Systemic Lupus Erythematosus (SLE, lupus)
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Definition of SLE o An inflammatory, multi-system autoimmune disease with a relapsing-remitting course with a wide spectrum of severity of disease
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Epidemiology of SLE o Incidence of SLE is5/100,000 in the U.S. o Ethnic incidence: Afro-Caribbean>Asian>Caucasian o Peak age of onset of SLE 20-40 o Females:Males = 9:1
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Aetiology of SLE (lupus) o Genetics
 Monozygotic twins 25% vs dizygotic 3%
 Multiple genes found to be more common in patients with SLE o 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 o Some drugs can induce a lupus-like syndrome
 E.g. Hydralazine, methyldopa, penicillamine, minocycline
 Drug induced SLE is associated with HLA DR-4
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Pathophysiology of SLE (lupus) o Possibly a defect in apoptosis that upsets immune tolerance mechanisms o T-cell abnormalities o Circulating immune complexes
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Presentation of SLE (lupus) o Systemic – fatigue often a prominent feature o 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 o 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 o Serositis
 Pleuritis – pleuritic chest pain
 Pericarditis – often asymptomatic
 Peritonitis – recurrent episodes of diarrhoea & abdominal pain o Mucocutaneous
 Photosensitivity
 Malar rash – fixed erythema over the malar eminences
 Oral ulcers
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 Discoid rash – erythematous, raised patches of keratotic scale, which progress to atrophic, depressed lesions. Affects ears, cheeks, scalp, chest, forehead
 Raynaud’s
 Livedo reticularis o Pulmonary
 Pneumonitis
 Interstitial lung disease
 PE
 Cardiac
 Myocarditis
 Libman-Sachs endocarditis – atypical sterile clusters of vegetations on posterior mitral valve leaflet o Neurological disorder
 Seizures
 Psychosis
 Psychiatric symptoms e.g. depression anxiety very common and often under-recognised
 Headache
 Aseptic meningitis
Investigations in SLE (lupus) o FBC
 Anaemia, leukopenia, lymphopenia, thrombocytopenia o ESR raised disproportionate to CRP (which is usually relatively normal) o Complement
 Low in disease flares
 Rising complement implies response to treatment o Immunology
 ANA +ve in 99% (some controversy over whether ANA negative SLE really exists)
 Anti-Sm (pathognomonic but poor sensitivity)
 Anti-dsDNA
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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 o Biopsy
 Renal
 Skin - often shows complement and immunoglobulin deposits at dermo-epidermal junction o Imaging dependant on organ involvement
 CXR, CT, echo, renal US, MRI can all be appropriate
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Treatment of SLE (lupus) o Lifestyle
 UV protection
 Minimise cardiovascular risk factors
 Patient education o Hydroxychloroquine - cornerstone of treatment
 Reduces flares and improves fatigue
 Prolongs life
 May be sufficient treatment for mild disease e.g. skin or musculoskeletal o Paracetamol and NSAIDs for analgesia o Steroids
 Short term courses for flares
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o DMARDS
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Dependant on disease manifestations
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Consider methotrexate for chronic arthritis
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Azathioprine or mycophenolate in moderate disease
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CNS or renal involvement requires aggressive treatment o High doses steroids o Azathioprine or mycophenolate o Cyclophosphamide (remember many patients are women of child-bearing age so can be difficult)
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Ciclosporin
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May require multiple agents o Biologics
 Used in refractory disease
 Rituximab (anti-CD20)
 Belimumab (blocks B lymphocyte stimulator)
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Complications of SLE o Cardiovascular disease (x5) o Infection o Antiphospholipid syndrome (APLS) o Osteoporosis
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Prognosis in SLE o 5-year survival is 95%
 Infection and cardiovascular disease key causes of mortality o Prognostically poor features in SLE:
 Multi-system disease
 Lupus nephritis
 Men o Drug-induced lupus improves once drug stopped
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No part of this document may be reproduced or shared without permission of Oxford Medical Education.