1b Rheumatoid And Other Inflammatory Arthritis Flashcards
What is the synovium?
1-3 cell deep lining containing macrophage-like phagocytic cells (type A synoviocyte) and fibroblast-like cells that produce hyaluronic acid (type B synoviocyte)
What enables the synovial fluid to be viscous?
It is rich in hyaluronic acid
What type of collagen makes up the articular cartilage?
Type 2 collagen
What proteoglycan plays a large role in the articular cartilage?
Aggrecan
What are the two main divisions of arthritis?
Osteoarthritis and rheumatoid arthritis
What are the key characteristics of OA?
lack of joint space
loss of articular cartilage
bony spurs - osteophyte
What are the two infectious causes of joint inflammation?
Septic arthritis and tuberculosis
What are the two forms of crystal arthritis?
gout
pseudogout
What are the two sterile inflammatory processes which can occur in joints?
Crystal arthritis
Immune mediated “autoimmune”
What causes septic arthritis?
Bacterial infection of a joint (usually caused by spread from the blood)
What are the risk factors for septic arthritis?
immunosuppressed, pre-existing joint damage, intravenous drug use (IVDU)
Describe the typical presentation of a joint with septic arthritis?
Acute red, hot, painful swollen joint
How many joints are commonly affected in septic arthritis?
mono-arthritis
What common symptom will patients with septic arthritis present with?
Fever
How is septic arthritis diagnosed?
Joint aspiration - send sample for urgent gram stain and culture
What are the common organisms which cause septic arthritis?
Staphylococcus aureus, Streptococci, Gonococcus
in what way is gonococcal septic arthritis an exception?
- effects multiple joints (polyarthritis)
- less likely to cause joint destruction
What is the treatment for septic arthritis?
Surgical wash out - lavage and intravenous antibiotics
What is gout caused by?
Deposits of monosodium urate (uric acid)
What are some causes of gout?
Genetic tendency
Increased intake of purine rich foods
Increased cell turn over eg chemotherapy
Reduced excretion (kidney failure)
What is the main risk factor for gout?
hyperuricaemia
What is pseudogout caused by?
deposition of calcium pyrophosphate dihydrate crystals
What are the risk factors for pseudogout?
background osteoarthritis, elderly patients, intercurrent infection
What are tophi?
aggregated deposits of MSU in tissue): often develop around hands, feet, elbows, and ears) – in other tissues
Describe the clinical features of gout?
Abrupt onset, usually monoarthritis
Which joint is most commonly affected by gout? What is it called?
Big toe 1st MTPJ (metatarsophalangeal joint) most commonly affected
(podagra)
What is a key investigation to do for any acute monoarthritis?
synovial fluid analysis
What is the shape of the crystals in GOUT vs PSUEDOGOUT?
Gout = needle shaped
Pseudogout = rhomboid / brick shaped
What is the Birefringence for GOUT vs PSUEDOGOUT?
gout = negative
pseudogout = positive
What is the primary site of inflammation in RA?
synovium
What is synovitis?
inflammation = of the synovial membrane
What are the three locations the synovium are found at?
Synovial joints
Tenosynovium
Bursa
What is extensor tenosynovitis?
inflammation of the tenosynovium surrounding tendons
- shows as patieng having incomplete extension of the little and ring finger
What are the key features of rheumatoid arthritis?
chronic condition
- poly arthritis
- pain swelling and early morning stiffness in and around the joints
- may lead to joint damage and destruction = seen as joint erosions on the radiographs
What is detected in the blood of patients with RA?
auto-antibodies
How is the contribution between genetics and the environment estimated?
look at the concordance of a trait in monozygotic and dizygotic twins
If the concordance rate for monozygotic twins > dizygotic twins, this indicates a genetic component.
What is the largest genetic risk factor for Rheumatoid Arthritis?
Strongest genetic risk factor = HLA-DR
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
What are the most common joints to be affected by RA?
Metacarpophalangeal joints (MCP)
Proximal interphalangeal joints (PIP)
What are the common extra-articular features of RA
Fever, weight loss
Subcutaneous nodules
What are the uncommon extra-articular features of RA?
