Positive Options for Living with Lupus (6 page)

Studies of assorted male and female hormone levels in humans with lupus are mostly inconclusive. Sometimes they are higher than average, sometimes lower, but not consistently so. An additional problem is that normal men and women both carry the same hormones; it is the
balance
between them that distinguishes the sexes.

A significantly lower-than-average level of one hormone
was
found in both men and women with lupus. This was a form of androgen called
dehydroepiandrosterone (DHEA),
which is a precursor of both the male hormone testosterone and the female hormones estradiol and progesterone. (The fluctuating balance of these two regulates fertility in women.) If something is in short supply, it is always possible that raising it will produce an improvement or confer protec-tion, as it did for the lab mice, so the role of DHEA in lupus is one avenue that is being investigated. Abnormal levels of another hormone, prolactin—which in women plays a major role in enabling POL text Q6 good.qxp 8/12/2006 7:39 PM Page 30

3 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
the production of breast milk—is being investigated in both men and women. See Chapter 11 for a discussion of drugs that affect these hormones.

It’s Not What You’ve Got, It’s What You Do

with It That Counts

Before we finish with hormones as a possible cause of lupus susceptibility, let us look at what happens to them in the body. Perhaps it is not the levels, or even the balance, of hormones that makes lupus sufferers different; perhaps it is how their bodies
metabolize
hormones—break them down and put them to use. Several other conditions are caused by a failure to metabolize something useful rather than a shortage of the raw material itself. For example, type 2 diabetes is caused not by underproduction of insulin, like type 1 is, but by the failure of the body to utilize the hormone. Other diseases are caused by the inability to break down and absorb the foods that contain essential nutrients even when the diet itself is not deficient.

After menopause, reduced levels of estrogens in the body make it more difficult for women to absorb calcium, even if they maintain a diet rich in the mineral, and this increases the risk of
osteoporosis—

brittle, easily broken bones (see Chapter 7).

Some studies have indeed found that lupus patients of both sexes metabolized estrogens differently from other people. This is an avenue researchers are continuing to explore.

Environmental Triggers and the

Infection Connection

Why, then, does one identical twin develop lupus while the other doesn’t, given that both share the same genetic vulnerability and MHC? The prevailing idea is that something in the environment triggers the disease, but since both twins are susceptible it figures that only one can have been exposed to the crucial trigger.

The most popular candidate for an environmental trigger is infection early in life. This theory is proposed for a number of diseases POL text Q6 good.qxp 8/12/2006 7:39 PM Page 31

T h e C a u s e s o f L u p u s

3 1

where the autoimmune system starts attacking the body’s own tissues. The hypothesis is that, faced with an infection, the immune system gets to work to fight it, but for some reason when the infection is vanquished, instead of withdrawing, the immune system turns its guns on healthy tissue. This could be what happens in insulin-dependent diabetes, in leukemia, and in rheumatoid arthritis; some quite-unnoticed infection flips the switch and starts the antibodies off in the wrong direction.

The infectious agents that best fit the profile of a lupus trigger are viruses. Viruses are cellular parasites. There are many varieties, and what they all have in common is that they break into a living cell, hijack its reproductive system to make little virus offspring, and lurk, concealed in the body, sometimes for years. Because they hide inside cells it makes it very difficult for the immune system to access and destroy them. Nevertheless the body usually manages to generate antibodies against a virus. The presence of such antibodies in the blood of a patient therefore becomes like the footprint of where a virus has been, even when the symptoms of an acute attack have gone.

Researchers hot on the trail of a lupus trigger have looked for antibodies that might reveal that particular viruses have been there.

Researchers connected with two studies, one in France and the other in the United States, thought they detected antibodies to a retrovirus, but were unable to link it to any known human variety such as HIV. Other researchers have looked for signs that infection by one of the
herpesviruses
might be responsible for triggering lupus or other autoimmune diseases. Herpes, as explained in the box titled “Know Your Virus” (on the next page), stays dormant in the body once it has invaded, flaring up occasionally—rather like lupus—usually when the body is under stress.

