Researchers find treatment for familial cold autoinflammatory syndrome

Dalhousie Medical School dermatologist Dr. Barrie Ross and his colleagues have successfully ended a 20-year quest to find a treatment for Familial Cold Autoinflammatory Syndrome (FCAS).

The rare condition, triggered by exposure to cold, causes severe discomfort and physical incapacity.

Through a clinical trial conducted at Capital Health in Halifax, Dr. Ross and his colleagues proved the overwhelming effectiveness of anakinra, a receptor-blocking medication, to ease the pain and suffering caused by FCAS. The study results were published this week in the Journal of Cutaneous Medicine and Surgery.

Dr. Ross, an adjunct professor in the Division of Dermatology, Department of Medicine at Dalhousie and Capital Health, had the rare honour of seeing his quest through from beginning to successful end. In 1986, the year her mother was diagnosed with kidney failure which is linked to FCAS, Anne Mallais visited Dr. Ross. She was on a crusade to find a cure for the debilitating condition that afflicts her and many of her family.

“From the time Anne came to see me, it was serendipity, the advancement of technology and perseverance that led to the clinical trial and the discovery of a treatment,” says Dr. Ross.

FCAS causes hives, fever, chills, myalgias, headache, stiffness and swelling, among other symptoms. “It's like you're freezing from the inside out,” says Rachel Doherty. “Your whole body contracts until you warm up, which can take hours or days.” Doherty took over the crusade to find a cure from her sister and participated in the clinical trial.

Following Mallais' visit, Dr. Ross encouraged a dermatology resident to research, write and later publish a paper that detailed the literature on what was then known as Familial Cold Urticaria. The paper caught the attention of researchers in Germany. The researchers later teamed up with Dr. Ross to discover the chromosomal site for FCAS. Six years after the discovery, Dr. Ross and a group of UK colleagues pinpointed the specific receptor responsible for FCAS. When triggered, the tumour necrosis factor (TNF) receptor starts the symptoms of FCAS.

“Once we pinpointed the pathway, we looked at other inflammatory conditions with a common pathway in search of potential treatments,” explains Dr. Ross. “A tip from a colleague turned us on to anakinra. It was an approved therapy for rheumatoid arthritis in Canada which meant that was safe to use.” The next step was a clinical trial.

Eight adults, all family members with long-standing FCAS, participated in the clinical trial in the fall of 2005. They received daily anakinra injections and all experienced complete symptom relief within 24 hours of their first injection. The relief lasted through the treatment period despite participants being subjected to cold on a daily basis. “The results were phenomenal,” says Dr. Ross. For Doherty it was surreal. “It was like one minute I was paralyzed and the next I was normal. When I went home, I walked around in circles not knowing what to do first.”

Anakinra (marketed by Amgen Corporation as Kineret) prevents the symptoms of FCAS by stopping the TNF receptor from being triggered. The clinical trial showed that it is 100 per cent effective when injected on a daily basis. About six hundred people around the world are afflicted by FCAS.