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A History of Lupus

Although Lupus is a twentieth century disease, initial descriptions probably go as far back as Hippocrates (~400BC) and Paracelcus (~1500AD), but the term 'Lupus Erythemateux' was coined in the 1850s by the Parisian physicians Cazenave and Clausit. They made the first description of the facial rash and skin ulceration resembling 'a bite from a wolf', from which some think lupus (Latin for wolf) derives its name. At about that time in Vienna, the dermatologist Ferdinand von Hebra published the first picture of the butterfly shaped facial rash that may also be the basis of the Lupus name. The ancient French word for mask such as those worn at masked balls is reported to be 'luoue'. Whatever the derivation of the name this butterfly shape has been successfully developed for the emblem of LUPUS UK today.

The first mention of lupus as we know it, was by Sir William Osler when in 1903, he described 20 young ladies with skin rashes and chest pain resulting from inflammation of the lining of the lung (pleurisy) or heart (pericarditis). In addition, these patients also had kidney disease, strokes and brain involvement severe enough to be fatal so that 18 had died within two years from presentation. The disease we recognise now is by no means so severe so that the prognosis has improved significantly.

The reasons for this change are widespread. Drug therapy has improved over this time (Table 1), particularly the use of antibiotics from the 1930s, which prevented infections that were the most common cause of death until that time. Equally, steroids introduced by Thorn in the late 1940s were useful in lupus patients and others with inflammatory joint diseases.

Table 1. Factors helping improve outcome in Lupus sufferers

More specific drugs for the treatment of SLE have been introduced such as the anti-malarial drug quinine (a forerunner of hydroxychloroquine) that helped improve the skin and joint symptoms in so many patients. Cyclophosphamide, which was derived chemically in the 1960s from mustard gas (used in World War 1), has saved patients lives preventing mortality from kidney failure and disability by stopping patients requiring dialysis.

However, part of the improvement is in diagnosis because lupus is not so severe as was first suspected. Blood tests for SLE including the LE cell by Hargraves in 1948, and the detection of anti-nuclear antibodies (ANA) by Friou in the USA and Holborow in the UK in the late 1950s have identified cases that would previously not have sought attention, because these patients are less likely to have the fatal combination of disease features.

Clinical and scientific research has shown that lupus patients have an immune system that seems to be disordered. As well as making antibodies against bacteria and viruses as does everyone else, lupus patients also make antibodies against their own tissues. These antinuclear antibodies or 'ANA' are now known to be the cause of some disease features. Prof. Isenberg has shown that antibodies against DNA probably play a significant role in kidney disease. Prof. Hughes has been instrumental in showing that antibodies against cardiolipin are responsible for the 'sticky blood' that makes lupus patients more likely to have blood clots, and Prof. Salmon from New York has shown that these are most likely to be responsible for the early miscarriages that lupus patients can get when pregnant.

While many would like to avoid animal based research, the mouse models of lupus have identified that there is unlikely to be just one cause for lupus. However the clinical similarities have also allowed drugs to be tested, and have assisted in identifying the way the dysfunctional immune system arises and produces damage. Not all drugs have been helpful in the animal models, but some like Cyclophosphamide, Azathioprine, Methotrexate and Mycophenylate have subsequently come into use for patients in the clinic. In addition, mouse models have shown that there are genetic factors that predispose to development of lupus features. One example is the single gene found more commonly in some mice that develop kidney disease that has a similarly abnormal gene in affected patients. This raises the possibility of targeting therapies in the future to certain disease features which by being more specific will hopefully have less side effects.

In the meantime, the newer treatments that are now coming through for lupus, have been developed from research in the 1980s and 1990s. In contrast to the drugs that down regulate the immune system in a relatively non-specific way and can therefore have many side effects, one new drug, called Rituximab, has the potential to be useful because it targets an abnormality restricted to lupus. Rituximab is specifically designed to kill the B-cells that make antibodies, and while this is not yet directed against those making the lupus-specific ANA, this is a significant advance over drugs like Cyclophosphamide. In addition, Rituximab has been used for ten years for patients with different diseases of B-cells in patients with lymphomas, so it is known to have few side effects. Initial studies by Prof. Isenberg have been successful in lupus patients, improving the SLE disease scores significantly. As predicted Rituximab treatment is followed by removal of some of the ANA from the circulation of patients. However, insufficient studies have been done to allow NICE and the SMC licensing bodies to examine its potential for SLE patients, but in the fullness of time it has the potential to be invaluable in its own right. In addition, newer drugs could be developed from Rituximab that could be yet more exclusive for lupus patients.

Henry Ford is renowned for his description of history as being "more or less bunk". However, Thomas Carlyle showed a greater understanding when he said, "What is all knowledge but recorded experience and a product of history". Lupus is a complex and difficult disease to live and work with but in this context this statement may be more appropriate and reminds us exactly how far patients have come since lupus was first identified and provides an incentive for us all to continue this process.

We are extremely grateful to Dr Max Field for producing this article.

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