|Year : 2014 | Volume
| Issue : 1 | Page : 60-62
Kikuchi-Fujimoto disease: A rare cause of generalized lymphadenopathy
Sachin R Agrawal, Veena Lakhotiya, Sheetal Ingale, Ajitprasad Jain
Department of Medicine, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, Wardha, India
|Date of Web Publication||15-Apr-2014|
Sachin R Agrawal
Department of Internal Medicine, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha 442 001, Maharashtra
Source of Support: None, Conflict of Interest: None
Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare benign condition of uncertain etiology mainly seen in young females. Although the disease presents most commonly as cervical lymphadenopathy and fever, it may rarely present as generalized lymphadenopathy. A 14-year-old female patient presented with multiple progressive swellings in the neck. On evaluation, she was found to have generalized lymphadenopathy. Histopathological examination of cervical lymph node confirmed the diagnosis of KFD. Paracortical area of coagulative necrosis with abundant karyorrhetic debris surrounded by various types of histiocytes at the periphery is the characteristic histological features of the disease. KFD is a rare benign self-limited disease of lymph node with resolution of signs and symptoms in 1-4 months. Differential diagnosis of KFD should be kept in mind in patients presenting with generalized lymphadenopathy since it may be misdiagnosed as more serious pathology like lymphoma.
Keywords: Kikuchi-Fujimoto disease, histiocytes, generalized lymphadenopathy
|How to cite this article:|
Agrawal SR, Lakhotiya V, Ingale S, Jain A. Kikuchi-Fujimoto disease: A rare cause of generalized lymphadenopathy. Int J Health Allied Sci 2014;3:60-2
|How to cite this URL:|
Agrawal SR, Lakhotiya V, Ingale S, Jain A. Kikuchi-Fujimoto disease: A rare cause of generalized lymphadenopathy. Int J Health Allied Sci [serial online] 2014 [cited 2021 Jan 21];3:60-2. Available from: https://www.ijhas.in/text.asp?2014/3/1/60/130620
| Introduction|| |
Kikuchi-Fujimoto disease More Details (KFD), also known as histiocytic necrotizing lymphadenitis is a rare benign disorder of uncertain etiology mainly present in young females. The disease presents most commonly as cervical lymphadenopathy associated with fever. Other presenting complaints can be night sweats, vomiting, weight loss, rash and arthritis especially in patients with extra nodal involvements. Rarely, the disease can manifest as generalized lymphadenopathy which can mimic like lymphoma. However detail histopathological examination of lymph node can distinguish it from the other serious pathology. Here, we report a case of KFD presenting as generalized lymphadenopathy diagnosed histologically on lymph node biopsy.
| Case Report|| |
The present case is about a 14-year-old young female patient who presented with the complaint of gradually progressive multiple swelling in the neck on both side since last 7 months [Figure 1]. This was associated with mild dry cough of 1 month duration. There was no history of weight loss, fever, night sweats, vomiting or rash over body. On examination, she had multiple lymph nodes in bilateral jugulo-diagastric, submandibular, posterior cervical area. The lymph nodes varied 2-7 cm in size, were firm in consistency, non-tender, mobile with normal overlying skin. Physical examination also revealed presence bilateral axillary and inguinal lymphadenopathy. Her temperature was 98°F with pulse of 82/min and blood pressure of 110/70 mmHg. Respiratory, cardiovascular and per abdomen examination did not reveal any positive finding.
Complete blood count showed hemoglobin of 10.2 g/dl, total leucocytes count of 7500/mm 3 , platelet count of 230,000/mm 3 and erythrocyte sedimentation rate of 20 mm/1 st h. Her renal parameters, liver profile were within the normal limits. Chest skiagram [Figure 2] showed the presence of mediastinal widening suggestive of mediastinal lymphadenopathy. Ultrasound examination of the abdomen showed the presence of periportal, peripancreatic and paraaortic lymphadenopathy. Fine-needle aspiration cytology (FNAC) from the cervical lymph node revealed the presence of extensive necrosis and inflammation. In view of inconclusive FNAC report, we performed a biopsy from the cervical lymph node. Histopathological examination of cervical lymph node [Figure 3] revealed relative preservation of nodal architecture with the presence of foamy histiocytes surrounding area of extensive necrosis in paracortical area. Histological examination did not show any granuloma formation which ruled out tuberculosis. There were no hematoxylin-bodies, Reed Stein Berg cells on histological examination. These findings were consistent with diagnosis of necrotizing phase of KFD. Serological tests for human immunodeficiency virus, toxoplasma, Epstein-Barr virus and cytomegalovirus were negative. Antinuclear antibody titer, anti-double-stranded deoxyribosenucleic acid titer and rheumatoid factor were negative. In view of long duration of illness; we started prednisone at 40 mg/day. She was discharged on steroid and followed-up in the outpatient department after 2 weeks to see for response. On follow-up there was approximately 50% decrease in size of cervical lymph node when compared with initial presentation. She was continued on steroid for another 2 weeks with a plan to taper the steroid after total duration of 4 weeks.
