Kikuchi–Fujimoto Disease as a Trigger to Systemic Lupus Erythematosus

Dear Editor,

Kikuchi–Fujimoto disease (KFD) is a rare, self-limiting condition, primarily presenting as lymphadenopathy with or without systemic symptoms. While cervical lymphadenopathy is most common, other regional lymph nodes can also be involved. ¹ KFD was first reported in Japan in 1972 and is more prevalent among Asians, with a female preponderance. ² Though the aetiology is unclear, a viral-autoimmune origin is the most accepted hypothesis. KFD often coexists with systemic lupus erythematosus (SLE), appearing before, after or concurrently with it.^3,4 But its potential role as a precursor or immune-priming event leading to SLE warrants further investigation into their shared pathogenetic mechanisms. We present a case where KFD, initially characterised by peripheral inguinal swelling, preceded the development of SLE.

A 31-year-old South Asian woman presented with left-sided pleuritic chest pain and shortness of breath for 20 days. She reported a year-long history of recurrent low-grade fever and oral ulcers. A year earlier, she experienced right calf inguinal swelling, and an excision biopsy revealed presence of histiocytes, plasmacytoid dendritic cells, eosinophilic granular material and abundant karyorrhectic debris surrounding a central zone of necrosis (Figure 1A and B). The histopathology, classically defined as histiocytic necrotising lymphadenitis, was consistent with KFD. Complete blood count (haemoglobin (Hb—13g/dL, white blood cell (WBC)—9.0 × 10³/mm³ and platelet—210 × 10³/mm³) and chest radiograph were normal. There was no other palpable lymph node or other systemic complaints. Ziehl-Neelsen staining and mycobacterial culture were negative. The patient was treated symptomatically with analgesics.

At presentation, her vital signs showed a respiratory rate of 28/min, temperature of 100.1°F, pulse rate of 108 beats/min and blood pressure of 128/88 mm Hg. Physical examination revealed pleural rub over the left lower infrascapular area, while other findings were unremarkable. Initial investigations, including haematological and biochemical profiles, were normal. A chest radiograph was clear, but a high-resolution computed tomography (HRCT) Chest scan showed minimal left pleural and mild pericardial effusion (Figure 1C and D). Pleural fluid aspiration was not possible.

Figure 1.

(A) Haematoxylin–Eosin Stain of the Lymph Node Biopsy Showing Distortion of the Lymph Nodal Structure, Expansion of the Paracortex by Mononuclear Cells and Areas of Fibrinoid Necrosis at Magnification × 40. (B) Haematoxylin–Eosin Stain of the Lymph Node Biopsy Showing Irregularly Shaped Pale Areas Composed of Histiocytes, Plasmacytoid Dendritic Cells, Eosinophilic Granular Material and Abundant Karyorrhectic Debris (Nuclear Dust) Surrounding a Central Zone of Overt Necrosis (Black Arrow) at Magnification × 400. (C, D) High-resolution Computed Tomography of Chest Showing Pericardial Effusion (Red Arrow) and Pleural Effusion (White Arrow).

Urinalysis revealed 3+ proteinuria without casts, crystals or red blood cells, and a 24-hour urine test (2,500 mg/24 hours) confirmed proteinuria. She tested positive for direct Coombs, antinuclear antibody (ANA, 1:640), antinucleosome and antihistone antibodies. Complement levels (C3: 110 mg/dL, C4: 35 mg/dL) were normal. Serologies for human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) were negative. Pulmonary function testing indicated mild restriction, and echocardiography confirmed mild pericardial effusion. Using the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) ⁵ 2019 criteria, she scored 13 points, confirming SLE.

A final diagnosis of KFD of peripheral lymph nodes preceding SLE was made. Treatment with prednisolone (30 mg daily), hydroxychloroquine (200 mg daily) and mycophenolate mofetil (1,000 mg twice daily) was initiated. Symptoms of chest pain and breathlessness resolved, and glucocorticoids were tapered over three months, with continued maintenance therapy. The patient remained asymptomatic for one year.

KFD is a benign, self-limiting disorder, typically resolving within months. However, its association with SLE, a multifaceted autoimmune condition, warrants careful monitoring. Although lymphadenopathy is common in SLE, it is excluded from the EULAR/ACR classification criteria. The cause of lymphadenopathy in SLE can be due to SLE itself, KFD, tuberculosis, sarcoidosis, Castleman disease and many others.

In our case, KFD progressed to SLE, but it also has the potential to trigger other autoimmune conditions like Sjögren syndrome, Wegener granulomatosis, Graves’ disease and Still disease. Given the potential for KFD to trigger severe autoimmune conditions, patients diagnosed with KFD require long-term follow-up to monitor symptom progression and detect emerging autoimmune disorders.