Abstract/Text
Kikuchi-Fujimoto Disease (KFD) was first described in Japan in 1972. The disease frequently mimics tuberculous lymphadenitis, malign lymphoma, and many other benign and malignant conditions. To our knowledge, there is no previous study comparing the clinical and laboratory characteristics of patients from different geographical parts of the world. We searched literature records beginning from 1991 and analyzed epidemiological, clinical, and laboratory data of 244 patients (including cases diagnosed in our institution) reported in 181 publications. Of the 244 cases, 33% were male and 77% were female. Mean age was 25 (1-64) and 70% was younger than 30. Most of the cases were reported from Taiwan (36%), USA (6.6%), and Spain (6.3%). Fever (35%), fatigue (7%) and joint pain (7%) were the most frequent symptoms, while lymphadenomegaly (100%), erythematous rashes (10%), arthritis (5%), hepatosplenomegaly (3%), leucopenia (43%), high erythrocyte sedimentation rate (40%), and anemia (23%) being the most common findings. KFD was associated with SLE (32 cases), non-infectious inflammatory diseases (24 cases), and viral infections (17 cases). SLE was more frequent in cases from Asia than Europe (28 and 9%, respectively). The disease was self-limiting in 156 (64%) and corticosteroid treatment was necessary in 16 (16%) of the cases. The mortality rate was 2.1%. Early diagnosis is crucial as the clinical and laboratory presentation generally imitates situations needing lengthy and costly diagnostic and therapeutic interventions. Additionally, association with SLE needs further investigation.
Guillaume Dumas, Virginie Prendki, Julien Haroche, Zahir Amoura, Patrice Cacoub, Lionel Galicier, Olivier Meyer, Christophe Rapp, Christophe Deligny, Bertrand Godeau, Elisabeth Aslangul, Olivier Lambotte, Thomas Papo, Jacques Pouchot, Mohamed Hamidou, Claude Bachmeyer, Eric Hachulla, Thierry Carmoi, Robin Dhote, Magdalena Gerin, Arsene Mekinian, Jérôme Stirnemann, Fréderic Charlotte, Dominique Farge, Thierry Molina, Olivier Fain
Kikuchi-Fujimoto disease: retrospective study of 91 cases and review of the literature.
Medicine (Baltimore). 2014 Nov;93(24):372-82. doi: 10.1097/MD.0000000000000220.
Abstract/Text
Kikuchi-Fujimoto disease (KFD) is a rare cause of lymphadenopathy, most often cervical. It has been mainly described in Asia. There are few data available on this disease in Europe. We conducted this retrospective, observational, multicenter study to describe KFD in France and to determine the characteristics of severe forms of the disease and forms associated with systemic lupus erythematosus (SLE). We included 91 cases of KFD, diagnosed between January 1989 and January 2011 in 13 French hospital centers (median age, 30 ± 10.4 yr; 77% female). The ethnic origins of the patients were European (33%), Afro-Caribbean (32%), North African (15.4%), and Asian (13%). Eighteen patients had a history of systemic disease, including 11 with SLE. Lymph node involvement was cervical (90%), often in the context of polyadenopathy (52%), and it was associated with hepatomegaly and splenomegaly in 14.8% of cases. Deeper sites of involvement were noted in 18% of cases. Constitutional signs consisted mainly of fever (67%), asthenia (74.4%), and weight loss (51.2%). Other manifestations included skin rash (32.9%), arthromyalgia (34.1%), 2 cases of aseptic meningitis, and 3 cases of hemophagocytic lymphohistiocytosis. Biological signs included lymphocytopenia (63.8%) and increase of acute phase reactants (56.4%). Antinuclear antibodies (ANAs) and anti-DNA antibodies were present in 45.2% and 18% of the patients sampled, respectively. Concomitant viral infection was detected in 8 patients (8.8%). Systemic corticosteroids were prescribed in 32% of cases, hydroxychloroquine in 17.6%, and intravenous immunoglobulin in 3 patients. The disease course was always favorable. Recurrence was observed in 21% of cases. In the 33 patients with ANA at diagnosis, SLE was known in 11 patients, diagnosed concomitantly in 10 cases and in the year following diagnosis in 2 cases; 6 patients did not have SLE, and 4 patients were lost to follow-up (median follow-up, 19 mo; range, 3-39 mo). The presence of weight loss, arthralgia, skin lesions, and ANA was associated with the development of SLE (p < 0.05). Male sex and lymphopenia were associated with severe forms of KFD (p < 0.05). KFD can occur in all populations, irrespective of ethnic origin. Deep forms are common. An association with SLE should be investigated. A prospective study is required to determine the risk factors for the development of SLE.
