Published online April 1, 2005
PEDIATRICS Vol. 115 No. 4 April 2005, pp. 1112 (doi:10.1542/peds.2005-0088)
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Detection of the Bartonella henselae Gene Sequence in Lymph Nodes of Children With Kikuchi's Disease

Ju-Young Chung, MD
Department of Pediatrics

Sang Woo Kim, MD
Department of Pediatrics

Tae Hee Han, MD
Department of Diagnostic Laboratory Medicine

Sung Jig Lim, MD
Department of Pathology
Sanggye-Paik Hospital
Inje University College of Medicine
763-1, Sanggye 7-Dong, Nowon-gu, Seoul 139-707, Korea

To the Editor.—

Kikuchi's disease (KD), also known as Kikuchi-Fujimoto disease or histiocytic necrotizing lymphadenitis, was first described in 1972 independently by Kikuchi1 and Fujimoto et al.2 Viral infection has been suggested as a possible etiology because of clinical manifestations such as fever, lymphadenopathy with a self-limited course, and occasional peripheral lymphocytosis. However, most studies failed to detect suspicious viral agents including Epstein-Barr virus, human herpesvirus 8, human herpesvirus 6, and parvovirus B19 in KD.3 Some bacterial agents including Yersinia enterocolitica, Toxoplasma, and Brucella were occasionally identified by serologic methods.3 Although KD is rare in children, it should be considered in the differential diagnosis of infections, collagen diseases, or malignancy. Cat-scratch disease (CSD) is a worldwide zoonosis caused by Bartonella henselae or Bartonella clarridgeiae and is characterized by a self-limiting regional lymphadenopathy associated with a cat scratch or bite. However, no history of animal contact can be elicited in a small percentage of patients with CSD. Atypical CSD is reported in up to 25% of cases. CSD is usually suspected clinically and confirmed by the detection of Bartonella DNA in lymph nodes by polymerase chain reaction (PCR). We investigated the presence of B henselae DNA in children diagnosed with KD. Twenty children who were diagnosed with KD at Sanggye-Paik Hospital, Inje University College of Medicine, from January 1998 to December 2004 were included in the study. DNA was extracted from lymph node specimens on slides and paraffin-embedded tissues. B henselae strain Houston was used for a positive control, and 2 different primers were used in this study. The PCR assay was performed by using the citrate synthetase (gltA) gene, an outer pair of primers consisting of TN-1 and TN-2, and an inner primer as described.4 Seminested PCR protocols for amplification of the pap31 gene of B henselae with primers PAPn1, PAPn2, and PAPns2 were as described.5 The PCR products were separated by electrophoresis on 1.5% agarose gels and visualized by staining with ethidium bromide. PCR products were sequenced in both directions, and sequence analysis was performed. The mean age of the 20 children with KD was 13 years (range: 5–17 years). Eleven patients were female. The lymph node lesions were located in the cervical area in 80% of the children, the submandibular area in 10%, and the axillary area in 5%. B henselae DNA was detected in 4 patients (25%). With the gltA primer, a positive PCR result was obtained from 4 patients (25%), whereas the pap31 primer amplified B henselae DNA in only 1 patient (5%). The amplification products were confirmed by sequence analysis. None of the negative controls were positive. We had performed seminested PCR assays by using different primers targeting the citrate synthetase (gltA) gene and pap31 gene of B henselae in lymph nodes of children with KD. A diagnosis of CSD by PCR from fine-needle aspiration and primary lesion specimens was reported to be minimally invasive and highly accurate.6 Typical pathologic findings are characteristic of, but not specific for, CSD. The results of our study suggest that B henselae may be an etiologic agent in some children diagnosed with KD. Additional studies are needed to clarify the association of B henselae with KD.

REFERENCES

  1. Kikuchi M. Lymphadenitis showing focal reticulum cell hyperplasia with nuclear debris and phagocytosis. Acta Hematol Jpn. 1972;35 :379 –380
  2. Fujimoto Y, Kojima Y, Yamaguchi K. Cervical subacute necrotizing lymphadenitis. Naika. 1972;30 :920 –927
  3. Onciu M, Medeiros LJ. Kikuchi-Fujimoto lymphadenitis. Adv Anat Pathol. 2003;10 :204 –211[CrossRef][Medline]
  4. Margolis B, Kuzu I, Hermann M, Raible M, His E, Alkan S. Rapid polymerase chain reaction-based confirmation of cat scratch disease and Bartonella henselae infection. Arch Pathol Lab Med. 2003;127 :706 –710[ISI][Medline]
  5. Zeaiter Z, Fournier PE, Raoult D. Genomic variation of Bartonella henselae strains detected in lymph nodes of patients with cat scratch disease. J Clin Microbiol. 2002;40 :1023 –1030[Abstract/Free Full Text]
  6. Avidor B, Varon M, Marmor S, et al. DNA amplification for the diagnosis of cat-scratch disease in small-quantity clinical specimens. Am J Clin Pathol. 2001;115 :900 –909[Medline]
PEDIATRICS (ISSN 1098-4275). ©2005 by the American Academy of Pediatrics



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T. A. Florin, T. E. Zaoutis, and L. B. Zaoutis
Beyond Cat Scratch Disease: Widening Spectrum of Bartonella henselae Infection
Pediatrics, May 1, 2008; 121(5): e1413 - e1425.
[Abstract] [Full Text] [PDF]

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