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an online version of the magazine Fall 2004
Features
Incurable, not Untreatable photo of Nancy Bechtle
 
  No one knows what ignites the scleroderma fire, or who will develop kidney failure or lung disease. But when Nancy Bechtle learned she has the rare condition, she demanded the name of the finest doctor in the nation.
BY MARY ann ayd
 
 
 
 

During the winter of 2000, Nancy Bechtle's hands morphed into alien appendages--blanching and going numb at the merest temperature dip, aching with carpal tunnel pain, ballooning to clumsy paws. Soon her feet followed suit, swelling to the point that donning shoes was impossible. And her skin! Why was it so hot, so stiff, so tight?

Four months passed before the San Franciscan, trekking from internist to rheumatologist to rheumatologist, finally learned that what was so rapidly sabotaging her appearance, her independence and her outlook did indeed have a name: scleroderma.

And then the real fear set in.

There’s nothing you can do, Bechtle kept hearing from the physicians she consulted. This is an incurable disease, Live as much as you can over the next two years.

Bechtle’s Web searches predicted the same stark future. “The information on the Internet was all about how fast you’ll die,” says the 66-year-old, “about all the different things that go wrong with your lungs, your esophagus, your kidneys—nothing that gave any hope whatsoever.”

But the petite woman who’d been presiding over the board of the San Francisco Symphony for 13 years, who loved to ski competitively and never turned down a chance to go scuba diving, wasn’t about to order a wheelchair. Surely someone, somewhere, had better answers.

Bechtle went to the heads of three of the nation’s top medical schools (Harvard, Stanford, and the University of California at San Francisco) and said, “Give me the name of the finest doctor for scleroderma in the country.” Each of them gave the same response.

 

*****

 

“We have this center. About all I do is take care of patients with scleroderma.”

Fred Wigley’s two-sentence introduction of himself is so low-key that it’s easy to blow right past the man making the statement. Wigley doesn’t like to talk about Wigley. He even seems a bit put off by the thought that anyone would turn their attention from the work going on at the Johns Hopkins Scleroderma Center, which he directs, to him. To those wanting to probe how he came to know so much about this one disease, he will allow that it was the idea of caring for the whole patient—“not just one aspect, like the heart”—that attracted him. “Scleroderma is a dreadful, complex disease that affects every aspect of a person’s life. It’s not only life-threatening but disfiguring. It changes your ability to function physically and psychologically. It’s a disease that needed someone to help, someone with the goal of curing it.”

But those who know Wigley medically see something quite different. To a person, his patients call him a man of extraordinary empathy. “He isn’t the center of the scleroderma universe,” says Nancy Bechtle’s husband, Joachim, “he’s the center of the universe. Or as a friend of ours said, ‘First there’s Fred, then God, then me.’”

In his nearly three decades of caring for patients with scleroderma and working to solve the enigma of their disease, Wigley has spurred close collaborations with Johns Hopkins plastic surgeons, dermatologists, pulmonologists, immunologists, cardiologists, vascular biologists, pathologists and psychiatrists. Today, faculty here are at work on more than a dozen scleroderma-related projects spanning basic science, clinical trials and epidemiology. Getting colleagues “fired up with interesting questions,” Wigley insists, “ is simply the Hopkins way.” But those he’s pulled in, who otherwise would never have encountered scleroderma patients, say it’s more than that.

One of Wigley’s fellow rheumatologists, Hopkins Bayview Chairman of Medicine David Hellmann, may put into words best the spirit that permeates the team. Hellmann, who recently read Malcolm Gladwell’s best-selling book The Tipping Point, says the book made a point of emphasizing the enormous importance of “connectors”—people who link other people together for the benefit of some cause or movement. “In scleroderma,” Hellmann says, “Fred Wigley is the ultimate connector.”

 

*****

 

 

Fred Wigley
> Fred Wigley: "The way I think about it is, if you're presented with a complex problem, there are two ways to deal with it: Run from it, or be challenged by it."

In the last dozen years alone, more than 1,700 patients have made their way to Wigley for treatment, some from as far away as Iraq. Nearly all arrive in desperation after having spent months just trying to get a diagnosis. Wigley understands completely why so few physicians recognize the disease or realize that incurable doesn’t mean untreatable.

Each year, scleroderma strikes only about 15 people per million, so even rheumatologists—the specialists who treat inflammatory diseases of the muscles, joints and connective tissue—may see only a handful of cases a year. And when they do, what makes the diagnosis so difficult is that symptoms can vary dramatically from one person to the next. Even the name of the condition is misleading. Scleroderma means “hard skin,” but one type of the disease doesn’t change the skin at all.

