Nights were a particular torment, and nothing but steroids seemed to help. What could be causing this?
The itch always felt worse at night. The 68-year-old woman willed herself to lie still and not give in to the urge to scrape her skin from her body. She often wore thick cotton gloves to protect herself from her own nails. And it helped — until she tore the gloves off to scratch the itch that tortured her arms, her belly, her legs and especially her feet. She shifted restlessly on the foldout sofa where she now slept to spare her husband her incessant movement.
Her nights were divided into long hours of lying on the lumpy sofa trying not to scratch, losing that battle and then occasionally falling asleep for a few minutes when exhaustion finally won. She hated seeing the raised red blotches marked with bloody scratches each morning. The rash started out of the blue one morning four months earlier. She had an itch on her stomach and was scratching it mindlessly as she slowly woke up. She lifted her pajama shirt and saw for the first time the irregular, roundish raised blotches of red that had since become her daily tormentors.
She immediately called her dermatologist. The nurse practitioner gave her a name for the rash — hives — and she prescribed a steroid cream. It didn’t help. When the hives were still driving her nuts two weeks later, the woman called her primary-care doctor. She took one look at the patient’s blotchy, scratched legs and feet and immediately prescribed a week of prednisone and referred her to the Asthma, Sinus & Allergy Program at Vanderbilt University Medical Center. The first available appointment was six weeks away, but someone would call if there was a cancellation.
No one ever called, and those six weeks were awful. The prednisone helped with the itch, but it returned with a vengeance when she ran out of pills. Despite her pleas, her doctor was uncomfortable continuing to prescribe this powerful steroid to treat a rash. She took two antihistamines a day, and that helped a little. She took as many baths as she could. But the rash was unrelenting. It moved around but never went away. Sometimes it was on her arms, sometimes her neck. Always her stomach, her back, her legs and her feet.
Nothing New in Her Life
Finally the day of her appointment arrived. She and her husband drove into Nashville to meet Dr. Basil Kahwash, the young specialist in allergy and immunology at Vanderbilt. He listened patiently as she told her story. She looked tired but otherwise well. Kahwash was reassured by the fact that her hives were not associated with bruising or pain, which could suggest a serious illness.
Had she started any new medications? No, she said, a hint of frustration in her voice. She had spent weeks trying to identify any triggers. No new medications, no new soaps or makeup. Her diet was the same as it had always been. There was nothing new in her life. Except these hives.
What she had, Kahwash told her, was chronic idiopathic urticaria (C.I.U.) — the medical term for hives that last longer than six weeks, where no cause can be identified. And most of the time, Kahwash acknowledged, a cause is never found. But the good news is that the itching and rash are usually easily controlled with medications. First steps involved aggressive skin care and lots of moisturizers. And a steroid cream can help. But high-dose antihistamines are the mainstay of treatment.
Hives are caused when a white blood cell known as a mast cell detects something interpreted as a foreign invader and releases a chemical called histamine. It’s the histamine that causes the itch and the swollen blotches. The patient was already taking an antihistamine, and that was a good start. That quiets the mast cells in the skin, Kahwash explained. Histamine is also made in the stomach, where it triggers the release of acids used in digestion. The antacid famotidine blocks this type of histamine and should help with the hives as well, he told her.
And because her symptoms were worse at night, Kahwash recommended the use of yet another antihistamine, diphenhydramine, at bedtime. This is a more potent antihistamine, usually taken at night because it causes drowsiness. Finally, a fourth drug, Singulair, could help stabilize the mast cell so that it would be less likely to release its store of histamine. This regimen worked for maybe 70 percent of his patients. Stay in touch, he encouraged her. If these didn’t work, there were other options.
Credit…Photo illustration by Ina Jang
Just Give Me the Steroids!
A week later, Kahwash received an email from the woman through his patient portal. She was still miserable — still covered with hives, still not sleeping at all. What was the next step? He immediately ordered an intravenous medication known as omalizumab. This monthly medication — often used to treat severe asthma — is a lab-made antibody that attaches itself to the mast cell to prevent the release of histamine. In one study, the drug eliminated both itching and hives in about half of patients who took it, and nearly everyone felt better after three months on it.
