Positive Options for Living with Lupus (9 page)

Hughes’ team described a disorder characterized by blood clotting in both arteries and veins. Pregnant patients with the problem had a tendency toward recurrent miscarriage, and all sufferers were at higher risk for stroke. (A stroke occurs when a clot of blood that has formed in a blood vessel breaks loose and travels to the brain, causing loss of function and sometimes death.) APS affects perhaps 1 to 2 percent of the POL text Q6 good.qxp 8/12/2006 7:39 PM Page 50

5 0

Po s i t i v e O pt i o n s fo r L i v i n g w i t h L u p u s
general population, but a very high proportion of lupus patients, to the extent that its presence is highly suggestive, if not conclusive, of the disease. The discovery was also important because it showed that not all the features of lupus were caused by inflammation.

(More about APS antibodies appears in Chapter 10.) 2. About 40 to 50 percent of lupus patients have an antibody known as anti-Sm (the “Sm” has no medical meaning; it comes from the name of the patient in whom it was first identified). The test for it is not particularly sensitive (a high percentage of people with lupus do not test positively), but it may be unique to lupus, hence highly specific (no false positives).

3. Elevated levels of anti-DNA, an antibody to the basic building block of life (deoxyribonucleic acid, found in the nucleus of all human cells), occur at some stage in at least 50 percent of people with lupus. Some researchers believe it may be unique to lupus, making it highly specific, though not particularly sensitive (many lupus sufferers test negatively).

4. Finally, there is an antibody found at high levels in the blood of people with lupus that, although not exclusive to them, is considered so significant that it war-rants the status of an ACR diagnostic criterion.

Antinuclear antibodies
(ANA) appear to react indis-criminately against material released from the nucleus of a cell when it has been destroyed. Although patients with other diseases—rheumatoid arthritis, liver disease, and some infections—as well as those on some drugs, also react positively to this test, a very high proportion of lupus patients (in some studies between 90 and 100 percent) test positive, which makes it one of the most sensitive tests available, although POL text Q6 good.qxp 8/12/2006 7:39 PM Page 51

D i a g n o s i n g L u p u s , Pa r t 2 : I n t h e L a b o ra t o r y
5 1

again, not highly specific. Yet another sign that an abnormal degree of cell destruction has taken place (all that broken furniture) is the presence of unusually high levels of freely circulating DNA in the blood of lupus patients. DNA properly belongs
inside
the nucleus of a whole cell, not wandering about in the bloodstream.

The last two antibodies listed are noteworthy and distinctive.

They are not the kind present in the blood because the patient had been exposed to and has fought off an infection like tuberculosis.

Nor are they the kind stimulated deliberately by vaccination to protect people against a future attack of an illness like measles. These are antibodies characteristic of autoimmune conditions; they do battle with the body’s own cells. These antibodies don’t react to in-tact tissues and organs, but rather to broken-down pieces of cells released during the autoreactive battle.

With few exceptions, normal cells in the body die eventually; the body is in a continual process of renewing and replacing itself, disposing of old, worn-out cells and building new ones, all with no disruption to the smooth running of the body as a whole. The process of normal, programmed cell death is known as
apoptosis,
from two Greek words that mean “falling away.” One avenue that scientists are exploring is that in autoimmune diseases something goes wrong with normal apoptosis. Instead of quietly falling away,

“elderly” cells totter on in a decrepit state, continuing to promote inflammation and abnormal autoreactive activity (see Chapter 11).

Other Signs, Other Diagnostic Techniques

I know this has been a long, rather difficult chapter, and it isn’t over yet. Please hang in there and read this section, even if you have skipped reading about some of the complicated antibody tests.

