Systemic lupus erythematosus

Август 3, 2022

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Systemic lupus erythematosus

Содержание

2. General characteristics Unknown etiology, multifactorial disease Involve joints, kidneys, mucous membranes, the central nervous system Variety
3. Epidemiology Prevalence: 50-100 /100.000 Incidence: 2-7 /100.000/year age at onset: 20-30 Female vs. male ratio: 9-10:1
4. Etiology Family history (1st degree relatives 1%) Genetic predisposition MHC genes: HLA DR2,DR3 DR4-DIL, DR5-APS non-MHC
5. Etiology Provoking factors Sunlight, UV light Infections Hormonal status:estrogen, prolactin Drugs Isoniacid Hidantoin Hydralazin Procainamid D
6. PATHOGENESIS Disturbed immune regulation: Pathologic antigen presentation Increased MHC expression Enhanced co-stimulation Cytokine imbalance (Th1/Th2) Decrease
7. Pathogenesis of SLE Provoking factors: Genetics predisposition (MHC and non-MHC genes Triggering factors (UV, drugs, infections)
9. Antigen targets for autoantibodies in SLE Nuclear antigens: ssDNA, dsDNA, histon, Sm, RNP Cytoplasmic antigens: SS-A,
10. General symptoms Weakness Fatigue Tiredness Fever Weight loss Hair loss Lymphadenopathy
11. CLASSIFICATION OF SKIN SYMPTOMS IN SLE (Sontheimer RD.Lupus 6:84-95, 1997) Lupus specific A. Acute cutan LE
12. Lupus specific skin symptoms Vespertilio=butterfly rash Acute cutan LE
13. Lupus specific skin symptoms DLE SCLE
14. Non-lupus specific skin symptoms vasculitis Raynaud phenomenon
15. Musculosceletal involvment of lupus Small joint symmetric non erosive polyarthritis Aseptic femur neck necrosis Osteoporosis Myositis
16. Polyserositis Pleuritis Pericarditis Peritonitis pleuritis pericarditis
17. Respiratory involvment Pleuritis Alveolitis obliterans Pulmonal fibrosis Pulmonal hypertension ARDS Pulmonal embolism
18. Cardiovascular involvments Pericarditis Myocarditis Cardiomyopathy Endocarditis non-infectious verrucosus endocarditis (Libman-Sacks endocarditis) subacute infectious endocarditis Valvulopathy Atherosclerosis
19. Pericarditis AMI Non-infectious endocarditis
20. Nomenclature of neuro-psychiatric symptoms of SLE (ACR ad hoc Committee, Arthritis Rheum. 42:599-608, 1999.) CNS Aseptic
21. Histopathologic classification of lupus nephritis (ISN/RPS) Weening JJ et al. J Am Soc Nephrol 15: 241-50,
22. Mesangial LN Diffuse LN
23. Other manifestations Haematology Leukopenia, lymphopenia AIHA/ Thrombocytopenia/Evans sy. Pancytopenia TTP, CAPS Lymphadenopathy/Splenomegaly Othe Vasculitis Pancreatitis, lupus
24. Laboratory tests and findings in SLE General inflammatory findings: ESR , normal CRP Haematology: pancytopenia, Kidney
25. Radiology and other examinations in SLE Chest X ray, CT (HRCT), breath test, scan Abdominal ultrasonograph
26. Classification criteria for the diagnosis of lupus according to the American College of Rheumatology (ACR) 1.
27. Differential diagnosis of SLE 1. Other polysystemic autoimmune disorders polyarthritis myositis, muscle weakness Raynaud’s sy. Sjögren’s
28. Monitoring of activity in SLE disease activity index: DAI Convulsion 8 Psychosis 8 Organic brain syndrome
29. Subgroups in SLE Subacute cutan lupus erythematosus Neonatal lupus erythematosus Drug-induced lupus SLE in elderly SLE
30. SUBGROUPS IN SLE 1. SUBACUTE CUTAN LUPUS (SCLE) Clinical characteristics: annular/psoriasiform skin eruptions photosensitivity (60-70%) less
31. SLE SUBGROUPS 2. NEONATAL LUPUS (NLE) Frequency: rare Cause: maternal autoantibodies passing through the placenta Clinical
32. SUBGROUPS IN SLE 3. SLE IN ELDERLY Onset: over the age of 60 Frequency: around 10%
33. SLE SUBGOUPS 4. DRUG-INDUCED LUPUS (DIL) Clinical characteristics: more frequent in elderly reversible milder kidney and
34. Negative prognostic factors in SLE Sex:male Age under 20 or above 50 Diffuse proliferative lupus nephritis
35. Causes of death In the early phase of the disease process Kidney failer Neurology involvement SLE
36. Therapy of lupus - General procedures Avoidance of UV lights Sunscreens Termination of the use of
37. Therapy of SLE Antimalarial drugs: hydroxichlorouin, chloroquin (Delagil) In the cases of arthralgia, arthritis, skin symptoms,
38. Therapy of SLE Steroids: methylpednisolon (Solu-Medrol, Medrol, Methypred) In acute flares and relapses in neonatal lupus:
39. Immunosupressives Methotrexat (Trexan) 7.5-20 mg/week, treatment of polyarthritis, vasculitis CAVE: bonemarrow and liver toxicity Azathiorpin (Imuran)
40. Immunmodulation Cyclosporin A (Sandimmun Neoral) In the cases of haematology involvement, membranous lupus nephritis dosis: 3
41. Potential targets in the therapy of SLE
43. Скачать презентацию

