Guideline for SLE management

1. Guideline for SLE management 高雄長庚醫院風濕過敏免疫科

2. Epidemiology of SLE

3. Subacute Cutaneous Lupus Erythematosus

4. Table 61-1. FREQUENCY OF CLINICAL SYMPTOMS IN SLE AT ANY TIME

5. Table 9-3. THE SPECTRUM OF ANAs

7. CAUSES OF POSITIVE ANTINUCLEAR ANTIBODIES

9. Serological Tests to Aid Diagnosis of SLE

10. Main patterns of autoantibody • Homogenous：Anti-histone • Peripheral：Anti-dsDNA, Anti-lamine • Speckled ：A large family of nonhiston antigens • -Coarse:Anti-Sm, Anti-U1-nRNP • -Fine:Anti-Ro, Anti-La • -Distinct speckles varying in number(PBC) • Anti-p80-coilin, Anti-p95 • Nucleolar ：Scleroderma or overlap syndrome • DNA topoisomerase:nucleolar speckles • PM-Scl:homogenous decorating nucleoli • Fibrillarin (U3-RNP):clummy nucleolar • NOR-90:nucleolar speckles • Centromere ：CREST syndrome, and PBC • Cytoplasmic ：ANCA,

11. ANA Negative Positive Peripheral (rim) Centromere Nucleoli Diffuse (honogeneous) No disease Lab error Treatment Remission Antigen XS Nephrotic syndrome Anti-dsDNA Histone Raynaud’s phenomenon Scleroderma Anti-nucleoprotein SLE SLE RA Drug LE SLE RA Drug LE CREST Sdleroderma Speckled RNP Sm RO (SS-A) La PcNA Scl-70 PM/Jo/Ku/Mi No specificity UCTD SLE RA Liver disease Mono Any chronic inflammatory disease SLE SLE SLE SLE Scleroderma PM/DM SLE MCTD RA Scleroderma UCTD Sogren’s syndrome Sogren’s syndrome

12. Tabel 1. CUTANEOUS CHANGES IN LUPUS ERYTHEMATOSUS

13. Table 61-2. MUSCULOSKELETAL MANIFESTATIONS IN SLE

14. Possible causes of leukopenia in SLE

15. Possible causes of anemia in SLE

17. Lupus lymphadeenitis (I)

18. Lupus lymphadeenitis (II)

19. Primary Respiratory System Involvement in Systemic Lupus Erythematosus

20. Pulmonary Involvement In SLE • Pleural disease • Acute lupus pneumonitis • Chronic interstitial lung disease • Pulmonary hemorrhage • Pulmonary embolism • Pulmonary vascular disease • Diaphragmatic dysfunction

21. Cardic manifestation of SLE

22. Common Clinical and Laboratory Findings in Lupus Nephritis

23. Characteristic Clinicopathologic Correlations in the Major Classes of Lupus Nephritis

24. Morphological Classification of Lupus Nephritis (modified WHO Classification)

25. INDICES OF ACTIVITY AND CHRONICITY IN LUPUS NEPHRITIS* *Individual lesions are scored 0 to 3+ (absent, mild, moderate, severe). Indices are composite scores for individual lesions in each category of activity or chronicity. Necrosis/karyorrhexis and cellular crescents are weighted by a factor of 2.

26. INDICATIONS FOR RENAL BIOPSY IN LUPUS NEPHRITIS

27. SLE and ESRD (1) • 5-22% of SLE patients progress to ESRD requiring H/D • In USA, Iupus nephropathy accounting for 1.4% off all ESRD • Decreased clinical and serological lupus activity following ESRD. Some theories had： • 1.Depressed cellular and humoral immunity • 2.Lack of mediators produced by the kidney • 3.Removal of lupus factors by dialysis itself • 4.Nature end point in SLE • Survival of lupus patients on dialysis versus non-SLE dialysis patients：no significant

28. SLE and ESRD (2) • Renal transplant graft survival of lupus versus non-lupus patients：no difference • Lupus patients have slightly better outcome with LR rather than CAD grafts • The transplantation time following dialysis need at least 3 months • Recurrence of transplanted allograft is often similar to histologic or immunofluorescent type as in the origin kidney, but it is a rare event.

29. NEUROPSYCHIATRIC MANIFESTATIONS IN SYSTEMIC LUPUS ERYTHEMATOSUS

30. PATHOGENETIC MECHANISMS CAUSING NEUROPSYCHIATRIC SYMPTOMS IN SYSTEMIC LUPUS ERYTHEMATOSUS

31. Pathogenesis of Neuropsychiatric Events in Patients with SLE † Intrathecal production or entrance through a blood-brain barrier disturbed by vascular injury.

32. FREQUENCY OF ABNORMAL LABORATORY TESTS COMMONLY USED IN THE EVALUATION OF NEUROPSYCHIATRIC LUPUS ERYTHEMATOSUS

33. Pathologic studies in NPLE

34. Proactive and preventive strategies in addition to lupus therapies(1) • Patients education programs, eliminate patient nonadherence • Monitor vital signs, update physical examination, and have laboratory work done • Adhere to a general conditioning exercise program to minimize osteoporosis and muscle atrophy • Cognitive therapy for lupus “fog”;biofeedback for Raynaud’s phenomenon • Counseling and stress management • Physical and occupational therapy, ergonomic work station evaluation

35. Proactive and preventive strategies in addition to lupus therapies(2) • Aggressive proactive management of blood pressure, blood sugars, serum lipids, and weight. Smoking cessation. • Yearly bone densitometry and osteoporosis prevention measures. • Annual electrocardiogram and chest x-ray • Prompt evaluation of all fevers • Periodic screening with carotid duplex scanning, treadmill, or stress testing; screening for, and prophylactic management of, antiphospholipid antibodies.

