Presenter: Intern 吳叡森 Supervisor: VS 沈靜芬醫師 INTERN SEMINAR Presenter: Intern 吳叡森 Supervisor: VS 沈靜芬醫師

OUTLINE Case presentation Kikuchi disease Epidemiology Pathology Clinical Manifestations Studies in Taiwan Statistics in NCKUH Back to our case 當然要改

CASE PRESENTATION

BASIC INFORMATION Name: 徐X峰 Gender: Male Age: 15 y/o Occupation: Student Admission: 99/12/01 Chart No.:052828XX

PAST HISTORY Meningitis (91/08) Epilepsy (91/11) with medical control for 3 years and subsided for 6 years (no medication now) No known drug allergy Vaccine: as scheduled in Taiwan (無自費) Development: no delayed history

ADMISSION C.C: Intermittent fever around 38.0˚C~39.0˚C and cough for more than 3 weeks PI: Intermittent fever 38˚C~39˚C Cough with whitish sputum 3 weeks Dizziness and headache Left neck mass Sore throat (-), dysphagia (-), body weight loss (-) 2002/12/01 PE: No specific findings Neck mass: left side, two: 7.5*4, 1.5*1cm Fixed, elastic, mild tenderness (+), local heat(-) 加度 On and off LMD 發現 neck mass 一開始沒有發現 病程拖久 Initial 不太一樣

LAB DATA Admission 12/1 WBC 5.5 RBC 4.79 Hb 14.3 Hct 41.3 MCV 86.2 MCH 29.9 MCHC 34.7 RDW 14.6 Plt 315 ESR 45 Seg 58 Eos Baso 1 Mono 7 Lymph 34 APTT 34.2 PT 12.6

LAB DATA Admission 12/1 BUN 10 Crea 0.77 eGFR GOT 44 GPT 23 ALK-P 129 Ca 8.9 P 4.0 LD 303 Na 135 K 4.4 Cl 96 CRP 42.6 C3 85.9 C4 36.6 U/A Negative black

IMAGE AND BIOPSY Neck echo: Multiple enlarged lymph nodes, level II, III, IV, V, and left supraclavicular

IMAGE AND BIOPSY Bilateral enlarged neck lymphadenopathies, and these nodules did not show central necrosis Suspect the inflammatory process Biopsy: Lymphoid hyperplasia Necrotizing lymphadenitis (Kikuchi's disease.)

DISCUSSION KIKUCHI’S DISEASE

EPIDEMIOLOGY Higher prevalence among Japanese and other Asiatic people, compared to Western Affected patients most often are adults younger than 40 years (range, 19 months to 75 years) Taiwan: 20+ Ratio: Female > Male, but was still controversial Xavier Bosch, MD,1 Antonio Guilabert, MD,2 Rosa Miquel, MD,3 and Elias Campo, MD 3--Enigmatic Kikuchi-Fujimoto Disease: A Comprehensive Review

PATHOGENESIS Viral or autoimmune, but wasn’t proven EBV, HPV-6, HPV-8 SLE CD-8 T cell Xavier Bosch, MD,1 Antonio Guilabert, MD,2 Rosa Miquel, MD,3 and Elias Campo, MD 3--Enigmatic Kikuchi-Fujimoto Disease: A Comprehensive Review----American Journal of Clinical Pathology. 2004;122(1) © 2004 American Society for Clinical Pathology— EBV, HPV-6, HPV-8 (?) 有人推測，但其他人做研究結論反而是沒有 SLE (?) 驗RA或ANA都沒有findings, 但這兩個疾病似乎真的有關聯 Xavier Bosch, MD,1 Antonio Guilabert, MD,2 Rosa Miquel, MD,3 and Elias Campo, MD 3--Enigmatic Kikuchi-Fujimoto Disease: A Comprehensive Review

CLINICAL MANIFESTATIONS Cervical lymphadenopathy is present in 56% to 98% of cases Posterior cervical triangle (88.5%), generally unilateral Lymph node size :0.5 to 4 cm (93.4%) Painful lymphadenopathy: 59% of patients. Generalized lymphadenopathy has been reported in 1% to 22% of cases Xavier Bosch, MD,1 Antonio Guilabert, MD,2 Rosa Miquel, MD,3 and Elias Campo, MD 3--Enigmatic Kikuchi-Fujimoto Disease: A Comprehensive Review

