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Next Lesson - Immunological Therapies
Core
Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that can manifest in multiple different ways depending on the organs affected. In SLE, autoantibodies that target a variety of autoantigens are produced, forming immune complexes that deposit in different areas of the body. This results in inflammation and damage to the tissues containing these autoantigens.
The incidence of SLE is about 400,000 worldwide, indicating that 400,000 new diagnoses of SLE are made each year. The prevalence is 3.41 million, indicating that at any given time, there are 3.41 million people living with SLE around the world (source).
Women are more likely to have SLE than men, with women making up approximately 3 million of those currently diagnosed with SLE. This shows that SLE disproportionally affects women more than men at a ratio of about 9:1.
It is thought to have a strong genetic component as a history of disease among first or second-degree relatives is a significant risk factor for developing the disease.
When examining a patient with suspected SLE, it is important to carry out a thorough examination as it can present in many ways and manifests through a range of body systems. A good way to approach such patients is by having a systematic approach such as the 'glove and sweater' approach which begins with an examination of the hands, arms, trunk, chest, and face.
In the hands, it is important to look for Raynaud’s phenomenon (a condition affecting the small blood vessels in the hands, particularly when exposed to cold), synovitis and skin rash. Further along the arms, patients can present with proximal muscle weakness (due to nerve involvement and fibromyalgia), rashes or large joint swelling. In the trunk, SLE can present with truncal rash or signs of pericarditis or pleuritic rub upon auscultation. Finally, in the face, SLE can cause alopecia, facial rashes (malar or discoid), and mouth ulcers.
A severe presentation of SLE is called lupus nephritis. It occurs when the immune complexes formed from the SLE autoantibodies develop in the kidneys and damage them. It commonly presents with a nephritic picture, such as hypertension and renal impairment, and may also be associated with significant proteinuria leading to oedema and foamy urine. Treatment of lupus nephritis is possible through treating the underlying SLE, but the damage may be irreversible and the presence of lupus nephritis is associated with a worse prognosis, often progressing to end-stage renal disease requiring dialysis.
Routine blood investigations to take when there is suspicion of SLE are full blood count, urea & electrolytes, liver function, CRP and ESR. These are to check for contraindications to treatment and to check for levels of systemic inflammation.
Specific blood tests related to SLE include the following (source):
Anti-nuclear Antibodies (ANA) - it is the most sensitive diagnostic test for SLE as it is present in up to 95% of patients with SLE. However, it can also be present in patients with other connective tissue disorders. This means that ANA is sensitive (a negative ANA makes SLE unlikely) but not specific, as a positive ANA can occur in many other conditions and even in healthy individuals.
Anti-dsDNA Antibodies (anti-dsDNA) - positive anti-dsDNA antibodies are highly predictive of SLE in patients with symptoms.
Anti-Smooth Muscle Antibodies - this antibody is almost exclusive to SLE (high specificity) but only present in about 20% of people with the disease (low sensitivity). It is thought to be increased in flare-ups of SLE.
Anti-Ro and La Antibodies - these are not specific for SLE as they are found in other rheumatic diseases such as Sjogren’s syndrome, rheumatoid arthritis, or systemic sclerosis.
Complement Factors - C3 and C4 complement factors tend to be low in patients with SLE.
Antiphospholipid Antibodies - anti-cardiolipin, lupus anticoagulant and anti-beta 2 glycoprotein: these should be tested in all patients with suspected SLE as they are used as indicators for increased risk of clotting complications such as strokes, transient ischaemic attack, pulmonary embolism, or miscarriage. They do not correlate with disease severity but can allow prevention of the above complications with treatment.
Most patients will have a positive ANA result, but this on its own is not enough to diagnose SLE. Usually, a combination of symptoms consistent with SLE, specific antibody results, and abnormal inflammatory markers are used to make an accurate diagnosis. Some of these values can help determine the severity of the disease or are related to specific subtypes of the diseases affecting specific organs more than others.
To confidently diagnose SLE, older classification systems required at least 4 out of 11 criteria. More recent criteria use a positive ANA as an entry requirement with additional weighted features to support classification. These can be memorised using the mnemonic SOAP BRAIN MD which stands for the following:
- Serositis (pleuritis, pericarditis)
- Oral ulcers
- Arthritis/Arthralgia
- Photosensitivity
- Blood (low results on an FBC - anaemia (low Hb), leukopenia (low lymphocyte count), and thrombocytopenia (low platelets)
- Renal abnormalities (proteinuria linked to lupus nephritis)
- ANA (anti-nuclear antibody) positive
- Immunological abnormalities (e.g. dsDNA, low C3/C4 etc.)
- Neurological abnormalities (e.g. seizures, memory loss)
- Malar Rash - also known as the butterfly rash, this is a red rash across the bridge of the nose and the cheeks
- Discoid Rash - round, coin-shaped lesions that mostly develop on the scalp or face. They are often scaly and red
Image - Malar rash. It is characteristically across the bridge of the nose and the cheeks
Creative commons source by Doktorinternet [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
Management will be tailored to the presentation and systems affected in each patient.
Conservative management involves lifestyle modifications such as the regular use of high-factor sunscreen to protect the skin from further damage resulting from photosensitivity.
In terms of pharmacological management, hydroxychloroquine is the disease-modifying anti-rheumatic drug (DMARD) of choice, unless contraindicated (then azathioprine or mycophenolate can be used). These reduce the disease burden and improve patient outcome. For cutaneous flare-ups, topical corticosteroids can be used (for example, hydrocortisone or more potent topical preparations depending on severity). In severe flare-ups, immunosuppressive therapy such as intravenous cyclophosphamide or mycophenolate mofetil may be used, depending on organ involvement.
Patients with moderate to severe forms of the disease should be monitored regularly at a specialist clinic. Finally, being a chronic disease, this might carry a psychological impact on patients which should be explored in a holistic manner and support provided when necessary.
Edited by: Dr. Maddie Swannack
Reviewed by: Dr. Thomas Burnell
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