Lecture 3-VCS80630-Fall 2023-Arthritis-S.Malek.pdf

ARTHRITIS Dr. Sarah Malek VCS 80630- Small Animal Surgery Fall 2023 LEARNING OBJECTIVES • Outline the definition and classification of arthritis • Describe general etiology and risk factors in developing osteoarthritis (OA) • List the diagnostic modalities for arthritic problems and the advantages...

ARTHRITIS Dr. Sarah Malek VCS 80630- Small Animal Surgery Fall 2023 LEARNING OBJECTIVES • Outline the definition and classification of arthritis • Describe general etiology and risk factors in developing osteoarthritis (OA) • List the diagnostic modalities for arthritic problems and the advantages and disadvantages of these modalities • Describe medical management options for OA • Define the current understanding of the efficacy of medical management options available for treatment of OA • Define the role of surgical options in managing OA DEFINITION OF ARTHRITIS • Arthritis: broad term encompassing inflammatory disease processes within synovial joints. • Osteoarthritis (OA, degenerative joint disease, osteoarthrosis): Aberrant repair and eventual degradation of articular cartilage in association with alternations in subchondral bone metabolism, periarticular osteophytosis, and a variable degree of synovial inflammation (synovitis). CLASSIFICATION OF ARTHRITIS Arthritis OA Immune-mediated Primary Secondary Infective Hemarthrosis Crystal induced OSTEOARTHRITIS (OA) OA CLASSIFICATION Primary (Idiopathic) Secondary to: • Developmental disorders • Hip and elbow dysplasia, osteochondritis dissecans • Joint instability • Cranial cruciate ligament rupture (CrCLR) • Trauma = traumatic arthritis • Articular fractures, traumatic luxations IMPACT OF OA In human medicine • 26.9 million people affected in 2005 • 30% increase over 10 years • Impaired quality of life • Direct and indirect costs In veterinary medicine • Affecting 20% of adult dogs • Impaired quality of life • Associated costs • More than 60% of adult cats ETIOLOGY OF OA Genetics • Ongoing studies in canine models in pursuit of candidate genes Aging • Influences joint structure and function Gender • Well-established sex hormonal effect in humans • Contradictory results in animal models Body weight and obesity Exercise and housing ETIOLOGY OF OA Body weight and obesity • Adipokines and joint • Leptin, and Adiponectin are main adipokines implicated in cartilage turnover • Induction of these adipokines induces inflammatory mediators • High fat diet is a risk factor for OA in dogs ETIOLOGY OF OA Exercise and housing • Increased lameness with exercise in OA dogs • Housing puppies on “slippery” floors is a risk factor for hip dysplasia and OA • Research on these environmental factors is sparse or weak PATHOGENESIS OF OA Cartilage • Loss of compressive stiffness and tensile strength Synovium • Source of pro-inflammatory products and pain Subchondral bone • Inflammation • Osteophyte formation and sclerosis Innate immune system activation • Propagation of inflammation End result = Pain and mobility impairment Pathogenesis of OA COMMON SITES OF OA • Hip • Elbow • Stifle • Shoulder • Any synovial joint is at risk IMMUNE MEDIATED POLYARTHRITIS (IMPA) CLASSIFICATION OF IMPA Non-Erosive • IMPA I-IV • I: Idiopathic • II: associated with remove site of infection • III: associated with gastrointestinal disease • IV: associated with neoplasia (paraneoplastic IMPA) • Polyarthritic-polymyositis syndrome • Systemic lupus erythematosus (SLE) and SLE related disorders • Drug induced IMPA • Breed associated IMPA (e.g., Shar-Pei fever) Erosive • Rheumatoid arthritis (RA): rare in cats and dogs • Polyarthritis of Greyhound *Feline chronic progressive polyarthritis: erosive and nonerosive forms INFECTIVE ARTHRITIS (SEPTIC ARTHRITIS) ETIOLOGY OF SEPTIC ARTHRITIS Direct inoculation • Most common • Previous articular or periarticular surgeries • Penetrating trauma (bite wounds) Pre-existing OA • Less common • Increased vascularity of synovium? Hematogenous spread • Uncommon • Bacterial endocarditis • Bacterial polyarthritis of kittens and puppies SEPTIC ARTHRITIS Involved organisms • Bacteria • Dogs: Staphylococcus and Streptococcus spp. • Cats: Pasteurella multicida and Bacteroides spp. • Other organisms • Borreliosis, Ehrilichiosis, etc. • Know endemic diseases in your area • Know travel history Typically a monoarthropathy HEMARTHROSIS HEMARTHROSIS Presence of blood in the joint • Transient or persistent inflammation Etiology • Trauma • Iatrogenic • Systemic coagulopathies • Congenital deficiencies • Disease related • Neoplastic • Synovial cell tumor CRYSTAL INDUCED ARTHRITIS • • • • Extremely rare in dogs Secondary due to diet in reptiles