FSF: Autoimmune vs. Autoinflammatory Disease

posted: by: Linda Tintle DVM Tags: "Clinic Specials" "News" 

I received the following questions emailed to me and I thought they were good ones.  I have edited the original email to omit personal details and follow it below with my response.

Please forgive my ignorance in my questions, as I am not a Vet. From what I gather, FSF is categorized as an autoimmune disorder.  From what I have read regarding autoimmune disorders, these types of disorders usually contain both a genetic predisposition and an environmental "trigger".

Lately I have been running across more and more theories in both Human and Veterinary Medicine, that the "trigger" component of many autoimmune disorders may be Vaccine related. With current US vaccine protocols being so much more aggressive than China's, I have to wonder if this isn't part of the reason that this disorder did not manifest strongly in the breed until they were established here in the US. I have read quite a bit lately that is challenging our current vaccine protocols and citing theories that Vaccines are responsible for a variety of autoimmune disorders in various breeds.  Is it POSSIBLE that this may be one of the primary "triggers" in FSF in the American Bred (and often heavily vaccinated) CSP?

Of course the trigger is only half the problem and we ultimately need to find the genetic factor that predisposes them for this, but, in the meantime, finding and eliminating (or limiting) exposure to these "triggers" may save many lives. Since there is so much focus on these theories at present, if vaccines MAY be our trigger for FSF, could it perhaps be possible to collaborate with some of these other current studies and groups and draw upon some of their resources for further study into this?

My response on Autoimmune vs. Autoinflammatory Disease:

Your questions are good ones and not uncommon. First is the confusion about autoimmune vs. autoinflammatory.  Shar-Pei have an autoinflammatory syndrome, not an autoimmune disorder.  There is a difference.  The immune system is tasked with differentiating between the body's self and anything that is non-self.  Its job is to remove anything that is non-self.  A result of this can be the process of inflammation. When the immune system mistakes self tissues for non-self and mounts an inappropriate attack, the result is an 'autoimmune' disease'.  For some reason, the immune system fails to recognize auto-antigens (def: auto-antigen - an antigen that, despite being a normal tissue constituent, is the target of a humoral (antibody) or cell-mediated immune response, as in autoimmune disease) as self.

The term 'autoinflammatory' syndrome has been attributed to the group of disorders characterized by unexplained recurrent attacks of inflammation without any evidence that this process is related to rejection of auto-antigen.  There is no evidence that Shar-Pei with FSF are targeting or deliberately rejecting any of their own antigens.  (def: antigen -any substance capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant combines with antibody or a specific receptor on a lymphocyte.)

In autoinflammatory syndromes, there seems to be a system wide disruption of the molecular basis of mediating and controlling inflammation - inflammation is a localized protective response elicited by injury or destruction of tissues, which serves to destroy, dilute, or wall off both the injurious agent and the injured tissue. It is characterized in the acute form by the classical signs of pain, heat, redness, swelling, and loss of function. It involves a complex series of events, including dilatation of arterioles, capillaries, and venules, with increased permeability and blood flow; exudation of fluids, including plasma proteins; and migration of white blood cells into the inflammatory focus.

(definitions from Dorland's Medical Dictionary: http://www.mercksource.com/pp/us/cns/cns_hl_dorlands.jspzQzpgzEzzSzppdocszSzuszSzcommonzSzdorlandszSzdorlandzSzdmd_i_07zPzhtm)

When I started breeding in the early 1980's, my line was out of the early Chinese dogs - direct imports not through Hong Kong. I began breeding my females to what I often refer to as the "stud of the month" (the big beautiful male that is winning all the shows at that moment and has everyone eying him enviously) and trying to change my dogs' look to the more desirable American type (big head, big meat-mouth, brush coat and lots of wrinkles).  I saw FSF with swollen hock syndrome for the first time in my line in the grand-daughter of a stud that died young of amyloidosis (my 4th generation).  When I did pedigree analyses for the heredity study, it was common to see it seem to skip a generation when it was introduced to a previously unaffected line and my experience was typical.

I think part of the misunderstanding here is because any stress can be a trigger for fever - including vaccination in some patients.  That stressor could also be a visit to the vet without vaccination for some S-P if it upsets them - or it could be grandchildren or dog show weekends or most commonly... completely randomly (sometimes in clusters and sometimes going for months and even years without an event).

But the observations you have drawn are from things that can trigger autoimmune disorders - and there is no evidence that FSF has a pathogenesis that is autoimmune.  So partnering with research into the underlying causes of autoimmune disease is not likely to help us understand FSF better - although it may help dogs that are affected by autoimmune disease and S-P are not exempt.

Some Shar-Pei that have never had a single vaccination in their entire lives have had recurrent FSF episodes and died of amyloidosis.

It is the hidden elevated background levels of chronic inflammation that predispose FSF patients to amyloidosis – whether or not they have 0, 1 or hundreds of fevers.  The fever event is a marker, a great big waving red flag, that they have this underlying autoinflammatory syndrome.

This is why I believe that Shar-Pei with FSF need some sort of DAILY treatment to reduce their inflammation.  Colchicine is the drug I reach for first but I am adding other supplements now as a result of my research into the health benefits of many of the supplements brought to my attention by people on this list and elsewhere.

Linda Tintle DVM