301 Arthritis Flashcards
What are rheumatic diseases?
Autoimmune, inflammatory disease caused by immune system affecting joints, tendons, ligaments muscles, bones & other organs
What is joint pain?
Loss of motion in a joint(s), localised inflammation (swelling, redness & warmth in affected area)
Common rheumatic diseases
Gout
Osteoarthritis
Septic arthritis
Spondylolisthesis
Rheumatoid arthritis
Seronegative spondarthritides
Reactive arthritis
What is osteoarthritis?
Onset
Relation
Affects what?
- Degenerative joint disease or osteoarthrosis, mechanical abnormalities, degradation of joints include articular cartilage & subchondral bone
- Slow
- Not related to any significant constitutional disorder
- Muscles not directly affected
Osteoarthritis signs and symptoms
Pain, causing loss of ability and often stiffness
Osteoarthritis prevalence
Most people >50 have some form
Not associated with raised ESR/CRP
Hand OA nodal osteoarthritis DIP joint or Heberden’s nodes
40% people >75 have knee OA
Causes & risk factors of osteoarthritis
- Obesity
- Traumatic injuries
- Repetitive stress injuries
- Aging
- Metabolic bone diseases
Management and treatment of osteoarthritis:
Lifestyle modification
Medications
Alternative treatments
- Weight loss, moderate exercise (with advice only), gait training
- Acetaminophen - PCM is 1st line
NSAIDs oral or topical such as naproxen, diclofenac - Glucosamine & chondroitin (help build cartilage), Vit C & fish oil, avocado-soybean, acupuncture, Tai Chi
What is spondylosis?
Degeneration of spine, commonly cervical & lumbar regions
OA of spine
Spinal condition degeneration of intervertebral discs L5/S1, L4/5 & neck
Spondylosis causes & risk factors
Daily wear & tear over time
Genetic tendency, being overweight, sedentary lifestyle (job) lack of exercise, injured spine or spinal surgery, smoking, mental health conditions, psoriatic arthritis
Spondylosis management
Analgesic, physical therapy, improvement in posture, alternative treatments
What is spondylolisthesis?
Cervical presents as?
Treatment
- More severe form of spondylosis
Slipped vertebra (1 bone of spine slips forward over another, causing damage to spinal structure)
Severe nerve pain (sciatica)
L5/S1 & C2/C3 - Cervical presents with finger tingling & headaches
Treat NSAIDs, amitriptyline
Cauda equina syndrome - severe spinal stenosis
What is septic arthritis (infectious arthritis)?
Caused by bacteria, however, mycobacteria, virus & fungi also implicated in few cases
Increase in use of prosthetic joints is increasing infection (2-10%)
How does septic arthritis happen?
Microorganism may invade joint by direct inoculation, by contiguous spread from infected periarticular tissue or bloodstream (more common)
Normal joint has protective components (synovial cells & synovial fluid)
Rheumatoid arthritis & systemic lupus erythematosus hamper this function, resulting in increased infection risk
Septic arthritis aetiology
- N.gonorrhoea & S.aureus - common with pathogenic invasion
- GI pathogens (Salmonella sp., Campylobacter jejuni, C difficile, Shigella sonnei, E histolytica) in reactive/post-exposure process cases
- Anaerobes isolated from 10% patients
- Viral infections may cause direct invasion
What do septic arthritic patients present with?
Infected joint with triad of fever (40-60%), pain (75%) and impaired range of motion along with low grad fever
Most common joint is knee (50%)
Septic arthritis treatment
- Adequate & timely infected synovial fluid drainage
- Appropriate antimicrobial therapy
- Immobilisation of joint to control pain
Antibiotic therapy (ceftriaxone, ciprofloxacin, cefixime, oxacillin, vancomycin, linezolid)
Seronegative spondyloarthropathy: family of joint disorders
- Ankylosing spondylitis (AS)
- Psoriatic arthritis (PsA)
- Inflammatory bowel disease (IBD) associated arthritis
- Reactive arthritis (formerly Reiter syndrome; ReA)
- Undifferentiated SpA
Often present with inflammatory joint pain with morning stiffness lasting for hours & improves with activities
NSAIDs often used to improve symptoms
Ankylosing spondylitis: prevalence
More common young men>women
Starts as lower back pain-joints where spine attaches to pelvic (sacroiliac joints) - stiffness, pain and poor sleep
Link males with human leucocyte antigen HLA B27
Movement with gentle exercise
NSAIDs, sulfasalazine, hydroxychloroquine & adalimumab or etanercept for severe active ankylosing spondylitis
What is psoriatic arthritis?
Common symptoms
Treatments
Synovitis which occurs in psoriasis individuals but without serum rheumatoid factor (a form of inflammatory seronegative spondyloarthropathy)
60% people psoriasis precedes arthritis
Spondylitis common & finger swelling
Methotrexate is commonly used
Etanercept & infliximab severe case
What is reactive arthritis?
Short-lived painful joint swelling shortly after a bowel, genital infection
What is systemic lupus erythematosus?
