Immune Mediated Polyarthritis and Other Polyarthritides

Question 1

Define polyarthritis and subdivide by causation

Answer 1

• Polyarthritis is neutrophilic inflammation in 2 or more joints

1. Infectious
2. Reactive
3. Primary or idiopathic
   
   • non-erosive
   • erosive

Question 2

Describe the differentiating signs of IMPA versus septic arthritis

Answer 2

Polyarthritis:

• Multiple small joints are affected
• Fever is commonly present: >50%
• Neutrophilic inflammation in multiple joints

Septic Arthritis:

• Single large joint most often affected
• Fever is common
• Recent surgery or trauma
• Previous known degenerative joint disease
• Chronic bacterial infection (skin/urinary tract)
• Lameness with a history of immunosuppression

Question 3

Discuss diagnostic testing options for infectious causes of polyarthritis

Answer 3

1. Arthrocentesis to confirm neutrophilic inflammation
2. Doxycycline trial - useful for Borrelia burgdorferi, anaplasma phagocytophilum, rickettsia richettsii and ehrlichia canis
   
   • ​​Response expected within 72 hours, and often before seroconversion
3. If systemic infection suspected:
   
   • Thoracic radiographs
   • Echo to assess for endocarditis
   • Abdominal ultrasound
   • Skeletal radiographs
   • Serological testing
4. Joint fluid culture - from most clinically affected joint
   
   • Often negative even when infection is present - subculture into blood culture medium
   • Negative when the infectious focus is distant to the joint
5. Consider specialised testing (serology, cultures) when in an endemic area and as required

Question 4

List the infectious causes of polyarthritis and describe diagnostic approach

Answer 4

1. Tick borne / rickettsial infection
   
   • In endemic areas, consider doxycycline trial prior to arthrocentesis
2. Leishmaniasis
   
   • Clinical signs can develop 3 months to 7 years after infection
   • Can see erosive changes on joint radiographs
   • Diagnosed via serology or visualisation of organism in mononuclear cells
3. Bacterial - rarely affects multiple joints
4. Mycoplasma
   
   • Rare and causes neutrophilic inflammation
   • diagnosis requires culture in special media or PCR
5. Bacterial L forms
   
   • Rare syndrome with subcutaneous abscesses and polyarthritis
   • Fistulating wounds can develop over joints
   • Requires special L-from culture media for growth
   • Difficult to identify with light microscopy - need electron microscopy
6. Fungal infection
   
   • Reactive, immunologically mediated, sterile polyarthritis most common
   • Direct joint involvement is possible
7. Viral infection
   
   • Calicivirus infection in kittens
   • spontaenous improvement in 2-4 days
   • mononuclear pleocytosis in the joint fluid

Question 5

List causes of reactive polyarthritis

(secondary to distant immunological stimuli)

Answer 5

1. Distant infection
2. Nonjoint, inflammatory (non-infectious) focus
3. Drugs
4. Vaccination
5. Distant neoplasia

Question 6

Discuss conundra in the diagnosis of reactive polyarthritis

Answer 6

1. Difficult to determine if the joint inflammation is primary or secondary to immune complex deposition
2. Presence of urinary tract infection, gingivostomatitis and chronic otitis can confuse the diagnosis
3. Incidental or concurrent infection is possible - especially urinary tract infection. These may not be causative
4. When another inflammatory disease is present - differentiating between two separate diseases, a primary disease with reactive polyarthritis or a single disease such as SLE can be difficult
5. Vaccination itself may cause polyarthritis or the disease may be triggered by immune stimulation in susceptible individuals.
6. Can be unclear if neoplasia causes polyarthritis or the two conditions coexist

Question 7

Discuss briefly the suspected pathogenesis in Shar Pei Autoinflammatory Disease

Answer 7

• Genetic condition
• Missense mutation in MTBP is highly associated
• Duplication mutation upstream of hyaluron synthase 2 (HAS2) has been found not causative of SPAID
• Mutation has a dominant mode of inheritance with incomplete penetrance - reason for variable age of onset
• Perivascular and diffuse inflammation (lymphocytes, plasma cells, eosinophils, mast cells)
• Affected dogs may also be predisposed to amyloid deposition

Question 8

Describe the variable history and clinical signs seen with SPAID

Answer 8

• Age of onset < 6 years and often < 2 years. Median 1 year in a recent genetics, survey based study
• Recurrent fever together with joint inflammation, especially hocks.
  
