We searched PubMed (January, 2009, to September, 2013) and Summon Search (January, 2009, to September, 2013) databases with the terms “systemic lupus erythematosus” and “lupus” in combination with the terms “epidemiology”, “classification”, “cardiovascular risk”, “lupus nephritis”, “CNS lupus”, “antiphospholipid syndrome”, “pregnancy”, “pathogenesis”, “presentation”, and “management”, with no language restrictions. We also searched the references of articles identified by this strategy and
SeminarSystemic lupus erythematosus
Introduction
Systemic lupus erythematosus is a challenging disease to assess and manage. The progress in our understanding of its aetiopathogenesis is notable. In this Seminar we provide an update on its clinical presentations and conventional management. We also review some of the many studies published in the past decade that used biological drugs, the development of which has been based on improved understanding of the causes of this disease. However, success in treatment of systemic lupus erythematosus with biological strategies is less impressive than that for rheumatoid arthritis. This difference is attributable to the complexity of the disorder and the likely diverse mechanisms that contribute to its clinical expression. This extra challenge makes the work of scientists, who seek to understand the disease better, and clinicians treating patients with lupus, more demanding.
Section snippets
Epidemiology
The incidence and prevalence of systemic lupus erythematosus seems to be increasing, probably because of both the identification of milder cases and improved survival. In 2007, a review outlined the geographical variability in disease incidence and prevalence. In the US population, the all race incidence was 5·1 per 100 000 per year and the prevalence was 52·2 per 100 000, with comparative figures of 3·8 and 26·2 in the UK, and 2·9 and 28·4 in Japan, respectively.1 These figures are
Revised classification criteria
Since the publication of the last Seminar on systemic lupus erythematosus in The Lancet in 2007,1 a major development has been the publication of the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria in 2012.8 This classification attempted to rationalise the clinical criteria and provided a modest expansion in recognised laboratory abnormalities (panel 1). Biopsy-proven nephritis compatible with systemic lupus erythematosus in the presence of antinuclear or
Pathogenesis
Systemic lupus erythematosus is a multifactorial disease with evidence of genetic susceptibility, environmental effects, and disturbances in both innate and adaptive immunity manifest by disturbances in apoptotic cell clearance, cytokines, B-cell immunity, and T-cell signalling. Although a detailed review of the pathogenesis of lupus has been published,9 we briefly summarise some noteworthy developments.
Deficiencies in components of the complement cascade are well known to predispose to the
Environmental and hormonal factors
Ultraviolet light is the most well described environmental trigger of systemic lupus erythematosus. Both ultraviolet A2 and ultraviolet B exposure, including through cosmetic sun tanning, can exacerbate skin disease in patients with the disorder.17 However, the consequent avoidance of sunlight can lead to vitamin D deficiency, which is inversely related to disease activity.18 Thus periodic assessment and replacement is needed for patients deficient of vitamin D.
Pathologically, the effect of
Cardiovascular risk
The recognition that atherosclerosis is closely linked with the immune system is reflected in the well described association of many chronic inflammatory disorders with a predilection for enhanced atherogenesis. Systemic lupus erythematosus is no exception.23, 24 Prevalence varies according to the study population, with estimates ranging from 6% to 10%.25 Most striking, however, is that in women aged 35–44 years with lupus, the risk of myocardial infarction is increased 50 times, compared with
Lupus nephritis
Both the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) groups have published revised guidelines for the assessment and management of lupus nephritis. The previous ACR guidelines, published in 1999, recommended use of glucocorticosteroids and cyclophosphamide as induction therapy for proliferative lupus nephritis. Mycophenolate mofetil was not widely available at that time. Since then several trials have shown non-inferiority of this drug to
CNS lupus
The pathogenesis of neuropsychiatric lupus is multifactorial, probably varies between individuals, and involves autoantibodies, immune complexes, and cytokines.39 20 autoantibodies detected in the serum or cerebrospinal fluid of patients with neuropsychiatric lupus have been reported.40 They were categorised into brain-specific (n=11) and systemic (nine) autoantibodies. Brain-specific autoantibodies included those binding neuronal, brain reactive (BRAA), N-methyl-d-aspartate receptor (NMDA),
Antiphospholipid syndrome
Antiphospholipid syndrome can be primary or secondary. It is characterised by recurrent venous or arterial thrombosis or pregnancy morbidity, and persistent presence of antiphospholipid antibodies. Although 30–40% of patients with lupus have antiphospholipid antibodies, the antiphospolipid syndrome complicates only 10–15% of cases of systemic lupus erythematosus. About 40 antiphospholipid antibodies have been described so far, but only three are used for the confirmation of diagnosis.41 Triple
Pregnancy
Previously, women with lupus, especially lupus nephritis, might have been advised against contemplating pregnancy. Lupus does not affect fertility, but contraception and pregnancy planning have great importance in the routine care of patients with lupus. Many pregnant women with active lupus will develop complications such as preterm birth and pre-eclampsia. A third of lupus pregnancies will result in a caesarean section.52 A major factor linked to these complications is increased lupus
New treatments
The table summarises the general approach to the treatment of systemic lupus erythematosus, and panel 3 the drugs commonly used. We focus on new developments in lupus treatment.
Increasingly, patients with lupus who do not respond to conventional immunosuppressive drugs are considered for targeted biological therapies aimed at cytokines, B and T lymphocytes, and B-cell activating factors. Blockade of B lymphocytes is of particular interest since lupus autoantibodies play an important part in the
Coping with the disease and quality of life
Non-pharmacological management of systemic lupus erythematosus is also important. The psychological effects of lupus include depression, fatigue, psychological distress, and difficulties with emotion-oriented coping.88 A study of 120 patients with this disorder showed that treatment of depression, and consideration of stress and insomnia, reduced fatigue.88 Of 154 Australian and UK patients with lupus, 26% were clinically depressed.89 Depression and insufficient suitable coping mechanisms and
Conclusion
Understanding of the pathogenesis of lupus is clearly growing. Encouragingly, this knowledge is being applied in clinical practice with improvements in classification, a better appreciation of lupus features and complications, and the development of new drugs. There is better understanding of the importance of other aspects of lupus management such as quality of life, mental health, prevention of complications such as atherosclerosis, and pregnancy morbidity, and they play an important part in
Search strategy and selection criteria
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