Immune-Mediated Polyarthritis (IMPA) is a relatively easy disease to understand, but what causes it can be confusing and affects the selection of treatment options.
What is IMPA?
Immune-mediated (aka autoimmune) conditions occur when the immune system is overactive and attacks the body in various ways. Hyperactive may be a more appropriate term because one part of the immune system is revved up and working in overdrive. Immune-mediated disorders have an underlying genetic predisposition, like they do in humans; this genotype association in affected dogs has recently been located on the DLA-79 allele (Dog Leukocyte Antigen) of the major histocompatibility complex (MHC) system. Other factors predisposing to overactive immune system responses include environmental factors like vaccines, drugs, food, chemicals or drugs as well as stress situations that act as “triggers” of this immune response.
Polyarthritis is an inflammation of multiple joints.
In the case of IMPA, white blood cells (aka neutrophils) invade the joints of the body. They are not supposed to be there. They are supposed to be fighting bacteria and pathogens in the surrounding tissues. This causes swelling of the joints, pain, and difficulty walking or standing. Other symptoms may crop up, too, such as weight loss, anorexia, fever, fatigue and can affect the lymph nodes draining the inflamed areas.
Forms of IMPA
The veterinary community first categorizes IMPA into either erosive or non-erosive type. We can tell the difference between the two based on x-ray results. Basically, erosive IMPA shows evidence of cartilage and bone destruction in one or more joints, but the non-erosive type does not.
The bodily reaction to the white blood cells entering where they are not supposed to go is termed a type III hypersensitivity antibody response that is found in both erosive and non-erosive IMPA. However, erosive IMPA has the additional element of a type IV hypersensitivity, which is a cell-mediated response.
Erosive IMPA is often equated to rheumatoid arthritis in humans and is rare in dogs. In fact, it is reported in less than 1% of the total IMPA cases. Going forward in this article, I will address non-erosive IMPA.
Idiopathic Non-Erosive IMPA
Idiopathic means we do not know the underlying cause that is creating the IMPA. However, to confuse matters, we have seen strong correlations between IMPA and other diseases. We just do not know how one is affecting or causing the other. So, we still classify them as idiopathic.
- Type I: No association with other diseases or triggers at this time.
- Type II: Associated with infection or chronic inflammation that is remote from the joints.
- Type III: Associated with gastrointestinal or hepatic (liver) disease.
- Type IV: Associated with neoplasia (abnormal growth of tissue that could be cancerous) separate from the joints.
Disease Associated Non-Erosive IMPA
Now, we have diseases that we know produce IMPA and have a direct connection. So, IMPA is not the primary disease, but the secondary problem or is concurrent with them.
- Systemic lupus erythematosus (SLE) – A multiple organ immune-mediated disease that often provokes IMPA or other immune-mediated conditions such as hemolytic anemia or thrombocytopenia (deficiency of blood platelets).
- Polyarthritis-meningitis syndrome – A syndrome in which steroid-responsive meningitis and arteritis (inflammation of the meninges and arteries that responds to steroid therapy) occurs with polyarthritis.
- Polyarthritis-polymyositis syndrome – A canine non-SLE syndrome of IMPA and polymyositis (degeneration of muscle tissue in several areas of the body).
Breed-Specific Non-Erosive IMPA
Thus far, researchers have identified two breed-specific forms of IMPA.
- Polyarthritis in Akitas – May occur at the same time as meningitis or other conditions. It is rare but appears to affect adolescent Akitas. More on this subject later…
- Chinese Shar-Pei Fever or Swollen Hock Syndrome – Autosomal recessive disease, which means both parents must have the recessive gene to create a dominant one. Amyloids (protein fragments) are accumulating throughout the body, which can lead to kidney and liver failure. Intermittent bouts of IMPA and fever are also symptoms. Please note: neither parent should ever be used for breeding again.
Drug-Induced Non-Erosive IMPA
Many drugs have been shown to induce IMPA and several other conditions. Phenobarbital and antibiotics (particularly sulfonamides) have been the main culprits. The IMPA reaction is usually delayed by 5-20 days after starting treatment. However, pet caregivers should be aware that each successive prescription heightens the possibility of inducing these conditions. So, if your companion dog did not have a reaction the first time with – let’s say to a penicillin – it does not mean he will not with the next same prescription.
