Treating Lupus with Medications

The vast majority of SLE patients can be treated successfully. Some patients have mild SLE that does not require any treatment although regular follow-up is still necessary. Even SLE patients who have required treatment can reasonably hope that a remission will occur when little or no treatment will be needed.

Ideally there should be only one physician in charge of supervising your illness and treatment and this approach is generally followed in the University Hospital Lupus Clinics across Canada. In these clinics, most patients are treated by physicians who have specialized in rheumatology (called rheumatologists). These physicians have received a particularly specialized training in lupus. As needed, consultation with other specialists is sought and many patients are also followed by physicians specialized in skin care (dermatologists), blood diseases (hematologists), kidney diseases (nephrologists) or immunologic diseases (immunologists).

In dealing with lupus, two approaches are used. First, the symptoms are treated if necessary and secondly, people with SLE are advised to avoid certain things that are known to cause a flare in some patients.

Medications to Treat the Symptoms of SLE

Drugs for Arthritis

Arthritis is probably the most common symptom of SLE and when it is mild no treatment may be needed. If the pain is more severe, many patients are satisfied with a basic pain medication such as acetaminophen (for instance, Tylenol or Atasol). Non-steroidal anti-inflammatory drugs (called NSAIDS for short) are often used when acetaminophen doesn't control the pain of arthritis. There are over 20 different drugs in this family of medications, including aspirin. Although some of the NSAIDS are available over the counter, it is best left to your doctor to decide which one you should use. Not every drug works well for every patient and you may have to try several NSAIDS before finding one that relieves your pain.

The NSAIDS may cause many side-effects, from stomach upset to changes in kidney function. Several of these side-effects can cause trouble as they may imitate lupus problems or complicate lupus problems that already exist. For this reason, NSAIDS are often prescribed to be taken for a short time only, with instructions to decrease the dose as the arthritis improves.

Hydroxychloroquine and chloroquine

The drugs hydroxychloroquine (Plaquenil ®)and chloroquine (Aralen ®) are very useful in treating sun sensitive skin rashes such as the discoid or the subacute types of lupus rashes. In many cases, rheumatologists prefer to use hydroxychloroquine because it is considered to be less toxic. However, dermatologists may prefer to use chloroquine to treat lupus rashes. This drug may also be tried if hydroxychloroquine is ineffective. While a sunscreen may often provide sufficient protection, some patients do get skin rashes in spite of the proper use of a good sunscreen. In these patients, hydroxychloroquine may be started in the spring and continued until the late fall.

Hydroxychloroquine is also used to treat lupus fatigue, arthritis and other milder symptoms of SLE. A recent study in several Canadian University Hospital Lupus Clinics has shown that hydroxychloroquine can help prevent flares in patients who have taken this medication continuously over a six month period.

At the relatively low dosage used in SLE (the dose is calculated based on the patient's weight), hydroxychloroquine seems to cause few problems. Apart from the pill's bad taste, the most common unwanted effect is some stomach upset. However, if hydroxychloroquine and chloroquine are taken in a high dose and over a long period of time, they may accumulate in the background of the eye (retina) and cause a loss of vision. In rare cases, blindness may occur. In over ten years of supervising patients on hydroxychloroquine, I have never seen a single case of damage to the eye but my more senior colleagues tell me that I probably will, eventually.

A series of precautions are taken to make certain that damage to the eye does not occur. Dosage is based on the body weight and, if possible, hydroxychloroquine is only used from spring to fall when the sun is the strongest. (However, many patients must take hydroxychloroquine for much longer periods.) Before hydroxychloroquine or chloroquine is started, patients must have their eyes examined by an eye doctor (ophthalmologist) and this examination should be repeated every six months. As well, patients started on these drugs should receive an Amsler grid and be told how to use it. The Amsler grid is a sheet of paper with many small squares (like a piece of graphing paper). Patients should inspect the squares regularly and if the lines are not clear, straight and square, they should see their eye doctor immediately. In my experience with hydroxychloroquine, eye damage will not get worse and sight will not be threatened if the drug is stopped at this early stage.