  • Also see erythema, thickened and pasty skin, otitis, ocular/conjunctival inflamation and gastrointestinal signs
• Generalised cutaneous mucinosis is common in the breed and may be linked to SPAID
• Fever and signs typically response to NSAIDs
• Condition may predispose to amyloidosis - can lead to PLN and hepatic failure and disease in many other organs

Question 9

Discuss historical and clinical exam findings with IMPA including assessment to help exclude major differential diagnoses

Answer 9

• Most dogs present with reluctance to walk or a stiff gait (lame in all four limbs).
• Fever is present in ~50% and anorexia, lymphadenopathy and weight loss (with chronicity) can be seen.
• Historical questions need to exclude recent drug administration, vaccination and travel to tick regions
• Physical examination needs to exclude cervical pain, metaphyseal (hypertrophic osteodystrophy) or long bone pain (panosteitis) and skin/mucosal changes to suggest SLE
• Presence of a heart murmur or arrhythmia may suggest endocarditis
• Carpi and tarsi momst often affected and swelling may or may not be palpable.

Question 10

Discuss routine clinicopathological testing when IMPA is suspected

Answer 10

• Routine CBC and biochemistry and urinalysis
  
  • mild leukocytosis
  • mild non-regenerative anaemia
  • elevated hepatic enzymes
    
    • may need further investigation
  • thrombocytopenia
    
    • concern for tick borne disease
    • Potential concurrent IMT - ie. not idiopathic IMPA
  • Proteinuria - assess UP:Cr and blood pressure
• Imaging only on a case by case basis. Radiographs are not typically indicated initially except with joint instability
• serology in endemic areas rarely indicated
• Arthrocentesis at least 3 joints to confirm polyarthritis

Question 11

Discuss treatment options for IMPA

Answer 11

1. Corticosteroids - 1-2 mg/kg q 24 hours. Lower doses may be effective for mild cases or those secondary to known trigger
2. Leflunomide - pyrimidine inhibitor
3. Mycophenolate / azathioprine - purine inhibitors
4. cyclophosphamide - rarely used now
5. cyclosporine - highly variable absorption and suppression of T cell induced IL-2 production.
6. Sulphasalazine - for type III (diarrhoea associated disease)
   
   • Issues proving link but can be trialed for mild cases
7. Chlorambucil - for cats

Question 12

Brief overview of history, signalment and clinical findings for dogs and cats with erosive polyarthritis

Answer 12

• History as for non-erosive disease often with a poor response to corticosteroids alone
• Median age - 5 years
• Joint instability is common with chronic disease
• ~1/3 of cases have fever, lethargy or inappetance
• Feline disease is very rare: 2 types
  
  • marked periosteal new bone formation
  • Primary bone lysis
• Rheumatoid factor positive in most cases

Question 13

Discuss the pathophysiology, diagnostic utility, sensitive and specificity of Rheumatoid factor for the diagnosis of rheumatoid arthritis

Answer 13

• RF is an autoantibody directed against IgG. First identified in rhematoid arthritis in people
  
  • antibodies may play a role in opsinisation and elimination of immune complexes
• Testing is indicated with inflammatory arthritis with instability or evidence of joint erosion. Chronic arthritis with instability may be the first sign.
• 70% sensitivity for clinically diagnosed disease
• specificity can be poor - major limitation to diagnostic utility
  
  • positive results with SLE, various infective arthritides, neoplasia and other systemic immune diseases
• The concentration can be both prognostic and useful for monitoring - intial response and relapse