Vaccine-Induced Non-Erosive IMPA
Of all the identified categories of IMPA, the veterinary profession generally recognizes only one environmental trigger: medications. Indeed, when IMPA is secondary to the other conditions listed above, we have strong theories about what constant environmental onslaught(s) or singular trigger is initiating them. However, the effects of vaccines as triggers – to this day – are often swept under the rug. As I always say, we can remove the drugs or change diets, but we cannot remove the chronic effects of vaccines (termed vaccinosis).
Remember, I just mentioned polyarthritis in Akitas. Dr. Susan Wynn and I studied eight affected puppies: five were closely related; and, three were male and the rest females. Initial signs of IMPA appeared 3 to 29 days following vaccination with polyvalent MLV or killed virus or both, with a mean reaction time of 14 days.
The dogs consistently exhibited cyclic febrile illness (fever) with signs of severe pain, usually related to the joints. Most of the dogs had elevated hepatic (liver) enzymes, creatine kinase (inflammation of the muscles), and blood urea nitrogen. Screening for rickettsial diseases was negative. (Rickettsial diseases are not the vitamin D deficiency, rickets, but are bacterial infections that cause typhus or spotted fevers.) Complete blood count tests revealed mild non-regenerative anemia, neutrophilic leukocytosis, and occasional thrombocytopenia. Joint aspiration and radiography of three dogs indicated non-septic, non-erosive arthritis. Juvenile IMPA in Akitas is a syndrome distinct from the noninfectious, non-neoplastic polyarthritis that is seen in other breeds, and it is heritable. The mechanism of disease development has not been elucidated, but it shares several features with the inherited Chinese Shar-Pei Fever syndrome.
Despite treatment for immune-mediated disease and pyrexia (raised body temperature), all eight dogs had relapsing illness and died or were euthanized by 2 years of age from progressive systemic amyloidosis and renal failure. Necropsies were performed on three dogs, two of which had glomerular amyloidosis and widespread evidence of vasculitis (inflammation of the blood vessels).
The history, signs and close association with immunization suggested that juvenile onset polyarthritis and subsequent amyloidosis in these Akitas likely was an autoimmune response triggered by the viral antigens or other components of the vaccines.
Since the modern Akita arose from a relatively small gene pool, understanding the potential environmental triggers of juvenile onset IMPA has immediate importance. Numerous agents have been implicated, including drugs, vaccines, viruses, bacteria, chemicals, and other toxins. Although the littermates from affected families typically end up in different locales, all undergo relatively standardized immunization procedures at a similar age.
Dr. Wynn and I are not the only ones who have found connections between IMPA and vaccines. Through a variety of diagnostic tests that ruled out other types of arthritis and comparing to other arthritic dogs, Bell et al. discovered that dogs with IMPA had significantly higher canine distemper antibodies circulating in their blood.
Treatment varies with IMPA if it is present as a primary disease or not. If you suspect your dog is showing signs of arthritis of any form such as osteoarthritis, I highly recommend getting an accurate diagnosis because the treatment protocols will be different and will entail a fine immune balancing act that will need to be under a veterinarian’s supervision. Additionally, please do not give immune boosters including vaccines to a dog with any immune-mediated disease without the expressed consent of your veterinarian. If in doubt, please contact a veterinary immunologist or us at Hemopet.
Bell, SC. “Canine Distemper Viral Antigens and Antibodies in Dogs with Rheumatoid Arthritis.” Research in Veterinary Science 50.1 (1991): 64-68. U.S. National Library of Medicine. Web. 22 Jan. 2017. http://www.ncbi.nlm.nih.gov/pubmed/2047594?dopt=Abstract.
Dodds WJ. 1999. More bumps on the vaccine road. Advances in Veterinary Medicine 41:715-32.
Dodds WJ. 2001. Vaccination protocols for dogs predisposed to vaccine reactions. Journal of the American Animal Hospital Association: May/June 2001, Vol. 37, No. 3, pp. 211-214.
Friedenberg SG, et al. Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs. Immunogenetics, 68(3):205-217, 2016.
Kiss, Caroline M., DVM, and Gregory C. Troy, DVM. “Recognizing and Treating Immune-mediated Polyarthritis in Dogs.” Veterinary Medicine. DVM360.com, 02 June 2014. Web. 22 Jan 2017. http://veterinarymedicine.dvm360.com/recognizing-and-treating-immune-mediated-polyarthritis-dogs?id=&pageID=1&sk=&date.