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General characteristics
Unknown etiology, multifactorial disease
Involve joints, kidneys, mucous membranes, the central

nervous system
Variety of antibodies
Symptoms vary greatly from person to person
Lupus tends to be chronic
Alternation between remission and relapse

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Epidemiology
Prevalence: 50-100 /100.000
Incidence: 2-7 /100.000/year
age at onset: 20-30
Female vs. male ratio:

9-10:1

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Etiology
Family history (1st degree relatives 1%)
Genetic predisposition
MHC genes: HLA DR2,DR3

DR4-DIL, DR5-APS
non-MHC genes: complement component, complement receptor, Fc receptors, CRP, cytokines, apoptotic genes (e.g., FAS)

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Etiology
Provoking factors
Sunlight, UV light
Infections
Hormonal status:estrogen, prolactin
Drugs
Isoniacid
Hidantoin
Hydralazin
Procainamid
D penicillinamin
Penicillins
Sulphonamids
TNF alpha blockers

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PATHOGENESIS
Disturbed immune regulation:
Pathologic antigen presentation
Increased MHC expression
Enhanced co-stimulation
Cytokine imbalance (Th1/Th2)
Decrease

of regulatory T cells
Distrubed apoptosis

Polyclonal B cell activation
Pathologic autoantibody production
Impaired clearance of immune complexes
Accumulation of IC
Complement activation

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Pathogenesis of SLE
Provoking factors: Genetics predisposition (MHC and non-MHC genes
Triggering

factors (UV, drugs, infections)
Hormonal status

Immune disregulation

Defect of clearance

Decreased Regulatory T cells activity

DNA,
Apoptotic cells

APCs

T cells
increased CD4+
actitivity

Autoreactive
B cells

Increased help:
citokines,
co-stimulation

Production
of Auto-AB

Increased IC
C’ activation
Organ damages

ADCC

aPL

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Antigen targets for autoantibodies in SLE
Nuclear antigens: ssDNA, dsDNA, histon, Sm,

RNP
Cytoplasmic antigens: SS-A, SS-B, ribosoma p protein, ANCA
Cells surface antigens: on endothel cells, erythrocytes, neutrophils, lymphocytes, platlets
Other antigens, plasma factors: Beta-2 glycoprotein I, phospholipids, immune globulins

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General symptoms
Weakness
Fatigue
Tiredness
Fever
Weight loss
Hair loss
Lymphadenopathy

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CLASSIFICATION OF SKIN SYMPTOMS IN SLE (Sontheimer RD.Lupus 6:84-95, 1997)
Lupus specific
A.

