Introduction to Rheumatology Flashcards
What is rheumatology?
A medical speciality dealing with diseases of the musculoskeletal system
Joints Tendons Ligaments Muscles Bones
What is a joint?
Where two bones meet
What is a tendon?
Cords of strong fibrous collagen tissue attaching MUSCLE TO BONE
What is a ligament?
Flexible fibrous connective tissue which connects BONE TO BONE
What is a fibrous joint?
A joint where there is no space between the bones
What is an example of a fibrous joint?
Bones of the skull
What is a cartilaginous joint?
Joints in which the bones are connected by cartilage eg spinal vertabrae
What are synovial joints, and an example?
Joints where there is space between the adjoining bones - known as the synovial cavity
What fills the synovial cavity?
Synovial Fluid
What are the three types of functional classifications of bones?
Synarthroses
Amphiarthroses
Diarthroses
What is meant by Synarthroses?
Joints with generally no movement
What is meant by amphiarthroses?
JOints which allows very limited movement
What is meant by diarthroses?
Joints which allow free movement of the joint
Which structural classification of joints correspond with diarthroses?
Synovial joints
Which functional classification of joints are both fibrous and cartilaginous joints associated with?
Synarthroses and Amphiarthroses
What are the three main components of the synovial joint?
Bone, joint cavity containing synovial fluid and Articular cartilage
What is the synovium?
A 1-3 cell deep lining containing macrophage-like phagocytic cells and fibroblast-like cells that produce hyaluronic acid
What are type A synoviocytes?
Macrophage-like phagocytic cells
What are type B synoviocytes?
Fibroblast like cells that produce hyaluronic acid
What is synovial fluid?
Hyaluronic acid-rich fluid which lubricates the joint and allows it to move smoothly
In what part of the synovial joint is type 1 collagen found?
Synovium
In which part of the synovial joint is type 2 cartilage found?
Articular cartilage
What is the articular cartilage made of?
Proteoglycans (Aggrecans) and Type 2 collagen
What are the specialised cells found in cartilage called?
Chondrocytes
What is cartilage composed of?
- Chondrocytes
2. ECM: Water, collage and proteoglycans (mainly aggrecan)
Does cartilage have a blood supply?
NO
Why does cartilage heal poorly after injury?
it has no blood supply
What is aggrecan?
A proteoglycan that possesses many chondroitin sulfate and keratin sulfate chains
Characterised by its ability to interact with hyaluronan to form larger proteoglycan aggregates
What are the two major divisions of arthritis?
Osteoarthritis and Inflammatory arthritis (RA)
What are the pathological changes associated with OA?
Cartilage worn out, and attempts made at bony remodelling
Describe the onset of OA?
Gradual, slowly progressing disorder
How does age affect OA?
Increases as age increase
What are the three joint most commonly affected with OA?
Joints of hands
Spine
Weight-bearing joints of lower limbs
Which joints of the hands are most commonly affected with OA
DIP - Distal interphalangeal joints (First joint in finger)
PIP - Proximal Interphalangeal Joints (Second joint in finger)
CMC - First Carpometacarpal joint (Thumb joint)
Which weight-bearing joints of the lower limbs are most commonly affected with OA?
Knees, Hips
Signs and Symptoms of OA? PRICES
Pain Range of motion is limited Instability Crepitus Enlargement of joint Stiffness
What is crepitus of a joint?
`Creaking, cracking grinding when moving the affected joint
what are heberen’s nodes?
Osteophyctes at the DIP Joints
What are bouchards nodes?
Osteophytes at the PIP joints
What are the radiological features of OA? JOSS
Joint Space Narrowing
Osteophytes
Subchondral bony sclerosis
Subchondral cysts
How will subchondral bony sclerosis appear on an X-Ray?
Increased white appearance
What are osteopytes?
Bony spurs
What are the 5 manifestations of inflammation?
Rubor - red Dolor - pain Calor - heat Tumour - swelling Loss of function
What are the physiological, cellular and molecules changes that occur during inflammation? IMAC
Increased blood flow
Migration of white blood cells into tissues
Activations of leucocytes
Cytokine production
What cytokines are produced during an inflammation reaction?
TNF-Alpha, IL1, IL6 and IL17
What are the two infection-related causes of joint inflammation?
Septic arthritis
Tuberculosis
What are the two types of crystal arthritis?
Gout
Pseudogout
What is an example of immune-mediated joint inflammation?
RA
What causes septic arthiritis?
bacterial infection of a joint, usually spread by blood
What are risk factors of septic arthritis?
Immunosuppressed, pre-existing joint damage and intravenous drug use
How many joints are usually affected in septic arthritis?
One joint
How is septic arthritis diagnosed?
Through joint aspiration - aspirate pus out the joint, and send to lab for culturing
once bacteria is known then treat with antibiotics
What are the four hallmarks associated with septic arthritis?
