A 28-year-old Japanese man was admitted to our hospital because of headache and remittent fever that had lasted for 12 days after a solar exposure. The patient had a history of atopic dermatitis from age 2 and had 5 previous episodes of aseptic meningitis with an undetermined aetiology between the ages of 21 and 27 years-old (Figure 1).
Upon admission, day 12, the patient was alert and had pyrexia of 39°C and severe headache with positive Kernig's Sign. The palpable tender lymph nodes with 10 mm in size were present on the right posterior neck, similar to a recent meningitis episode. No other neurological deficits were noted. Laboratory analysis revealed no abnormalities in the patient’s complete blood cell count or liver and thyroid function tests. His serum CRP and IgE levels were elevated, measuring 2.5 mg/dL (normal, <0.3) and 6950 mg/dL (normal, < 295), respectively. The cerebrospinal fluid (CSF) examination showed a crystal clear appearance and pleocytosis of 27 cells/mm3 (97% mononuclear cells) with a protein concentration of 31 mg/dL (normal, < 45). The CSF glucose/glycaemia ratio was 0.86 with sterile bacterial, tuberculosis and fungal cultures. A CSF polymerase chain reaction (PCR) assay for the herpes simplex virus (HSV) was negative. The patient recovered after the administration of non-steroidal anti-inflammatory drugs as a symptomatic treatment and was discharged in remission on day 26.
Subsequently, the patient was re-admitted on day 37 with headache and remittent fever. He was febrile with re-appearance of Kernig's Sign. The posterior cervical lymph nodes were enlarged and tender bilaterally. Additionally, the patient also had oral aphthae and skin rashes on his trunk along with atopic dermatitis. He was alert, and no focal neurological deficit was noted. A complete blood count revealed leukocytopaenia (2.7 x 109/L) with 1% of atypical lymphocytes. A biochemical examination showed abnormal levels with LDH 729 U/L (normal, <220), ferritin 2660 ng/mL (normal, 25–280) and an erythrocyte sedimentation rate of 59 mm/h (normal, <10). IgE and CRP assays exhibited higher levels than those of previous tests, with values of 10400 mg/dL and CRP 6.5 mg/dL being observed, respectively. Serum anti-nuclear and anti-neutrophil cytoplasmic antibodies and rheumatoid factor were within normal range. The complement 3 level was slightly elevated with 194 mg/dL (normal, 65–135). Human leukocyte antigen B51 was negative. The evidence of other infectious agents, such as human hepatitis viruses B and C, human T-cell lymphoma virus-1, syphilis, HSV-1 and 2, varicella-zoster virus (VZV), cytomegalovirus, Epstein-Barr virus (EBV), human herpes virus type 6 (HHV-6) and toxoplasmosis (Toxoplasma gondii) were not detected. A CSF examination revealed a pleocytosis of 16 cells/mm3 (97% mononuclear cells) and a protein concentration of 28 mg/dL, as well as a CSF glucose/glycaemia ratio of 0.75 with sterile bacterial, tuberculosis and fungal cultures. CSF PCRs for HSV, HHV-6, VZV and tuberculosis were negative. The patient’s CSF IgE level was not elevated (19 IU/ml, IgE index 0.03). Splenomegaly was present upon abdominal echograph. No enlargement of deep lymph nodes was detected using computed tomography. Moreover, brain magnetic resonance imaging showed no structural abnormalities.
An excisional biopsy of the involved posterior cervical lymph nodes was performed. The affected lymph nodes showed focal paracortical necrotic lesions (Figure 2A). Under a high power field, the lesion had abundant karyorrhectic debris with apoptotic bodies, numerous histiocytes and large lymphoid cells and scattered fibrin (Figure 2B). However, there were no neutrophils in the lesion. A portion of the phagocytic macrophage had crescent nuclei. Moreover, Giemsa stained sections highlighted the plasmacytoid dendritic cells clusters at the margins of the necrotic foci (Figure 2C). Immunohistochemical study demonstrated that the histiocytes expressed CD68 and myeloperoxidase (Figure 2D, E). Based on these pathological findings, the diagnosis of KFD was made.
The patient did not receive medication during his second admission. Also, his symptoms and CSF parameters spontaneously resolved within two weeks. His enlarged lymph nodes gradually decreased in size. The patient was discharged in remission on day 49, and he remains headache-free after 28 months of follow-up.