Systemic Lupus Erythematosus

Question 1

Systemic Lupus Erythematosus (SLE)

Answer 1

A multi-system inflammatory autoimmune disorder characterised by auto-antibodies
Most common presentations –> Arthalgia and rashes
Most serious –> Renal and brain

Question 2

Epidemiology of SLE

Answer 2

1:9/M:F . Peak onset between 20-40yrs

Incidence varies between populations – highest in african american women (1/250)

Question 3

Pathogenesis of SLE

Answer 3

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

Question 4

Risk factors for SLE

Answer 4

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)

Question 5

Cytokines in SLE

Answer 5

IL-10 and interferon-a are raised and their level tends to be related to level of SLE activity

Question 6

Drug induced SLE

Answer 6

Hydralazine, Isoniazid, procainamide & Penicillamine can induce a mild form of SLE (no renal or CNS involvement)

Question 7

Causes of tissue damage in SLE

Answer 7

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

Question 8

Clinical features of SLE

Answer 8

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

Question 9

Arthralgia in SLE

Answer 9

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

Question 10

Muscle pain in SLE

Answer 10

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

Question 11

Skin involvement in SLE

Answer 11

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

Question 12

Lung involvement in SLE

Answer 12

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

Question 13

Heart and CVS disease in SLE

Answer 13

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

Question 14

Renal involvement in SLE

Answer 14

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,

Question 15

CNS involvement in SLE

Answer 15

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

Question 16

Eye involvement in SLE

Answer 16

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

Question 17

GI involvement in SLE

Answer 17

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

Question 18

Blood investigations for SLE

Answer 18

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

Question 19

Autoantibodies in SLE

Answer 19

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

Question 20

General Management of SLE

Answer 20

Avoid sunlight and reduce CVS RFs

Many pts will not require anything more than NSAIDs –> Topical corticosteroids are widely used for cutaneous SLE

Question 21

Treatment of mild SLE symptoms

Answer 21

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

Question 22

Treatment of severe SLE symptoms

Answer 22

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

Question 23

Disease progression in SLE

Answer 23

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)

Question 24

SLE and Pregnancy

Answer 24

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

Question 25

Jaccoud’s arthropathy

Answer 25

a Rare manifestation of SLE where there is large joint deformity – resembles RA clinically

Question 26

Photosensitivity in SLE

Answer 26

Occurs in 40-50% of patients – particularly associated with anti-RO positive pts
Prolonged exposure can lead to acute flare ups,

Question 27

Raynaud’s phenomenon in SLE

Answer 27

Common - similar basic RFs and due to disease and may precede the development of other symptoms by many years

Question 28

Discoid Lupus

Answer 28

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

Question 29

Shrinking lung syndrome

Answer 29

Pneumonitis or atelectasis which lead to restrictive defects reducing volume can occur – thought to be neuromuscular in origin

Question 30

Libman-sacks syndrome

Answer 30

Aseptic mitral valve endocarditis which is very rarely seen in SLE

Question 31

Classes of Lupus Nephritis (LN)

Answer 31

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

Question 32

Management of Lupus nephritis by class

Answer 32

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)

Question 33

Tissue biopsies for SLE

Answer 33

Skin or kidney biopsies are most common – typically see IgG and complement deposition

Question 34

Imaging in SLE

Answer 34

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

Question 35

SLE and Cancer

Answer 35

Higher long term risk of certain cancers – mainly lymphoma

Question 36

Neonatal lupus syndrome

Answer 36

Rash, hepatitis and fetal heart block

Occurs in 2% of births where mothers have lupus and are anti-Ro or anti-La positive

Question 37

Is it Lupus

Answer 37

It’s never Lupus