Systemic Lupus Erythematosus (SLE)

Question 1

Define SLE.

Answer 1

Multi-system inflammatory autoimmune disorder. 4 out of 11 diagnostic criteria of the American College of Rheumatology provides 95% specificity and 85% sensitivity for SLE:

Question 2

List some of the ACR criteria for SLE.

Answer 2

• (1) Malar rash
• (2) Photosensitivity
• (3) Non-erosive arthritis
• (4) Renal disease (urine casts/proteinuria)
• (5) Neurological disease (psychosis/seizures)
• (6) Haematological (haemolytic anaemia/leukopenia/thrombocytopenia)
• (7) Immunological disorder (anti-dsDNA/anti-Sm/anti-phospholipid)
• (8) Antinuclear antibodies (ANA)
• (9) Discoid rash
• (10) Oral ulcers
• (11) Pleuritis or pericarditis (serositis)

Question 3

What is the aetiology of SLE?

Answer 3

Unknown

Tissue damage may be mediated by vascular immune complex deposition related to the auto-antibodies

Combination of hormonal,

• genetic (HLA clustering) and
• exogenous/environmental factors (e.g. drugs such as hydralazine and procainamide can cause a reversible SLE-like disorder)

Question 4

What is the pathophysiology of SLE?

Answer 4

• Antigen-driven immune-mediated disease characterised by high-affinity IgG antiboies to double stranded DNA and nuclear proteins.
• Normally tolerance to self antigens of B cells is established by regulatory and helper T cells.
• T cell dysregulation of B cells may arise –> autoimmunity
• Imapired clearance of endogeous materials of apoptotic cells in SLE, not cleared –> persistence of nuclear and cytoplasmic material –> modified to antigens –> immune respone

Question 5

What are the risk factors for SLE?

Answer 5

• Female
• Age 15-45yrs
• African/Asian descent in Europe/US
• Drugs – minocycline, isionazid, terbinafine, phenytoin, carbamazepine, sulfasalazine, monoclonal antibodies.
• Sun exposure - photosensitive rashes form criteria for diagnosis
• FH (>20% between monozygotic twins)
• Tobacco smoking

Question 6

What are the signs and symptoms of SLE? (general/specific body)

Answer 6

• General - fever, fatigue, weight loss, lymphadenopathy, splenomegaly, abdominal pain
• Fibromyalgia
• Raynaud’s phenomenon - in 30%
• Oral ulcers
• Skin rash - Malar, discoid, photosensitive and atypical rashes.
• Alopecia - hair thinning and loss
• Chest pain and SOB (pleuritis)
• Systemic involvement:
  
  • MSK -arthritis, tendonitis, myopathy, avascular necrosis of femoral head
  • Heart - pericarditis, myocarditis, arrhythmias, Libman-Sacks endocarditis (non-infective mitral valve disease), aortic valve lesions, hypertension
  • Lung - symptoms of pleuritis, pleural effusion, basal atelectasis, restrictive
  • Neuro - headache, stroke, cranial nerve palsies, confusion, chorea, fits, peripheral neuropathy,
  • Psych - depression, psychosis
  • Renal - symptoms of glomerulonephritis

Question 7

What is the skin involvement in SLE?

Answer 7

• Malar (butterfly) rash - affects cheeks and bridge of nose
• Discoid lupus - red, scaly patches (e.g. face), which later heal with scarring and pigmentation
• Photosensitivity rash - can be painful, pruritic ans last a few days, heals without scarring.

Other: Atypical - vasculitis (digital infarcts), urticaria, purpura, bullae, livedo reticularis, atypical erythema multiforme-like rash (Rowell’s syndrome), hair loss.

Question 8

What antibodies would you test for in SLE and which are most common?

Answer 8

• Anti-dsDNA: : 60% of cases.
• Rheumatoid factor: 30–50% of cases.
• Anti-ENA:
• Anti-RNP: 30% of cases.
• Anti-Sm: 30% of cases.
• Anti-Ro (SSA): 30% of cases.
• Anti-La (SSB): 15% of cases
• Anti-histone: In drug-induced lupus.
• Anti-phospholipid/Anti-cardiolipin: See anti-phospholipid syndrome.

Question 9

What investigations would you do in SLE? (go by system)

Answer 9

General:

• FBC - anaemia, leukopenia, thrombocytopenia; rarely pancytopenia
• U&E - elevated urea and creatinine
• ESR/CRP - raised
• Clotting - prolonges in those with antiphospholipid antibodied
• Complement - complement consumption - low C3 and C4 levels
• LFTs
• Urine - haematuria, casts (red cell, granular, tubular, or mixed) or proteinuria

Imaging:

• Radiographs - of joints
• CXR - pleural effusion, infiltrates, cardiomegaly
• ECG - exclude other causes of chest pain
• Echo - pericarditis, pericardial effusion, pulmonary hypertension
• CT
• MRI

Invasive:

• LP
• Renal biopsy - if glomerulonephritis suspected (focal, segmental, or global)
• Skin biopsy - immune deposits at the dermal-epidermal junction on immunofluorescence or non-specific inflammation