Contending with his inflamed and often painful skin condition, along with numerous futile efforts to treat it, would consume the next six years of Williams’s life. Nearly two dozen specialists were unable to figure out why the rash, which periodically spread to his face, would sometimes get better but never entirely disappear.
In the end, its unlikely cause turned out to be far more terrifying than Williams ever imagined. Subsequent treatment not only swiftly cleared up his skin, it also saved his life.
The case also left an indelible impression on Brian Poligone, a University of Rochester dermatologist and the ninth specialist Williams consulted, who finally figured out what was wrong. “It’s a really incredible story
. . .
and will be one of those cases that I bring up in my career,” said Poligone, 39.
Williams, 54, said he felt reassured when the first skin doctor gave him a topical cream. “This should take care of it,” he remembers the doctor telling him. But five months later, when various medicines had failed to eradicate the rash, he consulted a second dermatologist.
“He worked on it for probably a year trying different things” that didn’t help, Williams said. In January 2006 he began seeing a new dermatologist at the University of Rochester School of Medicine for “recalcitrant dermatitis.”
Williams said that the rash would leave dense clusters of small, painful blisters on his back, underarms and groin — any place he sweated. Even his feet were sometimes affected. “I tried not to sweat,” he recalled, and increasingly avoided even golf and yard work.
At its worst, the oozing pustules blanketed much of his face, sometimes causing his eyes to swell nearly shut. “I had to use a warm washcloth to open my eyes” in the morning, he recalled, and shaving was impossible. During such times, Williams said, he also tried not to schedule business meetings or travel, which was especially difficult when he was in negotiations to sell his company.
“It was brutal,” he said, although “most people didn’t really know what was going on unless it was on my face.”
Treatments with ultraviolet light, a mainstay therapy for a variety of skin ailments including psoriasis, helped because they made his skin less sensitive and painful. But none of the medications — steroids, antibiotics and even big guns such as methotrexate, which is used to treat cancer, and Cellcept, a drug to prevent rejection in transplant patients — eliminated the rash. Williams underwent several skin biopsies; all seemed to point to psoriasis.
‘What am I missing?’
On Sept. 23, 2009, Williams walked into the office of Poligone, a recent arrival from Yale School of Medicine. By then Williams had seen virtually all of Poligone’s partners in the Rochester dermatology group.
As he scanned his new patient’s hefty chart, Poligone saw that none of the eight dermatologists who preceded him had been able to pinpoint the underlying cause of the rash. “It’s very uncommon” for a patient to see so many doctors without a more definitive answer, said Poligone.
“I thought, ‘What am I missing?’ ” Poligone recalled. “More than anything, the patient’s in front of you and you’re trying to scramble to find appropriate treatment.” A rash and itching can have myriad causes, ranging from the prosaic (poison ivy) to the potentially fatal (lymphoma). Doctors did not even know whether Williams’s rash was a reaction to something internal or environmental. Over the years doctors considered and ruled out eczema, an unusual presentation of a cat allergy and stress.
Williams was having a bad flare on that initial visit, and Poligone prescribed a steroid shot as well as an antibiotic, because some of his lesions looked infected. Once again, the effect of the drugs was only temporary.
By January 2010, Williams was no better and Poligone prescribed azathioprine, a powerful and sometimes toxic drug that suppresses the immune system and is given to transplant patients. Williams recalls feeling increasingly frustrated. “I’d go in and say, ‘Listen, the things you’re doing are just suppressing it — we’ve got to try something’ ” to get rid of it.
But what? Another skin biopsy — the fourth — again indicated psoriasis.
In June 2010, Poligone decided to feature Williams in a monthly seminar called grand rounds, bringing in 20 specialists from Rochester to see if they might have any ideas. But instead of what he had hoped — some doctor piping up and asking “Have you thought of . . .?” there was, Poligone remembered, a lot of “head scratching” — and silence. No one had any ideas.
Three months later, Poligone decided to try again. Peter Heald, an emeritus professor of dermatology at Yale and Poligone’s mentor, was coming to Rochester to give a talk, and Poligone decided to hold a second grand rounds, hoping that Heald might have a suggestion about the case that had become among Poligone’s most difficult.
