SLE and antiphospholipid syndrome Flashcards
What is SLE?
Systemic lupus erythematosus (SLE) is a multisystem, autoimmune disease, involving complex pathogenetic mechanisms that can present at any age.
What are the risk factors for SLE?
Certain human leukocyte antigen DRB1 types are more common in lupus patients - e.g., DR3 and DR2.
Patients who have a defective C4 complement gene (C4A null allele) also develop a lupus-like illness.
Environmental factors include ultraviolet light, viruses (e.g., the Epstein-Barr virus) and some drugs.
It most commonly presents in women in the reproductive age group although SLE is increasingly recognised after the age of 40 particularly in Europeans.
Higher incidence rate in Afro-Caribbean patients.
What is the presentation of SLE?
Symptoms and signs are often nonspecific – e.g., fatigue (can be severe and debilitating), malaise, fever, splenomegaly, lymphadenopathy, weight loss, arthralgia and fatigue, oral ulcers, photosensitive skin rashes, pleuritic chest pains, headache, paraesthesiae, dry eyes (keratoconjunctivitis sicca) and dry mouth, Raynaud’s phenomenon, mild hair loss and myalgia.
Arthralgia often with early morning stiffness (polyarthritis)
Photosensitivity rash.
The classical feature is the malar (butterfly) rash, often precipitated by sunlight. It is erythematous and may be raised and pruritic. It spares the naso-labial folds.
Pulmonary involvement such as pleurisy
Pericarditis, HTN
Glomerulonephritis
Neuropsychiatric presentation includes anxiety, depression and psychosis.
How is SLE diagnosed?
The American College of Rheumatology Classification system for SLE suggests that a person may be classified as having lupus if four or more of the following 11 criteria are present (which do not have to occur at the same time but can be cumulative over a number of years):
- Malar rash.
- Discoid lupus.
- Photosensitivity.
- Oral or nasopharyngeal ulcers.
- Non-erosive arthritis involving two or more peripheral joints.
- Pleuritis or pericarditis.
- Renal involvement with persistent proteinuria or cellular casts.
- Seizures or psychosis.
- Haematological disorder: haemolytic anaemia or leukopenia or lymphopenia or thrombocytopenia.
- Immunological disorder: anti-DNA antibody or anti-Sm or antiphospholipid antibodies.
- A positive antinuclear antibody.
What are the investigations for SLE?
SLE is a multisystem autoimmune disorder. The diagnosis requires a combination of clinical features and the presence of at least one relevant immunological abnormality. If there is a clinical suspicion of lupus, blood tests including serological markers should be checked.
When SLE is suspected, useful screening investigations are urinalysis, FBC, ESR or plasma viscosity and antinuclear factor.
Urinalysis: as initial test for proteinuria/haematuria.
Other investigations will depend on system involvement - e.g., MRI brain scan, echocardiogram, renal biopsy.
Which antibodies are present in SLE?
Antinuclear antibodies (ANAs) are present in about 95% of SLE patients. If the test is negative, there is a low clinical probability of the patient having SLE. A positive ANA occurs in approximately 5% of the adult population and alone has poor diagnostic value in the absence of clinical features of autoimmune rheumatic disease.
The presence of anti-dsDNA antibodies, low complement levels or anti-Smith (Sm) antibodies are highly predictive of a diagnosis of SLE in patients with relevant clinical features. Anti-Ro/La and anti-RNP antibodies are less specific markers of SLE as they are found in other autoimmune rheumatic disorders as well as SLE.
Which antibodies should be tested in all SLE patients?
Antiphospholipid antibodies should be tested in all lupus patients at baseline, especially in those with an adverse pregnancy history or arterial/venous thrombotic events.
Confirmatory tests for antiphospholipid syndrome are positive lupus anticoagulant, anti-cardiolipin antibodies (IgG, IgM) and/or anti-beta-2 glycoprotein-1 (IgG, IgM) on two occasions at least 12 weeks apart.
What are the associated diseases of SLE?
APLS
Overlap syndromes: some patients with ‘lupus’ do not have pure SLE as described, but have overlapping features with other connective-tissue diseases, such as scleroderma, polymyositis, rheumatoid arthritis and Sjögren’s syndrome.
They are prone to other autoimmune conditions such as thyroiditis. They also have a higher incidence of drug allergy and an increased risk of infection.
Patients with SLE are also at increased risk of certain other comorbidities, including atherosclerosis, hypertension, dyslipidaemias, diabetes, osteoporosis, avascular necrosis and malignancies (especially non-Hodgkin’s lymphoma)
What is the management of SLE?