Abstract/Text
Histiocytic necrotizing lymphadenitis of Kikuchi and Fujimoto is a well-defined clinicopathologic entity of unknown cause. Both the Epstein-Barr virus (EBV) and human herpesvirus type 6 (HHV-6) have been suggested as potential etiologic agents. Twenty cases of Kikuchi-Fujimoto disease were studied for the presence of EBV DNA and HHV-6 DNA by the polymerase chain reaction (PCR), and in situ hybridization in the case of EBV. Cellular DNA from sections of formalin-fixed, paraffin-embedded lymph node tissue was amplified using the PCR technique and oligonucleotide primers to the EBV BamH1 W, lymphocyte-determined membrane antigen, or the EBNA-1 region. These studies were performed in three separate laboratories. In addition, 12 cases were examined by in situ hybridization, eight of which had shown at least one positive PCR signal for EBV. The presence of HHV-6 was assessed by PCR using primers to part of the pZVH14 sequence. Biopsy specimens from eight patients (40%) showed a strong positive signal for EBV in at least one laboratory, while an additional three specimens (15%) showed a weaker positive signal. Five cases studied showed rare positive cells by in situ hybridization, and one case had scattered positive cells. All samples lacked HHV-6 genomic templates. These findings indicate that HHV-6 does not play a role in the pathogenesis of Kikuchi-Fujimoto disease and do not implicate EBV as a causal agent for Kikuchi-Fujimoto disease, since EBV was detected in only a fraction of cases with a low number of positive cells detected by in situ hybridization. Further, some discrepancies were identified in the positive results for EBV in samples studied by multiple laboratories. These results indicate that inconsistent results by PCR may occur with very low levels of viral genomes and that different laboratories perform DNA amplification at different efficiencies. Alternatively, laboratory contamination may give rise to false-positive results. Therefore, a positive result for EBV should be interpreted with caution and should be confirmed by repeated study (PCR) or by independent methodology (in situ hybridization).
Abstract/Text
We report scattered indurated erythematous lesions that presented in an 18-year-old Japanese man with Kikuchi's disease (KD; histiocytic necrotizing lymphadenitis). A skin biopsy showed a proliferation of histiocytes and abundant nuclear debris without the presence of neutrophils, which is characteristic of KD. The specific dermatological and pathological details of KD have been yet to be fully described. In order to assess the typical skin features of KD better, we have reviewed all the previously well-documented reports of such lesions. As the clinical and histopathological cutaneous findings in KD are so heterogeneous, it is important that scattered indurated erythematous lesions should be included as one of the possible cutaneous manifestations of this disease.
Abstract/Text
Kikuchi-Fujmoto disease (KFD), also known as "histiocytic necrotizing lymphadenitis", is a rare lymphadenitis of unknown origin, but with an excellent prognosis. It is more common in Asia, but isolated cases are also reported in America, Africa and Europe. The disease can have an acute or subacute course, usually develops in 1 to 3 weeks, with spontaneous resolution in 1-4 months. The main clinical sign is cervical lymphadenopathy, especially in the posterior cervical triangle with bulky and painful lymph nodes, usually affecting only one side; rare cases of generalized lymphadenopathy can be seen. This common clinical presentation can also be accompanied by nausea, vomiting, weight loss, weakness, headache and arthralgia. An extranodal extension of the disease, including involvement of skin, eye, and bone marrow localizations, has been rarely described. Most patients have leukopenia or neutropenia with a relative leukocytosis. At an ultrasound exploration of the affected lymph nodes, a hypoechoic aspect can be seen, with an external, thick and irregular hyperechoic ring. As there are no specific tests for KFD, the final diagnosis is histologically-based from lymph node excisional biopsy. Histological examination shows paracortical foci of coagulative necrosis containing karyorrhectic debris, which are surrounded by numerous CD68+/myeloperoxidase (MPO)+ histiocytes, CD68+/CD123+ plasmacytoid dendritic cells, and a minority of small- to large-sized CD8+lymphocytes and immunoblasts. Differential diagnosis mainly includes systemic lupus erithematous (SLE)-related lymphadenopathy and large cell lymphoma. The histological absence of neutrophils, plasmacells, as well as hematoxylin bodies, is a feature which argues against the diagnosis of SLE. In addition, the absence of auto-antibodies and anti-nuclear antibodies is useful in ruling out an autoimmune disorder. Early diagnosis of KFD is crucial to prevent the patients undergo extensive investigations related to suspected malignant lymphomas or other diseases.
