1. 1 M G R - 구강 궤양과 전신 통증으로 내원한 60 세 여자 - Division of Rheumatology R2 김 지 연

2. 2 11260551 최 O 임 (F/60) Adm. 2008-08-13 C.C. ) 구강 궤양과 전신 통증 onset : remote- 2 weeks ago recent- 2 days ago P.I.) - 60 세 여자, 1997 년 간질성 폐질환 (IPF) 으로 진단 받은 후 간헐적으 로 호흡기내과 외래 F/U 중이던 환자로, 내원 2 주전부터 심한 통증 을 동반한 구강 궤양과 전신적 근육통, 관절통이 발생하여 방문함. - 2005 년 입 마르는 증상 있어 본원 류마티스 내과 외래에서 ‘Sjogren syndrome’ 또는 ‘ SLE’ 가 의심된다고 들었으나, 이후 F/U loss 됨.

3. 3 11260551 최 O 임 (F/60) Adm. 2008-08-13 PMHx.) –DM/ HTN/ TB/ Hepatitis( - / + / - / -) HTN: 2000 년 진단 - Amlodipine 5mg qd po med –97 년 IPF 진단 bronchoscopic lung Bx. : Chronic inflammation with fibrosis, compatible with IPF –05 년 입마름 증상으로 류마티스내과 refer R/O SLE, R/O Primary Sjogren syndrome –Decreased complement level (C3/C4 : 76/13) –ANA(+), Anti-dsDNA Ab : 8.2 IU/L (<7) 당시 Prednisolone 7.5mg qd for 2wks, Hydroxychloroquine, NSAIDs medication 후 F/U loss. PHx.) Smoking (-)Alcohol (-) Job : 가정주부

4. 4 General : fatigue (+) mild fever(+) chilling (-) sweating(-) weight loss(+) : 6kg for 3months Skin : rash (-) pigmentation (-) Itching (-) Head & Neck : headache (-) stiffness (-) Eye & ENT : oral ulcer (+) dry mouth (+) dry eye (-) Respiratory : cough (+) sputum (-) dyspnea (-) Cardiac : chest pain (-) orthopnea (-) palpitation (-) Gastrointestinal : A/N/V/D/C ( - / - / - / - / - ) abdominal pain(-) Urinary : dysuria (-) frequency (-) urgency (-) Musculoskeletal : generalized myalgia (+) weakness (-) numbness (-) arthralgia (+) : both shoulder, knee, and ankle Nervous : syncope (-) seizure(-) dizziness (-) 4 Review of systems - joint swelling(-) - redness (-) - heating sense (-)

5. 5 Vital sign) 120/90 – 64 – 20 – 36.5 ℃ Height/Body weight : 153cm/53.3kg BMI : 22.7 General appearance –Alert mentality, Acute ill-looking appearance Skin –Erythema nodosum like skin lesion (+) : Lt. shin Head and Neck –LN enlargement(-/-) –Rt. parotid gland enlargement (+) Eyes and ENT –Isocoric pupil with PLR(++/++), –Whitish conjunctivae, Pinkish sclerae –Conjunctival injection (+) : both eyes –Oral ulcer (+) Physical examinations - Left lateral side of tongue and lower lips - Discrete, oval shape aphtous ulcers, with whitish base

6. 6 Chest –Coarse breathing sound with crackles, both lower lung fields –Regular heart beat without murmur Abdomen –No abdominal tenderness, rebound tenderness –No hepatosplenomegaly Genital area –Normal vagina/minor-major labium –Ulcerative lesion (-) Neurology –Motor : intact, Sensory : intact Physical examinations

7. 7 #1. Painful oral ulcer #2. Generalized myalgia with arthralgia #3. Dry mouth #4. Interstitial lung disease (IPF), known #5. Hypertension, known Initial Problem lists

8. 8 #1. Painful oral ulcer #2. Generalized myalgia with arthralgia #3. Dry mouth #4. Interstitial lung disease ANA (+) Anti-dsDNA (+)

9. 9 #1. Painful oral ulcer #2. Generalized myalgia with arthralgia #3. Dry mouth #4. Interstitial lung disease ANA (+) Anti-dsDNA (+) → SLE with secondary Sjogren syndrome r/o Primary Sjogren syndrome

10. 10 Diagnostic criteria of Behcet’s disease → Behcet’s disease

11. 11 #1. SLE with secondary Sjogren syndrome r/o Primary Sjogren syndrome r/o Behcet’s disease #2. Hypertension, known Initial Assessment

12. 12 Diagnostic Plan #1. SLE with secondary Sjogren syndrome - ANA, anti-dsDNA, ENA profile - Complement level, Immunoglobulin profile #2. Primary Sjogren syndrome - Schirmer test, Rose Bengal test, Tear break-up time - Salivary gland scintigraphy - Salivary gland biopsy - antibodies to Ro/SSA and La/SSB #3. Behcet’s disease –Pathergy test, HLA B51 –OPH consult for uveitis

13. 13 CBC/DC ) 7,440/mm 3 – 12.3 g/dL – 36.8% - 156K (seg. 69.3%) PT(INR) 1.05 aPTT 34.9/34 sec ESR 93 mm/hr Chemistry ) TB/DB 0.50/ 0.16 mg/dL Na/K/Cl 138/ 4.3/ 101 mmol/L T-chol/Glu 183/ 78 mg/dL Ca/P/Mg 8.7/ 3.4/ 2.1 mg/dL AST/ALT 32/ 22 U/L LD/CK 381/ 27 U/L ALP/GGT 97/ 97 U/L BUN/Cr 6/ 0.7 mg/dL Prot/Alb 8.0/ 3.4 g/dL CRP 5.5 mg/dL Uric acid 5.7 mg/dL UA ) RBC 0-1 /HPF WBC 0-1 /HPF Protein(-) 13 Initial lab findings

14. 14 Chest PA (Adm.)

