Elizabeth Starrels sat in the examining chair of a Washington ear, nose and throat specialist in October 2012, weeping in frustration and pain.
For the previous four months, Starrels, then 52, had been battling painful mouth sores that were getting worse. Eating had become a near impossibility, and Starrels, who was largely subsisting on smoothies, had lost 20 pounds.
Her dentist and an oral surgeon told her she had thrush, a yeast infection caused by an overgrowth of fungi in the mouth that can result from antibiotics. The rinses and medicines they prescribed worked only briefly or not at all.
The ENT whom she saw next disagreed. He suspected that her problem was an inflammatory disease. When Starrels, a registered nurse who works at MedStar’s Georgetown University Hospital, broke down, telling the doctor she didn’t think she could live with the pain, his response was brusque.
“He told me I would have to learn to live with it — I had no choice,” she recalls. The doctor offered to prescribe an antidepressant.
Starrels said that the ENT’s reaction had a galvanizing effect: She didn’t need an antidepressant, but she did need someone who seemed interested and willing to help her. “As a nurse,” she said, “I could advocate for other people but not for myself.”
Two months and several additional doctors later, Starrels received a new diagnosis as well as effective treatment. She also found encouragement online, through a support group whose help she considers invaluable.
“I was so grateful to have a diagnosis and to know that there was a treatment,” she said, adding that her pain is now gone. Her chronic disease is in remission — one she hopes will be long-lasting.
Dramatic weight loss
In January 2012, nine months before she wound up in the ENT’s office, Starrels, who lives in Northwest Washington, woke up with frequent nosebleeds. She attributed them to dry air in her home and, because they were minor, did not seek treatment.
In May, she developed a stone in her salivary gland and received two 10-day courses of penicillin. These harmless stones, which form for unknown reasons, contain calcium and can cause pain and swelling if they block a duct, obstructing the flow of saliva.
Soon after she stopped the drug, Starrels developed painful mouth ulcers, similar to canker sores, which triggered the first of several visits to her dentist.
When the rinses and creams the dentist prescribed didn’t help, he referred her to an oral surgeon in his building. The oral surgeon told her he thought she had thrush, although she did not have its characteristic white patches, but rather, raw sores.
Starrels soon noticed that in addition to sores in her mouth that had spread to her gums, her gum tissue seemed to be sloughing off.
Eating had become incredibly painful, although drinking was tolerable. Starrels was living on protein shakes and smoothies as well as yogurt and sweet potatoes — foods that required little or no chewing and were not irritating.
The ENT diagnosed oral lichen planus, a chronic autoimmune disorder that has no known cause. The disorder, which causes mouth sores, is not contagious and is usually treated with topical numbing creams or, in more severe cases, corticosteroids such as prednisone, which reduces inflammation. A second specialist in oral medicine concurred but told her he had little new to offer.
Starrels decided it was time to look elsewhere.
In November, a few weeks after the ENT appointment, she traveled to Philadelphia to see an oral medicine specialist at the University of Pennsylvania. A week earlier, to her dismay, a spray of fluid-filled blisters had erupted on her chest.
The doctor peered into her mouth and told Starrels he didn’t think she had lichen planus. He suspected her problem was pemphigus vulgaris, a rare autoimmune disease, and urged her to see a dermatologist immediately to undergo a biopsy of the blisters, which could help confirm or refute the diagnosis.
Pemphigus vulgaris (and a related disorder called pemphigoid) is a serious and incurable disease that is usually caused by an overreaction of the immune system, which mistakenly attacks healthy skin cells, especially the mucous membranes. There are several types of pemphigus that cause painful blisters elsewhere on the body. Pemphigus vulgaris, the most common form, generally starts with mouth sores and progresses to eruptions elsewhere. It is not contagious and does not appear to be hereditary, although the disease is linked to genes that are more common in people of Mediterranean and Middle Eastern descent, and among Eastern European Jews.
The disease, most common in middle age and among the elderly, affects an estimated 3 in 100,000 people worldwide and is treated with a variety of medications that quell inflammation. Before the advent of corticosteroids, it was usually fatal.
“Everyone who has pemphigus carries a gene that increases the risk of disease, but only about 1 out of every 10,000 people who has the gene actually gets pemphigus,” said Grant J. Anhalt, a professor of dermatology at Johns Hopkins who specializes in treating blistering skin diseases. Scientists don’t know why only a fraction of those who carry the gene are affected.
Starrels was able to undergo a biopsy the day after her appointment at Penn. The procedure was performed by a dermatopathologist — a doctor trained in both dermatology and pathology — who is a partner of Starrels’s dermatologist. The biopsy yielded preliminary confirmation of pemphigus vulgaris, which was confirmed by pathologists at Johns Hopkins.
‘A very good treatment’
A few weeks later, at the recommendation of her dermatologist, Starrels saw Anhalt.
“He basically said, ‘There’s no cure for this disease, but I have a very good treatment,’” Starrels remembers him telling her, to her great relief.
Starrels’s case is typical, Anhalt said. It takes patients an average of six months to a year to receive a diagnosis, largely because the telltale symptom — mouth sores — has numerous causes and because pemphigus is rare. Her frequent nosebleeds, he said, were a harbinger of the disorder.
“Not thinking of pemphigus is the norm,” he said. “The real bell goes off when people have oral ulcers that don’t improve and then develop skin ulcers.”
By the time they see him, patients are understandably anxious. “They go online and see the pictures or read the blogs and think, ‘‘Oh my God, my life is over.”
Anhalt, who has treated 300 patients between the ages of 4 and 89 for various forms of the disease (one form of which he helped discover in 1990) has increasingly relied on periodic infusions of rituximab, a drug approved to treat rheumatoid arthritis and certain cancers. Last month, the Food and Drug Administration granted the drug, which is in a Phase III clinical trial, breakthrough therapy status, a designation that could speed its approval for pemphigus and facilitate insurance coverage. Other drugs, including prednisone and CellCept, an immunosuppressant drug often used to prevent organ rejection, are also prescribed, sometimes in combination.
Rituximab, which has been successful in severe cases where other drugs did not work, is expensive, costing around $20,000 for a round of treatment. Because it has not been approved to treat pemphigus, “getting it paid for can be a problem,” Anhalt said. Early treatment can result in faster and more durable remissions.
Starrels said that the diagnosis was a shock but that she was relieved to learn what was wrong and grateful to find a doctor who displayed both compassion and expertise.
“I had been in agony but was really trying to make the best of it,” Starrels said.
She began taking prednisone and CellCept and then underwent the first of three rituximab infusions. Her insurance covered the first round without difficulty. Coverage of the last round was initially denied, but it was covered after Starrels appealed.
Over a period of months, her sores and blisters cleared up and her pain vanished. Her first remission lasted 18 months. The average remission lasts between 1.5 to 2.5 years, Anhalt said, but he knows of one patient whose remission has exceeded a decade.
Starrels said she has found great support online, through the International Pemphigus and Pemphigoid Foundation, a California-based group founded by a patient. The group has connected her with other patients and has been hugely helpful in managing the emotional and practical aspects of living with a difficult disease.
“They really saved my life,” Starrels said.