Acute cutan LE /ACLE/
Butterfly rush
Generalised ACLE
photosensitivity.
B. Subacute cutan LE /SCLE/
Annular
Psoriasiform
C. Chronic cutan LE /CCLE/
Classical discoid lesions
Hypertrophic DLE
Lupus panniculitis
Mucosal ulceration
Others (L.tumidus, Lichenoid)

non-specific for Lupus
A. Cutan vascular symptoms
Vasculitis
Vasculopathy
Raynaud’s syndrome
Livedo reticularis
B. Non-scarring diffuse alopecia
C. Urticaria
D. Erythema exsudativum multiforme

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Lupus specific skin symptoms
Vespertilio=butterfly rash
Acute cutan LE

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Lupus specific skin symptoms
DLE
SCLE

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Non-lupus specific skin symptoms
vasculitis
Raynaud phenomenon

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Musculosceletal involvment of lupus
Small joint symmetric non erosive polyarthritis
Aseptic femur neck

necrosis
Osteoporosis
Myositis

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Polyserositis
Pleuritis
Pericarditis
Peritonitis
pleuritis
pericarditis

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Respiratory involvment
Pleuritis
Alveolitis obliterans
Pulmonal fibrosis
Pulmonal hypertension
ARDS
Pulmonal embolism

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Cardiovascular involvments
Pericarditis
Myocarditis
Cardiomyopathy
Endocarditis
non-infectious verrucosus endocarditis
(Libman-Sacks endocarditis)
subacute infectious endocarditis
Valvulopathy
Atherosclerosis of coronary

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Pericarditis
AMI
Non-infectious endocarditis

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Nomenclature of neuro-psychiatric symptoms of SLE (ACR ad hoc Committee, Arthritis

Rheum. 42:599-608, 1999.)

CNS
Aseptic meningitis
Cerebrovascular lesion
Demyelinating syndrome
Headache (migraine)
Chorea
Myelopathy
Convulsion
Psychosis
Acute confusing state
Cognitive dysfunction

PNS
Acute Guillain-Barré sy.
Disturbance in autonomic nervous system
Mononeuritis simplex/multiplex
Myasthenia gravis like
Cranial nerve lesion
Polyneuropathy

Brain infarct

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Histopathologic classification of lupus nephritis (ISN/RPS) Weening JJ et al. J

Am Soc Nephrol 15: 241-50, 2004

Class I. Minimal mesangial nephritis
Class II. Mesangial proliferative nephritis
Class III. Focalis lupus nephritis (<50% of glomeruli are involved)
A. Active lesions: focal proliferative GN
A/C. Active and chronic lesions: focal proliferativ and sclerosing GN
C. Chronic inactive lesions with glomerular scarring: focal sclerosing GN.
Class IV. Diffuse lupus nephritis (>50% of glomeruli are involved)
diffuse segmental (IV-s) type, when only a part of the involved glomeruli are affected
diffuse global GN (IV-G), when the entire glomeruli are affected
IV-S (A), IV-G (A),
IV-S (A/C), IV-G (C),
IV-S (C),
Class V. Membranous lupus nephritis
May associate with findings characterised in class III/IV.
Class VI. Sclerosing glomerulonephritis
>90% of glomeruli are sclerotic

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Mesangial LN
Diffuse LN

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Other manifestations
Haematology
Leukopenia, lymphopenia
AIHA/ Thrombocytopenia/Evans sy.
Pancytopenia
TTP, CAPS
Lymphadenopathy/Splenomegaly
Othe
Vasculitis
Pancreatitis, lupus hepatitis
Pepeticus ulcus/GI-bleeding
Mesenterial thrombosis/vasculitis
A./v. central

retinae thrombosis
Opticus neuritis
Chorioretinitis
Sicca sy.

