SAN FRANCISCO - "I've never seen a year like the past where there were so many pediatric derm studies," Dr. Robert Sidbury said.
New discoveries that support a genetic basis for alopecia areata; a mutation in a collagen gene that might mean greater susceptibility to vitiligo; and a promising report that stem cell transplantations can help children with epidermolysis bullosa are among the highlights that Dr. Sidbury shared at the seminar on women’s and pediatric dermatology sponsored by Skin Disease Education Foundation.
Epidermolysis Bullosa
One report offers some hope to children with recessive dystrophic epidermolysis bullosa (RDEB), an incurable blistering disease that is often deadly. The condition is associated with mutations of a gene that encodes for type VII collagen, said Dr. Sidbury, chief of the division of dermatology at Seattle Children’s Hospital and the University of Washington.
Researchers at the University of Minnesota, Minneapolis, found allogenic bone marrow stem cell transplantation without the mutation improved outcomes for children (N. Engl. J. Med. 2010:363:629-39).
Following immunomyeloablative chemotherapy, six children received stem cell transplantations (a seventh died from cardiomyopathy before the protocol started). All six experienced improved wound healing and had a substantial proportion of sustained donor cells in their skin. They also experienced decreased blister formation between 30 and 130 days post transplantation.
One child died at 183 days because of graft rejection and infection. The other five were alive at the time of publication, between 130 and 799 days following transplantation.
Future studies to determine the long-term benefits and risks of this therapy are warranted, the researchers wrote.
Dr. Sidbury was enthusiastic about this strategy to combat RDEB, but added, "We have to be cautious when the first reports like this come out. But this is about as exciting as any report that has come down the pike for this difficult-to-treat condition."
Alopecia Areata
Even though alopecia areata is among the most common autoimmune conditions, the etiology remains largely unknown. "I spin my wheels trying to explain the 'whys' [to patients]. In broad strokes, it is thought to be heritable," said Dr. Sidbury.
A recent genome-wide study lends additional support to the role of genetics (Nature 2010:466:113-7). "Genome-wide association studies are like throwing spaghetti at the wall, only the spaghetti is DNA, and you see what sticks," Dr. Sidbury said.
What stuck were 139 single-nucleotide polymorphisms significantly associated with alopecia areata. The researchers found these in a comparison of 1,054 affected people and 3,278 controls.
"Not surprisingly, there are genes that control targeted inflammation. We have always referred to alopecia areata as a swarm of bees around the follicle," Dr. Sidbury said. "What was really unusual was identification of a stress [induced] protein."
Dermatology researchers at Columbia University, New York, discovered this stress-induced protein, known as ULBP3, related to a cluster of genes on chromosome 6. They also found that people with active alopecia areata have greater expression of this protein in the dermal shaft of their scalp follicles, compared with controls.
Aberrant expression of these genes might induce or worsen alopecia areata in genetically-susceptible patients, Dr. Sidbury said. "So it seems there may be a danger signal that activates this ULBP3 protein and calls in all this [autoimmune] inflammation."
Dermatologists might soon have a more concrete answer for patients regarding the cause of alopecia areata if these results are borne out in future studies. "This does not mean we will have a therapy tomorrow, but maybe we will have a more targeted way to get rid of that inflammation in the future," he said.
Vitiligo
Genetic findings regarding another autoimmune condition, generalized vitiligo, were also published this year (N. Engl. J. Med. 2010: 362:1686-97).
Researchers in Colorado identified genetic alterations that may impart an increased susceptibility to generalized vitiligo. They did a genome-wide study and compared 1,514 vitiligo patients and 2,813 controls with similar ancestry. They found significant associations between vitiligo and specific single-nucleotide polymorphisms (SNPs) in genes that code for histocompatibility and immune processes, for example.
The location of several SNPs is the same for vitiligo and other autoimmune diseases, suggesting a common genetic etiology. They also discovered a more specific mediator of vitiligo, a loci that encodes for tyrosinase, which could be a target of future interventions. "I'm hopeful we’ll have better therapies in the future," Dr. Sidbury said.
SDEF and this news organization are owned by Elsevier. Dr. Sidbury had no relevant disclosures.
For information on counseling parents about food allergies in the atopic child, based on a fourth prominent study, read Damian McNamara's blog post on The Mole at www.skinandallergynews.com/views/the-mole-the-skin-allergy-news-blog.