Lung disease – nodules, fibrosis, pleuritis
Ocular inflammation e.g. episcleritis
Vasculitis
Neuropathies
Felty’s syndrome – triad of splenomegaly, leukopenia and rheumatoid arthritis
Amyloidosis = chronic inflammation causing increase in amyloid P
What is a subcutaenous nodules which is seen in RA?
Central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
What is a rheumatoid nodule?
nodule found on the ulnar border of the forearm where you might detect nodules - if they are present confirms the diagnosis of RA and is invariably associated with RF
What does the synovium become in RA?
proliferated mass of tissue (pannus) due to neovascularisation
lymphangiogenesis
inflammatory cell infiltration
What immune cells are found in the synovium in RA?
activated B and T cells
plasma cells
mast cells
activated macrophages
Describe the cytokine balance in RA?
Inbalance = more pro-inflammatory then anti-inflammatory
What are the pro inflammatory cytokines which are important in RA?
TNF Alpha
IL-1
What are the anti-inflammatory cytokines which are seen in RA?
IL-10, IL - 1 receptor antagonist
What is the dominant pro-inflammatory cytokine in RA?
The cytokine tumour necrosis factor-alpha (TNFα) is the dominant pro-inflammatory cytokine in the rheumatoid synovium
How do osteoclasts effect RA?
they increase bone resorption and bone erostion
How do synoviocytes contribute to RA?
increase joint inflammation which leads to painful swelling
How do chondrocytes contribute to RA?
Lead to cartilage deposition which results in joint space narrowing
What is the name of the anti-TNF drugs?
infliximab and adalimumab
What happens to haemaglobin levels in RA?
lowered - this is because the bone marrow gets depressed so haemaglobin is low
What are the two types of antibodies which are found in the blood of RA patients?
Rheumatoid factor and antibodies to citrullinated protein antigens
What are rheumatoid factor antibodies?
Antibodies which recognise the Fc portion of the IgG as their target antigen = they are typically IgM antibodies
What mediates the citrullination of peptides?
Peptidyl arginine deiminases (PADs)
What causes the citrullination of proteins in the lung epithelium?
smoking
antibodies to citrullinated peptides are highly specific for…
RA
What are the radiographic features of RA?
Soft tissue swellin
Peri-articular osteopenia
Bony Erosions
What are the ultrasound changes which occur in RA?
Synovial thickening
Increased blood flow
may detect erosions which are not seen on a plain X ray
What are DMARDs?
(disease-modifying anti-rheumatic drugs) =
drugs that control the disease process (usually immunosuppressive)
What is the first line regime in the treatment of RA?
IM or short course of oral steroids
Start combination DMARD therapy (usually Methotrexate + hydroxychloroquine &/or sulfasalazine)
What is the second line regime in the treatment of RA?
Biological therapies offer potent and targeted treatment strategies
New therapies include Janus Kinase (JAK) inhibitors : Tofacitinib & Baricitinib
How do steroids work?
Glucocorticoids bind the glucocorticoid receptor (GR)
GR resides in cytoplasm
On binding by glucocorticoids, steroid-GR complex translocates to the nucleus and binds DNA response elements, affecting transcription
What is the main bad side effect of glucocorticoids?
Cushings Syndrome
What is the key DMARD?
Methotrexate
How does methotrexate work?
Inhibits dihydrofolate reductase (”folate antagonist”)
Immunosuppressive/anti-inflammatory
What are the side effects of Methotrexate?
Nausea
Hair loss
Fall in WCC
Abnormal liver function
Pneumonitis
Infection risk
What is the biologic responsible for B cell depletion?
Rituximab - antibody against the B cell antigen, CD20
What is the biologic used to block IL-6 signalling?
Tocilizumab (RoActemra) – antibody against interleukin-6 receptor.
Sarilumab (Kevzara) – antibody against interleukin-6 receptor.
What is psoriatic Arthritis?
