This book is about a global health epidemic that threatens to affect each and every one of us. However, the seeds for this book were sown in my own health crisis. Like 23.5 million other Americans, I suffer from autoimmune disease, and it has ravaged my life, placing before me the greatest obstacles I have ever known. Pages of this book were written during different stays in the small white hospital rooms of Johns Hopkins Hospital, and many chapters were drafted during long bedridden months at home.
The greatest of these challenges began one fine spring afternoon as I was celebrating "Carpet Day" with my daughter. Carpet Day is our own personal mother-child holiday, celebrated only by us. On the first great spring day we take an old carpet and unroll it on our suburban drive. We bring pillows, chalk, snacks, and lemonade and lie there, reading and chatting, pretending it's the beach for a whole afternoon. On Carpet Day, you can almost hear the seagulls and feel the breeze from the ocean waves that we still won't visit for months. That day, we brought our golden retriever puppy outside with us. He saw a squirrel, and off he went. I bounded after him, or tried to, only to find that my left leg wouldn't follow my right. I hurtled headlong into the grass.
Over the next seventy-two hours, my left leg, then my right, then both arms lost all muscle control as my body underwent what was for me the all-too-familiar creeping paralysis of Guillain-Barré syndrome, an autoimmune illness in which the nerve's myelin sheaths are destroyed by the body's own immune system.
Guillain-Barré syndrome, or GBS, usually attacks a month or so after a patient has had a common viral or bacterial infection. Just three weeks earlier, I had had a stomach bug. My body's immune fighter cells had mounted a war to eliminate those germs, but once they'd achieved that goal, instead of ceasing their attack they turned on my own body in a deadly game of self-sabotage. With Guillain-Barré, the immune system gets its wires dangerously crossed and while trying to fight off the infectious agent also damages the myelin sheaths that wrap around all of our nerves like a protective insulation. The damage is so rapid that a patient's myelin sheaths and the axonal nerves they protect can be methodically and painfully stripped away leaving them entirely paralyzed within weeks, or even days.
It was the second time in four years that I had been paralyzed with GBS. Once before, in the spring of 2001, when my son was six and my daughter two, I had developed this same bizarre and devastating disease after a stomach bug. In 2001, physicians at the local emergency room confidently misdiagnosed my leg weakness and back pain as a back injury and prescribed bed rest. But instead of improving with rest, I lost nerve and muscle control in my legs by steady degrees over a period of nearly two weeks. One day I could stand on my toes, a few days later I couldn't quite manage it. A few days after that I couldn't flex my feet. A week later, I would stand up and try not to crash into the wall, but suddenly the wall would be there to greet me.
A day or two later, I attempted to get to my two-year-old after she bloodied her toe by stubbing it on the leg of my dresser, but I couldn't make it there, even on my knees. The communiqués my brain sent to my body to feel the floor beneath my feet simply didn't connect.
One afternoon my son, then six, tried to rouse me by showing me how competent he'd become overnight at tying his shoes, as if by some magical power he could banish his mom's bizarre inability to budge from bed.
"Look, Mom!" he called to me from downstairs, near the front door where we kept our shoes. "I tied my shoes! On my own!" There was a moment's pause, and then making a decision to ignore the no-shoes-in-the-house rule he clambered up the stairs to show me his handiwork, pride widening his smile.
"Great job, buddy." I tousled his hair and smiled back, ignoring the sneaker prints trailing behind him across the bedroom rug.
"Mom?" he asked, his tone uncertain. "Can you help me tighten the loops?" He put his foot up on the side of the bed. I tried to pull at both laces to make the floppy loops smaller but my fingers weren't strong enough.
"I can't manage it at the moment, buddy," I said. His face grew ashen and tight. I tried to comfort him, repeating a made-up acronym I sometimes used to soothe my children, hoping it would do the trick again. "Remember? My love for you is very FINE it is Forever, Infinite, Neverending, and Everywhere you go." We lay side by side, my words all I had to embrace him with as I struggled to hide my own panic. Why was I losing muscle control in my arms as well as my legs?
Within twenty-four hours, my breathing became shallow and short. It was clear I was facing something other than a back problem. I was admitted to Hopkins, where the neurologist who took my case ordered infusions of immunoglobulin, or other people's healthy immune cells, the standard treatment for GBS. In many first-time cases, but not all, GBS paralysis is 90-percent reversible with treatment, and the myelin sheaths begin to regenerate. It is a remarkable process. If left untreated, GBS can be fatal; the paralysis spreads to the lungs, and patients require intubation a tube inserted into the airway to prevent them from suffocating to death. In 2001, I recovered well with immunoglobulin treatments followed by months of physical therapy. Although I was left with strange neurological bells and whistles jingly nerve endings, tired, locked muscles, twitchy connections it seemed a minuscule price to pay for being able to walk unassisted again.
I was so very fortunate.
Still, other problems emerged. I was told that I also had leucopenia, a dangerously low white blood cell count. Leucopenia and GBS came on the heels of two earlier autoimmune diagnoses that had spanned the previous fifteen years. Small-fiber sensory neuropathy, which leads to a permanent loss of some of the normal sensation in the hands and feet, and hypothyroidism, or an underactive thyroid. In addition, I suffered from vasovagal syncope, a fainting and seizure disorder caused by the heart sending incorrect signals from the brain to the vagus nerve and failing to pump enough blood through the body, "cured" by doctors surgically implanting a pacemaker when I was twenty-eight.
Still, when Guillain-Barré struck a second time in April 2005, it came as a devastating shock. You simply were not supposed to get GBS twice. If you did, your chances of regenerating your nerves went from 90 percent to well, no one quite knew. Toward the end of my hospital stay in the rehabilitation center, my physical medicine specialist stood at my bedside one day, patting my leg. "You might not get any better than you are right now," she warned, her voice soft for the blow. "But that doesn't mean you should give up hope."
I had no intention of giving up hope. As a child, I had watched my father suffer through a constellation of what I have since learned were autoimmune illnesses: inflammatory bowel disease, rheumatoid arthritis, and leucopenia. By the time my father was forty-two years old, he could barely walk a step without wincing with joint pain, and his bowels were continually inflamed. He died without warning one August morning following routine abdominal surgery to remove inflamed parts of his duodenum. I was twelve. It turned out that the heavy steroids his rheumatologist had prescribed for his arthritis had eaten through the sutures his stomach surgeon had sewn in, and the peritonitis that ensued caused his body to go into shock and his heart to arrest. "Normal courses of antibiotics proved unsuccessful," read his death report.
We knew so little then. Still, thirty years later, when my own frightening journey through autoimmune disease began, it seemed to me that we knew little more than we had in my father's era.
As I lay on that hospital bed with Guillain-Barré for a second time in 2005, I couldn't help but compare my father's odyssey to my own. Like him, it seemed I possessed an irrationally overexuberant immune system. I lay in a hospital bed in the same medical institution, Johns Hopkins, one ward over from where my father had died from autoimmune-related complications at almost the very same age I was now. With a young son and daughter at home yet to raise, the similarities terrified me.
Back home, physical therapy, meditation, and an autoimmune-preventive diet all helped to bring incremental gains in mobility. I would later come to think of that time as a five-month journey around my room, often accompanied by my physical therapist at my side, as I sweated to graduate from wheelchair to walker to cane with no guarantee that I would improve. As one doctor explained, "You've had several forest fires, and each time it's harder and harder to get healthy regrowth." It was the second time in four years that my work as a journalist came to a sudden halt. Deadline after deadline passed. I was simply too weak to sit in front of a computer, let alone tap out words on the keyboard. I tried to get to the bathroom one night on my own, using my walker, without waking my husband to help steady me, but misjudged my stamina. On the way back I crashed into a window and fell in a heap on the floor, unable to get up on so much as one elbow. When you hear the phrase "and he scraped her up off the floor" and wonder what that really means, it means exactly what my husband did that night. He sat up and called my name out in confusion: where were my cries coming from? When he found me beneath the window he picked me up and laid me back in bed. We lay side by side, both too close to tears to risk words.
A few moments later, our son, ten then, crept silently into our room, having heard the commotion. He laid his head down in the dark beside me, his arm circling my waist from behind.
"Mom?" he said, his voice questioning, as he grasped my hand.
