• Clinical and Experimental Pediatrics
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• v.60 no.3
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• pp.77-85
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• 2017

Purpose: Fever is one of the most common symptoms in children. In previous studies, infectious disease was the most common cause of pediatric fever of unknown origin (FUO). The aim of this study is to investigate the etiology, clinical characteristics and prognosis of pediatric FUO in 21 century with more diagnostics available and to analyze the factors for certain disease categories. Methods: Among the children under 18 years old who were hospitalized at Samsung Medical Center from January 2000 to December 2014, the patients who met the criteria including fever of ${\geq}38.0^{\circ}C$ for longer than ${\geq}14days$ and failure to reach a diagnosis after one week of investigations were included. Results: Total 100 patients were identified. Confirmed diagnosis was achieved in 57 patients (57%). Among them, infectious diseases (n=19, 19%) were most common, followed by connective tissue diseases (n=15, 15%), necrotizing lymphadenitis (n=8, 8%), and malignancies (n=7, 7%). Children with fever duration over 28 days had a trend for higher frequency of connective tissue diseases (28.3%) except undiagnosed etiology. The symptoms such as arthritis, lymph node enlargement and only fever without other symptoms were significantly related with connective tissue diseases, necrotizing lymphadenitis and undiagnosed respectively (P<0.001). Ninety-two patients have become afebrile at discharge and 1 patient died (1%). Conclusion: Almost half of our patients were left without diagnosis. Although it has been known that infectious disease was most common cause of pediatric FUO in the past, undiagnosed portion of FUO have now increased due to development of diagnostic techniques for infectious diseases.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.29 no.6
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• pp.548-553
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• 2007

Kikuchi-Fujimoto disease is a rare disease first described in 1972 by Kikuchi and Fujimoto et al. The disease is described as a benign and unusual self-limiting histiocytic necrotizing lymphadenitis of unknown origin, which is characterized histologically by necrotic foci surrounded by histiocytic aggregates. is usually manifested with lymphadenopathy and high fever. This disease mostly affects young Asian women between 20 and 30 years of age and has rarely been reported in children. Main symptoms are indolent or light tender, enlarged lymph nodes in the neck area. The correct diagnosis requires the histologic examination of the lymph node. Kikuchi-Fujimoto disease is easily confused histologically and clinically with lymphoma and systemic lupus erythematosis histologically and clinically. Although it is an uncommon cause of fever of unknown origin, early recognition of KFD is very important and will minimize potentially harmful and unnecessary evaluations and treatments. We reported a case, a 23-year old man who had Kikuchi-Fujimoto disease with a literature review.

• The Korean Journal of Cytopathology
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• v.10 no.1
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• pp.35-42
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• 1999

The accuracy of fine needle aspiration cytology(FNAC) of the lymph node was investigated through a review of 176 FNAC cases and the corresponding biopsies. We chose 157 FNAC cases after the exclusion of 19 inadequate ones. Sensitivity of malignancy was 94.0%, specificity 100%, false negativity 6.0%, and false positivity 0.0%. The overall diagnostic accuracy was 96.8%. Sensitivity of metastatic carcinoma was 98.0% and that of malignant lymphoma was 87.9%. False negative cases included one metastatic carcinoma and four malignant lymphomas. The aspirates of metastatic carcinoma with false negativity exhibited a diffuse smear of keratin debris without viable cells, which led to the difficulty in differentiation from benign epithelial cyst. The cases of malignant lymphoma with false negative diagnosis were two Hodgkin diseases, one Lennert's lymphoma, and one peripheral T cell lymphoma in the histologic sections. On the analysis of 39 cases of tuberculosis, 17 cases(43.6%) were diagnosed as tuberculosis, 4(10.3%) as granulomatous lymphadenitis, 3(7.7%) as necrotizing lymphadenitis, and 15(38.5%) as reactive hyperplasia or pyogenic inflammation. Sensitivity of tuberculosis was 53.9%. In conclusion, lymph node FNAC is an excellent non-invasive diagnostic tool for the diagnosis of metastatic carcinoma. The diagnostic accuracy of malignant lymphoma could be improved with flow cytometry or polymerase chain reaction for antigen receptor genes. For the FNAC diagnosis of tuberculosis, AFB stain, culture, and PCR would be helpful as adjuvant techniques.

