Authors: Rita Baron-Faust,Jill Buyon
The Autoimmune Connection: Essential Information for Women on Diagnosis, Treatment, and Getting On With Your Life (12 page)
To be classified as having SLE, a woman needs to have 4 of the 11 criteria set by the American College of Rheumatology (ACR). Those four criteria need to be present at some point in time, but need not occur together. (Note: These criteria were originally intended for patients who wished to enter into clinical trials.)
- Malar rash (the classic raised, red rash that looks like a butterfly over the nose and cheeks)
- Discoid rash (red, raised patches with scaling and plugged follicles)
- Photosensitivity (an unusual reaction in the skin after being in the sun)
- Oral or nasal ulcers (usually painless ulcers, in the mouth or nose, most often the upper palate)
- Arthritis (tenderness, pain, and swelling in two or more joints)
- Serositis (fluid around the lining of the lungs or heart; this can be called pleurisy if it affects the lungs, pericarditis if it affects the heart)
- Kidney disorder (proteinuria)
- Brain disorder (psychosis or seizures)
- Blood cell disorder (hemolytic anemia, lymphopenia, leukopenia, or thrombocytopenia)
- A positive test for antinuclear antibodies (ANAs)
- Evidence of other autoantibodies (like anti-dsDNA antibodies, anti-SM antibodies, or antiphospholipid antibodies) including a false-positive venereal disease research laboratory test (VDRL)
Some doctors may diagnose SLE even if only three of these criteria are positive. ANAs can be positive in healthy women. A positive ANA is not specific for lupus, although it’s the reason most patients are referred to a rheumatologist.
In contrast, the autoantibodies to double-stranded DNA (
anti-dsDNA antibodies
) are very specific and with rare exceptions signify lupus. If two of the symptoms listed are present, a diagnosis of lupus is uncertain until more symptoms develop or other more specific blood tests produce positive results.
In the last several years another set of classification criteria have been published. These are quite similar to the ACR criteria.
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Under the 2012 Systemic Lupus International Collaborating Clinics Classification Criteria (SLICC), you need to have four criteria, with at least one being considered immunologic. However there is one important change. In the past, a patient might not be considered to have systemic lupus erythematosus if she only had kidney involvement and a positive ANA. With the new criteria, other symptoms do not have to be present and kidney involvement alone is sufficient if the biopsy is read as consistent with lupus.
Blood tests are an integral part of the workup for lupus. They can help to pin down a diagnosis since your symptoms may overlap with other diseases.
A complete blood count (CBC)
is a standard blood test in any diagnostic workup, measuring white blood cells, red blood cells, and platelets. In a lupus workup, it can flag problems such as
leukopenia
(a total white blood cell count below 4,000 cells per cubic millimeter) or
lymphopenia
(fewer than 1,500 lymphocytes per cubic millimeter) or
thrombocytopenia
(fewer than 100,000 platelets per cubic millimeter). Because white blood cell counts can fluctuate
in healthy women, it’s important that leukopenia and lymphopenia be detected on two or more occasions to satisfy the ACR classification. A CBC can also detect
hemolytic anemia
(a condition in which autoantibodies react against targets on red blood cells and destroy them, resulting in low red cell counts).
Antinuclear antibodies (ANAs)
will be positive in more than 95 percent of women with SLE. However, since the test can be positive in other autoimmune conditions, the results have to be considered along with a woman’s medical history and any clinical signs and symptoms of lupus that may be present. Since discoid lupus does not usually involve internal organs, the ANA test may be negative (or show very low levels of antibodies).
ANA test results include a
titer
(or quantity) of the antibody. This is a number based on how many times an individual’s blood must be diluted to get a sample free of antinuclear antibodies. So a titer of 1:640 shows a greater concentration of antinuclear antibodies than a titer of 1:320 or 1:160. As it turns out, the ANA titer doesn’t really indicate whether the disease is active or severe or what organs are affected. Once the ANA is found to be positive, it’s not that useful to repeat. Patients in extended remission can actually have no detectable ANAs, but others may always retain these antibodies, even in remission.
Antibodies to double-stranded DNA (anti dsDNA)
target DNA, which contains the genetic instructions in every cell. A positive anti-dsDNA test is considered highly specific for lupus. If this test is positive, you have a very strong chance of having SLE. Anti-dsDNA antibodies are found in 30 to 80 percent of women with lupus.
Antibodies that target DNA may sound pretty dangerous. Yet these antibodies rarely cross into the cell itself, but rather bind to DNA when it’s released from the cell and an immune complex is formed. Anti-dsDNA antibodies are usually associated with kidney disease, and that is why women with these antibodies need to have urine samples tested several times a year to check for protein (it’s done with a simple urine dipstick but is often quantitated by collecting urine over 24 hours). These antibodies also appear to track lupus activity; they can come and go with disease flares.
