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Immune Mediated Polyarthritis and Neutrophilic Inflammatory Joint Disease in our Feline Patients

kirsten johnsonBy Kirstin Johnson, DVM, DACVIM
angell.org/internalmedicine
internalmedicine@angell.org
617-541-5186

Inflammatory joint disease in cats is a rare disorder but should be suspected in a cat who either has an acute shifting-leg lameness, swollen joints, painful joints on flexion and or extension, or in a cat who refuses to walk and has systemic signs of illness such as lethargy, fever, and anorexia. In a minority of cats, only a single joint may seem painful and swollen when in actuality there is involvement of multiple joints. 1

In cats, unlike dogs, infectious causes of polyarthritis and inflammatory joint disease are much more common than primary or reactive immune disorders. And if present, these agents more typically directly infect the synovium versus cause a reactive polyarthritis where antigen-antibody complexes seed the joint and induce sterile inflammation. 1

Polyarthritis in cats is divided into 2 main categories that include erosive ‑ or perhaps better thought of as destructive ‑ arthritis and the more common non-erosive. Radiographs are used to determine which form the patient has.  Erosive arthritis is more difficult to manage.2 In some patients, erosive changes are not immediately recognized and repeat radiographs are recommended if a patient does not seem to be responding to therapy. Erosive arthritis in cats is typically caused by an immune condition however mycoplasma has also been implicated.3  In cases where destructive changes are documented, radiographs may reveal either periosteal proliferation or subchondral erosions. 1,2

Severe subchondral central and marginal erosions are indicative of feline rheumatoid-like arthritis which is an immune-mediated disease. Cats with this disease are not systemically ill but rather have a slow, progressive lameness and joint deformity which can include the collapse of the joint spaces. 1-4 Most of these cats are middle-aged. The Siamese may be overrepresented. 4

Periarticular perisoteal new bone formation is indicative of feline periosteal proliferative polyarthritis. This form of erosive polyarthritis is much more common than the rheumatoid-like condition previously mentioned.  Feline periosteal proliferative polyarthritis is most typically diagnosed in young adult males. Unlike with rheumatoid-like arthritis, these cats are more likely to be systemically ill with fever and lethargy along with a stiff gait, joint pain, and joint swelling. The carpi and hocks are often affected.  Radiographic changes may not be evident for 10-12 weeks following the start of clinical signs. Radiographs may initially reveal soft tissue swelling around the affected joints and some mild periosteal proliferation then overtime the proliferation worsens and extends beyond the joint leading to ankylosis.  Feline periosteal proliferative polyarthritis is mainly caused by immune-mediated disease, however, both mycoplasma and FeLV have been implicated. 1-3, 5

Infection within the joints is the most common cause of non-erosive polyarthritis. Following infection would be reactive polyarthritis as described above. Lastly, an immune problem leading to primary/ idiopathic polyarthritis or systemic lupus erythematosis (SLE) is the least common. 1,2 Cats with SLE have multiple concurrent immune-mediated problems such as skin lesions, glomerulonephritis, fever and a positive anti-nuclear antibody test. Himalayans, Persians and Siamese cats seem to be the most affected breeds. 6

Diagnosing inflammatory joint disease ultimately requires arthrocentesis which should be performed on multiple joints. Ideally, 5 or more joints are sampled.

Arthrocentesis is a safe procedure and not difficult to learn. Deep sedation or general anesthesia is required during collection of synovial fluid. The skin over the joint should be surgically prepared and the person collecting the fluid should be wearing sterile gloves. 25 gauge needles attached to 3cc syringes work best for collecting joint fluid in the cat.  Diagrams demonstrating landmarks for joint taps can be found in Small Animal Clinical Techniques Elsevier 2010.  Once through the skin and after entering the joint space, the plunger is pulled back about halfway to apply gentle negative pressure. The plunger should remain pulled back until joint fluid is seen coming into the hub of the needle and syringe. This can take a moment. Watch carefully and be patient since often times only a few drops of fluid are obtained. Once the joint fluid is collected, release the plunger before removing the needle and syringe to avoid blood contamination. If after entering the joint the needle hits bone, pull out slightly to enter the joint space, then apply negative pressure.

