Rheumatology Flashcards
Give the definition of a joint
Location where 2 bones meet
What are the 2 major divisions of joint disease
Inflammatory or Degenerative(OA)
Why does the classification of joint disease matter?
Treatment is different
Describe the epidemiology of OA
-more prevalent as age increases,
-previous joint trauma (e.g. footballers’ knees)
-jobs involving heavy manual labour
What is the onset of OA like?
Slow-gradual
Describe the pathological changes in OA
Cartilage loss, bony remodelling
What are the symptoms of OA
Joint pain
worse with activity, better with rest
Joint crepitus
creaking, cracking grinding sound on moving affected joint
Joint enlargement
e.g. Heberden’s nodes
Bouchard’s nodes
Limitation of range of motion
What are the typically affected joints of OA
Joints of the hand
Distal interphalangeal joints (DIP)
Proximal interphalangeal joints (PIP)
First carpometacarpal joint (CMC)
Spine
Weight-bearing joints of lower limbs
esp. knees and hips
First metatarsophalangeal joint (MTP)
What are the radiographic features of OA?
Joint space narrowing
Subchondral bony sclerosis
Osteophytes
Subchondral cysts
What are the 5 hallmarks of inflammation
- Dolor(Pain)
- Calor(Heat)
- Rubor(Redness)
- Tumor(Swelling)
- Loss of function
Physiological changes within an enflamed joint
-Increased blood flow
-Migration of white blood cells (leucocytes) into the tissues
-Activation/differentiation of leucocytes
-Cytokine production
E.g. TNF-alpha, IL1, IL6, IL17
What causes of joint inflammation are considered primary causes and what conditions do they commonly cause?
Immune-mediated (“autoimmune”)
Rheumatoid arthritis
Seronegative arthritis
Systemic lupus erythematosus (SLE)
What causes of joint inflammation are considered secondary causes(Bodily response due to noxious insult) and what conditions do they commonly cause
Infection
Septic arthritis
Tuberculosis
Crystal arthritis
Gout
Pseudogout
What causes of joint inflammation are considered sterile?
Crystal arthritis
Gout
Pseudogout
Immune-mediated (“autoimmune”)
Rheumatoid arthritis
Seronegative arthritis
Systemic lupus erythematosus (SLE)
What causes of joint inflammation are considered non-sterile?
Infection
Septic arthritis
Tuberculosis
Cause of septic arthritis
Bacterial infection of a joint
Risk factors of septic arthritis
immunosuppressed, pre-existing joint damage, intravenous drug use (IVDU)
Why is septic arthritis considered a medical emergency?
It can rapidly destroy a joint if left untreated
How does septic arthritis present?
-Acute red, hot, painful swollen joint
-Usually only 1 joint is affected* (monoarthritis-Can be polyarthritis with gonoccocus)
-Typically fever. Patient often systemically unwell
What organisms are common causes of septic arthritis?
Staphylococcus aureus, Streptococci, Gonococcus
Treatment of septic arthritis
Surgical lavage
What are the 2 main types of crystal arthritis and what’s the difference?
Gout
Caused by deposition of monosodium urate (MSU) (aka uric acid) crystals in/around joints
-> inflammation
High uric acid levels (hyperuricaemia) = risk factor for gout
Causes of hyperuricaemia:
Genetic tendency
Increased intake of purine rich foods
Reduced excretion (kidney failure)
Pseudogout
Caused by deposition of calcium pyrophosphate dihydrate (CPPD) crystals
-> inflammation
Risk factors: background osteoarthritis, elderly patients, intercurrent infection
Describe the features of gout
Abrupt onset
Usually monoarthritis
Big toe 1st MTPJ (metatarsophalangeal joint) most commonly affected (podagra)
Can also affects other joints: most frequently joints in the foot, ankle, knee, wrist, finger, and elbow
What investigations would you undertake to diagnose gout(bloods+radiographically)?
Bloods:
↑ C-reactive protein (CRP), marker of inflammation
↑ Serum urate
X-rays
-Usually normal initially
-If recurrent attacks/long-standing gout, juxta-articular erosions can develop
Joint aspiration and synovial fluid analysis for definitive diagnosis
What is the key investigation required for any septic joint
Synovial fluid analysis and aspiration
-Microbiology (gram stain, culture and sensitivities)
-Polarising light microscopy to detect crystals
How do you differentiate gout and pseudogout
What are the 2 main treatment methods of gout
Acute attack: reduce inflammation
Non-steroidal anti-inflammatory drugs (NSAIDs)
Glucocorticoids (“steroids”)
Chronic – need to reduce uric acid levels
Lifestyle – avoid purine-rich food, beer
Pharmacological: allopurinol, febuxostat (xanthine oxidase inhibitors)
3 main categories of autoimmune joint disease
Rheumatoid arthritis
Seronegative inflammatory arthritis
Systemic Lupus Erythematosus (aka SLE or ‘lupus’)
What is the primary site of pathology in rheumatoid arthritis?
Primary site of pathology is in the synovium
Synovitis = inflammation of the synovial membrane
What are the key features of rheumatoid arthritis?
