LUPUS - Diagnosis, Treatment, the Future
Dr Bridget Griffiths, Consultant Rheumatologist, Freeman Hospital, Newcastle-upon-Tyne
The following account is a summary by Dr Griffiths of a recent talk given to the North East Lupus Group on the diagnosis, treatment and future developments concerning SLE.
Introduction
SLE is one of the connective tissue disorders. Other such conditions include systemic sclerosis (scleroderma), dermatomyositis, polymyositis and primary Sjogren's syndrome. These conditions are known as autoimmune diseases. This term means that the body produces proteins called 'antibodies' that can attack the body's own tissues and cause inflammation. Lupus is a multi-system disorder. The disease can involve any organ within the body. In certain patients only one organ e.g. the joints or skin will be affected but in some individuals there may be involvement of multiple organs e.g. the skin, joints and kidneys. It is important to remember that every patient's lupus is different. Each patient will therefore experience a different set of symptoms. Some patients will have very mild disease and unfortunately a few patients will have very severe disease that may be life-threatening.
SLE is more common in women than men with a ratio of approximately 8:1. In women it often begins in the child bearing years i.e. late teens, twenties and thirties. The prevalence (the frequency of the condition) varies considerably according to a patient's racial origin. Lupus is particularly common in women of Afro-Caribbean origin (approximately 1 in 400) compared with individuals of northern European origin (approximately 1 in 2000). In individuals of Asian origin (Indian, Pakistani or Chinese) the prevalence is approximately 1 in 900. We are still unsure why one individual should develop lupus compared with another. We believe that the causes are multifactorial, with a combination of a genetic predisposition and environmental factors. The genetic cause is not just due to one gene, as is the case with some diseases e.g. cystic fibrosis, but a combination of genes. Family studies are underway to explore this further.
Diagnosis
To make a diagnosis of lupus we look for a pattern of symptoms, signs and blood results. As guidance we use the American College of Rheumatology (ACR) classification criteria. These were published in 1982 and modified in 1997. They are summarised in table 1. To classify a patient as having SLE, an individual must have four of the listed features. These do not all have to be present at one time but can be cumulative. For example an individual may develop a photosensitive rash (rash that develops after exposure to sunlight) at the age of nine, an inflammatory arthritis (joint pains associated with pain, swelling, stiffness and tenderness) affecting the small joints of the hand at the age of eighteen and then a malar rash (butterfly rash) at the age of nineteen. When she attends her GP or the rheumatologist, the blood tests show a positive ANA (antinuclear antibody) and raised anti-dsDNA antibody levels. In this example it would be fairly easy to diagnose SLE but often it is more difficult. Patients may initially develop very non-specific symptoms such as fatigue, weight loss and sweats. It may take several years for the more specific symptoms to appear and for the diagnosis to be made.
Assessment
When assessing the effectiveness of a patient's therapy we evaluate three areas: disease activity, damage and quality of life. Disease activity will vary from time to time. This can be captured in disease activity questionnaires and some blood tests. Disease activity is potentially reversible. We therefore need to identify if a patient is having a flare and increase treatment if necessary. Unfortunately, we are sometimes unable to switch off disease activity. If this is persistent then the patient may develop some damage to an organ. Although this can not be reversed we may be able to prescribe symptomatic treatment. It is also very important to assess the impact of a patient's lupus on their quality of life. Medication may help but sometimes it may be more appropriate to use relaxation techniques, coping strategies and pace activities. Overall, we want to try and help the patient to lead as normal a life as possible. We try to offer a holistic approach. When a patient attends our connective tissue clinic we will always test the urine to see if there is any blood or protein. This is a very sensitive way of detecting early inflammation affecting the kidneys. It also helps us to monitor a patient's existing kidney disease. We will also always check the blood pressure. It is important that a lupus patient has good blood pressure control, particularly if they have kidney involvement. Well maintained blood pressure helps the blood supply to the kidneys. We will run through a check list of possible symptoms that can affect a patient with lupus and establish if these are new, getting better or getting worse, so that we can tailor treatment accordingly. We will then tend to examine affected parts of the body e.g. the skin, joints or lungs. This again helps us to determine the appropriate treatment. At most clinic visits we will perform blood tests to check for inflammation and other markers of disease activity e.g. complement levels and anti-dsDNA antibody levels. We try to detect new symptoms/ organ involvement as early as possible so that we can begin treatment early. Some lupus patients may also need to undergo more specific investigations e.g. chest X rays, lung function tests, CT scans, MRI scans, ultrasound scans.
