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Systemic Lupus Erythematosus Definition. An inflammatory multi-system diseaseImmunologic aberrations: excessive auto-antibody production Tissue damage results from antibody and complement fixing immune complex depositionWide spectrum of clinical presentations Characterized by remissions and exacerbations.
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1. Systemic Lupus Erythematosus ?????
?-1800 ??? ???? ??? ?????? ??? ????? ???, ??"? ???? ??????? ?? ????? ???? ??? ???.
???? ?????? ??? ?????, ??? ???????? ?? ?????.?????
?-1800 ??? ???? ??? ?????? ??? ????? ???, ??"? ???? ??????? ?? ????? ???? ??? ???.
???? ?????? ??? ?????, ??? ???????? ?? ?????.
2. Systemic Lupus ErythematosusDefinition An inflammatory multi-system disease
Immunologic aberrations: excessive auto-antibody production
Tissue damage results from antibody and complement fixing immune complex deposition
Wide spectrum of clinical presentations
Characterized by remissions and exacerbations ???? ??-??????? ?? ????? ?? ??' ?????? ?????? ??? ?? ??????? ??????, ????? ????????? ???????? ??????? ?????? ??????? ???? ?????.
???????? ???????? ???? ????? ?????? ??? ?????? ???? ??? ?????? ????? ??? ????.
????? ?? ???? ??? ?? ??????? ??????????.???? ??-??????? ?? ????? ?? ??' ?????? ?????? ??? ?? ??????? ??????, ????? ????????? ???????? ??????? ?????? ??????? ???? ?????.
???????? ???????? ???? ????? ?????? ??? ?????? ???? ??? ?????? ????? ??? ????.
????? ?? ???? ??? ?? ??????? ??????????.
3. Epidemiology SLE - recognized worldwide
Prevalence in USA: 15-50 \ 100,000 (1:2000)
Incidence in USA: 1.8-7.6 \ 100,000\ year
F:M 9:1 ( at age: 14-64 )
Racial predisposition: x 3 more common in blacks ????? ????? ??? ?????.
?????? 1:2,000 ????"?.
?? ??? ?? 9:1 ????-????? ???? ??????.
?? ????? ??????? ?????????? ???? ?? ???? ????.????? ????? ??? ?????.
?????? 1:2,000 ????"?.
?? ??? ?? 9:1 ????-????? ???? ??????.
?? ????? ??????? ?????????? ???? ?? ???? ????.
4. Epidemiology in the young and elderly Peak incidence is at age 15-40
But: Onset may be at any age
In pre-pubertal and post menopausal:
female : male ratio 3:1
??? ????? ???? 15-40, ?? ????? ?????? ??? ???. ???? ??? ???????? ?? ???? ??? ????? ???? ??? 3:1, ???? ?? ????? ???????? ?????.??? ????? ???? 15-40, ?? ????? ?????? ??? ???. ???? ??? ???????? ?? ???? ??? ????? ???? ??? 3:1, ???? ?? ????? ???????? ?????.
5. Genetic Epidemiology SLE is a multi-genic disease
In < 5% of patients a single gene is responsible
Homozygous deficiencies of early components of complement (C1q, C1r, C1s, C4, C2) predispose to SLE
A null allele for C4A is the HLA-linked gene most consistently associated with susceptibility to SLE ???? ???? ?????-????, ????? ?-5% ??????? ???? ???? ?? ???.
??????? ???????: ????? ???????? ??????? ?? ????? (??? ?-C4a ?????????? ??? ?????).???? ???? ?????-????, ????? ?-5% ??????? ???? ???? ?? ???.
??????? ???????: ????? ???????? ??????? ?? ????? (??? ?-C4a ?????????? ??? ?????).
6. Genetic Epidemiology HLA class II genes are associated with
production of auto-antibodies
TCR genes and Ig genes may contribute to
susceptibility
FCgRIIA, FCgRIIIA predispose to SLE in some
ethnic groups
(possibly responsible for impaired IC clearing)
?? ??? ??? HLA ??????? ?????? ??????? ??????.
?? ??? ??? TCR ?-Ig ??? ??????????? ?-Fc-g-R.?? ??? ??? HLA ??????? ?????? ??????? ??????.
?? ??? ??? TCR ?-Ig ??? ??????????? ?-Fc-g-R.
7. Q: Which of the following statements regarding genetic predisposition in SLE is incorrect? ~ 10% of SLE patients have relatives with SLE
The concordance for monozygotic twins is 85%
Males need more susceptibility genes
Relatives of SLE patients have increased
incidence of auto-antibodies
5. Relatives of SLE patients have increased
incidence of other autoimmune diseases
?? ???? ????? ???? 2.?? ???? ????? ???? 2.
8. Genetic Epidemiology concordance for monozygotic twins: 24-58%
relatives of SLE patients have increased incidence of:
- SLE
- other auto-immune diseases
- auto-antibodies
~ 10% of SLE patients have relatives with SLE
males need more susceptibility genes
?????? ???????????? ?? ????? ?? 24-58%, ???? ??? ????, ?? ?? ????? ?????.
?????? ???' ?? ????? ?? ??????? ?????? ?????? ????' ????? ??????? ?????? ?-10%.
????? ?????? ????? susceptibility genes.?????? ???????????? ?? ????? ?? 24-58%, ???? ??? ????, ?? ?? ????? ?????.
?????? ???' ?? ????? ?? ??????? ?????? ?????? ????' ????? ??????? ?????? ?-10%.
????? ?????? ????? susceptibility genes.
9. Importance of Sex hormones Female predominance (9:1)
disease activity during menstrual period
increased disease activity in pregnancy
flares with oral contraceptive therapy
abnormally rapid testosterone metabolism
estrogenic metabolites persist longer ???? ????? ????? ???? ?? ??????? ??? ?????, ????? ????? ???? ???' ?????? ?????? ???????, ????? ???????? (??????).
????????? ?? ????????? ???? ???? ????? ??.???? ????? ????? ???? ?? ??????? ??? ?????, ????? ????? ???? ???' ?????? ?????? ???????, ????? ???????? (??????).
????????? ?? ????????? ???? ???? ????? ??.
10. Environmental Factors Ultraviolet light ( UVB )
Alfalfa sprouts, chemicals ( hydrazines) ?
Drugs (Resprim = Trimethoprim + sulphamethoxazole)
Infections (parvovirus, CMV, HCV )
Smoking ( Discoid LE ) ???? ????? ?????? ?? ??? ???? ??? ?????? ?????.
?? ?????? ????????, ???? ?? ??????:
????? ????? UV ????? ????? ???????? ????? ???????? (?? ?? ????) ?? ????? ?? ???????? ??? ??"? ??????? ???????????.
???? alfalfa, ????????? (hydrazines).
?????? ????????????? (resprim).
??????? ?????, ????? ???????? ??? ??? ?? ????? ????? ????? ?????. parvo-virus ???? ????? ???????, ??? ??? ?????. ?? ?? HCV ?-CMV.
????? ???? ???????? ????? ????? (discoid LE).???? ????? ?????? ?? ??? ???? ??? ?????? ?????.
?? ?????? ????????, ???? ?? ??????:
????? ????? UV ????? ????? ???????? ????? ???????? (?? ?? ????) ?? ????? ?? ???????? ??? ??"? ??????? ???????????.
???? alfalfa, ????????? (hydrazines).
?????? ????????????? (resprim).
??????? ?????, ????? ???????? ??? ??? ?? ????? ????? ????? ?????. parvo-virus ???? ????? ???????, ??? ??? ?????. ?? ?? HCV ?-CMV.
????? ???? ???????? ????? ????? (discoid LE).
11. Defective Immune Regulation B cell and T cell hyperactivity leads to:
T cell dependent auto-Ab production made in
high quantity
Subsets of auto-Abs and the Immune Complexes they form with Ag mediate tissue damage
Defective clearance of Immune Complexes
Defects in immune tolerance and apoptosis
Defects in T and natural killer regulatory cells ?? ????? ????? ???????? ?? ??' ??????:
????? ?????? ??? ?? ??? B ?-T ??????? ?????? ??? auto-Ab.
??????? ????? ??????? ???? ????? ??????.
?? ?? ????? ?? ?????????? ?????.
?? ???? ??????? ???????? ???????????.
?? ????? ???? T ?-NK.?? ????? ????? ???????? ?? ??' ??????:
????? ?????? ??? ?? ??? B ?-T ??????? ?????? ??? auto-Ab.
??????? ????? ??????? ???? ????? ??????.
?? ?? ????? ?? ?????????? ?????.
?? ???? ??????? ???????? ???????????.
?? ????? ???? T ?-NK.
12. Pathogenic auto-antibodies Mechanisms of damage Direct binding to tissue via charge or
cross-reactivity ( anti-DNA)
Production of Immune Complexes leads to complement mediated damage
Direct binding to cell membranes
( RBCs, Platelets) ????? ?? ???? ?? ????????? ?? ?? ????? ?? ???????? ????? (??? ?????????), ????? ?? ??????? ??????? ??? ???? ?"? ??????.????? ?? ???? ?? ????????? ?? ?? ????? ?? ???????? ????? (??? ?????????), ????? ?? ??????? ??????? ??? ???? ?"? ??????.
13. Clinical Manifestations of SLE Constitutional
non-specific but very common:
- Fatigue
- Fever
- Weight Loss
???????? ??????? ??????
?????? ????????????????? ???? ??????. ?? ?? ????????, ??? ???? ???? ????? ????? ?????? ??????? (???? ?? ????? ?? ??, ??? ???), ??? ?????? ?????. ?? ?-DD ????, ??? ?????? ?? ????? ?? ???? ?? ???????.???????? ??????? ??????
?????? ????????????????? ???? ??????. ?? ?? ????????, ??? ???? ???? ????? ????? ?????? ??????? (???? ?? ????? ?? ??, ??? ???), ??? ?????? ?????. ?? ?-DD ????, ??? ?????? ?? ????? ?? ???? ?? ???????.
