The 49-year-old woman knew as soon as she got out of bed that something was very wrong. A quick survey of her body revealed the source: Sprinkled around her bellybutton were a half dozen blisters. They were small — the largest maybe the size of a pencil eraser — and painful. They looked like the kind of blister you might get on your heel after wearing a new pair of shoes. Except they were on her belly.
She dressed carefully, choosing a pair of slacks that were a little loose around the middle. She put a long T-shirt under her sweater and hoped for the best. It was hard to concentrate at her job: The fleshy bubbles shot painful reminders every time she shifted position. When she got home, she immediately changed into a loosefitting dress. One of the blisters had ruptured, leaving an angry-looking raw red mark. She tried not to worry about it. It was September 2021; this was her first week back in the office after months of working at home, and she had too much on her mind already.
But the next day, there were a couple of more blisters. And the day after that. By the end of the week, her back and belly were dotted with a dozen of these odd bubbles. Another dozen had burst, leaving sores that seeped a clear fluid. At night, the opened blisters soaked through the gauze she applied, then through her pajamas and into the sheets. Every movement she made ripped open the weeping wounds that had dried, marrying flesh to fabric.
After a week of this, she took a sick day and began searching online for a dermatologist; after many calls, she found a practice where she could be seen the next day. The physician assistant who saw her was immediately concerned. After 40 years in practice, she had mastered the routine stuff — and this wasn’t routine. The patient told the P.A. that her skin had been extremely dry and itchy for months, but these blisters were new. As the P.A. examined the woman, she saw a few intact blisters but much of the woman’s torso was dotted with open splotches. This could be acne, she said. She would give her a cream for that. But it could also be a skin infection, and for that she prescribed an antibiotic. The patient should follow up in a couple of weeks so she could make sure things were moving in the right direction.
They weren’t. At the woman’s next appointment, her skin hadn’t improved. The P.A. brought in one of the dermatologists. This was clearly some kind of blistering disease, the doctor said. Possibly a type of disseminated infection called eczema herpeticum, which is caused by the herpes simplex virus. The doctor prescribed a potent steroid cream along with an antiviral medication to be taken for a week. That should clear things up, she told the woman confidently.
Blisters Everywhere
But over the next week, the blisters and the seeping spots that followed kept appearing. A second antibiotic was prescribed. More steroid creams.
At this point, everything she did hurt. The blisters were everywhere: on her arms, her legs and all over her back and stomach. They were even in her mouth and on her scalp. Sitting down was impossible. All she could do was perch at the very edge of the chair. When she went back, the determined P.A. brought in another dermatologist. He examined the woman closely and said: “I think this may be something called bullous pemphigoid. If it is, we can treat you.”
The P.A. explained that bullous pemphigoid (B.P.) is a rare autoimmune disease in which the body’s white blood cells create antibodies that attack the connection between the skin and the tissue below, causing these blisters. B.P. is treated with high-dose steroids, and when the disease cools off and blisters stop appearing, the steroids can be tapered down and sometimes stopped completely. The disease often resolves in a few months but can last for years.
She started taking 60 milligrams of prednisone every day. The drug was awful. She couldn’t sleep. She felt constantly hungry but at the same time bloated and full. She was weak. Her legs felt like each weighed 100 pounds. But the results were amazing. There were fewer new blisters. And the raw spots marking where old blisters had once been started healing. She took the prednisone for two months. Her skin got better, but she gained more than 20 pounds, and the weakness was so profound she could hardly get out of bed in the morning. The weight gain was depressing, but the weakness was intolerable.
Seeing how disabled she was, and how much her skin had improved, the P.A. lowered her dose. Almost immediately new crops of blisters arose. The P.A. increased the dose, but this woman clearly needed a different approach. She needed a doctor who specialized in these kinds of autoimmune diseases. There are internet groups for patients with B.P., the P.A. told the patient. They will know the best doctors for you. She was right. Through the International Pemphigus and Bullous Pemphigoid Foundation, she found a group of fellow sufferers online who lived not far from her on Long Island. They were unanimous in their recommendation: Dr. Allireza Alloo, an associate professor and attending physician at the Zucker School of Medicine at Hofstra/Northwell.
Hitting the Reset Button
When Alloo entered the exam room to meet his new patient, he could see how tired she was. And frustrated. She had been uncomfortable in her own skin for months, and the treatment was almost as bad as the disease. It started with the itch, she reported. She always suffered from dry skin in the icy depths of winter, but a couple of years earlier her skin got that same dry itchiness while she was vacationing with friends in balmy Hawaii. She bought her usual wintertime creams — moisturizers and low-dose steroid creams — and slathered herself at regular intervals. It helped, but the itch never went away completely.
Then she started getting canker sores — huge and painful ones. It hurt to eat. When one erupted in her mouth, she had to limit her diet to soups and shakes. And then the blisters started.
Alloo had her change into a gown and then did a full exam of her skin. Her blisters ranged from the size of a BB pellet to the size of a quarter. He could push down on them and they wouldn’t rupture or spread outward, as you might see with bullous pemphigoid. The skin over these blisters was thin, almost translucent. And they were delicate. Alloo could understand why the first dermatologists had thought she had B.P. That disease often starts with an intense itchiness before the blisters appear. But the disrupted tissue is deep, so the skin forming the blisters is thicker. And the blisters themselves are tense and not soft like these. This wasn’t B.P.
“You have pemphigus vulgaris,” Alloo told her, “and you are going to get better.” Pemphigus gets its name from the Greek word for blister. It was first described in the 18th century, and until the 20th century, with all its advances, every disease that caused blisters (and there are many) was called pemphigus. Pemphigus vulgaris is an autoimmune disorder, like B.P., but even rarer. In this disease, antibodies attack the connection between cells in the topmost layers of the skin so that it is easily separated from the layers below. An old test for the disease, called the Nikolsky test, was to rub the normal-appearing skin next to the blisters. In pemphigus, that skin often sheers off in thin sheets. Mouth sores are usually the disorder’s first symptom. Until recently the diagnosis was made solely by biopsy. Now a blood test can help identify the specific antibodies that do the damage.
As with B.P., Alloo explained to the patient, pemphigus can often be treated with steroids. But when these are not sufficient or cause intolerable side effects, the next step is often a medication called rituximab. This powerful immune-suppressing drug destroys the antibody-producing white blood cells. When the next generation of these cells are created, they no longer make the abnormal antibodies. It’s like hitting the reset button at a cellular level.
The patient had her first two doses of rituximab soon after that. Over the next few months her skin began to clear. It has been a year and a half since she started treatment, and she still hasn’t fully recovered; she expects she’ll need a couple of more doses of rituximab. But she is confident Alloo was right. She is going to get well again.
Lisa Sanders, M.D., is a contributing writer for the magazine. Her latest book is “Diagnosis: Solving the Most Baffling Medical Mysteries.” If you have a solved case to share, write her at Lisa.Sandersmdnyt@gmail.com.
