Systemic Lupus Erythematosus

Systemic lupus erythematosus (“lupus”) is an inflammatory autoimmune connective tissue disease. It is “systemic” because it affects multiple organs and systems and “erythematosus” refers to the typical red malar rash that occurs across the face. It presents with varying and non-specific symptoms. It is more common in women and Asians and usually presents in young to middle aged adults but can present later in life.

It often takes a relapsing-remitting course, with flares and periods where symptoms are improved. The result of chronic inflammation means patients with lupus often have shortened life expectancy. Cardiovascular disease and infection are leading causes of death.

 

Pathophysiology

SLE is characterised by anti-nuclear antibodies. These are antibodies to proteins within the persons own cell nucleus. This causes the immune system to target theses proteins. When the immune system is activated by these antibodies targeting proteins in the cell nucleus it generates an inflammatory response. Inflammation in the body leads to the symptoms of the condition. Usually, inflammation is a helpful response when fighting off an infection however it creates numerous problems when it occurs chronically and against the tissues of the body.

 

Presentation

SLE presents with non-specific symptoms:

  • Fatigue
  • Weight loss
  • Arthralgia (joint pain) and non-erosive arthritis
  • Myalgia (muscle pain)
  • Fever
  • Photosensitive malar rash. This is a “butterfly” shaped rash across the nose and cheek bones that gets worse with sunlight.
  • Lymphadenopathy and splenomegaly
  • Shortness of breath
  • Pleuritic chest pain
  • Mouth ulcers
  • Hair loss
  • Raynaud’s phenomenon

Investigations

  • Autoantibodies (see below)
  • Full blood count (normocytic anaemia of chronic disease)
  • C3 and C4 levels (decreased in active disease)
  • CRP and ESR (raised with active inflammation)
  • Immunoglobulins (raised due to activation of B cells with inflammation)
  • Urinalysis and urine protein:creatinine ratio for proteinuria in lupus nephritis
  • Renal biopsy can be used to investigate for lupus nephritis

 

Autoantibodies

SLE is associated with anti-nuclear antibodies (ANA). These are antibodies against normal proteins in the cell nucleus. Around 85% of patients with SLE will be positive for ANA. Performing an ANA blood test is the initial step in testing for SLE in someone with symptoms of the condition. Antinuclear antibodies can be positive in healthy patients and patients with other autoimmune conditions (e.g. autoimmune hepatitis). Therefore, a positive result needs to be interpreted in the context of their symptoms.

Anti-double stranded DNA (anti-dsDNA) is specific to SLE, meaning patients without the condition are very unlikely to have these antibodies. Around 70% of patients with SLE will have anti-dsDNA antibodies. The levels vary with disease activity, so they are useful in monitoring disease activity and response to treatment.

If you send a test for antibodies to extractable nuclear antigens (anti-ENA antibodies) the lab will check for antibodies to specific proteins in the cell nucleus. These are all types of antinuclear antibody:

  • Anti-Smith (highly specific to SLE but not very sensitive)
  • Anti-centromere antibodies (most associated with limited cutaneous systemic sclerosis)
  • Anti-Ro and Anti-La (most associated with Sjogren’s syndrome)
  • Anti-Scl-70 (most associated with systemic sclerosis)
  • Anti-Jo-1 (most associated with dermatomyositis)

 

Antiphospholipid antibodies and antiphospholipid syndrome can occur secondary to SLE. They can occur in up to 40% of patients with SLE and are associated with an increased risk of venous thromboembolism.

 

Diagnosis

You can use the SLICC Criteria or the ACR Criteria for establishing a diagnosis. This involves confirming the presence of antinuclear antibodies and establishing a certain number of clinical features suggestive of SLE.

 

Complications

Systemic lupus erythematosus affects many of the organs in the body. These effects are related to chronic inflammation.

Cardiovascular disease is a leading cause of death. Chronic inflammation in the blood vessels leads to hypertension and coronary artery disease.

Infection is more common in patients with SLE as part of the disease process and secondary to immunosuppressants.

Anaemia of chronic disease is common in SLE. It affects the bone marrow causing a chronic normocytic anaemia. Patients can also get leucopenia (low white cells), neutropenia (low neutrophils) and thrombocytopenia (low platelets).

Pericarditis is inflammation in the fluid filled sac around the heart. It causes sharp chest pain worse on lying flat.

Pleuritis is inflammation of the pleural lining of the lungs. This is also called pleurisy. It causes typical symptoms of sharp chest pain on inspiration.

Interstitial lung disease can be caused by inflammation in the lung tissue. This leads to pulmonary fibrosis.

Lupus nephritis occurs due to inflammation in the kidney. It can progress to end-stage renal failure. It is assessed urine protein:creatinine ratio and renal biopsy. The renal biopsy is often repeated to assess response to treatment.

Neuropsychiatric SLE is caused by inflammation in the central nervous system. It can present with optic neuritis (inflammation of the optic nerve), transverse myelitis (inflammation of the spinal cord) or psychosis.

Recurrent miscarriage is common in systemic lupus erythematosus. It is associated with other pregnancy complications such as intrauterine growth restriction, pre-eclampsia and pre-term labour.

Venous thromboembolism is particularly associated with antiphospholipid syndrome occurring secondary to SLE.

 

Treatment

As with most autoimmune conditions anti-inflammatory medication and immunosuppression is the mainstay of treatment. There is no cure and the aim is to reduce symptoms and complications. It will be guided by a rheumatology specialist. Treatment is usually titrated upwards to find the minimal medication with the least side effects required to control the symptoms.

First line treatments are:

  • NSAIDs
  • Steroids (prednisolone)
  • Hydroxychloroquine (first line for mild SLE)
  • Suncream and sun avoidance for the photosensitive the malar rash

 

Other commonly used immunosuppressants in resistant or more severe lupus:

  • Methotrexate
  • Mycophenolate mofetil
  • Azathioprine
  • Tacrolimus
  • Leflunomide
  • Ciclosporin

 

Biological therapies are considered for patients with severe disease or where patients have not responded to other treatments. The main options in SLE are:

  • Rituximab is a monoclonal antibody that targets the CD20 protein on the surface of B cells
  • Belimumab is a monoclonal antibody that targets B-cell activating factor

 

Last updated April 2019
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