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Laboratory tests and findings in SLE
General inflammatory findings: ESR , normal

CRP
Haematology: pancytopenia,
Kidney tests: sodium, potassium, carbamide, creatinine
enzymes: CK, AST/GOT, ALT/GPT, LDH (haemolysis, myositis, hepatitis)
Haemostasis: Lupus anticoagulant
Immunserology: IgG, C3, C4, CH50, ANA, aDNA, nukleosoma, histon, anti-Sm, anti-cardiolipin, anti-beta2-glikoprotein I.
Urine (protein!) and urine sediment (WBC, RBC, count)
24 hours urine collection: detection of protein

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Radiology and other examinations in SLE
Chest X ray, CT (HRCT), breath

test, scan
Abdominal ultrasonograph
ECG, echocardiography
Neurology examination: EEG, ENG, EMG, CT, MRI, test of cerebrospinal fluid
Biopsies: skin (vagy lupus band teszt)
kidney
muscles
n. suralis

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Classification criteria for the diagnosis of lupus according to

the American College of Rheumatology (ACR)
1. Butterfly rush
2. Discoid lupus
3. Photosensitivity
4. Oral ulceration
5. Polyarthritis
6. Nephritis
a. proteinuria over 0.5g/day
b. cellular casts
7. Pleuritis/pericarditis
8. Neuropsychiatric symptoms
a. convulsions
b. psychosis
4 or more symptoms are required for the diagnosis

9. Haematological alterations
a. haemolytic anaemia
b. leucopenia (4.0 G/l)
c. lymphopenia (1.5G/l)
d. thrombocytopenia (100G/l)
10. Immunologic alterations
a. anti-dsDNA
b. anti-Sm
c. anti-CL and/or LA
11. ANA

M Hochberg, 1997

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Differential diagnosis of SLE
1. Other polysystemic autoimmune disorders
polyarthritis
myositis, muscle weakness
Raynaud’s

sy.
Sjögren’s sy.
2. Haematologic malignancies
spleen and liver enlargement
lymphadenopathy
weight loss, fever
anaemia, thrombocytopenia
3. Infections
Fever, ESR and CRP↑
Subacute inf. endocarditis, valvulopathy
Rheumatic fever
Tuberculosis, relapsing serositis
Septicaemia, hepato-splenomegaly
Other infections, lymphadenomegaly, rushes

4. Malignant disorders
weight loss, subfebrility,
fatigue,
anemia,
ESR ↑,
recurrent thrombosis
5. Other diseases
TTP AIHA ITP AIDS

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Monitoring of activity in SLE disease activity index: DAI
Convulsion 8
Psychosis 8
Organic brain
syndrome 8
Visual field

defects (retinopathy) 8
Cranial nerve lesion 8
Lupus headache 8
Stroke 8
Arthritis 4
Myositis 4

Casts in urine 4
Haematuria 4
Proteinuria 4
Pyuria 4
New rushes 2
Alopecia 2
Oral ulcer 2
Pleuritis 2
Pericarditis 2
Low complement 2
Elevated aDNA 2
Fever 1
Thrombopenia 1
Leucopenia 1

Слайд 29

Subgroups in SLE
Subacute cutan lupus erythematosus
Neonatal lupus erythematosus
Drug-induced lupus
SLE in elderly
SLE

with APS

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SUBGROUPS IN SLE
1. SUBACUTE CUTAN LUPUS (SCLE)
Clinical characteristics:
annular/psoriasiform skin eruptions
photosensitivity (60-70%)
less

frequent kidney involvement (10%)
less common CNS symptoms (20%)
Laboratory signs: aSSA/aSSB antibodies (60-70%)
Therapeutical considerations:
sun screens
topical steroids
systemic low dose steroid
antimalarial drugs

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SLE SUBGROUPS
2. NEONATAL LUPUS (NLE)
Frequency: rare
Cause: maternal autoantibodies
passing through the placenta
Clinical

characteristics: generalised skin eruptions
hepato-splenomegaly
transient thrombocytopenia
autoimmun haemolytic anaemia
congenital heart block
Laboratory signs: aSSA/aSSB antibodies
ANA positivity
high a-dsDNA concentration
LE cell phenomenon
Special aspects of therapy: Corticosteroids
HIVIG
pace maker