Some patients describe a strangling sensation. Others say it feels like hot cement coursing through their veins. Joints can stiffen and ache. Raynaud’s phenomenon is almost universal, causing tiny blood vessels to spasm and close, fingers and toes to grow sensitive to cold, turn white and often become infected. Swallowing can become difficult. Skin—especially on the face and hands—may tighten, thicken, redden; itching may be intense. But worst of all, the disease can unpredictably mount a lethal assault on the heart, lungs or kidneys by choking and scarring the arteries that carry blood to these vital organs.

“In its more aggravated forms, scleroderma is one of the most terrible of all human ills,” wrote Sir William Osler, Hopkins’ first physician in chief and one of the first to define the disease. Those afflicted are “beaten down and marred and wasted” until they are literally mummies, “encased in an evershrinking, slowly contracting skin of steel.”

Today, researchers understand that behind all the misery are four biologic processes—autoimmunity, inflammation, blood vessel disease and tissue scarring—that somehow get in lockstep and produce abnormal growth of the connective tissue that normally supports the skin, internal organs, tendons and bones.

As in other autoimmune diseases such as lupus and rheumatoid arthritis, the body’s natural ability to attack invading viruses and bacteria goes haywire and mistakenly sees healthy body proteins as enemies. Redness, pain, heat and swelling signal that the immune system is on the warpath. In scleroderma the result is artery damage that restricts the amount of blood and oxygen being delivered to the body’s tissues. Then, in inflamed, oxygen-deprived areas, cells called fibroblasts make too much collagen—the “glue” that holds tissues together.

No one knows what ignites the scleroderma fire, why skin involvement can range from mild to crippling, who will develop kidney failure or lung disease, or when any symptom might subside or flare up. What is clear, says Wigley, is that the key to improvement lies in tailoring care to each person’s symptoms and stage of disease.

 

*****

 

When scleroderma commandeered her life, Nancy Bechtle was grateful that she’d already decided to step down from her position with the San Francisco Symphony. Getting in and out of a car or the bathtub was increasingly difficult, and the skin on her face and neck was so tight that if she tilted her head back, she could feel the pull all the way to her groin. She read about a drug that was supposed to help and begged a local physician to prescribe it. It did nothing. By the time she arrived at Johns Hopkins, the stress of trying to carry on normally—“when you’re not normal anymore”—was taking its toll. “I felt like I’d been injected with industrial sludge,” says Bechtle. “I was very depressed, and I’m not a depressed person.”

In Fred Wigley, for the first time, Bechtle found a physician who wasn’t advocating resignation. As he does with all new patients, Wigley spent two hours correcting the misinformation she’d picked up and literally drawing her pictures of the disease process as it was affecting her. “One of the most challenging things,” he says, “is to get patients not to talk in terms of their diagnosis and what people have told them about it, but to tell you their experience. Most have mild disease, but the advanced cases get all the press.”

Bechtle found it oddly comforting to hear Wigley explain that, since there is no magic bullet—no single drug or treatment that can sweep away scleroderma’s myriad ills—what he would do is fight every single symptom as it comes up. “You will get better,” Wigley said.

 

*****

 

When Fred Wigley first began focusing on the disease that’s driven his life’s work, he was just finishing his training and in the midst of a rheumatology fellowship at Johns Hopkins with the revered Mary Betty Stevens. It was 1976, and Wigley had become fascinated by Raynaud’s phenomenon. In about 10 percent of the general U.S. population, the sudden constriction of blood vessels in the fingers and toes that is usually triggered by cold or emotional stress occurs without any apparent underlying disease, and in those cases, it’s mild and relatively painless and once an attack subsides, blood vessels return to normal. But for people with scleroderma, whose blood vessels become scarred by autoimmune inflammation, Raynaud’s can be vicious. In about 25 percent of cases, oxygen-starved skin cells produce painfully disabling ulcers. If gangrene sets in, amputation of an affected finger can become inevitable.

Thirty years ago, the leading reason for death from scleroderma was renal failure brought on by blood vessel spasms in the kidneys similar to those caused by Raynaud’s in the hands and feet. If Raynaud’s was the culprit in the renal failure, Wigley wondered if it might also be occurring in the blood vessels of the lungs in scleroderma patients. So, in his first collaboration with a specialist outside his field, he began testing that hypothesis with pulmonology fellow Bob Wise.

The studies didn’t pan out, but Wise and Wigley did note something odd. In patients without scleroderma, blood content in the lung increased when they became chilled. In scleroderma patients, it didn’t change. After that, Wigley’s absorption with scleroderma never waned. One of his earliest coups was showing that the calcium channel blockers used to lower blood pressure and treat heart disease are also effective for Raynaud’s of the hands and feet.

 

hands affected by Raynaud's phenomenon
> Tight, thickened skin has immovably curled this scleroderma patient's fingers; the sores on her right hand are the produce of Raynaud's phenomenon.