14. Skin ManifestationsLE-specific lesions Acute: - malar butterfly rash
- generalized erythema
- bullous LE
Subacute cutaneous lupus
Chronic lupus:
- localized discoid
- generalized discoid
- lupus profundus ??????? ??????
Acute
????? ?????? ??? ????? ????, ????? ?????? ?????? ?? ?????? ???? ???. ????? ?????-?????? ??? ????? ????. ?? ??? ?????? ?? ????? ???. ???? ????? ????????????? ????.
?????? ??????? ???? ?? ?????????????.
????? ??????? ???????? ??????? ?????? ????.
??????? ?????? ??? ??????? ????.
Subacute
?? ?????? ???????, ?? ??? ?????:
?????????????? ???? ?????, ?????? ????? ???? ???? (???? ?-V, ??????).
????? ???????? (??????) ?? ??????? ?????? ????.
Chronic
?????????? ????? ????? ?? ??? ???, ????? ?????-????????? ????? ?????-????????? ????? ?? ??????? ?????. ????? ?????? ?????????, ????? ?? ???? ?? ????, ?? ??? ???? ?????.
??"? ??? ??? ???.??????? ??????
Acute
????? ?????? ??? ????? ????, ????? ?????? ?????? ?? ?????? ???? ???. ????? ?????-?????? ??? ????? ????. ?? ??? ?????? ?? ????? ???. ???? ????? ????????????? ????.
?????? ??????? ???? ?? ?????????????.
????? ??????? ???????? ??????? ?????? ????.
??????? ?????? ??? ??????? ????.
Subacute
?? ?????? ???????, ?? ??? ?????:
?????????????? ???? ?????, ?????? ????? ???? ???? (???? ?-V, ??????).
????? ???????? (??????) ?? ??????? ?????? ????.
Chronic
?????????? ????? ????? ?? ??? ???, ????? ?????-????????? ????? ?????-????????? ????? ?? ??????? ?????. ????? ?????? ?????????, ????? ?? ???? ?? ????, ?? ??? ???? ?????.
??"? ??? ??? ???.
15. Butterfly- malar rash
16. Generalized, photosensitive erythema
17. Bullous rash
18. Subacute cutaneous rash psoriatiform annular
19. Discoid rash
20. Skin Manifestations LE-nonspecific lesions Panniculitis
Urticarial lesions
Vasculitis
Livedo reticularis
Oral lesions
Non-scarring alopecia ??????? ?????? ?????? ??????, ????? ???????? ????? ???????????:
?????????? ???? ????-????? ????? ????? ??????.
????? ???????????.
????????? ??"? ?????? ???????, ???? ????.
Livedo reticularis ????? ????? ??????, "??? ???" ??? ?? ?? ?????? ????.
????? ???.
Alopecia ???? ???? ????? ????? ??????? ??? ?????? ??????? (??? ?? ?? ???????? ????). ??? ???? ???? ???? ???? ????????.??????? ?????? ?????? ??????, ????? ???????? ????? ???????????:
?????????? ???? ????-????? ????? ????? ??????.
????? ???????????.
????????? ??"? ?????? ???????, ???? ????.
Livedo reticularis ????? ????? ??????, "??? ???" ??? ?? ?? ?????? ????.
????? ???.
Alopecia ???? ???? ????? ????? ??????? ??? ?????? ??????? (??? ?? ?? ???????? ????). ??? ???? ???? ???? ???? ????????.
21. Panniculitis
22. Vasculitis with finger tip ulcers
23. Livedo reticularis
24. Alopecia (diffuse or patchy) Non-scarring if part of SLE flare Scarring if results from discoid
25. Skin biopsy:Lupus band test = immunofluorescent staining of IgG and complement deposits in dermo-epidermal junction ?????? ???????' ??? ????? ???? ??? ?-dermo-epidermal junction, ?? ??????? ?? ????????? ???????? ??????? ????? ??.
??? ??? lupus band test ??? ????? ?? ?????? ????? ??, ???? ?? ????? ?? ??.?????? ???????' ??? ????? ???? ??? ?-dermo-epidermal junction, ?? ??????? ?? ????????? ???????? ??????? ????? ??.
??? ??? lupus band test ??? ????? ?? ?????? ????? ??, ???? ?? ????? ?? ??.
26. Skin biopsy - SLE dermatitisThickened epidermal basement membrane (large arrows)Inflammatory infiltrates (small arrow) ??????? ??????? ????? ?-junction.??????? ??????? ????? ?-junction.
27. Skin biopsy - Discoid lesionHyperkeratosis (small arrow)Lymphoid infiltrates (thick arrow) Fibrosis of deep dermis ???????? ???? ????-???????, ????? ????????? ???? ?? ???????? ?????? ????? ????????.???????? ???? ????-???????, ????? ????????? ???? ?? ???????? ?????? ????? ????????.
28. Musculoskeletal Manifestations Arthritis: - the most common manifestation of SLE - non-erosive, rarely deforming (Jaccouds deformity) - synovial fluid- mild inflammation
- tenosynovitis-may be early manifestation
Myopathy:
- myositis = true inflammation
- myopathy 2nd to drugs: steroids, anti-malarials
??' ???????????????
??????
???????? ??? ?????? ????? ????? ?????? (95% ???? ??????? ??? ???? ?-RA). ??? ?? ???????? ????? ?????? ???-???????.
Jaccoud's arthrophy ????? ????????, ???? ??? ?????????, ??? ??? ???????, ???????? ????? ????? ?? ?????? ?? ????, ?? ???????? ????? ??? ?????? ???? ?? ????. ?????? ?????.
?????? ?????????? ?? ?????, ????? ????? ????????????.
??????
???? ????? ????? ????? ?????.
????? ??????? ????? ?????????? ?? ?????? ?????? ?????? ??????? ??????.??' ???????????????
??????
???????? ??? ?????? ????? ????? ?????? (95% ???? ??????? ??? ???? ?-RA). ??? ?? ???????? ????? ?????? ???-???????.
Jaccoud's arthrophy ????? ????????, ???? ??? ?????????, ??? ??? ???????, ???????? ????? ????? ?? ?????? ?? ????, ?? ???????? ????? ??? ?????? ???? ?? ????. ?????? ?????.
?????? ?????????? ?? ?????, ????? ????? ????????????.
??????
???? ????? ????? ????? ?????.
????? ??????? ????? ?????????? ?? ?????? ?????? ?????? ??????? ??????.
29. Jaccouds arthropathy
30. Renal Disease in SLE Proteinuria: 0.5 gr\ 24 hrs ( or > +3 )
Urinary casts: RBC,granular,tubular,mixed
Hematuria: > 5 RBC / high power field
Pyuria: > 5 WBC / high power field
prevalence: 30-65%
in 3-6% renal disease is first manifestation ????
???? ??? ?? ???? ?????? ?????? ????:
??????????? ?? ????? 0.5 ??' ?????.
?????? ???? (RBC, ??????????).
??????? ?? ????? 5 ??????' ????.
??????? ?? ????? 5 WBC ????.
?????? ?????? ?? ?????? ?????? ????? (3-6%), ?? ?? ???? (30-65%).????
???? ??? ?? ???? ?????? ?????? ????:
??????????? ?? ????? 0.5 ??' ?????.
?????? ???? (RBC, ??????????).
??????? ?? ????? 5 ??????' ????.
??????? ?? ????? 5 WBC ????.
?????? ?????? ?? ?????? ?????? ????? (3-6%), ?? ?? ???? (30-65%).
31. WHO Classification of Lupus Nephritis J Am Soc Nephrol 15: 241-250, 2004 Class I - Minimal mesangial LN (mesangial immune deposits seen by IF)
Class II - Mesangial proliferative LN
Class III- Focal proliferative LN (<50% of glomeruli with focal subendothelial immune deposits)
Class IV - Diffuse proliferative segmental LN (IV-S)
- Diffuse proliferative global LN (IV-G) (> 50% of glomeruli with subendothelial immune deposits)
Class V - Membranous LN (global or segmental subepithelial deposits)
Class VI - Advanced sclerosing LN (> 90% of glomeruli globally sclerosed)
?????????? ?? ?-WHO ?-lupus nephritis ??? ????? ???? ??? ???????? ?????:
????????? ???? ???? ??? ??????????? ????????? ????' ?????? ????.
Class 1-2 ???? ???? ???, ?? ????? ?????.
Class 6 ???????? ????????, ??? ??? ????.
Class 3-5 ???? ???? ????????.
?? ???? ???? ????? ???????.
?? ???????????? ???, ????? ????? ???? ??? ??????? ??"? ?????.
????? ??? ?????? ?????? ?????.?????????? ?? ?-WHO ?-lupus nephritis ??? ????? ???? ??? ???????? ?????:
????????? ???? ???? ??? ??????????? ????????? ????' ?????? ????.
Class 1-2 ???? ???? ???, ?? ????? ?????.
Class 6 ???????? ????????, ??? ??? ????.
Class 3-5 ???? ???? ????????.
?? ???? ???? ????? ???????.
?? ???????????? ???, ????? ????? ???? ??? ??????? ??"? ?????.
????? ??? ?????? ?????? ?????.
32. Renal disease in SLE Mild disease - Class II
Serious disease - Class III, IV, V
Clinical course:
- Class II:
hematuria, sub-nephrotic proteinuria, preserved GFR
- Class III and IV:
edema, HTN
nephritic sediment, mild-mod proteinuria, acute GFR
- Class V:
features of nephrotic syndrome, preserved/ gradual GFR
1 ????? ????????? ????.
2 - ????? ?? ???' ?? ????????.
3-4 ???? ???????????? ?? ????? ????????? ????-??????, ???? 3 ??????? (???? ?-50%) ?-4 ??????? (???? ?-50%).
5 membranous, ????? ????-?????.
