From the National Magazine

How to assess a patient with SLE

Dr Bridget Griffiths, Consultant Rheumatologist, Freeman Hospital, Newcastle upon Tyne

Background
Systemic lupus erythematosus is a multi-system disease. This means it can affect any organ system in the body e.g. the joints, skin, muscles and/or kidneys. In an individual, it can affect just one system or a combination of organs. Everybody's disease is different. Some patients may have very mild disease. Most will have mild to moderate disease but unfortunately a few patients may have very severe disease that significantly affects their quality of life and may even be life-threatening. Lupus is more common in women compared with men, with a ratio of approximately nine women affected to every man affected. In women, lupus commonly starts during the child-bearing years from the late teens to mid thirties. The prevalence i.e. the number of people affected in the population varies within different racial groups. In people of northern European origin it affects about 1 in 2000 people. It is more common in individuals of Asian origin, affecting about 1 in 900 people. Lupus is even more common in people of Afro-Caribbean origin, affecting 1 in 400 women. It is important for doctors to consider a diagnosis of lupus when a young woman presents with generally being unwell and with multiple symptoms.

We do not know why an individual develops lupus but believe it is due to a combination of factors. These are a mixture of genetic and environmental factors. No single gene is responsible for the development of SLE but some genes have been identified that may make an individual more prone to developing the disease. Some viruses may trigger the onset of the disease or be a cause of a flare of a patient's symptoms. Similarly ultra violet light can contribute to the onset of SLE or be responsible for a flare. Sometimes drugs can trigger SLE in susceptible people. For example sulfasalazine, a drug used to treat rheumatoid arthritis, may sometimes cause a switch in disease from rheumatoid arthritis to lupus. Minocyline is also an important example to remember. It is used to treat acne so is used in young women and may trigger lupus. The lupus may go away if the drug is stopped but sometimes the lupus will still persist.

How to make the diagnosis
SLE can be very difficult to diagnose. Sometimes a patient will have been unwell for several years before the diagnosis is made. In the early stages of the disease it can be difficult to make the diagnosis as the symptoms can be very non-specific and can also be present in many other conditions. These symptoms include fatigue, which can be very extreme, aches and pains and headaches. It may only be when the patient develops more specific symptoms such as swelling of the joints or the classic rashes associated with lupus that the diagnosis is considered. We use the American College of Rheumatology Classification Criteria (see table 1) to help us to make the diagnosis. Typically an individual will have four or more of these criteria. They do not have to be present at the time of assessment in the clinic but may have occurred over a number of years. The following is an example of how an individual may develop lupus over a period of ten years. At the age of 7 a girl develops a photosensitive rash i.e. a rash that occurs in sun exposed parts of the body after exposure to the sun. At the age of 14 she develops intermittent trouble with mouth ulcers. At the age of 16 she develops inflammation in her joints, which is associated with pain, swelling and stiffness, particularly in the mornings. At this stage blood tests are performed and the immunology blood tests reveal a positive antinuclear antibody (ANA) and a positive anti-double stranded DNA antibody consistent with a diagnosis of lupus.

Table 1: The 1982 revised ACR classification criteria - modified 1997

• Malar (butterfly) rash
• Discoid rash
• Photosensitivity
• Mouth ulcers
• Arthritis
• Serositis (pleurisy, pericarditis)
• Renal
• Neurological
• Haematological anaemia
       leucopaenia (low white cells)
       thrombocytopaeni (low platelets)
• DNA antibody
       Anticardiolipin antibody
       Lupus anticoagulant
• ANA positive

Assessment at the clinic appointment
In the clinic we try to adopt a holistic approach. We assess disease activity, quality of life and look to see if any damage to any organ has occurred. We also assess the effectiveness of the medication being used to treat the lupus and ensure it is not causing serious side effects. The benefit-risk ratio has to be acceptable to the patient and the doctor. We also assess any new conditions e.g. infection and determine if they are related to the disease directly or indirectly and whether this needs any modifications to the treatment.

Disease activity needs to be identified as it may be reversible and therefore if treated early can prevent damage to the organs. It also needs to be quantified so that the appropriate level of treatment can be determined. It can be assessed by asking screening questions to assess whether symptoms that may be related to lupus or not are present and if they are present whether they are becoming worse, staying the same or getting better. Such questions would include enquiry about fatigue, rashes, mouth ulcers, thinning of the hair, headache, numbness, pins and needles, breathlessness, chest pain, or Raynaud's. We will also examine the relevant part of the body as determined by the reply to the above questions e.g. observe a rash, listen to the chest, examine the joints. Inflammation of the kidneys is a relatively common problem in lupus patients. We can detect this early if we test a urine sample, using a sensitive reagent stick, looking for blood and protein. We can also detect kidney involvement if we find that the blood pressure is high. A urine sample and the blood pressure should therefore be checked at every hospital visit. All of these features can be recorded on a specially designed disease activity sheet. We use the BILAG (British Isles Lupus Assessment Group) disease activity index. The score obtained from this sheet guides the changes in treatment.