|Figure 3: Photomicrograph of lymph node showing characteristic coagulative necrosis (white arrow) surrounded by proliferative foamy histiocytes (black arrow) at the rim (H and E, ×40)|
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| Discussion|| |
KFD was initially described from Japan in 1971 by Kikuchi  and Fujimoto and Yamaguchi. simultaneously, however later on it was reported from a wide geographical distribution all over the world. The disease is more common in females when compared with males with nearly three-fourth of the patients under the age of 30 years.  Most of the patients present clinically as localized lymphadenopathy generally located to cervical groups of lymph node. Rarely other groups of lymph node like mediastinal or retroperitoneal may be involved.  Generalized lymphadenopathy is a rare presentation in KFD reported in 1-22% of cases. Other presenting complaints can be fever, rash, night sweats, nausea, vomiting and weight loss associated with hepatospleenomegaly and arthritis especially in patients with extra nodal involvements. 
The exact pathogenesis of the KFD is not clear. The clinical presentations of the disease, course and histological changes suggest an immune response of T cells and histiocytes to an infectious agent. Various studies have shown an association between various viral infections such as Epstein-Barr virus, human herpes virus, human T cell lymphotropic virus, parvovirus B19 and development of KFD. , However, a study done by George et al.  could not find the genome of Epstein-Barr and human herpes virus in patients of KFD. Hence, the role of viral etiology in etiopathogenesis of KFD remains controversial. Some authors have studied the role of autoimmunity in the pathogenesis of KFD due to its resemblance with systemic lupus erythematosus (SLE) with regards to age, sex and histopathogical characteristics. Imamura et al. in their study have proposed a hypothesis based on electron microscopic examination that KFD is a self-limited SLE like autoimmune disorder due to virus infected transformed lymphocyte.
Diagnosis of KFD is mainly based on biopsy of involved lymph node. FNAC of lymph node have been tried to diagnose this clinical entity. However, a study conducted by Tong et al. has shown a very high false positive rate (37.5%) of FNAC for diagnosing KFD. Hence, in spite of the benign nature of the disease, excisional biopsy of the lymph node should be performed to differentiate it from more serious pathology like lymphoma. A histological feature of KFD depends upon the stage of disease which is either proliferative or necrotizing. Proliferative stage mainly consists of various histiocytes, plasmacytoid monocytes and lymphoid cells containing karyorrhetic nuclear fragments and eosinophilic apoptotic debris. Necrotizing stage is characterized by irregular paracortical area of coagulative necrosis with abundant karyorrhetic debris surrounded by various types of histiocytes at the periphery. The important histological differential diagnosis of KFD includes SLE, herpes simplex lymphadenitis and lymphoma (non-Hodgkin's and Hodgkin's). Important points which helps in distinguishing SLE lymphadenitis from necrotizing phase of KFD includes the presence of hematoxylin-bodies (representing degenerated nuclei), plasma cell and absence of neutrophils, CD8+ lymphocytes in SLE lymphadenitis. In herpes simplex lymphadenitis, there are fewer surrounding mononuclear cells and neutrophils are usually present. Since clinically KFD can mimic lymphoma, it is crucial to identify the disease histologically. Features such as preservation of nodal architecture, presence of typical abundant reactive histiocytes, relatively low mitotic rates and absent of Reed Stein Berg cell favors the diagnosis of KFD.
KFD is mostly a self-limiting disease in the majority of patients with resolution of signs and symptoms in 1-4 months. Recurrence has been observed in 3-4% of the patients.  However; one recent study have shown higher recurrence rate of 20.5% among these patients.  No effective treatment has been established for KFD. Hence, only symptomatic treatment in the form of antipyretic, analgesic has been used to relieve the symptoms. Use of systemic steroid in three patients of KFD having persistent and prolong symptoms has led to significant benefits in symptoms;  however larger studies are required to confirm these findings. Rezai et al. have reported a case of KFD that was treated successfully with chloroquine and on recurrence with hydroxychloroquine. Each treatment has led to a very prompt response.
| Conclusion|| |
KFD is rare, benign condition of uncertain cause usually characterized by cervical lymphadenopathy and fever. However rarely it may present as generalized lymphadenopathy which may mimic clinically as lymphoma. Here, we report a case of KFD presenting as generalized lymphadenopathy so as to increase awareness about the condition among physicians and to avoid the unnecessary work-up for diagnosing the condition.
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[Figure 1], [Figure 2], [Figure 3]