6 ???????? ?? ??? ?-90% ??????????.
???? ???? ???????? ??:
?????? ?????? ????? ???? ???? ??????????.
?????? ?????? ?????? ???? ??? ??????.1 ????? ????????? ????.
2 - ????? ?? ???' ?? ????????.
3-4 ???? ???????????? ?? ????? ????????? ????-??????, ???? 3 ??????? (???? ?-50%) ?-4 ??????? (???? ?-50%).
5 membranous, ????? ????-?????.
6 ???????? ?? ??? ?-90% ??????????.
???? ???? ???????? ??:
?????? ?????? ????? ???? ???? ??????????.
?????? ?????? ?????? ???? ??? ??????.
33. Serositis in SLE Pleuritis - occurs in 30-60% of patients
Pericarditis - occurs in 20-30%
Peritonitis ????? ?? ????? ????.
???? ????????? (60% ???????).
?????????? (20-30%).
?????????? ???? ?? ????, ????? ?? ????? ?????.????? ?? ????? ????.
???? ????????? (60% ???????).
?????????? (20-30%).
?????????? ???? ?? ????, ????? ?? ????? ?????.
34. Cardiac Manifestations Pericarditis
Myocarditis
Endocarditis (Libman -Sacks endocarditis)
Coronary heart disease ??
?????????? ??? ????.
??????????.
??????????? ?????? ??????? ??????? ??? libmann sacks ????? ?????????.
???? ?? ????????? ???? ????? ?????????? ???????????, ?? ???? ???????????? ????.??
?????????? ??? ????.
??????????.
??????????? ?????? ??????? ??????? ??? libmann sacks ????? ?????????.
???? ?? ????????? ???? ????? ?????????? ???????????, ?? ???? ???????????? ????.
35. Pulmonary Manifestations Pleuritis
Pneumonitis - acute or chronic
Pulmonary hemorrhage - due to vasculitis
Pulmonary hypertension
Pulmonary embolism ?????
?? ???????? ?????? ??????:
????????? ??? ????.
??????????? ???? ????? ??????? ?????.
????? ????? ????? ????????? ???? ??? ??????, ?????? ?????, ????.
??"? ?????.
????? ????? ?? ?????? ??? ???????? ???.?????
?? ???????? ?????? ??????:
????????? ??? ????.
??????????? ???? ????? ??????? ?????.
????? ????? ????? ????????? ???? ??? ??????, ?????? ?????, ????.
??"? ?????.
????? ????? ?? ?????? ??? ???????? ???.
36. Question A 40 year old woman with a 20 year history of SLE
presents with:
chest pain, dyspnea and fever.
Current medications:
Prednisone 10mg, Methotrexate 15 mg/wk, Plaquenil 400mg/d
Which of the following are a possible diagnosis?
1. Pneumonia
2. Pleuritis / Pericarditis
3. Lupus pneumonitis
4. Pulmonary embolism
5. All of the above
???? ?? 40 ???? ????? ???? ?? ???????? ?? ?????. ????? ?? ????? ????, ???? ????? ????. ?????? ????????? ?-methotrexate ????? plaquenil (????? ??? ??????).
DD
???? ?????.
????????? / ??????????.
?????-???????????.
????? ?????.
???? ???? ????? ?????, ????? ??? ?? ???????????, ??? ?? ?? ?? ????? ?????. ?? ???? ????? ?? prodrome ?????? ?????? ??????? ?? ?????? ?-DD ???? ????. ?? ?? ??????????? ???? ??? ????-???????????, ?? ?? ?????-??????????? ???? ????? ???? ?? ?????????, ?? ?? ????? ???? ????-??????????.
?????? ?????? ???? ????? CT-angio. ???? ???? (???? ?????, ??-????????), ???? ????? ????. ????? ?????? ??' ??????? ??? ????? ???? ????? ????????.
?? ???? ?????? ?????? ?? ????? ????, ????? ???? ??????-???????????.???? ?? 40 ???? ????? ???? ?? ???????? ?? ?????. ????? ?? ????? ????, ???? ????? ????. ?????? ????????? ?-methotrexate ????? plaquenil (????? ??? ??????).
DD
???? ?????.
????????? / ??????????.
?????-???????????.
????? ?????.
???? ???? ????? ?????, ????? ??? ?? ???????????, ??? ?? ?? ?? ????? ?????. ?? ???? ????? ?? prodrome ?????? ?????? ??????? ?? ?????? ?-DD ???? ????. ?? ?? ??????????? ???? ??? ????-???????????, ?? ?? ?????-??????????? ???? ????? ???? ?? ?????????, ?? ?? ????? ???? ????-??????????.
?????? ?????? ???? ????? CT-angio. ???? ???? (???? ?????, ??-????????), ???? ????? ????. ????? ?????? ??' ??????? ??? ????? ???? ????? ????????.
?? ???? ?????? ?????? ?? ????? ????, ????? ???? ??????-???????????.
37. Hematologic Manifestations Anemia:
- in acute SLE:
coombs positive hemolytic anemia
- secondary to:
chronic disease, CRF, blood loss, drugs.
Leukopenia / Lymphopenia:
- in active disease
- secondary to drugs, infection ?????????
?? ?????? ?????? ????? ??????:
????? ?????? ???? (?????) ????? ????? ???????? ?? coombs ?????, ??? ??????? ???? ???????. ???? ????? ?? ????? ?????? ??????, ????? ??"? ?????, ????? ?? ?? ??? ??????. ?? ?? ?? ???? ?????? ????? ?????? (???? ????? ?? ?????). ????? ?????? ????? ??? ???????? ?? coombs ?????.
????????? ?????????? ???? ????? ?? ???? ??????? ???????' (imuran), ?? ???? ???????, ???? ????? ????.
Coombs ????? ?? ????? ???? ???????.?????????
?? ?????? ?????? ????? ??????:
????? ?????? ???? (?????) ????? ????? ???????? ?? coombs ?????, ??? ??????? ???? ???????. ???? ????? ?? ????? ?????? ??????, ????? ??"? ?????, ????? ?? ?? ??? ??????. ?? ?? ?? ???? ?????? ????? ?????? (???? ????? ?? ?????). ????? ?????? ????? ??? ???????? ?? coombs ?????.
????????? ?????????? ???? ????? ?? ???? ??????? ???????' (imuran), ?? ???? ???????, ???? ????? ????.
Coombs ????? ?? ????? ???? ???????.
38. Hematologic Manifestations Thrombocytopenia:
- anti-platelet abs- common, not always
associated with thrombocytopenia
- occurs in active SLE
- may be isolated finding
( ~ 50,000 without serious bleeding ) ?????????????? ??????? ???? ?????? ?????. ???????? ??????? ?? ?????? ?????????????.
?? ??? ????? ?? ????????????? ????? ??????? (?? ??????), ?? ??? ???? 50,000 ?????? ?? ??????.?????????????? ??????? ???? ?????? ?????. ???????? ??????? ?? ?????? ?????????????.
?? ??? ????? ?? ????????????? ????? ??????? (?? ??????), ?? ??? ???? 50,000 ?????? ?? ??????.
39. Neuropsychiatric SLE Central nervous system
Aseptic meningitis
Cerebrovascular disease
Demyelinating syndrome
Headache (migraine, benign intracranial pressure)
Movement disorder (chorea)
Myelopathy
Seizure disorder
Acute confusional state
Anxiety disorder
Cognitive dysfunction
Mood disorder
Psychosis
Peripheral nervous system
Guillain - Barre syndrome
Autonomic disorder
Mononeuropathy, single/multiplex
Myasthenia Gravis
Neuropathy, cranial
Plexopathyy
Polyneuropathy
??' ???????????????
?? ???? ???? ???????????, ?? ?? ???? ??????? ??????????? ????????????.
??????? CNS
??????? ?-Seizure disorder ???????? ????????? ??????. ???? ?? ???? DD ??????? ???:
????????? ?? ???????, ???? ?????? MS (??-???????????), ??? ??? ??? ???? ?????????, ???????, ??? ?????? ????, ?????? ??????????, ????, ??????, ???????, ???? ??????????????.
??????? PNS
?????????? (???? / ????), ?????? ?????? guillain barre.??' ???????????????
?? ???? ???? ???????????, ?? ?? ???? ??????? ??????????? ????????????.
??????? CNS
??????? ?-Seizure disorder ???????? ????????? ??????. ???? ?? ???? DD ??????? ???:
????????? ?? ???????, ???? ?????? MS (??-???????????), ??? ??? ??? ???? ?????????, ???????, ??? ?????? ????, ?????? ??????????, ????, ??????, ???????, ???? ??????????????.
??????? PNS
?????????? (???? / ????), ?????? ?????? guillain barre.
40. Question A 35 year old woman with a 5 year history of SLE
Currently on: Prednisone 40mg/d,
Azathioprine 100mg/d
Presents to the E.R with:
Fever
Acute confusional state
Focal neurological findings
???? ?? 35, ?? 5 ???? ???????? ?? ?????. ?????? ????????? ????????, ????? ?? ??? ????????? ??????, ??? ?????? ????, ???.???? ?? 35, ?? 5 ???? ???????? ?? ?????. ?????? ????????? ????????, ????? ?? ??? ????????? ??????, ??? ?????? ????, ???.
41. How would you manage her? Give her a sedative due to agitated/confused state
Give her IV Antibiotics
3. Give her pulse IV Solumedrol 1000mg
4. Perform a brain CT scan and lumbar puncture
5. Give her Heparin
?? ??????
????? ?????.
??????????? IV.
????????? (?????-????????).
CT ??? ?-LP ?? ?????? ??????.
?????.?? ??????
????? ?????.
??????????? IV.
????????? (?????-????????).
CT ??? ?-LP ?? ?????? ??????.
?????.
