Introduction to Rheumatology Flashcards
what does rheumatology deal with?
diseases of MSK system including:
joint, tendons, ligaments, muscles, bones
what is a joint?
where 2 bones meet
what is a tendon?
cords of strong fibrous collagen tissue attaching muscles to bone
what are ligaments?
flexible fibrous connective tissue which connects 2 bones
what are the components of a synovial joint?
synovium
synovial fluid
articular cartilage
what is the synovium?
1-3 cell deep lining containing macrophage-like phagocytic cells (type A synoviocytes) and fibroblast like cells that produce hyaluronic acid (type B synoviocyte)
type 1 collagen
what is synovial fluid?
hyalauronic acid-rich viscous fluid
what is articular cartilage made up of?
type II collagen
proteoglycan (Aggrecan)
what is arthritis?
disease of joint
what are the divisions of arthritis?
osteoarthritis (degenerative arthritis)
inflammatory arthritis (main type is rheumatoid arthritis_
what is inflammation?
physiological response to deal with injury/infection
what can excess/inappropriate inflammation reactions cause?
damage host tissue
what are the clinical signs of inflammation on examination?
- RED (rubor)
- Pain (dolor)
- Hot (color)
- Swelling (tumor)
- Loss of function
what pathological, cellular and molecular changes occur during inflammation?
- Increased blood flow
- Migration white boood cells (leucocytes) into tissues
- Activation/ differentiation of leucocytes
- Cytokine production e.g TNF-alpha, IL1, IL6, IL17
what are the causes of joint inflammation?
- Crystal arthritis
- Gout
- Pseudogout
- Immune-mediated (‘autoimmunie)
- Rheumatoid arthritis
- Seronegative spondyloarthropathies
- Connective tissue diseases
- Infection
- Septic arthritis
- TB
what is gout caused by?
deposition of urate (uric acid) crystals -> inflammation
what is a risk factor for gout?
high levels uric acid (hyperuricaemia)
what are the causes of hyperuricaemia?
- Genetic tendency
- Increased intake of purine-rich foods
- Reduced excretion (kidney failure)
what is acute gout?
Disease in which tissue deposition of monosodium urate (MSU) crystals occur as a result of hyperuricaemia and leads to:
gouty arthritis
tophi
what are tophi?
aggregated deposits of MSU in tissue
what does gouty arthritis commonly affect?
metatarsophalangeal joint of the big toe (1s MTP joint)
what are the signs of gouty arthritis?
- podagra
- Abrupt onset
- Extremely painful
- Joint red, warm, swollen and tender
- Resolves spontaneously over 3-10 days
what does an X-ray of gouty arthritis show?
juxta-articular rate bite erosions at the MTPJ of great toe
what are the investigations for gout?
joint aspiration- synovial fluid analysis
what is the management of gout?
- Acute attach- colcichine, NSAIDS, steroids
- Chronic- allopurinol
what is pseudogout?
- Pseudogout is a syndrome caused by deposition of calcium pyrophosphate dihydrate (CPPD) crystal deposition crystals -> inflammation
what are the risk factors for pseudogout?
- background osteoarthritis,
- elderly patients,
- intercurrent infection
what is the difference in the synovial fluid of gout and pseudogout?
what is the most common form of immune mediated inflammatory joint disease?
rheumatoid arthritis
what is rheumatoid arthritis?
chronic autoimmune disease
characterised by pain, stiffness and symmetrical synovitis (inflammation of the synovial membrane) of synovial (diarthrodial) joints
what is the pathogenesis of RA?
- Synovial membrane is abnormal 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
- There is an excess of pro-inflammatory vs. anti-inflammatory cytokines (‘cytokine imbalance
’
what is a healthy synovial membrane composition?
- 1 to 3 cell layer that lines synovial joints
- Contains macrophage-like (type A synoviocyte) and fibroblast-like (type B synoviocyte) cells and type I collagen
- Functions include the maintenance of synovial fluid, the hyaluronate-rich viscous fluid within joint space
what is the dominant cytokine in RA?
TNF-alpha
what are the effects of TNF-alpha?
how is TNF-alpha role in RA treated?