Cortisone and Prednisone

The single most important factor explaining the remarkable improvement in life expectancy of SLE patients has been the discovery of the steroid drug cortisone in 1948 and, shortly after, the related drug prednisone. Although the term cortisone continues to be used by patients and the public, SLE patients are now treated with the much more effective drug prednisone. This drug is the best inflammation-fighting drug available at the moment. Prednilosone is also used in Canada and, for some SLE patients, is the best drug available. These drugs are sometimes referred to as steroids, but they are not related to testosterone and the other anabolic steroids used by some athletes to build muscle.

The decision to prescribe prednisone is never made lightly by your physician. Prednisone is considered if the symptoms are not being well controlled by other treatment(s), if there is a concern that SLE may quickly get out of control unless prednisone is used or if SLE is severe and perhaps life-threatening.

On the bright side, prednisone is necessary for the successful treatment of many lupus patients. For some, it is a lifesaving drug and the single best drug available. However, this powerful drug has a dark side too. There is no doubt that prednisone can cause a wide variety of side-effects in both the short and the long term. If you are taking prednisone, it is important for you to know what these problems are. This information is included in Appendix Two at the back of the booklet, "Side-effects of prednisone". Patients will be happy to know that research is underway to find steroid drugs which would have the powerful inflammation-fighting action of prednisone with fewer unwanted side-effects.

At times, patients may be tempted to stop taking prednisone or to reduce or increase their dose. Perhaps they are fed up with the side-effects or perhaps they are feeling better or worse. It is important that patients taking cortisone understand how cortisone works and why stopping or changing the medication without the supervision of the physician is dangerous.

Cortisone is a chemical that is normally produced by the body, not a foreign substance. In fact, the body has a vital need for cortisone. When prednisone treatment is started, the body responds by stopping its own production of cortisone and the adrenal glands that produce it get sluggish and lazy. If prednisone is used for a period of time and then suddenly stopped, the body may not be able to start producing enough cortisone for some time. The result could be a life-threatening lack of cortisone (adrenal insufficiency). So prednisone should never be stopped suddenly. If you are tempted to stop taking your prednisone, do not do it. Rather, discuss the situation with your physician.

Other patients decrease or increase their dose on their own. This is unacceptable. If you feel well enough that you think prednisone could be decreased or if you feel worse and think that it should be increased, call your doctor. Never forget that both you and your doctor have worked very hard to improve your health. You should not put your improvement at risk by making any changes to your therapy.

Cyclophosphamide and Azathioprine

Cyclophosphamide (Procytox®) and azathioprine (Imuran®) are powerful drugs which are used in the treatment of certain SLE patients. One of these medications may be used when prednisone alone is unable to control SLE, when prednisone causes too many serious side-effects or when it is thought that combining the drug with prednisone may be better than using prednisone alone. These drugs work in SLE by changing the body's immune response and they are referred to as "immunosuppressive", "immunomodulatory" or "cytotoxic" drugs. Cyclophosphamide and azathioprine are usually given as pills and are generally not used together. As with other kinds of treatment, the decision to use one of these drugs is made on the basis of the symptoms and the condition of the patient. The dosage is based on the patient's weight.

Like all powerful drugs, the immunosuppressives have potential serious side-effects. The three most serious unwanted effects are changes to the bone marrow (where blood cells are produced) which may lead to a decrease in the number of red or white blood cells or platelets, increased risk of infections including infections to which we normally have resistance and a slightly increased risk of developing certain types of cancer. The risk of infection is particularly high when cyclophosphamide or azathioprine are combined with high doses of prednisone. Cyclophosphamide can also be associated with bleeding from the bladder (haemorrhagic cystitis) and failure of the ovaries to produce their normal output of hormones (ovarian failure). In practice, azathioprine is considered less toxic than cyclophosphamide. Obviously, these are very serious problems and patients taking these medications are watched very carefully by their physicians. Periodic blood tests are mandatory throughout the course of this therapy.