Some symptoms that aid diagnosis used to be on the ACR list but have been dropped. One is hair loss. About a quarter of lupus POL text Q6 good.qxp 8/12/2006 7:39 PM Page 52

5 2

Po s i t i v e O pt i o n s fo r L i v i n g w i t h L u p u s
patients experience hair loss, but there can be alternative explanations. Another is a condition known as
Raynaud’s phenomenon,
which is a bit like frostbite and can exist independently of, as well as in association with, lupus. Raynaud’s phenomenon is caused by a spasm of small blood vessels—
vasospasm—
which shuts off the circulation to the extremities, usually the fingers but occasionally the ears, nose, or toes, so that they turn white, then blue with cold, and then red and painful. More about this condition can be found in Chapter 9.

Other significant changes may show up in the blood of lupus patients; for example, the amount of complement—the antibody-support troops who figured in the description of inflammation earlier in this chapter—may be depleted as a result of prolonged inflammation. Other, more interesting, though not specific, antibodies may also add support to a diagnosis. But for now that’s quite enough about antibodies.

The St. Thomas’ Criteria

Before we can move on from diagnosis to the important business of how lupus patients are treated, I would like to return for a moment to the concept that says, “the eye of the experienced beholder is worth a laboratory-load of tests” that we encountered in Chapter 4.

Graham Hughes, who heads the lupus unit at St. Thomas’ Hospital and who was responsible for identifying Hughes’ syndrome, says in his book
Lupus: The Facts
that the ACR list, although invaluable for the purpose of
classifying
lupus, is restrictive when it comes to diagnosis. “It narrows the scope for lateral thinking in clinical medicine, something which lupus, above all, allows us in abundance,” he says.

Dr. Hughes has drawn up an alternative diagnostic list of fourteen lupus symptoms (eleven of which are summarized below) that may be detected in the doctor’s office from observation or the patient’s history. They have, he admits, no statistical justification. They are based “solely on the experiences gained in a huge clinical practice.”

(He also lists additional evidence that may be noted in laboratory tests, but these three criteria are not included below.) POL text Q6 good.qxp 8/12/2006 7:39 PM Page 53

D i a g n o s i n g L u p u s , Pa r t 2 : I n t h e L a b o ra t o r y
5 3

◗
“Growing pains.”
In the U.K. and the U.S. this is a label widely used for joint pains occurring during childhood and teenage years. While usually considered benign, they are often severe enough for the child to be taken to a doctor.

Some patients give a history of “rheumatic fever,” a label that persists, at least in the U.K., despite the condition’s almost total disappearance.

◗
Teenage migraine.
This symptom is associated with antiphospholipid (Hughes’) syndrome. Many patients over age thirty with cerebrovascular accidents (blood clots that migrate to the brain) give a past history of recurrent spontaneous abortions (miscarriages) in their twenties and

“migraine headaches” in their teens.

◗
Infectious mononucleosis.
Prolonged periods of patients having missed school due to infectious mononucleosis (sometimes called “glandular fever”) is a recurrent theme among lupus sufferers.

◗
Severe reaction to insect bites.
In Dr. Hughes’ book
Lupus: The Facts,
he says, “The skin is a major organ affected by lupus. It would be surprising if hypersensitivity to insect bites were not an important phenomenon in lupus.”

◗
Recurrent miscarriages.
Dr. Hughes again: “To be precise, this criterion is not truly a lupus criterion, but is an indicator of those lupus patients with the antiphospholipid or Hughes’ syndrome. Indeed, in our lupus pregnancy clinic we believe that if APS patients are excluded, then lupus itself is not a cause of recurrent spontaneous abortion.”

◗
Allergy to Bactrim or Septra (a common antibiotic drug)
or sulfonamide (an old sulfur-based antibacterial drug;
also called sulfa drug).
It is quite common for patients to report not only a history of severe rashes and other adverse POL text Q6 good.qxp 8/12/2006 7:39 PM Page 54

5 4

Po s i t i v e O pt i o n s fo r L i v i n g w i t h L u p u s
reactions to Septra, but also that the clinical onset of lupus coincided with their taking of the drug.