I tried to hide my wet eyes and clear my voice.
He pressed his face into the back of my neck, quietly, tentatively. "Mom?" he asked. "Don't you know that I'm old enough to know that even grown-ups can get scared?" Then he hesitated. "The only time I get really scared is when it gets all quiet at school," he said, his fingers tapping the ends of mine, one at a time, gently, rhythmically. "Like when we're about to take a test, and the only thing I can hear is the rustling of paper. And then I worry...what if you die before I get back home to see you again?"
My children had spent three-quarters of a year of their young lives with their mom either in the hospital or bedridden.
Scared? We were all terrified. Autoimmune diseases, which often strike when people are in their prime making them wonder whether they'll ever be lucky enough to get back on their feet again tend to have that effect. Like any family in which one member is felled with autoimmune disease, my husband, son, and daughter had been through hell as much as I had.
By the end of July, I got up and down the stairs with a cane for the first time. In August, four months after being discharged from the hospital, I was able to make it with a cane all the way to the mailbox a few yards down the sloped driveway on which we'd celebrated Carpet Day that April. It was a tremendous milestone, one I had been warned I might never reach. One day my in-home physical therapist and I headed out the door to test my stability walking across the bumpy grass in our wooded backyard. When I'd managed to go twenty or thirty feet he whisked the cane away. In September, my feet were strong enough to drive, and I drove my children to school for my daughter's first day of first grade and my son's entry into middle school.
A few months later, in December, my six-year-old daughter asked me to dance with her in the kitchen to a funny song we'd danced to together for years about a cow, funnily enough, who wouldn't listen to anyone who told her what she couldn't do.
"Can you dance, Mommy?" she asked.
"Let's see," I said, curious myself. We cranked the music, held hands, and stomped our feet and turned in circles as we shouted out the refrain, "No one can tell you who you oughta be or what you oughta do!" until we began to laugh with a raucous joy that morphed into tears, before we fell spent on the floor. The relief on my daughter's face was akin to that of Christmas morning Santa did come!
Still, my doctors could not guarantee that I would not plunge into more devastating autoimmune crises. As one told me, "All we can do is wait and see until another shoe drops then treat you as best we can." Sometimes, the shoe does drop and hard. In the spring of 2006, I caught a seemingly innocuous, low-grade gastrointestinal infection that would not go away. Six weeks later I landed in the hospital to treat a bowel neurological dysfunction a complication that arises in some who have had Guillain-Barré syndrome.
Because I am a journalist by trade, it was in some ways inevitable that my personal journey into autoimmunity would turn into a professional quest. I wanted to know what was being done to investigate autoimmune disease. Why didn't we as a society hear more about these illnesses both the problems they cause and research under way to combat them? What factors coalesced to cause autoimmune disease? Did environmental components play a role and if so, what were they? What could a patient do to stem the damage and prevent future crises? Driven by an urgent need for information, I sought out answers from the top researchers in the field.
It quickly became clear in talking to these cutting-edge scientists, however, that the story was far bigger: my own case was but one tiny part of an emerging, global health crisis one with disturbing and widespread implications for every American. During the same years that I have been waging my own battle with autoimmunity, researchers at dozens of top international institutions around the world have been documenting an alarming rise in autoimmune disease rates. In 2005, the National Institutes of Health (NIH) released a report called Progress in Autoimmune Diseases Research in which the director of NIH pronounced that nearly one hundred known autoimmune diseases such as multiple sclerosis, type 1 diabetes, rheumatoid arthritis, myositis, lupus, scleroderma, thyroiditis, Graves' disease, ulcerative colitis, Crohn's disease, myasthenia gravis, and eighty-some others now afflict 23.5 million people in the U.S., or one in twelve Americans, and these diseases are now on the rise worldwide for reasons unknown. The statistics are stark: over the past forty years, rates of lupus, multiple sclerosis, type 1 diabetes, and a range of other autoimmune diseases have doubled and tripled in Western countries around the world. Just as worrisome, rates are rising dramatically among children, as are other related syndromes in which the immune system becomes hypersensitive, such as food allergies and asthma. These growing numbers cannot be attributed to better diagnostic procedures or disease awareness alone. An escalating number of people in the industrialized world are facing diseases in which their immune systems are turning on and damaging their own bodies.
What is propelling this epidemic? Scientists the world over agree that the root cause of this frightening trend is environmental. Twin studies elucidate that two-thirds of the risk of developing autoimmune disease is acquired through some environmental trigger, genetic risk being the smaller part of the equation. Over the past decade, labs around the globe have proven definitive links between a list of commonly used industrial-age chemicals, heavy metals, and toxins and the development of numerous autoimmune diseases. As hundreds of industrial byproducts interact with the immune cells of our bodies, they are sabotaging an extraordinarily complex and fine-tuned blueprint for healthy cellular communication. Facing a dismal picture in which the numbers of people afflicted with autoimmune disease in industrialized countries continue to rise, the race to turn the tide of this worldwide trend has become a race against time.
This book explores this scientific race the watershed discoveries that are revolutionizing our understanding of the way the immune system functions and the complex, interlocking factors that cause it to go haywire; what role genes and environmental toxins play in who will be struck by disease; why scientists now believe that even people who are not genetically predisposed to autoimmunity may fall ill with these diseases; the groundbreaking interventions emerging out of today's top labs that promise to help halt the disease process; and ways in which we can each lessen the multitude of exposures that threaten our immune systems and our health.
Four decades ago, writer Rachel Carson, author of Silent Spring, demonstrated how our chemical age has altered our environment to the degree that the fertility and survival of many of the species with which we coexist are threatened. Then, as now, there is great resistance to the idea that environmental contamination can alter the health of both animals and people. Indeed, it has taken several decades for many researchers in the autoimmune-disease field to come to the conclusion that our contaminated environment is causing the human immune system to run amok. But the consensus is rapidly building. These pages lay bare this "inconvenient truth" one as disturbing to today's top scientists as global warming. My hope is that the chapters you are about to read will awaken a deep understanding about how the environmental changes of the industrial age and our twenty-first-century lifestyles are wreaking havoc with the immune cells of our own bodies.
We are our environment. What we put into it, we also put into ourselves. What we do to it, we also do to ourselves. The way in which our bodies are turning against themselves when autoimmune disease strikes serves, sadly, as a disturbing modern analogy for what we are doing to ourselves as a society as we continue to dump thousands of chemicals into the soil, water, and air that surround us. Our mass dependence on chemically manufactured home and lifestyle products and our diet of chemically processed foods, in many ways, constitute a great societal health experiment, as we continue to surround ourselves with thousands of chemicals whose properties we do not yet fully understand.
With our eyes open to that knowledge we can begin to make critical and profound choices, embarking on a journey of small steps that will slowly start to make all the difference between health and disease. As we educate ourselves about the consequences of our day-to-day lifestyles and strive to make the personal, political, and economic choices to counter those ill effects, we will be taking back our environment, our bodies, and our future. Copyright © 2008 by Donna Jackson Nakazawa
The Red Flag Disease
Between them, Jan Pankey and David Calhoun shared four decades of experience as physicians. Yet in the quiet dark of one August night in 2003, all that experience seemed to count for nothing. Something was going terribly wrong inside Jan's body, and neither husband nor wife could make sense of what was happening, or why.
It was shortly after midnight on the first night of a long-anticipated vacation in Montana when Jan awoke to a burning ache that encircled her upper chest. It was all she could do to draw in a breath. If Jan hadn't known better she might have thought she'd been pummeled with an iron rod across both front and back while she slept. Fumbling in the pitch black of their Idaho hotel room, where they had stopped en route to their final destination, Jan switched on the bedside lamp and stood for a moment in the circle of reassuring yellow light. Her legs felt unsteady. She couldn't feel the carpet beneath the soles of her feet. It took a blink or two for her mind to register that she was about to faint.
A minute later Jan came around to find herself staring at the coarse hotel rug, struggling to take in a full breath trying to piece together where she was and why her upper body was in so much pain. In that split second every nerve ending inside Jan Pankey's body stood on full alert, signaling that something ungodly was happening. She crawled to the bed to wake her husband.