These problems have led to a recent report from the American National Institutes of Health on the use of intravenous cyclophosphamide in patients with severe kidney involvement in SLE. In this form of treatment, a much larger dose is given by vein (approximately 10 to 15 times more than the daily dose when given in pill form). By repeating this treatment every 4 to 12 weeks, kidney inflammation was very much reduced as were the serious side-effects (including risk of cancer). Many University Hospital Lupus Clinics in Canada now use this treatment for serious kidney involvement as well as for certain types of serious SLE problems. The procedure can be done on an outpatient basis or during a short stay in hospital. It should be kept in mind that although this form of treatment is better, it is still far from harmless, is used only for SLE patients with very serious disease and that our experience with it is short.

Living with Lupus what to expect

A chronic illness, lupus is different for each individual, but it often appears in cycles, which can consist of:

- a 'flare', with severe acute symptoms needing medical attention;

- a 'chronic' phase, when symptoms may continue but are less severe;

- a 'remission', when symptoms may disappear completely for long periods, but can return.

In the chronic phase, and especially in the remission phase (when it is easy to forget to take care), a person with lupus needs to avoid situations that can bring on a flare. These include getting too tired, intense stress, poor diet or other factors noticed by patient or doctor.

Lupus is a serious condition, but diagnosis and treatment are improving. Today it can be treated and controlled. More and more people with lupus are finding that they can be active and productive.

S.L.E Foundation : Life without Lupus Video

Flares and What Triggers Lupus

In the simplest of terms, a lupus flare is when a person's lupus has been quiet or in remission, and then it becomes active again, either with new symptoms or a recurrence of old ones.

So what triggers an attack of lupus in someone? Scientists have noted some common features in many lupus patients. In some, exposure to the sun causes the sudden development of a rash, and then possibly other symptoms. In others, an infection ... perhaps a cold or a more serious infection ... does not get better, and then complications arise. These complications may be the first signs of lupus.

In still other cases, a drug taken for some illness produces the signaling symptoms. In some women, the first symptoms and signs develop during pregnancy. In others, they appear soon after delivery. Many people cannot remember or identify any specific factor. Obviously, many seemingly unrelated factors can trigger the onset of the disease.

Keeping a Flare at Bay

- Always take your medication as prescribed.
- Keep your doctor's appointments, even if you're feeling well.
- Avoid taking sulfa drugs (sulfonomides) that are used to treat infections such as bronchitis and urinary tract infections.
- Limit your exposure to sunlight; apply sunscreen before going outside during the day, and - ---- wear sun-protective clothing and a wide-brimmed hat.
- Reduce your risk of infections.
- Get plenty of rest.
Do not smoke.

The Causes of Lupus

The cause(s) of lupus is currently unknown, but there are environmental and genetic factors involved. Some environmental factors which may trigger the disease include infections, antibiotics (especially those in the sulfa and penicillin groups), ultraviolet light, extreme stress, certain drugs, and hormones.

Scientists believe there is a genetic predisposition to the disease, as lupus is known to occur within families. However, there is no known gene or genes which are thought to cause the illness. There are recent discoveries of a gene on chromosome 1 which is associated with lupus in certain families. Previously, genes on chromosome 6 called "immune response genes" were also associated with the disease. Only 10 percent of lupus patients will have a close relative (parent or sibling) who already has or may develop lupus. Statistics show that only about five percent of the children born to individuals with lupus will develop the illness.

Lupus is often called a "woman's disease" despite the fact that many men are affected. Lupus can occur at any age, and in either sex, although it occurs 10-15 times more frequently among adult females than among adult males after puberty or after the emergence into sexual maturity. The symptoms of the disease are the same in men and women. People of African, American Indian, and Asian origin are thought to develop the disease more frequently than Caucasian women. The reasons for this ethnic selection are not clear.

