Systemic Lupus Erythematosus Flashcards
What diseases come under the category of ‘connective tissue disease’?
SLE
Systemic sclerosis
Dermatomyositis/polymyositis
Sjogren’s syndrome
Mixed connective tissue disease
Which gender does SLE more commonly affect?
Females 9:1
Describe the presentation of SLE including some specific features.
Malaise, fatigue, weight loss, fever
lymphadenopathy
Specific features:
Butterfly rash
Alopecia
Arthralgia
Long history of Raynaud’s phenomenon
Describe the characteristics of the rash seen in SLE.
It tends to go across the nose
It may look a bit like acne
It is not painful or itchy
Some rashes become depigmented when the inflammation spreads to the dermis (depigmentation and scarring is irreversible)
Describe the pathogenesis of SLE.
SLE patients have a defect in apoptosis
Apoptotic cells are not cleared properly so they persist and expose their nuclear antigens and autoantibodies are generated against these nuclear antigens
The defect in apoptosis is combined with B/T cell hyperactivity
The overactive B cells are exposed to the nuclear antigens and the plasma cells begin to produce autoantibodies that circulate and form immune complexes
The immune complexes deposit in tissues and activate complement leading to inflammation
Chronic inflammation cuases tissue fibrosis and damage
What is the first investigation performed in the diagnosis of SLE?
Check for anti-nuclear antibodies (this is not specific for SLE though)
The pattern with which the antinuclear antibodies bind to the nuclear antigens is important in reaching a diagnosis. List some different patterns, the antigens and disease they are associated with.
Homogenous – DNA - SLE
Speckled – antibodies to Ro, La, Sm and RNP - SLE overlap syndromes
Nucleolar – topoisomerase – scleroderma
Fine speckled - Centromere – limited cutaneous scleroderma aka CREST
What conditions are associated with the presence of anti-Ro and anti-La antibodies?
Neonatal lupus syndrome
Subacute cutaneous lupus erythematosus
What are some other tests that can be done for SLE?
Measuring complement levels
Anti-cardiolipin antibodies
Lupus anticoagulant
Beta 1 glycoprotein
Describe the haematological features of SLE.
SLE is generally associated with low blood counts
Thrombocytopenia
Lymphopenia
Normocytic anaemia
Autoimmune haemolytic anaemia
What renal changes might occur in SLE?
Proteinuria
Haematuria
Active urinary sediment
List some clinical features that could help pre-empt severe attacks in SLE.
Malaise,
weight loss,
alopecia,
rash
List some laboratory markers that could help pre-empt severe attacks in SLE.
Raised ESR
Raised anti-dsDNA antibodies
Reduced complement levels
Describe the differences between mild, moderate and severe disease in SLE.
Mild – skin and joint involvement
Moderate – inflammation of other organs (e.g. pleuritis, pericarditis)
Severe – severe inflammation of vital organs
Describe the treatment of mild disease.
Paracetamol and NSAIDs - monitor renal function
Hydroxychloroquine (good for arthropathy and cutaneous manifestations)
Topical corticosteroids
Describe the treatment of moderate disease.
ORAL GLUCORTICOIDS
Start with a HIGH dose and titre downwards
Describe the treatment of severe disease.
Immunosupressants:
Mycofenalate
Rituximab
Cyclophosphamide – one used if there is severe organ involvement
Problem – infertility
Name and explain the mechanism of action of two new treatments for severe disease.
Mycophenolate mofetil
Reversible inhibitor of inosine monophosphate dehydrogenase
This is the rate limiting step in de novo purine synthesis
Lymphocytes rely heavily on de novopurine synthesis
Rituximab
Anti-CD20 antibody
Causes depletion of B cells
Useful in lupus nephritis
SLE has and early peak and a late peak in mortality. What are the usual causes of the two peaks?
Early – renal failure, CNS disease, infection
Late – MI and stroke
What can usually be seen on the blood film of a patient with SLE?
Schistocytes (evidence of microangiopathic haemolytic anaemia)
Teardrop cells
Spherocytes
Few leukocytes
Few platelets
Describe the appearance of a renal biopsy in a patient with SLE
Hypercellular
Mesangial proliferation
Crescent development
What is the aetiology of SLE?
Unknown - linked to HLA-RD3 and the environment (UV, drugs, microbal response)
What are the SLE - ACR criteria?
S-Serositis
O-oral ulcers
A-arthritis
P-Photosensitivity
B-Blood (all low)
Renal-proteinuria
Immunological- ANA, anti-dsDNA
N-neurological-seizures/psychosis
M-Malar rash
D- discoid rash
