What is the recommended diagnostic workup and management for a young Asian woman presenting with tender cervical lymphadenopathy, low‑grade fever, night sweats, occasional rash, mild leukopenia, elevated erythrocyte sedimentation rate, and mild transaminase elevation suggestive of Kikuchi‑Fujimoto disease?

Kikuchi-Fujimoto Disease: Diagnostic Workup and Management

In a young Asian woman presenting with tender cervical lymphadenopathy, low-grade fever, night sweats, rash, mild leukopenia, elevated ESR, and mild transaminase elevation, the diagnosis of Kikuchi-Fujimoto disease (KFD) should be confirmed by excisional lymph node biopsy showing characteristic histiocytic necrotizing lymphadenitis, followed by supportive care with NSAIDs or corticosteroids for severe symptoms, while excluding malignancy and systemic lupus erythematosus. 1, 2, 3

Clinical Recognition and Differential Diagnosis

Key Distinguishing Features of KFD

• KFD typically presents in young women (predominantly Asian ancestry) with tender cervical lymphadenopathy, fever lasting 1 week to 1 month, and constitutional symptoms including night sweats. 1, 2, 3, 4
• The presentation includes mild leukopenia (present in approximately 38% of cases), elevated ESR, and occasional rash—all consistent with this patient's presentation. 3
• Mild transaminase elevation can occur as part of the systemic inflammatory response. 3

Critical Differential Diagnoses to Exclude

• Kawasaki disease must be excluded, particularly given the cervical lymphadenopathy and fever, but this diagnosis requires fever ≥5 days plus ≥4 principal features (bilateral nonexudative conjunctivitis, oral mucosal changes, polymorphous rash, extremity changes, cervical lymphadenopathy ≥1.5 cm). 5, 6 The patient's presentation lacks the characteristic bilateral conjunctivitis, oral changes, and extremity edema/desquamation typical of Kawasaki disease. 5
• Malignant lymphoma must be ruled out, as KFD can mimic lymphoproliferative disorders. 1, 2 However, the patient's age >40 years would increase malignancy risk, while this patient appears younger. 6, 7
• Systemic lupus erythematosus (SLE) shares overlapping features with KFD and must be considered, as some patients develop SLE during follow-up. 1, 3

Diagnostic Workup Algorithm

Initial Laboratory Assessment

• Complete blood count with differential to document leukopenia (often with lymphocyte predominance in KFD, contrasting with Kawasaki disease which shows leukocytosis with neutrophil predominance). 5, 6, 3
• ESR and CRP to quantify inflammatory response. 5, 6
• Liver function tests (already showing mild transaminase elevation). 6
• Lactate dehydrogenase (LDH). 6

Imaging Studies

• CT scan of neck with contrast is the primary imaging modality for evaluating cervical lymphadenopathy and assessing node characteristics (size, consistency, distribution). 6
• Ultrasound can differentiate cystic from solid masses and guide biopsy procedures. 6

Definitive Diagnostic Procedure

• Excisional lymph node biopsy is required to establish the diagnosis of KFD, showing characteristic histopathological features including lymph node architectural effacement, histiocytic infiltration, and necrosis. 1, 2, 3
• Fine-needle aspiration is insufficient for diagnosis; complete excisional biopsy is necessary. 2, 3

Additional Testing to Exclude Mimics

• Tuberculin skin test (PPD) to exclude tuberculous lymphadenitis, which in adults accounts for >90% of mycobacterial cervical lymphadenopathy. 6, 8
• HIV serology if risk factors present. 6, 3
• Autoimmune serologies (ANA, anti-dsDNA) to screen for SLE, as KFD can be associated with or precede SLE development. 1, 3

Management Strategy

Acute Phase Treatment

• Most cases of KFD are self-limiting and resolve spontaneously within several weeks to months with supportive care alone. 1, 2, 9, 3, 4
• Symptomatic treatment with antipyretics and NSAIDs for fever and lymph node tenderness. 1, 9
• For severe cases with persistent high fever or debilitating symptoms, oral corticosteroids can be used (though no standardized dosing regimen exists in the literature). 1, 9, 3

Follow-Up and Monitoring

• Long-term follow-up is warranted due to recurrence rates of 3-4% and potential development of autoimmune diseases, particularly SLE. 1, 3
• Serial clinical assessments to monitor for complete resolution of lymphadenopathy and constitutional symptoms. 3
• Repeat laboratory testing to document normalization of leukopenia and inflammatory markers. 3

Critical Pitfalls to Avoid

Diagnostic Errors

• Never prescribe multiple courses of antibiotics without clear infectious etiology, as this significantly delays diagnosis of underlying conditions including malignancy. 6, 7
• Do not assume partial resolution after empiric treatment excludes serious pathology; infection can occur in underlying malignancy. 6, 7
• Failure to obtain excisional biopsy when diagnosis is uncertain can lead to missed malignancy or delayed diagnosis of treatable conditions. 2, 3

Management Pitfalls

• Do not confuse KFD with Kawasaki disease—Kawasaki disease requires urgent treatment with IVIG 2 g/kg within 10 days of fever onset to prevent coronary artery aneurysms, while KFD requires only supportive care. 5 The absence of bilateral conjunctivitis, oral mucosal changes, and extremity findings makes Kawasaki disease unlikely in this presentation.
• Recognize that while most KFD cases resolve spontaneously, severe relapsing cases exist that may require immunomodulatory therapy. 1
• Screen for and monitor for development of SLE, as some patients develop autoimmune disease during follow-up. 1, 3