Joann Anastasi never imagined that her body would betray her. At 51, she was a full-time hair stylist with plenty of extra energy for dancing and handicrafts. "I was always busy," she says. "I was a whirlwind." But all that changed when Anastasi began to feel sluggish and achy. At first, she assumed she was simply "running out of steam" as she aged. But over the course of several months, her symptoms intensified into a full-body assault--overwhelming fatigue, painful joints and muscles, hypersensitivity to cold, and hands so swollen she had to quit her job and her hobbies. On top of all that was the mystery of it all: nobody could tell her what was wrong. "I think they thought it was all in my head or I was just stressed or menopausal," she says. Finally--after more than a year of visits to four different specialists (an endocrinologist, an orthopedist and two rheumatologists, one of whom suggested antidepressants)--Anastasi, now 53, got a diagnosis. She had scleroderma, a "crazy disease," as she calls it, that hardens the skin and can ravage organs. "My body just turned on itself," says Anastasi, who nevertheless counts herself among the lucky ones: "At least now I know what I have."
Scleroderma belongs to a family of about 80 chronic illnesses called autoimmunedisorders. Their common trait: an immune system that attacks the body's own tissue. You've heard of some of them--multiple sclerosis, rheumatoid arthritis, Graves'disease. Others, like lupus, Sjogren's syndrome and ankylosing spondylitis are less well-known. They assault everything from the skin and nervous system to joints, muscles and vital organs--and they afflict at least 12 million Americans, three quarters of them women. "This is a horrible group of diseases," says Dr. Michael Lockshin, director of the Barbara Volcker Center for Women and Rheumatic Disease at the Hospital for Special Surgery in New York. "The immune system is supposed to be the ultimate arbiter of protection. In these diseases, what was supposed to protect the body begins to destroy [it]." To make matters worse, autoimmune diseases strike without warning, often during childbearing years, and can cripple or even kill. But the picture isn't completely bleak. New drugs that soothe the aches are now hitting the market, and researchers are busy devising even more sophisticated treatments. Perhaps the brightest hope is that doctors are now getting better at simply diagnosing these illnesses.
That isn't easy. Because the diseases mimic one another and are poorly understood, diagnosis can be drawn out, at best. Doctors often miss or even brush off vague problems like lethargy and joint pain--classic symptoms of autoimmune disease. A survey by the American Autoimmune Related Diseases Association found that 65 percent of patients were labeled as "chronic complainers" or hypochondriacs in the early stages of disease. That could change, though, as women learn more about autoimmunity, prompting their doctors to take complaints seriously. "Generally speaking," says Lockshin, who finally diagnosed JoAnn Anastasi, "the earlier you get someone into treatment, the better off they are."
Here's what seems to happen in autoimmune diseases: Healthy immune systems work around the clock to fight off viruses and bacteria. T cells, the soldiers of the body, monitor for foreign invaders or antigens. When necessary, they call out the troops--an army of B cells--to destroy the enemy. In most people, all works splendidly, keeping us well enough to march off to work every day. But in people with autoimmune diseases, the T cells go hay-wire: they somehow become confused, mistaking the self for an outsider and assaulting healthy tissue (diagram).
Scientists don't know why the system breaks down, but they have a number of theories. Hormones are a plausible culprit, since women are so much more likely than men to have autoimmune disorders. But the evidence is far from conclusive. It is possible, for instance, that testosterone protects against autoimmunity--and yet some men still suffer from the disorders. The role of female hormones is even more con- fusing. Some autoimmune diseases strike women in their 20s and 30s, when estrogen is high; others hit hardest before puberty or after menopause, when it's low. And during pregnancy (lots of estrogen), many women with rheumatoid arthritis and multiple sclerosis experience complete remission. Pregnant women with lupus, on the other hand, often find their symptoms exacerbated. "We don't know why women seem to have the corner on these diseases," says Dr. Denise Faustman, director of the Immunobiology Lab at Massachusetts General Hospital. "Autoimmune diseases are one big paradox."
