SYSTEMIC LUPUS ERYTHEMATOSUS 瑞金医院肾脏科 李晓

1. SYSTEMIC LUPUSERYTHEMATOSUS瑞金医院肾脏科 李晓

2. Introduction • SLE is a chronic, usually life-long, potentially fatal autoimmune disease characterized by inflammation in many different organ systems commonly involved skin and kidney.

3. Introduction • SLE is associated with the production of autoantibodies reactive with nuclear, cytoplasma and cell membrane antigens.

4. fatigue anemia fever rashes sun sensitivity alopecia arthritis pericarditis pleurisy vasculitis nephritis central nervous system disease Introduction

5. Introduction • F:M=7-10:1 • Child-bearing age（ 13 ~ 40 years old） • Prevalence in women China 113 per 100,000 USA 50 per 100,000

6. Etiology • Genetics HLA-DRw2 and HLA-DRw3 • Virus type C viruses isolated • Hormone estrogens (androgens) • Environment ultraviolet light • Drugs procainamide, alpha-methyldopa, D-penicillamine, quinidine, ...

7. Pathogenesis • The deposition of DNA-anti-DNA immune complexes • Antibodies to erythrocytes, granulocytes, lymphocytes, and macrophages

8. Genetic Environmental 1.Lymphoreticular 1.Infections (viral,bacterial,parasite) 2.Hormonal 2.Drugs 3. Metabolic 3.UV light B cell proliferation (nucleic acids,IC, cellular debris) B cell differentiation Genetic Autoantibody production 1.Anti-lymphocyte 2.Anti-nuclear 3.Other +Antigen Tissue deposition Inflammation

9. Pathology(1) • Hematoxylin bodies These basophilic staining bodies are nuclear debris, often associated with antinuclear antibody, and represent a correlate of the LE cell in vivo.

10. Pathology(2) • The spleen has “union skin lesions”, concentric fibrosis of the walls and surrounding tissues of the central and penicilliary arteries.

11. Pathology(3) • Nonbacterial verrucous endocarditis (Libman-Sacks) consists of vegetations on the heart valves or chordas tendiness

12. Pathology(4) • The renal pathology varies from mild to severe glomerular inflammation and variable interstitial involvement, is usually a mixture of proliferative and membranous changes. • Extensive crescent formation and substantial glomerular or interstitial scarring are unfavourable prognostic signs.

13. WHO classification • Class I Normal kidney • Class II Minimal or Mesangial lupus nephritis • Class III Focal proliferative lupus nephritis <25% • Class IV Diffuse proliferative lupus nephritis >50% • Class V Membranous lupus nephritis • Class VI Sclerosis lesions

14. Clinical Manifestations SLE is a highly variable disease. At the beginning only a single organ may be involved or many systems may be affected simultaneously. Fever, weakness, fatigability, or weight loss may be the first evidence of illness and are often insidious.

15. Clinical Manifestations • Skinmalar rash (the characteristic butter-fly), alopecia, oral ulcers, photosensitivity • Arthritis symmetrical, the proximal inter-phalangeal joints of the hands, metacarpo-phalangeal joints, wrists, and knees being most commonly affected. No bony erosion.

16. Clinical Manifestations • Serositis pleuritis or pericarditis • Renal disorder proteinuria/ hematuria, nephrotic syndrome, renal insufficiency • Heart nonbecterial verrucous endocarditis • Lung diffuse interstitial pneumonitis

17. Clinical Manifestations • Liver liver enlargement, liver enzyme elevation • Neurologic disorder seizures, psychosis • Hematologic problems anemia, thrombo-cytopenia

18. Laboratory Findings • Full blood count hemolytic anemia, leukopenia, thrombocytopenia, ESR • Urinalysis hematuria, proteinuria, red and white cell casts

19. Laboratory Findings • Immunological examination 1.LE cellThe antibody reacts with whole nuclei, coats the nucleus, and then is phagocytized, leading to the formation of the LE cell.

20. Laboratory Findings 2. Antinuclear antibodies (ANA) The best screening test for SLE. ANA are found in 95% of patients with SLE, often in high titer. However, ANA may be found occasionally in normals and sometimes in patients with other disorders, but usually in low titer.

21. Laboratory Findings 3. Anti-ds-DNA antibody High titers of anti-ds-DNA antibodies are seem only in SLE. Radioimmunoassay is used. This test should be carried out on all patients suspected of having SLE. 4.Anti-Sm antibodies Specific for SLE patients.

22. Laboratory Findings 5. Complement Markedly depressed complement levels including CH50,C4 and C3 are seen primary in patients with active lupus nephritis. The low levels probably reflect in vivo activation and fixation of complement components by CIC.

23. Laboratory findings • Lupus band test (LBT) Studies of nonlesional skin from patients with SLE about 50% of the patients have revealed deposits of immunoglobulin and complement proteins at the dermal-epidermal junction. • Renal biopsy is very important for the diagnosis of patients with SLE.