Psoriasis is an immune-mediated disease affecting the skin
Scaly red plaques on extensor surfaces (eg elbows and knees)
What is the dominant pathogenic pathway in psoriatic arthritis?
Dominant pathogenic pathway is interleukin-17/interleukin-23
(IL17-IL23)
Are rheumatoid factors present in psoratic arthritis?
no
What is the typical presentation of psoriatic arthritis?
Classically asymmetrical arthritis affecting IPJs
What are the other possible manifestations of Psoriatic Arthritis?
-Symmetrical involvement of small joints (rheumatoid pattern)
-Oligoarthritis of large joints
-Arthritis mutilans
-Spinal and sacroiliac joint inflammation
what is reactive arthritis?
Sterile inflammation in joints following infection elsewhere in the body
Common infections is urogenital and gastrointestinal
What are the common extra-articular manifestations of reactive arthritis?
Enthesitis (tendon inflammation)
Skin inflammation
Eye inflammation
What might be the first manifestation of HIV or Hepatitis C infection?
Reactive arthritis may be first manifestation of HIV or hepatitis C infection
Who is reactive arthritis commonly seen in?
Commonly young adults with genetic predisposition (e.g. HLA-B27) and environmental trigger (e.g. Salmonella infection)
What are the key differences between septic and reactive arthritis?
Septic - synovial fluid culture positive, need Abx theapry and joint lavage
reactive - sterile and no Abx, no lavage
What is inflammatory spondyloarthritis?
Anklosing spondylitis - primary inflammation of the spine and the sacroiliac joints
What are the extra-articular manifestations of SpA?
Peripheral joints, esp. tendon insertions (entheses), can also be affected
Extra-articular manifestations including anterior uveitis (iritis)
What are the three autoimmune causes of RA?
Rheumatoid arthritis
Seronegative spondyloarthropathies
Connective tissue disease
What is seen on an X ray of a patient with gout?
Juxta-articular ‘rat bite’ erosions at MTPJ of great toe
What is the treatment for an acute attack of gout?
Colchicine - tubulin disruption, less preferred to NSAIDs and steroids
NSAIDs
Steroids
What is the management of chronic case of gout?
Allopurinol - xanthine oxidase inhibitors reducing production of uric acid in the body
In rheumatoid arthritis, what causes the synovium to become pannus?
Neovascularisation - growth of new blood vessels
Lymphangiogenesis - new lymphatic vessel formation
Inflammatory cells
Activated B and T cells
Plasma cells
Mast cells
Activated macrophages
What is the biological therapy causing B cell depletion?
Rituximab - antibody against B cell antigen CD20
What are the 2 biological therapies inhibiting IL-6 signalling?
Tocilizumab (RoActemra) – antibody against interleukin-6 receptor
Sarilumab (Kevzara) – antibody against interleukin-6
-
What are 5 common clinical presentations of AS?
Lower back pain + stiffness
Early morning
Improves with exercise
Reduced spinal movements
Peripheral arthritis
Plantar fasciitis, achilles tendonitis
Fatigue
What is the relevance of doing a U&E in rheumatological diseases (give examples)?
They can affect the kidneys.
E.g. SLE → lupus nephritis; Vasculitis → glomerular nephritis; chronic inflammation in poorly controlled inflammatory disease → high levels of serum amyloid A (SAA) protein → SAA deposits in organs (AA amyloidosis; can happen in the kidneys)
Compare the radiographic changes seen in RA and OA.
RA: Joint space narrowing, osteopenia and body erosions
OA: Joint space narrowing, Osteophytes and subchondral sclerosis
What are osteophytes at the DIPJs and PIPJs termed respectively?
DIPJs - Heberden’s nodes
PIPJs - Bouchard’s nodes
Which type of arthritis is worse in the morning, and doesn’t generally improve?
RA
OA is bad in morning but improves with movement
What is the pattern of joint involvement in RA and OA?
RA - symmetric, bilateral
OA - random and asymmetric
Which are the two most common joints to be effected in RA?
PIP and MCP
Describe the difference in joint swelling seen in RA and OA?
RA - red, hot effusion
OA - bony
