Introduction

Kikuchi’s disease (KD) is a rare, benign, self-limiting disease of unknown etiology, characterized by regional lymphadenopathy and fever [1]. However, KD should be differentiated from relatively malignant causes of cervical lymphadenopathy such as toxoplasmosis, lymphoma, lupus, and tuberculosis, even though in sometimes it might present itself differently [2].

Involvement of the central nervous system (CNS) is rare in KD and only few cases of aseptic meningitis associated with KD have been reported, mostly in Korean and Japanese patients [3, 4]. Aseptic meningitis in KD might have similar clinical and laboratory findings with other meningitis [5, 6]. But, if meningitis is a dominant manifestation of KD, the finding that cerebrospinal fluid (CSF) displays elevated adenosine deaminase (ADA) that mimics tuberculous meningitis indicates that the diagnosis could be very difficult.

Case report

A 28-year-old man presented to our hospital with a 3-week history of headache accompanied by nausea and chillness. The patient had lost 4 kg in weight over the previous several weeks. There was no specific past medical history except a tonsillectomy at the age of 7. At admission, the patient had a temperature of 36.1 °C. A physical examination revealed bilateral tender cervical lymphadenopathy with multiple nodes measuring 1–1.5 cm in diameter. The patient’s headache became gradually aggravated and was associated with neck stiffness. Physical examinations and neurologic examinations did not reveal any other abnormalities.

Laboratory tests showed mild leukopenia (white blood cell count of 4,300/mm3) and an erythrocyte sedimentation rate (ESR) of 36 mm/h. The results of the laboratory test were aspartate transaminase (AST) level of 62 U/L, an alanine transaminase (ALT) level of 46 U/L, and a C-reactive protein level of 3.48 mg/dL. Brain magnetic resonance imaging (MRI) was unremarkable. CSF analysis revealed a slightly yellow color with an opening pressure of 30 cmH2O, white blood cell (WBC) count of 318/mm3 (monocyte 27 %), red blood cell (RBC) count of 0/mm3, glucose 60 mg/dL (serum glucose 149 mg/dL), protein 285 mg/dL, and ADA 18.9 U/L (serum ADA 67.3 U/L). Serum and CSF antibody test for cytomegalovirus, varicellar zoster virus, and herpes simplex virus were all negative.

The initial CSF findings with high CSF ADA and protein prompted a cautious consideration of the possibility of tuberculous meningitis was cautiously considered before getting results of tuberculous culture and polymerase chain reaction (PCR). The tentative diagnosis was tuberculous meningitis with cervical lymphadenopathy, and an anti-tuberculous regimen was commenced for treatment of the sustained headache and lymphadenopathy.

An excision biopsy of the enlarged cervical lymph node was done and the histopathology revealed subacute necrotizing lymphadenitis, which was entirely consistent with KD (Fig. 1). After the diagnosis, the anti-tuberculosis regimen was discontinued, and instead we began to administer prednisolone (1 mg/kg). Several days later, the patient’s headache started to improve. Follow-up CSF analysis at 7 days after steroid treatment showed clear CSF, WBC count of 27/mm3 (monocyte 7 %), glucose 63 mg/dL (blood glucose 127 mg/dL), protein 28 mg/dL, and ADA 3.5 U/L. The headache and lymphadenopathy continued to improve over the subsequent 4–6 weeks. The dosage of prednisolone was gradually reduced and tapered out over the next 2 months.

Fig. 1
figure 1

Microscopic view of the cervical lymph node biopsy specimen. Histiocytic infiltrate and abundant karyorrhectic debris were shown (H&E, ×400)

Full size image

Discussion

Our case is an unusual clinical manifestation of KD and it showed different presentations of KD from several points of view. Meningitis itself is a rare manifestation of KD and only a few cases of Korean and Japanese patients have been reported [3, 4]. In a Japanese case series [4], the CSF opening pressure of 150–300 mmH2O, WBC count of 49–1,685/mm3, protein levels of 26–200 mg/dL, CSF:serum glucose ratios of 0.32:0.6 were reported. CSF ADA level was normal or slightly elevated in previously reported cases [3, 7]. In our case, CSF pleocytosis and elevated opening pressure were similar to previous reports. But ADA of CSF and of serum markedly elevated than those of previous reports and the CSF protein level was also higher.

ADA is a protein that is associated with CD4 T cell immune response [8]. The immune response elicited after tuberculosis infection is critically dependent on CD4 T cells during both acute and chronic infection [9]. ADA is an enzyme that increases during tuberculous infection. We misdiagnosed this case as tuberculous meningitis because of an atypical presentation of symptoms and elevated CSF and serum ADA. Also, Korea is still a tuberculosis-endemic area although the prevalence of tuberculosis has decreased in recent times. The findings of nuclear debris and CD8 T cell-dominant lymph nodes in several immunohistochemical studies suggest that KD is a subacute necrotizing inflammatory condition with CD8 T cell mediated immune reaction. But, plasmacytoid T cells are a striking histopathologic feature of KD. Ultimately, these cells promote a CD4 T cell response and the cytotoxic immune reaction [6, 10]. Therefore, this response could have a role in elevated level of ADA in our case.

Generally, a final diagnosis of KD is made from the result based on an excisional biopsy of affected lymph nodes [6]. In histopathological findings, involved lymph nodes demonstrate reactive lymphoid follicles, expanded paracortex with circumscribed foci of necrosis, histiocytic infiltrate, and abundant karyorrhectic debris in hematoxylin-eosin stain [10]. Our case also showed these typical histopathological findings of KD with negative culture and stain for acid fast bacilli. Negative findings of AFB stain, PCR and culture for tuberculosis with definitive histopathological finding of KD made us exclude tuberculous meningitis. Clinically, several clues such as rapid improvement of CSF ADA, CSF pleocytosis, elevated protein, and headache more likely point to the KD-associated meningitis than tuberculous meningitis.

Misdiagnosis as tuberculous meningitis with subsequent empirical anti-tuberculous therapeutics can be definitely harmful to patients, especially due to long period of medication strategy [11]. However, KD has rarely been associated with fatalities and it can be treated successfully with corticosteroid alone [12]. ADA, which many clinicians believe is a pathognomonic laboratory finding of tuberculous meningitis, also can be elevated in KD. Detection of combined lymphadenopathy and excisional biopsy could give us a critical clue for the diagnosis of the meningitis associated with KD and differentiation from tuberculous meningitis.