1. 病案討論 -Systemic Lupus Erythematosus 曾素卿 2006/09 曾素卿 2006/09

2. The case General patient information Name: 林 ×× General patient information Name: 林 ×× Age:40 Gender:female Education: high Age:40 Gender:female Education: high Marital status: married Marital status: married Occupation: office lady Admission date:94/04/22 Discharge date:94/04/25 Chart No:61591622 Occupation: office lady Admission date:94/04/22 Discharge date:94/04/25 Chart No:61591622

3. Chief complaint Chief complaint Progressive lower limb edema and gain of body weight for about 10 days Progressive lower limb edema and gain of body weight for about 10 days

4. Present illness (Ι) Present illness (Ι) A 40-year-old woman was a case of SLE and diagnosed at 南門醫院 at age 19. She was under treatment at 東元醫院 and had received several cycles of pulse therapy. A 40-year-old woman was a case of SLE and diagnosed at 南門醫院 at age 19. She was under treatment at 東元醫院 and had received several cycles of pulse therapy. She had operation history of endometriosis s/p on MMH in 1994 and pregnancy with abortion (due to fever) for two times and an episode of interauterine death, followed by acute renal failure s/p hemodialysis for 3 months. She had operation history of endometriosis s/p on MMH in 1994 and pregnancy with abortion (due to fever) for two times and an episode of interauterine death, followed by acute renal failure s/p hemodialysis for 3 months.

5. Present illness ( Ⅱ ) Present illness ( Ⅱ ) She sustained from repeated cystitis and PIP in 2001/10 and followed by HPV infected She sustained from repeated cystitis and PIP in 2001/10 and followed by HPV infected vaginitis in 2002/7. Type Ⅳ lupus nephritis was told from renal biopsy at vaginitis in 2002/7. Type Ⅳ lupus nephritis was told from renal biopsy at 台大醫院. Mrs.Lin appeared to our clinic in 2004/2/6 with severe Raynaud’s phenomenom and digital vasculitic purpura which were also present over elbows, lower limbs and pretibial area. 台大醫院. Mrs.Lin appeared to our clinic in 2004/2/6 with severe Raynaud’s phenomenom and digital vasculitic purpura which were also present over elbows, lower limbs and pretibial area.

6. Present illness ( Ⅲ ) Present illness ( Ⅲ ) She was admitted to received pulse She was admitted to received pulse therapy and cystitis with vaginitis treatment during 93/05/14-93/05/20. She was admitted twice to our hospital due to finger and toe tips vasculitis and malar rash (2004/5, 2004/7) and herbal medicine induce flare. therapy and cystitis with vaginitis treatment during 93/05/14-93/05/20. She was admitted twice to our hospital due to finger and toe tips vasculitis and malar rash (2004/5, 2004/7) and herbal medicine induce flare.

7. Present illness ( Ⅳ ) Present illness ( Ⅳ ) Due to her eager for baby, she refused treatments as pulse and cytotoxics. However, recurrent lower limb edema with heavy proteinuria despite prednisolone and azathiprine. Hydroxychloroquine was withheld due to patient’s fear of skin hyperpigmentation. Due to her eager for baby, she refused treatments as pulse and cytotoxics. However, recurrent lower limb edema with heavy proteinuria despite prednisolone and azathiprine. Hydroxychloroquine was withheld due to patient’s fear of skin hyperpigmentation.

8. Present illness ( Ⅴ ) Present illness ( Ⅴ ) Her laboratory tests resulted in Her laboratory tests resulted in dsDNA=31.9>42>95>626>1850>3100>322>235>61>78> dsDNA=31.9>42>95>626>1850>3100>322>235>61>78> 44.5>144>10.9>40 44.5>144>10.9>40 C3/C4=25/10>26/10>38>57>50 C3/C4=25/10>26/10>38>57>50 ESR=41>75>91>83>72>53>51>57>50>49 ESR=41>75>91>83>72>53>51>57>50>49 alb=2.7>2.5>3.5>2.0 Uprotein=2.77>2.05>5.44>4.7g/day alb=2.7>2.5>3.5>2.0 Uprotein=2.77>2.05>5.44>4.7g/day

