Download A beginners guide to SLE

A beginners guide to SLE
Dr Mike Martin
St James’s Univ. Hosp.
Systemic Lupus Erythematosus
1. Autoimmune, inflammatory, multisystem disease
2. Associated with pathogenic autoantibodies
resulting in immune complex formation and
complement mediated tissue damage
3. Characterised by remissions & relapses
4. Variable course and prognosis
Auto-immune disease
• Antibody producing cells (lymphocytes and
•
•
•
plasma cells) are presented with antigen.
The antigen-antibody complex will be coated in
compliment (C3 + C4) – opsonisation.
These circulating complexes are normally
removed by the reticulo-endothelial system.
In auto-immune disease these complexes locate
to certain tissues and cause damage and
disease.
Factors contributing to
autoimmune disease eg SLE
• Genetic
• Hormonal
• Environmental
• Stress
•
SLE is more common in
•
Irrespective of
• women
• Afro-Caribbean and Asians
• country of birth
• social class
• place of residence
Johnson et al. Arthritis Rheum. 1995. 38: 551-558
Epidemiology
•
Prevalence
– total: 28/100,000
• female 50/100,000 = 1/2000
– In women: Afro-Carib1/500; Asian 1/1,000;
Caucasian 1/2,500
• Incidence: total 4/100,000
– female 7/100,000
Immunology
• The ready detection of numerous
antibodies to cellular components of the
nucleus, cytoplasm and cell membrane
has led to the concept that lupus is an
auto-immune disease. The major immune
response appears to be directed against
nuclear antigens. These anti-nuclear
antibodies are responsible for the LE cells
and immuno-fluorescence on tissue
sections.
• Lupus band test
High probability of SLE
• photosensitivity
• arthralgia and rash
• Raynaud’ or mouth ulcers
• pleurisy
• proteinuria
• haematologicl abnormalities
• abortion
• any neurological disorder
• fatigue / depression
Triggers for SLE
• Oestrogens
• Sunlight
• Infection
• Pregnancy
• Surgery
SLE: presenting clinical
features.
Arthritis or arthralgia
Skin involvement
Nephritis
Fever
Other
55%
20%
5%
5%
15%
SLE - Non-specific features
• Fatigue
• Muscle pains
•
•
•
•
Lymphadenoapthy
Fever
Loss of appetite
Weight loss
Organ involvement in SLE
• Joints
• Skin
90%
70%
• discoid lesions
30%
• alopecia
40%
• pleuro-pericardium
60%
• kidney
50%
• Raynaud’s
20%
• mucous membranes
15%
• CNS (psychosis/convulsions) 15%
• rashes
Classification criteria for
diagnosis of SLE (>4 of 11)
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•
•
•
•
•
•
Malar rash
Discoid rash
Photosensitivity
Oral ulcers
Arthritis
Serositis
Renal disorder
• Neurological disorder
– seizure or psychosis
• Haematologic disorder
– haemolytic anaemia
– leukopenia, lymphopenia
– thrombocytopenia
• Immunological disorder
– anti-DNA, anti-Sm
– anti-cardiolipin
– proteinuria > 0.5g
– cells &/or casts
• ANA positivity
• 4. Oral ulcers
• 5. Serositis
6. Arthritis
-arthralgia
-symmetrical, non-erosive
synovitis
-Jacoub’s arthropathy
(reducible deformities)
-Nodules possible
Raynaud’s
phenomenon
Livedo reticularis
Alopecia
diffuse or patchy
7.Renal disease
- consider biopsy if:
Proteinuria > 0.5 g/24 hours
red or white cells in urine
casts
creatinine clearance reduced (<80ml/min)
Proliferative glomerulonephritis
Membranous glomerulonephritis
7. Renal disease
• Always check urine for protein and blood
• Exclude infection/menstruation/ kidney
stones
•
• Check serum creatinine/creatinine clearance
• Exclude drugs (NSAIDS)
•
• Monitor blood pressure
8. Neurological disease
•
•
•
•
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Peripheral and/or central nervous system
SLE is great mimic
Hemiplegic migraine
Young stroke
Epilepsy
Aseptic meningitis
Cerebral Lupus
• Cerebral LE is a serious condition occuring
in up to 1 in 6 of SLE patients and can
cause prolonged headaches, seizures,
strokes, acute psychotic episodes and
severe depression. Anyone with cognitive
functional defects should be referred for
specialist advice.
9. Haematological clues
•
•
•
•
Leucopenia (lymphopenia > neutropenia)
Thrombocytopenia
Anaemia- not iron deficient
Tests for haemolysisCoomb’s test
haptoglobins
reticulocytes
10. Immunological screening tests
• CRP versus ESR/viscosity
• ANA
• RF
• IgG, IgA, IgM
11.
ANA - Indirect immunofluorescence
11
1
homogenous
• Bottom left: speckled
• Top left:
Top right:
Bottom right:
peripheral
nucleolar
Differential diagnosis of SLE
•
•
•
•
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RA
Other autoimmune/connective tissue disease
Infection
Drug-induced condition
Malignancy
• Post-viral fatigue syndrome
• Fibromyalgia
Further immunological tests
• For SLE: anti-dsDNA Abs
•
anti-ENA Abs (Ro, La, RNP, Sm)
C3, C4, C3d
For anti-phospholipid syndrome:
anti-cardiolipin Abs
APTT/Lupus anticoagulant test
• (detects prolongation of phospholipid dependent coagulation
tests due to antibodies acting as inhibitors of clotting test,
despite causing thrombosis in vivo- not reversed by addition
of normal serum)
Auto antibodies in SLE to:
• dsDNA
– 60% patients
– increased risk
kidney disease
– levels fluctuate
– RIA, ELISA,
Crithidia
Auto antibodies in SLE to:
• Cardiolipin
– 10–30%
– Thrombosis
– Foetal loss
• Histone
– Drug induced lupus
• Sm
– 10-30%
– ?kidney and CNS
disease
• RNP
– 10-30%
– “Mixed connective
tissue disease” (lupus,
systemic sclerosis and
myositis)
Ouchterlony – Passive immunodiffusion
• Ro and La
– 20-60% and
15-40%
– rashes &
neonatal lupus
and congenital
heart block
Antiphospholipid antibody syndrome
Recurrent venous or arterial thrombosis
Recurrent miscarriages
Thrombocytopenia
Anti-cardiolipin antibodies
Circulating lupus anticoagulant
(APTT, KCT, Russel Viper Venom test)
Treatment
• Sun-block lotions/creams
• Artificial tears and saliva
• NSAID’s
• Corticosteroids
• Hydroxychloroquine
• Immunosuppressants
• Warfarin
• Rituximab
Survival rates in SLE
5 years 93%
10 years 85%
15 years 79%
20 years 68%
20.4
% Survival of SLE
patients
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
(Abu-Shakra J Rheum 1995)
Primary causes of death
in early and late SLE
Active SLE
Infections
Other morbidity
Unrelated
Unknown
Early
26%
37%
19%
7%
11%
(Abu-Shakra J Rheum 1995)
Late
10%
30%
37%
13%
10%
Other points of interest in SLE
• Raynaud’s disease
• Septic arthritis
• Cardiovascular risk
• Osteoporosis
• Thrombosis
• Malignancy
The End