

• Lymph node architectural effacement with paracortical necrosis and debris 1, 3
• Histiocytic infiltration with immunoblasts 1, 3
• Absence of neutrophils (a key distinguishing feature) 3
• Patent sinuses 3

Atypical presentations occur in approximately 24% of cases and may include 3:

• Marked immunoblastic proliferation mimicking lymphoma
• Vasculitis and panniculitis (50% of atypical cases)
• Large atypical cells requiring immunohistochemistry with CD68 for diagnosis confirmation

Critical Differential Diagnoses

KFD must be distinguished from 6, 2, 4:

• Systemic lupus erythematosus (SLE) - shares features of fever and lymphadenopathy; lymph node biopsy is essential for differentiation 6
• Lymphoma - histologically can be confused with KFD, particularly in atypical presentations 1, 4
• Tuberculosis - commonly misdiagnosed due to similar presentation with fever and lymphadenopathy 2, 4
• Metastatic disease 4
• Reactive lymphadenitis from viral infections 4

Association with Autoimmune Disease

Important clinical pitfall: There is a recognized association between KFD and SLE 1, 2:

• KFD may occur before, simultaneously with, or after SLE diagnosis 2
• One study showed 12.5% of KFD patients developed SLE during follow-up 1
• Other autoimmune associations include IgA nephropathy 1

Management and Prognosis

KFD is self-limiting with no specific therapy required 1, 4:

• Most cases resolve spontaneously within weeks to months 1, 5
• Supportive care is the mainstay of treatment 4
• When diagnosed simultaneously with SLE, treatment with corticosteroids, hydroxychloroquine, and immunosuppressants may be necessary for the SLE component 2

Long-term follow-up is warranted due to 1:

• Potential for recurrence
• Risk of developing autoimmune diseases, particularly SLE
• Need to monitor for disease progression

Key Clinical Considerations

To avoid misdiagnosis 2, 3:

• Maintain high index of suspicion in patients presenting with persistent fever and cervical lymphadenopathy
• Recognize that atypical features are not rare (24% of cases) 3
• Perform excisional biopsy rather than fine needle aspiration for definitive diagnosis 4
• Correlate histopathology with clinical findings and use immunohistochemistry when atypical features are present 3
• Early accurate diagnosis prevents inappropriate therapy for tuberculosis or lymphoma 2