Lupus — “the wolf” — began stalking Debra McGann, a 40-year-old Waltham teacher, 15 years ago.
It made her deathly ill during all four of her pregnancies, and probably caused two of those pregnancies to fail.
It also triggered intermittent seizures and what McGann calls “little confusions.” For years, though, neither she nor her doctors had any idea that these and other neurological problems could be part of the disease’s treacherous march through the body.
Lupus has stalked 52-year-old Susan Shumaker of Cohasset for years, too, forcing her to give up her much-loved teaching job. Shumaker, too, suffered baffling neurological problems, including short-term memory loss, numbness on her scalp, “pins and needles” on her face and numerous small strokes — sometimes as many as 10 an hour — which made her temporarily unable to walk.
“It was terrifying,” she recalls. “I didn’t know what was happening,” and for months, neither did her doctors.
Today, “brain lupus,” a constellation of neurological and psychiatric problems including severe headaches, memory loss, strokes, seizures and even psychosis, is increasingly recognized as part of systemic lupus erythematosus, an immune system disease named for the characteristic facial rash that makes some patients look a bit like wolves with red cheeks.
For years, doctors have understood the basic mechanics of lupus: Misguided antibodies attack the body’s own tissues, often in the skin and joints, and sometimes, in organs like the kidneys as well, causing inflammation, pain and tissue damage.
Forty years ago, in fact, kidney failure was such a common consequence that half of all lupus patients died within four years of diagnosis. Today, thanks to better diagnosis and treatment, 90 percent live at least 10 years after diagnosis, and many live 20, 30 years or longer.
But increasingly, researchers are recognizing that tissue damage is not limited to joints and kidneys but often includes the brain as well.
Sometimes, brain damage occurs when antibodies made by the overactive immune system trigger blood clots, which can form in or travel to the brain, causing strokes. Sometimes, the destruction comes from misguided antibodies that cause inflammation of blood vessels in the brain, triggering seizures and memory loss. Sometimes antibodies or other immune substances called cytokines may directly attack brain tissue.
And sometimes, for obscure reasons, lupus simply causes spasms in blood vessels, resulting in decreased blood flow to parts of the brain, and often, migraine headaches, too.
However the damage occurs, two-thirds of people with lupus are now believed to suffer some kind of brain or behavioral problem, according to data presented at a recent conference at the New York Academy of Sciences.
Strokes, for instance, occur in 15 to 20 percent of patients, says Dr. Robert G. Lahita, a Columbia University specialist who organized the conference. Seizures occur in another 5 percent, he says.
And if one includes milder forms of depression, memory impairment and mood swings, as many as 90 percent of patients have neuropsychiatric problems from lupus, says Dr. Andrea Schneebaum, a lupus specialist at the Lahey-Hitchcock Clinic in Burlington.
Often, the depression is an emotional reaction to the stress of coping with a disease that can flare up painfully and unpredictably. But it may also be a “direct effect” of the immune disorder itself, says Dr. Malcolm Rogers, a Brigham and Women’s Hospital psychiatrist who treats many lupus patients.
In rare cases, people with lupus can become psychotic and wind up, improperly diagnosed, in mental institutions, says Henrietta Aladjem of Watertown, a patient advocate now in her 70s who has been in remission from lupus for 25 years.
Despite considerable progress, nobody really knows what causes lupus, though it is clear that the skin (or “discoid”) form of the disease can be triggered by ultraviolet light — and that avoiding sunlight and using sunscreens can help. At least six genes may be involved in the systemic form.
Nor does anyone know why lupus strikes disproportionately at women of childbearing age, though hormones, especially a tendency to convert one form of estrogen to another, are probably involved, says Lahita.
But doctors do increasingly understand how lupus wreaks havoc all over the body and how to deal with it.
In all of us, cells regularly die off through a process called apoptosis. As they die, they spill their contents, including bits of broken DNA, into the bloodstream. The immune system then makes antibodies that search out and get rid of this debris.
But in lupus patients, apoptosis seems to be excessive, and the body responds by making huge quantities of antibodies to clean up the mess, says Dr. Peter H. Schur, director of the lupus center at Brigham and Women’s Hospital.
Lupus patients, for instance, often make too much of an antibody called ANA, or antinuclear antibody. This antibody gloms onto broken bits of nucleus from dead cells, then the whole complex travels to the kidneys, clogging delicate tissues.
Lupus patients also make excessive amounts of antibodies against other substances in the body, including DNA itself, the proteins that hold DNA together, a protein called ribosomal P and fatty proteins called phospholipids.
The payoff for patients of this increasingly-detailed knowledge of lupus antibodies is that doctors can now track antibody levels to predict incipient flare-ups of disease.
High levels of antiphospholipid antibodies, for instance, can be a warning sign because they can trigger blood clots that can lead to strokes. Strokes can often be prevented by taking aspirin or other blood thinners, such as Coumadin.
High levels of a natural amino acid called homocysteine can also be a signal of increased risk of stroke, says Dr. Ronenn Roubenoff, a rheumatologist at Tufts University.
And brain scans such as PET and SPECT are also helping doctors detect incipient problems such as decreased blood flow to certain areas of the brain, which raises the risk of seizures and memory impairment. Once seizures occur, a growing array of drugs, including Dilantin, Phenobarbital, Tegretol, Depakote and Valproic acid, can help prevent further attacks.
A generation ago, says Schur, there wasn’t much doctors could do except prescribe high doses of corticosteroids such as Prednisone. High-dose steroids do a good job of damping down an overactive immune system, but they can also cause memory problems and leave a patient prey to infections.
Today, says Schur, doctors not only have better antibiotics to manage steroid-induced infections, but better immunosuppressants, too, including Imuran and Cytoxan, and a better sense of how to use them to block inflammation.
And now that doctors are sensitized to look for neuropsychiatric problems in lupus patients, they are getting better at using even simple paper and pencil tests to determine whether cognitive difficulties stem from damage to part of the brain or emotional reactions to the disease. Cognitive problems that stem from depression can be treated with antidepressants; those that stem from an inflammation in the brain can be treated with steroids.
Experimental drugs may soon play a growing role, too, including DHEA (dihydroepiandrosterone), a natural hormone not yet approved as a drug by the Food and Drug Administration, that seems to offset lupus symptoms in some patients.
The bottom line, says Schur, is that lupus “is not as bad as it used to be. There are a lot of things we can do.”
And that goes for brain lupus, too. If you have lupus and run into problems with memory or depression, don’t suffer in silence, says Schneebaum of Lahey-Hitchcock. You should “absolutely tell your doctor,” because treatments can help.
So can your attitude.
“You have two options,” says McGann, the Waltham teacher. “You can let the disease run your life, or you can let go of it and get on with your life the best you can. . . You don’t have to let it be the center of everything.”
Susan Shumaker agrees. While her memory problem has not gone away, she and her husband have learned to deal with it.
Initially, her mental problems were “very frightening for both of us,” Shumaker says, because she had to keep asking the same questions over and over. In fact, her memory problems meant they had to move back to the suburbs, because the city was too confusing.
But she has gradually learned little tricks — like setting timers in the kitchen to remind her to turn off the stove — and, more importantly, how to live day by day.
“My life has really been quite different from what I would have thought,” she says. But she manages well, thanks to “a strong spiritual life and a strong network of wonderful friends and family.”
SIDEBAR:
For more information on lupus, call:
- The Lupus Foundation of America, Massachusetts Chapter, 617-332-9014.
- The Lupus Foundation of America, toll-free national information number 1-800-558-0121.