Minocycline-induced Lupus Syndrome

by Dr Neil McHugh

Consultant Senior Lecturer in Rheumatology. Royal National Hospital for Rheumatic Diseases, Bath.

(First printed in Lupus UK News & Views, Spring 2000 Number 60)

Minocycline is an antibiotic used most commonly for the treatment of young people with troublesome acne. Minocycline is a convenient treatment for acne as it needs only to be taken once a day and it is an effective agent because it can penetrate well to the areas where it acts. In the U.K. there were an estimated 800,000 prescriptions for minocycline in 1993 and 188,000 individuals were started on minocycline for acne in 1995. However use dropped to about 70% of previous levels following a report from Leeds in 1996 of the occurrence of lupus and hepatitis in some individuals with acne on minocycline. About 50 cases of lupus associated with the use of minocycline have been reported in the literature and of course there will be many times that number that go unreported. Although the incidence of lupus in minocycline users still seems to be uncommon, it is now more widely recognised and consequently should be diagnosed more promptly.

With the help of Lupus UK (and more specifically funding from the Taunton-based Lupus UK Joni Andrews memorial Fund), we have been interested in studying minocycline-induced lupus syndrome more carefully in bath. We have been able to document a number of cases ourselves and retrieve blood samples from those that have been afflicted. A common pattern of presentation of the syndrome is the onset of swollen painful joints and in some cases a skin rash. Other symptoms may include a fever, sore throat, flu-like symptoms, headache and depression.

In a minority of cases, blood tests may indicate accompanying hepatitis. One feature of all cases is the long length of use minocycline before the lupus symptoms develop, often two to three years if not longer. Fortunately, as with other drug-induced lupus syndromes, the symptoms fully resolve once the minocycline had been stopped.

You will be aware that SLE is characterised by the presence of autoantibodies in the circulation. Instead of normal antibodies that hep ward off infection, autoantibodies are directed at one's own body particles as a result of abnormal regulation of the immune system. Anti-DNA antibodies are the best known autoantibodies that are present in most cases of SLE and help with the diagnosis, although other groups of antibodies that are specific for particular forms of lupus may also be present (e.g. anticardiolipin antibodies). the most striking finding in our study was the presence of another group of autoantibodies against certain proteins found in white cells called pANCA (antineutrophil cytoplasmic antigen). These p-ANCA antibodies were present in all cases providing the blood sample was taken from the time of exposure to minocycline or shortly after. Furthermore, the level of these antibodies declined with recovery from the syndrome and were not present in a control group of patients with acne not taking minocycline. p-ANCA antibodies are found in a number of other conditions and may be present in a small number of patients with SLE where there is no obvious trigger for the illness. Their presence in cases of minocycline-induced lupus not only serves as a useful marker for the illness, but offers an insight into how autoantibodies may occur when a particular drug or trigger or lupus is incriminated.

The other aspect we have been interested in is why only certain individuals develop lupus while on minocycline. We have been able to start studying the genetic factors that put those individuals at risk. So far we have found that there are associations with certain genes that regulate immunity called HLA antigens. All individuals with lupus on minocycline had a particular pattern of HLA antigens. It may be possible that there are even closer associations with linked genes that we are interested in studying further, as this may shed light on the type of genes likely to be involved in SLE in general.

There is no doubt that minocycline is a useful agent for treating acne that can be a worrying condition especially in young people. Its use will now be tempered with the knowledge that certain side effects including lupus can occur with prolonged use, and appropriate monitoring is required. the question whether the tetracycline antibiotics including minocycline as a group are safe studies to go by, and at least alternative antibiotics are generally available. In cases of SLE where no trigger for the illness is immediately apparent, there remains the hope that lessons learnt from reversible drug-induced lupus syndromes will mean better understanding of SLE and ways of tacking treatment.