Systemic Lupus Erythematous Flashcards
What is systemic lupus erythematous (SLE)?
SLE = inflammatory, multi-system autoimmune disorder with
=> arthralgia and rashes as most common presenting features
=> cerebral and renal disease as most serious problems
Who is most at risk from SLE?
Women > Men [9:1]
Peak age of onset = 20-40 yrs
African/carribean
Smokers (SLE more prevalent & severe)
The cause of SLE is unknown.
What are the predisposing factors to SLE?
- Hereditary
=> higher concordance rates in monozygotic twins (~25%)
=> 1st degree relative ~3% chance of developing SLE + 20% have autoantibodies - Genetic predisposition
=> HLA-B8, HLA-DR3
=> 20 genes linked inc. genes involved in T and B-lymphocyte function and genes related to autophagy - Sex hormone
=> pre-menopausal women mostly affected - Drugs
=> Hydralazine, isoniazid, procainamide can induce mild SLE (without cerebral / renal complications) - UV light
=> triggers flares of SLE, esp in the skin - Exposure to EBV
=> trigger for SLE
What is the pathogenesis in SLE?
Normal physiology:
Cells die by apoptosis and the cellular remnants appear on the cell surface that carry self-antigens
These antigens inc. DNA and histones => normally hidden from the immune system.
In SLE:
Removal of these self antigens by phagocytosis is impaired in SLE.
The self-antigens are taken up by antigen presenting cells and presented to T-cells => stimulate B cells to produce autoantibodies
The combination of the availability of self-antigens and failure of immune system to inactivate B and T-cells leads to:
=> autoantibodies forming either circulating complexes or deposit by binding directly to tissues
=> activation of complement + influx of neutrophils = inflammation
=> abnormal cytokine production = inflammation
What are the clinical features of SLE?
General: => Fever (50%) => Depression => Fatigue (75%) => Weight loss (50%)
Skin: => Photosensitivity => Butterfly rash => Vasculitis => Purpura => Urticaria
Eyes:
=> Sjögren’s (15%)
Nervous system (60%): => Fits => Hemiplegia => Ataxia => Polyneuropathy => Cranial nerve lesions => Psychosis => Demyelinating syndromes
Heart (25%):
=> Pericarditis
=> Endocarditis
=> Aortic valve lesions
Chest:
=> Pleurisy / effusions
=> Restrictive lung defect
Abdominal pain (15%)
Renal disease:
=> Glomerulonephritis (30%)
Myositis
Raynaud’s phenomenon (20%)
Joints (90%):
=> Aseptic necrosis
=> Arthritis in small joints
Blood (75%):
=> Anaemia (normochromic, normocytic or haemolytic Coombs +ve)
=> Leuko/lymphopenia
=> Thrombocytopenia
What are the most common clinical signs?
Joints related i.e. arthritis - 90%
Skin related - 85%
Blood - 75%
CNS - 60%
Chest - 50%
Renal - 30%
Heart - 25%
Abdo - 20%
Sjogren’s (eyes) - 15%
Describe the clinical features in the skin in SLE aka cutaneous SLE.
Classical butterfly rash affects central face in a rosacea-like distribution
Palmar erythema
Dilated nail-fold capillaries
Splinter haemorrhages ; Digital infarcts ; Purpura
Urticaria
Diffuse / scarring alopecia
Livedo reticularis (mottled/ purple-ish looking skin)
Raunaud’s phenomenon is common
Prolonged exposure to sunlight = exaccerbation of disease
What are the investigations for SLE?
Describe changes seen in:
Bloods tests
Autoantibodies
Serum complement
Histology
Imaging
Bloods:
- Full blood count:
=> leucopenia, lymphopenia ± thrombocytopenia
=> anaemia of chronic disease / haemolytic anaemia
=> ESR raised - U&E:
=> rises in advanced renal disease
=> low serum albumin or high urine albumin/creatinine ratio = indicators of lupus nephritis
3. Autoantibodies: => Anti-nucleur antibodies => Anti-dsDNA => Anti-Ro => Anti-Sm => Anti-La => Anti-phospholipid antibodies present in 25-40%
- Serum complement:
=> low C3 & C4 - Histology from skin biopsy & immunofluorescence:
=> deposition of IgG and complement seen in biopsies from kidney and skin - Diagnostic imaging:
=> CT head may show infarcts or haemorrhage with cerebral atrophy
=> MRI - lesions in white matter
How do you manage SLE?
- General measures
- Symptomatic therapy
- Corticosteroid + immunosuppressive therapy
- General measures:
=> protection from sun exposure i.e. SPF50+
=> smoking cessation
=> reduce cardiovascular risk factors
- Symptomatic therapy:
=> NSAIDs : anthralgia, arthritis, fever, serositis
=> Topical corticosteroids effective in cutaneous Lupus
=> Anti-malarials i.e. chloroquine, hydroxychloroquine : mild skin disease, fatigue, anthralgias not controlled by NSAIDs
- Corticosteroids & immunosuppressive drugs:
=> Single IM injections of long-acting corticosteroids or short courses of oral corticosteroids for arthritis, pleuritis, pericarditis
=> High dose oral corticosteroids + immunosuppressive drugs : renal / cerebral disease
=> High dose oral corticosteroids : severe haemolytic anaemia or thrombocytopenia
- Immunosuppresive drugs to maintain remission = mycophenolate mofeil & Azathioprine
- Monoclonal antibodies used in refractory disease i.e. Rituximab (against B-lymphocyte)
What is the prognosis for SLE?
SLE leads to a chronic illness with flares and periods of remissions.
In some patients, all signs of active disease resolve in time.
What are the 5 types of skin changes in SLE?
1) Chilblain LE: Cryoglobulin/cold agglutinin –ve:
=> treatment: antimalarials, steroids, pentoxifylline, or dapsone
2)Chronic cutaneous (discoid) LE:
=> Inflamed plaques + scarring ± atrophy;
=> may respond to reduced sun exposure, topical steroids, antimalarials (hydroxychloroquine)
3) Subacute cutaneous LE:
=> Widespread, non-scarring round or psoriasis-like plaques in photodistribution
=> ANA or Ro/La +ve.
4) Acute systemic lupus erythematosus (SLE):
=> Specific malar induration forming butterfly rash or widespread indurated erythema on upper trunk
5) Non-specific cutaneous LE phenomenon:
=> Vasculitis, alopecia, oral ulcers, palmar erythema, periungual erythema, Raynaud’s phenomenon
