Rheumatology Flashcards
What is Rheumatology?
The medical specialty dealing with diseases of the musculoskeletal system including:
Joints = where 2 bone meets
Tendons = cords of strong fibrous collagen tissue attaching muscle to bone
Ligaments = flexible fibrous connective tissue which connect two bones
Muscles
Bones
What are the main 2 types of joint disease?
Osteoarthritis
Inflammatory arthritis
How does inflammation manifest?
RED (rubor)
- PAIN (dolor)
- HOT (calor)
- SWELLING (tumor)
- LOSS OF FUNCTION
What physiological changes underpin inflammation?
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 are the 3 main causes of joint inflammation?
Crystal arthritis - gout, pseudo gout
Immune mediated - rheumatoid arthritis, seronegative spondyloarthropathies, connective tissue disease
Infection - Septic arthritis, TB
What happens in gout?
Gout is a syndrome caused by deposition of urate (uric acid) crystals -> inflammation
What is a major risk factor for gout?
High uric acid levels (hyperuricaemia) = risk factor for gout
What are the causes of gout?
Genetic tendency Increased intake of purine rich foods Reduced excretion (kidney failure)
What happens in pseudo gout?
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 can gout lead to?
Gouty arthritis
Tophi (aggregated deposits of MSU in tissue)
Where does gout typically affect?
metatarsophalangeal joint of the big toe (‘1st MTP joint’) podagra
How does gout present?
Abrupt onset
Extremely painful
Joint red, warm, swollen and tender
Resolves spontaneously over 3-10 days
What investigations are done for gout?
Joint aspiration, synovial fluid analysis
What is the management for gout?
Acute attack – colcihine, NSAIDs, Steroids
Chronic – allopurinol
What are the characteristics of gout crystals under polarising light microscopy?
urate crystals
needle shape
negative Birefringence
What are the characteristics of pseudo gout crystals under polarising light microscopy?
Calcium pyrophosphate dihydrate CPPD crystals
Brick shaped
positive Birefringence
What is the most common immune mediated inflammatory joint disease?
Rheumatoid arthritis
Define 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 Rheumatoid arthritis?
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 the role of TNF-alpha in RA?
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:
How was TNF-alphas role in RA validated?
arthritis validated by the therapeutic success of TNFα inhibition in this condition
TNFα inhibition is achieved through parenteral administration (most commonly sub-cutaneous injection) of antibodies or fusion proteins
What are the Key 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 - should really call this rheumatoid ‘antibody’ not ‘factor’
What is the pattern of joint involvement in RA?
Symmetrical
Affects multiple joints (polyarthritis)
Affects small and large joints, but particularly hands and feet
What are the commonest affected joints in RA?
Metacarpophalangeal joints (MCP) Proximal interphalangeal joints (PIP) Wrists Knees Ankles Metatarsophalangeal joints (MTP)
What are the primary sites of pathology in RA?
Synovial joints
Tenosynovium
Bursa
What are some common extra-articular features in RA?
Fever, weight loss
Subcutaneous nodules
What are some 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
How do subcutaneous nodules occur in RA?
Central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue Occur in ~30% of patients Associated with: Severe disease Extra-articular manifestations Rheumatoid factor
What are the two types of Antibodies found in the blood of RA patients?
Rheumatoid factor
Antibodies to citrulinated 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’
Citrullination of peptides is mediated by enzymes termed:
Peptidyl arginine deiminases (PADs)
What is the management for RA?
Treatment goal: prevent joint damage
Requires:
Early recognition of symptoms, referral and diagnosis
Prompt initiation of treatment: joint destruction = inflammation x time
Aggressive treatment to suppress inflammation
Drug treatment:
Disease-modifying anti-rheumatic drugs (‘DMARDs’) = drugs that control the disease process
What is 1st line treatment for RA?
methotrexate in combination with hydroxychloroquine or sulfasalazine
What is 2nd line treatment for RA?
Biological therapies offer potent and targeted treatment strategies
New therapies include Janus Kinase inhibitors : Tofacitinib & Baricitinib
Important roles for glucocorticoid therapy (prednisolone) but avoid long-term use because of side-effects.
Multidisciplinary approach also important e.g. physiotherapy, occupational therapy, hydrotherapy, surgery
What are Biological therapies?
Biological therapies are proteins (usually antibodies) that specifically target a protein such as an inflammatory cytokine
What are biological therapies used in RA Management?
- 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 Ankolysing spondylitis?
Seronegative spondyloarthropathy – no positive autoantibodies
Chronic sacroillitis – inflammation of sacroiliac joints
Results in spinal fusion – ankylosis
Common demographic: 20-30yrs, M
Associated with HLA B27
What is the clinical presentation of ankolysing Spondylitis?
Lower back pain + stiffness Early morning Improves with exercise Reduced spinal movements Peripheral arthritis Plantar Fasciitis, Achilles Tendonitis Fatigue
What bloods are done for AS?
Normocytic anaemia
Raised CRP, ESR
HLA-B27
What imaging is done in AS?
X-Ray MRI Squaring Vertebral bodies, Romanus lesion Erosion, sclerosis, narrowing SIJ Bamboo Spine Bone Marrow Oedema
What is the management for AS?
Physiotherapy
Exercise regimes
NSAIDs
Peripheral joint disease - DMARDs
What is Psoriasis?
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 different in psoriatic arthritis compared to RA?
Unlike RA, rheumatoid factors are not present (“seronegative”)
What are the clinical presentations of Psoriatic arthritis?
Classically asymmetrical arthritis affecting IPJs
But also can manifest as:
- Symmetrical involvement of small joints (rheumatoid pattern)
- Spinal and sacroiliac joint inflammation
- Oligoarthritis of large joints
- Arthritis mutilans
What investigations should be done for psoriatic arthritis?
X-rays of affected joints – pencil in cup abnormality
MRI – sacroiliitis and enthesitis
Bloods – no antibodies as seronegative
What is the management of 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 important extra-articular manifestations in Reactive arthritis?
Enthesitis (tendon inflammation)
Skin inflammation
Eye inflammation
What can reactive arthritis be a first manifestation of?
HIV or HepC infection
Who is affected by reactive arthritis?
Commonly young adults with genetic predisposition (e.g. HLA-B27) and environmental trigger (e.g. Salmonella infection)
When do you get symptoms of reactive arthritis?
1-4 weeks after infection( may be mild infection).
What is the treatment for Reactive arthritis?
Condition is usually self-limiting – can be managed with NSAIDS or DMARDs if required
Reactive arthritis is distinct from infection in joints (septic arthritis)
What happens in Systemic Lupus Erythematous SLE?
Lupus = a multi-system autoimmune disease
Multi-site inflammation: can affect any almost any organ.
Often joints, skin, kidneys, haematology. Also: lungs, CNS involvement
Associated with antibodies to self antigens (‘autoantibodies’)
Autoantibodies are directed against components of the cell nucleus (nucleic acids and proteins)
What autoantibodies can be helpful in SLE diagnosis?
- 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 the epidemiology of SLE?
F:M ratio 9:1
Presentation 15 - 40 yrs
Increased prevalence in African and Asian ancestry populations
Prevalence varies 4-280/100,000
