Family's three generations of mysterious skin disease solved
April 1, 2016
The cause of a mysterious skin condition experienced by three generations of a Flemish family in Belgium, as well as an effective treatment, have been identified by researchers from Belgium and Australia. Their findings were published in
The condition produced severe skin lesions, fever, pain, and exhaustion and has also been found in other Belgian families, as well as families in England and France, according to a press release. Half of the children in each generation of these families developed the
Inherited mutation identified
The investigators determined the condition was pyrin associated autoinflammation with neutrophilic dermatosis (PAAND), caused by a mutation in the MEFV gene. MEFV gene mutation is also associated with Familial Mediterranean fever (FMF),but where individuals need to inherit two copies of the mutant gene to develop FMF, only one copy is needed for PAAND, the authors note.
“Detailed work by clinicians told us that we were dealing with a genetic disease,” said Dr. Adrian Liston, the senior author on the paper and head of the Laboratory of Genetics and Auto Immunity at the University of Leuven in Flanders, Belgium. “Thanks to advances in
DNA sequencing technology we were able to sequence the genome of these patients and find the mutation causing the disease.”
According to the paper, the gene mutation disrupts regulation of the immune protein pyrin in such a way that the body reacts as if it had detected a bacterial skin infection, producing the inflammatory cytokine interleukin-1β (IL-1β). That inflammatory response produces the skin lesions, fever, and pain these patients experience.
Identifying IL-1β as the driver of the patients’ symptoms, the investigators tried treating one patient with the anti- IL-1β drug anakinra, which is usually prescribed for arthritis. The patient’s skin lesions rapidly cleared, and they recovered fully from the fevers and pain.
The paper’s lead clinical researcher, Dr. Carine Wouters, said in the release: “This is the synthesis of an intense collaboration between clinicians and scientists trying to understand this disease for almost 10 years. I am delighted to see how it has increased our understanding of rare mutations, and especially has opened a therapeutic perspective for these patients.” Dr. Wouters is a professor in the Faculty of Medicine at the University of Leuvin and a researcher in the university’s Laboratory of Pediatric Immunology.