© Copyright Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.
Abstract/Text
BACKGROUND AND PURPOSE: Although CT findings of Kikuchi disease (KD), or histiocytic necrotizing lymphadenitis, are reported in several case reports, large-scale analysis of the disease has not been undertaken. We characterized the clinical and CT findings in a large group of patients with KD.
METHODS: Between 1990 and 2002, 96 patients (68 women, 28 men; mean age, 24.4 years) underwent biopsy of the cervical lymph nodes and had histologically proved KD at our institution. We reviewed their clinical and CT findings and recorded the total number of affected nodes; location and size of the lymph nodes; and characteristic findings including necrosis, perinodal infiltration, and contrast enhancement.
RESULTS: We identified 1196 affected lymph nodes (12.5 nodes per patient). The affected lymph nodes were 0.5-3.5 cm (mean, 1.62 cm). Perinodal infiltration was found in 78 patients (81.3%). Eighty (83.3%) had homogeneous nodal contrast enhancement. Nine patients (9.4%) had lymph nodes with a focal low attenuation, and seven (7.3%) had ring-shaped lymph nodes. Unilateral and bilateral cervical lymph nodes were affected in 76 and 20 patients, respectively. Lymph nodes were mainly located at levels II (IIA, 174 nodes; IIB, 254 nodes), III (222 nodes), IV (160 nodes), and V (VA 126 nodes, VB 130 nodes). Follow-up CT in 32 patients showed complete resolution in 14 and partially improved lymphadenopathy in 18.
CONCLUSION: Awareness of the various CT appearances of KD and follow-up CT may be helpful for more accurate diagnosis of the disease.
Abstract/Text
OBJECTIVE: The purpose of this study was to determine whether a CT interpretation with imaging pattern analysis differentiates Kikuchi disease (KD) from the two more frequently encountered differential lymph nodes diagnoses of tuberculous lymphadenopathy (TL) and reactive hyperplasia (RH).
MATERIALS AND METHODS: Between January 2012 and July 2015, 20 patients with KD (6 men, 14 women; mean age, 27.80 years), 36 patients with RH (10 men, 26 women; mean age, 33.08 years) and 34 patients with TL (17 men, 17 women; mean age, 39.82 years) were pathologically diagnosed using US-guided fine needle aspiration biopsy, core needle biopsy, or surgical excisional biopsy. We recorded the total number, location, and size of the affected cervical lymph nodes, and two radiologists reviewed the characteristic imaging findings, including the presence of necrosis, cortical enhancement pattern, perinodal infiltration, conglomeration and nodal calcification, to form a consensus. In addition, we compared two attenuation indices on the nonnecrotic portion of the affected lymph nodes, nodal cortical attenuation (NCA) and the ratio of NCA to the adjacent muscle (NCA/M).
RESULTS: Conglomeration, enhancement pattern and NCA/M values were independent predictive CT features to distinguish KD from RH. Age and enhancement pattern discriminated KD from TL. Only the mean NCA/M value was a statistically significant CT feature (p = .008) in differentiating KD from both RH+TL. The mean NCA/M of KD (1.67 ± 0.20) was significantly higher than that of RH (1.49 ± 0.20) or TL (1.47 ± 0.21).
CONCLUSION: Our results indicate that in case of nonnecrotic lymphadenopathy, a higher NCA/M index can differentiate KD from RH and TL. In addition, the enhancement pattern according to the degree of necrosis discriminated between KD and TL in the case of necrotic lymphadenopathy.
Abstract/Text
OBJECTIVE: The purpose of this study was to document the sonographic findings of axillary lymphadenopathy in Kikuchi disease.
METHODS: The medical records and sonographic findings of 7 patients with a pathologic diagnosis of Kikuchi disease in the axillary lymph node by sonographically guided core needle biopsy (n=6) or excisional biopsy (n=1) were reviewed. On sonograms, lymph nodes were assessed for their distribution, size, shape, border, echogenicity, and internal architecture, and those sonographic features of each node were evaluated to determine whether the findings favored malignant or benign lymphadenopathy.