David quickly shook off sleep along with his bewilderment as to why his wife of twenty-eight years suddenly was writhing uncontrollably beside him in a hotel room a thousand miles from home and an hour from the nearest metropolitan hospital. Together they struggled to diagnose. Jan and David were well versed in the medical school mantra "When you hear hoofbeats, think horses, not zebras," and so they stuck to Jan's prior, known medical history rather than coming up with exotic could-be's. Recently, Jan, who was forty-nine, had started taking birth-control pills to help even out hormonal fluctuations and irregular periods. But that seemed of little consequence here. She'd also been plagued by bouts of indigestion, which her doctor had chalked up to gastritis, a chronic inflammation of the stomach and intestinal tract, due to a fairly common condition known as gastroesophageal reflux disease, or GERD. In GERD, the stomach overproduces gastric acid and the esophagus spasms, causing excess acid to rise into the fragile lining of the throat. It can be quite painful.
Jan and David concurred that Jan must be experiencing spasms in her esophagus due to her GI problems. David felt that Jan's asthma must be acting up, too; recent forest fires had plagued Montana's wooded areas and some neighborhoods, and the noxious smoke clouds had grown closer and more visible as the couple had neared the Idaho-Montana border. Still, severe chest pain was not usually indicative of asthma. Could asthma coupled with esophageal spasms produce so much pain? That was their best educated guess at one o'clock in the morning in the middle of nowhere.
Jan and David had left home early the day before with the goal of cycling more than a hundred miles of Montana's Glacier National Park, an expedition they had spent the past year planning. Jan had been feeling well enough you'd certainly never know that she suffered from any health issues to look at her. Slim and vitally active in the middle of life, she had already biked more than 3,300 miles in the previous twelve months. She held down a demanding professional schedule, commuting by plane from rural New Mexico to downtown Oakland, California, every two weeks to work long hours as a pediatric and neonatal anesthesiologist at Oakland's Children's Hospital. She was also a regular team member on physician-run medical missions overseas, helping children in third-world countries obtain lifesaving operations they might never otherwise receive.
The first night after departing for their big Montana trip fourteen hours in the car after they'd left behind the rural farming village where they lived near New Mexico's Rio Grande the couple had stopped at their Idaho motel just shy of the Montana border. Once settled in their room Jan and David had turned on the air-conditioning to help filter out the polluted soot from the smoking Montana fires that had drifted in behind them and hoped for a good night's rest. It was a few hours later that Jan's chest pain suddenly and inexplicably set in.
Then, just as unexpectedly, a few hours before dawn, the wrenching pain began to lift. Jan could take in a deep breath again. She told David she was feeling some relief. David felt reassured by Jan's slowly returning calm. He would later realize that it was a veneer Jan had perfected all too well after decades of reassuring parents with critically ill infants and soothing children who were about to undergo surgery.
That morning they crossed the border into southern Montana, where ash from the fires hung so thick in the air that you couldn't see across the street. Neighborhoods were being evacuated. As they got out of their Legacy station wagon to stretch their legs and survey the situation, Jan was seized again by debilitating chest pain and shortness of breath. She dropped to a crouch, gasping for air, unable to stand up.
Half an hour later David was wheeling Jan into the local hospital in Missoula. The emergency-room doctor reassured them that Jan's X-rays looked fine, except for a small, barely distinguishable anomaly: a slight shading along the lungs above the left half of her diaphragm, deemed insignificant. The doctor surmised that Jan's discomfort and she was now twisting in pain on the hospital gurney might be a kidney stone. Urinalysis ruled that out. Nor was Jan displaying signs of wheezing. The ER doctor, stumped, concluded that Jan and David's initial hunch had to be right: Jan was suffering from severe spasms in her esophagus due to her gastroesophageal reflux disease. In addition to the spasms themselves, Jan was experiencing muscle strain caused by the spasms along her chest wall. Or so the doctor thought.
The ER physician ordered an intravenous drip to be inserted in Jan's right forearm and dosed her with Demerol for pain as well as a sedative to help her relax. Afterward, Jan was given Prilosec for her gastritis and reflux, and was released. She felt she could and should go on with the trip.
Jan explained her feelings to David. "We've paid the money," she told him. "And I don't want to waste an opportunity we've been looking forward to all year because of stomach problems." Beneath her words David heard Jan's characteristic determination not to be a "wimp."
By the time the bike tour began later that afternoon, Jan wasn't so game, and she stayed behind at the hotel. But when the riders headed out again the next morning, she was resolute: she would ride the "sag wagon" for lagging bikers up the mountain a thousand feet, then coast down on her bike so that she could see the stunning vistas of glacier and rock she had driven so far to view. She was a veteran biker; what in the world could happen to her as she coasted down a mountain road? She donned her bike jersey, choosing one that would turn out to be all too fitting. Her jersey material was dotted with small red blood cells and sported the logo of the whimsical company that had made it, the Republic of Anaerobia literally meaning "the state of insufficient oxygen." Beneath the logo were the words Veni Vidi Vomiti. A twist on Julius Caesar's "Veni, vidi, vici" ("I came, I saw, I conquered"), Veni, vidi, vomiti was a hardcore no-sissy bike-til-you-drop insiders' joke: "I came, I saw, I vomited."
Jan began her glide down the mountain only to find that smog drifting from the fires nearly obliterated the view of the icy gorges and glaciered valleys. But that would turn out to be the least of Jan's worries. She had coasted another half mile in her red jersey when the now familiar vise of pain returned with a vengeance, nearly jolting her from her seat. She found it hard to pull in a breath. The scenery grew blurry. Colors turned to shades of black and white. She was close to passing out.
David discovered Jan crouched by her bike alongside the narrow mountain pass. All they could think of was getting back to the Albuquerque, New Mexico, medical center near their home where David was on staff, as fast as he could drive them.
Meanwhile, neither of them had a clue that in their empty pink adobe house near the Rio Grande the phone was ringing over and over again as the Missoula hospital's radiologist who had finally reviewed Jan's X-rays tried in vain to locate the couple.
They were halfway home still assuming the pain was due to a wicked combination of reflux and gastritis when Jan noticed a new problem. A hot, angry red line was moving up the vein in her right arm from where her IV needle had been. As a physician she knew a blood clot on sight. She knew that if it progressed it could easily block the flow of oxygen to her heart or lungs, causing a heart attack or even a life-threatening heart infection known as endocarditis. Jan took a dose of the antibiotics that she and David always carried in their first aid kit when traveling, and they stopped at a pharmacy for a heating pad to wrap around her arm to help disperse the clot both standard protocol. They passed a road sign pointing to a local hospital along the deserted highway. David looked at Jan questioningly.
She shook her head no. "I want to get home to medical care I know we can count on," she told him. With Jan's eyes locked on the crimson line to make sure it wasn't progressing, they headed home.
Eight hours later Jan Pankey lay prone on a gurney inside the Albuquerque Regional Medical Center ER in severe pain, breathing through an oxygen mask while a technician performed a scan of her chest. Jan watched from across the X-ray room as the picture of her lungs began to register on the machine. She didn't have her glasses on, but even so she could see the clots as they appeared on the scan. The technician stared at the screen in stunned silence, then turned to Jan and said, "Honey, I don't think you're going anywhere tonight."
The X-ray was startling. It looked as if someone had taken inch-sized bites out of several areas of each lung. Blood clots, or pulmonary emboli, had proliferated out of nowhere. Large clots were blocking several large arteries. Three of the five lobes in Jan's lungs weren't getting any blood at all, while the other two had been damaged by smaller clots. Together, clots had cut off 50 percent of the oxygen flow to Jan's lungs. The state of anaerobia indeed. It was a wonder Jan was still alive.
The ER physician on call later explained to Jan and David that the area above Jan's diaphragm that had appeared tinted in that first Missoula X-ray had been, no doubt, the first lung tissue to be injured.
The red line on Jan's arm hadn't progressed, so clearly the clots weren't originating from there. Additional ultrasounds revealed, however, that Jan's entire right leg vein was blocked from ankle to groin with a huge clot known as a deep vein thrombosis, or DVT. It was from this larger clot that smaller ones were traveling up to block the major arteries of her lungs. From torso to toes, Jan's blood was clotting up like sludge and no one could explain why.
