Saving Theresa: The race to stop an elusive killer

Theresa Slayton noticed the spots about five years ago. First on her thighs, then her torso, red circles with white centers. Within months, they were everywhere except her face.

"There were probably three summers where I never wore shorts," said Slayton, a 54-year-old rehab nurse near Scranton.

Unable to get a diagnosis, Slayton searched medical websites until she found an image that matched. Everything she read described Degos disease as an ultrarare and typically benign disorder - provided the lesions did not migrate to her internal organs.

Slayton learned to live with the spots. But starting in September 2014, "there were periods of severe abdominal pain, cramping, sometimes sharp pain to the point where I couldn't even roll over in bed," she recalled. "Once every couple of weeks it would happen."

At last, she found a doctor in Upstate New York who was making new discoveries about her disease.

He sent her to the Hospital of the University of Pennsylvania last fall, where physicians looking through a lighted tube pushed through an incision saw lesions throughout her abdominal cavity, up and down her intestines, and on her liver.

She had "systemic" Degos, a condition that afflicts perhaps a dozen or so people in the United States each year. The brittle spots of dead tissue, unable to flex as the gut churned, could perforate at any time, spreading bacteria and infection throughout her body.

One drug - first tried on the hunch of a New York pathologist five years ago and costing $500,000 a year - had brought several systemic Degos patients back from the brink of inevitable death. A second drug - discovered serendipitously by another doctor a short time later - had allowed them to survive.

But at least as many died despite the two treatments.

Slayton's situation was unique. Doctors diagnosed her systemic disease much earlier, giving them hope her case might chart a new path to a complete recovery.

There was no guarantee that prevention would work - or that her insurer would agree to pay for one of the most expensive drugs in the world.

In the past, rare disorders didn't draw much research attention. Patients endured frustration, pain, and financial ruin seeking answers. Before the Internet, many didn't even know others like them existed.

But as science unravels these diseases' genetic codes, that's changing. And the way they are studied - most often through the obscure molecular pathways they travel - is the model producing some of the most innovative treatments for a growing number of more common conditions, including some cancers.

These targeted medicines are often much more expensive than traditional therapies, said Peter A. Merkel, chief of rheumatology at Penn and an expert on rare diseases who is coordinating Slayton's treatment.

"You would have to be Donald Trump to be able to afford anything like this on your own," said Sue DuPont, the mother of a teenage boy who has become one of the first survivors of systemic Degos.

Ernie DuPont started developing the telltale red and white spots as a 15-year-old high school freshman in Albany, N.Y. Two years later, when a dermatologist diagnosed Degos and explained how serious it could be, the family was alarmed.

"The pastor at our church came over and we just sat and I remember praying for hours that night," Ernie said.

But he was in great physical shape, having set a school record for sit-ups - 88 in a minute - and played goalie on the varsity soccer team. He'd had a few abdominal pains, but a CT scan was clear.

"I'm thinking maybe I did dodge a bullet, maybe I didn't," Ernie said. Still . . .

His pediatrician had a suggestion. "He said, 'Lee Shapiro is the smartest doctor I know,' " Sue recalled. But the rheumatologist knew nothing about Degos.

They went to see Shapiro in September 2009, the start of Ernie's senior year. His pains were worsening. "I felt like someone was stabbing me, someone taking a knife and twisting it and turning it all throughout my abdomen," he said.

By Christmas Day, the pains were so severe, accompanied by fever and vomiting, that surgeons opened his abdomen. They found lesions lining the exterior of his intestines. One had perforated, and scar tissue created a blockage.

For Shapiro, the location of those lesions outside the colon helped explain why systemic Degos typically is diagnosed so late: Colonoscopies, the usual diagnostic tool, look only inside. That realization was how doctors in Philadelphia confirmed Theresa Slayton's disease before a catastrophe sent her to the ER. She and Ernie were the subjects of a paper about diagnosis that Shapiro's team recently published.

But all that was in the future. In late 2009, Ernie's bowels were dying, and he would soon be on a ventilator. Shapiro emailed a dozen colleagues, seeking any ideas to save his patient. One had heard about an astonishing case just weeks before in New York City and gave him the name of a pathologist whose idea had saved a man's life.

She responded from a meeting in Portugal.

As a young pathology resident in the late 1980s, Cynthia M. Magro had set herself a goal: Find tissue samples showing the patterns of interesting diseases. She was in the right place: Massachusetts General Hospital had a basement room with case records going back decades.

One night, she came across the file of a patient who had died in 1966 of a disease described in 1942 by a French dermatologist named Robert Degos.

Under a microscope, Magro examined a slice of tissue that had been preserved in a block of paraffin. "It was a novel pattern and it always stuck with me," said Magro, now a pathology professor at Weill Cornell Medical College.