The evidence from these studies is encouraging; some patients with lupus, and related autoimmune disorders, did indeed appear to have elevated levels of antibodies for some of the viruses considered. But then again, these are pretty common viruses; many people have been exposed to them, so nothing very solid has been proved POL text Q6 good.qxp 8/12/2006 7:39 PM Page 32

3 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
against them yet. Still, experts are confident they are looking in the right place for a lupus trigger in targeting viruses. Lupus expert Sheldon Blau says, “It is likely when the primary cause of lupus is found—and it
will
be found eventually—it will turn out to be a virus, whether a retrovirus, a herpesvirus or some other type that behaves in an unusual manner (or is permitted to behave in an unusual manner in some individuals, perhaps those with particular genetic characteristics).”

Blau advances yet another interesting hypothesis. Could autoimmune illnesses like lupus be triggered in people with the genetic susceptibility because they are subject to attack from
two or more
directions at the same time? In his book
Living with Lupus
(see Resources) he writes, “Perhaps the massive autoreactive activity in Know Your Virus

There are many groups and subdivisions of viruses. Viruses are composed of an inner core of genetic material—the bit that reproduces itself—surrounded by a coat of protein. In diagrams they look a bit like a chestnut or a sea mine, with a spiky outer layer. The genetic core may be made of either DNA (the same material humans are made of) or a slight variation called ribonucleic acid (RNA).

The DNA group includes a large family of viruses responsible for many childhood infections of the nose, throat, and eye. The bad members of this clan are the poxvirus, which is responsible for smallpox, the milder cowpox (from which smallpox vaccines are made), and the notorious herpesviruses. The name “herpes” comes from the Latin and Greek for “creep”; it is also the root word for “reptile” or “ser-pent.” Various members of the herpes tribe cause cold sores, genital sores, chickenpox, and shingles—conditions in which the blisters or lesions “creep” round the body. Once they have you, you have them for life. Herpesviruses are being investigated as candidates for a lupus trigger.

The RNA family of viruses also includes troublesome relatives.

The members of one group, called myxoviruses, make themselves at home in the mucous lining of the nose and throat (myxa is Greek for

“mucous”). Influenza is a myxovirus. Their close relatives, the para-myxoviruses, include measles, mumps, and scarlet fever. There is also a parainfluenza virus that causes coughs and colds. (The Greek prefix POL text Q6 good.qxp 8/12/2006 7:39 PM Page 33

T h e C a u s e s o f L u p u s

3 3

these conditions stems from a frenzied immune-system effort to stave off simultaneous acute infections by, say, a retrovirus
and
a herpesvirus.”

The Wolf’s Domestic Cousins: Pets

Viruses are not the only suspects in the search for an environmental lupus trigger. A particular group of people that we haven’t mentioned so far is more prone to lupus and other autoimmune disorders: pet owners.

By and large, diseases do not jump species. There are some in-famous exceptions, however, like swine flu and the recent cases of new-variant CJD contracted from diseased cattle; and children often catch the fungal infection ringworm from their pets.

para means “beside” or “closely related to.”)

Another group worth remembering is the retroviruses, a group you will hear a lot about. For some time it had been known that retroviruses caused illness in animals. Then in 1981 a retrovirus was found to be the cause of a rare form of human leukemia that damaged a group of cells that are part of the immune system, the T lymphocytes.

This retrovirus was christened “human T-cell lymphotropic virus,” or HTLV for short. Later, a similar retrovirus was identified (HTLV-2) and still later a third (HTLV-3). This last became perhaps the most famous and feared retrovirus in history. It is now better known as the human immunodeficiency virus—HIV. Over a period of years it wreaks such havoc in the immune system that, left untreated, it leads to death from AIDS.

But back to lymphocytes. In addition to T lymphocytes—the ones implicated in the rare leukemia and in HIV—there are also B lymphocytes. When a foreign invader is detected, B lymphocytes produce antibodies specifically to attack that particular invader (the antibodies are antigen-specific). Two types of T lymphocytes work alongside these B cells. T “helper” cells do exactly what the name implies; they support the work of B cells, partly by cleaning up the debris of the battle against foreign invaders. T “suppressor” cells do just the opposite.