Once the sample is obtained, the plunger should be pushed firmly into the hub of the needle to expel joint fluid. Since the joint may only yield a few drops, estimated cell counts are made from direct smears.  One or 2 drops can be carefully released onto slides to make direct smears without touching the needle to the slide.

For aerobic and anaerobic culture I recommend using pediatric blood culture vials. The use of broth-enriched media and incubation prior to culture greatly increases the rate of positive cultures. 7 The remaining joint fluid can by washed from the syringe by aspirating fluid out of the blood culture vial using this syringe then pushing it back into the vial. A sample of joint fluid should also always be submitted for mycoplasma species testing since this a common cause of polyarthritis in cats. 1 If systemic bacterial infection is suspected, blood and urine cultures are advised since positive joint cultures are difficult to obtain.

Because macroscopic and microscopic blood contamination is common during joint taps, a current CBC should be submitted with all joint cytologies.  Depending on the disease process, inflammation can be mild, moderate or marked.  In normal joints the estimated cell count is less than 3,000 cells/ul and comprised mostly of mononuclear cells and lymphocytes. Neutrophils should make up less than 10% of the cell population.8 Cats with osteoarthritis may have an increase in total number of cells/ul but no increase in neutrophils. Cats with polyarthritis demonstrate varying increases in cell numbers and percentage of neutrophils.  Neutrophils in these samples typically look normal. On rare occasions, in cats with tick-borne disease, a morulae may be spotted within a neutrophil. In acute or severe septic arthritis, the neutrophils may look toxic and or degenerative and intracellular bacteria may be seen. Other definitive diagnosis obtained from joint cytology may result from finding fungal organisms or detecting coronavirus within infected macrophages. 1

After documenting inflammation in multiple joints, every effort should be made to rule out an infection.  Careful screening for infectious diseases should include aerobic and anerobic bacteria including mycoplasma species, calicivirus, FeLV, FIV, FIP, as well as fungal and tick born infections endemic to the area in which the patient has been exposed.  Tick borne diseases that can cause polyarthritis in the cat include anaplasmosis, ehrliciosis and possibly Lyme disease. Fungal diseases that have been documented to cause polyarthritis in cats include cryptococcocus, bastomycosis, coccidiomycosis and histoplasmosis.1-3

Bacterial L-forms should be suspected if the animal has cellulitis or draining tracts.1 Screening for other conditions causing persistent antigenic stimulus leading to antigen-antibody complexes and reactive polyarthritis should also be conducted. They include remote infections from the joints such as pneumonia, pyelonephritis, toxoplasmosis and even a cat bite abscess as well as neoplasia.1,2  Therefore, imaging of the thoracic and abdominal cavity when looking for systemic fungal infections, neoplasia or remote infections may be indicated.

A careful history should be gathered regarding any recent vaccines or medications that the animal is on.  The modified-live calicivirus vaccine is the most commonly reported vaccine implicated in polyarthritis in the cat. The symptoms of fever and shifting leg lameness occur within 3 weeks after vaccination and resolve on their own with supportive care after about 2-5 days.1

Drug haptens can trigger a reactive polyarthritis. Haptens are small molecules that elicit an immune response only when attached to a large carrier such as a protein.  Most pharmaceuticals and antibiotics are small and are unable to elicit an immune response on their own. However, when bound to a serum protein or molecule expressed on the surface of body cells, the combined structure can lead to an antibody response. Drug haptens triggering a polyarthritis is more common in the dog but possible in the cat. Drugs that have been reported in the dog to trigger a polyarthritis include penicillins, cephalosporins, erythropeitin, sulfa drugs and phenobarbital.7 If a drug hapten is suspected to be a possible trigger, the drug should be stopped. After this, joint inflammation may resolve on its own or need a short course of anti-inflammatory medication.