CLINICAL MANIFESTATIONS Fever: 30% to 50% usually low-grade, upper respiratory symptoms Others: Body weight loss Nausea, Vomiting Sore throat Night sweats Lab: Usually within normal range Xavier Bosch, MD,1 Antonio Guilabert, MD,2 Rosa Miquel, MD,3 and Elias Campo, MD 3--Enigmatic Kikuchi-Fujimoto Disease: A Comprehensive Review

DIAGNOSIS On the basis of an excisional biopsy of affected lymph nodes Does not have a characteristic appearance on US or CT Variable, mimic lymphoma, tumor metastasis and tuberculosis Fine-needle aspiration cytology (FNAC) Accuracy: 56% If it was diagnosed, surgical bx. Isn’t necessary Underdiagnosed!? Miller WT Jr, Perez-Jaffe LA. Cross-sectional imaging of Kikuchi disease. J Comput Assist Tomogr. 1999;23:548-551.

HISTOLOGIC FEATURES Fragmentation, necrosis, and karyorrhexis Irregular paracortical areas of coagulative necrosis Abundant karyorrhectic debris Absence of plasma cells and neutrophils Large numbers of different types of histiocytes at the margin of the necrotic areas Karyorrhexis is the destructive fragmentation of the nucleus of a dying cell[1] whereby its chromatin is distributed irregularly throughout the cytoplasm

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Paracortical necrosis OUR CASE 2010 Paracortical necrosis Germinal center, 下面可看見necrosis Shape, follicle Germinal center Follicle- B-cell Paracortical- T-cell

different types of histiocytes OUR CASE 2010 different types of histiocytes karyorrhectic debris 下面可看見necrosis 碎karytosis 彎曲的histyocyte 核裂解 無發炎現象 No malignant, no granuloma, histiocyte = macrophage + dendritic cell Absence of plasma cells and neutrophils

CLINICAL COURSE Self-limited Lasts 1 to 4 months Recurrence rate of 3% to 4% has been reported

TREATMENT No specific treatment Symptomatic treatment measures to relieve distressing local and systemic complaints should be used (ex: analgesics, antipyretics, and rest) Cortico-steroids—controversial Awareness of mistaken of this disease! Analgesic 止痛 Antipyretic 退燒 characterized by multiple flares of bulky cervical lymphadenopathy and fever Jang YJ, Park KH, Seok HJ. Management of Kikuchi's disease using glucocorticoid. J Laryngol Otol. 2000;114:709-711.

STUDIES IN TAIWAN 高雄長庚 台大醫院 高雄榮總 桃園長庚小兒

Unilateral predominance STUDIES IN TAIWAN Clinical 高雄長庚 臺大醫院 高雄榮總 桃園長庚小兒 Study Period January 1986 to May 2002 March 1989 to September 2006 January 1994 to January 2004 January 1985 to December 2001 Population 6~16 y/o, 23 6~55 y/o, 195 9~54 y/o, 58 2~18 y/o , 64 M/F ratio 15/8 54/141 21/37 35/29 Fever 7 (30.4) 74 (37.9) 25 (43) 18 (85.7) Tenderness LN 5 (21.7) 104 (53.3) 29 (50) 32 (50) Lymphadenopathy, site Bilateral 4 (17.4) 45 (23.1) 12 (21) 11 (17.5) Right 12 (52.2) 63 (43.2) 19 (32.7) 52 (82.5) Left 7(30.4) 83 (56.8) 27 (46.5) Unilateral predominance

STUDIES IN TAIWAN Lab Data 高雄長庚 臺大醫院 高雄榮總 桃園長庚小兒 Leukocytopenia <3000, 28(18.9) <4000, 17(29) 26 (44.1) Elevated ESR >20, 15(78.9) >20, 8 (14) >30, 5(41.7) GOT (5~40) >45, 6(22.2) GPT (5~55) >40, 21(23.3) >45, 4(25) CRP (0~8) >0.8, 18 (38.3) >6, 7(12) >5, 5(26.3) LDH (100~200) >460, 42(52.5) >205, 4(7) Anemia M<13, F<12, 6 (10) 2 (3.4) Recurrence 14 (14.6) 8years 2 (3.1)

桃園長庚小兒 Prolonged fever: Unilateral, tender LN, Hepatomegaly, Skin rash Prolonged: >1 week Prolonged fever: Unilateral, tender LN, Hepatomegaly, Skin rash Non-prolonged fever: Bilateral lymphadenopathy

