Girl Suffering From Skin Genetic Skin Disorder May Benefit from Recent Stem Cell Research
By Laura Urbani, Pittsburgh Tribune-Review, November 19, 2007
Fallyn McNamara is enjoying her time as a new Daisy Scout and kindergartener as best as she can. But playing with her sisters, working on craft projects, and other seemingly ordinary activities are often difficult for this 5-year-old girl.
Every aspect of Fallyn's life is affected by recessive dystrophic epidermolysis bullosa, or EB. It is a genetic disease that is considered to be incurable. But adult stem cells could be the answer as research continues to make headway for a variety of conditions.
Her skin can be wounded, and take days and even weeks to heal itself, from just the slightest pressure: the tag on her t-shirt rubbing against her neck is enough to cause injury. Chronic and painful blistering of the skin characterizes EB.
The factors confine Fallyn to a wheelchair. She doesn't walk due to concerns about blistering on her feet from carrying her weight. She doesn't have the stamina to walk far anyway, but can a little bit if she has to.
"Her legs are more of a problem area than the rest of her body," said her father, Frank McNamara, a school bus driver.
Her meals are consumed using a gastro-intestinal tube.
"Her mouth is small," McNamara explained. "She doesn't have any cheek pockets anymore. She has a short tongue. Dental hygiene is an extreme issue."
Many individuals with EB have to deal with a problem that affects the hands: when blistered skin began to heal, Fallyn's fingers join together and become “mittened”. Fortunately, she was able to over come this with surgery in August that re-separated her fingers.
Also, help with Fallyn's care arrives each day in the form of a home health nurse, who changes her bandages daily among other things.
Despite her circumstances, a photographer receives a smile from Fallyn as he passes by. Her father says that going to school at West Hempfield Elementary School is one of her favorite things.
"Surprisingly," he added, "she has a lot of friends."
Serious and sometimes fatal complications can arise from EB. However, the condition is not fatal on it's own.
"It is an inherited disorder of skin where you find the anchoring proteins are defective," said Dr. Anthony Van Norman, a dermatologist with Westmoreland Dermatology Associates, serving Excela Health. "You're born with a bad protein," resulting in extremely fragile skin.
Van Norman compares the disease to a chain link fence that is missing a few links. The fence cannot stand upright properly because missing links create weaknesses. The proteins that make up our skin can be viewed in a similar light.
With the help of an EB mouse model and in collaboration with investigators at Columbia University, University of Minnesota researchers were able to correct the disease in mice using bone marrow. They tested various types of adult stem cells to determine which would give rise to the development of type VII collagen -- the protein people with RDEB lack. One type of immature cells from bone marrow proved to be the best at producing anchoring fibrils that bind the skin to the body.
This research gives hope to Fallyn and many others who are suffering from this disorder.
"Pretty much everything from the mouth to the anus can be affected in aggressive cases (of EB)," Van Norman said. "The day-to-day weight-bearing of walking and playing can cause blistering."
The disease is "relatively uncommon," he added.
Some form of EB is believed to affect about 12,000 Americans. This is according to The National Institutes of Health.
The disease has more than 20 variations, this challenge among others, has prevented doctors from having a better understanding of the condition prior to the past 30 years.
Aggressive variants of EB are seen once in every 500,000 births, whereas milder types are observed to occur once in every 50,000 births according to a recent report by Dr. Surasak Puvabanditsin, assistant professor of pediatrics at UMDNJ-New Jersey Medical School.
Some patients develop blisters only on the epidermis, or uppermost layer of the skin. Others blister deeper, and in the most severe cases, tissue breaks down in the bladder, lungs, stomach, esophagus, mouth and intestines.
"You can have EB simplex (a milder form of EB) and live a normal life span," Van Norman said. "You're going to have blisters and have to watch weight-bearing exercises. These are otherwise young, healthy kids. (But) the real aggressive cases are almost always a problem."
Fallyn's blisters haven't affected her lungs, stomach, intestines or bladder.
"She hasn't shown any problems past her voice box," McNamara said.
Since 1988, the role of “leader” in regards to EB research has been Stanford University School of Medicine's Department of Dermatology. A difference could be made in the lives of EB patients with the gene and protein therapy research scientists are doing there.
"It's an example of a disease that is a model for gene therapy or stem cell medicine," Van Norman said. "They are looking to replace these defective proteins. I think a conservative level of excitement exists because there have been some small successes."
At birth or soon after, symptoms of EB are apparent. Most families are aware of the possibility of having children with EB since the condition is genetic. A child's race or sex plays no role in their chances of being born with EB.
However, Fallyn's diagnosis was a complete shock say her parents.
"We never heard of this disease until she was born," McNamara said. "There is no prior family history of this."
Both parents carry the faulty gene, but genetic testing has revealed that neither parent has EB. McNamara and his wife, Cheryl, also have 9- and 7-year-old daughters who are healthy. But the older girls may encounter a problem later on in life if the decide to have their own children, since they may also carry the gene.
As soon as Fallyn was born, her father said that he knew something was wrong.
"Her lower legs were in very bad shape," he recalled. "From the knee down, her legs were 50 percent underdeveloped. Nobody's been able to say if it was improper development or damage after the fact from EB."
Only supportive and preventative treatments are available for patients with EB because there is no cure for the disorder.
High-protein diets are required by some patients who have severe wounds. Vitamin and iron supplements are also necessary in certain cases since EB patients can easily become anemic.
Psychological support from the whole family, minimizing deformities, avoiding dietary complications, protecting the skin against trauma, and preventing infection are the primary areas of care The Dystrophic Epidermolysis Bullosa Research Association of American (www.debra.org) suggests focusing on.
"The big issue with EB is wound care," Van Norman said. "You're managing chronic wounds. The big thing is wound infection that goes on to become blood-borne infection, sepsis."
Many patients may develop a type of skin cancer called squamous cell carcinoma. A variety of infections can also strike EB patients.
"The cause of death in the majority of cases is split between infection and skin cancer," Van Norman said.
A team effort is required to care for a patient with EB. Often, physical therapists, mental health care providers, nutritionists, ophthalmologists, wound care experts, dentists, and of course dermatologists are needed to properly take care of a patient.
"It's constant running between doctors' appointments and everything else," McNamara said.
Coping with such a life-altering disease is hard for anyone, let alone a child. Fallyn is no exception.
"One of her most profound comments is, 'I didn't want God to make me like this,'" her father said.
Stress compounds with the need for daily wound care. This makes the condition difficult on family members too.
"It's part of a normal routine now," McNamara said. "I'm able to cope with it. It does lead to strong strife. It puts limits on us as a family. Her sisters are often forced into helping with things."
During the summer months, heat makes her symptoms worse, so Fallyn must stay inside an air-conditioned house. This is an example of how new challenges are presented every day.
Collars and tags must be removed from all her clothing, and everything must be altered so it fits loosely. All her clothing must be made from soft material and she can't wear anything with heavy seams.
"Even car seats were an issue," McNamara said.
His concerns are clear, but still discusses his daughter's condition calmly. He accepts that her health restricts her activities, and that her bandages need to be changed daily.
"There are so many things I worry about for her," McNamara said. "I try to include her, to have friendships. ... Sometimes kids her age are scared of her. When she's bandaged up, she's not her prettiest."
He tries to make Fallyn's life as normal as possible despite any and all challenges she may face.
"Her personality is something else," McNamara said. "She gets a little rambunctious sometimes. That's the nature of kids."
Now, with the progress of stem cell research, new hope may be on the horizon for Fallyn. And her life may soon be normal than she has ever known.