Culturing joint fluid for aerobic bacteria, anaerobic bacteria and mycoplasma is challenging. If aerobic bacteria are suspected, blood and urine cultures should also be submitted. If anaerobic organisms are suspected an anaerobic culture of blood should also be submitted. Mycoplasma is one of the more common causes of non-erosive polyarthritis in the cat and has been associated with erosive polyarthritis.1.3 Although mycoplasma is spread hematogenously to the joints, it is difficult to culture from joint fluid even with specific culture media.1 PCR looking for Mycoplasma species submitted to Antech vs trying to culture the organism from joint fluid may be a more sensitive test.

In addition to demonstrating the presence of a bacterial infection, tick borne disease can also be difficult to diagnose in the cat. Treating cats with polyarthritis prematurely with immunosuppressive medications can cause their condition to worsen if infection is present. Therefore, even after ruling out infection with careful testing, it is still strongly recommended that patients be treated with supportive care including adequate pain management as well as doxycycline for 3 weeks before considering immunosuppressive therapy. 1

If testing yields an underlying cause leading to a reactive polyarthritis, the underlying cause should be treated or the drug discontinued. Depending on the disease process leading to reactive polyarthritis, immunosuppressive doses of steroids may be indicated to help control clinical signs. If no underlying or infectious cause is found and no response to doxycycline has been documented, immunosuppressive therapy can be implemented.

Medications that might be considered to treat immune mediated polyarthritis in the cat include glucocorticoids alone or glucocorticoids combined with leflunomide, cyclosporine, chlorambucil or methotrexate.1,2,4 If erosive changes are present and there has been no response to doxycycline more aggressive immunosuppressive therapy should be considered. One report treating cats with rheumatoid-like arthritis with a combination of methotrexate and leflunomide demonstrated obvious clinical improvement in 58% their patients.4

Ideally, medications are tapered after repeat joint taps confirm remission. If repeat joint taps are not feasible, immunosuppressive medications can be tapered after clinical remission is confidently established.  A multi-drug protocol and slower taper should be considered for more aggressive polyarthritis cases such as those that are erosive. Patients should be re-examined about 5-7 days after each taper to look for signs of relapse. If relapse is suspected, the patient should be put back on the previous dose of medications. Signs of relapse should be addressed immediately to avoid clinical signs that become more difficult to control. If relapse occurs, the speed of drug taper should also be slowed. Some patients will achieve and stay in complete remission after medications are discontinued while others require medical intervention long term to control their clinical signs.

References

  1. Lemetayer J, Taylor S. Inflammatory joint disease in cats; A diagnostic approach. J Feline Med Surg. 2014 Jul; 16 (7): 547-562.
  2. Bennet D, Nash AS. Feline immune-based polyarthritis: a study of thirty-one cases. J Small Anim Pract. 1988 August; 29(8): 501-523.
  3. Zeugswetter F, Hiimai KM, et al. Erosive polyarthritis associated with Mycoplasma gateae in a cat. J Feline Med Surg 2007 June; 9(3):226-231.
  4. Hanna FY. Disease modifying treatment for feline rheumatoid arthritis. Vet Comp Orthop Traumatol. 2005 Jan; 18 (2): 94-99.
  5. Pederson NC , Pool RR, O’Brien T. Feline chronic progressive polyarthritis. Am J Vet Res 1980 April; 41 (4): 522-535.
  6. Thompson MF. Lupus Erythematosus.Systemic (SLE). In:Blackwell’s Five Minute Veterinary Consult Clinical Companion Small Animal Emergency and Critical Care. Ames, Blackwell, Ames, IA. 2010:828-829
  7. Johnson KC, Mackin A. Canine immune-mediated polyarthritis. J Am Anim Hos Assoc 2012; 48: 71-82.
  8. Pacchiana PD, Gilley RS, et al: Absolute and relative cell counts for synovial fluid from clinically normal shoulder and stifle joints in cats. J Am Vet Med Asoc 2004 Dec; 225 (12): 1866-1870.

 

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