Before the meeting, Poligone said he sat down and listed four possible diagnoses: One was an Id reaction, a rash caused by a fungal infection, usually athlete’s foot. A second was necrolytic migratory erythema, or NME, a rash associated with a rare form of pancreatic cancer. NME is so rare that Poligone had never seen a case.
NME seemed unlikely. While he did have a rash, Williams did not have anemia, hyperglycemia, diarrhea or other characteristic symptoms, and multiple biopsies had not detected the abnormality.
“For the first time, I thought maybe the biopsies were lying,” Poligone recalled. Heald concurred and advised pursuing NME as a possible diagnosis.
Poligone ordered another skin biopsy — like its precedessors, it seemed to point to psoriasis — as well as two blood tests; one to measure the level of glucagon, a hormone produced by the pancreas, and another to measure his insulin level.
The tests were revelatory: Williams’s glucagon reading was 620 picograms per milliliter, far above the upper limit of normal of about 130. And his insulin level was 71 microunits per milliliter; the upper end of normal is 27.
The next step was a CT scan. The test, performed in December 2010, revealed a devastating finding: a cancerous tumor roughly the size of a plum in Williams’s pancreas. There was no doubt that Williams’s rash was NME and that he had a glucagonoma, a rare form of pancreatic cancer known as a neuroendocrine tumor. (Apple founder Steve Jobs succumbed to a different pancreatic neuroendocrine tumor called an insulinoma.)
1 in 20 million
Fewer than 250 cases of glucagonoma have been identified worldwide since 1942, and the American Association of Endocrine Surgeons estimates that about one in 20 million people annually will develop it. The tumor has no known cause, but in some cases a family history of cancer may be involved. (After his diagnosis, Williams discovered that his grandmother died of pancreatic cancer at age 68, although its specific type is not known.) Glucagonomas result from the overproduction of the hormone glucagon; this excess disrupts the production of insulin, which regulates blood sugar. About 70 percent of glucagonoma patients have NME, and many also lose weight, as did Williams, who had thought his gradual 30-pound weight loss was caused by the stress of dealing with the rash.
Surgery to remove the tumor is the preferred treatment because glucagonomas do not respond well to chemotherapy. Because such cancers, which grow slowly, tend to be detected only after they have spread beyond the pancreas, surgery cures only about 20 percent of such patients. Poligone said that he and his colleagues were pessimistic; Williams had had symptoms for more than six years, and they thought it was highly likely that his cancer had spread.
Poligone said he lined up an oncologist and a surgeon and then broke the news to Williams, who did not understand the gravity of his diagnosis at first.
“I really didn’t relate ‘tumor’ with ‘cancer’ until they told me I was going to be treated at the cancer center,” he recalled.
On Jan. 22, 2011, Williams underwent surgery. The results were the best anyone could have hoped for: The cancer had not spread to his lymph nodes or to his liver, and doctors believed they removed it all. Four weeks later, his rash was gone; subsequent tests have found no sign of cancer.
“We were very surprised it was contained,” Poligone recalled, adding that doctors believe his surgery was curative. Poligone said that a dermatopathologist who went back and examined all of Williams’s biopsy slides did not find specific evidence of NME. Other than the rash and weight loss, Williams had none of the other classic symptoms that might have prodded doctors earlier to suspect pancreatic cancer, nor did he seem seriously ill.
Instead, he seemed mostly eager to be rid of the rash. “He was, like, ‘You’re cutting into my golf time and work time, get me back,’ ” Poligone recalled, adding “I take the most solace that [his case] had an excellent outcome.”
Williams said that he remembers feeling increasingly tired but not really sick. Only in retrospect, he said, did he realize “how weak I’d become,” adding, “I feel like a new person.”
Sometimes he ponders the six years he spent seeing doctor after doctor about his miserable rash. “You think, ‘Geez, why didn’t they run this test two years earlier?’
“But then you think, ‘Hey, they figured it out.’ ”
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