Without knowing exactly what was causing Jan's condition, the ER physicians put her on the blood thinner Coumadin with the understanding that she would need to stay on it for several months to avert further crises. She stayed six days in the hospital before being discharged. But the second day home it didn't seem to matter that she was taking the full recommended dose of anticoagulants. Jan bent over to pick up a leaf that had fallen from a neglected plant in their foyer and felt "a hard thunk" in her chest that nearly toppled her. She called 911 and David, who was fifteen minutes away at work. The twenty-minute ride alone to the hospital in the back of the ambulance was terrifying.
"Even though I was wearing an oxygen mask I was gasping for every breath," Jan recalls. When David met the ambulance crew at the hospital, they confirmed what he already feared. Jan's situation was deteriorating.
The hospital was so full that day that they turned a U-shaped, curtained area of the emergency room into a temporary critical care unit to treat Jan. Kwaku Osafo-Mensah, a young lung specialist from Ghana who'd come to Albuquerque five years earlier after medical training at UCLA and Stanford, was rushed in to consult on Jan's case. Drawing the beige hospital curtains closed around her makeshift room in the busy ER, Osafo-Mensah quickly explained to Jan and David that even though Jan had been on blood thinners, X-rays showed that she had lost two more areas of lung. Her EKG had as many spikes and valleys as the Swiss Alps. Jan and David were terrified.
It was as if someone had punched a hidden self-destruct button inside Jan's lungs and there was no shutoff switch to be found. She knew that if they couldn't stop the clots from forming, she would lose all the pathways by which oxygen entered her bloodstream. What was unfolding inside her body was petrifying; it was as if she were being suffocated to death by her own blood cells.
Osafo-Mensah shook his head as he talked to his new patient, trying to nudge the pieces together. Jan's first embolisms had developed during a long, two-day car ride to Montana. And she was often sitting on airplanes commuting from New Mexico to Oakland. Perhaps both sedentary activities had led to exacerbated clotting. On top of that, anesthesiology is a pretty sedentary job, he explained to Jan. Still, it didn't add up. Not for someone like Jan Pankey who biked 150 miles a week.
Regardless of the diagnosis, Osafo-Mensah knew what he had to do if he was going to save Jan's life, and he knew there wasn't much time. He decided to immediately place a filter in the vein at the top of Jan's leg, known as the inferior vena cava, which pumps blood up from the lower two-thirds of the body. The filter would stop any clots before they traveled up to Jan's heart or lungs. That, along with an intravenous infusion of the blood thinner heparin, would prevent more clots from rising toward her lungs.
It worked. Jan went home again. But a disquieting mystery still lingered in the air. Why weren't blood thinners working for Jan as they did for other patients? Jan scheduled an appointment with her local internist and posed the question to her, only to be brushed off with the words, "Well now, that's chasing a real zebra." Jan never went to her again.
Still, the insertion of the blood filter had made some difference for Jan; she was no longer living in a state of full-out perpetual crisis. The clots blocking the pathway to her arteries had dispersed, allowing oxygen to flow into her lungs again except for the small percent of lung tissue that had died. Nevertheless, she felt so wiped out that she couldn't walk down a hall without pausing to catch her breath. Stairs were out of the question. Twelve hours of sleep did nothing to relieve her weariness. Many days, it was all she could manage to get out of her bathrobe and make a cup of tea by noon.
Despite the residual severe fatigue, weakness, and shortness of breath, she managed to attend a medical conference six weeks later. At the conference, as serendipity would have it, Jan met a dynamic young physician by the name of Alex Spyropoulos, whose passion was deciphering unusual clotting disorders. As the medical director and founder of the Clinical Thrombosis Center at Lovelace Sandia Health Systems in Albuquerque, Spyropoulos was presenting his research on designing new ways to use blood-thinning drugs. He also happened to be the author of a case report in a medical journal on a newly emerging autoimmune disease that dangerously altered clotting factors.
Reeling from what she calls a kind of "mortal exhaustion," Jan approached Dr. Spyropoulos after his hour-long lecture and put forth the question, "How could an active woman like me have recurring clotting even on blood thinners? What's happening to me?"
Two weeks later, Jan sat on an examining table inside Alex Spyropoulos's office, relaying to him a medical history that had stumped half a dozen physicians. In addition to all that she had been through physically, she told him, she'd also been experiencing some cognitive problems a kind of recurring brain fuzziness and forgetfulness that deeply concerned her. Hearing this, Spyropoulos looked up over his notes at Jan, one thick, black brow furrowed. It was his dedication to tough cases that had earned Alex the nickname of "Dr. Spy" among patients who were grateful for his detective-like zeal on their behalf. He had a hunch, he told Jan, that she was not yet on a high-enough dose of anticoagulants. Rather than worry her by playing out possibilities, he ordered extensive blood work and, for added insurance, wrote her a prescription on the spot, upping her dose of medication. "If you have what I think you have, the anticoagulants you're taking will not be sufficient to do the job," he told her, ripping the script off the pad and handing it to Jan.
One week later, Dr. Spyropoulos received Jan's blood work and found his earlier suspicions confirmed. He immediately called Jan's office at Oakland's Children's Hospital where she was working late. It was well into the evening and most of the hospital office lights were out. Jan still remembers hearing her line ring and rushing in to pick it up.
"I think I know what you have, Jan," Dr. Spyropoulos told her, excitement accelerating his delivery. Spyropoulos had already treated a number of patients with mysterious clotting problems who'd also reported the onset of "brain fog" as a debilitating symptom. When Jan's blood work hit his desk, so did Alex's eureka moment. Jan's blood showed the precise biomarkers for an autoimmune disease known as antiphospholipid antibody syndrome, or APS, an illness he'd seen too often of late in other thrombotic patients.
"I had no idea what he was talking about," Jan recalls. "I had never even heard of APS." She fumbled for pen and paper in her darkened office. The three other doctors who shared her workspace had already gone home, and the hospital was unusually quiet.
Spyropoulos explained to Jan that APS, also known as "sticky blood," or Hughes syndrome, was an autoimmune disease in which the body produces antibodies, or immune fighter cells, that mistakenly disable the very proteins in the blood that the body needs to prevent excessive clotting. Without these proteins, called phospholipids, your blood begins to clot and has no mechanism by which to stop clotting.
As Dr. Spy talked, Jan began to put the pieces together. One of the functions of the immune system is to act like a rapid-response swat team, reacting to any invading microorganism, such as viruses or bacteria, by producing antibodies fighter cells which seek out and destroy those unhealthy and often life-threatening organisms.
But in a wide range of autoimmune diseases, the body's immune cells lose their ability to read the difference between your own healthy cells and the foreign bacteria or viruses or other unrecognizable microscopic organisms from the environment around you that enter your body. They don't stop at merely disabling these invading foreign agents, they go on to destroy the body's own healthy tissue in deadly rounds of friendly fire. For reasons scientists are only now beginning to understand, the immune system goes on an erratic rampage, disabling the body itself.
In Jan's case, antibodies that were supposed to keep her healthy were instead attacking the very phospholipids that were instrumental to keeping her blood from clumping like cottage cheese in her veins.
Antibodies that turn on one's own tissue are known as autoantibodies antibodies meaning "fighter cells," auto literally meaning "self." As with many of the more newly recognized autoimmune diseases, isolating and testing for specific autoantibodies that point to the diagnosis of APS can be tricky to perform, and new blood tests for APS, in particular, are hard to compare from one lab to the next. At Jan's office visit several weeks later, Dr. Spyropoulos explained to her that her screening test was "positive for autoantibodies that show you have APS." Although a second follow-up blood test didn't confirm as high a level of those autoantibodies, nevertheless, Spyropoulos told Jan, "I think it fits. Your body is certainly acting like you have APS." In 2003, antiphospholipid antibody syndrome was a recently discovered disease; physicians had only known of its existence for twenty years. "There may be other antibodies involved that we don't yet understand or know how to test for," he admitted to Jan. "But that doesn't mean that we can't name and treat your disease."
Dr. Spy started Jan on much higher than usual doses of the heavy-hitting anticoagulant Coumadin, which is often required for patients with sticky blood. He also set her up on a constant home blood-monitoring program so that she could keep tabs on her coagulation levels around the clock. When Jan failed even on this regimen, he started her on long-term self-injections of an anticoagulant known as low-molecular-weight heparin, which had only recently been used to treat patients with APS who had not responded to Coumadin therapy.