- TNFα inhibition is achieved through parenteral administration (most commonly sub-cutaneous injection) of antibodies or fusion proteins
what are the features of rheumatoid arthritis?
-
Chronic arthritis
- Polyarthritis - swelling of the small joints of the hand and wrists is common
- Symmetrical
- Early morning stiffness in and around joints
- May lead to joint damage and destruction - ‘joint erosions’ on radiographs
- Extra-articular disease can occur
- Rheumatoid nodules
- Others rare e.g. vasculitis, episcleritis
- Rheumatoid ‘factor’ may be detected in blood
- Autoantibody against IgG
what are the patterns of joint involvement in rheumatoid arthritis?
symmetrical
affects multiple joints (Polyarthritis) >5
affects small and large joints, particularly hands and feet
what are the most commonly affected joints in RA?
- Metacarpophalangeal joints (MCP)
- Proximal interphalangeal joints (PIP)
- Wrists
- Knees
- Ankles
- Metatarsophalangeal joints (MTP)
what is the primary site of pathology in rheumatoid arthritis?
synovium
what are the common synovium inflammation pathologies?
what are the common extra-articular features in RA?
- Fever, weight loss
- Subcutaneous nodules
what are the uncommon extra-articular features of RA?
- vasculitis
- Ocular inflammation e.g. episcleritis
- Neuropathies
- Amyloidosis
- Lung disease – nodules, fibrosis, pleuritis
- Felty’s syndrome – triad of splenomegaly, leukopenia and rheumatoid arthritis
what are RA subcutaneous nodules?
- Central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
- Occur in ~30% of patients
what are RA subcutaneous nodules associated with?
severe disease
extra-articular manifestations
rheumatoid factor
what are the 2 types of antibodies in RA?
rheumatoid factor
antibodies to citrullinated protein antigens (ACPA)
what is rheumatoid factor?
- Antibodies that recognize the Fc portion of IgG as their target antigen
- typically IgM antibodies i.e. IgM anti-IgG antibody !
- Positive in 70% at disease onset and further 10-15% become positive over the first 2 years of diagnosis
what are ACPA?
- Antibodies to citrullinated peptides are highly specific for rheumatoid arthritis
- Anti-cyclic citrullinated peptide antibody ‘anti-CCP antibody’
what enzymes is citrullination of peptides mediated by?
- Peptidyl arginine deiminases (PADs)
what is the treatment goal of RA?
prevent joint damage
what does preventing joint damage in RA require?
- Early recognition of symptoms, referral and diagnosis
- Prompt initiation of treatment: joint destruction = inflammation x time
- Aggressive treatment to suppress inflammation
what are the drug treatments for rheumatoid arthritis?
- Disease-modifying anti-rheumatic drugs (‘DMARDs’) = drugs that control the disease process
-
1st line treatment:
- methotrexate in combination with hydroxychloroquine or sulfasalazine
-
2nd line:
- Biological therapies offer potent and targeted treatment strategies
- New therapies include Janus Kinase inhibitors : Tofacitinib & Baricitinib
what drug is important in RA treatment but avoided in long term use?
glucocorticoid therapy (prednisolone)- avoided long term due to side effects
what multidisciplinary management can be used in RA?
physiotherapy, occupational therapy, hydrotherapy, surgery
what is biologic therapy?
- are proteins (usually antibodies) that specifically target a protein such as an inflammatory cytokine
what are the types of biologics in RA?
- Inhibition of tumour necrosis factor-alpha (‘anti-TNF’)
- antibodies (infliximab, and others)
- fusion proteins (etanercept)
- B cell depletion
- Rituximab – antibody against the B cell antigen, CD20
- Modulation of T cell co-stimulation
- Abatacept - fusion protein - extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to modified Fc (hinge, CH2, and CH3 domains) of human immunoglobulin G1
- Inhibition of interleukin-6 signalling
- Tocilizumab (RoActemra) – antibody against interleukin-6 receptor.
- Sarilumab (Kevzara) – antibody against interleukin-6 receptor.
what is the difference between osteoarthritis and RA?
- Destruction joints at distal joints rather than MCP joints in RA
- Deformity also present in RA
- RA may have osteopenia or bony erosions
what other conditions can cause inflammatory arthritis?