Chronic arthritis
Polyarthritis
Early morning stiffness in and around joints
May lead to joint damage and destruction - ‘joint erosions’ on radiographs
Auto-antibodies usually detected in blood
Extra-articular disease can occur
e.g. ocular inflammation, interstitial lung disease, nodules, vasculitis
Describe the pattern of joint involvement in rheumatoid arthritis
Symmetrical
Affects multiple joints (polyarthritis)
Affects small and large joints, but particularly hands, wrists and feet
Commonest affected joints:
Metacarpophalangeal joints (MCPJs)
Proximal interphalangeal joints (PIPJs)
Wrists
Knees
Ankles
Metatarsophalangeal joints (MTPJs)
What is the difference between the synovium in normostasis and rheumatoid arthritis
Healthy synovial membrane:
1-3 cell layer that lines synovial joints
Contains:
macrophage-like (type A synoviocyte)
fibroblast-like (type B synoviocyte) cells
type I collagen
Functions: maintenance of synovial fluid
In rheumatoid arthritis:
The synovium becomes a proliferated mass of tissue (pannus) due to:
Neovascularisation
Lymphangiogenesis
Inflammatory cells:
activated B and T cells
plasma cells
mast cells
activated macrophages
Recruitment, activation and effector functions of these cells is controlled by a cytokine network
Excess of pro-inflammatory vs. anti-inflammatory cytokines (‘cytokine imbalance’)
What is TNF-a
The cytokine tumour necrosis factor-alpha (TNFα) is the dominant pro-inflammatory cytokine in the rheumatoid synovium
Its pleotropic actions are detrimental in this setting
Def of pleotropic
Having more than one effect
What are the actions of TNF-a
-Proinflammatory cytokine release
-Hepcidin induction
-PGE2 production
-Osteoclast activation
-Chondrocyte activation
-Angiogenesis
-Leukocyte accumulation
-Endothelial cell activation
-Chemokine release
What has been discovered to be the most effective treatment of rheumatoid arthritis
Dominant detrimental role of TNFα in rheumatoid arthritis validated by the therapeutic success of TNFα inhibition
TNFα inhibition is achieved via intravenous infusion or sub-cutaneous injection of antibodies or fusion proteins
What is the level of CRP in blood cultures of RA, OA and SA?
RA: Raised
OA: Normal
SA:Raised
OA is not inflammatory so doesn’t produce CRP
Which of RA, OA and SA has a low haemoglobin?
RA
What are the 2 types of antibodies normally found in the blood of RA patients?
- Rheumatoid factor
- Antibodies to citrulinnated protein antigen (ACPA)
What are rheumatoid factor antibodies types Ig_?
Usually IgM that bind to the Fc region of IgG
Why is testing for rheumatoid factor bad for diagnosing RA?
- Only pos in 80% of patients
- Is present in other conditions
What is citrullination?
What is the clinical test used to detect ACPAs?
anti-cyclic citrullinated peptide antibody ‘anti-CCP antibody’
What is different in testing for anti-CCP antibodies rather than rheumatoid factor?
-anti-CCP antibodies are more commonly associated with RA than RF is
-anti-CCP antibodies are also more commonly associated with more erosive/aggressive disease
What are the radiographic features of RA?
Soft tissue swelling
Peri-articular osteopenia
Bony erosions
Erosions occur only in established disease.
The aim of modern therapy is to treat EARLY before erosions (permanent damage) has occurred
Apart from X-ray, give 2 other imaging methods used to detect RA and give the radiographic signs of RA in one of them
Ultrasound (US) is a much better test for detecting synovitis. US changes in RA:
Synovial hypertrophy (thickening)
Increased blood flow (seen as doppler signal)
May detect early erosions not seen on plain X-ray
US (usually of hands and wrists) can be performed alongside clinical assessment in a dedicated early arthritis clinic
MRI can also be used but expensive and time-consuming
Give the main 3 principles of RA treatment
Early recognition of symptoms, referral and diagnosis
Prompt initiation of treatment: joint destruction = inflammation * time
Aggressive pharmacological treatment to suppress inflammation
What are DMARDs?
Disease-modifying anti-rheumatic drugs
Immunomodulatory drugs that halt or slow the disease process
Methotrexate, Hydroxychloroquine, Sulphasalazine
What are NSAIDs?
(non-steroidal anti-inflammatory drugs)
e.g. ibuprofen, naproxen, diclofenac
Historically used but increasingly less relevant
Can provide partial symptom relief but do not prevent disease progression
Unfavourable long-term side-effect profile
What is first and second line treatment for RA?
Why are glucocorticoids less commonly used in long term treatment of RA?
Poor side effect profile
Outline the overarching differences between OA and RA
What is seronegative arthritis and give a few examples
Family of conditions with overlapping clinical features and pathogenesis
Unlike rheumatoid arthritis, RF and CCP antibodies not present in blood (“seronegative”)
BUT they are immune-mediated
What is psoriatic arthritis and give its hallmarks
Psoriasis is an autoimmune disease affecting the skin
Scaly red plaques on extensriaor surfaces (eg elbows and knees)
~10% of psoriasis patients also have joint inflammation
Varied clinical presentations:
-Classically asymmetrical arthritis affecting IPJs
(interphalangeal joints)
But also can manifest as:
-Symmetrical involvement of small joints (rheumatoid pattern)
-Oligoarthritis of large joints
-Spinal and sacroiliac joint inflammation
What is reactive arthritis?
Sterile inflammation in joints following infection elsewhere in the body
Give the common infections causing reactive arthritis
urogenital (e.g. Chlamydia trachomatis)
gastrointestinal (e.g. Salmonella, Shigella, Campylobacter infections)
What is the symptomalogy/aetiology of reactive arthritis
Important extra-articular manifestations include:
Enthesitis (tendon inflammation)
Skin inflammation
Eye inflammation
Reactive arthritis may be first manifestation of HIV or hepatitis C infection
Commonly young adults with genetic predisposition (e.g. HLA-B27) and environmental trigger (e.g. Salmonella infection)
Symptoms follow 1-4 weeks after infection and this infection may be mild
Reactive arthritis NOT the same as infection in joints (septic arthritis)
How can you differentiate between reactive and septic arthritis?
Give the overall classifications of joint diseases