24. Criterion 1. Malar rash 2. Discoid rash 3. Photo- sensitivity 4.Oral ulcers Definition Fixed erythema, flat or raised, over malar eminences, spare the nasolabial folds. Skin rash as a result of unusual reaction to sunlight Usually painless Criteria for Classification of Systemic Lupus Erythematosus (1982)

25. Criterion 5.Arthritis 6.Serositis 7.Renal disorder 8.Neurologic disorder Definition Nonerosive arthritis involving two or more peripheral joints, characterized by tenderness swelling or effusion a)Pleuritis OR b)Pericarditis a)Persistent proteinuria >0.5g/d OR b)Cellular casts: red cell, granular, hemoglobin, tubular, or mixed a)Seizures OR b)Psychosis

26. Criterion 9.Hematologic disorder 10.Immunologic disorder 11.Antinuclear antibody Definition a)Hemolytic anemia OR b)Leukopenia OR c)Lymphopenia OR d)Thrombocytopenia a)Positive LE cell preparation OR b)Anti-DNA OR c)Anti-Sm OR d)False-positive serologic test for syphilis

27. For the purpose of identifying patients in clinical studies, a person shall be said to have systemic lupus erythematosus if any 4 or more of the 11 criteria are present.

28. Therapy • Patients with SLE usually need more than normal rest. • Ultraviolet light should be avoided. • Stress, including surgery, infections, childbirth, abortions, and psychological pressures, may exacerbate disease.

29. Therapy 1. Nonsteroidal anti-inflammatory drugs (NSAID) such as aspirin and ibuprofen are useful for arthritis, serositis, and fever. Indomethacin 25-50mg tid p.o. Side effects Gastrointestinal tract hemorrhage Renal tubular-interstitial lesions

30. Therapy 2. Antimalarials is effective for skin involve-ment, it also may help treat arthritis and other manifestations Chloroquine 0.25 to 0.5 qd p.o.

31. Therapy 3. Corticosteroids may be necessary in patients with severe involvement. prednisone 1mg/Kg/ day prednisonelone 800-1000mg qd iv.gtt

32. Therapy 4. Immunosuppressive drugs Cyclophosphamide (CTX) 0.5-1g/m2 Azathioprine 1-2mg/Kg/day p.o. Cyclosporine A 3-5mg/Kg/day p.o. 5. Chinese medicine 雷公藤多甙片 10-20mg tid p.o.

33. Steroids • Prednisone remain the best effective and rapidly acting immunomodulator therapy. • Typical initial treatment pred. 1mg/Kg/day ×4-12 weeks

34. hypertension osteoporosis diabetes atherosclerosis avascular necrosis Cushingoid appearance insomnia striae agitation risk of infection The toxicities of chronic steroids

35. Cyclophosphamide • CTX is considered the mosteffective cytotoxic in the management of lupus renal disease. • The side effects are less in patients treated with parenteral route of CTX than oral CTX.

36. bone marrow suppression with peripheral cytopenias permanent ovarian failure with infertility hemorragic cystitis alopecia liver injury risk of infection theoretic risk of malignancy The major toxicities of CTX

37. RHEUMATOID ARTHRITIS

38. Introduction • RAis a chronic, systemic inflammatory disorder of unknown etiology characterized by the manner in which it involved joints. • Progressive joint destruction and deformityleads to variable degrees of incapacitation. • F:M=2-3:1 40-60 years old

39. Etiology • Genetic factorsHLA-DR4 • Infection

40. Etiology • Rheumatoid factors (RF) are antibodies with specificity for antigenic determinates on the Fc portion of human or animal IgG. Currently, the most popular notion that RF arise as antibodies to “altered”autologous IgG.

41. Ab Ab HLA pathogen

42. Pathology • Synovitis edema, cell proliferation Rheumatoid pannus, a vascular granulation tissue composed of proliferation fibroblasts, numerous small blood vessels, and various numbers of inflammatory cells. • Vasculitis a widespread necrotizing arteritis of small and medium sized arteries

44. Pathology • Rheumatoid nodules Characteristic histologic changes in nodules showing granulomatous foci with central zones of cell necrosis, surrounded by a palisade of proliferated mononuclear and peripheral fibrosis and chronic inflammatory cell infitration.

45. Clinical features The onset of RA is frequently heralded by prodromal symptoms such as fatigue, anorexia, weight loss, weakness and generalized aching and stiffness. *Joint disease * Extraarticular manifestations

47. Clinical features • Joint disease The small joints of the hands, the wrists, knees, and feet are most commonly involved. It usually is bilateral, symmetrical, and polyarticular.

48. Clinical features • Joint disease • Morning stiffness • Swelling • Typical hand deformities • Limited joint motion

49. Clinical features • Extraarticular manifestations • Rheumatoid nodules • Vasculitis • Pleuropulmonary manifestations • Cardiac manifestations • Neuropathy • Sjogren’s syndrome

50. Laboratory findings • Anemia of moderate degree • ESR  a useful parameter for assessing response to therapy • C-reactive protein  • RF 70% but not specific • CIC  , complements 