Pain, redness, hot, swelling, and fever
What is a lavage?
A surgical wash out
What are common organisms that are involved septic arthritis?
Staph aureus, Streptococci, Gonococcus
In what was is gonococcal septic arthritis an exception?
It often affects multiple joints (polyarthritis), and is less likely to cause joint destruction
What are the crystals found in gout made of?
Urate (uric acid) crystals
What is the main risk factor for gout?
Hyperuricaemia - high levels of uric acid
What are the causes of hyperuricaemia?
Genetics
Increased intake of purine-rich food
reduced excretion due to kidney failure
What are the crystals in pseudogout made of?
Deposition of calcium pyrophosphate dihydrate (CPPD)
What are the risk factors for pseudogout
Elderly, history of osteoarthritis and intercurrent infection
Why are beer drinkers highly vulnerable to gout?
Beer contains high levels of purine, which gets broken down into uric acid, resulting in more deposition at the joints
What are the crystal deposits found in gout called?
Tophi
What is the most common joint to become affected with gout?
Metatarsophalangeal - bone in toe
What is podagra?
Gout of the big toe
What feature is seen on X-rays in gout?
Rat bit erosions
How is the diagnosis of crystal out made?
Through aspirating fluid from the affected joint and examining it under a microscope using polarised light
What is seen in synovial fluid analysis which would indicate a positive test result for gout?
Needle shaped crystals with negative birefringence
What is seen in synovial fluid analysis which would indicate a positive test result for pseudogout?
Rhomboid shaped crystals with positive birefringence
What is RA?
Rheumatoid arthritis is a chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis of synovial joints
What is synovitis?
Inflammation of the synovial joints
What are the key features of rheumatoid arthritis?
There is swelling of the small joints in the hands and wrists, symmetrical and early morning stiffness is also seen
What feature is seen on radiographs when a patient has RA?
Joint erosions
What may be detected in the blood of patients with RA?
Rheumatoid factor - this is an autoantibody against IgG
What is the pattern of joint involvement in RA?
Symmetrical and affects multiple joints - polyarthritis
What are the most commonly affected joints with RA?
Metacarpophalangeal MCP PIP Wrists Kness Ankles Metatarsophalangeal MTP
In RA, where is the primary site of pathology?
The synovium
What clinical feature of patients is consistent with extensor tenosynovitis
incomplete extension of the little and ring finger
What clinical feature of patients is consistent with extensor tenosynovitis
incomplete extension of the little and ring finger
What is a bursa?
A bursa is a closed, fluid-filled sac that works as a cushion and gliding surface to reduce friction between tissues of the body.
What are some common extra-articular features of RA?
Fever, weight loss, subcutaneous nodules
What is vasculitis?
Blood vessel inflammation
What is episcleritis?
Inflammation of the eye
What is amyloidosis?
Build up of an abnormal protein called amyloid
What is Felty’s Syndrome?
Triad of splenomegaly, leukopenia and RA
Where are RA nodules most commonly found?
Distal to the elbow and in the hands
what are RA nodules
They are a central area of fibrinoid necrosis surrounded by histiocytes and a peripheral layer of connective tissue
In RA, the synovium becomes a proliferated mass of tissue. What causes this?
Neovascularisation
Lymphaniogenesis
An infiltrate of inflammatory cells
What inflammatory cells are present in the synovium during RA?
Activated B and T cells, Plasma cells, Mast cells and macrophages
What controls the requirement of inflammatory cells during RA?
An extensive cytokine imbalance - more pro-inflammatory cytokines than anti-inflammatory
What is the dominant pro-inflammatory cytokine in RA?
Tumour necrosis factor alpha - TNFa
What produces the cytokine TNFa seen in RA?
The activated macrophages in the rheumatoid synovium
What affect does TNFa have on osteoclasts?
Activates them, leading to more bone reabsorption and thus bone erosion
What affect does TNFa have on synoviocytes?
Triggers joint inflammation which leads to pain in the joints and swelling
What effect does TNFa have on chondrocytes?
Leads to cartilage degradation, thus resulting in joint space narrowing
How is inhibition of TNFa achieved?
Through parenteral administration of either antibodies or fusion proteins.
What are the 2 types of autoantibodies that are found in blood of patients with rheumatoid arthritis?
Rheumatoid factor
Antibodies to Citrullinated protein antigens (ACPA)
What are Rheumatoid factor antibodies?
Antibodies that recognise the Fc portion of IgG as their target antigen.
Typically IgM antibodies i.e. IgM anti-IgG antibody.
Citrullination is mediated by enzymes termed…
peptidyl arginine deaminase (PADs).
What does peptidyl arginine deaminase convert arginine into?
citrulline
What is the overall treatment goal for rheumatoid arthritis and what does this goal therefore require?