Patients often require considerable counselling about their individual prognosis and symptoms. Avoid sun exposure as much as possible and use sun screens. Identify and treat any underlying cause (e.g., anaemia, depression) and encourage regular aerobic exercise.
Joint and muscle pains, headaches, and musculoskeletal chest pains respond to simple analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) - the latter should be used with caution because of gastrointestinal, renal and cardiovascular risks.
Lupus patients should be offered the flu vaccination; they should not receive live vaccinations.
Glucocorticoids and immunosuppressive therapy are indicated when neuropsychiatric SLE is thought to reflect an inflammatory process (optic neuritis, transverse myelitis, peripheral neuropathy, refractory seizures, psychosis or acute confusional state) and in the presence of generalised lupus activity.
Antiplatelet/anticoagulation therapy is indicated when manifestations are related to antiphospholipid antibodies, particularly thrombotic cardiovascular disease.
What is the management of mild SLE?
Treatments for mild non-organ threatening disease include the disease-modifying drugs hydroxychloroquine and methotrexate, and short courses of NSAIDs for symptomatic control. These drugs allow for the avoidance of or dose reduction of corticosteroids.
Prednisolone at a low dose of up to 7.5 mg/day or less may be required for maintenance therapy. Topical preparations may be used for cutaneous manifestations and intra-articular injections for arthritis.
High factor UVA and UVB sunscreen are important in the management and prevention of UV radiation-induced skin lesions. Patients must also be advised about sun avoidance and the use of protective clothing.
What is the management of moderate SLE?
The management of moderate SLE involves higher doses of prednisolone (up to 0.5 mg/kg/day), or the use of intramuscular or intravenous doses of methylprednisolone.
Immunosuppressive agents are required often to control active disease and are steroid-sparing agents. They can also reduce the risk of long-term damage.
Methotrexate, azathioprine, mycophenolate mofetil, ciclosporin and other calcineurin inhibitors should be considered in cases of arthritis, cutaneous disease, serositis, vasculitis, or cytopenias if hydroxychloroquine is insufficient.
For refractory cases, belimumab or rituximab may be considered.
What is the management of severe SLE?
Patients who present with severe SLE including renal and neuropsychiatric manifestations need thorough investigation to exclude other aetiologies including infection.
Treatment is dependent on the underlying aetiology (inflammatory and/or thrombotic) and patients should be treated accordingly with immunosuppression and/or anticoagulation.
Immunosuppressive regimens for severe active SLE involve IV methylprednisolone or high-dose oral prednisolone (up to 1 mg/kg/day) to induce remission either on their own or more often as part of a treatment protocol with another immunosuppressive drug.
Mycophenolate mofetil or cyclophosphamide are used for most cases of lupus nephritis and for refractory severe non-renal disease.
Biologic therapies belimumab or rituximab may be considered, on a case-by-case basis, where patients have failed other immunosuppressive drugs due to inefficacy or intolerance.
Intravenous immunoglobulin and plasmapheresis may be considered in patients with refractory cytopenias, thrombotic thrombocytopenic purpura, rapidly deteriorating acute confusional state and the catastrophic variant of antiphospholipid syndrome.
Are contraceptive pills safe for people with SLE?
Oestrogen hormones can exacerbate lupus but the lowest-dose oestrogen oral contraceptive pill can be prescribed cautiously, providing there is no history of migraine, hypertension or thrombosis and providing anticardiolipin antibodies are negative. However, there is an increased risk of thrombosis.
Can people with SLE get pregnant?
Fertility is normal and pregnancy is safe in mild or stable lupus. In severe lupus, pregnancy should be delayed until the disease is better controlled:
- Morbidity in pregnancy is common, especially if the woman has antiphospholipid antibodies.
- Complications include recurrent early loss of pregnancy, pre-eclampsia, intrauterine growth restriction and preterm delivery. Women are at increased risk of thrombosis, especially in the puerperium.
- The risks of pregnancy are greatly increased in the presence of lupus nephritis, hypertension and active disease, especially at the time of conception.
Low molecular weight heparin and low-dose aspirin are now the treatment of choice for women with APLS and a history of miscarriage.
Which antibodies that exist in SLE is dangerous to the baby?
Ro (SSA) and La (SSB) positivity in SLE is dangerous as these antibodies are able to cross the placenta and can result in neonatal lupus. This can include a lupus rash, complete heart block and blood abnormalities such as cytopaenias.