Calcium pyrophosphate deposition in joints (pseudo-gout) Gout is not reported in dogs or cats • Sodium urate crystal deposition in joint • Dalmatians can have hyperuricosuria but do not get gout DIAGNOSIS OF ARTHRITIS Clinical signs Diagnostic imaging • Radiography • Computed tomography (CT) • Magnetic resonance imaging (MRI) • Other modalities Laboratory tests Direct joint assessment Other modalities CLINICAL SIGNS History • Acute onset: traumatic/septic arthritis, IMPA • Chronic and insidious onset • Mixed Orthopedic examination • Joint pain and stiffness • Variable degrees of lameness and muscle atrophy • Shifting lameness: IMPA or multiple joint OA • +/- Joint instability • Joint swelling: traumatic/septic arthritis, IMPA, OA flare up Physical examination • Fever can occur in septic arthritis, IMPA IMAGING MODALITIES Radiography • Most common and available • Not sensitive in early stages • Not relevant for • Synovial, subchondral bone or cartilage lesions • Does not correlate well with clinical severity Radiographic signs of arthritis • Presence of erosive lesions: erosive IMPA • Non-specific and variable in severity • Joint effusion • Intra-articular mineralization and osteophytes • Subchondral bone sclerosis IMAGING MODALITIES CT • Less sensitive for soft tissue assessment than MRI • Useful in complex joints with superimposition • Examples: elbow, tarsus, temporomandibular joint • Combined CT and arthrography • Micro-CT: research applications only IMAGING MODALITIES MRI • Superior quality and sensitivity compared to radiography • Excellent for studying joint components • Cartilage defects, volume and thickness • Non-cartilaginous abnormalities • Disadvantages: cost, equipment, requires anesthesia IMAGING MODALITIES Ultrasound Safe, low cost, minimally invasive • Limited penetration through mineralized tissues • Limited window • Interobserver variability • Scintigraphy (Technetium99m radionuclide) Combined scintigraphy and CT • SPECT : Single-photon emission computed tomography • PET/CT: Positron-emission computed tomography • Increase use in humans • Mostly research applications LABORATORY TESTS Hematology, serum biochemistry, urinalysis • Can be non-specific • None directly related to OA or traumatic arthritis • +/-Inflammatory leukogram in septic arthritis • Changes associated with subtypes of IMPA Serology • Disease specific • Antinuclear antibody assay for SLE • 4DX snap tests for Lyme disease, etc. LABORATORY TESTS Aseptic arthrocentesis Gross synovial fluid analysis • Viscosity tests for hyaluronic acid (HA) • String test • Mucin clot (Rope’s test) • Acetic acid clots hyaluronic acid • Color • Volume • Protein Synovial fluid cytology • EDTA containers • Cell population and ratio is important SYNOVIAL FLUID ANALYSIS Condition Total cell count % of in synovial fluid Mononuclear cells % of Neutrophils Normal <2 x 109/L 94-100 0-6 OA 2-5 x 109/L 8-100 0-12 Rheumatoid arthritis 8-38 x 109/L 20-80 20-80 Non-erosive IMPA 4-370 x 109/L 5-85 15-95 Infective arthritis 40-267 x 109/L 1-10 90-100 SYNOVIAL FLUID ANALYSIS Culture of synovial fluid • Aseptic collection • Synovial fluid and/or synovial membrane • No additive tube <blood culture media • Bacteria and fungal cultures Histopathological examination • Synovial biopsy DIRECT JOINT ASSESSMENT Arthroscopy or arthrotomy • Gross examination of the joint • Subjective and objective assessment of abnormalities • May be used for therapeutic interventions • Obtaining samples for test • Synovium, bone biopsies for histopathological, cytological examination and culture TREATMENT OF ARTHRITIS Septic arthritis • Joint lavage • Address cause • Culture-directed systemic antibiotic therapy • Recheck culture every 4-6 weeks until negative • Continue 4-6 weeks after negative culture Immune mediated • Immunosuppressive or immuno-modulating therapy • See your internal medicine lectures Hemarthrosis and crystal induced arthritis • Treat underlying cause All the above arthritic conditions result in secondary OA CLASSIFICATION OF ARTHRITIS Arthritis OA Immune-mediated Primary Secondary Infective Hemarthrosis Crystal induced OA MANAGEMENT No curative options available= No treatment Management • It is progressive • No approved disease modifying OA drugs (DMOADs) • Multifactorial disease Multimodal approach • Weight management • Modified activity • Medical management • Surgical management OA MANAGEMENT OA MANAGEMENT Weight management • Body weight increases initiating causes of OA such as hip dysplasia • Diet restriction has been shown to decrease prevalence and severity of OA in dogs • Adjust intake for gradual weight loss • Balance exercise with patient mobility level OA MANAGEMENT