Report on the NIH Congress on Systemic Autoinflammatory Diseases

November 6-11, 2005 I attended FMF and Beyond, The Fourth International Congress on Systemic Autoinflammatory Diseases, which was hosted by the National Institutes of Health in Bethesda, Maryland.  I was the only veterinarian in attendance among 240 invited attendees from all over the world and represented the Shar-Pei as an animal model for these episodic fever disorders in humans.

It was exciting, educational, enlightening and depressing all at once.  There are many similarities between the autoinflammatory disorders that have been described in humans and Familial Shar-Pei Fever (FSF)-Amyloidosis.  As these scientists continue to work to describe the mechanisms behind how these disorders develop, a clearer picture of why these patients suffer as they do and how they might be treated is emerging.

The recent research by Drs. Francesca Puppo, Elaine Remmers and Dan Kastner at Dr. Kastner’s laboratory at the NIH-NIAMS has verified that Shar-Pei do not have significant mutations in the previously identified candidate genes for FMF and other human autoinflammatory fever disorders.  They have one more candidate gene to examine more closely after we reviewed some of the more unusual clinical aspects of FSF at this congress (I brought lots of photos).  One of the depressing facts that emerged from the presentations was that only about half of all human Familial Mediterranean Fever (FMF) patients have had identified mutations in the MEFV locus.  Half of all human patients still cannot be identified definitively by a genetic test.  The next stage of the research at Dr. Kastner’s lab will be to do linkage analysis on Shar-Pei samples to try to find a mutated gene that contributes to their autoinflammatory episodic fever disorder.  We hope that finding this abnormal gene will help Shar-Pei by making early diagnosis possible and give us a new idea of where other mutations causing similar disease in humans might be located.  I am hopeful that we will find one mutation or polymorphism because all our dogs descend from a small group of affected founders.

The cytokine IL-1b appears to be very important and recombinant IL-1 receptor antagonists are becoming a staple of treatment in many of these autoinflammatory disorders.  This may explain why dipyrone, which has been shown to block IL-1b induced fever, worked so well in treating Shar-Pei fever until the FDA/CVM removed it from the U.S. veterinary market a few years ago.  I am going to explore whether we could get the drug compounded for experimental use in FSF patients and I discussed the drug with physicians who may be able to use dipyrone in human patients in countries where it continues to be available.

Apparently serum hyaluronan (mucin) levels have not been measured in any of these human patients and I spoke with an expert on amyloidosis from the U.K. at the congress about possibly investigating this area.  Dr. Avery was able to reproduce my research conducted at Cornell with Drs. Rivas and Quimby in the early 1990s that demonstrated chronically elevated IL-6 levels in Shar-Pei with a history of episodic fever and in those with affected relatives.  She will soon be looking at other parameters including measurements of CRP and SAA which are used now in human medicine to monitor efficacy of colchicine and other treatments.

I had a long conversation with two sisters who have FMF and who are in the early stages of amyloidosis.  They believe that the source of colchicine is very important and that it is easily rendered useless if handled improperly – particularly by exposure to heat and sunlight.  They were very aware of the disorder in Shar-Pei and were hoping that our dogs would serve as an important animal model for their disease and that the canine research would benefit both Shar-Pei and people.  Dr. Francesca Puppo prepared a poster presentation describing FSF and the work at their lab and it was very well received and generated thought provoking discussion among some of the world’s premier scientists in this area.  I have been reading scientific papers on this subject for about 15 years and I was truly honored to have the opportunity to meet and speak with this group of international researchers whose genius, intellectual curiosity and compassion for their patients was awe-inspiring.

The intense and mentally challenging presentations on the molecular genetics of these disorders were juxtaposed with sessions featuring clinicians interviewing patients suffering from these diseases.  It was heartbreaking to hear what these people have lived through and more so to listen to parents describe the short painful lives of their children that had died.  Our dogs are very special and much loved and I hope that by finding answers to their afflictions, we can help both animals and people.

Many in the Shar-Pei community have been extremely generous by completing detailed questionnaires and providing blood samples from their dogs.  I am very grateful to those who have gone to great lengths to cooperate with the studies at Drs. Avery and Kastner’s laboratories especially members of the Centennial Club, Dr. Jeff Vidt and his clients, and my own clients - especially Barbara LaVere - and a special thanks to Lee Arnold for ensuring that the AKC/CHF expeditiously approved our grant to Dr. Avery outside the normal grant approval cycle.  I ask that you consider a donation to the Chinese Shar-Pei Charitable Trust today to help fund this very worthy research:  www.cspcharitabletrust.org which is administered through the AKC Canine Health Foundation.

Linda J.M. Tintle D.V.M.
CSPCA Health Through Education Committee Member
Chinese Shar-Pei Charitable Trust Research Liaison
wvc@warwick.net
www.wvc.vetsuite.com