Today, Jan has expert supervision of her case and is better able to manage her disease. But myriad threats still lurk in her future. Patients with APS have a dramatically increased risk of migraine, sudden stroke, multiple sclerosis (MS), and lupus, the latter a disease in which the immune system develops antibodies that can mistakenly attack a range of organs in the body, including the joints, kidneys, heart, lungs, brain, and skin. Like all autoimmune patients, Jan is statistically three times more likely than others to be struck with more autoimmune diseases down the road.
Meanwhile, four years after her diagnosis, the side effects from the drugs Jan takes pose additional problems. She lives with constant bruising that she describes as "permanent bands of discoloration across my abdomen." Recently, she knocked her foot against the side of a swimming pool, and what started as a tiny bruise morphed into a black and blue hematoma from heel to toe, requiring a trip to the ER.
Those kinds of crises are commonplace for her now. But Jan doesn't just worry about what might happen if she were to be insufficiently anticoagulated again. She worries, she says, "about uncertainties like how long will I be able to stay in medicine?" Already, Jan has opted to retire early from the operating room, concerned that the damage APS has done to areas of her brain and her resulting brain fog might jeopardize her ability to keep "the promise I make to all my kids' parents that I will do my best to take care of them in the operating room." Having stepped out of anesthesiology she has decided, instead, to work with children in palliative and hospice care.
She and David also want to backpack again, but she asks, "Will we be able to? What if I bleed and we're too far from help?" She also dreams of rejoining overseas medical missions to help children. But she's not willing to risk falling sick far from U.S. borders. "U.S. doctors don't know much about autoimmune diseases in general and APS in particular," she explains. "What about doctors in the remote parts of India or Belarus or Kenya or Brazil or the other places I have worked?"
Despite all this, she pushes herself to ride her bike, swim, and even run as often as she can. She pushes herself, she says, "because I'm afraid if I stop, I'll never get going again."
In a certain light, it makes sense that six out of the seven doctors whom Jan saw completely missed her disease. Healthy women in the prime of life rarely have lung clots, much less APS. Still, doctors didn't miss Jan's disease just because blood clots seem a counterintuitive diagnostic call in a hard-core cyclist, or because APS is a relatively rare disease. Statistically, Jan's chances of having APS at the age of forty-nine were greater than her risk of having ovarian cancer or leukemia uncommon cancers that physicians routinely test for when telling symptoms appear. In fact, recent studies reveal that antiphospholipid antibodies are found in 2 to 5 percent of the population. As many as a quarter of women with recurrent miscarriages end up being diagnosed with the autoimmune disease APS, and one in five women who've suffered blood clots in the legs or strokes in the prime of life test positive for APS, making it more prevalent in women than leukemia and ovarian cancer combined.
No, the real reason doctors missed Jan's syndrome is because APS falls into the category of one of nearly one hundred autoimmune diseases that doctors have only in the last decade begun to recognize and understand. Almost every one of Jan's physicians failed to see that she was suffering from an autoimmune condition because, like most day-to-day practitioners, they remain uninformed about how to recognize patients who are suffering from these diseases in the first place. Because Jan's disease was autoimmune in nature, they missed the call.
The Cold, Hard Numbers
Most of us, at some juncture in our lives, have played out in our minds how devastating it would be to have our doctor hand down a cancer diagnosis or to warn us that we are at risk for a heart attack or stroke. Magazine articles, television dramas, and news headlines all bring such images home. But consider an equally devastating health crisis scenario, one that you rarely hear spoken about openly, one that receives almost no media attention. Imagine the slow, creeping escalation of seemingly amorphous symptoms: a tingling in the arms and fingers, the sudden appearance of a speckled rash across the face, the strange muscle weakness in the legs when climbing stairs, the fiery joints that emerge out of nowhere any and all of which can signal the onset of a wide range of life-altering and often debilitating autoimmune diseases.
Imagine, if you can: the tingling foot and ankle that turns out to be the beginning of the slow paralysis of multiple sclerosis. Four hundred thousand patients. Excruciating joint pain and inflammation, skin rashes, and never-ending flu-like symptoms that lead to the diagnosis of lupus. One and a half million more. Relentless bouts of vertigo the hallmark of Ménière's. Seven out of every one thousand Americans. Severe abdominal pain, bleeding rectal fissures, uncontrollable diarrhea, and chronic intestinal inflammation that define Crohn's disease and inflammatory bowel disease. More than 1 million Americans. The incapacitating weakness and burning pain that accompany the inflammation of the joints and other organs and lead to the crippling effects of rheumatoid arthritis. More than 2 million patients. Dry mouth so persistent eight glasses of water a day won't soothe the parched throat and tongue and the mysterious swallowing difficulties that are the first signs of Sjögren's. Four million Americans. And, with almost every autoimmune disease, intolerable, life-altering bouts of exhaustion. If fatigue were a sound made manifest by the 23.5 million people with autoimmune disease in America, the roar across this country would be more deafening than that of the return of the seventeen-year locusts.
And yet, despite the prevalence of autoimmune disease, surveys show that more than 90 percent of people cannot summon the name of a single autoimmune disease when asked to name one specifically. Think of it other than walkathons for multiple sclerosis, how many fundraising walks or lapel ribbons have you seen for autoimmune disease in general? Nearly 24 million Americans are suffering from an autoimmune illness, yet nine out of ten Americans cannot name a single one of these diseases. It boggles the mind.
Each of these nearly one hundred autoimmune diseases derails lives. Taken collectively, these diseases, which also include type 1 diabetes, Graves' disease, vasculitis, myasthenia gravis, connective tissue diseases, autoimmune Addison's disease, vitiligo, rheumatoid arthritis, hemolytic anemia, celiac disease, and scleroderma (see the appendix for full list) are now the number-two cause of chronic illness in America and the third leading cause of Social Security disability behind heart disease and cancer. (Acquired immune deficiency syndrome, or AIDS, by contrast, is not an autoimmune disease; in fact, it is entirely different. In AIDS a virus attacks the immune system and destroys it, whereas in autoimmune disease, the immune system leads the attack, mistaking the body's tissue for an invader and turning on the body itself.) Autoimmune diseases are the eighth leading cause of death among women, shortening the average patient's lifespan by fifteen years. Not surprisingly, the economic burden is staggering: autoimmune diseases represent a yearly health-care burden of more than $120 billion, compared to the yearly health-care burden of $70 billion for direct medical costs for cancer.
To underscore these numbers, consider: while 2.2 million women are living with breast cancer and 7.2 million women have coronary disease, an estimated 9.8 million women are afflicted with one of the seven more common autoimmune diseases: lupus, scleroderma, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, Sjögren's, or type 1 diabetes, almost all of which can lead to potentially fatal complications. Or, slice these statistics another way: while one in sixty-nine women below the age of fifty will be diagnosed with breast cancer, according to estimates, as many as one in nine women of childbearing years will be diagnosed with an autoimmune illness, which strike three times as many women as men and most often strike patients in their prime. According to the National Institutes of Health, autoimmune disease affects far more patients than the 9 million Americans who have cancer and the 16 million with coronary disease.
"The Western Disease": A Rising Epidemic
Even as autoimmune diseases remain underrecognized and underaddressed, the number of patients afflicted with these illnesses has been steadily growing. Yet few of today's practicing physicians are aware of the escalating tsunami of epidemiological evidence that now concerns top scientists at every major research institute around the world: evidence that autoimmune diseases such as lupus, MS, scleroderma, and many others are on the rise and have been for the past four decades in industrialized countries around the world:
Mayo Clinic researchers report that the incidence of lupus has nearly tripled in the United States over the past four decades. Their findings are all the more alarming when you consider that their research has been conducted among a primarily white population at a time when many researchers believe lupus rates are rising most significantly among African Americans.
Over the past fifty years multiple sclerosis rates have tripled in Finland, corroborating data reported in Scotland, England, the Netherlands, Denmark, and Sweden, where rates of MS have been rising at nearly 3 percent a year. Multiple sclerosis rates in Norway have risen 30 percent since 1963, echoing trends in Germany, Italy, and Greece, where MS rates have doubled over the past thirty to forty years.
