Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with the potential to affect the skin, joints, kidneys, lungs, nervous system and serous membranes. It is characterised by the production of a number of antinuclear antibodies.

Epidemiology

The prevalence of SLE varies worldwide with higher numbers found among black, Asian and Hispanic people, and tends to be worse in these ethnic groups.¹ In women, prevalence rates vary from 164 (white) to 406 (African American) per 100,000.² The female to male ratio varies with age but in women of childbearing age the ratio is 11:1, thus the increased frequency of SLE among women has been attributed in part to an effect of oestrogens.

Aetiology

The aetiology of SLE is not completely understood but it is known to be multifactorial. Genetic factors play a role – as seen by the high concordance rate of SLE in monozygotic twins (14-57%).³ Hormonal factors such as oestradiol and progesterone are clearly indicated as SLE is most common in women of child-bearing age. Also the use of oestrogen-containing contraceptives is associated with a 50% increase in risk of developing SLE.⁴

Numerous immune defects have been described in SLE:

• An increase in circulating plasma cells and of a subset of memory B-cells is associated with disease activity in SLE⁵

• A decrease in cytotoxic T-cells and in functions of suppressor T-cells⁶

• Impaired generation of polyclonal T-cell cytolytic activity⁷

• An increase in helper (CD4+) T-cells and helper function by both CD4+ and CD8+ T-cells⁸

• Polyclonal activation of B-cells and abnormal B-cell receptor signalling⁹

• Defects in B-cell tolerance, perhaps related to defects in apoptosis and/or complement deficiency, lead to prolonged lives of B-cells⁹

• Environmental factors such as UV light, silica dust and viruses such as Epstein-Barr virus (EBV)¹⁰ have all been linked to the aetiology of SLE.

Clinical presentation

Constitutional symptoms such as fatigue, fever, weight loss and myalgia occur in most patients at some point during their illness. 

Musculoskeletal manifestations

At some point, over 90% of patients with SLE have polyarthralgias or polyarthritis, typically with a migrating and symmetrical pattern.¹¹

Mucocutaneous

Butterfly rash, discoid lesions, alopecia, Raynaud’s phenomenon.

Renal involvement

Clinically apparent in up to 50% of patients, the remainder most likely have subclinical involvement. 

Pulmonary

Pleural effusions, pneumonitis, interstitial lung disease, pulmonary hypertension, alveolar haemorrhage can all occur in patients with SLE. Pulmonary function tests (PFTs) can be significantly abnormal, with restrictive abnormalities being the most prominent feature.

Cardiovascular

Increased risk of coronary artery disease due to premature atherosclerosis.

Neurological

Cognitive defects, delirium, psychosis, seizures, headache.

Ophthalmological

Keratoconjuctivitis sicca.

Diagnosis

The American College of Rheumatology (ACR) has developed criteria to classify patients with a diagnosis of SLE. Four of the 11 criteria must be met.

Laboratory tests that are useful in diagnosing SLE and/or out-ruling differentials include:

• Full blood count, urea and electrolytes, creatine kinase

• Erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP)

• Urinalysis

• Antinuclear antibodies (ANA), antiphospholipid antibodies, antibodies to double-stranded DNA (dsDNA), anti-Smith (Sm) antibodies

• Serum complement levels C3 and C4. 

Autoantibodies

ANA is the best diagnostic test for SLE and should be performed whenever SLE is suspected.¹² The ANA is positive in significant titre (usually 1:160 or higher) in virtually all patients with SLE. There is a group of patients with fibromyalgia-like manifestations and a positive ANA. These patients differ clinically from patients with definite SLE and generally do not merit the diagnosis of SLE.¹³

Active SLE (particularly lupus nephritis) is often preceded by a rise in IgG anti-double-stranded DNA titers, a fall in complement levels (especially CH50, C3 and C4), and an elevation in complement split and activation products. Persistently low serum levels of complement C1q are associated with continued activity of proliferative glomerulonephritis.

Imaging

Diagnostic imaging may be valuable but is not routinely obtained unless indicated by the presence of symptoms, clinical findings or laboratory abnormalities, eg:

• Plain radiographs of involved joints

• Renal ultrasonography to assess kidney size/scarring

• Chest radiography

• Echocardiography 

• Computed tomography (CT), eg. for suspected pancreatitis, interstitial lung disease

• Magnetic resonance imaging (MRI), eg. for focal neurologic deficits or cognitive dysfunction

• Biopsy: histological diagnosis of nephritis.

Treatment

Disease activity and severity determines treatment, ie. extent and degree of organ dysfunction. This is determined by the history, clinical examination, functional and serological tests. General treatment measures such as sun protection – strict use of sun block (both UVA and UVB radiation), diet and nutrition, exercise, smoking cessation and immunisations are encouraged.

Treatment of specific organ dysfunction

NSAIDs are effective in the treatment of musculoskeletal complaints, fever, headache and mild serositis. Individual joints may benefit from intra-articular injection of glucocorticoid; severe polyarthritis flare-ups may be treated with intravenous ‘pulse therapy’ consisting of 1,000mg of methylprednisolone daily for three days.¹² The use of prednisone for maintenance therapy should be limited to 10mg or less daily. Skin manifestations can be treated with topical NSAIDs, glucocorticoids or an antimalarial such as hydroxychloroquine (this requires ophthalmological monitoring).¹³ Systemic glucocorticoids can be used until a steroid-sparing agent can take effect. Doses of 5-15mg of prednisolone are used for non-organ-threatening disease, or 1-2mg/kg/day of prednisolone for organ-threatening disease. There are a variety of steroid-sparing immunosuppressive agents, the choice of which depends on the clinical manifestations and severity. These include methotrexate, azathioprine, mycophenelate mofetil, cyclophosphamide and rituximab.

In pregnancy

Fertility rates are the same as for the general population. However, pregnancy with SLE can be associated with complications: exacerbation of the disease, foetal loss, intrauterine growth retardation, pre-term delivery, neonatal lupus. Ideally patients should be in remission for at least six months prior to pregnancy. Exacerbations may vary from a range of 7-33% in women who were quiescent during the six months prior to pregnancy to a range of 61-67% in those who have active disease at conception.¹⁴ Pre-eclampsia complicates pregnancy in approximately 13% of patients with SLE, which can increase to 66% in patients with renal disease.¹⁵ Thus increased monitoring during pregnancy is needed (creatinine, urine protein: creatinine ratio, anticardiolipin antibodies, complement – CH50/C3/C4, anti-dsDNA antibodies).

Medications with a high risk of causing birth defects are contraindicated during pregnancy. These include mycophenelate, cyclophosphamide, methotrexate and warfarin. Azathioprine and glucocorticoids can be used safely.

Prognosis

SLE has a varied clinical course – usually relapsing and remitting. It carries a five-year survival rate of 90%, with prognosis ultimately determined by organ involvement.¹⁶ Although survival rates have improved, over one-half of patients with SLE have permanent end-organ damage. The clinical manifestations of SLE evolve over time. Thus, a patient who presents with skin and joint disease remains at risk for renal disease even after having SLE for many years. Continued monitoring, even when the disease appears to be clinically inactive, is essential.

As SLE is a chronic disease, patients’ understanding of their own responsibility in managing their condition is imperative – that is compliance with lifestyle modifications, medications and doctor’s appointments. An ongoing partnership between the general practitioner and the rheumatologist is essential in the long-term management of patients with SLE.  

References available on request