• Childhood Kidney Diseases
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• v.12 no.2
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• pp.227-232
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• 2008

A 16-year-old girl presented with proteinuria and microscopic hematuria detected through mass urinary screening and was diagnosed as having suspected postinfectious glomerulonephritis by renal biopsy. However, heavy proteinuria did not respond to angiotensin converting enzyme inhibitor therapy. After 6 months, cervical lymphadenitis developed and a neck node biopsy showed subacute necrotizing lymphadenitis. After an additional 2 months, she developed facial erythema and thrombocytopenia. A repeat renal biopsy demonstrated lupus nephritis class IV. She was treated with pulse methylprednisolone(500 mg/day intravenously for 3 consecutive days) followed by oral deflazacort and monthly intravenous cyclophosphamide pulse(1 g/$m^2$) for 6 months. We report a case diagnosed as systemic lupus erythematosus(SLE) during medical follow-up after urinary screening.

• Pediatric Infection and Vaccine
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• v.14 no.2
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• pp.129-135
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• 2007

Purpose : Kikuchi disease is a subacute necrotizing lymphadenitis characterized by fever, cervical lymphadenopathy and benign self-limiting course in young women especially, but rare in children. Their etiopathology is still unknown, but involved viruses and autoimmune mechanism were proposed. We investigated the clinical and laboratory characteristics of Kikuchi disease in children. Methods : Five patients were diagnosed of Kikuchi disease from January 2001 to June 2006 in Kyunghee University Hospital. We reviewed their medical records retrospectively and analyzed clinical and laboratory findings. Results : The mean age of 5 patients (male to female ratio; 2:3) was 9 yr 9 mon(range: 8 yr 2 mon-12 yr 6 mon). The chief complaints were sustained fever and cervical lymph node that was unilateral, tender and swollen. All patients were treated with antibiotics before diagnosis was made, and rash developed in 2 patients. One patient showed necrotic change in ultrasound with which we suspected Kikuchi disease. Three patients were examined by CT scan additionally. The interval between admission and cervical lymph node excisional biopsy ranged from 6 days to 15 days, and mean period was 9.6 days. All pathological findings were compatible to necrotizing lymphandenitis. Conclusion : Unnecessary laboratory and imaging studies, and treatment with antibiotics tend to be done before making diagnosis, and that caused prolonged hospitalization. Therefore we studied the clinical and laboratory characteristics of Kikuchi disease in children.

• Tuberculosis and Respiratory Diseases
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• v.42 no.1
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• pp.105-109
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• 1995

Pulmonary involvement of salmonella infection is very rare and only one case of salmonella empyema had been reported in Korea. A 53-year-old woman presented to Kyung Hee Medical Center with 2-months history of left chest pain and mild fever. 3 months prior to admission, the patient was taken to laparoscopic laser cholecystectomy due to gall stone in other hospital. Chest X-ray taken on admission day showed pneumonic infiltration at left lower lung field with pleural effusion. Salmonella Group B was identified from the cultures of stool, blood, and pleural fluid. After consecutive therapy with two weeks of ceftriaxone and three weeks of ciprofloxacin combined with repeated pleural aspirations, the patient was recovered and discharged. But she was readmitted two months later due to fever and generalized malaise. The result of blood culture showed growth of Salminella Group B. The excisional biopsy of right supraclavicular lymph node disclosed necrotizing lymphadenitis. She was recovered clinically and no more bacteremia occurred after two weeks of ciprofloxacin therapy. We present very rare case of empyema due to salmonella infection and review the pertinent literature.

• Clinical and Experimental Pediatrics
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• v.49 no.8
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• pp.875-881
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• 2006

Purpose : The aims of this study were to analyze the clinical characteristics of children with Kikuchi's disease(KD) at a medical center and to investigate the etiologic role of human herpesvirus 8(HHV 8) or Epstein-Barr virus(EBV) in children with KD. Methods : Twenty six children who were diagnosed as KD between Jan. 1998 and Dec. 2005 were included. Medical records were reviewed on the clinical characteristics of children with KD. Follow up data were collected by chart review and telephone contact. Polymerase chain reaction(PCR) was performed in order to detect HHV 8 DNA, and in situ hybridization(ISH) was perfomed in order to detect EBV RNA from 20 lymph node tissues. Results : There were 15 girls and 11 boys with a mean age of 13 years. Posterior cervical lymph nodes were involved in 72 percent(18/25) of the patients. Extracervical lymphadenopathy was associated in one patient. Fever was an associated symptom in 31 percent(8/26) of the patients. Leukopenia was observed in six (46 percent) patients. The cervical lymphadenopathy usually resolved spontaneously within 6 months. Only one patient had a recurrence of lymphadenopathy with fever during follow-up. No children with KD in our series developed systemic lupus erythematosus. HHV 8 DNA was not amplified by nested PCR in any of the cases, and all cases were negative for EBV RNA by ISH. Conclusion : KD should be differentiated as a cause of cervical lymphadenopathy in children. HHV 8 and EBV may not play major causative roles in KD in children.

