Systemic Lupus Erythematosus Flashcards
Systemic Lupus Erythematosus (SLE)
A multi-system inflammatory autoimmune disorder characterised by auto-antibodies
Most common presentations –> Arthalgia and rashes
Most serious –> Renal and brain
Epidemiology of SLE
1:9/M:F . Peak onset between 20-40yrs
Incidence varies between populations – highest in african american women (1/250)
Pathogenesis of SLE
Auto-antibodies against nuclear antigens
Damage is either by direct binding of these autoantibodies to tissue or the formation of immune complexes –> activates the complement system causing neutrophilic infiltration + increased cytokines
Risk factors for SLE
Genetics – 25% MZ concordance, 3% risk if 1st degree relative affected, Genes for HLA A1,B8 and DR3 + complement system are implicated
Female sex hormones – premenopausal women most effected (also XXY men), HRT increases the risk of a flare
UV light and EBV are considered triggers for the disease or skin flare ups (UV light esspecially)
Cytokines in SLE
IL-10 and interferon-a are raised and their level tends to be related to level of SLE activity
Drug induced SLE
Hydralazine, Isoniazid, procainamide & Penicillamine can induce a mild form of SLE (no renal or CNS involvement)
Causes of tissue damage in SLE
Skin & kidneys –> Immune complex or IgG deposition and complement activation - may also be neutrophil/lymphocyte infiltration
Systemic vasculitis can occur and immune complex deposition can cause synovial inflammation and arthralgia
Clinical features of SLE
Vary greatly between patients – most patients will have fatigue/malaise, arthralgia and skin problems – fever is common during flares
Constitutional symptoms do not tend to correlate with disease activity or organ involvement
Organ involvement is rarer and more serious
Arthralgia in SLE
The most common feature (>90%) - similar presentation to RA with symmetrical small joint pain – clinically normal but can be slight soft tissue swelling - joint deformity/erosion are rare
Muscle pain in SLE
Myalgia will be seen in 50% of patients but true myositis only in 5% – is myositis is present there may be an overlap syndrome with myositis and SLE
Skin involvement in SLE
85% have some skin involvement – butterfly erythema across the face is characteristic but vasculitic (urticara & purpura) lesions of the finger tips & nail folds can occur
Also: Livdeo reticularis, palmar/plantar rashes, changes in pigmentation and scarring alopecia
Lung involvement in SLE
50% of pts will have at some point in the disease – most common –> Bilateral, recurrent pleurisy & exudate effusions
Shrinking lung syndrome, pulmonary fibrosis or intra- pulmonary haemorrhage are rare complications
Heart and CVS disease in SLE
Involved in 25% – small effusive pericarditis or mild myocarditis (causing arrhythmia) are the most common. Aortic valve lesions and cardiomyopathy can also occur.
Vascular complications are more commonly seen if there is overlap with APS but there is a general increased MI/CVA risk in SLE
Renal involvement in SLE
Only in 30% of pts – 1/3 of them will reach ESRF within 10yrs
Six classes of lupus nephritis (prognosis is best with types I,II and V) – management is controlling oedema & HTN,
CNS involvement in SLE
Flucating symptoms are seen in up to 60% of pts – mild depression and rarely more severe psychiatric symptoms occur
multiple mechanisms of cerebral damage and MRI findings are usually increased white matter signal –> migraine, epilepsy, ataxia, meningitis, CN lesions or polyneuropathy can occur
Eye involvement in SLE
Retinal vasculitis –> infarcts (cytoid bodies) –> appear as hard exudates and haemorrhages
Also: episcleritis, conjunctivitis or optic neuritis –> blindness is uncommon
Secondary Sjogren’s occurs in 15% of cases
GI involvement in SLE
Mouth ulcers are common and may be a presenting feature
Usually initally painless but may become infected
Mesenteric vasculitis can cause bowel infarcts
Liver/pancreas involvement is uncommon
Blood investigations for SLE
