Only now, almost 200 years after it was first described, Israeli and other
researchers have discovered the genetic basis for the severe skin disease
pytiriasis rubra pilaris (PRP), which affects people of all backgrounds around
After more than a decade, the lead researchers at Tel Aviv’s
Sourasky Medical Center finally identified mutations in the gene CARD14 that
codes for a very important regulator of inflammation in the skin. The mutations
associated with PRP lead to increased inflammatory activity within the skin, due
to abnormal function of CARD14. The prevalence of the disease may be as many as
one in 5,000 people.
The team – headed by dermatology department chief
Prof. Eli Sprecher and including Dana Fuchs, a doctoral student in his lab –
published their paper on Sunday in the American Journal of Human Genetics. “The
discovery of the PRP gene was a long and chaotic journey, with many dead ends
and false routes; at some point, we were unsure whether all the participating
families had the same disease,” they said in the paper.
PRP used to be
considered an immunological skin disorder, but it is in fact due to a genetic
defect in the epidermis, the outer layer of the skin. Also known as Devergie’s
disease, it causes broad swatches of reddish-orange, scaly skin patches on the
body and face, itching, serious flaking and thickened bumps around hair
follicles in the scalp. Although most patients are over age 50, it may attack
people of any age and any race or nationality, with men and women equally
The CARD14 protein is strongly expressed in the epidermis, said
Sprecher: “This is really shifting the focus of our attention from the immune
system to the skin. The skin is often perceived as a passive victim of abnormal
immunological activation in inflammatory skin diseases like PRP and psoriasis.
In fact, it may play a more important, and even perhaps primordial
“More importantly, mutations in CARD14 are found in only a portion
of PRP patients but were also recently found by a US group in a subset of
psoriasis patients. No matter how you look at the data, these two sets of facts
actually demarcate a new medical entity comprising individuals affected by two
diseases once thought to be separate conditions, but in fact caused by the very
same genetic defect,” he continued.
The discovery was made thanks to the
intensive study of four affected families, three in the US and one in Holland,
who suffer from the skin disease. But the disease affects Israelis as
well as other people around the world.
This is not the first time that
genetics is redefining disease classification in dermatology, but it may be one
of the first discoveries that is likely to have major therapeutic implications,
Sprecher added. “Indeed, the mechanism found to be defective in our patients
suggests that they may respond better than others to drugs known to interfere
with the pathway found to be hyperactive in our studies.”
The Jerusalem Post on Sunday that some of the people who in the past were
thought to have PRP actually had a different skin disease – a type of psoriasis
– caused by the same gene mutation. But not all those with psoriasis have this
gene defect, he said. A sign of this was that some patients reacted positively
to phototherapy (light treatment), while others’ conditions worsened with
Once the gene involvement is known and we know the molecular path
involved in it, we can better know what medications to treat it. There are side
effects involved, but it’s worth doing it,” said Sprecher.
possible medications are injections of tumor necrosis tactor (TNF) antagonists
and interleukin 1 antagonists.
The research team also included Ofer Sarig
of Sourasky Medical Center, Noam Shomron of Tel Aviv University, Maurice van
Steensel of Maastricht University, Jouni Uitto of Thomas Jefferson University,
Philip Fleckman of the University of Washington and Gabriele Richard at GenDx.