• Pediatric Infection and Vaccine
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• v.11 no.2
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• pp.170-175
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• 2004

Purpose : We experienced 7 patients with Kikuchi-Fujimoto disease(KFD) who had presented a prolonged fever and lymphadenopathy. The clinical and the laboratory aspects of the patients were analyzed. Methods : The medical records of the 7 KFD patients, who were confirmed by excisional lymph node biopsy from January 1996 through December 2003, were retrospectively analyzed. Results : The mean age of the children was $11.4{\pm}2.8$ years(ranging from 8 to 15 years). The male to female ratio was 1.3 : 1. The median duration of the fever prior to admission and the total duration of the fever were 12 days(ranging from 5 to 65 days) and 27 days(ranging 9 to 75 days), respectively. One patient had supraclavicular lymphadenopathy, 5 had cercical involvement, and 1 had axillary lymphadenopathy. All the histologic findings of the lymph nodes biopsies showed the characteristic findings consistent with KFD such as paracortical necrosis with karyorrhexis and an increase in the number of phagocytic histiocytes and atypical lymphocytes. As for the laboratory findings, leukopenia($3,800{\pm}700/mm^3$), anemia(hemoglobin, $11.0{\pm}1.2g/dL$), an elevated erythrocyte sedimentation rate($42{\pm}17mm/hr$), and a relatively low C-reactive protein level($1.3{\pm}0.9mg/dL$) were noted. Four patients received conservative therapy with antipyretics, and 3 patients were treated with prednisolone. Conclusion : KFD is a rare disease, yet should be considered in the differential diagnosis for older children with prolonged fever and lymphadenopathy.

• Childhood Kidney Diseases
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• v.16 no.2
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• pp.138-141
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• 2012

Rituximab, a chimeric anti-CD20 IgG1 monoclonal antibody, has been used as a rescue therapy for steroid-dependent or refractory nephrotic syndrome. However, the adverse effects of rituximab are yet to be investigated. We report a case of a 9-year-old boy with steroid-dependent nephrotic syndrome who developed Kikuchi-Fujimoto disease after several cycles of rituximab therapy. Kikuchi-Fujimoto disease is a benign, self-limited necrotizing histiocytic lymphadenitis of unknown etiology. In the present case, Kikuchi-Fujimoto disease developed when the peripheral blood B-cell count of the patient was at nadir, and the lesion regressed slowly but spontaneously after recovery of the B-cell count. To our knowledge, although the pathologic diagnosis of Kikuchi-Fujimoto disease was unavailable, this is the first report of Kikuchi-Fujimoto disease with clinical diagnosis as a possible adverse effect of rituximab.

• Clinical and Experimental Pediatrics
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• v.49 no.12
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• pp.1282-1286
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• 2006

Purpose : The causes of prolonged fever have changed during the years and are influenced by age, geographic location and availability of diagnostic facilities/techniques. The aim of the present study was to determine the causes of prolonged fever, to know the proportion and outcomes of undiagnosed children. Methods : We reviewed patients with fever persisting for more than 2 weeks in duration, with documented temperatures of $38^{\circ}C$ on several occasions, or uncertain diagnosis after intensive study of 1 week duration in other hospitals who were admitted to Pusan National University Hospital during the period from July 1999 to June 2004. Results : Fifty-four (59.0 percent) were boys and thirty-seven (41 percent) were girls. Forty-six cases were less than 6 years and 45 cases were more than 6 years; the mean age was $6.48{\pm}6.56years$. In 62 cases (68.1 percent), the fever had persisted for 2 to 3 weeks before admission and in 26 cases (28.6 percent), had lasted longer than a month. Final diagnosis had been reached in 66 of 91 children (72.5 percent). The most common cause was infection (38/91), followed by collagen vascular disease (12/91), immune deficiency (3/91), neoplasia (2/91), and miscellaneous disease. Tuberculosis was the most common infectious cause. The causes of fever were not revealed in 25 cases. Outcome on discharge were as follows; 77 cases (84.6 percent) were improved, 10 cases (11.0 percent) discharged without improvement and 4 cases (4.4 percent) expired. Conclusion : The most common cause of prolonged fever in Korean children remains infection, but the incidence of infection was decreased as compared with previous studies. Tuberculosis is the most common among infectious causes. As Kikuchi disease (subacute necrotizing lymphadenitis) represented a significant cause of prolonged fever, it should be considered if a patient has neutropenia with lymphadenopathy. Undiagnosed patients with prolonged fever (27.5 percent) have increased over previous studies.