Polyarthritis with acute onset and attacks own healthy organs and tissues
Less joint disturbance than rheumatoid
Symptoms of systemic lupus erythematosus:
Mouth
Skin
Heart
Abdomen
Blood
Muscle and joints
Kidneys
Lungs
Others
- Mouth & nose ulcers
- Butterly flash & red patches
- Endocarditis, atherosclerosis, inflammation of the fibrous sac
- Severe abdo. pain
- Anaemia, high BP
- Pain & arthritisaches, swollen joints
- Haematuria
- Pleuritis, pneumonitis, pulmonary embolism, pulmonary haemorrhage
Systemic lupus erythematosus:
Counselling points
Treatments
- Avoid sun, more common in younger women, autoimmune
- Hydroxychloroquine, low dose prednisolone, methotrexate, rituximab if severe
What is rheumatoid arthritis?
Signs and symptoms
Causes
- Autoimmune disease due to chronic, systemic inflammatory disorder, usually affects joints symmetrically, may initially begin in couple of joints only, most frequently attacks wrists, hands, elbows, shoulders, knees & ankles
- Flexible synovial joins are affected
- Herpes virus, hormone, environment, multiple genetic alleles, family Hx of RA, autoimmunity
Sarcoidosis:
Symptoms
Types
Treatment
- Weight loss, fever
- Red swollen tissue called granulomas mainly in lungs & skin
- Acute, chronic
- MTX, prednisolone, hydroxychloroquine, infliximab
Rheumatoid arthritis progression
Progressive involvement of joints usually starts in small joints
Anaemia common
Rheumatoid factor
TATT (tired all the time)
Changes in RA affected joints:
Synovial membrane
Synovial liquid
Cartilage
Capsule
Bone
- Inflamed
- Major cell types - neutrophils
- Cartilage thinning/loss
- Inflammation, pannus (major cells T-lymphocytes, macrophages), pannus (minor cells - fibroblasts, plasma cells, endothelium, dendritic cells)
- Bone loss
Rheumatoid arthritis symptoms
Lumps
Fatigue
Joint pains
Anaemia
Tenderness
Joint stiffness
Diagnostic criteria (patient must present t least 4 of below criteria)
- Morning stiffness
- At least 3 joints involved
- Hand joints
- Symmetrical arthritis
- Rheumatoid nodules
- Positive rheumatoid factor
- Radiographic changes
Rheumatoid arthritis: treatment
- Analgesic and NSAIDs
- Steroids
- Disease modifying anti-inflammatory drugs (DMARDs)
- Biologics
- Improved QoL
External triggers of rheumatoid arthritis
Cigarette smoking, infection or trauma lead to autoimmune reaction
Clinical presentation of rheumatoid arthritis
- Insidious onset with fever, malaise, arthralgias, weakness before progress to joint inflammation
- Persistent symmetric polyarthritis (synovitis) of hands & feet, progressive articular deterioration, difficulty performing activities of daily living (ADLs), other constitutional symptoms
Common sides of rheumatoid arthritis:
Upper extremities
Lower extremities
- Metacarpophalangeal joints, wrists, elbows, shoulders
- Ankles, feet, knees, hips
Rheumatoid arthritis: epidemiology
- Globally 3 per 10,000 cases with 1% prevalence (peak 35-50 yrs)
- Women 3x more affected, difference diminished with older age
- 1st degree relactive with 2-3 fold increase risk
- About 1% of UK population
- Adults & children: common onset (30) 40-50 years, older onset in men
Rheumatoid arthritis: risk factors
Genetics
Lifestyle
Hormonal
- HLA-DR4 allele increases severity & development
- Increased smoking duration linked with increasing complexity/symptoms, red meat intake, vit D deficiency, excessive coffee consumption, high salt intake
- Disproportionate between female & male (prolactin)
Rheumatoid arthritis pathophysiology:
Phase I
Phase II
Phase III
Phase IV
- Interaction (genetic & environmental risk factors)
- Production of RA autoantibodies (rheumatoid factor & anti-cyclic citrullinated peptide (anti-CCP)
- Begin arthralgia or joint stiffness with no clinical evidence of arthritis
- Development of arthritis (early undifferentiated arthritis)
Rheumatoid arthritis pathophysiology: cytokines
B and T cells inappropriately enter joint releasing…
TNF-a
IL-1, 6, 8
TGF-b (transforming growth factor)
FGF (fibroblast growth factor)
PDGF (platelet-derived growth factor)
Which cause synovium to release proteolytic enzymes, destroying bone & cartilage
Rheumatoid arthritis diagnosis:
Combination of
Differential diagnosis
- History, symptoms, blood tests, X-ray
- Ankylosing spondylitis, gout, polymyalgia, psoriatic arthritis, systemic lupus erythematous, tuberculosis
Diagnostic criteria of rheumatoid arthritis
ACR/EULAR 2010 Rheumatoid Arthritis Classification Criteria
Joint involvement, serology, acute-phase reactant, duration of symptoms
Rheumatoid arthritis lab test findings:
Inflammatory markers (ESR/CRP)
IgM-RF
Anti-CCP
ANA
ENA
Alk phos, platelets, WCC
Albumin
- Usually raised in active disease
- Present 80% of RA
- Present in most of RA
- Differentiate types of disease
- Same as above
- Raised
- Decreased
Serology in rheumatoid arthritis: C reactive protein (CRP)