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SUBGROUPS IN SLE
3. SLE IN ELDERLY
Onset: over the age of 60
Frequency: around 10%
Clinical

characteristics: musculo-skeletal symptoms
serositis
pulmonal involvement: pulm. fibrosis
skin rushes
decreased female:male ratio
sicca sy.
milder
Diff. dg.: exclusion of cancer is required!
Therapeutic considerations: low dose corticosteroids
NSAID

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SLE SUBGOUPS 4. DRUG-INDUCED LUPUS (DIL)
Clinical characteristics: more frequent in elderly
reversible
milder
kidney and CNS

involvement are rare
DLE is rare
more frequent pulmonal symptoms
Laboratory signs: slow acetylators
associated with HLA DR4
H2A, H2B histone antigens
are the major epitops
Therapy: cessation of provoking drug
corticosteroids

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Negative prognostic factors in SLE
Sex:male
Age under 20 or above 50
Diffuse proliferative

lupus nephritis
CNS manifestations
Anti-phospholipid antibodies
Endocarditis

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Causes of death
In the early phase of the disease process
Kidney failer
Neurology

involvement
SLE Activity
In the later phase of the disease process
Cardiovascular event
Thromboembolism
Malignant disorders
In both:
infections

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Therapy of lupus
-
General procedures
Avoidance of UV lights
Sunscreens
Termination of the use of

provoking drugs
Avoidance of contraceptive pills
Adequate antibiotics therapy

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Therapy of SLE
Antimalarial drugs: hydroxichlorouin, chloroquin (Delagil)
In the cases of arthralgia,

arthritis, skin symptoms, serositis
Dosis: 200-400 mg/die
Side effect: ocular complications

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Therapy of SLE
Steroids: methylpednisolon (Solu-Medrol, Medrol, Methypred)
In acute flares and relapses
in neonatal

lupus: dexamethason 4 mg/die
Dosis: start with 0.5-1 mg/bwkg, then slowly decreased dosis
Pulse steroid: 1 g/3 days
Side effects!

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Immunosupressives
Methotrexat (Trexan)
7.5-20 mg/week, treatment of polyarthritis, vasculitis
CAVE: bonemarrow and liver

toxicity
Azathiorpin (Imuran)
1-2 mg/bwkg/day, multiorgan involvement
CAVE: bonemarrow and liver toxicity
Cyclophosphamid (Cytoxan)
500-1000 mg/m2/month for 6 months, then same amount/3 months for 1.5 years (NIH protocol)
In the cases of lupus nephritis, alveolitis, vasculitis, CNS involvement
CAVE:bonemarrow and liver toxicity

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Immunmodulation
Cyclosporin A (Sandimmun Neoral)
In the cases of haematology involvement, membranous

lupus nephritis
dosis: 3 mg/bwkg/day
Mycophanolat mophetil/Mycofenol acid (Cellcept/Myfortic)
In the case of lupus nephritis max. 3 gr/day
Diamino diphenylsulphon (Dapson)

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Systemic lupus erythematosus

Содержание

General characteristicsUnknown etiology, multifactorial diseaseInvolve joints, kidneys, mucous membranes, the central

EpidemiologyPrevalence: 50-100 /100.000Incidence: 2-7 /100.000/yearage at onset: 20-30Female vs. male ratio:

EtiologyFamily history (1st degree relatives 1%)Genetic predisposition MHC genes: HLA DR2,DR3

EtiologyProvoking factorsSunlight, UV lightInfectionsHormonal status:estrogen, prolactinDrugsIsoniacidHidantoinHydralazinProcainamidD penicillinaminPenicillinsSulphonamidsTNF alpha blockers

PATHOGENESISDisturbed immune regulation:Pathologic antigen presentation Increased MHC expressionEnhanced co-stimulationCytokine imbalance (Th1/Th2)Decrease

Pathogenesis of SLEProvoking factors: Genetics predisposition (MHC and non-MHC genes Triggering

Antigen targets for autoantibodies in SLENuclear antigens: ssDNA, dsDNA, histon, Sm,

General symptomsWeaknessFatigueTirednessFeverWeight lossHair lossLymphadenopathy

CLASSIFICATION OF SKIN SYMPTOMS IN SLE (Sontheimer RD.Lupus 6:84-95, 1997)Lupus specificA.