9. Present illness ( Ⅵ ) aCLIgG=7.8>17.3GPL/ml(N 17.3GPL/ml(N<10), aCLIgM=3.2>9.8MPL/ml( 9.8MPL/ml(<7) within 4 months. The antibodies included Sm(-) RNP(+) SSA(-) SB(-) cryoglobulin(-). cryoglobulin(-). Marked lower limb edema developed for the past one week with difficulty performing daily activity.Albumin level on 4/19 yielded 2.0. She is admitted for albumin supplement and also pulse therapy. Marked lower limb edema developed for the past one week with difficulty performing daily activity.Albumin level on 4/19 yielded 2.0. She is admitted for albumin supplement and also pulse therapy.

10. Past Medical History Past Medical History Systemic lupus erythematosus Systemic lupus erythematosus Hyperlipidemia (mixed type) Hyperlipidemia (mixed type) Severe Raynaud’s phenomenon Severe Raynaud’s phenomenon

11. Physical Examination Physical Examination Vital sign:T:36.3 P:98 R:20 BP:120/74 Vital sign:T:36.3 P:98 R:20 BP:120/74 Status:ill-looking Status:ill-looking Cons:clear, alert Cons:clear, alert General:recent weight change(+) fatigue(+) General:recent weight change(+) fatigue(+) gain of body weight:3-4 kg/10 days gain of body weight:3-4 kg/10 days Skin:rash(+) lumps(+) pruritus(+) Skin:rash(+) lumps(+) pruritus(+) Extremities:bilateral legs pitting edema L ’ t ＞ R ’ t Extremities:bilateral legs pitting edema L ’ t ＞ R ’ t

12. Dx Dx 1.Systemic lupus erythematosus with lupus 1.Systemic lupus erythematosus with lupus nephritis class Ⅳ with peripheral nephritis class Ⅳ with peripheral vasculitis with flare(hypoalbuminemia, vasculitis with flare(hypoalbuminemia, heavy proteinuria) s/p pulse therapy heavy proteinuria) s/p pulse therapy 2.Acute pharyngitis 2.Acute pharyngitis 3.Hyperlipidemia(mixed type) 3.Hyperlipidemia(mixed type) 4.Severe Raynaud’s phenomenon 4.Severe Raynaud’s phenomenon 5.Insomia 5.Insomia

13. Drug profile 藥物劑量 / 頻次 / 使用 方法 / 時間 4/224/234/244/25 Prednisolone(5 mg) tab po 6# st 4# qd Methylprednisolone (500 mg) 2 vial in D5W 100 cc iv drip qdqd Albumin 25% 1 BT iv drip qdqdqd Lasix(20 mg) 1 amp post albumin iv qdqdqd Lasix (40 mg) tab po 1#bid1#q8h1#q8h1#qd Lipitor(10 mg) po 1#qd pm Brown mixture 15 cc po qidqidqidqid

14. Problem list Problem list 1.SLE with lupus nephritis class Ⅳ with peripheral vasculitis 1.SLE with lupus nephritis class Ⅳ with peripheral vasculitis 2.Hypoalbuminemia 2.Hypoalbuminemia 3.Hyperlipidemia(mixed type) 3.Hyperlipidemia(mixed type)

15. Discussion SLE with lupus nephritis class Ⅳ with peripheral vasculitis S: S: progression lower limb edema and gain of body progression lower limb edema and gain of body weight for about 10 days weight for about 10 days O: O: 1.Gain of body weight:3-4 kg/10 days 1.Gain of body weight:3-4 kg/10 days 2.Extremities:bilateral legs pitting edema L’t ＞ R’t 2.Extremities:bilateral legs pitting edema L’t ＞ R’t