- Measures a specific acute-phase reactant and is more specific
- Rises and falls more quickly than ESR
- More expensive
Present peaks in levels during flare ups and troughs in remission
Serology in rheumatoid arthritis: erythrocyte sedimentation rate (ESR)
- Affected by different factors therefore is less accurate than CRP
- Decreases slowly after inflammation subsides
Present peaks in levels during flare ups and troughs in remission
Serology in rheumatoid arthritis: rheumatoid factor (RF)
- Not an indicator of RA but in already diagnosed RA being RF seropositive indicates inclination towards a more aggressive symptomatology
Serology in rheumatoid arthritis: Anti-cyclic citrullinated peptide antibody (Anti-CCP)
- More specific than RF with less false positives
- More expensive than RF
Non-pharmacological management of RA
Physiotherapy
Exercise, diet
Psychological/education
Stress reduction
Surgical interventions
Pharmacological management of RA
NSAIDs
Glucocorticoids
DMARDs
Biologicals
Rheumatoid arthritis: analgesics and NSAIDs
Pain is predominantly inflammatory
NSAIDs can worse CV risk factors associated to RA
Role for paracetamol, opioids and TCAs
Pro-thrombotic effect of COX2 inhibitors
Consider oral NSAIDs (including traditional and COX2 selective) to control pain or stiffness
Acknowledge GI, liver & cardio-renal toxicity & risk factors like age & pregnancy
Rheumatoid arthritis: glucocorticoids
Offer short-term treatment to manage flares in adults with recent-onset or established disease to rapidly decrease inflammation
In adults with established, continue long-term when long-term complications have been discussed AND all other treatments offered
Rheumatoid arthritis: steroids
Medium length course of oral prednisolone starting with 60mg/day gradually reduced to 7.5mg over 7 weeks
Methylprednisolone acetate (Depo-Medrone) 120mg IM on PRN basis
DMARDs: Methotrexate
S/Es
Gold standard for RA but with associated risks
Liver impairment, neutropenia, anaemia, pneumonitis, nausea
DMARDs: sulfasalazine
S/Es
Pro-drug, activated in colon in sulfapyridine with anti RA effects due to inhibition of transcription factors
Cough, diarrhoea, fever
DMARDs: leflunamide
S/Es
Inhibits replication of activated lymphocytes
Diarrhoea
DMARDs: hydroxychloroquine
Interferes with antigen presentation & activation of immune response
Ocular toxicity
Rheumatoid arthritis: DMARDs
Offer 1st line cDMARD monotherapy ideally within 3 months of diagnosis
(Methotrexate, leflunomide, sulfasalazine)
Escalate dose as tolerated
Consider short-term bridging with glucocorticoid
Offer additional cDMARD in combo
(Oral methotrexate, leflunomide, sulfasalazine, hydroxychloroquine)
Rheumatoid arthritis: biologicals
Biologic meds. originated from living cells
Large, highly complex molecular structures
Classified according to MOA: TNF-alpha inhibitors, interleukin inhibitors, Janus Kinase inhibitors, phosphodiesterase type 4 inhibitor, T cell co stimulator
1st TNF alpha inhibitor was infliximab
Expensive
Rheumatoid arthritis: biologicals in combination
Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab & abatacept, ALL in combo with methotrexate recommended if:
- Disease is severe, DAS28 >5,1 and
- Disease not responded to intensive combo of DMARDs and
- Companies provide certolizumab pegol, golimumab, abatacept & tocilizumab as agreed with patient access schemes
(Can be used without methotrexate due to C/I or intolerance when above criteria met)
Rheumatoid arthritis: treatment for adults with severe active RA who have inadequate response to DMARDs including 1 TNF inhibitor
Rituximab in combo with methotrexate
Given no more frequently than every 6 months
Only give if adequate response from initiation (improved DAS28 1.2 points or more)
Rheumatoid arthritis: typical patient journey
Patient present to GP
Initiation analgesia/NSAIDs and referred to rheumatology
If diagnosis RA confirmed treatment with 1 or 2 DMARDs start
If patient DAS29 remains >5.2 after 6 months, biologic started
What autoimmune conditions are related to reactive arthritis?
RA: A disease where the immune system attacks the body, which can cause symptoms similar to lupus
Ankylosing spondylitis: A disorder in the group of spondyloarthritidies, which also includes ReA
How is tuberculosis linked to autoimmune disorders?
- Tricks immune system into attacking own lung tissue - autoimmunity, causing eye and joint inflammation & skin rashes
- Have autoantibodies as result of imbalanced immune response
- Pulmonary TB and Vit D deficiency have high autoantibodies
- Immune dysregulation related to TB can reactive TB in inflammatory diseases
Infliximab MOA
Binding to soluble and insoluble forms of TNF-a so cannot bind to receptors
Inhibiting TNF-a by blocking intracellular signalling that leads to gene transcription & biologic activity
Infliximab suppresses immune system, reducing inflammation