Treatment
It is very important to remember that everybody's lupus is different. Two patients' treatment for lupus can therefore be very different. Before describing the different drug treatments for SLE, I will discuss some nonpharmacological measures. Learning to pace yourself and adopting relaxation techniques that can be used during normal day to day life can help. Sunlight can cause a flare of lupus so it is important to avoid strong sunlight, particularly the midday sun and use a high factor sun block and wear a hat when you have to be outside in the sunny weather. The drugs that we use in treating patients with SLE can be divided into three categories: immunosuppressants, symptomatic treatments and prophylactic treatments. Immunosuppressants dampen down the immune system and prevent the disease from progressing in the long term e.g. prednisolone, azathioprine. Symptomatic treatments are used to provide relief of symptoms on a day to day basis e.g. nonsteroidal anti-inflammatory drugs (NSAIDS). Prophylactic drugs are used to prevent the complications of lupus or prevent drug side effects. For example if a patient requires long term prednisolone we will consider prescribing drugs to maintain bone density and prevent osteoporosis. Similarly if a patient is found to have 'sticky blood' i.e. the presence of antiphospholipid antibodies then we will recommend that the patient takes low dose aspirin to prevent clots from occurring. Hydroxychloroquine This is an anti-malarial drug (i.e. used to prevent malaria) but is also very useful in the treatment of SLE. It is particularly helpful in treating the skin and joint symptoms associated with lupus. Sometimes it will also improve fatigue. Patients are warned that this drug may very occasionally affect their vision. If a patient develops a change in their vision or sees haloes then they should stop the drug and report this to their rheumatologist or GP.
Prednisolone
Prednisolone works as an anti-inflammatory drug and immunosuppressant. It is a very good drug. However in the long term it can sometimes cause troublesome side effects such as osteoporosis, diabetes and high blood pressure. We therefore try to keep the dose as low as possible. It can be given in tablet form or as injections into the joint, into the muscle or into a vein. To help keep the dose of steroids as low as possible, we often add a steroid-sparing drug e.g. azathioprine, methotrexate.
Azathioprine
This is a steroid-sparing drug and is often used to treat lupus, particularly if patients have involvement of their kidneys, lungs or nerves. The dose tends to be calculated on body weight. This drug can affect the bone marrow and cause a low white cell count or platelet count or sometimes cause inflammation of the liver. It is therefore important that the patient has regular drug safety-monitoring blood tests whilst taking this medication. If abnormalities do occur then they will usually disappear if the dose is reduced or the drug is stopped.
Methotrexate
This is another steroid-sparing drug. It is particularly good for treating arthritis. It has the advantage of being taken just once per week. The dose varies according to response. Again, some patients may develop bone marrow or liver problems whilst taking the drug so it is important that the patient has regular drug safety-monitoring blood tests. Some patients may experience a sore mouth or nausea with this drug but the frequency of these side effects is reduced by co-prescribing folic acid.
Cyclophosphamide
This is a strong treatment which is reserved for use in lupus patients with very active inflammation in the kidneys, lungs, brain or nerves. It can be given as a tablet on a daily basis but is more usually given into the vein as a 'pulse' over an hour every two to four weeks for a course of treatment. Sometimes it can cause nausea so the patient receives additional medication to prevent this. Occasionally it can cause inflammation of the lining of the bladder but this can be prevented by the patient drinking lots of fluid on the day of the treatment and taking some special tablets caused mesna. If a patient receives a high dose of this treatment then their fertility may be affected; this needs to be discussed with the treating rheumatologist.
The Future
The prognosis of a patient with SLE has improved considerably over the last twenty years. This is due to a combination of factors. Treatment has become more intensive and starts earlier. There is greater awareness of the disease amongst the general public, general practitioners and general physicians. It is an exciting time in the field of rheumatology. Targeted therapies, called monoclonal antibodies, are being developed to specifically block pathways involved in the cause of SLE. Several of these drugs are being assessed in clinical trials. However, it will be some time before we know the outcome.
Table 1: Brief summary of the ACR classification criteria for SLE
Malar rash (butterfly rash)
Discoid rash
Photosensitivity (rash after exposure to sun)
Mouth ulcers
Inflammatory arthritis
Kidney inflammation
Inflammation of the nerves/ brain
Pleurisy (inflammation of the lining of the lungs), pericarditis (inflammation of the outer layer of the heart)
Low white cell count, low platelet count
Raised anti-dsDNA antibody levels, presence of antiphospholipid antibodies
Presence of ANA antibodies
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