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Arthritis: immune-mediated

icanis

Synonym(s): immune-mediated polyarthritis, IMPA


Introduction

  • Multiple, simultaneous, bilaterally symmetrical synovial inflammation causing inflammatory polyarthritis. Also known as "immune-mediated polyarthritis" (IMPA). Officially, 5 or more joints must be affected for the condition to be termed "polyarthritis", but usually it is assumed that if 3 or 4 joints are confirmed to be affected via joint taps, then multiple other joints will also be affected.
  • Cause: chronic antigenic stimulation is assumed to be the cause of  polyarthritis but, in most cases, a source of this antigenic stimulation is not detected, in which case the IMPA is called "idiopathic". When an underlying antigenic trigger is recognized, the IMPA is called "reactive".
  • Signs: stiffness, lameness, unwillingness to walk, pyrexia and, occasionally, joint swelling.
  • Diagnosis: cytopathology of joint fluid.
  • Treatment: immunosuppression.
  • Prognosis: fair/guarded.

Pathogenesis

Etiology

  • In the most common form of immune-mediated polyarthritis, non-erosive IMPA, no underlying etiology can be identified, and an underlying etiology is also uncommonly identified in the less erosive polyarthritis. However, in some dogs, an underlying trigger can be identified, or at least suspected.
  • Idiopathic polyarthritis Arthritis: polyarthritis - idiopathic.
  • Modern techniques have demonstrated distemper antigens in synovial fluid of some dogs with immune-mediated arthropathies and distemper antibodies in circulation, and distemper antigens may therefore be initiating cause for synovial inflammation in some dogs.
  • Rheumatoid arthritis Arthritis: rheumatoid.
  • Erosive polyarthritis of greyhounds Arthritis: polyarthritis - Greyhound.
  • Systemic lupus erythematosus Systemic lupus erythematosus.
  • Drug-induced arthritis. Sulphonamide antibiotics are the most commonly implicated drug.
  • Poyarthritis/polymyositis syndrome Polyarthritis / polymyositis syndrome.
  • Steroid-responsive meningitis-arteritis (SRMA) Steroid-responsive meningitis-arteritis (SRMA).
  • Enteropathic arthritis.
  • Lymphocytic plasmacytic synovitis.

Pathophysiology

  • Two groups are classifed:
    • Erosive Arthritis: erosive. Erosive polyarthritis tends to have a severe clinical presentation but, fortunately, is very uncommon (about 1% of all polyarthritis cases in dogs) compared to non-erosive polyarthritis. Erosive polyarthritis is somewhat similar (albeit not identical) to rheumatoid arthritis in people, an erosive polyarthritis that can lead to severe joint damage.
    • Non-erosive Arthritis: non-erosive. Non-erosive polyarthritis is the most common form of polyarthritis in dogs, and tends to be a chronic lingering disease without erosion or joint destruction. Chronic severe cases can, on occasion, eventually become erosive and lead to joint damage and destruction.
  • There is a classification system which divides non-erosive immune-mediated polyarthritis into 2 types:
    • Idiopathic ("uncomplicated"): no known causes. Condition often causes a persistent joint inflammation without erosion, although progression to erosion is possible The most common form of IMPA (over 50% of dogs with IMPA).
    • Reactive: associated with underlying disease elsewhere in the body that then leads to secondary joint inflammation. Reactive immune-mediated polyarthritis is then subdivided into 3 subcategories:
      • Reactive: associated with infective or inflammatory disease elsewhere, which serves as an antigen source for persistent immune complex formation. Interestingly, because of this process, while the underlying disease can be infectious, the joint damage is immune-mediated caused by immune complexes, and the inflamed joint itself can be sterile and free of the infectious agent.
      • Enteropathic: associated with gastrointestinal disease, which leads to an increase in intestinal permeability to foreign antigens, resulting in chronic formation of immune complexes.
      • Neoplasia-related: associated with malignancy. Tumor cells may act as a source of chronic antigenic stimulus.
  • Antigen → antigen/antibody complex (immune complex) releases into the blood circulation → immune complex localizes and persists (mechanism unknown) in synovial membrane → damaged microvascular endothelium in supporting layer of synovial membrane.

