- Michael J Richards, MD, FRACP
Michael J Richards, MD, FRACP
- The Royal Melbourne Hospital
- Victoria, Australia
Kikuchi disease, also called Kikuchi-Fujimoto disease or Kikuchi histiocytic necrotizing lymphadenitis, was originally described in young women and is a rare, benign condition of unknown cause usually characterized by cervical lymphadenopathy and fever. Histopathology of the involved lymph nodes differentiates Kikuchi disease from several more serious conditions that it may mimic.
While the pathogenesis of Kikuchi disease is unknown, the clinical presentation, course, and histologic changes suggest an immune response of T cells and histiocytes to an infectious agent. Numerous inciting agents have been proposed, including Epstein-Barr virus (EBV) [1,2], human herpesvirus 6, human herpesvirus 8 , human immunodeficiency virus (HIV), parvovirus B19 , paramyxoviruses, parainfluenza virus, Yersinia enterocolitica, and Toxoplasma. In one report, EBV was detected by in situ hybridization in tissue in all of 10 patients examined [5,6], but immunohistochemistry detected EBV-encoded protein in only 1 of these patients. An observation that is consistent with a viral etiology is increased levels of interferon-alpha and of other proteins stimulated by interferon-alpha including 2',5'-oligoadenylate synthetase and tubuloreticular structures in the cytoplasm of stimulated lymphocytes, histiocytes, and vascular endothelium .
Apoptotic cell death mediated by cytotoxic CD8-positive T lymphocytes is the principal mechanism of cellular destruction [8-10]. Histiocytes may act as enhancers. The apoptosis appears to be induced by the Fas-Fas ligand system. Morphologic characteristics of apoptotic cells including nuclear chromatin condensation and fragmentation along the nuclear membrane with intact organelles and histiocytes phagocytosing karyorrhectic debris (apoptotic bodies) are found on transmission electron microscopy.
A possible role for interferon-gamma and interleukin (IL)-6 in the pathogenesis of this syndrome is suggested by one study of four men with biopsy-proven Kikuchi disease . During the acute phase of illness, these patients had elevated serum levels of interferon-gamma and IL-6 but not interferon-alpha, tumor necrosis factor, or IL-2. The interferon-gamma and IL-6 levels returned to normal during convalescence. Subsequent reports support this role . Analysis of lymph node biopsies in patients with Kikuchi disease show T-bet-expressing CD4 cells accompanied by T-bet-positive CD8 and B cells .
Kikuchi syndrome shares sex and age predisposition as well as histologic features with systemic lupus erythematosus (SLE). Tubuloreticular structures in the lymphocytes and endothelial cells in patients with SLE have been observed to be similar to those seen in Kikuchi disease. One ultrastructural study proposed that Kikuchi syndrome reflects a self-limited, SLE-like autoimmune condition caused by virus-infected transformed lymphocytes . (See "Epidemiology and pathogenesis of systemic lupus erythematosus".)
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