Ⅰ. INTRODUCTION

Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease, KFD) was first reported by Kikuchi and Fujimoto in 1972^1,2) and is known to occur mainly in females under 30 years of age. The pathogenesis of histiocytic necrotizing lymphadenitis is still unclear, and there are only a few reports suggesting relevance to viral infection, bacterial infection, and systemic lupus erythematosus (SLE).³⁾ Clinically, acute or subacute painful lymphadenitis (0.5–4 cm) progresses over 1–3 weeks and occurs predominantly in the posterior cervical triangle.⁴⁾ KFD is benign, mostly self-healing, and can be misdiagnosed as various diseases. Thus, accurate diagnosis is needed. In this study, we present a case of KFD in the right cervical lymph node area, which was successfully treated with prednisolone (PSL).

Ⅱ. CASE REPORT

A 52-year-old female was admitted to our hospital with persistent febrile sense, right cervical swelling, odynophagia, and fatigue. The patient had no other medical history. Right submandibular swelling with fever, fatigue, and chills were observed on clinical examination.

At the time of admission, the initial clinical diagnosis was a right submandibular abscess. There was no specific cause of abscess in the oral cavity. Computed tomography (CT) showed right cervical lymph node enlargement at level II and no abscess (Fig. 1A, B). Ultrasonography of the right neck showed the presence of multiple conglomerate lymph nodes and the largest node being 2.14 × 1.38 mm at level II (Fig. 1C, D). Abdominal CT was performed to determine the cause of the fever; however, there was no specific finding.

Laboratory tests revealed increased C-reactive protein (CRP) (5.96 mg/dL), erythrocyte sedimentation rate (ESR) (41 mm/h), and ferritin (421.6 ng/mL). The level of lactate dehydrogenase (200.0 U/L) was normal.

The provisional diagnosis was KFD, SLE, or tuberculosis. The result of real-time PCR for mycobacterium tuberculosis and non-tuberculosis mycobacterium was negative. Antinuclear antibody and antineutrophil cytoplasmic antibody screenings were negative. The serum level of complement C3 was normal; however, the serum level of complement C4 was slightly elevated (48.4 mg/dL). Fine-needle aspiration biopsy (FNAB) was performed for further differential diagnosis. FNAB revealed scattered histiocytes with oval or crescentic nuclei around reactive lymphocytes, which may indicate KFD (Fig. 2). PSL (Solondo®) was orally administered (15 mg/day) as a corticosteroid. After oral administration, fever and lymphadenopathy were rapidly reduced in 12 hours. PSL was maintained at 15 mg/day for 14 days. Fever (normal range), lymphadenopathy, and pain were markedly attenuated. Thereafter, the PSL dose was tapered to 5 mg/day, and the treatment was terminated after 7 days. Recurrence of KFD or adverse event was not observed for 1 years.

Ⅲ. DISCUSSION

The etiology of KFD has not been clearly elucidated. KFD has been reported to be associated with infections. Viral infections include Epstein-Barr virus, human herpes virus 6, human herpes virus 8, cytomegalovirus, and parvovirus B19.^5,6,7) Bacterial infections are also possible causative agents, such as toxoplasma.⁸⁾

The difference in prevalence between males and females varies widely among studies. Nevertheless, it is considered to occur more frequently in young women under 30 years of age.³⁾ Cervical lymphadenopathy occurs in 80% of the cervical lymph nodes. The involvement of the posterior cervical triangle has been reported to be the most common, followed by the axillary and supraclavicular lymph nodes.⁴⁾ The most common symptoms are fever, fatigue, sore throat, and joint pain. In addition, erythematous rash, arthritis, and hepatosplenomegaly are secondary to lymphadenopathy.³⁾ Common CT findings in KFD include multiplicity, homogeneous contrast enhancement (83.3%), perinodal infiltration (81.3%), and necrosis (16.7%).⁹⁾ CT features may mimic those of lymphoma. However, the lymph nodes in KFD are not as large as those in lymphoma.¹⁰⁾ The nodes exhibit a mixed or heterogeneous pattern on sonograms, surrounded by a thick and irregular zone.¹¹⁾ Serology tests have demonstrated that KFD is presented with mild neutropenia and increased CRP and ESR.¹²⁾ The lymph nodes in KFD show apoptotic necrosis, karyorrhectic debris, histiocyte proliferation, plasmacytoid dendritic cells, and CD8 T cells with the lack of neutrophils.¹³⁾

The clinical features of KFD may resemble those of tuberculous lymphadenitis or malignant lymphoma; thus, early diagnosis will minimize unnecessary evaluation and treatment.¹⁴⁾ The traditional method of KFD diagnosis is excisional biopsy of the lymph nodes. Diagnosis with FNAB alone is generally not sensitive enough to provide a reliable diagnosis (overall accuracy of 56.3%).¹³⁾ However, it is difficult to conclude that excisional biopsy of the lymph nodes through an extra-oral approach is the best approach for both patients and surgeons because of the invasiveness. Therefore, if diagnosis through FNAB is more effective with clinical, radiological, and serological examinations, FNAB could be a minimally invasive and reliable diagnostic tool. The histologic features of KFD in FNAB include phagocytic histiocytes with abundant peripheral crescent-shaped nuclei and phagocytosed karyorrhectic or eosinophilic granular debris. There are almost no neutrophils. Nonphagocytic histiocytes with twisted nuclei and delicate chromatin and immunoblasts are present.¹⁵⁾ FNAB is valuable for the differential diagnosis of KFD and tuberculous lymphadenitis or malignant lymphoma with a large number of activated lymphoid cells.

After the diagnosis of KFD, observation is the most common management strategy due to the self-limiting, benign condition of KFD.³⁾ PSL is useful for patients with KFD who have long-lasting fever despite using nonsteroidal anti-inflammatory drugs. However, the optimal dose and duration of PSL are unknown.¹⁶⁾

In an ultrastructural study, KFD was found to be similar to self-limited SLE.¹⁷⁾ SLE is known to develop from KFD in some cases. Therefore, KFD should receive periodical clinical and serological follow-up for several years to detect the possible evolution of SLE.¹⁸⁾ The recurrence rate has been reported as 3–7%.¹⁹⁾ The period from the initial diagnosis to relapse varies from several weeks to over 10 years. Patients who experience fatigue, extranodal involvement, and a long symptomatic duration are more likely to have recurrence.²⁰⁾

In this study, the patient had a high fever of over 38 °C with right neck swelling and chills. In the case of fever, neck swelling, and chills, bacterial infection of the deep neck spaces should be suspected; however, there was no specific origin of bacterial infection. Therefore, lymphadenopathy was suspected. Hematological, radiological, and pathological methods can be used to diagnose KFD. Excisional biopsy of the lymph nodes may be difficult to be accepted as a potential method for diagnosis because of the conservative treatment approach for KFD. FNAB may be an excellent diagnostic tool when combined with radiological and serological examinations.

The administration of corticosteroids for the treatment of KFD may show therapeutic effects within a few days. Therefore, accurate and rapid diagnosis is important, and pathological examination is essential.

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