1. 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

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

3. CASE PRESENTATION

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

5. 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

6. 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

7. 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

8. LAB DATA Admission 12/1 BUN 10 Crea 0.77 eGFR GOT 44 GPT 23 ALK-P 129Ca
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

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

10. 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.)

11. DISCUSSION KIKUCHI’S DISEASE

12. 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

13. 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

14. 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

15. 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

16. 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:

17. 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

18. KD

19. KD

20. KD

21. 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

22. 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

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

24. 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:

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

26. 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

27. 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)

28. 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

29. 桃園長庚小兒
Prolonged fever:
Leukocytopenia,
Anemia

30. 高雄榮總

31. 桃園長庚小兒

32. 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

33. IN NCKUH

34. AGE

35. 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

36. 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

37. 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

38. 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)

39. 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:
Miller WT Jr, Perez-Jaffe LA. Cross-sectional imaging of Kikuchi disease. J Comput Assist Tomogr. 1999;23:
Jang YJ, Park KH, Seok HJ. Management of Kikuchi's disease using glucocorticoid. J Laryngol Otol. 2000;114:
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

40. 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