Bilateral anterior uveitis as an unusual manifestation of Kikuchi–Fujimoto disease

S. H. Kim, S. J. Kim, H. Chung, H. S. Lee1, H. B. Kim2 and K. H. Park3

Department of Ophthalmology, College of Medicine, Seoul National University and 1 Department of Pathology, 2 Department of Infectious Diseases and 3 Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul, Korea

Correspondence to: K. H. Park, Department of Ophthalmology, Seoul National University Bundang Hospital, #300 Kumi-dong, Bundang-gu, Seongnam city, Kyunggi Province, Korea. E-mail: jiani4{at}snu.ac.kr

SIR, Kikuchi–Fujimoto disease (KFD) is a subacute necrotizing lymphadenitis of unknown origin and is usually a self-limited cause of fever and lymph node enlargement [1]. KFD may be associated with a wide spectrum of immune diseases, such as polymyositis [2], systemic lupus erythematosus [3], arthritis [4] and uveitis [5]. However, as far as we are aware the simultaneous development of KFD and uveitis has not been reported. Here, we present the first case of KFD involving the development of bilateral anterior uveitis during the disease course, and compare fluorescence-activated cell sorting (FACS) assay results of inflammatory cells in aqueous humor with those of lymph node tissue immunohistochemical staining.

A 16-yr-old Asian boy was referred to the Department of Internal Medicine with a spiking fever of unknown origin of up to 40°C of 3 weeks’ duration. Physical examination revealed multiple, non-tender right cervical lymph node enlargements of diameter 0.5–1 cm. Laboratory testing showed mild leucopenia (2140/mm3) with elevated C-reactive protein (6.11 mg/dl) and an erythrocyte sedimentation rate of 41 mm/h. Immunological tests were negative for syphilis, toxoplasmosis, cytomegalovirus, parvovirus B19 and human immunodeficiency virus. IgG antibodies for Epstein–Barr virus (EBV) were positive but IgM antibodies were negative, suggesting a previous EBV infection. Blood culture was negative and no specific finding was observed by bone marrow biopsy. Chest computed tomography showed no evidence of pulmonary tuberculosis or sarcoidosis. Acid-fast staining for tuberculosis was negative and angiotensin-converting enzyme was within the normal range. Antinuclear and anti-double stranded DNA antibodies were negative and the clinical features of systemic lupus erythematosus were absent. Anti-neutrophil cytoplasmic antibodies (ANCA), rheumatoid factor and human leucocyte antigen (HLA) B-27 were negative. Neck computed tomography revealed multiple lymph node enlargements with necrosis in the right side of the neck. Lymph node biopsy showed findings compatible with KFD, including necrotic change and pronounced karyorrhexis, and histiocyte and lymphocyte infiltration without neutrophils. Immunohistochemical staining revealed that most lymphocytes stained as CD3+ T cells and that there were increased numbers of CD8+ cytotoxic-suppressor T cells. CD56+ natural killer cells were rare, and histiocytes were positive for CD68 and myeloperoxidase.

Two days after the diagnosis, he consulted an ophthalmologist complaining of conjunctival injection and visual blurring in both eyes, which had developed during the previous night. He and his family members did not have any history of uveitis. An ocular examination showed bilateral anterior uveitis and aqueous cells were graded as 4+; however, keratic precipitate or hypopyon was not noted. Evidence of posterior segment involvement, such as retinal vascular sheathing or vitreous cell, was absent. Fluorescein retinal angiography showed normal findings. Aqueous humor was sampled from both eyes at the ophthalmic presentation, and was negative for EBV by the polymerase chain reaction. A FACS assay of inflammatory cells in the aqueous humor showed that lymphoid cells were mainly T cells, with predominance of CD8+ cells over CD4+ helper cells. The proportion of CD56+ T cells was increased, and they were mainly CD8+ cells (Fig. 1). His best corrected visual acuity was 20/25 in both eyes. After 3 weeks of topical steroid therapy, the intra-ocular inflammation resolved completely and visual acuity improved to 20/20 in both eyes. The fever subsided spontaneously 2 weeks after the ophthalmic consultation and the lymph node enlargement subsequently resolved. During the follow-up period of 6 months, the uveitis did not recur.