Chronic disease

  • Immune-mediated polyarthritis is often a persistent and chronic disease.
  • Due to:
    Either Continued or recurrent presence of antigens.
    Or Failure of immune system to adjust after antigens eliminated.
    Or Initial synovial damage exposes or alters self-antigens → auto-antibody formation → reaction between auto-antibodies and self-antigens → formation of further immune complex → chronic inflammation.

Cell-mediated immune response

  • Persistent antigens → infiltration of T- and B-lymphocytes and mononuclear cells in supporting layers and fibrinous exudate in synovial membrane.
  • Non-erosive forms: inflammatory cells in joint fluid are predominantly neutrophils.
  • Erosive forms: chronic synovitis → production of proliferative granulation tissue (pannus) → invades articular cartilage → erodes the cartilage into subchondral bone → joint destruction by various enzymes (matrix metalloproteinases) produced by pannus and inflamed synovium.

Systemic manifestations

  • Mostly, the systemic manifestations of immune-mediated polyarthritis are associated with the accompanying fever and triggering of the systemic inflammatory response:
    • Fever, lethargy, depression, inappetence.
    • Inflammatory leukogram.
    • Mild anemia of chronic disease.
    • Mild hypoalbuminemia and mild to moderate hyperglobulinemia.
  • Due to immune complex hypersensitivity or auto-antibody formation, uncommonly, other organ systems can also be affected, eg myositis, glomerulonephritis, anemia, thrombocytopenia, skin lesions Systemic lupus erythematosus Arthritis: polyarthritis - idiopathic.

Timecourse

  • Signs may have insidious onset and be present for weeks to months before diagnosis, and can linger for years if treatment is inadequate or discontinued.

Diagnosis

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Treatment

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Rhoades A C, Vernau W, Kass H, Herrera M A, Sykes J E (2016) Comparison of the efficacy of prednisone and cyclosporine for treatment of dogs with primary immune-mediated polyarthritis. JAVMA 248 (4), 395-404 PubMed.
  • Shaughnessy M L, Sample S J, Abicht C, Heaton C, Muir P (2016) Clinical features and pathological joint changes in dogs with erosive immune-mediated polyarthritis: 13 cases (2004–2012). JAVMA 249 (10), 1156-1164 PubMed.
  • Foster J D, Sample S, Kohler R, Watson K, Muir P, Trepanier L A (2014) Serum biomarkers of clinical and cytologic response in dogs with idiopathic immune-mediated polyarthropathy. JVIM 28 (3), 905-911 PubMed.
  • Johnson K C, Mackin A (2012) Canine immune-mediated polyarthritis: part 1: Pathophysiology. JAVMA 48 (1), 12-17 PubMed.
  • Johnson K C, Mackin A (2012) Canine immune-mediated polyarthritis: part 2: Diagnosis and treatment. JAVMA 48 (2), 71-82 PubMed.
  • Lowrie M, Penderis J, McLaughlin M, Eckersall P D, Anderson T J (2009) Steroid responsive meningitis-arteritis: a prospective study of potential disease markers, prednisolone treatment, and long-term outcome in 20 dogs (2006-2008). JVIM 23 (4), 862-870 PubMed.
  • Kohn B (2008) Canine immune-mediated polyarthritis. European Journal of Companion Animal Practice 17 (2), 119-125 VetMedResource.
  • Stull J W, Waldner C, Carr AP, Evason M (2008) Canine immune-mediated polyarthritis: Clinical and laboratory findings in 83 cases in western Canada (1991-2001). Can Vet J 49 (12), 1195-1203 PubMed.

Other sources of information

  • Stone M (2017) Immune-mediated polyarthritis and other polyarthritides. In: Textbook of Veterinary Internal Medicine. Ed: Ettinger S J, Feldman E C, Cote E, Elsevier, St. Louis.
  • Taylor S M, Scott, Moncrieff J C (2014) Joint disorders. In: Small Animal Internal Medicine. Ed: Nelson R W, Couto C G, Elsevier Mosby, St. Louis.

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