Immune-mediated Polyarthritis

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Immune-mediated joint disease is a condition in which the immune system is stimulated to cause an inappropriate inflammatory response in one or usually multiple joints. The condition is sometimes termed idiopathic immune-mediated polyarthritis, reflecting an unknown cause of the condition that involves multiple joints.

Inflammation of the lining of the joints causes an increase in white blood cells in the joint fluid. This causes joint swelling and pain.

As with most diseases of the immune system, female animals are at increased risk of getting the disease. The disease is also most commonly seen in younger to middle-aged animals. All breeds may be affected.

What to Watch For

  • A stiff stilted gait
  • Reluctance to walk or stand
  • Swelling of one or more joints, which may also feel warm
  • Shifting or multiple leg lameness
  • Fever
  • Anorexia
  • Lethargy

    Diagnosis

  • A complete physical and orthopedic exam

  • Complete blood test (CBC)

  • Biochemical profile

  • Urinalysis with culture and sensitivity

  • Arthrocentesis of the affected joints by inserting a needle into the joint space and aspirating a sample of synovial fluid. Microscopic cytology examination of the fluid is required to evaluate for any abnormalities. The fluid is also cultured.

  • X-rays of the affected joint or joints

  • Chest and abdominal X-rays

  • Immune profile-includes rheumatoid factor (RF) and antinuclear antibody (ANA)

  • Infectious disease titers including Lyme disease, ehrlichia and Rocky Mountain spotted fever

    Treatment

  • Treatment with immunosuppressive drugs is the main therapy. Prednisone is usually the drug of choice, although other immunosuppressive drugs may be added to the treatment if needed.

  • Intravenous fluid support may be required in debilitated animals.

    Home Care and Prevention

    Carefully monitor your pet for improvement or deterioration. Animals tend to respond to therapy quickly, but relapses may occur, especially as drug dosages are decreased. Drugs need to be slowly decreased over time. Careful communication with your veterinarian is essential.

    Animals on immunosuppressive therapy are more susceptible to infection and need to be monitored closely for changes in behavior, appetite or general condition. Periodic blood tests are needed when animals are on certain immunosuppressive drugs.

    Initially, strict rest is recommended, but as your pet improves, normal activity may resume.

    There are no known measures that can be taken to prevent the occurrence of immune-mediated joint disease. Knowledge of what breeds may be at risk and the associated clinical signs may allow for earlier diagnosis.

    If your pet has had immune-mediated disease, future vaccinations should be used with caution. An appropriate vaccination schedule should be discussed with your veterinarian.

  • Idiopathic immune-mediated polyarthritis is caused by an abnormal immune system response. The joints of one, or typically, multiple joints are identified as abnormal and an inflammatory reaction occurs with increased numbers of white blood cells entering the joint space. The white blood cells, themselves, release various chemical mediators that create further swelling and inflammation. Joint pain and many times fever are noted due to the inflammatory response. An obvious swelling in the joints may or may not be noted. If joint swelling is not present, the diagnosis may be quite difficult to establish.

    There are no consistent signs of the disease and many of the signs are fairly general and may be seen with many other conditions. Animals with this disease generally feel ill and reluctant to move, which may be interpreted as lethargy rather than joint pain or stiffness. Sometimes the only noted clinical problem is a fever of unknown origin, and a very involved work up might be needed before a diagnosis can be established.

    Animals with polyarthritis often experience shifting leg lameness or multiple limb involvement, again causing potential confusion. Additionally, the signs of polyarthritis may be acute (happening very quickly) or chronic (long standing). Oftentimes, animals seem to improve for a short time on their own, but usually their clinical signs return or become even worse. It is not uncommon for an animal that has been intermittently ill for months return to the hospital with polyarthritis.

    If polyarthritis is suspected, it is important to establish the diagnosis of idiopathic immune-mediated disease. Since there is no specific diagnostic test that will confirm the idiopathic disease the diagnosis must be based on exclusion of other potential causes of polyarthritis.

