Systemic Lupus Erythematosus (SLE, lupus)

Definition of SLE

An inflammatory, multi-system autoimmune disease with a relapsing-remitting course with a wide spectrum of severity of disease

Genetics
- Monozygotic twins 25% vs dizygotic 3%
- Multiple genes found to be more common in patients with SLE
Hormonal influence
- Disparity in incidence between men and women is reduced post-menopause age
- Potentially an infectious trigger but uncertain
Anti-TNF therapy can induce lupus
Some drugs can induce a lupus-like syndrome
- E.g. Hydralazine, methyldopa, penicillamine, minocycline
- Drug induced SLE is associated with HLA DR-4

Systemic – fatigue often a prominent feature
Arthritis – usually affecting small joints, may be asymmetrical and pain often out of proportion to swelling
- Jaccoud’s arthropathy: A deforming non-erosive polyarthropathy with ulnar deviation and MCP subluxation, deformities can be reduced
Renal disorder (lupus nephritis) – presents with proteinuria, haematuria, ARF, CKD, hypertension, nephrotic syndrome
- 1 = sedimented
- 2 = mesangial
- 3 = proliferative <50%
- 4 = proliferative >50% (most are in this category)
- 5 = membranous
- 6 = sclerosed
Serositis
- Pleuritis – pleuritic chest pain
- Pericarditis – often asymptomatic
- Peritonitis – recurrent episodes of diarrhoea and abdominal pain
Mucocutaneous
- Photosensitivity
- Malar rash – fixed erythema over the malar eminences
- Oral ulcers
- Discoid rash – erythematous, raised patches of keratotic scale, which progress to atrophic, depressed lesions. Affects ears, cheeks, scalp, chest, forehead
- Raynaud’s phenomenon
- Livedo reticularis
Pulmonary
- Pneumonitis
- Interstitial lung disease
- PE
Cardiac
- Myocarditis
- Libman-Sachs endocarditis – atypical sterile clusters of vegetations on posterior mitral valve leaflet

FBC
- Anaemia, leukopenia, lymphopenia, thrombocytopenia
ESR and CRP
- ESR often raised disproportionate to CRP (which is usually relatively normal)
Complement
- Low in disease flares
- Rising complement implies response to treatment
Immunology
- ANA +ve in 99% (some controversy over whether ANA negative SLE really exists)
- Anti-Sm (pathognomonic but poor sensitivity)
- Anti-dsDNA
  - Sensitivity 70%
- Anti-Ro and anti-La antibodies in about 15% (And increase the risk of neonatal heart block)
- Anti-histone Ab in drug induced lupus
- Rheumatoid factor – positive in 25%
- Anti-cardiolipin/lupus anticoagulant/anti B2 glycoprotein
Biopsy
- Renal
- Skin – often shows complement and immunoglobulin deposits at dermo-epidermal junction
Imaging dependant on organ involvement
- CXR, CT, echo, renal US, MRI can all be appropriate

Lifestyle and multidisciplinary approach
- Patient education
- UV protection
- Minimise cardiovascular risk factors
Hydroxychloroquine – cornerstone of treatment
- Reduces flares and improves fatigue
- Prolongs life
- May be sufficient treatment for mild disease e.g. skin or musculoskeletal
Paracetamol and NSAIDs for analgesia
Steroids
- Short term courses for flares
DMARDS (disease modifying anti-rheumatic agents)
- Dependant on disease manifestations
- Consider methotrexate for chronic arthritis
- Azathioprine or mycophenolate in moderate disease
- CNS or renal involvement requires aggressive treatment
  - High doses steroids
  - Azathioprine or mycophenolate
  - Cyclophosphamide (remember many patients are women of child-bearing age so can be difficult)
  - Ciclosporin
  - May require multiple agents
Biologics
- Used in refractory disease
- Rituximab (anti-CD20)
- Belimumab (blocks B lymphocyte stimulator)

5-year survival is 95%
Infection and cardiovascular disease key causes of mortality
Prognostically poor features in SLE:
- Multi-system disease
- Lupus nephritis
- Men
Drug-induced lupus improves once drug stopped