16. Discussion SLE with lupus nephritis class Ⅳ with peripheral vasculitis O: 3.Lab data( 一 )unit Normal range 4/194/224/23 Hbgm/dL11.0-16.013.512.312.0 WBC 10ˆ3/u l 4.00-10.009.108.607.00 RBC 10ˆ6/u l 4.20-5.503.993.83 Ht％34.0-50.035.934.6 MCVfl80.0-98.090.090.3 Platelet 10ˆ3/u l 140-450211

17. Discussion SLE with lupus nephritis class Ⅳ with peripheral vasculitis O: 3.Lab data( 二 )unit Normal range 4/194/234/24 Anti- dsDNA IU/mlnegative:<10equivocal:10-15positive:>1544.3 E.S.R.1hr mm/H R 0-1285 Creatinine MG/D L 0.5-1.10.30.4

18. Discussion SLE with lupus nephritis class Ⅳ with peripheral vasculitis O: Lab data( 三 ) 24 hrs urine (1900 ml) Protein 452 MG/DL= 8.58 g/day Creatinine H 59.7 MG/DL=ClCr=196 ml/min

19. Discussion SLE with lupus nephritis class Ⅳ with peripheral vasculitis Assessment: Assessment: 1.This patient is belong to WHO grade IV, [diffuse proliferative lupus nephritis (DPLN) affecting >50% of glomeruli] aggressive immunosuppression is recommended. 1.This patient is belong to WHO grade IV, [diffuse proliferative lupus nephritis (DPLN) affecting >50% of glomeruli] aggressive immunosuppression is recommended. If untreated, develop end-stage renal disease (ESRD) within 2 years. If untreated, develop end-stage renal disease (ESRD) within 2 years.

20. Discussion SLE with lupus nephritis class Ⅳ with peripheral vasculitis Assessment: Assessment: 2.This patients with dangerous proliferative forms of glomerular damage and proteinuria (>500 mg per 24 h) therefore, aggressive immunosuppression is indicated (usually systemic glucocorticoids plus a cytotoxic drug) but proteinuria is less likely to improve on lupus nephritis immunosuppressive therapies. Lupus nephritis tends to be an ongoing disease, with flares requiring re-treatment over many years. 2.This patients with dangerous proliferative forms of glomerular damage and proteinuria (>500 mg per 24 h) therefore, aggressive immunosuppression is indicated (usually systemic glucocorticoids plus a cytotoxic drug) but proteinuria is less likely to improve on lupus nephritis immunosuppressive therapies. Lupus nephritis tends to be an ongoing disease, with flares requiring re-treatment over many years.

21. Discussion SLE with lupus nephritis class Ⅳ with peripheral vasculitis Assessment: Assessment: 3.Treat with monthly intravenous cyclophosphamide,500 to 1000 mg/m2 body surface area for 6 months,along with high-dose corticosteroids (usually initially pulse methylprednisolone,1000 mg/d for 3 days,followed by prednisone,40 to 60 mg/d,for the first month), may be benefit for this patient. 3.Treat with monthly intravenous cyclophosphamide,500 to 1000 mg/m2 body surface area for 6 months,along with high-dose corticosteroids (usually initially pulse methylprednisolone,1000 mg/d for 3 days,followed by prednisone,40 to 60 mg/d,for the first month), may be benefit for this patient.

22. Discussion SLE with lupus nephritis class Ⅳ with peripheral vasculitis Assessment: Assessment: 4. Due to her eager for baby, this patient 4. Due to her eager for baby, this patient refused treatments. refused treatments. Therefore consider other drugs like Therefore consider other drugs like azathioprine or mycophenolate. azathioprine or mycophenolate.

23. Discussion SLE with lupus nephritis class Ⅳ with peripheral vasculitis Assessment: Assessment: 5. Azathioprine (a purine antagonist) added to glucocorticoids probably reduces the number of SLE flares and the maintenance glucocorticoid requirement; however, this approach requires several months to be effective, and cyclophosphamide is effective in a higher proportion of patients. Daily oral azathioprine may have fewer adverse effects than daily oral cyclophosphamide; 5. Azathioprine (a purine antagonist) added to glucocorticoids probably reduces the number of SLE flares and the maintenance glucocorticoid requirement; however, this approach requires several months to be effective, and cyclophosphamide is effective in a higher proportion of patients. Daily oral azathioprine may have fewer adverse effects than daily oral cyclophosphamide;