    Many other diseases that stimulate an inflammatory reaction can actually cause a similar immune response in the joints. The diagnosis of idiopathic immune-mediated disease is only made after these other conditions are ruled out. Diseases that can cause similar symptoms as immune-mediated polyarthritis include:

  • Trauma. A traumatic injury to a joint usually causes an acute joint swelling and lameness. The injury may be a soft tissue injury with joint swelling which results in inflammation or bleeding into the joint. Fractures of the bones involving the joint can also lead to severe joint effusion and pain.

  • Chronic degenerative joint disease or osteoarthritis is a very common cause of multiple joint swellings and stiffness. Commonly referred to as arthritis, animals are typically not ill. Osteoarthritis is caused by joint laxity, conformational problems or injury and many times is seen in older animals. The joint swelling that results is caused by an increase in joint fluid due to chronic inflammation, and or an actual increase in bone size due to bony proliferation around the joint.

  • Infectious joint disease. Several causes of infectious polyarthritis may be confused with the immune-mediated disease. Septic (bacterial) arthritis can be caused by either an external wound, or it can be spread by the blood from another area of the body. Typically only one joint is affected but it can also occur in multiple joints. The most common forms of infectious polyarthritis are the tick-borne diseases that include Lyme disease, ehrlichiosis and Rocky Mountain spotted fever. These diseases may cause polyarthritis alone, or be associated with other systemic symptoms. Other more unusual causes of infectious arthritis include fungal and viral agents.

  • Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple body systems. The joints are common sites of inflammation, although the blood, kidneys, muscles, nerves and skin can also be affected.

  • Rheumatoid arthritis is an immune-mediated disease that causes a bone-deforming, erosive polyarthritis. Multiple joints are often affected and the disease is chronic and painful.

  • Polymyositis, or inflammation of the muscles, and meningitis, which is inflammation of the lining of the spinal cord, are separate diseases that have several causes including immune-mediated. The diseases can cause generalized pain, a stiff gait and fever, and may be confused with polyarthritis.

  • Certain breeds are associated with breed specific polyarthropathy. Greyhounds, usually under two years, may develop an erosive bone deforming polyarthritis of their distal extremities. The shar-pei breed may develop a disease called "shar-pei fever", categorized by fevers and swellings of the hock and carpal joints. Over time, severe kidney disease may develop. Akitas, boxers, Weimaraners, Bernese mountain dogs, German shorthair pointers and beagles have been known to develop a polyarthritis or a polyarthritis/meningitis syndrome that affects young dogs.

  • Reactive polyarthritis is a term used to describe polyarthritis secondary to a primary disease process. Reactive polyarthritis is caused by prolonged stimulation of the immune system by a number of agents. It is fairly uncommon. Primary causes include: chronic bacterial, fungal or parasitic infections, gastrointestinal disease, tumors, long-term therapy with certain drugs and reactions to vaccination.

  • Diagnosis In-depth

    The diagnosis of immune-mediated polyarthritis is made in two parts. First, your veterinarian must establish a diagnosis of polyarthritis, which is often difficult. Once the polyarthritis is diagnosed, a cause needs to be determined. Since the diagnosis of immune-mediated polyarthritis is based on the exclusion of other causes, a significant work-up is usually required. Diagnostic tests include:

  • CBC. The CBC is an important test used in evaluating the white and red blood cell lines. Elevations in white blood cells may indicate an inflammatory response, signs of infection or a neoplastic (cancer) process. The red cell line is used to check for anemia, which may be seen with many infectious, neoplastic or immune-mediated processes. The platelets, which are the blood cells responsible for clotting, are also counted. Decreases in the platelet count may be seen with tick borne diseases, SLE or neoplastic disease.

  • Biochemical profile. Many internal metabolic conditions are monitored through the biochemical profile. Kidney function is assessed as SLE commonly can cause kidney damage. Occasionally kidney damage is also seen with the tick borne diseases. Liver disease may be noted, as inflammation of the liver may be present as a primary cause of reactive polyarthritis.