RESULTS: Of the 7 patients (1 man and 6 women; mean age +/- SD, 34.3+/-7.7 years), 29 affected lymph nodes (5-38 mm; mean, 14.8+/-7.2 mm) were identified on sonograms. The sonographic characteristics were as follows: the shortest axis/longest axis ratio of the node (mean, 0.595) was 0.5 or greater in 22 nodes (76%); the border was sharp in 16 (55%); the cortex was hypoechoic in 20 (69%) and isoechoic in 9 (31%); the hilum was narrow in 1 (4%) and absent in 16 (55%); and cortical thickening was found in 13 (45%, concentric in 6 and eccentric in 7). Nineteen lymph nodes (66%) were classified as having malignant-favoring features, and 10 (34%) were classified as having benign-favoring features.
CONCLUSIONS: Many axillary lymph nodes in Kikuchi disease look suspicious sonographically. When lymph nodes in the axilla show suspicious findings on sonograms of relatively young patients, Kikuchi disease can be considered a possible differential diagnosis, and image-guided percutaneous biopsy should be done.
Abstract/Text
We conducted a clinicopathologic study of 79 cases of Kikuchi's disease. Our results confirmed that Kikuchi's disease is a distinctive type of necrotizing lymphadenitis that affects primarily the cervical lymph nodes of young adults and has a self-limited clinical course. However, female predominance was not as striking as heretofore reported. A low, but possible, recurrence rate of 3.3% was documented. Extranodal cutaneous involvement occurred in one patient who had a more severe and protracted clinical course. Classification of the histopathologic changes into three histologic types was proposed: proliferative, necrotizing, and xanthomatous types. These three types differed in certain aspects of their clinical features. Immunohistologic analysis revealed that the predominant cells of the lesions were various types of histiocytes, including the enigmatic plasmacytoid monocytes. A variable number of CD8(+) T cells correlating with the duration of the disease was detected. B cells were nearly absent, and only an insignificant number of OPD4(+) T cells was present. Eight cases studied by the flow cytometric DNA analysis all showed a diploid DNA content. Although the histologic changes of Kikuchi's disease were variable, the findings were sufficiently distinctive to permit accurate diagnosis. Malignant lymphoma and especially lupus lymphadenitis can be mistaken for Kikuchi's disease; thus differentiation is crucial.
Abstract/Text
Histiocytic necrotizing lymphadenitis, or Kikuchi's disease, is a self-limiting cervical lymphadenitis of unknown origin. Since no specific treatment has been reported for Kikuchi's disease to date, once a diagnosis of Kikuchi's disease has been established, the role of the physician has been limited only to treating the symptoms. Sometimes, however, the clinical manifestations of the disease can be very distressing for the patients. Thus, a more aggressive form of treatment may be required for the patients who suffer from severe and persisting symptoms and recurrence. We present three cases of Kikuchi's disease that benefited significantly from systemic administration of prednisone.
Fumika Honda, Hiroto Tsuboi, Hirofumi Toko, Ayako Ohyama, Hidenori Takahashi, Saori Abe, Masahiro Yokosawa, Hiromitsu Asashima, Shinya Hagiwara, Tomoya Hirota, Yuya Kondo, Isao Matsumoto, Takayuki Sumida
Recurrent Kikuchi-Fujimoto Disease Successfully Treated by the Concomitant Use of Hydroxychloroquine and Corticosteroids.
Intern Med. 2017 Dec 15;56(24):3373-3377. doi: 10.2169/internalmedicine.9205-17. Epub 2017 Oct 11.
Abstract/Text
Kikuchi-Fujimoto disease (KFD) is a benign disease of unknown etiology characterized by lymphadenopathy and a fever. For the majority of patients with KFD, the course is self-limited; however, the optimum method of managing recurrent cases has not yet been established. We herein report a case of a 42-year-old Japanese woman with KFD (confirmed by a lymph node biopsy). Although high-dose prednisolone (PSL) rapidly induced remission, she experienced four recurrences on treatment tapering. Concomitant use of hydroxychloroquine (HCQ) with low-dose PSL induced continuous remission. This is the first case to suggest the effectiveness of HCQ for recurrent KFD in a Japanese patient.
