SYSTEMIC LUPUS ERYTHMATOSUS Flashcards
Define systemic lupus erythmatosus.
Systemic lupus erythematosus (SLE) is a heterogeneous, inflammatory, multisystem autoimmune disease in which antinuclear antibodies occur (often years before clinical symptoms).
What are the defects in SLE?
Failure of self tolerance by the T and B cells
Defects in apoptosis system
Which virus has been implicated as a possible trigger for SLE?
EBV
To make a positive diagnosis of SLE what are the antibodies that we are looking?
Anti-nuclear antibodies (ANA)
Are ANA’s specific to SLE?
No. The different subtypes are present in a number of connective tissue disorders including Sjögren’s syndrome, scleroderma, mixed connective tissue disease, polymyositis, dermatomyositis, autoimmune hepatitis and drug induced lupus.
What is c1q?
It is a subtype of compliment involved in clearing debris of apoptosic cells.
How might a patient with suspected SLE present? (Name 3 symptoms)
Butterfly rash
Fatigue
Joint pain
Are CRP and ESR both classically raised in SLE?
No. Normally only ESR is raised. However, if there is infection at the time, then CRP may well be raised.
What are some of the monoclonal antibodies that are used in the treatment of SLE?
Rituximab
Belimumab
Erpratuzamab - currently undergoing trials
What is the peak age for females to develop symptoms of SLE?
50-54
What is the peak age for males to develop symptoms of SLE?
70-74
What is the ratio of women to men in terms of those affected by SLE?
10:1 - 5:1
What are the risk factors for developing SLE?
Certain HLA-DRB1 types e.g DR3 and DR2 Also HLA-B8 Defective C4 complement gene - develop a lupus-like illness UV light EBV Drugs
What are the drugs that can induce Lupus?
Chlorpromazine - antipsychotic
Methyldopa - Parkinson’s
Hydralazine - Anti-hypertensive
Isoniazid - TB
d-Penicillamine - Immunosuppressive for RA
Minocycline - broad spectrum tetracycline antibiotic
How might someone with suspected SLE present to their GP?
Fatigue Malaise Fever Weight loss Arthralgia with early morning stiffness Oral ulcers Photosensitive skin rashes - malar rash, urticaria Pleuritic chest pain Headache Paraesthesia Dry eyes Dry Mouth Raynaud's phenomenon Mild hair loss
What part of the face does the classic malar rash seen in SLE not affect?
Naso-labial fold
What is Raynaud’s phenomenon?
Excessively reduced blood flow in response to cold or stress, causing discoloration (white then blue then red) of fingers.
Which connective tissue disorders are associated with Raynaud’s phenomenon?
Scleroderma Systemic lupus erythematosus Rheumatoid arthritis Sjögren's syndrome Dermatomyositis Polymyositis Mixed connective tissue disease Cold agglutinin disease Ehlers-Danlos syndrome
What is the possible underlying pathophysiology of SLE?
Apoptotic cells and cell fragments inefficiently cleared by phagocytes.
They are then transferred to lymphoid tissue- taken up by APCs.
Self antigens including nuclear constituents eg: DNA and histones- these are presented to T cells- they stimulate B cells to produce auto-antibodies.
Clinical manifestations due to antibody formation and development and deposition of immune complexes, complement activation and influx of neutrophils and abnormal cytokine production.
Specifically which cytokines are increased in serum concentration in SLE?
IL-10
IFN-α
Which population (in terms of race) is most at risk of developing SLE?
Afro-Caribbean
What is discoid lupus?
A benign variant of SLE where only the skin is involved. So facial rash with erythematous plaques.
What are the 11 parts of the diagnostic criteria of SLE and how many does the criteria require the patient to have?
1) Malar flush
2) Discoid rash
3) Photosensitivity
4) Oral ulcers
5) Non erosive arthritis
6) Serositis
7) Renal disorder
8) CNS disorder
9) Haematological disorder
10) Immunological disorder
11) Antinuclear antibody (+ve in >95%)
4 or more of the 11
On examination what signs might you pick up in someone with suspected SLE?
Very non specific Splenomegaly Lymphadenopathy Rashes Any signs associated with complications of SLE
What investigations would you order for someone with suspected SLE?
Blood test: FBC ESR CRP Autoantibodies
Other investigations depending on involvement from specific body parts.
What might the FBC reveal in someone with suspected SLE?
Normochromic, normocytic anaemia.
Leukopenia
Thrombocytopenia
What pattern of results with regard to ESR and CRP would you expect to see in someone with SLE?
ESR raised but normal CRP unless there is intercurrent infection or serositis.
What is the most sensitive autoantibody present in patients with SLE, with 95% of all patients having this auto-antibody?
ANA
Which auto-antibody can be used to reflect disease activity in the 70% of SLE patients that have this auto-antibody?
Anti-dsDNA - high specificity but only 70% sensitivity.
A rise in antibody titre might indicate that immunosuppression needs to be increased.
What is the most specific antibody present in 30-40% of patients with SLE?
Anti-Sm
Which antibody, also called anti-SSA, is associated with several autoimmune diseases such as SLE and Sjogren’s syndrome?
Anti-Ro
Which antibody might indicate mixed connective tissue disease with overlap of SLE, scleroderma and myositis?
Anti-RNP
Which anti-mitochondrial antibody is sometimes found in SLE patients, as well as syphillis and anti-phospholipid syndrome?
Anti-cardiolipin
How are levels of complement affected in SLE patients and specifically which forms of complement are affected?
C3 and C4 are decreased
C3d is actually increased with disease activity
What type of complement is C3d, often found to be increased with increase in disease activity in SLE patients?
A degradation product
What are the complications associated with SLE?
Atherosclerosis Hypertension Dyslipidaemias Diabetes Osteoporosis Avascualar necrosis Malignancy
Which malignancy is especially associated with SLE?
Non-Hodgkin’s lymphoma
What are the pharmacological treatment options for managing a SLE patient?
Paracetamol NSAIDs for joint and muscle pain.
Corticosteroids (some risks though)
Hydroxychloroquine (malaria tablets) - useful for skin lesions, myalgia and malaise
What drugs might be given to someone with life-threatening SLE?
Cyclophosphamide Mycophenolate High dose prednisolone Methatrexate Ciclosporin Belimumab (B-cell inhibitor) Intravenous immunoglobulins
What non-pharmacological form of therapy can be offered to a SLE patient with life-threatening disease?
Plasma exchange
What are the leading causes of death in SLE patients?
Renal failure Cerebral disease (often epilepsy) Infection Cardiovascular disease related to atherosclerosis Malignancy (Non-Hodgkins Lymphoma)
Which antibody is often used as an indicator of drug induced lupus?
Anti-histones
Which antibody, also called Anti-SSB, is mainly associated with Sjogren’s syndrome but is also present is about 15% of SLE patients?
Anti-La