42. What does the differential diagnosis include? Infection - meningitis/ encephalitis
Active CNS Lupus
Toxic \ Metabolic
Thromboembolic
?-DD ???? ????? ????? ???? (??? ?????? ?????), ??? ??????? ?????, ????? (??? ?????? ??????????????? ??? ????????? ?????? ?? ???????), ???? ?????-?????? ?? ????.?-DD ???? ????? ????? ???? (??? ?????? ?????), ??? ??????? ?????, ????? (??? ?????? ??????????????? ??? ????????? ?????? ?? ???????), ???? ?????-?????? ?? ????.
43. Anti-Nuclear Antibodies (ANA) ANA : abs directed against nuclear antigens
may occur in other systemic rheumatic diseases
most frequent and highest in titer in SLE
Positive in 98% of SLE patients
detected by indirect immuno-fluorescence ?????? ?????
ANA ?????? ?????? ?? ?????. ????? ???? ???????? ???? ??????, ?? ?????? ??????, ????? ?????? ???????? ???????? ?????, ?? ????? ??? ???? ??????. ?????? ??? ?? ??? ????, ?? ???? ????? ??????????, RA. ?? ??? ??? ???? ????? ??? ??????? ???. ?? ??, ?? ???? ????? ?? ??? ??? ????? (?? ?? ??? ??? ????').?????? ?????
ANA ?????? ?????? ?? ?????. ????? ???? ???????? ???? ??????, ?? ?????? ??????, ????? ?????? ???????? ???????? ?????, ?? ????? ??? ???? ??????. ?????? ??? ?? ??? ????, ?? ???? ????? ??????????, RA. ?? ??? ??? ???? ????? ??? ??????? ???. ?? ??, ?? ???? ????? ?? ??? ??? ????? (?? ?? ??? ??? ????').
44. Patterns of IF ANA staining Homogenous (diffuse) - dsDNA, histone
SLE, drug induced SLE, RA
Speckled
MCTD, SLE, Sjogren, Systemic Sclerosis
Nucleolar
Systemic Sclerosis, Sjogren, SLE
Rim (peripheral) - dsDNA histones
characteristic of SLE ????? ???????? ??? ?"? ???????' ?? ???? ?????? ?? 4 ?????? ?????: ???????, speckled, ?????????? (???? ???????? ?? ??????????), ?????.
????? ?????? ????? ??? ?? ??????.????? ???????? ??? ?"? ???????' ?? ???? ?????? ?? 4 ?????? ?????: ???????, speckled, ?????????? (???? ???????? ?? ??????????), ?????.
????? ?????? ????? ??? ?? ??????.
45. Patterns of Immuno-fluorescence ANA staining
46. ANAs ANAs can be divided into:
those directed against dsDNA
those directed against ssDNA
those directed against histones
those directed against non-histone nuclear proteins : nucleic acid-protein complexes ???? ??? ?????? ?-ELISA ???? ?? ??????.
?????? ANA ???? ??? ??????:
dsDNA.
ssDNA ??"? ???? ??-???????.
??? ????? ????? ????????.
??? ????? ????? ??-????????? (?. ?????).???? ??? ?????? ?-ELISA ???? ?? ??????.
?????? ANA ???? ??? ??????:
dsDNA.
ssDNA ??"? ???? ??-???????.
??? ????? ????? ????????.
??? ????? ????? ??-????????? (?. ?????).
47. ANAs in SLE Autoantibody
anti- ds DNA
anti- ss DNA
anti- Histones
anti- Sm ( Smith)
anti- RNP
anti- Ro ( SSA)
anti- La ( SSB) Prevalence
50-60%
60-70%
70%
30%
35%
30%
15% ???????? ??????? ??????:
Anti-dsDNA (???? ?????????) ?-50-60% ???????. ?????? ???? ???????, ??? ???? ???? ?"?, ?? ?? ??? ??????.
Anti-smith (anti-sm) ????? ????? ????? Smith ?-30% ???????, ???? ???? ???? ?? ?????? ???, ?? ?? ?????, ?? ?? ?? 30%.
????? anti-ssDNA (60%), anti-histone (70%), anti-Ro (SSA 30%), anti-La (SSB - 15%), anti-RNP (35%). ?? ???? ???? ?? ?? ????????.???????? ??????? ??????:
Anti-dsDNA (???? ?????????) ?-50-60% ???????. ?????? ???? ???????, ??? ???? ???? ?"?, ?? ?? ??? ??????.
Anti-smith (anti-sm) ????? ????? ????? Smith ?-30% ???????, ???? ???? ???? ?? ?????? ???, ?? ?? ?????, ?? ?? ?? 30%.
????? anti-ssDNA (60%), anti-histone (70%), anti-Ro (SSA 30%), anti-La (SSB - 15%), anti-RNP (35%). ?? ???? ???? ?? ?? ????????.
48. Anti DNA antibodies in SLE Anti ss- DNA:
nonspecific and not in clinical use
Anti-ds DNA: specific for SLE
Clinical use important:
- levels correlate with disease activity
- presence and level associated with risk for
renal disease
- pathogenic effect mediated through direct
binding to glomeruli or immune-complex
mechanisms. Anti-ssDNA ?? ?????? ??? ??????, ????? ?? ?????? ???????? ?????.
Anti-dsDNA ??????, ??? ?????? ?????? ???? ???????? ????? ???? ?????? ????? ????????. ?? ???, ??? ?? ?????? ????? ???? ???????? ????? ??????? (?????? ??? 14). ??? ???? ????????? ???????? ?????, ??? ???? ??? ?????? ?????.Anti-ssDNA ?? ?????? ??? ??????, ????? ?? ?????? ???????? ?????.
Anti-dsDNA ??????, ??? ?????? ?????? ???? ???????? ????? ???? ?????? ????? ????????. ?? ???, ??? ?? ?????? ????? ???? ???????? ????? ??????? (?????? ??? 14). ??? ???? ????????? ???????? ?????, ??? ???? ??? ?????? ?????.
49. Clinical Associations of Auto-antibodies in SLE ?? ?????????? ??????? ???????? ??????? ??????:
Anti-dsDNA (50%) ???? ?????? ?? ???????.
Anti-ssDNA ?? ??????, ??? ??????? ??????, ?? ??????.
Anti-histone ?? ?????, ?? ???? ?-drug induced lupus.
Anti-Ro ??? ??????? ?? sub-acute ?-heart block ?????. ??????? ??? ?????? ??? ????? ????? ??????? ???? ????.
Anti-Sm (30%) ??????, ?? ???????.
Anti-RNP mixed connective tissue disease.
APLA ???? ???? ?????, ?-30% ??????? ???? ?????????? ?? ???????? ?????? ??????.?? ?????????? ??????? ???????? ??????? ??????:
Anti-dsDNA (50%) ???? ?????? ?? ???????.
Anti-ssDNA ?? ??????, ??? ??????? ??????, ?? ??????.
Anti-histone ?? ?????, ?? ???? ?-drug induced lupus.
Anti-Ro ??? ??????? ?? sub-acute ?-heart block ?????. ??????? ??? ?????? ??? ????? ????? ??????? ???? ????.
Anti-Sm (30%) ??????, ?? ???????.
Anti-RNP mixed connective tissue disease.
APLA ???? ???? ?????, ?-30% ??????? ???? ?????????? ?? ???????? ?????? ??????.
50. Diagnosis of SLE Based on a combination of clinical manifestations and laboratory findings
which may occur simultaneously or serially
Classification criteria are used for research ????? ?? ????? ??? ????????? ?? ?????? ??????? ?????? ?????.
?? ?????? ?????? ?? ???? ?? ??????. ???? ?? ????????????? ?????? ?? ANA ???? ????? ??? ??? ?????? ???? ????? ????? ?? ?????????, ??? ?? ????? ?? ??????. ????? ??????? ???? ?-suspected lupus, ?? ??? ?? ???? ?? ?? ???????????.
?????????? ????? ????? ?????? ????. ??????? ??????????? ??????? ?????? ??????.????? ?? ????? ??? ????????? ?? ?????? ??????? ?????? ?????.
?? ?????? ?????? ?? ???? ?? ??????. ???? ?? ????????????? ?????? ?? ANA ???? ????? ??? ??? ?????? ???? ????? ????? ?? ?????????, ??? ?? ????? ?? ??????. ????? ??????? ???? ?-suspected lupus, ?? ??? ?? ???? ?? ?? ???????????.
?????????? ????? ????? ?????? ????. ??????? ??????????? ??????? ?????? ??????.
51. Classification criteria of SLE Criterion
Malar Rash
Discoid rash
Photosensitivity
Oral ulcers
Arthritis
Serositis
Renal disorder
Neurologic disorder
Hematologic disorder Definition
- Fixed erythema, malar distribution
- Erythematous raised patches with
scaling, atrophy, scarring
- Skin rash as result of sunlight
- Oral\ nasopharyngeal, usually painless
- Nonerosive, 2 or more joints
- Pleuritis OR Pericarditis
-Proteinuria > 0.5gr or >+3 OR
cellular casts
- Seizures OR Psychosis
- Hemolytic anemia OR
Leukopenia < 4000/ mm3 OR
Lymphopenia <1500/mm3 OR
Thrombocytopenia < 100.000/mm3
?????????? ??????
???? 4/11 ????? ?????.
????? ????.
????? ??????????.
?????????????? ????? ?????? ????.
????? ??? ???? ???? ????', ?????? ??? ?? ????? ??? ?? ?????? ???. ???? ????? ?? ?? ??? ?????? ?? ?????.
???????? ??? ???????, ???? ?????? ?? ????.
???????? ????????? ?? ??????????.
???? ?????? ?? ??????????? ?? ??? 0.5 ???.
?????????? ???????.
????????? ????? ????????, coombs ?????, ????????? ???? ?-4,000, ????????? ???? ?-1,500, ?????????????? ???? ?-100,000.
?????? ???? ??????? anti-dsDNA, anti-Sm, false positive VDRL, APLA.