View larger version (37K):
[in this window]
[in a new window]
 
FIG. 1. Fluorescence-activated cell sorting (FACS) assay of inflammatory cells in the aqueous humor of a patient with Kikuchi–Fujimoto disease. Lymphoid cells were mainly CD3+ T cells, with a predominance of CD8+ cytotoxic-suppressor T cells over CD4+ helper T cells. The proportion of CD56+ natural killer T cells was increased, which were mainly CD8+ cytotoxic cells.

 
Kikuchi–Fujimoto disease, first described by Kikuchi and Fujimoto in 1972, is a benign, self-limited disease of unknown origin that often manifests as enlarged cervical lymph nodes and fever [1]. Laboratory abnormalities are usually non-specific and leucopenia is frequently observed. The histological features are characteristic but are occasionally confused with SLE or lymphoma. An immunohistochemical study revealed an increase in CD8+ lymphocytes with a relative paucity of CD56+ cells and histiocytes expressing CD68+ and myeloperoxidase [6,7]. The cause of this disease is unknown, though autoimmune or various infectious origins, including EBV and human herpes virus type 6, have been suggested [7, 8].

The patient we describe here had clinical and pathological features compatible with KFD and simultaneously developed bilateral anterior uveitis. As far as we know, only one case of KFD developing uveitis has been reported. However, in that case bilateral panuveitis developed some 2 yr later. Furthermore, no cell analysis was presented. In our case, bilateral anterior uveitis developed during the course of KFD and subsided with the disappearance of fever and lymphadenopathy. In addition, a FACS assay of aqueous humor showed findings similar to those obtained by the immunohistochemical staining of lymph node tissue, although the proportion of CD56+ natural killer T cells was increased in the aqueous humor. This may be evidence for a shared pathogenesis between KFD and concomitant anterior uveitis.

In conclusion, we present a case that developed bilateral anterior uveitis as a rare manifestation of KFD. A full ophthalmological examination is needed in patients with KFD to reveal the presence of uveitis.

The authors have declared no conflicts of interest.

References

  1. Norris AH, Krasinskas AM, Salhany KE, Gluckman SJ. Kikuchi–Fujimoto disease: a benign cause of fever and lymphadenopathy. Am J Med 1996;171:401–5.[CrossRef]
  2. Wilkinson CE, Nichol F. Kikuchi–Fujimoto disease associated with polymyositis. Rheumatology 2000;39:1302–4.[Free Full Text]
  3. Chen YH, Lan JL. Kikuchi disease in systemic lupus erythematosus: clinical features and literature review. J Microbiol Immunol Infect 1998;31:187–92.[Medline]
  4. Douglas M, Bradbury R, Kannangara S, Mitchell D. Arthritis as an unusual manifestation of Kikuchi–Fujimoto disease. Rheumatology 2003;42:1010–2.[Free Full Text]
  5. Taguri AH, McIlwaine GG. Bilateral panuveitis: a possible association with Kikuchi–Fujimoto disease. Am J Ophthalmol 2001;132:419–24.[CrossRef][ISI][Medline]
  6. Pileri SA, Facchetti F, Ascani S, et al. Myeloperoxidase expression by histiocytes in Kikuchi's and Kikuchi-like lymphadenopathy. Am J Pathol 2001;159:915–24.[Abstract/Free Full Text]
  7. Felgar RE, Furth EE, Wasik MA, Gluckman SJ, Salhany KE. Histiocytic necrotizing lymphadenitis (Kikuchi's disease): in situ end-labeling, immunohistochemical, and serologic evidence supporting cytotoxic lymphocyte-mediated apoptotic cell death. Mod Pathol 1997;10:231–41.[ISI][Medline]
  8. Hollinsworth HC, Peiper SC, Weiss LM, Raffeld M, Jaffe ES. An investigation of the viral pathogenesis of Kikuchi–Fujimoto disease-lack of evidence for Epstein–Barr virus or human herpes virus type 6 as the causative agents. Arch Pathol Lab Med 1994;118:134–40.[ISI][Medline]
Accepted 12 May 2004





This Article
Full Text (PDF)
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Disclaimer
Request Permissions
Google Scholar
Articles by Kim, S. H.
Articles by Park, K. H.
PubMed
PubMed Citation
Articles by Kim, S. H.
Articles by Park, K. H.
Related Collections
Other Rheumatology