Immune-Mediated Polyarthritis (IMPA)
in the Cavalier King Charles Spaniel

• What It Is
• Symptoms
• Diagnosis
• Treatment
• What You Can Do
• Research News
• Related Links
• Veterinary Resources

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Immune-mediated polyarthritis (IMPA) is an idiopathic form of arthritis, causing recurring episodes of lameness and joint swelling, usually in mulitple joints. It is a commonly diagnosed inflammatory disease in dogs and  has been reported in cavalier King Charles spaniels in at least five published veterinary journal articles.

What It Is

IMPA can be “erosive” or “non-erosive. The erosive condition is known as rheumatoid arthritis (RA). The non-erosive type is called idiopathic because there is no evidence of any primary disease nor any serological (blood serum) evidence regarding its immunological properties.

Idiopathic forms of polyarthritis in dogs have been classified into four types:

Type I: Uncomplicated Arthritis: polyarthritis with none of the associations reported in the other types.
Type II: Reactive Arthritis: Polyarthritis associated with an infective disease process remote from the joints, such as a respiratory or urinayr tract infection.
Tpye III: Enteropathic Arthritis: polyarthritis associated with gastro-intestinal disease; such as gastro-enteritis, ulcerative colitis
Type IV: Neoplastic Related Polyarthritis: polyarthritis associated with neoplastic disease remote from the joints.

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Symptoms

Polyarthritis produces swelling and tenderness at one or more of the affected dog's joints. The main symptoms are joint pain, stiffness, lameness. The affected dog also likely will have a high fever and appear anorexic and/or lethargic. In some cases, the dog has no swelling or lameness but shows signs of a vague systemic illness.

The most commonly affected joints are the carpal (wrist), tarsal (hock), stifle (knee joint), and elbow.

Non-erosive IMPA typically also produces lesions (open sores) on the skin near the affected joints.

Erosive IMPA lesions can result in damage to the soft-tissues which support the affected joints, and also the bones at those joints. Dogs with erosive IMPA may develop unstable joints due to damage or destruction of the soft-tissue structures.

In a November 2016 article, a team of Wisconsin and Michigan researchers studied the clinical records of 79 dogs diagnosed with immune-mediated polyarthritis (IMPA). Of those 79 dogs, 13 had erosive IMPA, of which, two were cavalier King Charles spaniels. The 13 affected dogs had erosive lesions in their carpal joints. The estimated median synovial fluid lymphocyte count for dogs with erosive IMPA was significantly greater than that for dogs with nonerosive IMPA. Results indicated erosive IMPA most commonly affected the carpal joints of middle-aged small-breed dogs. (See from this article, at above left, the carpus of an 8-year-old spayed female Cavalier King Charles Spaniel with subjectively moderate subchondral bone lysis accompanied by severe synovial swelling -- in x-ray at right.)

Courtesy of The Dog Channel

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Diagnosis

Several procedures normally are performed to diagnose IMPA, the primary one being the collection and examination of fluid samples from the sac of the synovial membrane situated at the affected joints. Biopsies of the synovial membrane, muscle, and skin also may be taken.

X-rays (radiographs) of the affected joints, chest, and abdomen will be taken, especially to determine if any bone damage or loss has occurred. X-rays are used to look for changes in the joints which would indicate that the IMPA is erosive rather than non-erosive.

Blood serum and other testing should be performed to determine the presence of, or rule out, other causes such as bacterial infections. Urinalysis may be performed, to screen for the presence of proteinuria, a common abnormality found in dogs otherwise diagnosed with non-erosive IMPA, according to this May 2022 article.

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Treatment

Treatment may vary depending upon the type of IMPA. If evidence of infections have been identified, antibiotics will be administered. Typically, drugs to suppress the immune system,  such as leflunomide or prednisone, are the drugs of choice to deal with inflammation at the joints, with dosages increased if necessary.

Cytotoxic drugs, which affect the growth and action of some cells that cause joint pain,  swelling,  and damage due to arthritis, likely will be prescribed, particularly if the IMPA is resistant to prednisone. They include cyclophosphamide (Cytoxan), azathioprine (Imuran), and methotrexate (Rheumatrex, MTX, Amethopterin). Cytotoxic drugs rarely are used for more than 8 weeks and require periodic monitoring of blood cell counts.