To resolve it, scientists are now exploring the link between pregnancy and autoimmune diseases. In a study published last year, doctors found that fetal cells, which often persist in a mother's blood for years after delivery, may play a role in scleroderma. Women who had given birth to baby boys had substantially more fetal cells in their bodies than women without the disease. Researchers believe that the leftover cells somehow trip up the mother's immune system--the way a computer virus disrupts software--and trigger an attack.
Genetics also plays a role. Although there does not seem to be "a gene for" autoimmune diseases, a cluster of genes seems to increase susceptibility. It is not uncommon to find a bevy of autoimmune diseases within a single family. Jeanie Sanchez, 39, of Plainview, Texas, was diagnosed with lupus 11 years ago. Her nose and cheeks are covered in a red, butterfly-shaped rash--a telltale sign of the disease. Her sister also has lupus. A brother has diabetes, and their mother died of scleroderma at 52. Now Sanchez is worried about her four children, especially her daughter, Lydia, 5. "Sometimes I just sit and stare at her and wonder if that beautiful little face is going to be covered like mine someday," says Sanchez, "or if she'll get something worse."
Lydia could be spared. Though genes are considered critical, some scientists believe that an outside trigger, such as an infection, ultimately provokes disease. So far, the most conclusive connection is between strep throat and rheumatic fever, an autoimmune disorder. A severe, untreated case of strep increases your risk of getting this disease weeks later. Last year, Harvard University scientists reported another potential link: in laboratory mice, 75 percent of animals injected with the herpes virus (simplex 1) developed an autoimmune eye disease. Noninfectious substances may also be players. Long-term use of certain drugs, including ones that treat abnormal heartbeats or high blood pressure, can provoke symptoms that are indistinguishable from lupus. And for years silicone has been under attack by women who had breast implants and later developed autoimmune disorders. While a federally appointed scientific panel last year concluded that there is no direct evidence to support the claim, it didn't rule out the possibility of a connection.
Autoimmune patients would love to know what sparked their condition, but what they really want is good treatment. Conventional drugs work well at taming symptoms and alleviating pain, but many have serious side effects. Nonsteroidalanti-inflammatories, or NSAIDs (aspirin, ibuprofen and stronger prescription drugs), and steroids both reduce swelling. But the first group can corrode the stomach, and the second thins the bones and skin. The toughest drugs, immunosuppressants, restrain the immune system--but also leave patients highly susceptible to infection.
The good news is that researchers are now developing more carefully targeted remedies with fewer side effects. Many of the recent advances, including COX-2 inhibitors, have been made in rheumatoid arthritis. Though they aren't necessarily better than NSAIDs at reducing inflammation, COX-2s appear to be gentler on the stomach. In a trial of Celebrex, the first COX-2 approved by the Food and Drug Administration, researchers found that 0.2 percent of patients taking the drug developed stomach bleeding or ulcers, compared with 2 to 4 percent of prescription NSAID users. Other drugs in development home in on the mechanism of autoimmunity rather than treating its aftermath: an enzyme called tumor necrosis factor, or TNF, is believed to play a critical role in autoimmunity. Enbrel, a drug that blocks TNF, was approved by the FDA last November. And at the University of Texas, doctors are testing an extract from a 2,000-year-old Chinese herbal remedy called Lei Gong Teng (loosely translated as the "thunder-god vine") in patients who have not been helped by conventional therapies. The research is still in its infancy, but Dr. Peter Lipsky, the center's director, reports that the compound is reducing symptoms with little toxicity. Says Lipsky: "The Chinese wouldn't use something for several thousand years that didn't work."
Research is ongoing in other diseases as well. In lupus, researchers are testing a drug that destroys B cells believed to cause kidney damage. And in multiple sclerosis, a recently approved drug, glatiramer acetate, appears to be working as a decoy, seducing immune cells away from healthy tissue. Perhaps the boldest new therapy of all is a vaccine--not a conventional one that stimulates the immune system, but a highly targeted one that suppresses rogue T cells before they provoke disease. One such T-cell vaccine now being tested is showing promise in some patients with MS. "Finally," says Dr. Noel Rose, an immunology professor at Johns Hopkins University, "we're taking major steps forward." Perhaps one day those steps will stamp out the pain for good.