August 15, 2000
By LINDA VILLAROSA
Abby Bernstein feels as if she has been told that she has just about every ailment in the book. Over the past 12 years, dozens of medical specialists have informed her that she has the flu, drug allergies, mononucleosis, Epstein-Barr virus, a gallbladder problem and even food poisoning.
And, of course, she has been told several times that she has absolutely nothing, despite chronic bouts of nausea, fever, fatigue, skin lesions and swelling in nearly every joint in her body, including her jaws.
"I was a doctor's nightmare," said Ms. Bernstein, a 41-year-old legislative director for a union in Washington.
Now Ms. Bernstein knows differently. She suffers from two distinct disorders -- autoimmune hepatitis and rheumatoid arthritis. What these two illnesses have in common is that they are both autoimmune diseases, part of a large family of disorders, which, according to the National Institute of Allergy and Infectious Disease, strike an estimated 14 million Americans. Some estimates run as high as 50 million. The vast majority of those afflicted are women.
Though the causes remain unclear, autoimmune diseases are set off when an out-of-control immune system causes the body to attack its own tissues. The diseases can attack the skin, nervous system, the joints and any of the organs. They include the familiar (rheumatoid arthritis, Type 1 diabetes, multiple sclerosis, lupus, psoriasis and Graves' disease) and the obscure (autoimmune hepatitis, Sjogren's syndrome and polymyositis).
Like Ms. Bernstein, people with autoimmune disorders often move from doctor to doctor, trying to piece together the confusing puzzle of symptoms, which sometimes disappear as quickly as they come. Even after an autoimmune disorder is diagnosed, patients can often do little beyond treating the various symptoms of the disease. And diagnosis, the American Autoimmune Related Diseases Association says, takes an average of five years and seven doctors.
And, more confusingly, new research points out that many, if not most, people who have an autoimmune disease have more than one, which may require treatment by many different specialists and a number of medications.
"If I wanted to, I could quit my job and just go to the doctor every day," Ms. Bernstein said. "But at this point I know more than they do. The one who's really managing my care is me."
Despite confusion about the diseases, some doctors are looking at the disorders as a group and focusing on their connection -- an overactive immune system. More experts are linking them in diagnosis and prescribing treatments that work for more than one disorder, and researchers are studying the immune system for a common cause, and, eventually, a cure.
"These various illnesses have the same etiology, and we should group them together the way we do with different cancers," said Virginia Ladd, the president of the autoimmude disease association, an advocacy organization in Eastpointe, Mich. "But unfortunately, we have no autoimmunologists, no autoimmune clinics and no autoimmune department in institutions. Things are changing but it can still end up being very frustrating for patients and their families."
When the immune system is functioning properly, its job is to ward off invaders like viruses and bacteria. In people with an autoimmune disease, however, the immune system works overtime, mistakes the body's own cells for intruders and assaults its own cells and tissues.
Why the body would turn on itself remains unclear. But there are theories. Some blame female hormones, particularly estrogen, which may explain why autoimmune diseases are three times as common in women as in men, especially women in the childbearing years.
"Autoimmunity is basically a women's problem," explained Dr. Michael D. Lockshin, the director of the Barbara Volcker Center for Women and Rheumatic Disease at the Hospital for Special Surgery in New York. "For one, women have more vigorous immune responses. Compared to men, they have a higher antibody response to the same inciting agent, be it a virus, infection or a vaccination."
The menstrual cycle, with its hormonal ups and downs, also creates monthly changes in a woman's immune system. Recently, researchers have looked at how the immune system is affected during and after pregnancy, a period marked by drastic hormonal swings. During pregnancy, when estrogen levels are high, for example, the immune system goes into a kind of "sleep mode," mainly to prevent the mother from rejecting her fetus. After delivery, the immune system kicks in again, sometimes too much, which can result in an autoimmune disorder, most commonly in the thyroid.
Still, hormonal swings do not completely explain autoimmune disorders and may even cloud the picture. For example, although some autoimmune disorders, like rheumatoid arthritis and multiple sclerosis, go into remission when a woman is pregnant, others, like lupus, worsen.
Moreover, viruses, bacteria, parasites, medication and even stress can set off an autoimmune disease. It may be that one of these agents causes inflammation, which somehow brings on an autoimmune response. It is well established, for example, that a bout of strep throat can set off rheumatic fever, an autoimmune disorder.
A new theory, known as the hygiene hypothesis, postulates that improvements in sanitary conditions, including the multitudes of antibacterial products lining drugstore shelves, have somehow caused immune systems to become hypersensitive to outside agents.
"The hygiene hypothesis is a popular and interesting theory," said Dr. Noel Rose, a professor of pathology and immunology at Johns Hopkins. "But there isn't much firm evidence to support it. It could be that there is more autoimmune disease now because people are living longer and have more time to manifest it. It remains uncertain."
What is more clear is that genetics plays an important role. "In the last five years, there has been increasing evidence that autoimmune diseases run in families," said Ms. Ladd of the disease association. "And not just the same disease: in one family, the mother could have lupus, the daughter Type 1 diabetes and the sister psoriasis." Ms. Ladd, who has had lupus for more than 30 years, notes that in her own family, 5 of 13 siblings have one type of autoimmune disorder or another.
Dr. Catharine Shaner, 41, a pediatrician in Allentown, Pa., knows all too well the reality of inherited autoimmune disease. She has both Sjogren's syndrome, marked by very dry eyes and mouth, and fibromyalgia, which is strongly suspected to be autoimmune in nature and causes fatigue and muscle pain. Laura, her 13-year-old daughter, has rheumatoid arthritis.
Between them, they see 15 doctors, and take 18 medicines a day.
"For us, there's definitely a family connection," said Dr. Shaner, who has had to quit her practice. "Along with Laura and me, my mother and one of my brothers have hypothyroidism."
For the most part, patients have been able to do little more than find ways to ease their lists of symptoms. Some take a drug, or several, to ease the pain and inflammation common to lupus, rheumatoid arthritis and many other autoimmune disorders. Nonsteroidal anti-inflammatories, like ibuprofen or stronger prescription drugs, are extremely common, but they can also cause stomach problems.
The newer Cox-2 inhibitors also reduce swelling and are gentler on the digestive system. Other patients take immunosuppressants, like steroids, that offer a wholesale suppression of the immune system, but these have more serious side effects. Still other patients stick to treatments specific to their diseases, like insulin for Type 1 diabetes or synthetic thyroid for autoimmune thyroid disorders.
Meanwhile, scientists continue to discover treatments for symptoms. For example, researchers reported recently in The New England Journal of Medicine that human growth hormone, combined with a high-protein diet, significantly eased symptoms of Crohn's disease, which affects the digestive tract. And a number of medications are in the works for lupus and psoriasis.
Most encouraging have been two treatments belonging to a new class of drugs called biologics. They work by taking aim at specific proteins that, when overproduced, cause some autoimmune diseases.
For example, Enbrel, from the Immunex Corporation, was approved last year for rheumatoid arthritis and juvenile rheumatoid arthritis, and, according to patients and doctors, helps control swelling and pain.
Remicade, from Centocor Inc., is prescribed for Crohn's and rheumatoid arthritis, disorders that affect different body systems. It also shows promise for treating other autoimmune diseases, including psoriasis.
Now, patients are fighting to remain upbeat.
Dr. Shaner concluded: "We are not crazy. We are not lazy. We are people
who need earlier diagnosing, better treatments, increased effort by employers
to keep us in the workplace and a real attempt to unearth the underlying
malfunction behind our symptoms. And we need it now."