24. Discussion SLE with lupus nephritis class Ⅳ with peripheral vasculitis Assessment: Assessment: 6.A recent prospective study in Chinese patients with lupus nephritis comparing daily oral mycophenolate plus prednisolone for 12 months to daily oral cyclophosphamide plus prednisolone for 6 months followed by oral daily azathioprine plus prednisolone showed good improvement in 80% of patients in both groups at 1 year of follow-up and fewer adverse effects with mycophenolate. 6.A recent prospective study in Chinese patients with lupus nephritis comparing daily oral mycophenolate plus prednisolone for 12 months to daily oral cyclophosphamide plus prednisolone for 6 months followed by oral daily azathioprine plus prednisolone showed good improvement in 80% of patients in both groups at 1 year of follow-up and fewer adverse effects with mycophenolate.

25. Discussion SLE with lupus nephritis class Ⅳ with peripheral vasculitis Assessment: Assessment: 7.Pregnancy and lupus: 7.Pregnancy and lupus: this patient should avoid becoming pregnant this patient should avoid becoming pregnant before disease stable. before disease stable.

26. Discussion SLE with lupus nephritis class Ⅳ with peripheral vasculitis Plan: Plan: 1.Recommended drug treatment: 1.Recommended drug treatment: pulse therapy :systemic glucocorticoids(0.5~2mg/kg per day orally or 1000 mg of methylprednisolone sodium succinate intravenously daily) for 3 days. pulse therapy :systemic glucocorticoids(0.5~2mg/kg per day orally or 1000 mg of methylprednisolone sodium succinate intravenously daily) for 3 days. maintenance therapy: combine corticosteroids(5~10 mg/day)and immunosuppressive drugs[azathioprine (1~2 mg/kg/d) or mycophenolate(500~1500 mg/d)]. maintenance therapy: combine corticosteroids(5~10 mg/day)and immunosuppressive drugs[azathioprine (1~2 mg/kg/d) or mycophenolate(500~1500 mg/d)].

27. Discussion SLE with lupus nephritis class Ⅳ with peripheral vasculitis Plan: Plan: 2.Goal: 2.Goal: There is no cure for SLE, and complete sustained remissions are rare. Therefore, the physician should plan to control acute, severe flares then develop maintenance strategies that suppress symptoms to an acceptable level and prevent organ damage. There is no cure for SLE, and complete sustained remissions are rare. Therefore, the physician should plan to control acute, severe flares then develop maintenance strategies that suppress symptoms to an acceptable level and prevent organ damage.

28. Discussion SLE with lupus nephritis class Ⅳ with peripheral vasculitis Plan: Plan: 3.Monitoring parameters: 3.Monitoring parameters: It is useful to follow tests that indicate the status of organ involvement known to be present during SLE flares. These might include hemoglobin levels, platelet counts, urinalysis, and serum levels of creatinine or albumin. There is great interest in identification of additional markers of disease activity. Candidates include levels of anti-dsDNA antibodies, several components of complement (C'3 is most widely available), activated complement products, soluble interleukin (IL) 2, and urinary monocyte chemotactic protein 1. It is useful to follow tests that indicate the status of organ involvement known to be present during SLE flares. These might include hemoglobin levels, platelet counts, urinalysis, and serum levels of creatinine or albumin. There is great interest in identification of additional markers of disease activity. Candidates include levels of anti-dsDNA antibodies, several components of complement (C'3 is most widely available), activated complement products, soluble interleukin (IL) 2, and urinary monocyte chemotactic protein 1.