Bedinvetmab (Librela, Beransa) is a injectable solution to alleviate pain associated with osteoarthritis (OA) in dogs. It is administered monthly. It is a monoclonal antibody which binds to and targets Nerve Growth Factors (NGF), which have key involvement in OA pain. It is manufactured by Zoetis. In May 2023, Zoetis announced that the USA Food & Drug Administration approved Librela (bedinvetmab injection) for the control of pain associated with osteoarthritis (OA) in dogs. Zoetis stated in its press release that Librela is the first and only once-monthly, anti-NGF monoclonal antibody treatment for canine OA pain and is approved as safe and effective in providing long-term control of OA pain symptoms in dogs, which can improve their mobility and overall quality of life.

Nevertheless, bedinvetmab is the subject of controversy due to reports of unanticipated adverse reactions, including ataxia, hind-end weakness, inability to walk, new or worsened seizures, pancreatitis, and organ damage. Among expressed concerns are that blocking NGF may prevent its known protective and reparative roles elsewhere in the body. See this May 2015 article and this October 2023 article.

Synovetin OA is a "conversion electron therapeutic veterinary device" which is injected into the dog's elbow joints which are afflicted with osteoarthritis to reduce pain and inflammation of the synovial membrane which lines the elbow (synovitis).

Palmitoylethanolamide (PEA) is a N-acylethanolamine molecule in a family of long-chain fatty acid amides called ALIAmides. PEA has been found in rat and mice studies to limit hyperactvity in immune cells and thereby control inflammatory responses and resulting tissue damage. PEA is produced by the animal's body as needed in response to certain types of injuries. PEA is a product of normal fatty acid synthesis from palmitic acid. It is found in many common foods, particularly palm oil, soy beans, egg yolks, and peanuts.  The commercial version is most commonly manufactured from palm oil*.

Not all PEA is alike. There are three types of PEA.

• Basic PEA is insoluble in water and therefore the oral intake of it (rather than being injected directly into the abdomen) has very poor bioavailability, meaning that it does not get absorbed well in the dog's gut.

• Micronized PEA (m-PEA) is a patented technique that reduces the diameter of PEA particles, making them absorbable in the intestine, which has been found to be more effective than ordinary naive PEA in activating PEA levels in blood plasma in dogs.  See this August 2014 article.

• Ultra-micronized PEA (um-PEA), also patented, reduces the PEA particle size further, to enable it to cross the blood-brain barrier, likewise has been found to be much more effective than naive PEA.  See this August 2014 article.

If a PEA product is not advertised as being micronized or ultra-micronized, then Dr. Clare Rusbridge advises that "You probably are wasting your money." A variety of brands of micronized and ultra-micronized PEA are offered on-line.

There are no published veterinary journal articles about treating canines with PEA for osteoarthritis (OA). This is very limited research regarding a combination of ultramicronized PEA (um-PEA) and quercetin (PEA-Q), first in rats and finally in dogs.

The rat research has been an August 2017 article. The authors report that a combination of ultramicronized PEA and quercetin (PEA-Q), given orally to 10 rats. They reported:

"PEA-Q is a novel co-ultramicronized formulation of PEA and quercetin whose effects were investigated in two pre-clinical models of OA pain in rats. Oral administration of PEA-Q decreased pain sensitivity, improved locomotor function, reduced inflammatory signs and mediators and lowered histological damage score."

 In that article, the authors go to great lengths to suggest that their "collective observations presented here propose that PEA-Q shows promise for multimodal pain management in canine and feline OA."

In a September 2018 report, 13 dogs diagnosed with chronic OA and lameness received supplements of PEA-Q for four weeks, at the rate of 24 mg/kg per day. Pain scores were taken, showing successful improvement in 7 of the dogs by the second week. Lameness also reportedly improved durint the treatment period.

Nevertheless, at least one PEA vendor advertises that PEA alone (meaning, not even ultramicronized PEA and not combined with quercetin) "may be beneficial for ... Osteoarthritis pain". So, Buyer Beware. See more about this type of hazard below.