Rates of autoimmune thyroiditis have risen steadily over the past several decades.
Rates of type 1 diabetes are perhaps the most telling. Data over the past forty years show that type 1 diabetes, a disease in which immune cells attack the insulin-producing beta cells in the pancreas, has increased fivefold. The story regarding childhood-onset type 1 diabetes is more disturbing. Studies show that the number of children with type 1 diabetes is skyrocketing, with rates increasing 6 percent a year in children four and under and 4 percent in children aged ten to fourteen.
Rates of numerous other autoimmune diseases scleroderma, Crohn's disease, autoimmune Addison's disease, and poly-myositis show the same alarming pattern.
As with all epidemiological research, it can be more art than science to tease out what percentage of these rising rates is the result of more people being diagnosed with a disease because physicians are more aware of it, versus the increase from a genuine rise in the number of people falling ill. Yet the researchers behind these epidemiological studies hold that something more than an improved ability among doctors to diagnose autoimmune diseases is driving these numbers upward.
Norwegian epidemiologists, for instance, argue that rising rates are "due to a real biological change of the disease" rather than being caused solely by better diagnostics and are concerned by the higher occurrence of autoimmunity in urban than in rural areas. Swedish and German researchers concur that enhanced diagnostics alone cannot explain today's significant increases in MS. Type 1 diabetes researchers insist that today's rapid rise in this disease cannot be explained by either better diagnostics or by more people suddenly becoming genetically susceptible to type 1 diabetes; rather, a change in environmental factors is the "more plausible explanation." At the Mayo Clinic researchers are beginning to ask if rising rates of lupus are the result of an increased exposure to environmental triggers of some unknown origin. Because autoimmune disease is spreading in almost every industrialized nation, scientists the world over have dubbed it "the Western disease."
A Growing Autoimmune Patient Load
While epidemiological studies provide a global portrait of an autoimmune-disease crisis in the making, it is through patients' eyes that it takes on more personal meaning. And nowhere is this more evident than at the offices of Dr. Michelle Petri, clinical director of the Johns Hopkins Lupus Center, at the Johns Hopkins Outpatient Center in downtown Baltimore, Maryland. Dr. Petri is a heavy hitter in the field of rheumatology and a nationally known speaker on lupus. Many of the people she treats have waited months for an appointment in order to confirm a diagnosis or gain better treatment for such rheumatic autoimmune diseases as lupus and antiphospholipid syndrome. Some of them are local residents who live merely a few blocks away from her office, while other patients fly thousands of miles to see her.
On one recent Thursday evening, Dr. Petri has just finished seeing the last of her forty patients for the day. Outside the glass-paneled hallways that stretch along the clinic's waiting area, the afternoon light has long disappeared into the bank of gray clouds that seem to settle at dusk over this downtrodden part of Baltimore. But Petri shows no signs of flagging. A small powerhouse of a woman, Petri's freckled, youthful face and boyish cropped hair contrast with strands of newly appearing gray and gold-framed glasses that hint at years spent bent over medical texts, papers, and lab work. She pushes her glasses up as she peers down at her watch, noting with little surprise that she has clocked another thirteen-hour stint between patients, paperwork, and rounds. Petri missed the first of several of our telephone interviews, scheduled to take place at eight-thirty p.m. one night, because she'd been working such late hours she hadn't been home long enough to realize that her phone was out of order.
Over the course of her thirty-year career, Petri has witnessed a dramatic rise in patients with lupus. In the 1960s there were only 150 to 200 lupus patients registered in the Hopkins Rheumatology Clinics. Today, there are 1,700 lupus patients registered from the immediate neighborhood alone. "The population in Baltimore is going down, and yet the number of people coming to our clinic from Baltimore with autoimmune disease is going up," she says. In an administrative building nearby sits the lupus clinic records room. In the twenty-by-twenty-foot space loom four walls of filing cabinets enough to easily fill up the four walls in your local 7-Eleven packed with patient files that, twenty years ago, would have fit neatly into a few metal drawers. Although Petri has no way of conducting formal epidemiologic research through her clinic, the continued rise in the percent of patients afflicted in her own small urban area is, she says, a "very disturbing" sign.
Certainly, some of the increase that Petri and other clinicians are seeing in lupus is due to the improved treatment many patients receive through kidney dialysis and transplants, which help them live longer (the longer patients survive, the larger the overall patient number). And the skill with which physicians diagnose lupus has improved somewhat in many large metropolitan hospital centers. However, this increase in lupus "is so enormous," says Petri, part of it can only be explained by an increase in the incidence of lupus itself.
Petri's emphatic tone reveals her concern for her patients' well-being as well as her frustration over how little physicians understand about why so many people's immune systems are attacking their own healthy tissue. In hopes of helping other doctors catch autoimmune disease earlier in their patients, before irreversible tissue damage has already occurred, Petri spearheads an international task force to rewrite the symptom list and lab criteria for diagnosing lupus.
The fact that so many front-line practitioners are ill trained in how to diagnose these diseases can result in patients facing costly delays both physically and emotionally in getting the help they need. As Dr. Ahmet Hoke, associate professor of neurology and neuroscience at Johns Hopkins Medical Institutions and a colleague of Petri's who treats numerous patients with autoimmune neurological disorders, explains, "Most of the autoimmune patients we see here have already been to several doctors and often they've been struggling for diagnoses for years. We see those patients who slip through their doctors' diagnostic fingers."
Patients On The Sidelines
Patients like Jan often feel they pay a high price for the fact that so many doctors remain ignorant of the autoimmune-disease epidemic. "I saw a total of six doctors before I got the diagnosis of APS," Jan says. "And yet relatively speaking I consider myself lucky. I was diagnosed within months of becoming ill. It takes most patients with autoimmune disease years to find a doctor who has enough faith in them to really listen to what they're experiencing." Even then, as we shall see in subsequent chapters of this book, few doctors are well versed in piecing together the moving-target symptoms and in interpreting the complex biomarkers in lab tests that are necessary to accurately diagnose autoimmunity.
Jan pauses as we talk over tea at her kitchen table, the three dogs that she and David have rescued over the past decade settled on the floor around her. As we talk, she glances out the window past the cacti garden she and David have painstakingly planted. For a moment, her short, sandy curls catch sparks of sun reflecting off a truck traversing the dirt road in front of her New Mexico home, and her expression shifts from that of an incredulous patient to steely physician. "The time devoted to autoimmune diseases in medical education is dismally small," she says. "I learned more about syphilis than autoimmune diseases in medical school, and in the twenty years since not much has changed for med students. The sad thing is that there is a huge number of patients out there who are completely off the radar screen of most docs."
For years, one of these patients was Kathleen Arntsen, a forty-four-year-old sales professional from Verona, New York. After five years of searching for a diagnosis for what would turn out later to be myasthenia gravis, a disease in which sufferers develop severe muscle fatigue and disabling weakness, Kathleen was told by a doctor she'd been to eight times, "We've given you every test known to man except for an autopsy. Would you like one of those too?" For half a decade, she says, "I was treated like an absolute fruitcake. No one could tell me what was wrong with me, much less treat me."
Arntsen's story is not unusual. The average patient with autoimmune disease sees six doctors before attaining a correct diagnosis. Recent surveys conducted by the American Autoimmune Related Diseases Association reveal that 45 percent of patients with autoimmune diseases have been labeled hypochondriacs in the earliest stages of their illnesses. Some of this, no doubt, has to do with the fact that 75 percent to 80 percent of autoimmune disease sufferers are women, who are more easily dismissed by the medical establishment when hard-to-diagnose symptoms arise. In half of all cases, women with autoimmune disease are told there is nothing wrong with them for an average of five years before receiving diagnosis and treatment. Patients most especially women are often left feeling both confused and marginalized, or worse, labeled as psychosomatic malingerers.