Hormonal factors may explain why lupus occurs more frequently in females than in males. The increase of disease symptoms before menstrual periods and/or during pregnancy support the belief that hormones, particularly estrogen, may somewhat regulate the way the disease progresses. However, the exact reason for the greater prevalence of lupus in women, and the cyclic increase in symptoms, is unknown.

Lupus Lab Tests: Other Autoantibodies

In those individuals with a positive ANA, additional tests can be done for certain particular antibodies that may better establish a diagnosis of SLE. The knowledge of which particular antibody is responsible for the positive ANA test can sometimes be helpful in determining which autoimmune disease is present. For instance, antibodies to DNA (the protein that makes up the body's genetic code) are found primarily in SLE. Antibodies to histones (DNA packaging proteins) are usually found in people with drug-induced lupus, but may also be found in those with SLE. Antibodies to the Sm antigen are found almost exclusively in lupus, and often help to confirm the diagnosis of SLE. Antibodies to RNP (ribonucleoprotein) are found in a number of connective tissue diseases. When present in very high levels, RNP antibodies are suggestive of mixed connective tissue disease, a condition with symptoms like those of SLE, polymyositis, and scleroderma.

Antibodies to Ro/SS-A are found in people with either lupus or Sjogren's syndrome, and are almost always found in babies who are born with neonatal lupus. Antibodies to Jo-1 are associated with polymyositis, while antibodies to PM-Scl are associated with certain cases of polymyositis that also have features of scleroderma. Antibodies to Scl-70 are found in people with a generalized form of scleroderma, and antibodies to the centromere (a structure involved in cell division) are found in people with a limited form of scleroderma which tends to have a chronic course.

Complement
Laboratory tests which measure complement levels in the blood may also be helpful to the physician in making a diagnosis of SLE. Complement is a blood protein that destroys bacteria and also influences inflammation. Complement proteins are identified by the letter "C" and a number. The most common complement tests are C3, C4, and CH50. If the total blood complement level is low, or the C3 or C4 complement values are low and the person also has a positive ANA, some weight is added to the diagnosis of lupus. Low C3 and C4 complement levels in individuals with a positive ANA may signify the presence of active disease, especially kidney disease.

Biopsy

Sometimes examination of a tissue sample (biopsy) can be helpful in making a diagnosis. The biopsy is one of the best ways to evaluate an organ or tissue. The procedure involves removal of a small sliver of tissue, which is then examined under a microscope. The doctor can use the biopsy to identify the amount of inflammation and damage to the tissue. Further tests can be performed on the specimen to determine whether the problem is due to lupus or is caused by some other factor such as infection or medication. Almost any tissue can be biopsied. The most common sites biopsied in lupus are the skin and kidney. The results of the biopsy, like any other laboratory test, should be examined in combination with the individual's medical history and clinical findings.

Tests to Assess Disease Activity

When a person diagnosed with lupus develops new or recurring symptoms, laboratory testing of blood or urine can help determine if the symptoms are due to an increase in lupus activity. Disease activity correlates with a rise in:

-CRP (C-reactive protein) binding
-Sedimentation rate, or ESR
-Anti-DNA
-Liver and kidney function tests (AST, ALT, BUN, creatinine)
-CPK (muscle enzyme)
-Urine protein or cellular casts

Disease activity also correlates with a fall in:

-CBC (white blood cell count, hemoglobin, platelets)
-Complement components
-Serum albumin

Putting It All Together

The interpretation of all these tests, and their relationship to symptoms, can be difficult. When a person has many symptoms and signs of lupus and has positive tests for lupus, it is easier for physicians to make a correct diagnosis and begin treatment. It is more common for an individual to report vague, seemingly unrelated symptoms of achy joints, fever, fatigue, or pain, and to have negative or borderline test results. Fortunately, with growing awareness of SLE, an increasing number of physicians will consider the possibility of lupus in the diagnosis. While these tests are useful only when their strengths and limitations are understood, in the hands of skilled physicians these are important tools that assist in diagnosing lupus.