- Ankylosing spondylitis
- Psoriatic arthritis
- Reactive arthritis
- Systemic lupus erythematous (SLE)
what is the demographic for ankylosing spondylitis?
20-30 yrs, Male
what is ankylosing spondylitis?
- Seronegative spondyloarthropathy – no positive autoantibodies
- Chronic sacroillitis – inflammation of sacroiliac joints
- Results in spinal fusion – ankylosis
what is ankylosing spondylitis associated with?
HLA B27
what is the clinical presentation of ankylosing spondylitis?
- Lower back pain + stiffness
- Early morning
- Improves with exercise
- Reduced spinal movement
- Peripheral arthritis
- Plantar fasciitis, Achilles tendonitis
- Fatigue
what are the bloods in ankylosing spondylitis?
- Normocytic anaemia
- Raised CRP, ESR
- HLA-B27
what imaging is taken in ankylosing spondylitis and what signs are seen?
- X-Ray
- MRI
- Squaring Vertebral bodies, Romanus lesion
- Erosion, sclerosis, narrowing SIJ
- Bamboo Spine
- Bone Marrow Oedema
what is the management for ankylosing spondylitis?
- Physiotherapy
- Exercise regimes
- NSAIDs
- Peripheral joint disease – DMARDs (don’t work for spinal inflammation)
what is psoriatic arthritis?
- Psoriasis is an autoimmune disease affecting the skin (scaly red plaques on extensor surfaces eg elbows and knees)
- ~10% of psoriasis patients also have joint inflammation
what is the difference between RA and psoriatic arthritis?
- Unlike RA, rheumatoid factors are not present (“seronegative”)
- Varied clinical presentations (PA):
- Classically asymmetrical arthritis affecting IPJs
what can psoriatic arthritis manifest as?
- Symmetrical involvement of small joints (rheumatoid pattern)
- Spinal and sacroiliac joint inflammation
- Oligoarthritis of large joints
- Arthritis mutilans
what are the investigations for psoriatic arthritis?
- X-rays of affected joints – pencil in cup abnormality
- MRI – sacroiliitis and enthesitis
- Bloods – no antibodies as seronegative
what is the managemet for psoriatic arthritis?
- DMARDs – methotrexate
- Avoid oral steroids – risk of pustular psoriasis due to skin lesions
what is reactive arthritis?
- Sterile inflammation in joints following infection especially urogenital (e.g. Chlamydia trachomatis) and gastrointestinal (e.g. Salmonella, Shigella, Campylobacter infections) infections
what are the extra-articular manifestations of reactive arthritis?
- Important extra-articular manifestations include:
- Enthesitis (tendon inflammation)
- Skin inflammation
- Eye inflammation
what might reactive arthritis be first manifestation of?
may be first manifestation of HIV or hepatitis C infection
who is reactive arthritis common in?
- Commonly young adults with genetic predisposition (e.g. HLA-B27) and environmental trigger (e.g. Salmonella infection)
when do the symptoms start in reactive arthritis?
symptoms follow 1-4 weeks after infection and this infection may be mild
how can reactive arthritis be managed?
Condition is usually self-limiting – can be managed with NSAIDS or DMARDs if required
what is lupus?
Lupus = a multi-system autoimmune disease
Multi-site inflammation: can affect any almost any organ. (Often joints, skin, kidneys, haematology. Also: lungs, CNS involvement)
what is systemic lupus erythematosus associated with?
- Associated with antibodies to self antigens (‘autoantibodies’)
- Autoantibodies are directed against components of the cell nucleus (nucleic acids and proteins)
what can be a useful diagnostic in SLE?
autoantibodies:
- Antinuclear antibodies (ANA):
- High sensitivity for SLE but not specific.
- A negative test rules out SLE, but a positive test does not mean SLE.
-
Anti-double stranded DNA antibodies (anti-dsDNA Abs):
* High specificity for SLE in the context of the appropriate clinical signs.
what is a typical sign of SLE?
molar/ butterfly rash
what is the epidemiology of SLE?
- F:M ratio 9:1
- Presentation 15 - 40 yrs
- Increased prevalence in African and Asian ancestry populations