As her career progressed, Magro became an expert in autoimmune disorders related to C5b-9, a rapid series of events that normally ends with the release of proteins able to bore into invading cells and destroy them. When the defense mechanism goes haywire, it targets the endothelial cells that make up blood vessels. This seemed to be happening in Degos, as well.

Meanwhile, Magro became director of a pathology laboratory, where she would occasionally diagnose Degos. One biopsy came to her for examination in late 2009. The patient, a middle-aged lawyer, was in bad shape at Weill Cornell's New York-Presbyterian Hospital.

Magro thought back to a drug she had encountered more than a decade earlier. Later approved for two other rare diseases, eculizumab seemed to inhibit the same autoimmune events that were killing blood vessels in Degos patients.

Magro persuaded Alexion Pharmaceuticals Inc. to provide the medicine for the lawyer on a compassionate-use basis. The Food and Drug Administration signed off on the experiment.

Doctors, facing an unconscious patient in cardiac and respiratory failure with nothing to lose, eventually hooked up the IV bag on a Friday evening in October 2009.

To the astonishment of his doctors, the lawyer woke up on Saturday morning and asked what the fuss was about.

As it turned out, Magro's insight saved his life but could not repair the damage Degos already had done. That would require another discovery.

After hearing back from Magro, Shapiro wrangled an eculizumab donation for his teenage patient, with the same dramatic result. Ernie got well enough to finish high school and even play recreational soccer, to his mother's dismay.

After several months, though, he lost feeling in a hand and had trouble speaking. Tests showed a series of mini-strokes. He had to drop out of college.

Shapiro again needed help - and got it from a patient.

Shapiro directs the Steffens Scleroderma Center in Albany, which specializes in a group of disorders that affect connective tissue, causing symptoms that vary widely from person to person.

There was a similarity between Ernie's skin lesions and the spots on a longtime scleroderma patient. The woman turned out to have Degos disease, limited to the skin.

She also had been having trouble breathing - a common side effect of scleroderma. Her cardiologist put her on IV treprostinil, a drug approved for severe pulmonary hypertension.

"She came back three months later dramatically improved," Shapiro said. "She could walk a golf course, whereas before she was short of breath walking just a hundred feet."

And, she pointed out, her spots had faded.

"That was what gave me the idea of using the treprostinil for Ernie," said Shapiro, who persuaded the pharmacy benefits manager for Ernie's health insurance to cover the medicine off label. The medicine - pricey but nowhere near the cost of the first drug - appears to help the body rebuild blood vessels.

The cause of the disease itself is unknown, although there is some evidence that it runs in families. Ernie's younger sister, Jennifer, started developing skin spots when she was 15, the same age he did. But she is now nearly 20, and there has been no sign of spread.

Ernie, now 24, has slowly improved despite some setbacks, and is finishing college.

The lawyer in New York City is on treprostinil, too. His initial damage was so severe he must receive nutrition through a tube, but he has been eating more and is able to work.

Both patients will likely be on both drugs for life.

"We don't dare stop treatment," Shapiro said.

Alexion no longer provides its phenomenally expensive drug to Degos patients free. Some governments that offer universal health care refuse to pay the cost: "Husband makes heart-breaking plea for potentially life-saving drug for Irish mum who suffers from rare disorder," read one of several recent headlines.

In the U.S., however, at least a half-dozen private insurers have agreed to pay. Slayton's approval came through on a third-level appeal just before Halloween.

Every other Thursday, she drives 3½ hours from northeastern Pennsylvania to Penn, where a nurse hooks up an IV for the 35-minute eculizumab infusion.

Success is hard to measure, as the goal is prevention - the absence of a catastrophic intestinal tear that doctors were certain would occur but had no idea when. But she says her abdominal pains are gone.

Shapiro is preparing to submit a request to her insurer to cover the second drug, treprostinil, which is made by United Therapeutics Corp. of Silver Spring, Md., and costs more than $60,000 a year.

Once again, it will be a unique coverage request. Experimental use of the drug has kept other patients alive. But Slayton appears to be healthy.

The question is: What will it take for her to stay that way?

Among these sites you will find databases of rare diseases, links to patient organizations and support groups, lists of physicians with expertise in the disorder, and information about drug development:

Genetic and Rare Disease Information Center, National Institutes of Health: 888-205-2311, https://rarediseases.info.nih.gov/gard

National Organization for Rare Disorders: 800-999-6673, http://rarediseases.org

(organizes Rare Disease Day on Feb. 29)

Office of Orphan Products Development, U.S. Food and Drug Administration: 301-796-8660, http://1.usa.gov/1ihNeFI

dsapatkin@phillynews.com

215-854-2617

@DonSapatkin