ANA ??? ???? ??????.?????????? ??????
???? 4/11 ????? ?????.
????? ????.
????? ??????????.
?????????????? ????? ?????? ????.
????? ??? ???? ???? ????', ?????? ??? ?? ????? ??? ?? ?????? ???. ???? ????? ?? ?? ??? ?????? ?? ?????.
???????? ??? ???????, ???? ?????? ?? ????.
???????? ????????? ?? ??????????.
???? ?????? ?? ??????????? ?? ??? 0.5 ???.
?????????? ???????.
????????? ????? ????????, coombs ?????, ????????? ???? ?-4,000, ????????? ???? ?-1,500, ?????????????? ???? ?-100,000.
?????? ???? ??????? anti-dsDNA, anti-Sm, false positive VDRL, APLA.
ANA ??? ???? ??????.
52. Classification criteria of SLE Criterion
10. Immunologic disorder
11. Anti-nuclear antibody
Definition
- anti-dsDNA OR
- anti- Sm OR
- false positive VDRL /
anti-phospholipid antibody
Abnormal titer of ANA in
absence of drugs known to
cause DIL
53. Drug Induced Lupus Clinical manifestations of SLE that:
- appear while taking a drug - resolve on discontinuation of the drug
10% of the incidence of SLE
Clinical features are less severe than SLE.
Common features: fatigue, weight loss, fever, arthritis, serositis, cytopenias.
Uncommon features: CNS and renal involvement Drug induced
???? ?????? ??? ?????, ?? ????? ?? ????? ?????? (10% ???????? ?????).
?????? ?????: ?????? ???, ?????????, ????????, ????????.
??????? ???? ?? CNS ?????? ???? ??????.Drug induced
???? ?????? ??? ?????, ?? ????? ?? ????? ?????? (10% ???????? ?????).
?????? ?????: ?????? ???, ?????????, ????????, ????????.
??????? ???? ?? CNS ?????? ???? ??????.
54. Drug Induced Lupus ANA-positive
Anti-Histone - positive in > 90%
nonspecific - found in SLE as well
Anti-DNA - negative
complement usually normal
serology resolves slowly on drug discontinuation
??????: ANA ????? ?-anti-histone ????? ??? 90% ???????, ??? ?? ??????, ?? ????? ?? ?????? ????, ?? ?-anti-DNA ????? ??? ????? ??????.
???? ?????? ??????. ?-SLE ?? consumption ?? ????? ??????? ?????? (C4, C3) ??? ????? ??? ?????. ?? ??? ???? ???????, ??? ??????? ?????. ?? ?? ??? ????, ?? ????????? ????? ????? ??????. ?-drug induced ??? ????.
????????? ????? ??? ???? ???? ???????? ?????? ??????.??????: ANA ????? ?-anti-histone ????? ??? 90% ???????, ??? ?? ??????, ?? ????? ?? ?????? ????, ?? ?-anti-DNA ????? ??? ????? ??????.
???? ?????? ??????. ?-SLE ?? consumption ?? ????? ??????? ?????? (C4, C3) ??? ????? ??? ?????. ?? ??? ???? ???????, ??? ??????? ?????. ?? ?? ??? ????, ?? ????????? ????? ????? ??????. ?-drug induced ??? ????.
????????? ????? ??? ???? ???? ???????? ?????? ??????.
55. Drugs associated with Drug Induced Lupus Definite: Hydralazine (5-10%) , Procainamide (15-20%), Chlorpromazine, Methyldopa, Isoniazid
Possible association: Phenytoin, Penicillamine, Quinidine
Questionable association: Gold salts, Griseofulvin ?????? ??????: hydralazine (??"?) ?-procainamide (?????? ???) ????.
????? ?????? ??????? ????, ????? ?? ?????? ?? ???, ???? ?????.?????? ??????: hydralazine (??"?) ?-procainamide (?????? ???) ????.
????? ?????? ??????? ????, ????? ?? ?????? ?? ???, ???? ?????.
56. Management of SLE
57. The Challenge Treat Active Lupus
Prevent Damage from:
- Active lupus
- Corticosteroids
- Immunosuppressive agents ?????
?? ???? ???? ?????? ?? ?-DD ??????.
???? ????? ??? ?????? ????.
Damage index ??? ????? ????? ???? ?????? ???????, ?? ?? ??????????? ??????????' ?????? ???. ???? ????? ?? ?? ????? ??????.?????
?? ???? ???? ?????? ?? ?-DD ??????.
???? ????? ??? ?????? ????.
Damage index ??? ????? ????? ???? ?????? ???????, ?? ?? ??????????? ??????????' ?????? ???. ???? ????? ?? ?? ????? ??????.
58. Treatment of active SLEOrgan System Approach Use the drug with the:
- Least side effects
- Lowest dose to control disease
- Long term damage prevention
Mild disease: Avoid Steroids
Severe disease: Aggressive treatment ???? ???? ????? ????? ????? ????? ?????.
???? ?????? ?????? ???? ????? ?????, ?? ??? ?????? ????? ???? ??? ????? ???? (?? ?? ??? ?????? ?????? ?????).
?? ????? ??? ?? ??? ?????????, ?? ????? ????? ??????? ?????.
?? ????? ??? ?????????, ?????????? ???? ????? ?????????.???? ???? ????? ????? ????? ????? ?????.
???? ?????? ?????? ???? ????? ?????, ?? ??? ?????? ????? ???? ??? ????? ???? (?? ?? ??? ?????? ?????? ?????).
?? ????? ??? ?? ??? ?????????, ?? ????? ????? ??????? ?????.
?? ????? ??? ?????????, ?????????? ???? ????? ?????????.
59. Treatments for SLE NSAIDs
Corticosteroids
Hydroxychloroquine (Plaquenil)
Chloroquine (Aralen) Antimalarials
Quinacrine ( Mepacrine; Atabrine)
Methotrexate
Azathioprine
Cyclophosphamide
Cyclosporine
Mycophenolate Mofetil (Cellcept)
IVIG
Thalidomide
??????
NSAIDs ???????, ??????. ???? ?????? ?????? ??????????. ??????? ???????? ????? ??????? ?????? ???.
?????????.
????-??????.
???????'.
??????? ?????????.??????
NSAIDs ???????, ??????. ???? ?????? ?????? ??????????. ??????? ???????? ????? ??????? ?????? ???.
?????????.
????-??????.
???????'.
??????? ?????????.
60. Corticosteroids Effective for the suppression of all SLE manifestations
NOT justified for Arthritis
Moderate doses (20-30mg\d) sufficient for: pleuritis\ pericarditis
High doses (1mg\kg) required for:
Nephritis, CNS disease, Severe hemolytic anemia or thrombocytopenia
IV pulse 1gr methylprednisolone sometimes used for refractory nephritis or life threatening disease ????????? ???? ??? ??????, ?? ?? ????? ??? ??????. ????????? ?????? NSAIDs ?????-??????!
???? ?????? ?????????? / ?????????? ???????? ????? ?? 200-30 ?"? / ?"?.
??????? ?????? ?? ????? ???????? ???, ????????????? ???, CNS ?????? 1 ?"? / ?"?.
Pulse therapy 1 ??' ?? ???? ???????? ???????? ??? ?? ???? ????? ????.????????? ???? ??? ??????, ?? ?? ????? ??? ??????. ????????? ?????? NSAIDs ?????-??????!
???? ?????? ?????????? / ?????????? ???????? ????? ?? 200-30 ?"? / ?"?.
??????? ?????? ?? ????? ???????? ???, ????????????? ???, CNS ?????? 1 ?"? / ?"?.
Pulse therapy 1 ??' ?? ???? ???????? ???????? ??? ?? ???? ????? ????.
61. Anti-MalarialsHydroxychloroquine, Chloroquine, Quinacrine Effective for the treatment of :
Fatigue, Arthritis, Skin disease
Prevents SLE flares
Lowers cholesterol levels
Anti-aggregant effect ???? ??????
?????? ?-RA ???? ???? ??????.
Hydroxychloraquie, chloroquine ??????, quinacrine ???, ?? ?? ????.
??????? ??????? ?????-?????? ??????, ????????, ???? ???.
?? ?? ?????? ??????? ?? ?????.
???? ??? ?? ?? ?? ??????? ??? ??? ???? ?? plaquinin ????? ?????? ????? (????? ??? ????? ?? ???? ?????).
??? ???? ???????????? ???? (?? ????? ??????).???? ??????
?????? ?-RA ???? ???? ??????.
Hydroxychloraquie, chloroquine ??????, quinacrine ???, ?? ?? ????.
??????? ??????? ?????-?????? ??????, ????????, ???? ???.
?? ?? ?????? ??????? ?? ?????.
???? ??? ?? ?? ?? ??????? ??? ??? ???? ?? plaquinin ????? ?????? ????? (????? ??? ????? ?? ???? ?????).
??? ???? ???????????? ???? (?? ????? ??????).
62. Methotrexate May be effective as a steroid sparing agent in the treatment of:
- arthritis
- skin disease Methotrexate
?????? ????? ????? ?? ???? ????? ??? ????? ??? ?????-??????.Methotrexate
?????? ????? ????? ?? ???? ????? ??? ????? ??? ?????-??????.
63. Used mainly for nephritis
May be used for major organ involvement
- Azathioprine: P.O. 2-3mg\kg
- Cyclophosphamide :
IV pulses 0.5-1.0gr/m2 q month than q3 months for 2-3 yrs
- Cyclosporine: P.O. 1-3mg\kg\d
- Mycophenolate Mofetil (Cellcept) : P.O. 1-3gr\d Immunosuppressive agentsAzathioprine, Cyclophosphamide, Cyclosporine, Cellcept ???????'
Azathioprine, Cyclophosphamide, Cyclosporine, Cellcept ???? ?????? ??????, ?-cellcept ?? ???.