PEA's fellow ALIAmide, micronized palmitoyl-glucosamine (m-PGA), has been teamed with curcumin (m-PGA-Cur) to treat dogs with osteoarthritis. In an October 2020 report of 181 dogs diagnosed with OA, they were given m-PGA-Cur for 2 months in addition to their conventional medications. The dogs were scored for lameness and pain at the start of the study and each 30 days thereafter, along with having the dogs' owners evaluate their dogs' mobility impairment and pain behaviors. At the end of the study, 74% of the owners scored their dogs' quality of life as improved, and 87% of the 27 participating veterinarians expressed satisfaction with the addition of m-PGA-Cur in the daily management of the OA. This was not a controlled clinical trial, however.

In a February 2023 article, m-PGA and curcumin again were teamed (m-PGA-Cur) to treat 58 dogs having chronic OA pain. All of the dogs had been treated with meloxicam and continued to do so during the 18-week testing period. The aim of the study was to determine if adding m-PGA-Cur to the treatment regime enabled the meloxicam to be tapered at the rate of 25% during the first 8 weeks of combined treatment without experiencing worsening of pain. The investigators found that 75% of the dogs were assessed as having no pain increases 10 weeks after the withdrawal of meloxicam. They concluded that the m-PGA-Cur was able to maintain the level of pain relief previously maintained only by the meloxicam.

Read more about PEA on our PEA webpage.

* Palm oil: The palm oil cultivation industry has been destroying rainforests in Sumatra and Borneo in Indonesia and Malaysia, the only habitats of orangutans. If you are going to obtain PEA, we suggest that you do so only from vendors whose PEA has been manufactured with palm oil from sustainable sources and not the deforestation of rainforests.  Read more about finidng sources of sustainable palm oil at www.orangutanlandtrust.com. To avoid palm oil as the source of PEA, read the ingredients descriptions on the brands of PEA in which you are interested.

Nutraceuticals are nutrients necessary for supporting or improving normal structure and function of the weight-bearing joints. They have been found to:

• Support or enhance metabolism of cartilage cells (chondrocyte) and joint membranes (synoviocyte) -- an anabolic effect;

• Inhibit damaging enzymes within synovial fluid and cartilage -- a catabolic effect;

• Inhibit formation of thrombi in small blood vessels supplying the joint (antithrombolic).

The most common nutraceuticals are glucosamine and chondroitin. Glucosamine regulates the synthesis of collagen in cartilage, and may provide mild anit-inflammatory effects. Crystalline glucosamine sulphate has the greatest efficacy and bioavailablity for osteoarthritis. Chondroitin sulfate inhibits destructive enzymes in joint fluid and cartilage. Both of them also contribute to the building blocks synthesis of glycoaminoglycans and proteoglycans) for the formation and repair of cartilage.

Undenatured type-II collagen (UC-II), a patented form of collagen extracted from the cartilage of the chicken’s sternum, has been found effective in reducing pain and discomfort experienced by dogs suffering from (osteoarthritis.

Microlactin (Duralactin) is a nutraceutical consisting of a protein concentrate derived from the milk of hyper-immunized cows, called hyper-immune milk factor (HIMF). It reportedly impedes inflammation and can be used safely in dogs. It is slow to respond to pain, taking a week to two weeks for maximum effectiveness.

Cannabinol (CBD) is is a cannabinoid compound produced from hemp and marijuana (Cannabis Sativa) plants. CBD oil mimics the endocannabinoid molecules which the dog’s (and our) body produces in several different organs. They play roles in reducing pain, regulating inflammation, and affecting the immune system, by initially binding to receptors in the brain.

CBD is non-psychoactive, unlike tetrahydrocannabinol (THC), another cannabinoid compound from marijuana, which is considered psychoactive by altering the mental state, and can be highly toxic to dogs.

Varieties of CBD: Cannabidiol-based veterinary products are derived mainly from hemp (Cannabis sativa) and must contain less than 0.3% tetrahydrocannabinol (THC). This form of CBD can be processed into “full spectrum” or “broad spectrum” and also may be in the form of a “distillate”, in which all THC has been removed, or in the form of CBD “isolate”, which is a purifed powder.

• Full Spectrum: Full spectrum CBD contains other extracts found in the cannabis plant, including terpenes, and up to 0.3% THC.

