Arthritis Flashcards
In a study by Pavarotti 2020 in VCOT, what was injected into canine joints with arthritis resulting in improved lameness and canine brief pain inventory scores?
Autologous and purified microfragmented adipose tissue.
Gradual improvements in kinetic data were also observed up to day 180.
In a study by Lattimer 2022 in VRU, what intraarticular injection was associated with improved CBPI responses in dogs with low to intermediate grade OA of the elbow?
A tin radiocolloid. Is retained in the joint and emits a low dose of radiation to reduce synovitis.
In a study by Shipley 2022 in JFMS, what was the affect of amantadine on owner perceived outcome measures in cats with osteoarthritis?
Outcome measures were improved with the use of amantadine compared to placebo, although activity levels were reduced as per an activity monitor.
In a study by Cunningham 2022 in JFM, what was the effect of Dasuquin supplementation on client specific outcome measures in cats with OA?
No effect was noticed as compared to placebo.
What are the broad categories of arthritis?
Inflammatory (immune mediate, infective), and non-inflammatory (degenerative).
What is the most common form of arthritis in dogs?
Osteoarthritis.
Defined as the aberrant repair and eventual degradation of articular cartilage in association with alterations in subchondral bone metabolism, periarticular osteophytosis, and a variable degree of synovial inflammation.
Is primary or secondary osteoarthritis more common?
Secondary in dogs, primary in cats.
What are some potential causes of OA?
- Genetics.
- Age.
- Body weight.
- Obesity.
- Gender status.
- Exercise, diet and housing.
How does age impact joint cartilage, potentially contributing to OA?
Increasing age results in less uniform production of aggrecan molecules byu chondrocytes, less ability to imbibe water, and reductions in compressive stiffness. Additional reductions in repair mechanisms and cellular activity favor the loss of tissue.
How does obesity potentially contribute to OA?
Diet restriction has been shown to reduce the prevalence of hip dysplasia as well as OA of the shoulder and elbow joints.
Obesity is though to contribute to overload on the joints, may alter joint alignment, and is associated with a systemic subclinical proinflammatory state (increased circulation of adipokines such as TNF and IL-6).
How does gender status potentially contribute to OA?
Neutering may affect likelihood of developing OA.
- Neutered Boxers 1.5 x more likely to develop hip dysplasia.
- Increased risk of CCLR in neutered animals.
- Males 1.8 x more likely to develop elbow dysplasia than females (effect of neutering unclear).
How does exercise, diet and housing potentially contribute to OA?
- Puppies housed on slippery surfaces may be at increased risk of hip dysplasia or OA.
- High dietary intake of fat and high proportion of energy derived from fat may be a risk factor for development of elbow OA.
- Exercise by running after balls and sticks may increase the risk factor of elbow and elbow dysplasia.
Describe the pathogenesis of OA.
What structures are involved in the process of osteoarthritis?
- Articular cartilage.
- Synovium.
- Subchondral bone.
What are the factors that lead to loss of articular cartilage during osteoarthritis?
- Degradation of the ECM results in increased water content and loss of cartilage stiffness. Chondrocytes compensate through enhanced proliferation but eventual failure of compensatory mechanisms leads to cartilage loss.
- Inflammatory cytokines Il-1, Il-17, IL-18, and TNF-a upregulate MMPs and proteolytic enzymes.
- Expression of COX-2 and prostaglandin E2 results in degradation of aggrecan and type II collagen.
- Reactive oxygen species (such as NO) inhibit matrix synthesis, activate MMPs and cause apoptosis.
- Aggrecenases and MMPs are upregulated.
How does the synovium play a role in the development of OA?
Release of cartilage breakdown products likely provokes release of collagenase, proteolytic enzymes, and catabolic cytokines (IL-1B, TNF-a) from macrophages and synovial cells.
May also be a key tissue in the origin of pain.
How does the subchondral bone play a role in the development of OA?
Osteophyte formation and subchondral bone sclerosis are key features of OA. Osteophytes arise in the periosteum at the junction of the cartilage and bone, and can contribute to clinically relevant symptoms.
What is thought to be responsible for pain in OA?
Normal loading of the joint does not induce pain, however this is not the case with OA. May be due to:
- During OA C-fibers (or silent nociceptors) are recruited and increase input to the spinal cord (may be mediated by inflammatory mediators; TNF-a, IL-6, PGE, substance P).
- Central sensitization (COX enzymes may play a role). Inhibition of COX-2 may inhibit NO-induced cell death.
What is an example of primary OA?
Osteoarthritis of the small joints of the manus and pes.
Cats may also have primary OA of the elbow.
What is an example of a validated owner questionnaire for the assessment of OA in dogs?
Canine orthopedic index.
What are some radiologic features of OA?
Note: osteophytes are not pathognomonic for OA (i.e. they can be induced by other types of arthritis). Their value as a staging tool is also controversial.
What are some diagnostic tools in the assessment of OA?
- Radiography.