??????? ????? ???????? ??? ?-major organ involvement ???????? ?-steroid sparing ??????? ?? ?????????? ??????? ?? ??????.???????'
Azathioprine, Cyclophosphamide, Cyclosporine, Cellcept ???? ?????? ??????, ?-cellcept ?? ???.
??????? ????? ???????? ??? ?-major organ involvement ???????? ?-steroid sparing ??????? ?? ?????????? ??????? ?? ??????.
64. Treatment of Lupus Nephritis Induction: - Corticosteroids - IV Cyclophosphamide \ q month
- Mycophenolate Mofetil (Cellcept) ?
Maintenance: - IV Cyclophosphamide \ q 3 mo - Azathioprine - Mycophenolate Mofetil ( Cellcept ) - Cyclosporine ????? ?????? ???????
????? ???????? ??????, ??? ???? ???? ????? ??? ????? ???????.
??????? ?????? ???????????? ????????? ?-maintenance.
?????????: ????????? ?? IV ?????' ??? ????? ???? ???.
??????: ?????' 3 ?????? ???? ?????? ????.
?? ?? ?????? ????? ?? ????? ???????, ?????? ????? ?????? ?????? ????, ???? ?? ?????? ??????: cellcept, ??????? ??????'.????? ?????? ???????
????? ???????? ??????, ??? ???? ???? ????? ??? ????? ???????.
??????? ?????? ???????????? ????????? ?-maintenance.
?????????: ????????? ?? IV ?????' ??? ????? ???? ???.
??????: ?????' 3 ?????? ???? ?????? ????.
?? ?? ?????? ????? ?? ????? ???????, ?????? ????? ?????? ?????? ????, ???? ?? ?????? ??????: cellcept, ??????? ??????'.
65. Cyclophosphamide side effects Infection
- frequency - 45%
- sequential infusions
- WBC < 3000
Premature ovarian failure
- cumulative dose
- age: < 25 yrs - 6%
> 31 yrs - 67%
Malignancy
leukemia, gynecologic malignancies, bladder ?????? ????? ?? ?????'
IV ??????? ??? ????????? ??????'.
?"? ?????? ???? ??? ???? ????? ?????? (6% ???? ???? 25, ???? 67% ?? ???? ?????? ??? ??? 31). ??? ????? ????? ????? ???? ????????? ?? ????? ?????, ?? ????? ????? ??"? ????? ??? ????? ??.
?????????, ????? ?? ????????.?????? ????? ?? ?????'
IV ??????? ??? ????????? ??????'.
?"? ?????? ???? ??? ???? ????? ?????? (6% ???? ???? 25, ???? 67% ?? ???? ?????? ??? ??? 31). ??? ????? ????? ????? ???? ????????? ?? ????? ?????, ?? ????? ????? ??"? ????? ??? ????? ??.
?????????, ????? ?? ????????.
66. Mycophenolate Mofetil ( MMF = Cellcept) Immunosuppressive for:
kidney, liver and heart transplant
Inhibitor of :
Inosine Monophosphate (IMP) dehydrogenase
- key enzyme in de novo purine synthesis
- glycosylation of adhesion molecules in T and B cells
Inhibits:
- proliferation of T and B lymphocytes
- production of abs
- generation of cytotoxic T cells
- recruitment of leukocytes to sites of inflammation
MMF
?-cellcept ????? ???????, ????? ???????' ?????? ????? ???, ?? ?????.
???? inosine monophosphate dehydrogenase (??????? ???????), ???? ???? ???? ????: T, B, ???????, ???? ??????????.MMF
?-cellcept ????? ???????, ????? ???????' ?????? ????? ???, ?? ?????.
???? inosine monophosphate dehydrogenase (??????? ???????), ???? ???? ???? ????: T, B, ???????, ???? ??????????.
67. MMF or IV Cyclophosphamide for Lupus Nephritis Ginzler et al. NEJM 2005 140 pts class III, IV, V (24 week trial)
MMF (71 pts) CTX (69 pts)
At 12 weeks:
- Complete remission 16 4
- Partial remission: 21 17
- Death 0 3
- Severe infections 1 6
- Diarrhea 15 2
Conclusion:
- MMF more effective than CTX in inducing remission
- severe infections : less with MMF ????: 71 ????? ????? cellcept ??? ?????', ???? ???? ???????, ?? ???? ????, ???? ???????, ??-????? ???????.
???? ???? ?????? ?????' ??????? ????????.????: 71 ????? ????? cellcept ??? ?????', ???? ???? ???????, ?? ???? ????, ???? ???????, ??-????? ???????.
???? ???? ?????? ?????' ??????? ????????.
68. Sequential Therapies for proliferative LNContreras G et al. NEJM 2004 59 patients: class: III-12; IV-46; Vb-1
Induction:
IV CYC (0.5-1gr/m2) q mo for up to 7 pulses + steroids
Maintenance (1-3 yrs):
- IV CYC q 3 months
- AZA 1-3 mg/kg/d
- MMF 0.5-3 gr/d ????? ????????? ?? ?????'.
????? ?????? ?? ????? ???? ???????? ??? ??????? ?? cellcept.????? ????????? ?? ?????'.
????? ?????? ?? ????? ???? ???????? ??? ??????? ?? cellcept.
69. Future possible treatments for SLETreatments designed to effect specific processes LJP 394: B cell toleragen: cross links anti-DNA receptors on B cells
Anti IL-10: IL-10 is increased on correlates with disease activity
Anti-CD40 ligand: prevents T cell activation
CTLA4Ig: blocks CTLA4 on activated T cells from binding to B7 on B cells
Anti C5 complement
C1q immunoadsorption: removes immune complexes
Anti CD 20 (Rituximab):CD20 is B cells restricted ag- leads to B cell depletion
Anti-BLyS: anti B Lymphocyte Stimulator protein which is elevated in SLE
40 ??? ?? ??? ????? ?????? ??????.
???? ????? ???? ??????? ???????? ??????, ??? ??? IL-10.
???? anti-CD20 (rituximab ????????), ???? depletion ?? ??? B, ?? ?????? ????? ???? ?????? ??????.
Anti-BLyS ????? ?????? ?? ??? B (?? ???? depletion) ??? ????? ????? ??? ?? ??' ?????? ??? depleteion.40 ??? ?? ??? ????? ?????? ??????.
???? ????? ???? ??????? ???????? ??????, ??? ??? IL-10.
???? anti-CD20 (rituximab ????????), ???? depletion ?? ??? B, ?? ?????? ????? ???? ?????? ??????.
Anti-BLyS ????? ?????? ?? ??? B (?? ???? depletion) ??? ????? ????? ??? ?? ??' ?????? ??? depleteion.
70. Corticosteroids- the price: Avascular Necrosis of Bone
Osteoporosis with Fracture
Hypertension, Hyperglycemia
Premature Atherosclerosis
Quality of life:
Weight, Cushingoid Habitus, Mood changes ?????? ??? ???? ????? ??????, ????? ????? ????? ???? ???? ?????? ???? ???? ?? ?????? ?????.
????? ?????? ????????? ????? ????????????, a-vascular necrosis, ?????????????, ???????????? ?????? ?? ????? ?????.?????? ??? ???? ????? ??????, ????? ????? ????? ???? ???? ?????? ???? ???? ?? ?????? ?????.
????? ?????? ????????? ????? ????????????, a-vascular necrosis, ?????????????, ???????????? ?????? ?? ????? ?????.
71. Distribution of DamageJohns Hopkins Cohort 25.2% musculoskeletal
15.0% neuropsychiatric
12.6% ocular
11.7% renal
10.4% pulmonary
10.1% cardiovascular
7.4% gastrointestinal
7.4% skin
6.1% diabetes
2.5% malignancy
1.2% premature
gonadal
failure
??? ????? ?????? ???
??? = ????? ???? ????? ?????.
????????????? (25%) a-vascular, ?????????????.
?????-????????
?????
???????
????? ??????
?????? ????????, ????? (?????????).??? ????? ?????? ???
??? = ????? ???? ????? ?????.
????????????? (25%) a-vascular, ?????????????.
?????-????????
?????
???????
????? ??????
?????? ????????, ????? (?????????).
72. SLICC Damage Index SLICC:
Systemic Lupus International Collaborating Clinics
Damage = nonreversible change not related to active inflammation, present for 6 months Damage index (SLICC) - ??? ???? ???? ???? ??? ??? ??????? ?????? ??.Damage index (SLICC) - ??? ???? ???? ???? ??? ??? ??????? ?????? ??.
73. Damage in SLE - Coronary Artery Disease Major cause of morbidity
Bimodal pattern of mortality in SLE:
early - due to disease and infection
late - due to Cardiovascular disease
prevalence: 8-10%
Hydroxychloroquine- may be protective:
reduces cholesterol, anti-aggregation properties ???? ?????? ????? ????????? ??? ???? ?????.
???? ????? ???????? ?"? ??? ?????'.
Plaquinin ???? ????? ???.???? ?????? ????? ????????? ??? ???? ?????.
???? ????? ???????? ?"? ??? ?????'.
Plaquinin ???? ????? ???.
74. Prevalence of cardiovascular disease in SLE Hospitaliztion of young SLE women compared to non SLE:
- 2-3 times more likely to have MI
- 3.8 times more likely to have CHF
- 2.1 times more likely to have CVA
SLE women age 35-44: 50 times more likely to have MI compared to women of similar age (Framingham offspring study)
????? ????? ?? 2 ???? ???????? ???? MI, ?? 3.8 ???? CHF ??? 2.1 ???? CVA.
?? ?? 50 ???? ????? ?-MI.
?? ?? ?????? ????? ???? ????? ?? ???? ??????, ???"? ???? ?? ???? (????: ICD ?????? ?? 35 ??????? ????? ???? 16).????? ????? ?? 2 ???? ???????? ???? MI, ?? 3.8 ???? CHF ??? 2.1 ???? CVA.
?? ?? 50 ???? ????? ?-MI.