桃園長庚小兒 Prolonged fever: Leukocytopenia, Anemia

高雄榮總

桃園長庚小兒

IN NCKUH Materials and Criteria: 2000~2010 Under 20y/o children when diagnosed Diagnosed in NCKUH 21 but 1 was diagnosed in義大= 20 Male:6, Female:14 Pathologic report key word: Kikuchi

IN NCKUH

AGE

CLINICAL MANIFESTATION Items Ratio % Fever 13/19 68 Lymphadenopathy, site Post. Triangle 19/20 95 Ant. Triangle 1/20 5 Laterality Left 8/20 40 Right 10/20 50 Bilateral 2/20 10 Size <3 or =3cm 15/20 75 >3cm 5/20 25 Number <3 or =3個 13/20 65 Multiple 7/20 35 Tenderness

LAB DATA-CONCISE Items Ratio % Leukocytopenia (<3200) 6/18 33 Anemia (M<13, F<12) Thrombocytopenia (<150) 2/17 12 Thrombocytosis (>370) 1/17 6 Elevated GOT (>40) 3/17 18 Elevated GPT (>55) 1/16 Elevated CRP (>10) 7/14 50 Elevated LDH (>200) 14/16 88

BACK TO OUR CASE 15 y/o, boy, with prolonged fever for 3 weeks, and bulging left neck mass Lab data showed uneventful hemogram, but elevated CRP and ESR Histology showed typical paracortical necrosis compatible with Kikuchi’s disease He recovered well under steroid treatment with further follow up

TAKE HOME MESSAGE Kikuchi should be kept in mind for cervical lymphadenopahy Biopsy was the only diagnosis NOT ultrasound or CT Lab data wasn’t precise of prediction The patient should be followed for several years (controversial)

REFERENCES Xavier Bosch, MD,1 Antonio Guilabert, MD,2 Rosa Miquel, MD,3 and Elias Campo, MD 3--Enigmatic Kikuchi- Fujimoto Disease: A Comprehensive Review Ohshima K, Shimazaki K, Kume T, et al. Perforin and Fas pathways of cytotoxic T-cells in histiocytic necrotizing lymphadenitis. Histopathology. 1998;33:471-478. Miller WT Jr, Perez-Jaffe LA. Cross-sectional imaging of Kikuchi disease. J Comput Assist Tomogr. 1999;23:548- 551. Jang YJ, Park KH, Seok HJ. Management of Kikuchi's disease using glucocorticoid. J Laryngol Otol. 2000;114:709- 711. Hsin-Ching Lin, Chih-Ying Su and Shun-Chen HuangKikuchi’s Disease in Asian Children-Pediatrics 2005;115;e92-e96 Clinical Presentations, Laboratory Results and Outcomes of Patients with Kikuchi’s Disease: Emphasis on the Association Between Recurrent Kikuchi’s Disease and Autoimmune Diseases Chien-Yu Cheng, Wang-Huei Sheng, Yi-Chun Lo, Chen-Shuan Chung, Yee-Chun Chen, Shan-Chwen Chang* Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. Hsin-Liang Yu1*, Susan Shin-Jung Lee1, Hung-Chin Tsai1, Chun-Kai Huang1,Yao-Shen Chen1,Hsi-Hsin Lin1, Shue-Ren Wann1,Yung-Ching Liu1, Hui-Hwa Tseng 2 Clinical manifestations of Kikuchi’s disease in southern Taiwan 1Section of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital,Kaohsiung; and 2Department of Pathology, National Yang-Ming University, Taipei, Taiwan*Current affiliation: Department of Internal Medicine, Kaohsiung Municipal Min Seng Hospital,Kaohsiung, Taiwan Chih-Hsien Chuang, MD,* Dah-Chin Yan, MD,* Cheng-Hsun Chiu, MD, PhD,*Yhu-Chering Huang, MD, PhD,* Pen-Yi Lin, MD,* Chin-Jung Chen, MD,* Meng-Hsiu Yen, MD,* Tseng-Tong Kuo, MD, PhD,† and Tzou-Yien Lin, MD* Clinical and Laboratory Manifestations of Kikuchi’s Disease in Children and Differences Between Patients With and Without Prolonged Fever

THANKS FOR YOUR ATTENTION!! 特別感謝 病理部、湘琳學姊 凡榆、建豪、俊德、緯喬、以勤