Systemic Lupus Erythematosus (SLE)

Systemic autoimmune condition that mainly involves the skin, joints, kidneys, blood cells, and nervous system but can affect almost any organ system

Aetiology

• Autoimmune
• Genetic predisposition - HLA genes
• Hormonal factors - ↑ oestrogen
• Environmental factors - UV light, bacterial/viral infection, some medications

Risk factors

• Higher prevalence in women (9:1)
• Usually presents in childbearing years - 20-40

• More common and more severe in those of Afro-Caribbean, Hispanic American, Asian, and Chinese ethnicity

Pathophysiology

• Immune system attacks cells and tissues resulting in inflammation and tissue damage, also involves the formation of immune complexes (type III hypersensitivity)

1. Loss of immune regulation results in increased and defective apoptosis

2. Necrotic cells release nuclear materials which act as auto-antigens

3. Auto-immunity results from exposure to nuclear and cellular auto-antigens

4. B and T cells stimulated and autoantibodies are produced

5. Auto-antigens and autoantibodies form immune complexes which circulate and become deposited in the basement membrane (type III hypersensitivity)

6. Activation of complement which attracts leukocytes which release cytokines

7. Cytokine release perpetuates inflammation which causes necrosis and scarring

Clinical presentation

Non-specific symptoms

• Fever

• Fatigue

• Weight loss

Cutaneous features

• Photosensitive rash - can occur anywhere on the body but is typically seen on the face (malar rash)

• Non-scarring alopecia

• Oral/nasal ulcers

• Raynauds phenomenon

• Small erythematous lesions on neck, shoulders, and forearms (spares the face)

• 10% of cases of SLE

• Non-cancerous chronic skin condition

• Erythematous raised scaling plaques with active inflammation, triggered by UV light exposure

• Affects face, neck and head

• Associated with increased risk of developing SLE (10-15% risk)

Musculoskeletal

• Arthritis - synovitis or tenderness of at least 2 joints with >30 mins of early morning stiffness
• Unlike in RA, deformities are reducible and should not affect joint function (e.g. patient should be able to make a fist)

• Arthralgia

• Myalgia

• Jaccouds arthropathy - non-erosive reversible joint disorder that can occur after repeated bouts of arthritis, occurs in 10-35% of SLE patients

Systemic involvement

• Renal - lupus nephritis

• Neurological - seizures, psychiatric change (delirium, psychosis), headache, cranial nerve disorder

• Serositis - pleural or pericardial effusion, acute pericarditis

• Haematological - leukopenia, thrombocytopenia, haemolytic anaemia, lymphadenopathy

Investigations

• Diagnostic: ≳4 critera (at least 1 clinical and 1 lab critera) OR biopsy-proven lupus nephritis with positive ANA or anti-DNA

Autoantibodies

• Present in almost all SLE patients - SLE unlikely if test is negative

• Can also be present in other diseases e.g. other connective tissue disease, thyroid disease, liver disease

• Present in lower titers in up to 20% of the healthy population

• Anti-dsDNA
• Present in 60% of lupus patients and very highly specific
• Titre correlates with disease activity
• Associated with lupus nephritis

• Antiphospholipid antibodies (APLS)
• Lupus anticoagulant, anti-cardiolipin antibodies, anti-beta-2 glycoprotein 1 antibodies
• Associated with venous and arterial thrombosis and recurrent miscarriage
• Also associated with livedo reticularis - net like skin discolouration, most commonly over thighs

• Anti-Ro - if present in mother can be associated with neonatal lupus and congenital heart risk for baby

• Anti-Smith - highly specific for lupus but only positive in ~30% patients

Other lab tests

• Leukopenia, thrombocytopenia, haemolytic anaemia

• Low complement levels - activation and consumption related to disease activity
• C3 and C4 - particular association with renal and haematological disease

• Anti DNA antibodies are toxic to the kidney - should always do a urine dipstick in any patient with suspected SLE

• Proteinuria >0.5g in 24 hours indicates lupus nephritis, may also be blood present or red cell casts

• After positive urine dipstick perform biopsy to confirm nephritis

Imaging

• May be used to look for organ involvement e.g. chest for interstitial lung disease, MRI brain for cerebral vasculitis

Management

General management

• Sun protection measures

• Minimize steroid use

• Monitor disease activity using SLEDAI score

Pharmacological management

• Hydroxychloroquine

• Short course of NSAIDs for symptomatic control

• Steriods - IA for arthritis, topical for cutanous manifestations

• Hydroxychloroquine

• Acute flareups - immunosuppressants (e.g. azathioprine)/ oral steroids (short periods) to try and induce remission

• Treat organ complications appropriately

• e.g. in lupus nephritis or CNS lupus

• Treatment tends to involve IV steriods and cyclophosphamide

• Other therapies such as IV immunoglobulin and rituximab may be necessary

Monitoring

• anti-dsDNA antibodies and complement levels should be checked regularly, as well as urinalysis for blood or protein

• BP and cholesterol should be monitored due to increased CVD risk

Complications

• Increased prevalence of avascular necrosis, usually of the femoral head, which may relate to steriod use