Anti-SSA/Ro and anti-SSB/La antibodies are antibodies directed against normal cellular components called Ro, or Sjögren’s syndrome A (SSA), and La, or Sjögren’s syndrome B (SSB). SSA and SSB are detected in
approximately 40 percent and 15 percent, respectively, in individuals with SLE. Common clinical features associated with these antibodies are skin rashes worsened by sun exposure, and dry eyes and mouth (these antibodies are detected in 75 percent of women with Sjögren’s syndrome). It’s important to know about antibodies to Ro and La when planning a pregnancy, since some women with anti-Ro and anti-La antibodies can have children with heart problems and transient skin rashes (
pages 89
to
92
).
Anti-Smith antibodies (anti-SM)
are present in around 25 percent of women with SLE. They are also directed against nuclear material in the cell (they’re related to and coexist with anti-ribonucleoprotein antibodies, anti-RNP). Anti-Smith antibodies are specific to lupus and are among the criteria for a diagnosis. Anti-SM antibodies are believed to occur more frequently in African American and Asian women than in Caucasians.
Anti-Ro, anti-La, and anti-SM antibodies are usually detected using a test called an
enzyme-linked immunoabsorbent assay (ELISA)
, in which serum (the clear part of blood not containing any cells and devoid of clotting factors) is analyzed. An ELISA is capable of detecting very small quantities of these antibodies.
Antiphospholipid antibodies (aPLs)
are increased in a third of women with SLE, as well as in women with antiphospholipid syndrome.
Antiphospholipid antibodies
can cause damage to blood vessels and act against proteins in blood to promote clotting problems in the veins (leg clots, lung clots) or the arteries (heart attack, stroke). There are several types of antiphospholipid antibodies, each of which can be related to an increased risk of clotting anywhere in the body and/or low platelet counts. These antibodies are also associated with miscarriages, since they can cause blood clots in the placenta.
There are four basic types of antiphospholipid antibodies (aPLs), and each is detected by a different test. These are
anticardiolipin antibodies
(
aCL
, which come in three types, IgG, IgA, and IgM),
anti-beta2glycoprotein I
(
B2GPI
, which also come in the same three types as the aCL), the
lupus anticoagulant
(
LAC
, which is a funny name since it does not cause bleeding but rather clotting), and a
false positive test for syphilis
(see next paragraph). As many as half of patients who test positive for LAC have lupus; up to 47 percent of lupus patients have elevated aCLs. The LAC may be the most highly associated with blood clots and poor pregnancy outcomes. IgG autoantibodies of high titer are also more worrisome than lower titers.
The venereal disease research laboratory test (VDRL)
is actually a test for syphilis, but a positive VDRL does not mean you have syphilis. The antiphospholipid antibody in a lupus patient recognizes a similar structure on the syphilis bacteria (another case of molecular mimicry). So a positive VDRL signals the presence of that antibody. In the overwhelming majority of patients, when tested against more specific components of syphilis bacteria, the test is negative (so lupus patients have a false positive VDRL).
Complement levels
are used to gauge lupus activity, usually by measuring two specific components of complement, C3 and C4. Again, it’s helpful to think of complement as the bullets of a gun. When levels are low, it may mean the complement “bullets” have been fired and caused tissue damage. In some cases, women may be born with a low C4, and it may be hard to tell whether that stems from an inherited deficiency or actual disease activity. It’s like a bank account: it can be low because you didn’t deposit enough money or because you withdrew too much (as in the case of active lupus). Your doctor may measure these levels at all visits to see if they predict disease flares.
Skin biopsy
is done if you have a rash (often a sign of
discoid lupus
). A small biopsy of skin will be taken from the rash area to look for markers of inflammation.
A urine dipstick test for protein in the urine
is simple, but extremely important. Excessive protein in the urine means the kidney is losing protein. To more accurately measure the quantity of protein lost, it may be necessary to collect urine over a period of 24 hours. A microscopic examination of the urine may reveal abnormalities, such as red blood cell or white blood cell casts (abnormal elements derived from red and/or white cells), and kidney
glomerular
cells. A kidney biopsy may be done if urine or blood tests indicate evidence of kidney disease.