Arntsen was fortunate to find her way eventually to Johns Hopkins University's neuromuscular clinic and later to Michelle Petri for confirmation, consultation, and validation regarding her polyautoimmune disorders, which include lupus, Sjögrens, Graves' thyroid disease, APS, psoriasis, Raynaud's disease, and myasthenia gravis. Yet despite having an accurate set of diagnoses, Arntsen's autoimmune illnesses have forced her to give up almost everything she once equated with normal life in order to preserve the stamina to get through each day. Once a healthy young woman on a full scholarship to Colgate University, where she was captain of the women's rugby team, Arntsen now has to stop and pick up each knee as she goes up the stairs. "I coexist," she says, "with bone-gnawing pain." For years, her long flame of red hair, which once reached her tailbone, turned scarce and thin, the fallout of her autoimmune thyroiditis, coupled with drug side effects. In the past decade she has spent almost a year and a half in the hospital during her most severe lupus flares. Although she is carefully monitored, there is little the medical establishment can offer Kathleen for her lupus and myasthenia gravis other than steroids, a healthy diet, and boatloads of rest especially since no new U.S. Food and Drug Administration-approved drugs have been developed for lupus in more than forty years.
Kathleen's debility and exhaustion, which have taken a permanent toll on her life and career, will never go away. A top-performing sales rep for an insurance company while in her thirties, Arntsen, who used to run three miles a day, now lives on Social Security disability which, she says ruefully, allows time for "my new full-time job seeing specialists." She gets going each day by around noon and spends what stamina she has left volunteering at the Lupus Foundation of Mid and Northern New York, which has become her "baby," although it can hardly begin to make up for the fact that "the chance to be a mother has been stolen from me." The best Kathleen and her husband of fifteen years can hope for is that with the careful monitoring of diet, stress, and sleep, she will have more good days than bad.
To look at Kathleen, however, you would never guess what she has been through or what she faces each morning at the start of her day. Like many people who suffer from autoimmune diseases, Kathleen's symptoms remain largely invisible. And as was the case with cancer several decades ago, those who have the disease tend not to talk about it.
"People don't see what lies behind the scenes in most autoimmune diseases," she says. "Because we go through ups and downs, you might see us on a good day, between severe flares, when we seem to be perfectly fine. You don't know that we've just spent six weeks in hell." Few can imagine, she adds, that behind her bedroom door even on one of these good days, Kathleen has to take twenty-two medications about an hour before she tries to get up, just so she can handle the pain when her feet hit the floor. "By the time you run into me at the grocery store at two o'clock in the afternoon and say hello to me, I'm ready to nod and say, 'Oh, I'm fine, how are you?'" Kathleen worries, she says, that because autoimmune disease so often remains hidden from public view, she and other women like her will continue to be stigmatized as malingerers.
A Case of Blinded Science
How is it that autoimmune diseases have remained so obscure? Why do so many of these diseases go undiagnosed for so long, and why do we have so little comfort and treatment to offer the patients who suffer from them? The answers to these questions require a step back in time, to half a century ago.
The medical age of wonders began seventy years ago, and what an age of miracles it was. When my own grandfather, C. Donald Larsen, a research biochemist and founding member of the National Cancer Institute, served as head of the cancer research grants program at the National Institutes of Health in 1955, he walked into medical laboratory settings every day that, world over, boasted little more than test tubes, microscopes, and Bunsen burners. As a young thirty-eight-year-old scientist in 1939, he had already become world renowned for being the first to demonstrate that cancer-causing chemicals could pass through the placenta and later cause tumors in offspring. Yet his was only one small speck of discovery in the burgeoning age of miracles.
In the span of the next thirty to forty years scientists discovered a range of antibiotics, invented vaccines that would wipe out polio and prevent hundreds of thousands of deaths from rubella and typhus, and America began the war on cancer. Heart surgeons were opening up chest cavities in living patients and transplanting hearts, pacemakers were invented, and neonatal care began to save infants so small it seemed God's hand had reached down from heaven itself and snatched them from death.
Yet, ironically, during the same time span in which cures for ancient scourges were tumbling out of laboratories, the medical establishment had no idea that autoimmune diseases even existed. Scientists, in general, were clinging to an erroneous presumption that the body's immune system could not turn on itself; researchers were convinced that an autoimmune response was simply not possible. This presumption set forth in the early 1900s by Nobel laureate Paul Ehrlich, a charismatic German immunologist who termed this theory horror autotoxicus stood as dogma across the immunology domain for more than half a century.
It would take a young PhD and dedicated medical student to slowly begin to turn the theory of horror autotoxicus upside down. In 1951, as a newly minted twenty-three-year-old PhD from the University of Pennsylvania, Noel Rose and his pregnant wife, Deborah, packed all their meager belongings into the back of an ancient, rear-dragging Oldsmobile station wagon and journeyed north from Philadelphia to the State University of New York at Buffalo. Back then, the little-explored and poorly understood domain of immunology the study of how the immune system functions in the body was hardly a bustling field, and few labs existed where a young PhD could go to complete his medical studies in the field, much less support a new wife and coming child.
Today Rose, a genteel seventy-nine-year-old whose generous smile spreads nearly as wide as his signature bow tie, serves as director of the Center for Autoimmune Disease Research at the Johns Hopkins School of Medicine and Bloomberg School of Public Health. Back then, Rose considered himself fortunate to receive an invitation from Ernest Witebsky and his immunology team at the University of Buffalo to serve as a junior faculty member. Part of the appeal of moving to Buffalo was the fact that Witebsky was the scientific grandson of Nobel laureate Paul Ehrlich. Ernest Witebsky was a student of Hans Sachs, who, in turn, had been one of Paul Ehrlich's principal protégés. Witebsky was the inheritor of the Ehrlich mantle and was universally recognized as a vigorous champion of the horror autotoxicus theory.
Assigned one part-time assistant and a ten-by-ten office that also served as his lab, Rose set to work. At Witebsky's request, Rose was seeking to prepare a pure form of thyroglobulin, the major protein of the thyroid gland, in a natural, unadulterated form for use in other experiments Witebsky was busy conducting at the time. Rose had worked with rabbits for years, and all those long hours spent amidst rabbit cages had led him to develop a severe allergy to rabbit fur. He often had to wear a mask in order to help circumvent an asthma attack. Nevertheless, Rose quickly succeeded.
In one of the final steps involved in creating this pure thyroglobulin and assuring it was not altered, Rose injected that thyroglobulin derived from rabbit thyroids back into his rabbits. Later, however, when he examined the rabbit thyroids, he was shocked by what he saw. The rabbit thyroids were inflamed and that should not have happened. They had produced antibodies to the thyroglobulin and developed lesions in their thyroids. Thyroid lesions signaled that the presence of an antigen a foreign invader that is capable of causing the production of an antibody had caused the rabbits' immune systems to turn on and destroy their own thyroid tissue. Almost all of the rabbits had slowly developed a disease that mimicked the human disorder known as Hashimoto's thyroiditis. Although Hashimoto's was already a recognized disease in 1951, its cause had remained unknown. That Hashimoto's might be caused by the immune system attacking the cells of the thyroid was a concept that stood completely at odds with horror autotoxicus. Yet in that small postdoc lab, fifty years ago, Rose was staring at proof positive of autoimmune disease a completely revolutionary idea at the time.
"I sat there for a long time, looking at the results with a mixture of awe and fear," Rose recalls. "It was one of those marvelous and rare eureka moments in science when you realize that you're on the edge of an important new discovery. But I was also afraid. I realized that it would be difficult to convince my mentor as well as the world that I was right."
For the next several years, Rose worked, at Witebsky's urging, to run his experiments again and again to correct for any possible errors. Finally, Witebsky too became convinced: when an antigen from the thyroid gland was introduced into the body, the body's fighter antibodies could mistakenly damage the patient's own cells in devastating blasts of self-sabotage, resulting in thyroid diseases such as Hashimoto's and hypothyroidism. Together, Rose and Witebsky published their findings.
By 1957, the concept of autoimmune disease was born though it would be another ten years or more before it was accepted. Yet despite Rose's startling discovery and despite the growing number of scientists whose quiet work would, over the next several decades, substantiate his findings medical schools continued to churn out specialists who were taught horror autotoxicus: the body's immune system could not develop an autoimmune response. For Rose, it was a train wreck in the making: while fellow scientists could and should have been ferreting out potential causes for autoimmune disease, no one was even on the case.
It was a classic case of what twentieth-century scientific philosopher Thomas Kuhn once termed "normal science." Science is conservative in nature, unwilling to abandon ideas without persuasive evidence. The overwhelming majority of scientists accept a single scientific ideology as the starting point from which they form their own viewpoint the pathway from which they view the entire scientific landscape to the degree that they cannot overturn that ideology, even if research begins to show that it is blatantly leading them astray.