Early on, he recognized he’d need a collection of like-minded physicians who specialized in all the organs the disease attacks to work with him. One by one, Wigley began turning to colleagues all over the medical center—and asking them to help care for his patients. Today, it is the availability and cohesiveness of this group of experts that gives the Johns Hopkins Scleroderma Center its special niche.

“Fred’s profound concern, his interest, draws you in,” says Bob Spence, a wound care expert whose two decades of experience with scleroderma began when Wigley asked him to take care of patients with ulcerated sores caused by Reynaud’s.

Jennifer Haythornthwaite, a behavioral psychologist Wigley’s enlisted to study how the pain and debilitating symptoms caused by the disease affect patients, especially those whose face and hands have become distorted, says, “Fred works hard at getting others as passionate about scleroderma as he is.”

Even Wigley’s chairman, Rheumatology Director Antony Rosen, admits that without Wigley’s prodding, he probably wouldn’t have included scleroderma in his investigations of how the body’s immune response goes awry. “He’s good at framing the questions,” says Rosen, “like, Why do some patients have more lung disease?” Together with his wife, Livia, and Wigley, Rosen has discovered an important part of the earliest stages of the autoimmune response. “Eventually,” Rosen says, “we’ll be able to predict autoimmunity and find a way to turn it off.”

Wigley’s old colleague Bob Wise, who now directs Hopkins’ pulmonary function lab, has become a key player and over the years has helped define the lung diseases caused by scleroderma, which are indeed another form of Raynaud’s. In some patients, inflammation makes the lungs stiffen and scar, limiting their ability to exchange oxygen and carbon dioxide. About 10 percent may develop severe constriction of the lungs’ blood vessels, resulting in life-threatening pulmonary hypertension.

Invariably, the heart also becomes affected when pulmonary vessels or tissues are diseased, and the right side—normally a low-pressure system—can end up struggling to pump blood to the lungs. “It’s like two different weather fronts coming in,” explains cardiologist Hunter Champion, “and you end up with a thunderstorm. The right ventricle fails because it can’t compensate for high lung pressure.”

Hopkins is one of the few places in the country that will even consider a lung transplant for people with a systemic disease like scleroderma. But the procedure—a last-ditch option—can be offered only to certain patients. For those who have problems with swallowing, stomach emptying and reflux, caused by a malfunctioning esophagus, a transplant would be too risky.

After the skin, says gastroenterologist Bill Ravich, the second most common organ this condition affects is the esophagus (“It just stops working because of scar tissue.”), leaving patients with severe reflux problems. “It’s the major reason they can’t be accepted for a transplant. We’re trying to define how much reflux makes a lung transplant unwise due to the risk of aspiration.”

Of all the specialists on the team, Wigley’s young rheumatology colleague Laura Hummers probably works most closely with him. She joined the faculty a year ago, after finishing her three-year rheumatology fellowship here. “I hadn’t decided whether to do bench or clinical research, so I looked for a place that offers both,” she says. “When I watched Dr. Wigley work, it all clicked.”

Today, she’s deep into a project with a Dartmouth cardiologist exploring the possibility that in scleroderma the body’s ability to make new blood vessels is undermined. She’s also Wigely’s right arm in providing clinical care (“I review all the new patients, so we can see the sickest right away”). Of Wigley, Hummers says, “He’s exactly the kind of doctor I want to be—an amazing mentor with superb clinical skills who cares deeply about every single one of his patients. He’ll see 30 in one day. I wonder if he sleeps.”

 

*****

 

For weeks after Wigley decided on a treatment for Nancy Bechtle’s scleroderma, the medication—an immunosuppressant ordinarily used to prevent organ rejection in people who’ve had a heart or kidney transplant—seemed to have little effect. Then, says Bechtle’s husband, Joachim, “I noticed one day when I was massaging Nancy’s hands and feet that I could squish a little more skin together.” Soon, she could wriggle her feet into her ski boots.

Finally, about a year and a half ago, it was clear that Bechtle had improved so much that she could go off the drug. Today, she looks—and feels—her pre-scleroderma self. She’s returned to the slopes and been diving in the Pacific. She still keeps chemical hand-warmers and gloves at the ready, but even her Raynaud’s attacks have subsided.

The only problem is, she still has scleroderma. At any time, her old symptoms could resurface, or new, more frightening ones could appear.

One day, overwhelmed by thoughts of what the disease could still do to her, she e-mailed Wigley one question: “What if I go over a cliff?”

His reply, which she only later realized had been posted in the wee hours, Baltimore time, went straight to her heart: “I will have a net there for you.”

 
 
 
 
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 Incurable, Not Untreatable
 
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