What are the typical clinical presentations of Kikuchi-Fujimoto disease?

Clinical Presentation of Kikuchi-Fujimoto Disease

Kikuchi-Fujimoto disease typically presents as tender, unilateral cervical lymphadenopathy in the posterior cervical triangle accompanied by fever, predominantly affecting young women of Asian descent. 1, 2

Primary Clinical Features

Lymphadenopathy Characteristics

• Cervical lymph nodes are usually unilateral, tender, 1.5-4 cm in diameter, and located in the posterior cervical triangle (in contrast to Kawasaki disease which affects the anterior cervical triangle). 1
• Multiple enlarged nodes are typically present rather than a single node, which helps distinguish this from bacterial lymphadenitis. 1
• Generalized lymphadenopathy is rare but can occur. 3
• Ultrasound shows a hypoechoic aspect with an external, thick and irregular hyperechoic ring. 3

Fever Pattern

• Low-grade fever is common and accompanies the lymphadenopathy. 2, 4
• Night sweats frequently occur alongside the fever. 2, 4

Associated Symptoms

Common Accompanying Features

• Headaches are frequently reported. 2
• Skin rash may be present. 2, 5
• Mild hepatosplenomegaly can occur. 1
• Weight loss, nausea, vomiting, and sore throat are less frequent but recognized symptoms. 4, 3

Less Common Manifestations

• Arthralgia and arthritis may develop. 5, 3
• Fatigue and weakness are reported. 5, 3
• Extranodal involvement (skin, eye, bone marrow) is rare. 3

Laboratory Findings

• Leukopenia or neutropenia with relative lymphocytosis is characteristic. 3
• Pancytopenia can occur in some cases. 5
• Elevated inflammatory markers (ESR, CRP) are typically present. 6

Demographic Pattern

• Predominantly affects young women, especially those of Oriental-Asian origin. 2
• The disease has worldwide distribution but higher prevalence in Japanese and other Asian populations. 4

Clinical Course

• Self-limited disorder with spontaneous resolution within 1-4 months. 1, 4
• Disease typically develops over 1-3 weeks with an acute or subacute course. 3
• Recurrence is rare (3-4% of cases). 1

Critical Diagnostic Pitfalls

Distinguishing from Kawasaki Disease

• Kikuchi-Fujimoto affects posterior cervical nodes while Kawasaki disease affects anterior cervical nodes. 1
• Kawasaki disease requires ≥5 days of fever plus ≥4 principal features (bilateral nonexudative conjunctivitis, oral changes, polymorphous rash, extremity changes, cervical lymphadenopathy ≥1.5 cm). 6
• In Kawasaki disease, multiple nodes are present with retropharyngeal edema or phlegmon on imaging. 6

Distinguishing from Bacterial Lymphadenitis

• Bacterial infection typically presents with a single node with hypoechoic core on ultrasound, warmth, erythema of overlying skin, and localized tenderness. 6
• Kikuchi-Fujimoto shows multiple enlarged nodes without these suppurative features. 1

Other Important Differentials

• Must distinguish from systemic lupus erythematosus, malignant lymphoma, tuberculosis, and other infectious lymphadenitis. 2, 4
• The absence of neutrophils, plasma cells, and hematoxylin bodies on histology argues against SLE. 3
• Absence of auto-antibodies and anti-nuclear antibodies helps rule out autoimmune disorders. 3

Definitive Diagnosis

• Diagnosis requires excisional lymph node biopsy showing paracortical foci of coagulative necrosis with karyorrhectic debris, surrounded by CD68+ histiocytes and CD8+ lymphocytes. 4, 3
• Three histological patterns are recognized: proliferative, necrotizing, and xanthomatous. 2

Associated Conditions

• Associations noted with viral infections (EBV, HSV, VZV). 2
• Associations with autoimmune disorders including SLE, Sjogren's syndrome, rheumatoid arthritis, and Hashimoto's thyroiditis. 2, 5
• Cases reported following mRNA COVID-19 vaccination. 7
• Patients should be followed for several years to monitor for possible development of systemic lupus erythematosus. 4