Multiple blood tests will usually be performed at each clinic visit. We check for inflammation in the blood using the ESR and CRP blood tests. We check haematology to exclude anaemia, low white cell counts or low platelet counts which can all occur in patients with SLE. We check biochemistry to ensure that the kidney and liver blood tests are normal. We often perform more specialised tests to assess the immunology. Positive antinuclear antibodies and anti double stranded DNA antibodies are typically found in a patient with lupus, but these antibodies may be absent in some patients. When a patient first attends we perform a whole battery of tests to see which antibodies are present, which helps us to look for patterns of disease within lupus patients. For example patients with the anti Ro antibody may be more prone to developing rashes and a dry mouth. Patients with anti RNP may have severe Raynaud's. We also look for 'sticky' blood when a patient first attends clinic and from time to time. The presence of these antibodies is associated with an increased risk of developing a clot or thrombosis. If the antibodies are present then it may be advisable to take a medication to 'thin' the blood such as a junior aspirin. Depending upon the symptoms and findings on examination, we may have to perform more specific tests e.g. ultrasound of the kidneys, chest X ray, ECG, echocardiogram, MRI scan or lung CT scan.

As stated above we need to prevent damage to any organ. This can be done by treating a flare of lupus appropriately, by preventing a complication of lupus or preventing a complication due to treatment. For example lupus patients are more prone to developing atherosclerosis (furring of the arteries) so measures need to be taken to reduce this such as checking cholesterol and treating it if it is high and advising patients to stop smoking. Sometimes treatment with steroids that was necessary at the time of a flare or to control the disease in general can lead to osteoporosis ('thinning of the bones'). This can be monitored by performing a bone density scan (DEXA scan). If the bone density is lower than it should be then we can use medication to improve this and prevent complications in the future.

As mentioned above, when assessing a patient in clinic we try to adopt a holistic approach. This includes assessment of how the disease is affecting an individual regarding their ability to continue their previous activities such as working, running a home and looking after children. We also assess how the individual is coping with their illness; different people cope in different ways and some find it harder than others. We sometimes assess this formally using a questionnaire e.g. the short form 36 (SF36). The questionnaire has been used in many conditions. It records a patient's function e.g. if there is any difficulty walking half a mile, ability to climb a flight of stairs. It also scores psychological aspects e.g. ability to go out and socialise, and mood. A couple of rheumatology units are also developing quality of life questionnaires specifically for patients with lupus: Leeds has developed the SLEQoL and Blackburn the LupusQoL.

How to decide on a treatment
The aims of treatment are to suppress disease activity, prevent organ damage and improve a patient's quality of life. As previously stated, everybody's lupus is different so their treatment needs to be tailored according to their needs. Non-pharmaceutical measures can be very important and easily adopted. Pacing one's self and spreading out activities can help fatigue. Avoiding sunlight and using a high factor sun block can help to prevent a flare. Using relaxation techniques e.g. pilates and other coping strategies may make it easier to cope with the disease. Drug treatments can be divided into three groups: those that dampen down the over active immune system and help to control the disease in the long term (immunosuppressants); those that treat symptoms and work on a day to day basis to help joint symptoms e.g. non-steroidal anti-inflammatory drugs (NSAIDs); and those used to prevent complications e.g. lower cholesterol, improve bone density.

Treatments can be placed in a pyramid according to their frequency of use and potency (see figure 1). Hydroxychloroquine has lots of benefits and is particularly good at treating arthritis and rashes and can sometimes improve fatigue. Prednisolone is required if there is a moderate to severe amount of inflammation. However, high doses of steroids are not good in the long term so we introduce immunosuppressants such as azathioprine, methotrexate and ciclosporin A so that we can reduce the steroid dose. For very severe disease causing inflammation in the kidneys, lungs or brain then we use cyclophosphamide with high doses of steroids. These are best given into the vein at intervals of 2 - 4 weeks according to the patient's symptoms. A patient will usually receive a course of this treatment e.g. 6 pulses and then the disease will be reassessed and if it has settled down then the treatment can be switched to less strong immunosuppressants. All of these drugs are strong and may cause side effects, so as well as monitoring the effectiveness of the treatment, we need to look for side effects e.g. low white cell counts and raised liver function tests. A patient therefore needs to attend for regular drug safety monitoring blood tests. This may be done by the GP or at the hospital.

The number of treatment options is now expanding. Newer drugs used to treat lupus include mycophenolate and rituximab. Mycophenolate was initially used in transplant patients to prevent rejection. Rituximab is a 'designer' drug that targets specific white cells called B cells. Both of these drugs are being formally assessed in clinical trials at the present time. Other drugs are being developed and will also be studied in clinical trials. This is therefore a very exciting time for the rheumatologists treating lupus patients and for the patients as potential treatment options are increasing. The prognosis has already improved with more intensive treatment and better awareness of the condition leading to earlier referral to the specialist but I believe with the introduction of these newer drugs the prognosis will further improve.

The personnel
The assessment and treatment of the lupus patient is best carried out by a team of professionals experienced in looking after these patients. Doctors from different specialities e.g. rheumatology, renal and dermatology will often look after one patient. Good communication is essential and the treatment may be best co-ordinated by holding combined clinics. Dedicated connective tissue clinics may also improve a patient's treatment. These clinics will have slightly longer appointment slots than the general rheumatology clinic and have slots available for an emergency when a patient develops a significant flare. Nurses in the out patient clinic, on the day case unit or on the ward will all come into contact with lupus patients. The connective tissue nurse specialist is the key nurse within the team. She has experience at looking after patients with these complex conditions and can provide advice, education, counselling and support to patients and their families and carers.

Summary
Everybody's lupus is different. We try to adopt a holistic approach. We aim to dampen down disease activity that is reversible so that we prevent organ damage. We try to help the patient to improve their quality of life and maintain their previous activities. We tailor treatment according to a patient's symptoms and severity of disease. We monitor the effectiveness of the treatment but we also look for side effects so that the treatment can be modified if necessary.

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