  • A urinalysis should always be done in the work-up for polyarthritis. A urinalysis is needed to assess kidney function, and to check for signs of infection. A culture is also generally recommended, since long-term immunosuppressive therapy may be required for treatment of the disease.

  • Arthrocentesis is needed to make a definitive diagnosis of polyarthritis. Multiple joints should be sampled and the fluid submitted for cytologic evaluation and culture. Analysis of immune-mediated joint fluid typically has an increased number of inflammatory cells. Other causes of polyarthritis may have different cytologic characteristics; however, tick borne diseases and other causes of immune-mediated diseases such as SLE will show similar cytologic findings as the idiopathic disease, and thus require different diagnostic tests to differentiate the conditions.

  • Radiographs of the affected joints are important to determine if the joint disease is causing an erosive arthritis that is sometimes seen in septic arthritis, and commonly seen in rheumatoid arthritis. Idiopathic immune-mediated disease is typically a non-erosive polyarthritis.

  • Chest and abdominal radiographs are useful to rule out underling diseases. Tumors, infections, foreign bodies and stones may all be a cause of chronic immune stimulation.

  • Immune profile. RF and ANA titers can be submitted to help diagnose rheumatoid arthritis and SLE. The tests, if positive, help in establishing a diagnosis but are not definitive.

  • Infectious disease titers for Lyme disease, ehrlichia and Rocky Mountain spotted fever are helpful in ruling out these causes of polyarthritis. Many times they are the only way to differentiate the idiopathic disease from infectious causes.

  • If indicated, an abdominal ultrasound, echocardiogram or blood culture might be required.

    Therapy In-depth

  • Prednisone. Prednisone is the most common and generally most effective drug used in the treatment of immune-mediated polyarthritis. When given at high dosages, it causes suppression of the immune response. Improvement of the clinical signs is usually seen quickly, within 48 hours. To induce remission, high doses are given at the start of therapy. If remission occurs, dosages are gradually decreased and eventually stopped, over 4 to 9 months. If remission is difficult to achieve, a relapse has occurred, or there are unwanted side effects from the prednisone, additional immunosuppressive drugs are required.

  • Azathioprine (Imuran). Imuran is usually the next immunosuppressive drug used in the treatment of the disease. It is usually used together with prednisone, allowing for lower prednisone dosages, but can be used as a maintenance drug. The drug requires 2 to 3 weeks to become effective. Azathioprine can cause bone marrow suppression, but used with caution, it can be very effective.

    Generally, prednisone and Imuran are the most effective drugs used to treat the disease. In refractory cases, the following drugs may be of benefit:

  • Cyclophosphamide (Cytoxan). This drug causes potent immunosuppression, but needs to be used with care due to potent bone marrow suppression.

  • Chrysotherapy (gold salt therapy). Gold containing compounds have anti-inflammatory properties that may be useful in treatment. Intramuscular injection (sodium aurothiomalate) or oral preparations (auranofin) are available, but the drug may take a month or more to be effective.

  • Optimal treatment for your pet requires a combination of home and professional veterinary care. Follow-up can be critical, especially if your pet does not improve rapidly. Administer all medications as directed. Alert your veterinarian if you are experiencing problems treating your pet.

    Even after your pet has gone into remission, careful observation is required. The signs of polyarthritis may recur even while on medication. Early recognition improves the chances of a second remission. This is especially important as immunosuppressive drugs are decreased.

    Routine follow-up veterinary examinations are important while your pet is being treated. Subtle changes in joint size, shape or conformation may be noted.

    Monthly blood tests are required (CBC and platelet counts) if your pet is receiving Imuran. The tests may be required more frequently if receiving Cytoxan.

    If your pet is experiencing unusual behavior, it may be a side effect from the prednisone. The most common side effects include: increased thirst, urination and appetite; panting; lethargy; weakness; and muscle atrophy. Depending on the severity of these signs, the dosage may need to be adjusted and/or additional immunosuppressive drugs started.

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