- MRI: allows assessment of soft tissue and bony structures. The thin nature of canine cartilage may make cartilage assessment challenging. Contrast enhanced MRI may aid in detection of differences in glycosaminoglycan content of the cartilage.
- CT: not that useful for assessing OA, but can be used to identify underlying pathology/initiating cause.
- Scintigraphy using technetium linked to a diphosphonate carrier can provide information on bone remodelling. Not yet clinically studies in dogs and cats.
- Arthroscopy: most useful modality, allows assessment of cartilage with degeneration graded by the modified outerbridge scale.
- Synovial fluid analysis: allows categorization of the type of arthritic process present.
What are some management options for OA?
- Weight management (mitratapide; microsomal triglyceride transfer protein inhibitor).
- Exercise.
- Medical management:
a. Symptom modifying agents (NSAIDS, amantadine, gabapentin, acetaminophen, codeine, corticosteroids).
b. Structure modifying agents (polysulfated glycosaminoglycans, pentosan polysulfate).
c. Nutritional management (chondroitin sulfate, glucosamine sulfate, essential fatty acids).
d. Mesenchymal stem cell therapies.
- Surgical management (joint debridement and micropick, joint replacement. arthrodesis and salvage procedures).
- Euthanasia.
What are the expected cell counts of the synovial fluid for various forms of arthritis?
Describe the archidonic acid pathway.
What is the predominant eicosanoid associated with inflammatory conditions produced by the arachidonic acid pathway?
PGE2
Increased in synovial fluid with OA. Associated with vasodilation, increased vascular permeability, edema, decreases the nociceptive threshold.
What are the two isoforms of COX?
COX-1: constitutive form.
COX-2: inducible form (upregulated in the presence of inflammation).
What is the COX-1:COX-2 ratio of an NSAID?
The amount of drug required to inhibit 50% activity of each enzyme.
What is a potential effect of COX inhibition on leukotriene production from arachidonic acid?
Inhibition of COX may cause an increase in production of leukotrienes.
LTB4 is a potent chemotactic agent that attracts neutrophils and inflammatory cells. This may explain the less than complete relief provided by NSAIDs, and production of COX/LOX inhibitors may be beneficial.
Arthodesis of which joints is most well tolerated in dogs?
Tarsus, carpus, shoulder.
Stifle and elbow result in marked functional abnormalities.
What is the cause of IMPA?
Unknown. May involve abnormal B-cell and T-cell interaction with subsequent production of rheumatoid factor, antibodies, and release of inflammatory cytokines.
Immune mediated glomerulonephritis and ITP may occur concurrently due to immune complex deposition or autoantibody formation.
In erosive forms of IMPA what causes the erosive disease?
Proliferative granulation tissue (pannus) forms and invades the margins or articular cartilage and subchondral bone. Release of proteolytic enzymes is associated with destruction of the ECM.
What are the clinical signs of IMPA?
May be variable, acute or chronic.
Most common cause of pyrexia in dogs with fever of unknown origin.
Severe erosive forms may result in joint deformities and limb instability.
How is diagnosis of IMPA confirmed?
- Cytology (requires samples from three different joints).
- Synovial biopsy if fluid unable to be obtained.
- Additional testing to classify the type of IMPA:
a. Articular imaging.
b. CBC/biochem, urinalysis
c. Serology (for rheumatoid factor or anti-nuclear antibody titer [systemic lupus erythematosus]).
What CBC/biochem/urinalysis changes might be seen in a patient with IMPA?
CBC: anemia of chronic disease, thrombocytopenia, leukocytosis, neutrophilia with a left shift.
Biochem: azotemia, hepatic enzymopathy, decreased serum albumin (protein losing nephropathy), increased globulins.
Urinalysis: proteinuria (glomerulopathy).
What are the classifications of IMPA?
1) Nonerosive.
a. Idiopathic (type 1, 50%)
b. Infection remote from joint (type 2, 25%)
c. Associated with GI disease (type 3, 15%)
d. Paraneoplastic (type 4)
e. Multisystem disease (systemic lupus erythematosus).
f. Breed associated.
2) Drug induced.
3) Erosive
a. Rheumatoid arthritis
b. Polyarthritis of Greyhounds
c. Feline chronic progressive polyarthritis
What is the most common type of IMPA?
Non-erosive idiopathic.
Carpal and tarsal joints most commonly affected by pain and swelling.
Diagnosis of exclusion.
Can treatment of the underlying infection or neoplasia in cases of type 2 or 4 IMPA lead to resolution of signs?
Yes, but not always.
What is the most common drug implicated in drug induced IMPA?
Sulfonamides (particularly large breed dogs, especially Dobermans).
Withdrawal of the drug normally results in resolution of the clinical signs in 1-3 days.
What is systemic lupus erythematosus?
Multisystem immune mediated disorder associated with the appearance of antinuclear antibodies.
How is systemic lupus erythematosus diagnosed in dogs?
Presence of major clinical signs AND presence of antinuclear antibodies.
