SLE College Lecture Flashcards
What is the female to male ratio of prevalence?
9:1
Which ethnicity is SLE more common in?
Afro-Caribbeans > Asians > Aborigines > Caucasians
What is the 10 year survival rate
80-90%
What is the standardized mortality ratio?
3
What is the pathogenesis of SLE?
Genetic predisposition > known/unknown trigger > activation of immune cascade > deposition of immune complexes
What is the genetic pattern of factors
Likely combination of common variations in multiple genes. Monogenetic defects are rare
What are some single gene defects?
Deficiencies of complement components - eg C1q deficiency
TREX1 gene mutations
What epigenetic mechanism is the cause of drug-induced lupus
DNA hypomethylations eg procainamide and hydralazine
What % of first degree relatives have SLE?
4.5% (Priori 2013)
What is the immunopathogenesis of SLE?
Decreased phagocytosis and increased cellular apoptosis leads to increase apoptotic materal serving as potential autoantigens > trigger inflammatory cascade
Which receptor is activated by self nucleic acids in immune complexes?
Toll-like receptors
What is abnormal about B cells in lupus?
Elevated levels of B cell survival factors BAFF/BLyS and APRIL
What are some triggers of SLE/flares
UV light Infection Smoking Environmental pollutant (silica) Pets
Which medications more commonly induce lupus?
Procainamide Hydralazine Minocycle Diltiazen Penicillamine Isoniazid TNF inhibitor induced lupus
What is the natural history of drug induced lupus
Usually self resolves with redrawal of medication
What is the relationship between oestrogen and lupus
More oestrogen increases the risk of lupus
eg early menarche
What are common symptoms of SLE?
Fatigue
Fever
Mucocutaneous
MSK
What are some mucocutaneous manifestations?
Acute
- localised - malar rash (nasolabial fold sparing)
Subacte
- Annular papulosquamous, or both - 50% associated with SLE
Chronic
- Discoid lupus most common
Other
Panniculitis
Alopecia
What is factors increase the risk of SLE with discoid lupus?
Positive ANA, FBE abnormalities, generalised disease
Is lupus alopecia reversible?
Yes, will regrow as disease is controlled
Are oral ulcers painfull or painless?
Can be both
What is the pattern of MSK manifestation?
Usually symmetrical, polyarticular, migratory arthralgias with predilection to knees, wrists, and finger joints
What’s Rhupus?
RA/SLE overlap - presence of anti-CCP antibodies
What are the cardiovascular manifestations?
Pericarditis
Myocardial disease
Valvular disease
CAD
What is Libman Sacks endocarditis
Verrucous (wart like) sterile valvular lesions at edge of aortic, mitral or tricuspid valves
What is the prevalence of interstitial lung disease?
Rare
What are less common resp manifestations of SLE?
Pulmonary hypertension
Vanishing lung syndrome
Alveolar haemorrhage
What are the GI manifestation of SLE?
Hepatitis
Ileal and colonic perforation
What are the haematological manifestations of SLE?
Cytopenias Coombs positive haemolytic anaemia Evans syndrome Thrombocytopenia Lymphadenopathy Splenomegaly
What is Evans syndrome?
Autoimmune haemolysis and ITP
What is the most common neuropsychiatric manifestation?
Cognitive impairment
What is the pattern of myelitis in SLE?
Grey matter
White matter
What is the classification of renal disease?
Class I to VI
What diagnostic criteria is used for SLE?
1997 ACR classification criteria
- 4 manifestations
2012 SLICC-ACR classification criteria
- 4 or more. 1 clinic and 1 immunologic or biopsy-proven lupus nephritis with positive ANA
What are the autoantibodies?
ANA - required for lupus Dx
Is ANA/ENA a good marker of disease activity?
No
What is anti-Sm (Smith) associated with?
Renal and CNS disease
What is anti-dsDNA highly associated with?
SLE disease activity, nephritis, and TNFi-induced SLE
What are chemical meaures of disease activity?
ESR/CRP
High anti-dsDNA ab
Low C3/C4
What are general Mx options
Avoid triggers - UV light, oestrogen, sulfonamide Vitamin D repletion Cardiovascular risk modification Vaccination (avoid live vaccinations) Steroid SE's Minimise steroid
What are options of minor disease?
Hydroxychloroquine
NSAIDs
Steroid
Methotrexate/Azathioprine
What are options for major disease?
High dose steroid until remission
DMARD - Azathioprine, methotrexate, leflunomide, cyclophosphamide, cyclosporine/tac, mycophenolate
Rituximab
Who should get hydroxychloroquine?
Any patient with active disease
What is the mechanism of hydrochloroquine?
immunomodulatory?
What are the major SE’s of hydroxychloroquine?
Retinal toxicity - high dose, long term use, pre-existing disease
When to screen with hydroxy?
Baseline the annually after five years
What are the treatment principles for lupus nephritis?
Depends on histological type
Which lupus nephritis classes require immunosuppression?
3 and 4 +/- 5
How do you treat class 3 and 4 LN
Initially pulse IV steroids
Then either mycophenolate or cyclophosphamide induction
What are types of mycophenolate?
Mycophenolate mofetil and myfortic
When do you evaluate for response post induction for LN?
6 months
What do you use for maintenance for LN 3 + 4
Mycophenolate or azathioprine
What biologics are used in SLE?
B cell targeting therapies
- Rituximab (LUNAR and EXPLORER trials)
- Belimumab
What is the target of Belimumab
Targets B cell survival factors BAFF/Blys
What is the impact of lupus on pregnancy?
Higher faetal and maternal mortality
How do you differentiate lupus disease from pre-escampsia?
anti-dsDNA
Complements levels
Haematuria
Which antibodies should oyu check before pregnacny?
Anti-phospholipid
Anti-RO and La
What are the implications of pos antiphospholipid ab in pregnancy?
Asymt - low dose aspirin
Prior obstetric morbidity - low aspirin and prophylactic clexane
Prior thrombosis - therapeutic clexane - cont 6 months postpartum
What are the manifestations of anti-Ro and La antibodies?
Rash, haematologic, hepatic
Complete heart block
Which drugs can you continue in pregnancy?
Hydroxychloroquine, AZA, steroids
Which drugs can’t you use in pregnancy?
Methotrexate
NSAIDs (third trimester for ductus arterosis closure)