Lab Tests for Lupus: The Antinuclear Antibody (ANA or FANA) Test

The immunofluorescent antinuclear antibody (ANA or FANA) test is a sensitive test for lupus, since it is present in 97 percent of those with the disease. When three or more typical clinical features are present, such as skin, joint, kidney, pleural, pericardial, hematological, or central nervous system findings as described above, a positive test confirms the diagnosis.

The ANA test is positive in almost all individuals with systemic lupus, and is the most sensitive diagnostic test currently available for confirming the diagnosis of systemic lupus when accompanied by typical clinical findings. A negative ANA test is strong evidence against lupus as the cause of a person's illness, although there are very infrequent instances where SLE is present without detectable anti-nuclear antibodies. ANA-negative lupus can be found in people who have anti-Ro (SSA) or antiphospholipid antibodies. However, a positive ANA test, by itself, is not proof of lupus since the test may also be positive in:

• other connective tissue diseases such as scleroderma, Sjogren’s syndrome, rheumatoid arthritis, and thyroid disease, as well as liver disease and juvenile arthritis
• individuals being treated with certain drugs, including procainamide, hydralazine, isoniazid, and chlorpromazine
• viral illnesses such as infectious mononucleosis, and other chronic infectious diseases such as hepatitis, lepromatous leprosy, subacute bacterial endocarditis, and malaria
• other autoimmune diseases, including thyroiditis and multiple sclerosis

The test can even be weakly positive in about 20 percent of healthy individuals. While a few of these healthy people may eventually develop lupus symptoms, the majority will never develop any signs of lupus or related conditions. The chances of a person having a positive ANA test increases as he or she ages.

Finally, as many as 30-40 percent of asymptomatic first degree relatives (siblings, parents, and children) of people with lupus may have a positive ANA test.

ANA Titers (number) and Patterns

ANA reports include a titer (pronounced TY-tur), and a pattern. The titer indicates how many times the lab technician had to dilute plasma from the blood to get a sample free of the antinuclear antibodies. For example, a titer of 1:640 shows a greater concentration of anti-nuclear antibodies than a titer of 1:320 or 1:160.

The apparent great difference between various titers can be misleading. Since each dilution involves doubling the amount of test fluid, it is not surprising that titers increase rather rapidly. In actuality, the difference between a 1:160 titer and a 1:320 titer is only a single dilution. This does not necessarily represent a major difference in disease activity. ANA titers go up and down during the course of the disease, and a high or low titer does not necessarily mean the disease is more or less active. Therefore, it is not always possible to determine the activity of the disease from the ANA titer.

A titer above 1:80 is usually considered positive. However, some laboratories may interpret different titer levels as positive, so one cannot compare titers from different laboratories.

The pattern of the ANA test can sometimes be helpful in determining which autoimmune disease is present and which treatment program is appropriate. The homogeneous (smooth) pattern is found in a variety of connective tissue diseases, as well as in people taking particular drugs such as certain anti-arrhythmics, anti-convulsants or anti-hypertensives. This pattern is also the one most commonly seen in healthy individuals who have positive ANA tests. The speckled pattern is found in SLE and other connective tissue diseases, while the peripheral (rim) pattern is found almost exclusively in SLE. The nucleolar (a pattern with a few large spots) pattern is found primarily in people who have scleroderma.

Because the ANA is positive in so many conditions, the results of the ANA test have to be interpreted in light of the person's medical history, as well as his or her clinical symptoms. Thus, a positive ANA alone is never enough to diagnose lupus. On the other hand, a negative ANA argues against lupus but does not rule out the disease completely.

A Positive ANA Does Not Equate to Having a Disease

The ANA should be looked at as a screening test. If it is positive in a person who is not feeling well and who has other symptoms or signs of lupus, the physician will probably want to conduct further tests for lupus. If the ANA is positive in a person who is feeling well and in whom there are no other signs of lupus, it can be ignored. If there is any doubt, a consultation with a rheumatologist should clarify the situation.