I was diagnosed with lupus when I was 23—that was more than 30 years ago. Back then, very little was really known about lupus. I was passed around from one doctor to another. I was told I had multiple sclerosis, I had a malignant brain tumor, I had rheumatoid arthritis, it was a psychosomatic illness . . . just about any illness you can think of, depending on what symptom I was having at the time. I was having seizures. And I went through a lot of torturous tests because they thought I had a brain tumor. I
was sent to a rheumatologist, a neurologist, and a neurosurgeon, and I was even sent to a psychiatrist, who said a lot of it was all in my head. Unfortunately, I went home and I tried to convince myself that my symptoms were imaginary. But of course that was the wrong thing to do; nothing was imaginary.My symptoms just kept getting worse . . . I went from specialist to specialist, and no one tried to put together a whole picture. I was finally diagnosed through a kidney biopsy in 1967. I remember when they told me I had lupus, they said I wouldn’t live a year. Well, I’m still here. I’ve had heart trouble, and the lupus has affected my lungs and my kidneys. . . . I also have back problems and I have some trouble getting around these days. But I don’t let anything drag me down. And I was fortunate to finally find a doctor who knew something about lupus, and who was aggressive in treating it. I credit my longevity to aggressive doctors, to good treatments, and to God.
J
ANE
, 63
The most important thing to keep in mind is that lupus is a fluctuating disease; you can experience periods of remission in which the disease is quiet, and flares, in which the disease is active, like the swings of a pendulum. The pattern varies from one person to the next. However, a lupus flare does not necessarily mean that your disease is progressing or that permanent damage to the internal organs is occurring. Flares can have a number of triggers, including emotional stress, exposure to sunlight, infections, and certain medications.
The stress connection is very real. One 2001 study from Germany looked at blood levels of cytokines after acute psychological stress in women with lupus, rheumatoid arthritis, and healthy women and found stress-induced increases in
interferon gamma
and
interleukin 4 (IL-4)
in the women with SLE and RA, suggesting that changes in cytokine patterns may be responsible for flares.
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In most cases, lupus flares involve physical changes that may be accompanied by abnormalities in the blood analysis. So your doctor will assess lupus activity
by taking a history, performing a physical exam, and drawing blood for testing. The degree of activity can actually be measured, and there are several scoring systems developed for this purpose. One such “score sheet” is the
SLEDAI (SLE Disease Activity Index).
This is a list of various physical findings and blood tests. The SLEDAI score literally adds up the number of problems; the more points, the more disease activity. This scoring system is generally used for clinical trials, but some physicians do use the system for keeping track of disease. While keeping score is not the point, it may be helpful to understand just how sick you are by reviewing how the SLEDAI score sheet is used (and you may find it useful for tracking your own symptoms). Many of the symptoms are the same as those in the ACR diagnostic classification (
pages 70
to
71
).
A mild flare (in some cases a three point or more change in the score) is likely to consist of any one of the following: a new or recurrent facial rash, hair loss, photosensitivity, mouth or nose ulcers, and unexplained fevers. Increased fatigue can be part of a lupus flare, but the SLEDAI doesn’t factor it in, although other lupus activity score sheets do. A moderate flare might include joint swelling and pain in more than two joints, pleuritis, or pericarditis. A severe flare (SLEDAI scores greater than 12) generally indicates more internal organ involvement, such as the kidneys or brain, and almost always requires treatment with high doses of glucocorticoids. But the degree of a problem also varies. Depending on the degree of activity, flares are treated differently.
On the other hand, disease progression (and any potential damage) is assessed using the SLE damage index, which records damage or permanent injury to a particular organ that has occurred after the diagnosis of lupus. The damage may be due to lupus itself or may have been caused by treatments. For example, cataracts are a side effect of glucocorticoids, not lupus per se. The purpose of a damage index is to have an assessment of the total health status of a patient over time. Like the SLEDAI, the damage index is generally used only in clinical studies and academic centers where lupus is being researched.
While the SLEDAI and damage index are useful, a careful physical examination and the appropriate lab tests will usually provide all the information your rheumatologist needs. Even without scales and scoring, physicians must assess lupus from at least two perspectives—how sick a patient is or how active her disease is at the time of a visit, and how the lupus has affected a patient’s health in general over time. It’s hoped that early treatment, where necessary, can prevent permanent damage to organs or tissues.
You can take preventive measures to reduce the risk of flares. Learning stress-reduction techniques can help you minimize stress-induced flares. Getting regular exercise should help combat fatigue and muscle weakness. If you’re photosensitive, avoiding excessive sun exposure and using sunscreen when you’re out in the sun will usually prevent rashes. If you smoke, stop smoking. Not only can it trigger flares and skin damage, but it’s the number one risk factor for heart and blood vessel disease—and cardiovascular disease follows lupus like a shadow.
Living with the unpredictability of lupus flares can be challenging. Which symptoms are the hardest, and who does best? An ongoing study of 400 patients with SLE, run by the University of Texas-Houston Health Science Center and the University of Alabama at Birmingham, found that fatigue and pain were the two most difficult symptoms for patients. But women who were able to cope with their disease from the time they were first diagnosed did much better. Because stress can also play a major role in lupus flares, learning stress-reduction exercises can be very beneficial, as can joining a support group where women can learn more effective coping strategies to help manage both the physical and emotional effects of their disease.