Modified activity • Regular, moderate, controlled exercise may be beneficial in OA patients • Role of physical rehabilitation in OA patients is under investigation in dogs and cats OA MANAGEMENT Medical management • Symptom-modifying agents • Candidate Disease-Modifying Agent Drugs (DMOADs) • Medical devices • Nutritional management (nutraceuticals) • Regenerative medicine (biologics) MEDICAL MANAGEMENT Symptom-modifying drugs • Non-steroidal anti-inflammatory drugs (NSAIDs) • Others • Amantidine (NMDA receptor antagonist): weak • Gabapentin (GABA analogue): little evidence • Acetaminophen (NOT in CATS!) • Combined with codeine in dogs • Codeine: weak • Corticosteroids: controversial • Tramadol: weak MEDICAL MANAGEMENT NSAIDs • Aspirin (acetylsalicylic acid) since 1899 • Mechanism of action • Cycloxygenase (COX) inhibition • Lipoxygenase (LOX) inhibition • Inhibition of neutrophil activation • Proposed central nervous system effects (LOX) Most NSAIDs PGE2 Receptors EP2 EP2 EP3 EP4 Currently Approved NSAIDs for Dogs Generic Name Mechanism of Action Carprofen COX 2 > COX 1 inhibition Deracoxib COX 2 > COX 1 inhibition COX 2 > COX 1 inhibition COX 2 > COX 1 inhibition COX 1>COX 2 and LOX inhibitor COX 2 > COX 1 inhibition Etodolac Meloxicam Tepoxalin Firocoxib Robenacoxib Galliprant COX 2 > COX 1 inhibition PGE2 receptor (EP4) antagonist Side Effects Gastric ulceration, vomiting, anorexia, liver disease, possible kidney effects Gastric ulceration, vomiting, anorexia, possible kidney or liver disease; avoid in dogs with KCS Gastric ulceration, vomiting, anorexia, possible colitis, possible kidney or liver disease Gastric ulceration, vomiting, anorexia, possible colitis, possible kidney or liver disease Gastric ulceration, vomiting, anorexia, possible colitis, possible kidney or liver disease Vomiting, diarrhea, anorexia, lethargy, pain, somnolence, hyperactivity Decreased appetite, vomiting, soft feces, diarrhea, melena Vomiting, diarrhea, anorexia, lethargy, buccal ulcer, immune mediate hemolytic anemia Currently Approved NSAIDs for Cats MEDICAL MANAGEMENT Candidate DMOADs Insufficient supportive data for clinical efficacy • Examples: • Polysulfated glycosaminoglycan (Adequan®) • Monoclonal anti-body against nerve growth factor (NGF) • 2022: Frunevetmab (Solensia™) for cats • 2023: Bedinvetmab (Librela™) for dogs Medical devices • Radiosynoviorthesis (RSO); Synovetin OA® in dogs MEDICAL MANAGEMENT Considered Food = Minimal FDA supervision Nutraceuticals • Essential fatty acids • Omega 3 fatty acids: precursors to eicosanoid hormone family • E.g., fish oil derived eicosapentaenoic acid • Moderate supportive data for clinical efficacy • Chondroitin sulfate and glucosamine sulfate & Glucosamine hydrochloride • Chondrocyte stimulation and anti-inflammatory effects • E.g., Dasuquin®, Cosequin®) • Weak evidence for clinical efficacy MEDICAL MANAGEMENT Regenerative medicine/biologics • Targeted therapies • Antagonists, antibodies, gene therapy against inflammatory mediators (anti- IL-1, TNF-α ) • Stem cell therapy • Adult multipotent stem cells • Sources: adipose tissue, bone marrow, etc. • Platelet derived products • Platelet rich plasma (PRP), Autologous conditioned plasma (ACP) • Controversial clinical efficacy results Currently not recommended as standard of care in OA treatment in people or animals MEDICAL MANAGEMENT Summary of medications in OA • NSAIDs are the only supported drug for managing OA • Omega 3 fatty acids have moderate evidence for efficacy • Everything else should be used with caution • Owner awareness of efficacy data • Side effects • Cost • Monitor evidence of efficacy data OA MANAGEMENT Surgical options for OA • All are salvage procedures • Articular surface debridement • Stimulation of fibrocartilage repair • Joint resurfacing • Partial joint replacement • Autograft, allograft, synthetic graft • Total joint replacement (i.e., hip, elbow, stifle, tarsus) • Arthrodesis • Amputation? PREVENTATIVE MEASURES Breeding strategies • Reducing OA causing diseases in population Surgical treatment of underlying causes of OA • Treating join instability • Angular limb deformity correction • Fracture stabilization • Joint incongruities TAKE HOME MESSAGES • Arthritis is an umbrella term for inflammatory joint diseases • Osteoarthritis (OA) is secondary to other arthritic pathologies, joint incongruity or trauma to the joint • OA can predispose the joint to development of septic arthritis • Medical management strategies for OA results in symptomatic relief but not cure • NSAIDs are the main pharmaceuticals used in pain management for OA patients • Surgical options once OA develops are salvage options not curative