After six weeks on the omalizumab, the woman got back in touch. Just give me the steroids, she pleaded. That was the only thing that helped. To Kahwash, daily low-dose steroids were a last resort. Prednisone had too many side effects to use long-term until all other avenues had been exhausted. And he had one more option: a powerful but targeted immune-system suppressor called cyclosporine. It is most commonly used in organ transplantation. This was a big gun, but it was still preferable to prednisone. Kahwash started her on a low dose of cyclosporine.
Her next appointment with him was three weeks later. When she arrived, Kahwash was shocked to see that her hives were just as bad as they were when he first saw her. Had the diagnosis been wrong? People often think that hives are a response to an outside trigger — an allergic reaction — but that’s almost never the case with urticaria that lasts for weeks. C.I.U. is usually caused by overreactive mast cells. What makes them overreact is still not well understood. Still, treatment is usually straightforward. But Kahwash hadn’t made a dent in this patient’s hives despite high doses of two antihistamines, two mast-cell stabilizers and cyclosporine.
So what else could this be? There are a handful of autoimmune diseases that can cause chronic hives. A form of autoimmune thyroid disease can do it. Lupus too. It’s a rare symptom in both, but possible. Another disease, mastocytosis, involves the body simply creating too many mast cells, with that proliferation causing all sorts of misery, including chronic hives. Finally, a handful of food allergies might do this. These mostly occur in children, and usually the reaction comes right after the food is eaten, so the link between food and reaction is rarely a mystery. But there is an exception, an allergy described just over a decade ago — an allergy to meat. Many people who have this allergy report that their worst symptoms happen in the middle of the night, hours after a meat-filled dinner. All these possibilities were rare, but so were her tough-to-treat hives. Kahwash sent the patient to the lab to get tested for each of them and started her on a higher dose of cyclosporine.
A Small Price to Pay
The test results came back the following week. Her thyroid was fine. It wasn’t lupus. It wasn’t mastocytosis. The test for the meat allergy took longer. But it finally provided the answer: The patient had developed an allergy to meat.
Kahwash had seen this allergy in a handful of his patients and knew it was a strange one. Most allergies are triggered by proteins, but this was a reaction to galactose-?-1,3-galactose (known as alpha-gal for short), a sugar. And the reaction to the allergen took hours, not minutes, to appear. Strangest of all, this allergy is triggered by a tick bite. In the United States, the lone star tick, found predominantly in the Southeast, has been identified as the vector. In other countries — it has been reported on every continent except Antarctica — other ticks are involved.
Alpha-gal syndrome was first recognized in the early years of the 21st century when a physician noticed that allergic reactions to a chemotherapeutic drug containing galactose-?-1,3-galactose were much more common in the Southeast than in the rest of the country. That suggested an environmental trigger. Then in 2009, a group of allergy specialists at the University of Virginia noticed that some of their patients developed symptoms ranging from hives to anaphylaxis when they were exposed to alpha gal in mammalian meat. Two years later, the same group linked that allergy to bites from the lone star tick.
Kahwash called the patient with the news. Did she remember getting bit by a tick? She did not. And she didn’t hike or bike in the countryside, so getting bit by a tick seemed unlikely. Nor did she see any link between the foods she ate and her hives, though she acknowledged that she and her husband did eat meat most days. What mattered most, Kahwash told her, is that she had indeed tested positive for the allergy. Try giving up meat from all animals with hooves, as well as milk products, and see if that helps, he advised. And then he waited. He didn’t have to wait long. The patient soon reported that after being completely off meat and milk for a week, she felt great. For the first time in months, she was completely hive-free, itch-free and, most important, able to sleep.
That was a year ago. She hasn’t eaten red meat since Kahwash suggested the link, though she finds that she can still eat cheese and milk. Recently the doctor asked if she would like to be retested. The allergy goes away over time — usually within five to seven years. He could monitor the levels indicating her allergy and let her know when she might try meat again. Her answer was quick and clear: No, thank you! Not eating meat seemed a small price to pay for the luxury of good nights of sleep and days forever free of hives and the irresistible scratching at an insatiable itch.
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.