◗
Agoraphobia (fear of open spaces) or claustrophobia
(fear of enclosed spaces).
It is known that the central nervous system is involved in lupus. Dr. Hughes believes that evidence of abnormal fears in a patient’s history indicate a pre-lupus warning. He says, “The history, varying from panic attacks in shops to fear of motorway [highway] driving, for example, is sometimes protracted, lasting months or years. In many cases, the history is not volunteered, or the episodes are considered unrelated or ‘something from the past.’ ”

◗
Finger flexor tendonitis (difficulty in extending the fingers flat caused by joint and tendon inflammation).
The patient says, “I cannot say my prayers.” Dr. Hughes values this as a lupus pointer because it varies from the pattern of finger-joint inflammation seen in other connective tissue diseases like rheumatoid arthritis.

◗
Premenstrual exacerbations (problems).
All rheumatic diseases are influenced by the menstrual cycle, and none more so than lupus. Some patients are almost immobilized during the two to three days preceding menstruation. Dr.

Hughes: “It is my practice in some cases to alter the dose of medication during this time. Although difficult to quantify, I believe that significant premenstrual disease flare is sufficiently prominent in lupus to be included in this alternative list.”

◗
Family history of autoimmune disease.
This is self-evident common sense. Dr. Hughes comments, “In old-fashioned history-taking, the family history is important. Lupus is genetically determined, and the presence of other autoimmune diseases in the family (including thyroid disease) is worthy of inclusion in the clinical scoring system.”

POL text Q6 good.qxp 8/12/2006 7:39 PM Page 55

D i a g n o s i n g L u p u s , Pa r t 2 : I n t h e L a b o ra t o r y
5 5

◗
Dry Schirmer’s test (the doctor sticks a sliver of blotting
paper into the lower eyelid).
According to Dr. Hughes, the test is “highly irritant and only if the patient has some abnormality of the tear duct—as in lupus or
Sjögren’s syndrome—
will the paper remain dry. In a patient with vague or nonspecific symptoms, a bone-dry Schirmer’s test points towards one of the autoimmune diseases.”

In conclusion, Dr. Hughes says, “All of us can diagnose lupus in the presence of a butterfly rash,
nephritis
[kidney disease], and alopecia [hair loss]. The challenge comes at the other end of the spec-trum; the atypical case; the mild case; the differential between real disease versus no organic disease whatsoever; the ailing teenage daughter of a known lupus patient.”

POL text Q6 good.qxp 8/12/2006 7:39 PM Page 56

Chapter 6

Treating Lupus with Drugs,

Part 1

Lupus is a fiendish beast to track down, hence the immense effort to arrive at a diagnosis. Once the doctors are pretty sure they have it in their sights, however, the plan of attack can be made. Lupus has many manifestations, and treatment is inevitably tailored to the severity of the patient’s symptoms. The protocol for treating the illness comprises four main drug groups:

1. Painkilling nonsteroidal anti-inflammatory drugs (NSAIDs) 2. Antimalarials

3. Steroids

4. Immunosuppressants

Up to the middle of the last century, lupus was so poorly understood that doctors had little science to guide them; hence they adopted the “let’s-see-if-this-will-do-any-good” principle still somewhat in use today. Serendipity and the law of averages mean that such pragmatism quite often produces a hit. There may also be dis-asters, and success via serendipity does not greatly advance our understanding of the disease process. The other snag of the approach
56

POL text Q6 good.qxp 8/12/2006 7:39 PM Page 57

Tre a t i n g L u p u s w i t h D r u g s , Pa r t 1

5 7

is that even when a drug appears to work against some symptom of a disease, unanticipated and harmful side effects, or the emergence of subgroups of people who are particularly vulnerable to them, emerge only later. These are some of the reasons why
therapeutics
—

that is, treatment of illness with drugs—advances these days by means of properly controlled trials that demonstrate effectiveness and side effects before new, experimental treatments are licensed for general use (see the box “Randomized Clinical Trials (RCT): The Therapeutic Gold Standard,” on pages 58–59).