Positive Options for Living with Lupus (8 page)

less harmful than action that might turn out to be wrong. A celebrated doctor observed that, of the patients who came to his consulting room, 50 percent would get better whatever he did, 25

percent would get worse whatever he did, and 25 percent might actually benefit from what he could do. The advantage of WoE was that he reduced the people needing help by the half who recovered, and his success rate doubled to 50 percent of the remainder. Of course it’s not as simple as that, but WoE still often figures in a modern doctor’s notes. Even in chronic conditions like lupus, a pattern, or an additional confirmatory symptom, may appear while you are waiting for those all-important laboratory tests.

Diagnosis by hypothesis. This is the classic scientist’s approach, not unlike Sherlock Holmes’. Postulate a diagnosis and then try to disprove it. It’s thorough, but lengthy, so in some ways not unlike WoE. Something will probably happen to the patient that illumi-nates things while the doctor is hypothesizing.

Diagnosis by computer. This increasingly popular technique is as new as WoE is old. It has its advantages: The computer gives access to a range of expertise in addition to the doctor’s own. It may throw up some curious options—the computer can’t see the patient coming through the surgery door—but among them may be something the doctor hadn’t thought of.

◗ ◗ ◗

Faced with a long row of check marks in a list of the clinical signs for lupus, a primary-care physician would treat the presenting symptoms but also refer the patient to a rheumatologist. He or she would also order laboratory tests that would help confirm his or her provisional diagnosis of lupus. These tests are explored in the next chapter.

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Chapter 5

Diagnosing Lupus, Part 2:

In the Laboratory

Around a hundred and fifty years ago, observed or “clinical” symptoms, as described in the last chapter, were all the doctor had to go on to diagnose lupus (or any other illness), and they were not usually conclusive. These days, doctors can call up a raft of sophisticated laboratory tests. A sample of blood or of another bodily fluid or tissue may be taken in the doctor’s office, but the analysis is completed by machines and skilled technicians in the pathology laboratory. Advanced and expensive imaging technology that reveals details inaccessible to the human eye is also available. It makes you realize why primary-care physicians often complain that they are just a staging post in modern medicine.

The American College of Rheumatology (ACR) diagnostic criteria include important evidence that can’t be detected at a primary-care consultation but requires laboratory tests. Up to this point it has been sufficient for us to say that most lupus symptoms are caused by inflammation—inflammation prompted by an unexplained malfunction of the immune system. But if we are to go further and explain how the disease is detected in the laboratory, we need to look at the inflammatory process and its causes in more detail.

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Inflammation: The Good News and the Bad

Inflammation feels the same wherever it occurs, whether in the form of a sore throat, a splinter, a corn, or arthritic joints. It causes warmth, redness, swelling, and pain. The amount of inflammation, hence the severity of the symptoms, is usually proportional to the severity of the injury or infection.

The body is a self-maintaining, self-repairing organism. Inflammation, though it may feel unpleasant, is actually a signal that the attack/defend/repair armory of the immune system is at work.

There are a number of weapons in this armory—WMD: weapons of microscopic destruction, if you wish—each of which has a slightly different role to play in coordinating attack and in returning the immune system to normal afterward. White cells, or lymphocytes (the name indicates cells produced in the lymph glands, among other places), are the foot soldiers of inflammation. As mentioned earlier, they are subdivided into B cells and T cells. The T

cells have their own role in fighting viruses and tumors, and they also influence the behavior of B cells.

At the start of an attack, B cells produce antibodies specifically tailored to repel the invader. “Helper” T cells assist in this task, along with back-up troops called
complement.
These proteins complement the activity of antibodies in neutralizing the antigen. The embattled cluster of warring antigen, antibody, and complement is called an
immune complex
. If you think of it like the line of scrim-mage in a football game, or a knot of big guys in a barroom brawl, you can see why inflammation causes so much damage to surrounding tissues, particularly the kidneys in lupus: What results is the equivalent of broken glass, splintered furniture, and torn curtains.

The objective is to destroy the antigen, but a lot more gets damaged in the process. During the battle, damaged cells at the site of infection or injury send out alarm calls in the form of chemical messengers called
cytokines
to summon the foot soldiers. Many different forms of these chemical messengers are active in inflammation: Some put out the call to battle; others tell the troops to back off when the enemy is vanquished. T “suppressor” cells come onto the POL text Q6 good.qxp 8/12/2006 7:39 PM Page 46

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scene later to tell the B cells to back off when their work is done (more on them later).

While the inflammation rages, the blood supply to the battlefield is increased, producing redness and warmth, and the body’s temperature rises. Clear fluid and white cells pass through the walls of the blood vessels into the surrounding tissues, causing swelling and pain as a result of the pressure upon the tissues. The fluid di-lutes poisons and is mildly antiseptic, and the white cells engulf, break down, and remove any foreign particles, such as bacteria, that they encounter, cleaning up the battlefield so that reconstruction can begin. The fluid—called inflammatory exudate—has the same capacity as blood to clot, and it will seal off clean wounds, such as those resulting from a surgical operation or minor infection. The clot causes the edges of the wound to stick together so that new tissue can grow to heal the breach.

