Systemic lupus erythematosus Flashcards
What is SLE
Systemic autoimmune disease
Chronic relapsing and remitting
What is the genetic association
Unknown aetiology –multi-factorial genetic
(HLA-DR3)
What systems are are invoved in the pathology
Mutli-system: CNS Heart Kidney Blood Heart Skin and Joints Foetus Lungs
Who are most likely to get lupus
Most likely Female (10:1 ratio)
Probably young when started (age of onset15-47)
Increased risk in Afro-Caribbean/Asian
Outline the pathogenesis
Innate susceptibility (HLA type/immunoregulatory genes/ complement/hormones)
+
Environmental stimuli
Leads to
Autoimmune proliferation and
autoantibody production
T/F- anti-nuclear antibodies is diagnostic of lupus
F….. up to 5% of population have this
Outline the stages leading to SLE
A. Loss of self-tolerance
B. Production of auto-antibody
C. Desposition of immune complexes
D. Immune complex inflammation
E. Tissue fibrosis and damage
What happens in loss of self tolerance
Failure to clear apoptotic cells, exposing nuclear antigens to immune system
APCs such as DCs take up nuclear antigens, they are recognised internally by TLRs
APC may present the self-antigen to autoreactive cell
What happens in production of autoantibody
Pathomnemonic
Autoreactive T cells provide help to B cells, producing large quantities of autoantibody
The antibodies form immune complexes
What happens with deposition of immune complexes
Circulating ICs not cleared and become deposited in tissues like kidney or skin
What happens in immune complex associated inflammation
IC deposited in tissues not cleared, and elicit inflammation with complement activation (classical pathway) and activation of macrophaes and neutrophils via surface Fc receptors which bind IgG
What happens in fibrosis and damage
Production of pro-inflammatory and pro-fibrotic cytokines. Leads to irreversible tissue damage
Clinical features of SLE:
Presentation
Malaise, fatigue, fever, wt loss
Lymphadenopathy
Clinical features of SLE:
Specific features of SLE
- Butterfly rash (=malar rash), alopecia
- Arthralgia
- Raynaud’s phenomenon
Clinical features of SLE:
- Inflammation kidney, CNS, heart, lung
- Accelerated atherosclerosis
- Vasculitis
SLE criteria
Use the ACR criteria
S-Serositis
O-oral ulcers
A-arthritis
P-Photosensitivity
B-Blood (all low)
Renal-proteinuria
Immunological- ANA, anti-dsDNA
N-neurological-seizures/psychosis
M-Malar rash
D- discoid rash
Differential diagnosis with SLE
ANA positive due to infection/malignancy
Other autoimmune CTD
Cutaneous SLE- without systemic involvement
Drug induced Lupus-
Drugs inducing lupus
procanamide, hydrazine, quinidine, isonizaide
How is SLE diagnosed
ANA antibodies
Other
Haem
Renal
What diseases associated with thedollowing antinuclear body patterns
Homogenous
Speckled
Nucleolar
Fine speckled
Homogenous: Abs to DNA …. SLE
Speckled- Abs to Ro, La, Sm, RNP… SLE/overlap
Nucleolar- Abs to topoisomerase….. scleroderma
Fine speckled- Abs to Centromere… CREST (limited custanous scleroderma
Other than ANAs what other antibodies might you check
Anti-dsDNA and Sm more specific for SLE but less sensitive
Anti-Ro and/or Lo- common in subacute cutaneous LE. Neonatal lupus syndrome and Sjorens
Outline ‘other tests’ for SLE
- Increased complement consumption
- Anti-cardiolipin antibodies
- Lupus anticoagulant
- ß1 glycoprotein
Haematology lab tests in SLE
- Lymphopaenia, normochromic anaemia
* Leukopaenia, AIHA, thrombocytopaenia
Renal lab tests in SLE
Proteinuria, haematuria
Active urinary sediment
How is severeity of SLE assessed
- Identify pattern of organ involvement
- Monitor function of affected organs
- Renal
- Lungs/CVS -
- Skin, haematology, eyes
- Identify pattern of autoantibodies expressed
- Anti-dsDNA, anti-Sm - renal disease
- Anti-cardiolipin antibodies
What are the signs of disease activity in SLE
- Wt loss, fatigue, malaise, hair loss
- Alopecia
- Rash
What are the lab diagnoses of disease activity in SLE
- ESR
- Increased complement consumption
- Increased anti-dsDNA
- Other Abs e.g ANA and CRP poor indicators
What is mild, moderate and severe SLE
MILD:
-joint +/- skin involvement
MODERATE:
- inflammation of other organs
- pleuritis, pericarditis, mild nephritis
SEVERE:
-sever inflammation in vital organs: sever nephritis, CNS disease, pulmonary disease, cardiac involvemnet, thombcytopenia
Treatment of mild SLE
Paracetemol +/- NSAID (monitor renla function)
Hydroxychloroquine (in arthropathy, cutaneous manifestations and mild diseases activity)
Topical corticosteroids
Treatment of severe SLE
Oral steroids or IV methylprednisolone
+ Immunosupressants- severe organ disease
- Cyclophosphamide
- Mycofenalate Mofitil (MMF)
- Rituximab (anti-CD20 monoclonal anti-body) for Lupus Nephritis
Maintenance treatment with low dose oral steroids (<5mg/day) and immunosuppressants (methotrexate, azathioprine or MMF)
Why do lupus patients need sun bock
lupus is very photosensitive
What if lupus patuets get pregnant
Anti-RO antibodies in pregnancy- need to be monitored due to risk of congenital HB
When is hydroxychloroquine used?
Hydroxychloroquine commonly used for skin and joint disease
Prognosis and survival of lupus
15 year survival : no nephritis 85%
nephritis 60%
When is prognosis worse in lupus
Prognosis also worse if black, male,
low socio-economic status
What is going to be causig mortality in SLE
Early mortality:
Active lupus
- Renal failure
- CNS disease
- Infection
Late mortality: Myocardial infarction (due to accelerated atherosclerosis)
Overal treatment strategies for SLE
Symptomatic
Immune-modulating
Immunosuppressive
What do the clinical features of SLE depends on
Organ affected