Major clinical signs include; skin lesions, polyarthritis, hemolytic anemia, glomerulonephritis or substantial proteinuria, polymyositis, leukopenia, and thrombocytopenia.
Breed associated IMPA in the Shar-Pei is associated with what disease?
Amyloidosis (Shar-Pei fever). Particularly effects the tarsal joints. Prognosis is poor due to amyloid induced renal failure.
What characterizes rheumatoid arthritis?
Deforming symmetric polyarthritis, associated with synovitis of joints and tendon sheaths, articular cartilage loss, erosion of juxta-articular bone, and, in most patients, the presence of IgM rheumatoid factor.
How is rheumatoid arthritis diagnosed?
Classical rheumatoid arthritis is diagnosed when seven of the following criteria are met. Definite rheumatoid arthritis when five are satisfied.
What joints are most commonly affected by rheumatoid arthritis?
Stifle, then carpus, hip, elbow, tarsus.
Bilaterally symmetric arthritis is common. Erosions may take time to develop.
Is an elevated rheumatoid factor definitively diagnostic for rheumatoid arthritis?
No, is only one of the criteria used. Can be elevated in many chronic inflammatory disease processes.
What is feline chronic progressive polyarthritis?
An immune mediated polyarthritis most commonly seen in young male cats.
Has both erosive and non-erosive forms. Can be similar to rheumatoid arthritis but are rheumatoid factor negative and typically effects less joints.
What are the criteria for feline chronic progressive polyarthritis?
- Erosive polyarthritis
- Marked proliferation of periosteal new bone at affected joints
- Negative for rheumatoid factor in the blood
- Enthesopathies
- Disease affecting hocks and carpi
What is the treatment for IMPA?
- Elimination of the inciting cause (if possible).
- Immunosuppression (prednisone +/- cyclophosphamide, azathioprine, cyclosporine, leflunomide).
- TNF-a antagonists used for the treatment of rheumatoid arthritis in people, but have not been used in dogs/cats.
- Surgical management (arthrodesis, excision arthroplasty, joint arthroplasty [joint replacement]).
What are potential causes of bacterial infective arthritis?
Bacterial invasion of joints from hematogenous localization, direct penetration, or local spread from adjacent tissues.
Post-operative infection is the most common cause.
What are some risk factors for development of bacterial infective arthritis?
Previous surgery, preexisting joint disease.
The stifle, elbow and carpus are most frequently affected.
What are the most common bacteria implicated in septic arthritis in dogs and cats?
Dogs: staph and strep species.
Cats: pasteurella and bacteroides.
What are the two types of post-operative bacterial septic arthritis?
Type 1: typically acute and associated with complications of wound healing, and signs of systemic infection.
Type 2: chronic infections with a delayed presentation (6-24 months) due to a small inoculum or low bacterial virulence.
When is bacterial septic arthritis in multiple joints most likely to occur?
Immature patients or immunocompromised.
In puppies or kittens it is typically secondary to omphalophlebitis, streptococcal pharyngitis, or uterine or mammary infection in the bitch/queen.
Staphylococcus canis is the most frequently implicated organism.
What determines the extent of articular cartilage damage in patients with bacterial septic arthritis?
Number, type, and virulence of the organism present; the extent to which the organisms multiply; and the local and general immunity of the patient.
What are the sequelae of bacterial infection in the joint?
- Release of proteolytic enzymes (MMPs) from synovial cells.
- Release of inflammatory cytokines (TNF-a, IL-1) from macrophages in the synovium.
- Degradation of aggrecan and the collagen network.
- Deposition of fibrin.
How is bacterial septic arthritis diagnosed?
- Typical clinical signs and history
- Synovial fluid analysis (>50 x 10^9 cells/L and 40% neutrophils strongly suggested of sepsis).
- Culture (recommended in blood culture bottle). Frequently negative even with infection.
Definite diagnosis if all 3 criteria are met, probably if 1 and 2 are present.
If there is no response to three different antimicrobials when treating presumptive septic arthritis a diagnosis of probable IMPA can be made.
Can erosive changes occur in the joint secondary to septic arthritis?
Yes, can appear within 10-14 days in uncontrolled infection.
What are treatment options for bacterial septic arthritis?
- Systemic antimicrobials for 28 days with repeat arthrocentesis and synovial fluid analysis at the end of the period. If the cell count has not returned to normal and the neutrophil percentage is still above 3%, continued antimicrobial therapy is recommended.
+/- surgical intervention (although no indications this is warranted unless gross contamination of the joint is evidence. This can include:
1) Joint irrigation.
2) Arthroscopic inspection and lavage.
3) Open exploratory laparotomy.
+/- use of local AB delivery systems (can be absorbable, such as calcium sulfate, or nonabsorbable, such as PMMA).
How quickly should a response be observed following initiation of antimicrobial therapy for bacterial septic arthritis?
24-48 hours
Aside from bacteria, what are some other infective causes of arthritis?
- Borrelial.
- Mycoplasmal.
- Protzoal.
- Fungal.
- Rickettsial.
- Mycobacterial.
