Freeman Reflects on Caring for Patients with Rare Immune Syndromes
When Dr. Alexandra Freeman arrived at NIH 20 years ago, little was known about the rare disease she would come to focus on—Job’s syndrome. Drawn to NIH by the opportunity to help people with immune disorders and study their condition over time, she now shares lessons learned along the way and new reasons for hope.
Freeman primarily sees patients with Job’s syndrome, which afflicts less than 900 people worldwide and yet is the more common in a group of hyperimmunoglobulin E syndromes (HIES). These genetic diseases cause chronic problems throughout the body including severe lung, skin, bacterial and fungal infections as well as joint, bone and dental issues.
“It’s a tricky disease,” said Freeman, a senior clinician at NIH and director of NIH’s primary immune deficiency clinic. “One thing that makes it really challenging is that people often look way better than they are.”
Over the years, Freeman has met with nearly 200 children and adults with Job’s syndrome who are part of a natural history study. The systemic problems usually change with age, she noted. Children tend to have recurring eczema, skin infections and pneumonia. The adults, as they age, have more difficulty with arthritis, spine disease, cardiovascular disease and intestinal issues.
“We try to give them a lot of medical education and talk about how hard it is having a disease that, if doctors have heard of it, they don’t know much about it,” Freeman said. “We try to empower them and help them to ask the right questions.”
Freeman also promotes collaborations across and beyond NIH toward better understanding specific aspects of the disease.
Thanks to one collaboration with a group at the University of North Carolina, “We now think the lung disease in part is from problems in the immune system but also from problems in the lung epithelium,” she said. This progress is important toward better treating adult patients who frequently are hospitalized with lung disease.
Freeman also is collaborating with a radiologist at NIH to analyze brain and heart imaging as well as NIH investigators who study wound healing. These and other collaborations are paving the way for new therapies.
One hopeful sign is that her patients are living longer. “Things have gotten a lot better over the years in terms of survival,” Freeman noted. When she first came to NIH, few Job’s patients lived past 50. Now, her oldest patient recently turned 74. She attributed the longer lifespan to earlier diagnosis, better understanding of the disease and better treatments, such as improved antifungal medications to tackle fungal pneumonia.
Another newer treatment, an eczema injection, has also been lifechanging for many of her patients, so much so that it might help explain the sudden baby boom in her young adult patients. As their skin and quality of life improve, she said, more of her patients are having children.
Although many of the chronic medications her patients regularly take are unsafe during pregnancy, Freeman is increasingly discussing family planning options with her patients. “Now, our patients are living longer, feeling better and more men and women are having children,” she said.
Freeman started her career as a pediatric infectious disease physician. She studied biology at a small college in Minnesota, then attended medical school at Georgetown University. After completing her residency at Yale New Haven Children’s Hospital and a fellowship at Northwestern University, Freeman began caring for children who were immune compromised due to cancer, bone marrow transplants, HIV or other immune deficiency disorders.
Freeman and her family then moved back to the Washington area as she had landed a job at NIH’s National Institute of Allergy and Infectious Diseases (NIAID). There, she auspiciously met Dr. Steven Holland, an NIH immunology expert, who suggested she study Job’s syndrome.
In 2005, Freeman began caring for Job’s patients. Two years later, the genetic cause was discovered and she began writing review papers and giving talks while working with her growing patient cohorts. It was a stimulating time to be working in this specialty.
“It was this explosion of new diseases that were being described that I got to be the clinician for,” Freeman said.
“NIH is so special,” she noted. “You could not do what I do anywhere else.” A big city hospital might see a few of these patients over time but NIH can fly them in and give them free care. “We can see so many more patients—no matter their background—and level the playing field, provide medication and care for them. It’s the perfect setup.”
Freeman is heartened by the support network created among patients who have come to NIH.
“Because we can bring them here, they can form their own community, which is important for their health care and advocacy,” she said.
The outlook is hopeful. There have been huge advances in the last 15 years and there are new therapies on the horizon. Freeman said, “Every generation is doing so much better than the generation before and we expect things to keep improving.”