Arthritis Flashcards
What is rheumatoid arthritis?
An autoimmune disorder primary affecting joints resulting in warm, swollen, painful joints
Symptoms typically worse after rest- morning stiffness in and around joints
Affects multiple joints
What is the main kind of inflammation in rheumatoid arthritis?
Synovial inflammation Includes: - synovial joints - Tenosynovium surrounding tendons - Bursa Synovial membrane is abnormal in rheumatoid arthritis
What occurs to the synovium in rheumatoid arthritis?
Synovium becomes a proliferated mass of tissue due to:
Neovascularisation
Lymphangiogenesis
Inflammatory cells: activated B and T cells, plasma cells, mast cells, activated macrophages
What is the role of cytokine in rheumatoid arthritis?
There is a cytokine imbalance between pro-inflammatory and anti-inflammatory cytokines (cytokine imbalance)
The cytokine TNF- alpha is the dominant pro-inflammatory cytokine in rheumatoid synovium.
What are the roles of TNF- alpha?
Osteoclast activation
Chondrocyte activation (cartilage destruction)
Angiogenesis
Leukocyte accumulation
Endothelial cell activation (upregulation of E-selectin and VCAM-1)
Chemokine release (RANTES, MCP-1, IL8, SDF-1)
Pro-inflammatory cytokine release (IL1, IL6, IL23, GM-CSF)
Hepcidin induction
PGE2 production
How can we treat rheumatoid arthritis?
TNF-alpha inhibition- can be done through injecting antibodies or fusion proteins
What 2 antibodies are found in rheumatoid arthritis?
Rheumatoid factor
Antibodies to citrullinated protein antigens (ACPA)
What are rheumatoid factor antibodies?
Antibodies recognise the Fc portion of IgG as their target antigen
Typically IgM antibodies
They form complexes which trigger inflammation
What are antibodies to citrullinated protein antigens?
Antibodies to citrullinated peptides are highly specific for rheumatoid arthritis
E.g. Anti- cyclic citrullinated peptide antibody (anti-CCP antibody)
Cirtrullination of peptides is mediated by enzymes termed peptidyl arginine deiminases
What are symptoms of rheumatoid arthritis?
Chronic arthritis:
- polyarthritis- swelling of small joints of hands and wrists common
- symmetrical
- may lead to joint damage and destruction
Extra-articular disease:
- rheumatoid nodules
- fever
- weight loss
Subcutaneous nodules
What causes subcutaneous nodules?
Central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
Associated with: rheumatoid factor, extra- articular manifestations, severe disease
What drugs can we use to treat rheumatoid arthritis?
Disease modifying anti-rheumatic drugs (DMARDs)
1st line treatment is methotrexate (folate antagonist) in combination with hydroxychloroquine or sulfasalazine
2nd line treatment is biological therapies inc. Janus kinase inhibitors: Tofacitinib and Baricitinib
Glucocorticoid therapy- avoid long term use
Multi- diciplinary approach e.g. physiotherapy, occupational therapy, surgery etc.
What biological treatments can we use for rheumatoid arthritis?
These are proteins that specifically target a protein such inflammatory cytokines e.g:
- Inhibition of TNF-alpha- antibodies (infliximab), fusion proteins (etanercept)
- B cell depletion- Rituximab (antibody against B cell antigen CD20)
- Mediation of T cell co-stimulation- Abatacept
- Inhibition of IL-6 signalling- Tocilizumab (RoActemra) and Sarilumab (Kevzara)- both antibodies against IL6 receptor
What is septic arthritis?
Bacterial infection of synovial joint (usually caused by spread from blood)
Its a medical emergency and needs to be treated immediately
Usually 1 joint is affected (monoarthritis)
What are risk factors and symptoms of septic arthritis?
Risk factors: Immunosupressed, pre-existing joint damage, IV drug use
Symptoms: Acute pain, red, hot, swelling of joint
How is septic arthritis diagnosed and what are common organisms that cause it?
Joint aspiration. Send sample for gram stain and culture
Common organisms: s. aures, streptococci, gonococcus (usually affects multiple joints and less likely to cause joint destruction)
How is septic arthritis treated?
Surgical washout and IV antibiotics
What is crystal arthritis?
There are 2 main types:
Gout
Pseudogout
What is gout crystal arthritis?
