Systemic Lupus Erythematosus - Outcome and Origins
David Isenberg
United Kingdom
Systemic lupus erythematosus (SLE) is a complex autoimmune rheumatic disease whose outlook has improved significantly from the 1950’s when 50%, 4 year survival was noted, to the present when around 80%, 15 year survival is generally recorded. However significant numbers of patients continue to die early from lupus and its morbidity is also significant in some patients. In a cohort of 442 patients with lupus followed up in the Centre for Rheumatology at University College London between 1978 and 2005, 65 patients died with an average age of 47.1 years. The major causes of death were infection, cancer and atherosclerosis. We have recorded deaths in several young teenagers and others in their early twenties. Thus, although the outlook for patients with lupus is much improved and newer, principally biological agents, now offer the prospect of far more focussed and appropriate treatment for this disease, there is a continuing need to understand rather better its precise aetiopathogenesis.
Many patients with lupus are interested to know the cause of the condition. I have found a useful analogy over the years to be a comparison with a game of cards. The name of the game is ‘health’. The cards are not however marked the Ace of diamonds, the 2 of Clubs etc, but rather one card is marked female sex, another male sex, another HLA A3, or B7, or DR3, another is marked exposure to Epstein-Barr virus and yet another high fat diet etc. Imagine that the cards are shuffled and that the hand which is dealt consists of all of those factors known to be associated with lupus it will become clear that the disease is not due to a single cause but rather to a conspiracy of genetic, hormonal and external factors which interact to cause the disease. The analogy can be extended by using the suits of cards to represent groups of factors. Thus hearts may be used to represent sex which emphasises the importance of sex hormones likely to be significantly involved given that the ratio of females to males with lupus is approximately 10 to 1. Clubs can be used to represent the genetic factors evident from the simple observation of concordance amongst monozygotic twins for lupus (25%) compared to dizygotic twins (2%). Spades may be used to represent the critical triggering factors such as ultraviolet radiation and infection. The Diamond shape (much beloved by the immunologists in their diagrams!) can be used to represent the critical antibodies which are clearly an important part of the aetiopathogenesis. We are truly on the threshold of some exciting therapeutic developments in lupus and it remains very satisfying that these developments are based upon a much better understanding of the precise cause of SLE.