36. Therapies for lupus patients with skin lesions(1) • General • Avoid sun: clothing, sunscreens, avoid hot part of day with most UV-B light, camouflage cosmetics • Stop smoking (so antimalarials works better) • Thiazides and sulfonylureals may exacerbate skin disease

37. Therapies for lupus patients with skin lesions(2) • Routine therapy • Topical steroids, intralesional steroids • Hydroxychloroquine • Oral corticosteroids • Dapsone for bullous lesions

38. Therapies for lupus patients with skin lesions(3) • Advanced therapy for resistant causes • Subacute cutaneous lupus: mycophenylate mofetil, retinoids, or cyclosporine • Discoid lesions: chloroquine, clofazimine, thalidomide, or cyclosporine • Lupus profundus: dapsone • Chronic lesions over 50% of body: topical nitrogen mustard, BCNU, or tacrolimus • Vasculitis: may need immunosuppressives

39. Therapy for lupus patients with arthritis(no internal organ involvement) • First line: NSAIDs • Cyclooxygenase-2 specific inhibitors (but may induce thrombotic risk in patients with antiphospholipid antibodies) • Low dose hydroxychloroquine(200mg twice a day)

40. Indications of high dose corticosteroid therapy in lupus patients • Severe lupus nephritis • CNS lupus with severe manifestations • Autoimmune thrombocytopenia with extremely low platelet counts (e.g.<30000/mm3) • Autoimmune hemolytic anemia • Acute pneumonitis caused by SLE. • Others: severe vasculitis with visceral organ involvement, serious complications from serositis (pleuritis, pericarditis, or peritonitis)

41. Life-Threatening Manifestations of SLE: Responses to glucocorticoids(1) • Manifestations often responsive to glucocorticoids • Vasculitis • Severe dermatitis of subacute cutaneous lupus erythematosus or SLE • Polyarthritis • Polyserositis—pericarditis, pleurisy, peritonitis • Myocarditis • Lupus pneumonitis

42. Life-Threatening Manifestations of SLE: Responses to glucocorticoids(2) ~(continue) • Glomerulonephritis—proliferative forms • Hemolytic anemia • Thrombocytopenia • Diffuse CNS syndrome—acute confusional state, demyelinating syndromes, intractable headache • Serious cognitive defects • Myelopathies • Peripheral neuropathies • Lupus crisis—high fever and prostration

43. Life-Threatening Manifestations of SLE: Responses to glucocorticoids(3) • Manifestations not often responsive to glucocorticoids • Thrombosis—includes strokes • Glomerulonephritis—scarred end-stage renal disease, pure membranous glomerulonephritis • Resistant thrombocytopenia or hemolytic anemia—occurs in a minority of patients; consider splenectomy, cytotoxics, danazol, or cyclosporine/neoral therapies • Psychosis related to conditions other than SLE, such as glucocorticoid therapy

44. Therapy for patients with lupus nephritis • Previously untreated patients with active lupus nephritis or severe manifestations ( decreased renal function and /or high-grade proteinuria) • First line: high doses of corticosteroids (about 1mg/kg/day) • Cytotoxic drugs or other immunosuppressive drugs

45. The indications of cytotoxic drugs use in the treatment of lupus nephritis • Active and severe GN despite treatment with high dose prednisone • Responded to corticosteroids but require an unacceptably high dose to maintain a response. • Unacceptable side effects from corticosteroids. • Chronic damage on a renal biopsy and other indicators of a poor prognosis.

46. Systemic therapies for nonorgan-threatening lupus • Nonsteroidal anti-inflammatory drugs • Antimalarials • Thalidomide • Hormonal interventions: dehydroepiandrosterone, testosterone patches, bromocriptine, prolactin • Immunosuppressive therapies: azathioprine, methotrexate, leflunomide

47. The management of organ-threatening lupus • Existing immunosuppressive therapies: cyclophosphamide, mycophenolate mofetil, cyclosporine A, fludarabine, cladribine (2-CDA) • Apheresis • Intravenous immunoglobulin • Various biologic agents: BlyS inhibitor, CTLA-4Ig, LL2IgG • Stem cell transplantation

48. Use of Cytotoxic Drugs in SLE : Azathioprine • requires 6–12 months to work well • 1–3 mg/kg/day(initial dose) • 1–2 mg/kg/day(maintenance dose) • Advantage:probably reduces flares, reduces renal scarring, reduces glucocorticoid dose requirement • Side effects: Bone marrow suppression, leukopenia, infection(herpes zoster), infertility, malignancy, early menopause, hepatic damage, nausea

49. Use of Cytotoxic Drugs in SLE: Cyclophosphamide • requires 2–16 weeks to work well • Initial dose:1-3 mg/kg/day orally or 8–20 mg/kg intravenously once a month plus mesna • Maintenance dose:0.5–2 mg/kg/day orally or 8–20mg/kg intravenously every 4–12 wks plus mesna • Adverse effects:probably reduces flares, reduces renal scarring, reduces glucocorticoid dose requirement • Adverse effects: marrow suppression, leukopenia, infection, infertility, malignancy, menopause,cystitis,nausea

50. The treatment in lupus patients with autoimmune thrombocytopenia • Splenectomy • Danazol • Immunosuppressive or cytotoxic drugs: azathioprine, cyclophosphamide • Intravenous immunoglobulin(IVIG)