15. 15 Viral markers –Anti HCV Ab : negative –Anti HIV Ab : negative –HBs Ag / Anti HBs Ab : all negative VDRL : negative Immunoglobulin –IgG 3330 mg/dL (694~1618 mg/dL ) –IgA 607 mg/dL (68~378 mg/dL) –IgM 842 mg/dL (60~263 mg/dL) –IgE 30.8 mg/dL (<100 IU/mL) RA factor 270 IU/mL (<20IU/mL) Anti - CCP AbNegative 단백 면역 검사

16. 16 ANA –Discrete speckled 1:640 Anti-dsDNA Ab : 8.7IU/L Lupus anticoagulant : negative Anticardiolipin Ab : negative C3 137(88~201 mg/dL ) C4 20.3 mg/dL (15~45 mg/dL ) C-ANCA : negative P-ANCA : 2+ 단백 면역 검사

17. 17 anti-RNP Negative anti-Sm Negative anti-SSA (Ro) 3+ anti-SSB (La) Negative anti-Scl-70 Negative anti-Jo1 Negative anti-CENP B Negative anti-PCNA Negative anti-dsDNA Negative anti-Nucleosome Negative anti-PM-Scl Negative anti-Histone Negative abti-Ribosomal P prot. Negative anti-AMA-M2 Negative ENA profile

18. 18 Knee, Ankle and Shoulder X-ray

19. 19 Bone Scan → Both shoulder joints 의 mild arthritic change

20. 20 Salivary scan and biopsy Salivary gland biopsy –Salivary gland with chronic lymphocytic sialoadenitis –Focus formation(+) - Salivary gland with chronic lymphocytic sialoadenitis - Focus formation (+)

21. 21 Opthalmic examinations Schirmer test : negative –Rt eye : > 5mm/5mins –Lt eye : > 5mm/5mins Tear break – up time : WNL

22. 22

23. 23 Pathergy test : negative HLA-B51 : positive Evaluation for Behcet’s disease Recurrent oral ulcer Erythema nodosum like skin lesion (+) : Lt. shin

24. 24 1. Major criteria (i) Recurrent aphthous oral ulcerations (ii) Skin lesions (any of the four) (a) Erythema nodosum (b) Subcutaneous thrombophlebitis (c) Folliculitis, acne-like lesions (d) Cutaneous hypersensitivity (iii) Ocular lesions (any of the three) (a) Iridocyclitis (b) Chorioretinitis, retino-uveitis (c) Definite history of (a) and/or (b) 2. Minor criteria (i) Arthritis without deformity and ankylosis (ii) Epididymitis (iii) Gastro-intestinal lesions characterized by ileocaecal ulcers (iv) Vascular lesions compatible with Behcet’s disease (v) CNS symptoms compatible with Behcet’s disease 3. Diagnosis (i) complete type Four major symptoms apparent during the clinical course (ii) incomplete type (a) Three major symptoms or two major and two minor symptoms (b) Typical ocular symptoms and another major symptoms or two minor symptoms apparent during the clinical course (iii) Suspected type Some major symptoms apparent but not fulfilling the above two, or typical minor symptoms recurred (iv) Subtypes (a) Intestinal Behcet’s disease (b) Vascular Behcet’s disease (c) Neuro- Behcet’s disease 4. Findings helpful in diagnosis (i) Cutaneous needle reaction (ii) Inflammatory reaction : rise in ESR, positive CRP, and increase in number of peripheral WBC (iii) HLA-B51 (B5) Int J Tissue React 1988;10:59-65

25. 25 Diagnostic criteria of SLE ?

26. 26 #1. Primary Sjogren syndrome with ILD #2. Behcet’s disease, suspected type Diagnosis

27. 27 # HD 2

28. 28 Abdomen US finding

29. 29 Abdomen CT

30. 30 Neck CT

31. 31 Chest CT

32. 32 Gastroscopy → Biopsy: Chronic gastritis

33. 33 PET-CT - Porta hepatis and Lt. gastric region : SUV 12 - Lt. parotid area : SUV 4.5

34. 34 Left parotid gland biopsy

35. 35 Marginal zone B cell lymphoma, low grade Immunohistochemical finding CK (+) Kappa (+) Lambda (+) CD3 (-) CD20 (+) Left parotid gland biopsy

36. 36 BM exam

37. 37 #1. Primary Sjogren syndrome with ILD #2. Behcet’s disease, suspected type #3. Marginal zone B cell lymphoma, low grade Final diagnosis

38. 38 Treatment #1. Primary Sjogren syndrome with ILD #2. Behcet’s disease, incomplete - Hydroxychloroquine - low dose steroid - colchicin - rebamipide 100mg bid - NSAIDs #3. Marginal zone B cell lymphoma, low grade  혈액종양 내과로 전과 후, Chemotherapy (CVP #1) 시행 - cyclophosphamide - vincristine 2mg - PDL