• Broad Spectrum: Broad spectrum CBD also contains some other cannabis compounds but no more than trace amounts of THC.

• CBD Isolate: CBD isolate is pure CBD and contains no other cannabis plant compounds.

• Naked CBD: Naked CBD describes CBD oil by itself, as opposed to being capsultated or microcapsulated or combined with any other substance, such as deoxycholic acid (DCA).

• Liposomal CBD: This is an orally administered encapsultated CBD which is packaged within liposomes, small fatty cellular sacs which improve bioavailability of the CBD by enabling it to be withstand digesstion in the stomach and degradation in the liver. Lipsomal CBD was tested on dogs in this September 2020 article.

• Cannabidiolic acid (CBDA) is an acid precursor of CBD. It forms CBD when heated. It has been shown in some studies to be more potent that CBD for treating rats. It has been found to be more readily absorbed into the human bloodstream than CBD. Aa theory is that adding CBDA to doses of CBD may make the CBD more absorbable. In this September 2020 article, the investigators found that CBDA is absorbed at least twice as well as CBD in dogs within a 24 hour period, with some differences depending upon the medium used to deliver the oral treatment.

The most canine studies of CBD thus far have been regarding osteoarthritis (OA). The results have been fairly favorable, with the clear exception of one study, the  one reported in the March 2021 article. Each of them is summarized below.

Interestingly, only one of the studies thus far has included any cavalier King Charles spaniels. And in the March 2020 article below, the two CKCSs were singled out  as requiring the highest dose of CBD to achieve any measurable relief.

In a July 2018 article, researchers report on a study of 16 dogs to determine the safety of CBD extract and its efficacy in allevieating pain in dogs diagnosed with osteoarthritis (OA). The equal mix of CBD and carboxylic acid of CBD (CBDA), was administered at 2mg/kg every 12 hours for 4 weeks. The treated dogs were:

"... perceived to be more comfortable and active. There appear to be no observed side effects of the treatment ... dogs undergoing OA treatment for a month duration. There were some dogs with incidental rises in alkaline phosphatase that could be related to the treatment. Further long-term studies with larger populations are needed to identify long-term effects of CBD rich industrial hemp treatment, however short term effects appear to be positive."

In a March 2020 article about a pilot study of 32 osteoarthritic dogs, in which two cavalier King Charles spaniels were included, hemp-derived CBD oil administered to the dogs reportedly "appears to positively affect dogs with chronic maladaptive pain by decreasing their pain, thereby improving their mobility and quality of life." The specific ingredients of the CBD oil and its dosages were:

"At the initial evaluation and enrollment, qualified dogs received a CBD oil product at a dose of 0.25 mg/kg delivered on food QD for 3 days and then morning and night (approximately every 12 hours). The product given was a certified organic, cold-pressed hemp seed oil infused with 1,000 mg of full-spectrum hemp extract derived from organically grown hemp plants, cultivated in Colorado. Full-spectrum extract includes cannabinoids (such as cannabidiolic acid, CBD, cannabigerol, cannabichromene), flavonoids, terpenes, and other constituents within the cannabis plant."

Most interestingly, the investigators singled out the two CKCSs:

"Among these 30 dogs, the dose of CBD needed to achieve a positive effect ranged from 0.3 up to 4.12 mg/kg BID. The 2 dogs in the study requiring the highest dose of the CBD product were both Cavalier King Charles spaniels (not related to one another), and neither of these dogs experienced any changes/elevations in liver enzymes."

In an August 2020 article, 9 dogs being treated for chronic osteoarthritis-related pain with conventional medications were dosed with oral transmucosal (OTM) cannabidiol (CBD) (2 mg/kg) every 12 hours for 12 weeks. The investigators report that the Pain Severity Score and the Pain Interference Score were significantly lower in CBD than in the control group of 12 other dogs, and the Quality of Life Index was significantly higher in the CBD group. They concluded:

"The addition of OTM CBD showed promising results. Further pharmacokinetics and long-term studies in larger populations are needed to encourage its inclusion into a multimodal pharmacological approach for canine osteoarthritis-related pain."