?? ?? ?????? ????? ???? ????? ?? ???? ??????, ???"? ???? ?? ???? (????: ICD ?????? ?? 35 ??????? ????? ???? 16).
75. Risk factors for cardiovascular disease in SLE Hypertension
Hyperlipidemia
Diabetes Mellitus
Obesity
Active SLE:
- chronic inflammation leads to endothelial damage
- anti-endothelial abs, anti-phospholipid antibodies
??????? ?????-??????????
???? ??????? ??"?.
????????????.
?????? ?????? ?????? ???? ??? ???? ??????, ??? ??????? ???? ?????? ??? ?-APLA ?? ????? ????????????? ?????.
???? ?????? ?? ?? ????? ??????: ????? ?????', ?????, ????? ?"? ????? ??????? ??? ????? ????? ????? ?? ??????? ???, ???? ??? ???? ?????.??????? ?????-??????????
???? ??????? ??"?.
????????????.
?????? ?????? ?????? ???? ??? ???? ??????, ??? ??????? ???? ?????? ??? ?-APLA ?? ????? ????????????? ?????.
???? ?????? ?? ?? ????? ??????: ????? ?????', ?????, ????? ?"? ????? ??????? ??? ????? ????? ????? ?? ??????? ???, ???? ??? ???? ?????.
76. Prognosis Survival:
90-95% at 2 years
82-90% at 5 years
71-80% at 10 years
63-75% at 20 years
Poor prognostic factors:
- creatinine, nephrotic syndrome
- hypertension
- thrombocytopenia
- African- American race
- low socioeconomic status
????????? ???? ?????.
????? ??????????? ????: ???????? ????, ?????? ???????, ??????????????, ???? ????-??????? (????? ????, ?????? ???? ??? ?????? ?? ???? ?????? ??????), ??? ?????-??????? ???? (???? ?????? ?????).????????? ???? ?????.
????? ??????????? ????: ???????? ????, ?????? ???????, ??????????????, ???? ????-??????? (????? ????, ?????? ???? ??? ?????? ?? ???? ?????? ??????), ??? ?????-??????? ???? (???? ?????? ?????).
77. ?????? ???? ???????? ?? ?????.?????? ???? ???????? ?? ?????.
78. Pregnancy and SLE 1950s:
- in SLE: pregnancy is not advised
- termination should be offered
1990s:
- 10-30% flare during pregnancy / postpartum
- most flares are minor ??????
??? ????' ??? ???? ?????? ?? ????? ???? ???????.
???????? ???? ????? ???????, ?? ?? ?????? ?????? ?????? ???????.
????? ?-50' ???? ????? ??? ????? ?????.
??? ????? ?-90' ??????? ???? ?????? ??????? ??? 10-30% ??????? ??????? ?? ???? ?????, ????? ???? ?? ??????? ?????? ????.??????
??? ????' ??? ???? ?????? ?? ????? ???? ???????.
???????? ???? ????? ???????, ?? ?? ?????? ?????? ?????? ???????.
????? ?-50' ???? ????? ??? ????? ?????.
??? ????? ?-90' ??????? ???? ?????? ??????? ??? 10-30% ??????? ??????? ?? ???? ?????, ????? ???? ?? ??????? ?????? ????.
79. Q: Which statement is incorrect regarding pregnancy in lupus SLE patients are less fertile ( low fertility rate)
SLE patients have higher frequency of premature labor.
3. SLE may flare during pregnancy and postpartum
4. Neonatal lupus occurs due to transplacental
transmission of maternal auto-abs
5. Most well controlled lupus patients can become pregnant and give birth to healthy children
?? ???????? ????? ?? ???? ???? ???? ????????
????? ???? ?????? ????? ????. ?? ???? ?????? ?????? ??????, ?? ??? ???? ??? ??? ????? ???????.?? ???????? ????? ?? ???? ???? ???? ????????
????? ???? ?????? ????? ????. ?? ???? ?????? ?????? ??????, ?? ??? ???? ??? ??? ????? ???????.
80. Pregnancy Outcomes in SLE Johns Hopkins Cohort Fertility rates: normal
2-2.4 pregnancies\patient
Preterm
< 37 weeks 40.5% < 36 weeks 32.1%
Pregnancy loss 10-30%
1st trimester 6.0%
2nd trimester 7.1% ?? ???? ????? ??????? ????? ?????.
?????? ??? ????? ?? ????? ?????? ????? ????? ??? ??? ???? ?????.?? ???? ????? ??????? ????? ?????.
?????? ??? ????? ?? ????? ?????? ????? ????? ??? ??? ???? ?????.
81. The Mother in SLE Risk factors for exacerbation:
- active disease 3-6 months before conception
- pre-existing renal disease
Conception during remission:
10-30% risk of flare.
Mild lupus rarely exacerbates in pregnancy
Severe exacerbations: in 20% of pregnancies
??????? ????? ?????? ??????? ???????? ???? ????. ?????? ?????? ???? ????? ???? ??? ???? ??????? ?? ?? ?? ???? ??????? ?????, ?? ????? ?????? ?? ??? ??? ?? ?? 10-30% ????? ???????? (??? ??? ???).
????????? ???? ??????? ?-20% ??????????.
????? ??????? ????? ???? ????? ????? ???? ??????.??????? ????? ?????? ??????? ???????? ???? ????. ?????? ?????? ???? ????? ???? ??? ???? ??????? ?? ?? ?? ???? ??????? ?????, ?? ????? ?????? ?? ??? ??? ?? ?? 10-30% ????? ???????? (??? ??? ???).
????????? ???? ??????? ?-20% ??????????.
????? ??????? ????? ???? ????? ????? ???? ??????.
82. Management of SLE flares in pregnancy Prednisone
IV Pulse methylprednisolone
NSAIDs ( during 1st trimester )
Plaquenil
Azathioprine
Cyclosporine
??????? ???? ??? ?????????, NSAIDs ???????? ?????, plaquinin (???? ???? ??? ?? ????? ?? ??? ??????? ?? ????? ???? ??????), ??????? (?? ????? ?? ?? ????), ?????' ?? ??? ?????.??????? ???? ??? ?????????, NSAIDs ???????? ?????, plaquinin (???? ???? ??? ?? ????? ?? ??? ??????? ?? ????? ???? ??????), ??????? (?? ????? ?? ?? ????), ?????' ?? ??? ?????.
83. Neonatal Lupus 1. Neonatal cutaneous lupus
2. Congenital heart block
Due to placental transmission of maternal IgG abs
Occurs in women with:
- anti Ro\SSA , anti La\SSB, anti U1 RNP
Prevalence of neonatal lupus in mothers
with the auto-abs: 2-5%
The mother may be :
asymptomatic, have: SLE, Sjogren syn, other rheumatic disease. Neonatal lupus
???? ???????? ?????? ?????. ???? ????? ???? ????? ???? ?? heart block. ?? ?? ???? ??? ???????, ???? ???? ????? ???? ?? ?? ?????? (???? ??? ????).
???????? ???????? anti Ro, anti La, anti RNP.
?????? neonatal lupus ??????? ?? ??????? ?????? 2-5%.
??????? ?????? ????? ?????? ????? ????? ??? ??? ????? ?? ???? ???????? ?? ??????? ???.
???? ????? ??????? ??? ???? ???????.Neonatal lupus
???? ???????? ?????? ?????. ???? ????? ???? ????? ???? ?? heart block. ?? ?? ???? ??? ???????, ???? ???? ????? ???? ?? ?? ?????? (???? ??? ????).
???????? ???????? anti Ro, anti La, anti RNP.
?????? neonatal lupus ??????? ?? ??????? ?????? 2-5%.
??????? ?????? ????? ?????? ????? ????? ??? ??? ????? ?? ???? ???????? ?? ??????? ???.
???? ????? ??????? ??? ???? ???????.
84. Neonatal cutaneous lupus Neonatal cutaneous lupus ???? ??? sub-acute cutaneous. ???? ?????? ?????? ??? ???? ?????????? ?????? ?????? ???.Neonatal cutaneous lupus ???? ??? sub-acute cutaneous. ???? ?????? ?????? ??? ???? ?????????? ?????? ?????? ???.
85. Congenital heart block (CHB) Prevalence: 1:20,000 births ( 0.005%)
anti Ro \ anti La + should have weekly echocardiographies at 18-25 weeks
complete block: in 90% of reported cases
60% require pacemakers, 30%-die
recurrence - 13% Congenital heart block ???? ????, ???? ????? ???? ????? ??????? ?"? US. ???? ??????? ???? ???? 13%, ???? ????? ???.Congenital heart block ???? ????, ???? ????? ???? ????? ??????? ?"? US. ???? ??????? ???? ???? 13%, ???? ????? ???.
86. Management of congenital heart block Prophylactic treatment of high risk mother -
not helpful.
Treatment of identified block: T. Dexamethasone 4mg\d
Rationale for treatment of identified block:
- reduce generalized inflammatory insult - lower titer of maternal auto-abs.
??? ??? ??? ????? ????????? ????? ????.
?? ?????? ??? ?????? dexamethazone ?? ???? ????, ????? ?????? ??? ??????? ??? ????? ????? ????????.
????? ??? ????? ???.??? ??? ??? ????? ????????? ????? ????.
?? ?????? ??? ?????? dexamethazone ?? ???? ????, ????? ?????? ??? ??????? ??? ????? ????? ????????.
????? ??? ????? ???.
88. Female, 19 years old single, Israeli born 1995:
Fever
Sore throat
Polyarthritis
Systolic murmur 2/6
Initial working diagnosis: Rheumatic Fever ????: ?????? ????? ???? 19 ??? ?? ???, ??? ????, ???????? ???????.
???? ??? ?? rheumatic fever ????? ????'.????: ?????? ????? ???? 19 ??? ?? ???, ??? ????, ???????? ???????.