Lupus specific skin symptomsVespertilio=butterfly rashAcute cutan LE

Lupus specific skin symptomsDLESCLE

Non-lupus specific skin symptomsvasculitisRaynaud phenomenon

Musculosceletal involvment of lupusSmall joint symmetric non erosive polyarthritisAseptic femur neck

PolyserositisPleuritisPericarditisPeritonitispleuritispericarditis

Respiratory involvmentPleuritisAlveolitis obliteransPulmonal fibrosisPulmonal hypertensionARDSPulmonal embolism

Cardiovascular involvmentsPericarditisMyocarditisCardiomyopathyEndocarditis non-infectious verrucosus endocarditis (Libman-Sacks endocarditis) subacute infectious endocarditisValvulopathyAtherosclerosis of coronary

PericarditisAMINon-infectious endocarditis

Nomenclature of neuro-psychiatric symptoms of SLE (ACR ad hoc Committee, Arthritis

Histopathologic classification of lupus nephritis (ISN/RPS) Weening JJ et al. J

Mesangial LNDiffuse LN

Other manifestations HaematologyLeukopenia, lymphopeniaAIHA/ Thrombocytopenia/Evans sy.PancytopeniaTTP, CAPSLymphadenopathy/SplenomegalyOtheVasculitisPancreatitis, lupus hepatitisPepeticus ulcus/GI-bleedingMesenterial thrombosis/vasculitisA./v. central

Laboratory tests and findings in SLEGeneral inflammatory findings: ESR , normal

Radiology and other examinations in SLEChest X ray, CT (HRCT), breath

Classification criteria for the diagnosis of lupus according to

Differential diagnosis of SLE1. Other polysystemic autoimmune disorders polyarthritis myositis, muscle weakness Raynaud’s

Monitoring of activity in SLE disease activity index: DAIConvulsion 8Psychosis 8Organic brain syndrome 8Visual field

Subgroups in SLESubacute cutan lupus erythematosusNeonatal lupus erythematosusDrug-induced lupusSLE in elderlySLE

SUBGROUPS IN SLE1. SUBACUTE CUTAN LUPUS (SCLE)Clinical characteristics: annular/psoriasiform skin eruptions photosensitivity (60-70%) less

SLE SUBGROUPS2. NEONATAL LUPUS (NLE)Frequency: rareCause: maternal autoantibodies passing through the placenta Clinical

SUBGROUPS IN SLE3. SLE IN ELDERLYOnset: over the age of 60Frequency: around 10%Clinical

SLE SUBGOUPS 4. DRUG-INDUCED LUPUS (DIL)Clinical characteristics: more frequent in elderly reversible milder kidney and CNS

Negative prognostic factors in SLESex:maleAge under 20 or above 50Diffuse proliferative

Causes of deathIn the early phase of the disease processKidney failerNeurology

Therapy of lupus-General proceduresAvoidance of UV lightsSunscreensTermination of the use of

Therapy of SLEAntimalarial drugs: hydroxichlorouin, chloroquin (Delagil)In the cases of arthralgia,

Therapy of SLESteroids: methylpednisolon (Solu-Medrol, Medrol, Methypred)In acute flares and relapsesin neonatal

Immunosupressives Methotrexat (Trexan)7.5-20 mg/week, treatment of polyarthritis, vasculitis CAVE: bonemarrow and liver

ImmunmodulationCyclosporin A (Sandimmun Neoral) In the cases of haematology involvement, membranous

Potential targets in the therapy of SLE

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