Treatment goal - Prevent joint damage.
This requires early recognition of symptoms and referral from GP to a rheumatologist, prompt initiation of treatment (joint destruction gets worse with time) and AGGRESSIVE treatment to suppress inflammation.
What are DMARDS?
Disease-modifying anti-rheumatic drugs
What is the 1st line treatment of RA?
Methotrexate in combination with with hydroxychloroquine or sulfasalzine.
What is the 2nd line treatment of RA?
Biological therapies.
New therapies include Janus Kinase inhibitors: Tofacitinib and Baricitinib
Why should the long term use of prednisolone be avoided?
There can be severe side effects
What are biological therapies?
Antibodies that target a specific protein such as an inflammatory cytokine
WHat biologicals are used to inhibit TNF?
Antibodies (infliximab and others)
Fusion proteins (etanercept)
What Biologicals are used for B-cell depletion?
Rituximab - Ab agains the B-cell antigen CD20.
What fusion protein is used as a biological to modulate T cell co-stimulation?
Abatacept
Which two drugs are used as biologicals to inhibit IL-6 signalling?
Tocilizumab (RoActemra) - Antibody against IL-6 receptor
Sarilumab (Kevzara) - Ab against IL-6 receptor.
What MDT approaches are important in the management of rheumatoid arthritis?
Physiotherapy, OT, hydrotherapy, (surgery → barely needed)
Why might treatment with infliximab and rituximab be rejected by a patient?
Both have Fab regions which have a mouse sequence hence they are chimeric (human/mouse) antibodies.
Patient likely to develop antibodies to this mouse component → Effect of drugs on TNF and CD20 respectively will wear off.
What is the difference in joint pattern between RA and OA?
RA = symmetrical OA = asymmetric
What is the difference in the speed of onset between RA and OA?
RA is rapid, OA is slower
What is the difference in the hand joints affected between RA and OA?
RA = PIP and MCP OA = DIP and Thumb CMC
What is the difference in the swelling of the joint between RA and OA?
RA = effusion, red, warm OA = bony
What happens to ESR/CRP in RA?
Elevated
Are osteophytes found in OA or RA?
OA
Is osteopenia common in RA or OA?
RA
Are bony erosions present in RA or OA?
RA
Where do bony erosions initially occur in RA?
At the margins of the joint where the synovium is in direct contact with the blood
What is the difference between the causes of joint space narrowing in rheumatoid and osteoarthritis?
In OA this is the primary abnormality whereas in RA it is caused by secondary damage due to synovitis.
What is psoriatic arthritis?
Autoimmune disease affecting skin (scaly red plaques on extensor surfaces)
Are rheumatoid factors present in patients with psoriatic arthritis?
No - they are seronegative
- What is the classical clinical presentation of psoriatic arthritis?
Classically asymmetrical arthritis affecting IPJs
What else can psoriatic arthritis manifest as other than the classical presentation?
Symmetrical involvement of small joints (rheumatoid pattern)
Spine and sacroiliac joint inflammation
Oligoarthritis of large joints
Arthritis mutilans
What is reactive arthritis?
Sterile inflammation in joints following injection especially urogenital (e.g. Chlamydia trachomatis) and GI (salmonella, Shigella, Campylobacter infections)
What are the important extra-articular manifestations of reactive arthritis?
Enthesitis (another form of tendon inflammation)
Skin inflammation
Eye inflammation
Reactive arthritis may be the first manifestation of what 2 infections?
HIV and Hep-C infection
How long do symptoms follow for reactive arthritis after infection?
1-4 weeks
What are the key differences between septic and reactive arthritis?
Septic - positive synovial fluid, Reactive - sterile
Antibody therapy used in septic, not reactive
Joint drainage/lavage can be used in SA, not Reactive
What is SLE?
Systemic lupus erythematous
What is the pathophysiology of SLE?
Autoantibodies are directed against components of the cell nucleus (nucleic acids and proteins).
How can Anti-nuclear antibodies be used in the diagnosis of SLE?
Antinuclear antibodies (ANA) - high sensitivity for SLE but not specific. Negative test rules out SLE, but positive doesn’t mean patient has SLE.
Negative Anti-Nuclear Antibody test. Does this patient have SLE?
No
What are the two clinical tests for SLE?
ANA
Anti0double stranded DNA antibodies
Which test for SLE has a higher specificity?
Anti-double stranded DNA antibodies
Which sex does SLE affect mre commonly?
Females (9:1)
In which ethnic populations is there an increase prevalence of SLE?
African and Asian ancestry populations.
What does SLE present as clinically?
Malar / Butterfly rash
What is arthritis mutilans
Bones around the joints get completely dissolved, causing telescoping of the fingers resulting in shortening of the fingers and excess skin