In a September 2020 article, 15 dogs diagnosed with osteoarthritis were divided into 3 groups and administered (a) 20 mg/day (0.5 mg/kg) naked CBD, (b) 50 mg/day (1.2 mg/kg) naked CBD, or (c) 20 mg/day liposomal CBD for 30 days. The dogs were tested on the first and last days for four different movements:   sitting to standing, lying to standing, walking, and running. The investigators report that, among the 5 dogs receiving 20 mg/day of naked CBD, there generally were no improvements noted among all four movement categories. As for the 5 dogs being dosed 50 mg/day, there were "significant improvements" among all four assessment categories, as also were the 5 dogs receiving 20 mg/day liposomal CBD.

In a March 2021 article, 23 dogs with naturally occurring osteoarthritis of appendicular joints received 2.5 mg/kg of a CBD isolate in hempseed oil for six weeks. The investigators measured outcome objective gait analysis, activity counts (via accelerometry) and clinical metrology instruments. They report finding no differences noted between the CBD group and the placebo group at any time point for any of the recorded outcome measures. As adverse events, then noted elevation in liver enzymes in a majority of the dogs, and vomiting in two. They concluded that, "The pilot data from this study do not support the use of CBD as a symptom-relieving agent for canine OA."

See our Cannabis webpage for additional details about CBD, including delivery methods, bioavailability, dosages, and adverse reactions.

Laser therapy, called "photobiomodulation" (PBM), which is continuous wave laser treatments at acupuncture sites, is a treatment option, either with or without medication.

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What You Can Do

Owners may provide their affected dogs with supplements such as glucoamine HCI, methylsulfonylmethane (MSM), N,N-Dimethylglycine HCI (DMG), and manganese. Retail combinations of these supplements include Vetri-Science GlycoFlex Joint Support.

An aid to cavaliers suffering from arthritis is an elevated dog food bowl. The Ergo Feeder (above) is an example.

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Research News

January 2024: Cavaliers ranked fourth among 84 cases of immune-mediated polyarthritis cases in one UK hospital study. In a January 2024 article, UK researchers (Judith Cruzado Perez [right], Victoria Travail, Valerie Lamb, Darren Kelly) reviewed 84 cases of canine immune-mediated polyarthritis at one UK animal hospital during the years 2011-2021. Dogs with neutrophilic inflammation in 2 or more joints were included. Three of the dogs (3.5%) were cavalier King Charles spaniels. The object of the study was to describe the patients, their symptoms, physical condtions, treatments, and outcomes. They concluded that "IMPA carries a fair prognosis, but relapses occur in many cases and euthanasia due to relapsing or refractory disease is not uncommon."

May 2022: Cavaliers were the second most prevalent breed in a UK study of dogs with immune-mediated polyarthritis (IMPA). In a May 2022 article, UK veterinary researchers Lucy A. Barker (right), S. McManus, S. Adamantos, and V. Black examined the medical records of 58 dogs diagnosed with idiopathic non-erosive immune-mediated polyarthritis (IMPA) to determine the clinical role which proteinuria may play in IMPA and to determine if proteinuria resolves on the treatment of the underlying IMPA. The most common affected breed was the cocker spaniel at 8.6%, followed by the cavalier King Charles spaniel at 7%. They found that proteinuria was a common abnormality in IMPA-affected dogs being studied and appears to frequently resolve on the treatment of the underlying disease.

November 2016: Cavaliers were 15+% of dogs with erosive immune-mediated polyarthritis (IMPA). In a November 2016 article, a team of Wisconsin and Michigan researchers (Magen L. Shaughnessy, Susannah J. Sample, Carter Abicht, Caitlin Heaton, Peter Muir)  studied the clinical records of 79 dogs diagnosed with immune-mediated polyarthritis (IMPA). Of those 79 dogs, 13 had erosive IMPA, of which, two were cavalier King Charles spaniels. The 13 affected dogs had erosive lesions in their carpal joints. The estimated median synovial fluid lymphocyte count for dogs with erosive IMPA was significantly greater than that for dogs with nonerosive IMPA. Results indicated erosive IMPA most commonly affected the carpal joints of middle-aged small-breed dogs. (See left carpus of an 8-year-old spayed female Cavalier King Charles Spaniel with subjectively moderate subchondral bone lysis accompanied by severe synovial swelling -- in x-ray at right.)

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