They act like a damper or governor, making sure B cells don’t get overenthusiastic in their activity. The T suppressor cells fail to do their job in several autoimmune diseases.

POL text Q6 good.qxp 8/12/2006 7:39 PM Page 34

3 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
The wolf’s domestic cousin, the pet dog, is implicated in lupus.

The fact that dogs develop lupus became widely known in the U.S.

when, in the early 1990s, the first President George Bush and his wife, Barbara, both developed a condition called Graves’ disease, an autoimmune illness of the thyroid gland. At the same time it was discovered that the Bushes’ dog, Millie, had lupus.

Tess’s Story

Tess, a university student, developed lupus while t aking finals.

Her family had been watching anxiously for the illness ever since Tess had started her periods, because her mother also had lupus.

She had discovered the illness during the 1950s, when she had become pregnant and then lost the baby. Tess managed to complete her finals, and once she started taking an antimalarial drug the rash that had appear ed on her f ace, back, arms, and c hest began to calm down. During summer vacation she took it easy, and it looked as though the first flare-up was behind her. Then she noticed a funny thing. Her cat Jinxy was off her food, was re-luctant to move from her cushion, and when she did move she appeared stiff and in pain. Chunks of her fur ev en started to come out. Tess took Jinxy to the vet, who discovered that the cat had severe ulcers in her mouth. He called the condition “stoma-titis,” a general term for inflammatory disorders of the mouth.

But Tess was convinced her cat had lupus. “Cats don’t ge t lupus,” insisted the vet, but he agreed to give Jinxy a corticosteroid injection. Within a few days she appeared to get better.

Unusual anecdotes do not constitute proof. However, where dogs are concerned there is solid evidence that they do suffer from a form of lupus, exhibiting symptoms similar to humans, including arthritis, skin lesions (mostly around the nose) that are aggravated by sunlight, and kidney problems. The canine condition also shows a similar pattern of flare-up and remission, and responsiveness to the same drugs. So could there be transmission between pet and owner? A small study published in
The Lancet
in 1992 offers some support to this notion. A group of dogs owned by patients with lupus was compared with an outwardly healthy group owned by non-POL text Q6 good.qxp 8/12/2006 7:39 PM Page 35

T h e C a u s e s o f L u p u s

3 5

sufferers, and also with a group of dogs diagnosed as already having lupus. To all outward appearances the lupus patients’ dogs were perfectly healthy, but when their blood was tested it was found to have significantly higher levels of the antibodies characteristic of lupus sufferers’ blood than were found in both the healthy control animals and the dogs known to have lupus! Something linked the lupus humans and their dogs, but what exactly? A link between pet owner-ship and a higher incidence of other autoimmune diseases has also been found, though it is not always supported by blood tests demonstrating that pets and owners carry the same antibodies.

Scientists are always reminding us that just because two things happen at the same time, or follow each other, it doesn’t mean that one
causes
the other. It could be coincidence. It could be that both events share a common cause, some environmental trigger or infectious agent that affects pets and humans who live together. One thing is certain, however: Pets and their human owners don’t share the same genetic susceptibility!

Other Possible Environmental Triggers

One or two other possible lupus triggers have been investigated.

Smoking is known to trigger a flare-up in people with lupus. A number of recent studies point to smokers being as much as two times more susceptible to lupus as nonsmokers. A similar effect has been noted with other autoimmune diseases.

Evidence that an environmental pollutant is contributing to an illness is usually found in the form of
clusters
—that is, an increased incidence of a disease in particular localities or geographical areas.

Clusters of juvenile leukemia were discovered in areas around a nuclear power plant in Sellafield, England, suggesting that the plant was in some way triggering the illness. Pesticides and certain industrial toxins have been implicated in other diseases. Lupus clusters are very rare. One was reported in Arizona in the mid-1990s, and exposure to pesticides or other industrial contaminants was postu-lated as a possible cause but not backed up by firm evidence.