29. Discussion SLE with lupus nephritis class Ⅳ with peripheral vasculitis Plan: Plan: 4.Patient education 4.Patient education · Stress the importance of compliance with drug regimen · Stress the importance of compliance with drug regimen and follow-up visits. and follow-up visits. · When starting treatment with prednisone, inform · When starting treatment with prednisone, inform patients about weight control, low-fat diet, and patients about weight control, low-fat diet, and exercise. exercise. · Advise patients about proper use and side effect · Advise patients about proper use and side effect profiles of other medications used in treating SLE. profiles of other medications used in treating SLE. · Counsel the patient about the importance of developing · Counsel the patient about the importance of developing a social support system that will provide feedback a social support system that will provide feedback about lupus self-management behaviors, problem solving, about lupus self-management behaviors, problem solving, and alternate solution planning. and alternate solution planning.

30. Discussion SLE with lupus nephritis class Ⅳ with peripheral vasculitis Plan: Plan: 5. Institute measures to prevent steroid-induced osteoporosis. 5. Institute measures to prevent steroid-induced osteoporosis..Vitamin D and calcium supplementation.Vitamin D and calcium supplementation. Weight-bearing exercise. Weight-bearing exercise.Bisphosphonates or HRT; unless otherwise.Bisphosphonates or HRT; unless otherwise contraindicated, alendronate and HRT can both be used. contraindicated, alendronate and HRT can both be used.

31. Discussion Hypoalbuminemia S/O: S/O: 1.Lab data 1.Lab data unit Normal range 4/194/224/23 Albumin GM/D L 3.5-5.02.01.92.2

32. Discussion Hypoalbuminemia Assessment: Assessment: 1.Hypoalbuminemia,a characteristic feature of the nephrotic syndrome, results from augmentation of both urinary albumin lossess and the catabolic rate of albumin. 1.Hypoalbuminemia,a characteristic feature of the nephrotic syndrome, results from augmentation of both urinary albumin lossess and the catabolic rate of albumin. 2.This is a temporary measure, since the infused albumin only transiently increase serum albumin and is promptly excreted in the urine. 2.This is a temporary measure, since the infused albumin only transiently increase serum albumin and is promptly excreted in the urine.

33. Discussion Hypoalbuminemia Plan: Plan: 1.Recommended drug treatment: 1.Recommended drug treatment: 25% albumin 1BT iv drip, then 25% albumin 1BT iv drip, then furosemide(40mg) 1 amp for 3 days. furosemide(40mg) 1 amp for 3 days.

34. Discussion Hypoalbuminemia Plan: Plan: 2.Goal: 2.Goal: treatment of the underlying disorder and an adequate protein diet combined with intervention aimed at reducing protein excretion may be beneficial. treatment of the underlying disorder and an adequate protein diet combined with intervention aimed at reducing protein excretion may be beneficial.

35. Discussion Hypoalbuminemia Plan: Plan: 3.Monitoring parameters: 3.Monitoring parameters: periodic measurement of serum albumin levels. periodic measurement of serum albumin levels. 4.Diet: 4.Diet: an adequate protein diet. an adequate protein diet.

36. Discussion Hyperlipidemia(mixed type) S/O: S/O: 1.Lab data 1.Lab data unit Normal range 4/23 Total Cholesterol MG/DL130-230321 TriglycerideMG/DL35-165335

37. Discussion Hyperlipidemia(mixed type) Assessmrent: Assessmrent: 1.Lipid abnormalities including TC and TG have been described in this patients. 1.Lipid abnormalities including TC and TG have been described in this patients. 2.This patients are at an increased risk for atherosclerotic cardiovascular disease. Since the lipid abnormalities seen in nephrotic syndrome are associated with accelerated atherosclerosis. 2.This patients are at an increased risk for atherosclerotic cardiovascular disease. Since the lipid abnormalities seen in nephrotic syndrome are associated with accelerated atherosclerosis.

38. Discussion Hyperlipidemia(mixed type) Plan: Plan: 1.Recommended drug treatment: 1.Recommended drug treatment: Atorvastatin 10 mg qd am(without regard to time of day and with food if desired) Atorvastatin 10 mg qd am(without regard to time of day and with food if desired) 2.Acquire other lipoprotein level eg. LDL, HDL. 2.Acquire other lipoprotein level eg. LDL, HDL.

