Review Article: Immune Mediated Polyarthritis

Pathophysiology and presentation

Immune mediated polyarthritis may be more common than recognised, as clinical signs can sometimes be subtle.

Generally, it is defined as neutrophilic inflammation affecting two or more joints and is an example of a type-III hypersensitivity reaction. Immune system stimulation leads to formation of immune complexes, which circulate and deposit in the basement membrane of synoviocytes, triggering immune-mediated inflammation within the joint.

The classic presentation is an animal with a shift-ing leg lameness, or a gait described as ‘walking on eggshells’, often in conjunction with systemic signs such as lethargy, pyrexia, anorexia, vomiting and diarrhoea. Acute and more chronic presentations can occur, and cases may just present with generalised stiffness, or as a fever of unknown origin. In these cases, careful palpation of the joints may reveal joint pain or effusion (fig. 1.1). Although a palpable joint effusion is often present, absence does not rule out a poly-arthritis. Disease morbidity can range from mild through to severe.

fig. 1.1 – there is marked effusion of the talocrural joint

Most often, the distal limb joints are affected first, with more proximal joints becoming affected later in the disease course. In addition, the vertebral articulations may be affected leading the patient to present with spinal pain. Less commonly, joints such as the temporo-mandibular joint may be affected.

Categories

Immune mediated polyarthritis can be divided into two categories; erosive and non-erosive, with radiography being used to distinguish between the two. Non-erosive polyarthritis is more common, and again can be divided into categories (see Types 1-4 below) according to the underlying cause.

Type 1: Idiopathic (primary auto-immune) is the most common type. Typically, this affects young to middle aged dogs, and is a diagnosis of exclusion.
Type 2: Secondary to a distant focus of infection.
Type 3: Secondary to GI disease.
Type 4: Secondary to neoplasia (paraneoplastic syndrome).

In addition, idiosyncratic drug reactions are an uncommon cause (e.g. potentiated sulphon-amides in black and tan dogs), and infection with Borrelia burgdorferi (the causative agent of Lyme disease) can trigger polyarthritis. If in a Lyme endemic area, or there is a history of tick exposure, serology may be worthwhile to look for exposure to Borrelia. A negative result makes this unlikely to be the cause of the clinical signs, though a positive result only confirms exposure and does not prove causation – it is thought only around 5-10% of seropositive dogs will develop clinical signs. Unfortunately, as spirochetes are rarely present in the blood or joint fluid, PCR of blood or joint fluid is poorly sensitive for diagnosis. PCR carried out on a tissue biopsy from the tick attachment site is much more sensitive. However, as clinical signs usually arise several weeks after tick exposure, the original attach-ment site is rarely known. Treatment of Lyme disease is usually with doxycycline at 10mg/kg SID for 4 weeks – with care taken to avoid oesophagitis.

The disease can also occur as part of the auto-immune condition systemic lupus erythematosus, and alongside other conditions such as poly-myositis and steroid responsive meningitis arteritis.

Diagnosis

Neutrophilic joint inflammation is confirmed using arthrocentesis (fig 1.2). If possible, multiple joint taps should be taken, especially from the carpal and tarsal joints. Ideally at least 3 – 4 joints should be sampled. Samples should be sent for cytology, and if enough fluid is available, total nucleated cell count. If bacterial infection is a consideration, joint fluid in blood culture medium should be submitted.

fig, 1.2 – Synovial fluid demonstrating
Non-degenerate neutrophils

Radiography should be carried out to assess if the polyarthritis is erosive or non-erosive, though the non-erosive form is more common (fig. 1.3). A good history and clinical exam will help to determine if an underlying or concomitant disease process may be present. Further investigations such as haematology and biochemistry, urinalysis, thoracic and abdominal imaging, and Borrelia serology may be required depending on the case. It is worth trying to rule out secondary causes, since resolution of the polyarthritis will often depend on this in these cases.

fig 1.3 – Carpal radiographs from an advanced case of erosive polyarthritis. Joint swelling, subchondral bone lysis, collapsed joint spaces and peri-articular oste-ophytosis are present.

Treatment

If no other cause can be found and the poly-arthritis is suspected to be idiopathic, then the mainstay of treatment is usually immuno-suppressive treatment with corticosteroids. Opinions differ as to the dose used, and how quickly this should be tapered, however most clinicians will start with a dose of prednisolone around 2mg/kg/day and aim to taper down over several months once remission has been achieved. Additional use of ciclosporin or azathioprine can be considered for refractory cases, and some more recent studies have looked at using leflunomide or ciclosporin as mono-therapies, which may be an option if prednisolone is contraindicated. If the disease is secondary, then treatment of the underlying problem will often lead to resolution of the polyarthritis.

Monitoring

Some clinicians advocate serial arthrocentesis to monitor response to treatment, however often clinical response is used instead, since repeat arthrocentesis usually requires sedation or anaesthesia, along with the concomitant expense. Some more recent studies have investigated using C-reactive protein as a surrogate marker for joint inflammation. As this test is now increasingly available in the Practice setting, it could provide a good compromise for monitoring, with a measured reduction in C-reactive protein likely correlating with improvement in joint inflammation.

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