FBC -> leuco-/lympho-/thrombocyto- penia are possible, anaemia of chronic disease, ESR raised in relation to activity, CRP normal,
U+Es –> will rise only in advanced renal disease, low albumin or high urine prot/creat ratio are early signs
Autoantibodies –> Full ANA screen and APS as well
Complement –> C3 & C4 will be reduced in active disease
Autoantibodies in SLE
SLE – Anti-dsDNA (70%), anti-RO (40-60%), Anti-LA (15%), Anti-Sm (10-25% if white, 30-50% black), Anti-UI-RNP (30%),
Drug induced lupus – Anti-histone
General Management of SLE
Avoid sunlight and reduce CVS RFs
Many pts will not require anything more than NSAIDs –> Topical corticosteroids are widely used for cutaneous SLE
Treatment of mild SLE symptoms
If NSAIDs are insufficient antimalarials (chloroquine or hydroxychloroquine) can be used (require eye checks)
IM or oral steroids for severe flares of arthritis/pluerisy/pericarditis – these may require long term steroids
Treatment of severe SLE symptoms
Renal or cerebral disease –> high-dose oral steroids+ mycophenolate to induce remission -> azathioprine for maintenance
Severe haemolysis –> high-dose oral steroids
Anti-CD20 (rituximab) can be used in refractory cases
Disease progression in SLE
Episodic course with exacerbation separated by complete remission
Can be chronic & persistent
10yr survival is >90% - early deaths are renal/cerebral disease or infection – later MI/CVA is more common
Progressive joint destruction is rarely seen but pts may develop deformity (ulnar deviation)
SLE and Pregnancy
Fertility is usually unaffected although there is a risk of recurrent miscarriage if APS antibodies are present. Exacerbations can occur during pregnancy and are frequent postpartum – treatment should be continued and HTN particularly controlled. Pts with anti-RO or anti-LA have 2% risk of neonatal lupus syndrome
Jaccoud’s arthropathy
a Rare manifestation of SLE where there is large joint deformity – resembles RA clinically
Photosensitivity in SLE
Occurs in 40-50% of patients – particularly associated with anti-RO positive pts
Prolonged exposure can lead to acute flare ups,
Raynaud’s phenomenon in SLE
Common - similar basic RFs and due to disease and may precede the development of other symptoms by many years
Discoid Lupus
A benign form of lupus where only the skin is involved – well defined erythematous plagues form on the face and lead to scarring and pigmentation
Shrinking lung syndrome
Pneumonitis or atelectasis which lead to restrictive defects reducing volume can occur – thought to be neuromuscular in origin
Libman-sacks syndrome
Aseptic mitral valve endocarditis which is very rarely seen in SLE
Classes of Lupus Nephritis (LN)
I - minimal change mesangial - immune deposits, asymmptomatic
II - Mesangial proliferative - hypercellularity+matrix expansion - mild
III - Focal - 50% of glomeruli - most common & severe - nephrotic syn. with HTN and renal insufficiency
IV - diffuse proliferative - aggressive and renal failure is common
V - Membranous - 10-20% of pts, can co-occurs with III or IV, alone has good prognosis
VI - Advanced sclerosing ->90% lost function - ESRF
Management of Lupus nephritis by class
I - asympomatic so no treatment but monitor
II - Usually benign but may need courses of steroids
III, IV & V - Steroids & cyclophosphamide/mycophenolate used to induce remission and azathioprine or mycophenolate used for maintenance – biologics (rituximab) can be used for short courses
VI - no treatment (dialysis or transplant)
Tissue biopsies for SLE
Skin or kidney biopsies are most common – typically see IgG and complement deposition
Imaging in SLE
CT may show infarcts or haemorrhages with general signs of atrophy
MRI can detect white matter changes which CT cannot but it can be difficult to distinguish vasculitis from thrombi
SLE and Cancer
Higher long term risk of certain cancers – mainly lymphoma
Neonatal lupus syndrome
Rash, hepatitis and fetal heart block
Occurs in 2% of births where mothers have lupus and are anti-Ro or anti-La positive
Is it Lupus
It’s never Lupus