39. Discussion Hyperlipidemia(mixed type) Plan: Plan: 2.Goal: 2.Goal: a. Reduce the risk of atherosclerosis in patient with SLE. a. Reduce the risk of atherosclerosis in patient with SLE. b. NCEP( National Cholesterol Education Program)-ATP Ⅲ suggested TC level<200 mg/dl and TG<150 mg/dl. b. NCEP( National Cholesterol Education Program)-ATP Ⅲ suggested TC level<200 mg/dl and TG<150 mg/dl.

40. Discussion Hyperlipidemia(mixed type) Plan: Plan: 3.Monitoring parameters: 3.Monitoring parameters: Lipid levels after 2-4 wks; LFTs, CPK. Lipid levels after 2-4 wks; LFTs, CPK. It is recommended that liver function tests(LFTs) be performed prior to and at 12 wks following both the initiation of therapy and elevation in dose, and periodically (eg. semiannually) thereafter. It is recommended that liver function tests(LFTs) be performed prior to and at 12 wks following both the initiation of therapy and elevation in dose, and periodically (eg. semiannually) thereafter.

41. Discussion Hyperlipidemia(mixed type) Plan: Plan: 4.Patient education: 4.Patient education: Dietary therapy and lifestyle modifications should be tried for 3 months. Dietary therapy and lifestyle modifications should be tried for 3 months. Nondrug and drug therapy should be initiated simultaneously. Increasing physical activity will aid in the treatment of hyperlipidemia and improve cardiovascular health. Nondrug and drug therapy should be initiated simultaneously. Increasing physical activity will aid in the treatment of hyperlipidemia and improve cardiovascular health.

42. 謝謝聆聽, 敬請指教 !!

43. 1.WHO has classified lupus nephritis as six grades, the patient belong to grade ? (d) a. Ⅰ (no histologic changes) b. Ⅱ (proliferative changes confined to the mesangium) c. Ⅲ (proliferative changes in tufts of 10 to 50% of glomeruli) d Ⅳ (diffuse proliferative affecting>50% of glomeruli) 2.Which drug has become the standard drug used for controlling life- (a) threatening active lupus nephritis, particularly in patients whose renal biopsies show WHO grades III, IV, and V proliferative or membranoproliferative forms of nephritis? a.cyclophosphamide b.azathioprne c.mycophenolate a.cyclophosphamide b.azathioprne c.mycophenolate 3.Which one is side effect of cyclophosphamide? (e) a. high rate of irreversible ovarian or testicular failure b. nausea c. malaise d. alopecia e. 以上皆是 4.Wnen flare, anti-ds DNA and serum C 3 will be? (c) a. high anti-ds DNA, high C 3 b. low anti-ds DNA, low C 3 c.high anti- ds DNA, low C 3 d. high anti-ds DNA, high C 3. 5. 使用 statins 藥物時, 要監測何值 ? (d) a. lipid level b. liver function tests c. CPK d. 以上皆是

44. Document at least four of the following American College of Rheumatology classification criteria Positive ANA Positive ANA Malar rash Malar rash Discoid lupus Discoid lupus Photosensitivity Photosensitivity Oral ulcers Oral ulcers Arthritis Arthritis Serositis Serositis Renal disorder Renal disorder Neurologic disorder Neurologic disorder Hematologic disorder Hematologic disorder Immunologic disorder Immunologic disorder

45. 1.If the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective). 1.If the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective). 2.Maternal SLE should be controlled with prednisone/prednisolone at the lowest effective doses for the shortest time required. 2.Maternal SLE should be controlled with prednisone/prednisolone at the lowest effective doses for the shortest time required. 懷孕分級 azathioprine D mycophenolate C prednisolone C

46. Atherosclerosis is a process that occurs over time, and discontinuing lipid-lowering agents during pregnancy is not likely to adversely affect the overall outcome of hypercholesterolemia treatment Atherosclerosis is a process that occurs over time, and discontinuing lipid-lowering agents during pregnancy is not likely to adversely affect the overall outcome of hypercholesterolemia treatment 懷孕分級 懷孕分級 statins X fibrate C cholestyramine C ezetimibe C