The immunological impostor: Kikuchi-Fujimoto disease vs systemic lupus erythematosus

Kikuchi-Fujimoto disease (KFD), or histiocytic necrotising lymphadenitis, is a rare, benign, self-limiting inflammatory disorder of uncertain aetiology. Initially described in Japan in 1972, it has since been reported globally across ethnicities.¹ KFD typically affects young adults and often mimics more serious conditions such as systemic lupus erythematosus (SLE) and lymphoma, leading to diagnostic delays.²

We report the case of a 29-year-old woman of Samoan descent who presented with fever, malaise and painful cervical lymphadenopathy. She was initially discharged from the emergency department with presumed viral illness and a 7-day course of Augmentin. When she re-presented twice over the following days with persistent fever and lymphadenopathy, further investigations were prompted.

Examination showed bilateral tender cervical lymph nodes and a papular rash on the forearm and back. Blood tests revealed mild pancytopenia (haemoglobin 107g/L, white blood cell count 1.4x10⁹/L, platelets 107x10⁹/L) and elevated C-reactive protein (CRP; 30mg/L) and lactate dehydrogenase (LDH; 1,109U/L). Computed tomography (CT) scan of the neck, chest, abdomen and pelvis showed widespread lymphadenopathy and splenomegaly, raising concern for lymphoma. Autoimmune screening demonstrated antinuclear antibody (ANA titre of 1:320), but negative anti-double stranded DNA antibody (anti-dsDNA), extractable nuclear antigen (ENA) and antiphospholipid antibodies. Serum complement levels and urinalysis were normal.

A bone marrow biopsy showed reactive trilineage haematopoiesis without malignancy. Lymph node biopsy demonstrated histiocytic necrotising lymphadenitis consistent with KFD. Skin biopsy showed non-specific inflammation and mucin deposition, raising differential of lupus. Given the ANA positivity and systemic features, hydroxychloroquine was initiated and rheumatologist review arranged.

At rheumatology clinic follow-up she reported gradual resolution of symptoms, including rash and lymphadenopathy. Two months from the initial hospital presentation she remained clinically well, except for diffuse alopecia, which was later explained by long-standing iron deficiency secondary to menorrhagia. She reported occasional use of tranexamic acid during her periods and intermittent use of oral iron supplementation. Review of her records showed that her serum ferritin levels had ranged between 6 and 13µg/L. ANA titre had decreased to 1:80, with negative dsDNA, normal serum complements and CRP 3mg/L. The rheumatologist concluded the presentation was most consistent with KFD rather than SLE. Hydroxychloroquine was tapered and ceased. Eight months from the initial hospital presentation she remained asymptomatic, with no fever, fatigue or painful neck lumps. Her laboratory findings were normal, and she was discharged from follow-up. A repeat CT scan was not performed as her symptoms had fully resolved and it was considered unnecessary given her return to baseline health. The patient had two CT scans during her inpatient stay. The first, a contrast-enhanced CT of the neck and chest, was performed on 5 August 2024 due to neck lumps and fever. Two days later, on 7 August, she underwent a contrast-enhanced CT of the abdomen and pelvis to complete evaluation, as lymphoma was suspected.

Discussion

KFD commonly presents with fever and cervical lymphadenopathy in young women.^2–4 While initially thought to predominantly affect Asian populations, it occurs in diverse ethnic groups.¹ In Aotearoa New Zealand, data on incidence among Pacific peoples are limited, but clinicians should be aware of its presentation.

Laboratory findings in KFD are variable. Leukopenia is reported in up to 43% of cases, with occasional thrombocytopenia or pancytopenia.^5,6 Elevated LDH and transient ANA positivity may occur, sometimes mimicking early SLE.⁷ Biopsy is essential to confirm diagnosis and exclude malignancy or autoimmune disease. Histologically, KFD shows patchy necrosis with abundant histiocytes and karyorrhectic debris, with absence of neutrophils.⁸

Management is supportive. Most cases resolve within weeks to months. Non-steroidal anti-inflammatory drugs (NSAIDs) may help with symptoms, while corticosteroids or hydroxychloroquine are reserved for severe or persistent disease.

Conclusion

This case highlights KFD as an important differential in young women with fever and lymphadenopathy, even among Pacific populations. It underscores the need for tissue diagnosis, awareness of potential overlap with autoimmune disease and the importance of multidisciplinary input for optimal care.

View Figure 1–4.