Systemic Lupus Erythematosus (SLE)
Causes and Risk Factors
SLE is a complex autoimmune disease, thought to develop from a genetic predisposition combined with environmental triggers that lead to autoantibody production and systemic inflammation.
Main causes and risk factors: [Ref]
| Category | Specific factors |
|---|---|
| Demographics |
|
| Environmental triggers |
|
| Medications |
The above drugs would cause a reversible “drug-induced lupus” – which is fully reversible upon cessation of the medications |
Known triggering factors for a SLE flare:
- Sunlight exposure
- Infections
- Hormonal changes
Clinical Features and Diagnosis
The full 2019 EULAR/ACR classification criteria for SLE have been taken into account but not reproduced in full.
Instead, the sections below are based on the main classification domains, with important diagnostic and examination-relevant points highlighted where appropriate. Also note that the criteria were primarily intended for research classification.
An initial work-up of suspected SLE would include:
| The “lupus panel” (serology) |
|
| Routine blood test |
|
| Urine studies |
|
Clinical Features
Clinical features of SLE as per body system: [Ref]
| Body system | Clinical features (those in bold are included in the 2019 EULAR/ACR diagnostic criteria) |
|---|---|
| Constitutional |
|
| Mucocutaneous |
One might have noticed that both non-scarring and scarring alopecia are mentioned as a feature of SLE; explanation:
Relationship between SLE and cutaneous lupus: SLE is a multisystem autoimmune condition that may present with systemic and/or cutaneous manifestations. Cutaneous lupus (erythematosus) primarily affects the skin. It may occur independently as a cutaneous-limited condition or alongside systemic diseases (i.e. SLE), depending on the subtype:
|
| Musculoskeletal |
Jaccoud arthropathy (in SLE) vs rheumatoid arthritis
|
| Serosal |
|
| Neuropsychiatric |
|
Serology and Inflammatory Markers
Autoantibodies (serology): [Ref]
| Test | Interpretation | Notes |
|---|---|---|
| Antinuclear antibody (ANA) | The main screening antibody for SLE. It is highly sensitive (~95%) but has poor specificity
A positive result should prompt testing for more specific autoantibodies |
+ve ANA is required as the entry criterion for the 2019 EULAR/ACR classification criteria
-ve ANA makes SLE unlikely, while a +ve ANA is seen in ~5% healthy adults |
| Anti-dsDNA antibodies | A specific but less sensitive marker for SLE | A SLE-specific antibody
+ve anti-dsDNA makes SLE very likely Anti-dsDNA antibodies have a role in monitoring disease activity as it correlates with disease activity (esp in lupus nephritis) |
| Anti-Smith (Sm) antibodies | A specific but less sensitive marker for SLE | A SLE-specific antibody
+ve anti-Smith makes SLE very likely |
| Antiphospholipid antibodies | Includes anticardiolipin, or anti-β2-glycoprotein I, or lupus anticoagulant | Antiphospholipid antibodies are seen in ~20-40% cases of SLE, but they are not considered SLE-specific antibodies
Also see the Antiphospholipid Syndrome (APS) article |
Other autoantibodies, including anti-Ro/SSA, anti-La/SSB and anti-RNP, may also be positive in SLE. However, they are less specific for SLE because they can occur in other connective tissue diseases. They are NOT included as SLE-specific antibodies within the EULAR/ACR classification criteria.
Inflammatory markers: [Ref]
- ↓ Complement levels (C3 and C4)
- ↑ ESR
- Normal CRP
- CRP is typically normal in active SLE
- ↑ CRP in a patient with SLE suggests infection or inflammation unrelated to SLE
Other Investigations
| Investigations | Typical finding in SLE |
|---|---|
| FBC |
|
| Renal investigations |
Renal investigations are important as lupus nephritis can be clinically silent initially. Initial screening:
If renal involvement is present → renal biopsy (see the Nephrotic and Nephritic Syndromes article for more information) |
| Biopsy | Skin biopsy can confirm cutaneous lupus |
Complications
| Body system | Complications |
|---|---|
| Cardiovascular |
Patients are also at significantly higher risk of vascular thrombosis, microvascular kidney disease, and pulmonary hypertension (esp. in those with antiphospholipid bodies) |
| Renal |
See the Nephrotic and Nephritic Syndromes for more information on lupus nephritis |
| Musculoskeletal |
|
| Immune |
This is driven by both use of immunosuppressive therapy and SLE itself (e.g. leukopaenia) |
| Cancer |
|
Management
Conservative / General Management
| Category | Description | Rationale |
|---|---|---|
| Sun protection |
|
UV exposure is a direct trigger for SLE flares |
| Cardiovascular risk reduction |
|
Cardiovascular disease is a major cause of premature death in SLE |
| Infection prevention |
|
SLE itself and the use of immunosuppressive drugs increase risk of infection |
Pharmacological Management
Prior to starting immunosuppressive medications, it is important to screen for the following infections:
- Tuberculosis
- Hepatitis B and C
- HIV
- HPV
Cornerstone therapy: hydroxychloroquine
- Recommended to ALL patients unless contraindicated
- To prevent flares, reduce damage and improve survival
Further therapy is guided by disease severity (simplified):
| Disease severity | Key clinical indications | Specific therapies |
|---|---|---|
| Mild | No organ threat
|
|
| Moderate |
|
|
| Severe |
|
|
Options for refractory disease:
- Belimumab
- Rituximab
- IVIG / plasmapheresis for emergencies
Monitoring
Patients with active SLE should be reviewed at least every 1-3 months (or 6-12 months in those with stable disease), with the following assessment:
- Blood pressure
- Urinalysis and renal function
- Blood tests
- Anti-dsDNA antibodies
- Complement levels (C3/C4)
- FBC, CRP, LFTs
The following should be assessed at least once a year:
- Vitamin D levels
- Routine cancer screening (esp. cervical screening) – as per national guidelines
- Cardiovascular risk factors
- Immunoglobulin levels
Drug-Induced Lupus
Typical presentation: [Ref]
- Musculoskeletal and constitutional symptoms are common
- Serositis (esp. pleuritis) is a hallmark
- Mucocutaneous manifestation is uncommon
The key feature distinguishing drug-induced lupus from SLE is that it is usually reversible: clinical symptoms typically resolve within weeks to months after the causative medication is discontinued.
Typical serology: [Ref]
- +ve ANA
- +ve Anti-histone antibodies
- -ve Anti-dsDNA and anti-Sm antibodies