Systemic Lupus Erythematosus Health Article

Summary

Systemic lupus erythematosus is an autoimmune connective-tissue disorder with a wide range of clinical features, which predominantly affects women, especially from certain ethnic groups. Diagnosis is based on clinical assessment supported by investigations, including the finding of autoantibodies. Treatments range from antimalarial agents to corticosteroids and immunosuppressive agents. This Seminar draws attention to advances in the epidemiology, genetics, cardiovascular risks, lupus nephritis, CNS disease, the antiphospholipid syndrome, assessment of disease activity and damage, and pregnancy related and quality of life issues. New therapeutic approaches, such as biological agents and mycophenolate mofetil, will also be discussed.

Systemic lupus erythematosus is a multisystem, autoimmune, connective-tissue disorder with a broad range of clinical presentations. There is a peak age of onset in young women between their late teens and early 40s and women to men ratio of 9:1. Ethnic groups, such as those with African or Asian ancestry, are at greatest risk of developing the disorder, which can be more severe than in white patients. This disorder is a chronic illness that can be life threatening when major organs are affected, but more commonly results in chronic debilitating ill health. Factors such as sunlight and drugs could trigger the disorder, but no one cause has been identified and systemic lupus erythematosus has a complex genetic basis.

Epidemiology

The most striking studies of the epidemiology of lupus examined the development of autoantibodies years before the onset of clinical features of lupus and antiphospholipid syndrome. ^2,3 The investigators used the US Department of Defense serum repository, which contains about 30 million samples from service personnel taken at baseline and on average alternate years. They identified 130 individuals with systemic lupus erythematosus and reported that 72 developed autoantibodies to DNA on average 2·7 years and up to 9·3 years before diagnosis. The researchers also described the frequency of other autoantibodies, such as antinuclear, antiRo, antiLa, antiSm, antiRNP, ² and antiphospholipid antibodies ³ before the development of clinical disease. Antinuclear antibodies arose earlier than antiDNA antibodies and several of these patients had a rise in the antiDNA titres just before diagnosis. AntiSm and antiRNP antibodies appeared shortly before diagnosis, suggesting a peak of autoimmunity, resulting in clinical illness. The data also suggest that autoantibodies alone do not necessarily result in clinical disease and that other factors, possibly genetic and environmental, could be important. We might in the future be able to predict the onset of clinical features of lupus by clinical assessment and monitoring of the development of various lupus autoantibodies.

The frequency of lupus could be increasing because milder forms of the disease are being recognised. For example, Uramoto and co-workers ⁴ examined the incidence of the disorder in Rochester, MN, USA, and noted that it had more than tripled from 1·51 per 100,000 in the 1950–79 cohort to 5·56 per 100,000 between 1980 and 1992. In this study, although survival in the later cohort was worse than in the general population, there were clear improvements in survival rates over the 1950–79 cohort. ⁴ Trager and colleagues ⁵ suggested that patients with lupus nowadays could have a milder form of the disease and a better chance of survival than patients described several decades ago, probably because of an earlier diagnosis of milder disease. However, despite these improvements in survival, fatigue and other quality of life measures might not have improved.

A review of 32 studies has summarised the incidence and prevalence of systemic lupus erythematosus in several countries and documented the increased disease burden, especially in non-white populations. ⁶ Although there was wide variation in the prevalence of lupus worldwide, the highest prevalences were reported in Italy, Spain, Martinique, and the UK Afro-Caribbean population.

This disease is more common in women with African ancestry but is thought to be rare in west Africa, suggesting that environmental factors can contribute to the development of lupus in women whose ancestors migrated from that region. However, when women who had recently migrated from west Africa were examined, the prevalence of lupus was similar to that seen in Afro-Caribbean women but was much lower in European women. ⁷ These data suggest that systemic lupus erythematosus is fairly common in west Africa and that there is a genetic basis for the higher risk of lupus in these women.