A Case of KiKuchi-Fujimoto Disease/Histiocytic Necrotizing Lymphadenitis in 25 years old African American Female

Kikuchi-Fujimoto disease, also known as histiocytic necrotizing lymphadenitis, is a self-limiting condition that primarily affects adult females less than the age of 40. The characteristic clinical presentation of Kikuchi-Fujimoto disease is recurrent fevers, benign lymphadenopathy, and other systemic symptoms. The etiology of this syndrome is still unclear. Pathogenesis, according to clinical presentation and histological changes, suggests an immune response with the involvement of T cells and histiocytes. It has been proposed that Kikuchi-Fujimoto disease progression involves three distinct phases: proliferative, necrotizing, and xanthomatous phase. The histology of the involved lymph node demonstrates paracortical expansion of histiocytes, plasmacytoid dendritic cells, and CD8+ T cells. Moreover, areas of apoptotic necrosis are present in addition to characteristic absence of neutrophils. No specific laboratory tests currently exist that can diagnose Kikuchi-Fujimoto disease directly. Instead, the diagnosis requires histopathological and immunohistochemical examination in order to exclude other diseases with entirely different treatment course. Exclusion of lymphoma and systemic lupus erythematosus is imperative to avoid unnecessary and detrimental treatment. Treatment of Kikuchi disease involves only supportive measures because independent spontaneous resolution of this disease occurs within a 4-month period.

The gender, age, symptoms, histological characteristics, and immunohistochemical profile supports the diagnosis of Kikuchi-Fujimoto disease.

Discussion
Low grade fever and painless moderate sized cervical lymphadenopathy in a previously well young woman is the most common clinical manifestation of Kikuchi-Fujimoto disease [3,6]. According to Bosch et al, patients may also experience painful lymphadenopathy. The affected lymph node size can vary from 0.5-4 cm with rare occurrence of enlarged lymph nodes greater than 6cm. 30% to 50% of patients with Kikuchi disease can present with symptoms of upper respiratory infection, weight loss, nausea, vomiting, sore throat, and night sweats [7]. According to the retrospective literature review by Kucukardali et al. on 244 cases of Kikuchi-Fujimoto disease, the most common signs and symptoms are and not limited to: lymphadenopathy (100 %), fever (35%), rash (10%), arthritis (7%), fatigue (7%), hepatosplenomegaly (3%) [8].
Due to unspecific laboratory and imaging characteristics, definitive diagnosis of Kikuchi-Fujimoto disease is centered on excisional lymph node biopsy and subsequent histopathological assessment [9,10]. Despite the self-limited nature of this syndrome, excisional lymph node biopsy is necessary in order to exclude clinically similar conditions requiring further aggressive therapy [7].
In terms of histology, the affected lymph nodes demonstrate focal, well-circumscribed, paracortical necrotizing changes. High power view of the necrotic foci demonstrates areas of karyorrhexis, pyknosis, karyolysis in addition to scattered fibrin deposits with collections of the crescentic histiocytes ( Figure 2&3). Plasmacytoid dendritic cells are often found clustered at the margins of the necrotic foci [9,[11][12][13]. Scanty plasma cell will be seen if not absent.
In addition, the absence of neutrophils and eosinophils is a distinguished characteristic of this syndrome. A mixture of large to small lymphocytes are also present. The numerous presences of large lymphocytes with immunoblastic morphology in a background of karyorrhectic debris and scattered tangible body of macrophages, can often mislead the diagnosis towards high-grade lymphoma [9,[11][12][13]. These necrotic foci may be single or multiple with varying degree of necrosis that differ from case to case [7,9,[11][12][13].  As the disease progress, the histological appearance will also change accordingly. The early proliferative phase is characterized with follicular hyperplasia and paracortical proliferation of T-cells, B-cells, plasmacytoid monocytes, lymphocytes, and histocytes (Figure 4). Numerous apoptosis in the background of this proliferative picture is also a distinguishing feature. As the disease progress to the later necrotizing phase, the histological appearance will progressively change to show necrosis with the absence of neutrophil  Similarly, B-cell linage of large cell lymphoma can be excluded with lack of CD20, CD79a, or PAX5 expression. [9,12]. Flow cytometrical analysis may be utilized in difficult and confusing cases.

It is a difficult task to differentiate Kikuchi Fujimoto disease
from systemic lupus erythematosus due to near resemblance and occasional identical histological presentation. Useful differentiating features that favors Kikuchi disease includes abundance of CD8 positive cytotoxic T cells around the necrotic areas, scanty plasma cell presence, and absence of neutrophils and eosinophils [7,14].
Differentiating features that favors SLE/autoimmune disease includes the presence of hematoxylin bodies, Azzopardi phenomenon, reactive follicular hyperplasia, scanty cytotoxic t-cells, abundance of plasma cells, and capsular and pericapsular inflammation [7,14].
Due to close histological resemblance and morphology of these two diseases, it is of diagnostic importance, especially in ambiguous situations, to also review patient laboratory data and clinical history [9,[11][12][13] [16]. Therapy is mainly focused on alleviating symptoms which include relief of fever with antipyretics and reduction of lymph node tenderness with analgesics [9,12,13].

Conclusion
Kikuchi disease, despite its benign lymphadenopathy and self-limited clinical course, requires vigilant examination in order to exclude conditions with overlapping clinical and histological features requiring further aggressive therapy.