It wasn't for another decade that scientists around the country began to wake up at first one by one, and then in droves to what Rose and his colleagues had long known: autoimmune responses could be triggered to affect virtually every organ and system of the body. Meanwhile, as this startling autoimmune connection came to light, different groups of specialists quickly scrambled to claim whole sets of diseases as their own. Rheumatologists, discovering that the root cause of rheumatoid arthritis was the body attacking and inflaming its own tissue, claimed arthritis, lupus, and all other joint-related autoimmune illnesses as rheumatologic disorders. Neurologists, discovering that in a whole host of diseases MS, myasthenia gravis, myositis, Guillain-Barré syndrome the body was destroying parts of its neuromuscular system, became designated specialists in those diseases. Likewise, bowel disorders Crohn's disease, ulcerative colitis, and inflammatory bowel disease were farmed out to the gastroenterologists.
By the early 1970s autoimmunity was finally an accepted precept and yet there was no one standing on the mountaintop, looking down at these various specialists' fiefdoms and seeing how the roads leading to them intersected or asking what the common biological origins or treatments for these diseases might be.
Certainly no one was asking what triggered these diseases. What was wreaking havoc with the intricate inner workings of the human immune system in populations throughout the industrialized world?
In fact, up until the mid 1990s, no one had bothered to figure out how many Americans had an autoimmune disease. Numbers on how many Americans have each type of cancer in each state have been collected by the National Cancer Institute since 1973; the National Center for Health Statistics and the Centers for Disease Control have collected data on cancer since the early 1900s. Yet it was only a decade ago that scientists first began to cast about for a general sense of how many Americans might be afflicted with autoimmune disease. In 1995, Noel Rose approached Virginia Ladd, president of the then fledgling American Autoimmune Related Diseases Association (AARDA), the only autoimmune advocacy organization that encompasses all of the autoimmune diseases, and said, "We have got to find the numbers." Ladd, a small but determined gray-haired dynamo who had founded the organization, was able to come up with only five thousand dollars to fund the project, a paltry sum in the high-roller arena of scientific research. With that, Rose hired a PhD candidate, giving her about a month to ferret out how many patients had each of the twenty-five autoimmune diseases they would be counting. Two years later, Rose's student came up for air with the astounding statistic that 9 million patients were suffering from those twenty-five autoimmune diseases alone as many patients as had cancer.
In what is called the epidemiology of epidemiology, Rose and his PhD candidate were able to take those figures and extrapolate to the fifty-five other recognized autoimmune diseases that had not yet been included in their study. They arrived at the figure of 22 million one in twelve people who were being taken down by an enemy within. Twenty-two million, for a set of diseases no one was looking at, was a startling statistic.
Since that time, NIH has revised that number to be as high as 23.5 million as more diseases are recognized as autoimmune and are added to the tally. Still, say many advocates, the actual number of patients may be far higher: a recent NIH report states that many autoimmune patients are never properly diagnosed. And existing epidemiological studies on how many individuals have each autoimmune disease have been sparse at best.
One of the more interesting diseases that is not yet officially under the autoimmune umbrella lies in the field of cardiology, where researchers have recently shown that the autoimmune process is deeply implicated in atherosclerosis the narrowing and hardening of the arteries from the slow buildup of plaque which is implicated in 1.2 million heart attacks a year. In 2005, Mayo Clinic researchers reported that rheumatoid arthritis patients carry twice the risk of heart failure as other patients. Other studies show similar elevated risk of heart disease among patients with lupus, diabetes, and MS. Researchers believe that some of the genetic variants that predispose a patient to autoimmune disease are the same genetic variants that predispose a patient to heart disease.
Although the exact means by which autoimmune disease is linked to atherosclerosis is only now becoming clear, significant evidence suggests that somewhere in the disease sequence the cascade of plaque building up on the arterial wall, inflammation, the rise of C-reactive protein levels, and the atherosclerotic plaque erupting an immune response against the self is involved, just as in autoimmune disease in other parts of the body. Researchers believe that the triggering event may be viral. Recent studies show that in artherosclerosis the body's immune cells mount an attack against the proteins in a common virus, cytomegalovirus, and in the process become confused, mistakenly attacking the arterial walls themselves.
Michelle Petri, who is involved in a trial to treat lupus patients prophylactically with Lipitor, a potent anticholesterol drug thought to lower the risk of heart attack, says that "the risk is fifty times greater of having a heart attack if you have lupus."
The concern here extends beyond the autoimmune patients who may develop heart disease. It encompasses those with atherosclerosis who do not know that autoimmunity is involved in their disease and who may be unaware that they are more susceptible to other autoimmune diseases as well.
The Postwar Chemical Explosion: A New Plague of Autogens
During the four or five decades that science lingered at the sidelines at best, underinvestigating autoimmune disease, at worst, ignoring it another cultural drama was unfolding in America, the portentous ramifications of which were also slipping under the national radar. Throughout the exact same decades that science was dismissing autoimmunity, the wheels of big industry were moving into high gear across the American landscape, augmenting the greatest industrial growth spurt of all time.
All across America, production plants were starting to spring up in town after town, as corporations ramped up production of thousands of novel products manufactured through brilliantly efficient new chemical processes. New pesticides were being introduced to boost crop yields, prolong the shelf life of produce, keep lice, fleas, roaches, and termites out of the home, and zap dandelions from the lawn. Ingenious new chemicals were starting to be employed to help manufacture everything Americans demanded to make their lives easier, simpler, and more luxurious from plastics to hair shampoo, detergents, brake linings, carpet pads, cold creams, dry cleaning fluid, foam cushions, paint strippers, household cleansers and bleaches, and bigger, grander cars. Almost overnight, Americans began to find themselves inundated with and clamoring for the suburban home products, packaged goods, and manufactured foods churned out by mega-industry. Over four short decades between 1940 and 1980 factory plumes came to shroud small towns, fleets of trucks spewed diesel exhaust as they transported a myriad of newly manufactured goods from coast to coast, and the ChemLawn truck began to circle the cul-de-sacs in neighborhood after neighborhood.
The coincidence in timing between a medical community turning a blind eye to a mysterious, growing set of diseases with an unknown set of triggers and a society's rapid swell in production of everything from SUVs to Teflon pans to furniture stuffed with flame-retardant foam would turn out to be an ominous one, altering the well-being of millions of Americans.
Together, these two seemingly unrelated trends would set in place two of the key factors that would establish a "perfect storm" enabling an autoimmune epidemic to gather force and take hold. And both would go far in explaining not only why millions of autoimmune sufferers like Jan Pankey and Kathleen Arntsen would be underdiagnosed, undertreated, and marginalized once they did become ill, but why their bodies were so much more likely to turn against their own healthy tissue in an autoimmune reaction in the first place.
For nearly half a century, as big industry flourished, scientists sat idle in the lull of a gathering storm, not only missing today's autoimmune disease epidemic in the making but blinded to its possible causes.
During these same decades, the idea that chemicals from our industrial age could trigger cancer would become so widely accepted that the term "carcinogens" would emerge as a household word by the 1970s. But science would be sluggish to accept the idea that chemicals could have similar effects on the human immune system. So slow that, even to this day, there still exists no comparable word to "carcinogens" in the world of immunology. The best we can do to describe the notion that environmental chemicals might be linked to autoimmunity is to use the clunky phrase "environmental autoimmune disease triggers," which is analogous to saying "environmental cancer disease triggers" instead of, simply, "carcinogens." The term "autogen," I believe, might prove useful for this purpose, and I will use that term to describe chemical triggers to autoimmune disease throughout the remainder of this book.
It would, in fact, be 2005 before the head of one of the most prestigious research institutes in the country would herald the call, stating that the link between autoimmune disease and environmental contaminants from our manufacturing age had become "the next tobacco and cancer." Research results would begin to mount, showing that it is the very chemical by-products of the goods we demand to live more convenient lives that are sabotaging the blueprint of how our bodies are meant to interact with Mother Nature. But getting this claim to be taken seriously was going to prove a very tough sell. Copyright © 2008 by Donna Jackson Nakazawa