Caused by deposition of urate (uric acid) crystals
High uric acid levels (hyperuricaemia) is a risk factor
Causes of hyperuricaemia = genetic tendency, increased uptake of purine rich foods, reduced excretion (kidney failure)
What is pseudogout crystal arthritis?
Caused by deposition of calcium pyrophosphate dehydrate crystals (CPPD)
Risk factors: background osteoarthritis, old age, intercurrent infection
What are clinical features of gout?
Typically presents as acute monoarthritis of rapid onset First metatarsophalangeal joint affected most commonly Also frequently affected: joints in foot, ankle, knee, wrist, finger and elbow Crystal deposits (tophi) may develop around hands, feet, elbows and ears
How does gout present on an X-ray?
X-rays may show juxta articular ‘rat bite’ erosions
These erosions are specific to gout
How can we diagnose crystal arthritis?
Aspirate fluid and examine under a microscope using polarised light
Gout: needle shaped crystals with negative birefringence
Pseudogout: rhomboid shaped crystals with positive birefringence
What is psoriatic arthritis?
Psoriasis is an autoimmune disease affecting the skin
~10% of psoriasis patients have joint inflammation
Rheumatoid factors arent present
Classically asymmetrical arthritis affecting interphalangeal joints
How can psoriatic arthritis also manifest as?
Symmetrical involvement of small joints
Spinal and sacroiliac joint inflammation
Oligoarthritis of large joints
Arthritis mutilans- bones around joint get absorbed
What is reactive arthritis?
Sterile inflammation in joints following infection, especially urogenital and GI infection
May first be manifestation of HIV or Hep C
Commonly affects young adults with genetic pre-disposition and environmental trigger
Symptoms follow 1-4 weeks after infection
What are important extra-articular manifestation of reactive arthritis?
Enthesitis (tendon inflammation)
Skin inflammation
Eye inflammation
What is systemic lupus erythematosus?
Lupus means multi-system autoimmune disorder
Multi-site inflammation
Often affects joints, skin, kidney, lungs, CNS
What causes SLE?
Antibodies are directed against components of cell nucleus
How can we diagnose SLE?
Detection of:
- Antinuclear antibodies: Higly sensitive for SLE but not specific. A negative test rules out SLE but a positive test doesn’t mean SLE
- Anti- double stranded DNA antibodies (anti-dsDNA Abs): highly specific for SLE in context of appropriate clinical signs
What are symptoms of SLE?
A malar or butterfly rash
What is osteoarthritis?
A long term chronic disease characterised by deterioration of cartilage joints which results in bones rubbing together creating stiffness, pain and impaired movement
It affects the chondral cartilage
Inflammation occurs in late disease
What causes degradation of articular cartilage membrane?
Inflammatory mediaters inc. :
- Proteinases (e.g. metalloproteinases and aggrecanases)
- Inflammatory cytokine ( IL-1beta and TNF-alpha) which enhance synthesis of proteinases and the catabolic factors
What are risk factors of osteoarthritis?
Age Obesity Hereditary Females gender, menopause RA sequellae Osteoneurosis Oestrogen deficiency Metabolic syndrome Injury e.g. cruciate ligament rupture Infection disease involving bone
What does osteoarthritis mainly affect?
Knee
Hip
Spine
Fingers
What are symptoms and signs of osteoarthritis?
Joint pain- worse with activity, better with rest
Joint crepitus- creaking, crunching, grinding sound
Joint instability
Joint enlargement
Joint stiffness after mobility
Limitation of range of movement
What are radiographic features of osteoarthritis?
Joint space narrowing
Subchondral sclerosis
Osteophytes
Subchondral cysts
How is osteoarthritis diagnosed?
Look- any deformities
Feel- can you feel fluid?
Move- what is the range of movement?
Special tests- e.g. anterior drawer to test anterior cruciate ligament
What are conservative treatments of osteoarthritis?
weight loss analgesics physiotherapy avoid exacerbating activity Injections
What injections can be given for osteoarthritis?
Steroids
Lubrication gel
Platelet rich plasma
Stem cells?
What are operative treatments of osteoarthritis?
Replace (hip/ knee) Realign (knee/ big toe) Exercise (toe) Fuse (big toe) Athroscopy if loose bone in joint Denervate (wrist)
What is the impact of strengthening exercises in osteoarthritis?
Decrease pain and increase function
Physical training rather than passive therapy
What are reconditioning exercises?
Low impact, continuous movement for 15- 30 mins 3x a week
