I went to the emergency room 16 times for allergies and asthma as a college freshman. Each time I was given a prescription for an EpiPen, an auto-injector pen that administers a dose of epinephrine, used for the emergency care of an acute allergic reaction.
I was told to figure out what I was allergic to. I tried very hard but couldn’t. All my life, I have had hives, eczema, asthma, atopic dermatitis, sinusitis, and food allergies. Somehow the college environment made things worse. The college was frightened, too, and asked me to live in the infirmary for a semester. What should have been a joyous beginning of independent college life was hampered by continuous allergic reactions. That semester was a low point. Little did I know that the solution would be in my genes, that it would change medical practice, and it would launch me into a new career.
My family and children also had severe allergies. As a child, my grandparents once threw a big party, and I stood in the corner crying because I thought hives ruined the look of my sundress. My aunt noticed my distress and said, “Look at my hives! See? We all have hives,” and that normalized the situation for me then and for many years to come.
My children, too, had hives, eczema, asthma, atopic dermatitis, sinusitis, food allergies, and anaphylaxis, but now we also have eosinophilic gastrointestinal diseases, which nearly killed my younger daughter, who was hospitalized for 30 days at Hackensack University Medical Center in 2006 when she was almost 2 years old. No one could figure out what was wrong, but she had uncontrollable diarrhea and vomiting. She stopped walking, her gums began to bleed, and she was down to 17 pounds. Malnutrition set in. They came in and put a heart monitor on her, telling me that “things didn’t look good.” One day she lay in bed and said, “Help me, Mommy!” I lost it. This was my moment of greatest despair.
In 2008, I sought out a new allergist, Dr. Lisa Ellman-Grunther, in New York. It took most of the morning for her to do an intake on me and my two children because our cases were complex. She didn’t think we had ten diseases: She thought we had one disease with ten symptoms. She felt I had a genetic flaw, and blood tests revealed I had an elevated serum tryptase, blood markers that usually indicate a severe allergic reaction, but I was sitting calmly in her office. How could this be?
She became a staunch advocate and referred me to the National Institutes of Health (NIH), which investigates challenging cases. They invited me to Bethesda, MD, and in the end, they called me to say they couldn’t find anything.
I sat on my kitchen floor, cried, and called a friend. She asked what difference a diagnosis would make. I decided then that I would keep investigating until I found an answer. I decided to be persistent about finding a better treatment.
In 2011, my children were still sick with eosinophilic gastrointestinal disease, and we needed more help, so we traveled to the Cincinnati Children’s Hospital Medical Center. Liz had skin flushing, indicating the presence of too many allergic mast cells, during an endoscopy to look at her esophagus and stomach. The doctors were trying to explain to me what an elevated tryptase was! I said I knew about it because I had that problem, too. But they said it couldn’t be inherited. I asked them to humor me: check my other child for an elevated tryptase. Turns out that both children had elevated tryptases, and we were referred back to the NIH. How could this be? It contradicted conventional wisdom.
Drs. Joshua Milner and Jonathan Lyons at the NIH invited us to participate in a clinical trial, which eventually extended to my parents and 19 members of my family. I asked two questions: 1) Were we related to the other families with similar symptoms participating in the same clinical trial? And 2) What evolutionary purpose would a gene like this serve to remain inheritable? They liked my questions. They invited me and other participants to a town hall-style conference in March of 2016.
With a lecture and a whiteboard, the scientists illustrated that there was a gene responsible for allergic severity. Drug companies had been alerted and were beginning to seek a cure, even though this might take 15 years. The interim treatment was high doses of antihistamines, a biologic drug called Xolair designed originally for asthma, and H2 blockers like Pepcid. Our participation in a clinical trial led to a new discovery and would help people with severe allergies whose doctors might otherwise have dismissed them and remained untreated. This was a quality-of-life improvement for everyone involved. The doctors named it HaT: hereditary alpha tryptasemia.
I asked recently if Dr. Lyons remembered me, and he replied, “Of course I remember you!” He went on to say, “I led the project and have continued to lead the effort to understand this genetic trait for over a decade and was the first to realize that it was likely common (before we later proved it was). I also developed the genetic test that is currently used to diagnose HaT.”
My children and I felt better with treatment. The drug companies did find a cure, but it’s astronomically expensive and not a viable market alternative. The NIH said they continued to be interested in us because the effects are increased, or more severe with each additional gene copy. We have three extra copies of the gene and yet we were working, playing, and raising families. Some people have only two copies and have sought disability. The syndrome is found only in white Caucasians of European descent and is prevalent in about 6 percent of the population. However, only 20 percent of those are triplicates like us.
My prior question about evolutionary benefits remains unsolved. Dr. Lyons explained, “We do not know if it protects against anything … yet. There are very strong genetic arguments to be made that it was selected for in Europe in relatively recent human evolutionary history. Some, but not all, of those arguments are akin to those made for sickle cell disease (which protects from malaria.)”
A lot more needs to be done to help people with intractable health problems, especially for those whose symptoms defy conventional answers. Removing the bureaucratic burdens for physicians, such as unnecessary paperwork and billing forms, will enable the experts to spend more time advocating for patients like me in their practice. Dr. Ellman-Grunther went above and beyond to fill out extensive paperwork to refer me to the NIH in 2008.
Watching the NIH research process in real-time also inspired me to obtain a PhD. At age 52, I am now a postdoctoral fellow at the University of Pennsylvania School of Nursing because I want to keep seeking answers to tough questions. I hope my research will help get better care for people with intellectual and developmental disabilities (IDD).
The NIH recently designated persons with disabilities as a health disparities population. I recently received my first NIH grant to use novel methods to create the first individual risk profiles for people with IDD, so their care can be better suited to their needs.
I want to find the fault lines and fix them. Being a professional problem solver—first as a mom and now as a researcher—inspires me.
Lynne Moronski is a post-doctoral research fellow.
