1. SYSTEMIC LUPUS ERYTHEMATOSUS 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. Introduction fatigue anemia fever rashes sun sensitivity alopecia
arthritis
pericarditis
pleurisy
vasculitis
nephritis
central nervous system disease

5. Introduction F:M=7-10:1 Child-bearing age （ 13 ~ 40 years old）
Prevalence in women
China 113 per 100,000
USA 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 Infections
(viral,bacterial,parasite)
2.Hormonal Drugs
3. Metabolic 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
Skin malar 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 cell The 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. Criteria for Classification of Systemic Lupus Erythematosus (1982)
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

25. two or more peripheral joints, characterized by tenderness swelling
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. a)Positive LE cell preparation OR b)Anti-DNA OR c)Anti-Sm OR
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 mg 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 to 0.5 qd p.o.

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

32. Therapy 4. Immunosuppressive drugs Cyclophosphamide (CTX) 0.5-1g/m2
Azathioprine mg/Kg/day p.o.
Cyclosporine A 3-5mg/Kg/day p.o.
5. Chinese medicine
雷公藤多甙片 mg 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. The toxicities of chronic steroids
hypertension
osteoporosis
diabetes
atherosclerosis
avascular necrosis
Cushingoid appearance
insomnia
striae
agitation
risk of infection

35. Cyclophosphamide
CTX is considered the most effective 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. The major toxicities of CTX
bone marrow suppression with peripheral cytopenias
permanent ovarian failure with infertility
hemorragic cystitis
alopecia
liver injury
risk of infection
theoretic risk of malignancy

37. RHEUMATOID ARTHRITIS

38. Introduction
RA is a chronic, systemic inflammatory disorder of unknown etiology characterized by the manner in which it involved joints.
Progressive joint destruction and deformity leads to variable degrees of incapacitation.
F:M=2-3: years old

39. Etiology
Genetic factors HLA-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 

51. Laboratory findings Synovial fluid
Radiology Bony decalcification localized to or most marked adjacent to the involved joints and not just degenerative changes
Rheumatoid nodules

52. Proposed 1987 Revised American Rheumatism Association Criteria for Rheumatoid Arthritis
Morning stiffness for at least one hour and present for at least six weeks
Swelling of three or more joints for at least six weeks
Swelling of wrist, metacarpophalangeal or proximal interphalangeal joints for six or more weeks
Symmetric joint swelling

53. Proposed 1987 Revised American Rheumatism Association Criteria for Rheumatooid Arthritis
Hand roentgenogram changes typical rheumatoid arthritis that must include erosions or unequivocal bony decalci-fication
Rheumatoid nodules
serum rheumatoid factor by a method positive in less than 5% of normals

55. Four or more criteria must be present to diagnose rheumatoid arthritis.

56. Treatment Relief of pain reduction or suppression of inflammation
minimizing undesirable side effects
preservation of muscle and joint function
return to a desirable and productive life

57. Treatment Treatment pyramid for RF Experiment drugs
Penicillamine, Steroids
Antimalarials, Gold salts
Asprin, NSAIDs, Analgesics
Education, Rest, Exercise, Social service

58. Treatment Drug therapy Nonsteroidal antiinflammatory drugs (NSAIDs)
eg: indomethacin, ibuprofen
Side effects

59. Treatment Drug therapy
the slow acting drugs including gold, antimalarials and penicillamine
eg: chlorquine, gold salts (auranofin), CTX
corticosteroid
eg: prednisone

60. Treatment Physical measures
Appropriate and skilled therapy can provide notable benefit for the RA patient.
Orthopedic surgery
can be preventative or reparative