If the enemy is not swiftly routed, pus may form, composed of inflammatory exudate and broken-down cells of dead bacteria and white cells. (You may need to blow your nose, clear your throat, or lance an abscess.) The bone marrow and other blood-forming tissues are stimulated to produce yet more white cells. Ultimately, in the normal course of events, inflammation is self-limiting: T suppressors call a halt once the infection is cleared or the wound healed. However, in autoimmune diseases like lupus and rheumatoid arthritis, “it ain’t necessarily so.”

Immune System Malfunction

Autoimmune diseases affect players in the immune system. For example, the AIDS virus attacks T helper cells, depleting them so that people with the disease eventually succumb to a range of opportunistic infections that a healthy immune system would normally take in its stride. In lupus, as in rheumatoid arthritis, the problem is an overactive immune system. The antibody-producing B cells increase eight- to tenfold, and the T suppressor cells, designed to suppress antibody production once the alien invader has POL text Q6 good.qxp 8/12/2006 7:39 PM Page 47

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been vanquished, are in short supply. B cells that produce antibodies with no obvious enemy to attack are called
autoreactive
—in other words, reacting to the body itself—and one of the things they appear to attack is immature T suppressor cells, which may explain the shortage of mature active ones in people with lupus.

A healthy immune system, like other body systems, depends on balance—on the right number of actors playing their parts at the right time, delivering the right lines, and then leaving the stage. For more than thirty years scientists have known that in lupus, B cells continue to produce antibodies when there is nothing to attack, and they have been trying to fathom why. Is it that the B cells are still getting messages (via those important cytokines) to attack, or are they failing to get the message (from other important cytokines) to stop? And is that because too many “Attack!” messages go out, or too few “Back off!” messages? Is the problem too many or too few message senders—helper T cells or suppressor T cells—or is it that the right messages get scrambled and don’t get through to the overactive B cells? When you realize how complex the interaction of these immune-system actors is, you can see how difficult it is to un-ravel which part of the play has gone wrong. From the point of view of scientists trying to put things right, it means lots of different places where they can try to intervene.

There is a colorful cartoon version of the inflammation battle-ground, plus a depiction of what goes wrong in lupus, on the Lupus Society of Alberta website (see Resources).

Messages in Blood

From the point of view of the doctors trying to make a diagnosis, there are lots of potentially malfunctioning components to look for in the lupus patient’s blood. The blood is the body’s transport system, and a great deal of information can be obtained by unpacking the things carried around the body in the bloodstream at any one time. Other bodily functions are also informative: urine, the fluid inside joints or spinal cord, blood-pressure readings, and recordings POL text Q6 good.qxp 8/12/2006 7:39 PM Page 48

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of the electrical activity of the heart and brain. But in lupus blood tests are vital. So if you have it, resign yourself to having a lot of needles stuck into you.

In addition to the clinical symptoms outlined in the last chapter, the remainder of the ACR diagnostic criteria for lupus are detected from blood tests. Here is a list of them:

◗
Hematological (blood) abnormalities
—These usually show up in a complete blood count (CBC), a procedure as basic as taking a pulse or blood-pressure measurement.

Almost all lupus patients will have some abnormal factor in their blood at some time in their illness. There could be a shortage of
erythrocytes
(Greek for “red cells”), the red blood cells that carry oxygen around the body. Shortage of red blood cells is called anemia (the names for things in blood often end in
-emia,
from the Greek for “blood”). Or there may be a shortage of white cells, the ones that fight disease, a condition called leucopenia (Greek for “white”

and “deficit”). Or there could be a shortage of blood-clotting cells, called
platelets
or
thrombocytes
(Greek for

“clotting cells”); this leads to excessive bleeding, in the form of either bruises or the bursting of small blood vessels in the skin, or sometimes it leads to the failure of a wound to heal properly.

Doctors also test the rate at which red cells in unclotted blood form sediment at the bottom of a test tube, a simple, nonspecific test called the
erythrocyte sedimentation rate
(ESR).
If there is inflammation or increased autoimmune activity in the body, the cells break down and the sediment collects more rapidly. The test is simple but rather crude, with several limitations. For instance, sedimentation may speed up for all sorts of reasons, for example because the patient has an infection or from any number of inflammatory conditions other than lupus; and indeed patients can be quite ill but have a normal ESR. Then again, it slows POL text Q6 good.qxp 8/12/2006 7:39 PM Page 49

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down if the patient is taking certain common drugs, like penicillin, diuretics, or vitamin A. But a doctor who has taken a thorough history will be alerted to this complication.

Blood may also be tested for C-reactive protein (CRP), which is produced by the liver in response to inflammation.

Like ESR the presence of CRP is an indicator of acute inflammation, though not specifically for lupus. It is more sensitive than ESR because it is only rarely found to be abnormally high in the blood of healthy people. Both ESR

and CRP are useful when it comes to monitoring the success or otherwise of treatment.

◗
Immunological disruption
—As explained, in lupus there is a massive increase in the number of antibodies circulating in the patient’s blood. Several different sorts are found, and four are highly significant for lupus:

1. The antiphospholipid antibody, which is responsible for an illness called
antiphospholipid antibody syndrome
or APS (a syndrome is a group of symptoms that occur together). Another name for the condition is

“sticky” blood syndrome or Hughes’ syndrome, after Graham Hughes, head of the Lupus Research Clinic at St. Thomas’ Hospital, in London, and one of the foremost experts on the disease (see his books or Triona Holden’s
Positive Options for Antiphospholipid Syndrome (APS),
in “Further Reading”). In 1983, Dr.