???? ??? ?? rheumatic fever ????? ????'.
89. History and laboratory work-up Weight loss, fatigue
Hair loss for past months, photosensitive rash
Raynauds phenomenon
Lab:
ANA +, anti-DNA - 30%, low C3
CBC, chemistry, urine - normal
anti-cardiolipin IgG -positive
lupus anticoagulant- positive
Echocardiogram: mild mitral regurgitation ????? ??? ?? RF: ????? ?????, ???? ?????, ????? ???? ????? ??????? ???????, ????? ??????? ????, ?????? raynaud (???? ??? ?????? ??????).
???? ?? ???? ????? ?????? ??? ???????? ?? ??? ???.
????? ?????? ????? ??????? ANA ?????, ????-??"? ?????, ????? ???? (????? ????? consumption), ??? ????, ???? APLA, ???? ?"? ???????? ???.
?? ?? ??????????: ????????, ANA, anti-DNA, APLA.
??? ?? ??? ????, ?? ??? ?? ???? ???????.????? ??? ?? RF: ????? ?????, ???? ?????, ????? ???? ????? ??????? ???????, ????? ??????? ????, ?????? raynaud (???? ??? ?????? ??????).
???? ?? ???? ????? ?????? ??? ???????? ?? ??? ???.
????? ?????? ????? ??????? ANA ?????, ????-??"? ?????, ????? ???? (????? ????? consumption), ??? ????, ???? APLA, ???? ?"? ???????? ???.
?? ?? ??????????: ????????, ANA, anti-DNA, APLA.
??? ?? ??? ????, ?? ??? ?? ???? ???????.
90. Treatment and Course Plaquenil 200 mg x 2\d
Naxyn 500 mg X 2\d
nearly asymptomatic for 1 year ????? ?? plaquenil ?????-?????????? ????? ??????.????? ?? plaquenil ?????-?????????? ????? ??????.
91. 1996: Flare Polyarthritis
elevated anti-DNA ( 87%)
low complement
microscopic hematuria, RBC casts, proteinuria: 1.7 gr/24 hrs
preserved CCT
Kidney biopsy:
focal proliferative glomerulonephritis ( Class III) ???? ??? ????? ?? ???????: ????? ?????, ???????, ?????? ?? ??????? ??????, ????? ?????? ????.
???? ??? ???????, ????? FPGN ????? 3.
?? ????? ????? ?? ????? ??? ?? ????, ?? ?? ????? ?????? ?? ?? ????? ????? ???? ??? ?????.???? ??? ????? ?? ???????: ????? ?????, ???????, ?????? ?? ??????? ??????, ????? ?????? ????.
???? ??? ???????, ????? FPGN ????? 3.
?? ????? ????? ?? ????? ??? ?? ????, ?? ?? ????? ?????? ?? ?? ????? ????? ???? ??? ?????.
92. Treatment T. Prednisone 60 mg\d
IV Cyclophosphamide 500mg\m2
- once a month for 6 months
- once every 3 months
Continue: Plaquenil 200mg x 2\d ???? ???? ???????? ????????, ?????? ?-plaquenil (??????).???? ???? ???????? ????????, ?????? ?-plaquenil (??????).
93. Course Initial response:
resolution of arthritis and proteinuria
persistent hematuria
normalization of C3 C4, drop in anti-DNA (22%)
prednisone dose tapered to 12.5 mg\d ????? ????? ???? ??????.????? ????? ???? ??????.
94. 1997: Flare 1 week prior to 8th CTX pulse Polyarthritis
severe nephrotic syndrome:
proteinuria: 11gr\24hrs
albumin: 2.0 gr\dl
microscopic hematuria
drop in complement
rise in anti-DNA - 45% ??? ?????? ??? ??? ????????? ???????? ??????.
??????????? ?? 11 ??', ?????? ????, anti-DNA ????.
?? ?????? ??? ??? ????? ????????.??? ?????? ??? ??? ????????? ???????? ??????.
??????????? ?? 11 ??', ?????? ????, anti-DNA ????.
?? ?????? ??? ??? ????? ????????.
95. Histologic class transformation?
Repeat kidney biopsy- suggested but not done due to:
non- occluding Renal Vein Thrombosis
2 episodes of pleuritic chest pain- suspected Pulmonary embolism ????? ????? ??????? ????? ???? ?? ?? ???????? ???? ??? ????.
??? ????? ?? ????? ???? ???? ???? renal vein thrombosis. ??? ?????? ??? ???????? ???? ????? ?? ?-PE (?? ???? ????).????? ????? ??????? ????? ???? ?? ?? ???????? ???? ??? ????.
??? ????? ?? ????? ???? ???? ???? renal vein thrombosis. ??? ?????? ??? ???????? ???? ????? ?? ?-PE (?? ???? ????).
96. Treatment IV Heparin, followed by Warfarin ( INR-2.5)
IV pulse Methylprednisolone 1 gr\d for 3 days followed by Prednisone 60 mg\d
IV pulse Cyclophosphamide 800 mg\m2 once a month
???? ????? ?????? ????? ??? ?????? (?? ???? ????? ??????? ?? ????-??????????).
????? pulse ?? ?????????.
????? ????? ????????? ??? ????? ?????? ???? ????.???? ????? ?????? ????? ??? ?????? (?? ???? ????? ??????? ?? ????-??????????).
????? pulse ?? ?????????.
????? ????? ????????? ??? ????? ?????? ???? ????.
97. Course Gradual improvement in proteinuria - 2 gr\24 hrs
normalization of anti-DNA, increase in C3 C4
Avascular necrosis - both knees, both shoulders
after 3 months:
Cyclophosphamide switched to Azathioprine
Prednisone tapered to 15 mg\d
??? ???? ?-11 ??' ????? ?-2 ??'.
??? ????? ????? ????????? a-vascular necrosis ???? ??????? ???? ??????? ??????.
???? 3 ?????? ?????? ????? maintenance ???????? (?? ??? ????? ???? ???? ????????, ?? ??? ???? ????? ?????).??? ???? ?-11 ??' ????? ?-2 ??'.
??? ????? ????? ????????? a-vascular necrosis ???? ??????? ???? ??????? ??????.
???? 3 ?????? ?????? ????? maintenance ???????? (?? ??? ????? ???? ???? ????????, ?? ??? ???? ????? ?????).
98. 1998: Flare Pancytopenia
Nephrotic syndrome: - protein 5.5 gr\24hrs - albumin 1.2 gr\dl - anasarca
Treatment:
IV pulse methylprednisolone 1 gr/ 3 days
IV cyclophosphamide 1000 mg/m2
????? ??? ?? ???????????. ?? ?? ????????? ???? ?????? ?? ??????, ??? ?? ?????? ???? ?????? ?? ??????.
????? anasarca ?? ??????? 1.2, ??????????? ???.
??? ???? ????????? ???? ????? ?????? (?? ??? ?? cellcept, ??? ??????? ??).????? ??? ?? ???????????. ?? ?? ????????? ???? ?????? ?? ??????, ??? ?? ?????? ???? ?????? ?? ??????.
????? anasarca ?? ??????? 1.2, ??????????? ???.
??? ???? ????????? ???? ????? ?????? (?? ??? ?? cellcept, ??? ??????? ??).
99. Course Neutropenic fever - post cyclophosphamide
- resolved with antibiotics
No improvement in proteinuria or activity of disease.
Management?? ????? neutropenic fever ??????????, ??? anasarca. ???? ?"? ???????????.
??? ???????????? ?????, ??? ???????????? ???? ???? ????? ????????. ?????? ?? ????? renal shutdown.????? neutropenic fever ??????????, ??? anasarca. ???? ?"? ???????????.
??? ???????????? ?????, ??? ???????????? ???? ???? ????? ????????. ?????? ?? ????? renal shutdown.
100. Treatment Supportive: IV salt free albumin
high dose diuretics
ACE inhibitors
Cyclosporine - 5 mg\kg
Prednisone - 60 mg\d
???? ?? ????? ????: ???????? ????????.
???? ?? ???????????, ???? ??????.???? ?? ????? ????: ???????? ????????.
???? ?? ???????????, ???? ??????.
101. Course Gradual marked improvement:
resolution of pancytopenia
resolution of proteinuria, normalization of albumin
normalization of anti-DNA and complement
persistent microscopic hematuria ???????????? ?????, anti-DNA ??? ??????, ????? ?? ???????, ?? ???? ?? ????????? (???? ???? AVN ???).???????????? ?????, anti-DNA ??? ??????, ????? ?? ???????, ?? ???? ?? ????????? (???? ???? AVN ???).
102. Problems unable to reduce prednisone below- 12.5 mg\d
unable to reduce cyclosporine doses
Azathioprine added as steroid sparing and cyclosporine sparing
??? ???? ?????? ?? ?-gingiva, ?????????.??? ???? ?????? ?? ?-gingiva, ?????????.
103. Course Remission for 18 months
no proteinuria, normal anti DNA, C3, C4
Planned pregnancy
Treatment during pregnancy:
Plaquenil, Azathioprine, Prednisone 10mg\d
Low molecular weight Heparin
Delivered healthy baby at term
Mild flare 2 months postpartum: proteinuria < 1 gr\d
Controlled with prednisone
???? ?????? ?? ??"?, C3, C4 ??????, ????? ???.
???? ?? plaquenil ?? ???????, ???? ???????, ?? ???? ??? ?????? ???????.
???? ????? ???? ??????, ???? ?? ??????? ??? ??? ???? ????? (??????????? ?? ???? ?-1 ??').
???? ?? ?? ??? ???.???? ?????? ?? ??"?, C3, C4 ??????, ????? ???.
???? ?? plaquenil ?? ???????, ???? ???????, ?? ???? ??? ?????? ???????.
???? ????? ???? ??????, ???? ?? ??????? ??? ??? ???? ????? (??????????? ?? ???? ?-1 ??').
???? ?? ?? ??? ???.