Rheum Flashcards
Define osteoarthritis
Non-inflammatory degenerative disorder of the synovial joints characterised by loss of articular cartilage and new bone formation
Why does prevalence of osteoarthritis increase with age?
Cumulative effect of trauma and decrease in neuromuscular function
Give 7 risk factors for osteoarthritis
- Age
- Trauma
- Joint hyper-mobility
- Other joint conditions - RA
- Genetic factors
- Obesity
- Occupation - heavy manual/sports
Which cells maintain cartilage?
Chondrocytes
Where are chondrocytes embedded?
Extracellular matrix containing:
Type 2 collagen
Proteoglycans (hyaluronic acid etc.)
How are chondrocytes involved in the pathogenesis of OA?
Articular cartilage damage triggers chondrocytes to decrease proteoglycan production and increase type 1 collagen production.
How is the extracellular matrix affected by the increase in type 1 collagen?
less elastic, chondrocytes undergo apoptosis
What happens when chondrocytes undergo apoptosis/
cartilage weakens and flakes off into the joint space - joint mice
What triggers synovitis?
- Synovial Type 1 cells attempt to remove joint mice
2. Macrophages and lymphocytes release pro-inflammatory cytokines
What is fibrillation of the articular cartilage?
flaking off
What happens as a result of the synovitis and fibrillation?
- Eburnation of exposed bone due to friction
- Subchondral cysts in sclerotic bone
- Attempts to reform articular cartilage - calcifies and forms osteophytes.
space
space
How is OA treated?
- Physio and weight loss
- Analgesia (NSAIDs)
- Intra-articular steroids
- Intra-articular hyaluronic acid
- Replacement arthroplasty
Which knee deformity can happen as a result of OA in the medial compartment of the knee?
Genu varus (bow legged)
What classical findings on XR for OA?
LOSS
- Loss of joint space
- Osteophytes
- Subchondral sclerosis
- Subchondral cysts
Which inflammatory marker is more likely to be raised in OA?
CRP
What conditions can predispose to spinal OA?
disc prolapse or degeneration
What conditions can be caused as a result of spinal OA?
Spondylolisthesis
Spinal stenosis
What is spondylolisthesis?
Displacement of one vertebrae over the other (usually L5-S1)
Which joints of the hand are commonly affected in OA?
DIPJ
PIPJ
Carpometacarpal joints
What is the surgical treatment of OA?
Fusion
Joint replacement
Osteotomy Bone shortening
Arthroscopy for loose bodies
space
space
space
space
What does the fibrous joint capsule extend to become?
Periosteum
What is fibrous capsule lined by?
Synovium
What cells are present in the synovium and what is their function?
Synoviocytes
Type A - remove debris (macrophagic)
Type B - produce synovial fluid (fibroblastic)
What are the three types of joints?
Synovial
Fibrous
Cartilaginous
Which joints are affected in RA?
Synovial
Describe the disease process in RA.
Inflammation and thickening of the synovium with infiltration of lymphocytes and macrophages with IL-1, IL-6, and TNF-a production.
Stimulates proliferation of pannus and angiogenesis. Pannus erodes into cartilage and bone.
What are the two pathological characteristics of pannus?
- Inflammation - chronic inflammatory reaction with macrophage, lymphocyte, and plasma cell infiltration
- Proliferation - tumour like mass which grows over cartilage
What is the role of RANKL in RA?
RANKL binds to RANK and stimulates osteoclasts to break down bone
What is the role of RF and anti-CCP in RA?
bind to their targets and form immune complexes in the joint
What is RF?
rheumatoid factor
IgM antibody which binds to constant Fc portion of alterred IgG
What is anti-CCP?
binds to citrullinated proteins (citrullinated vimentin and type 2 collagen)
amino acid arginine is converted to citrulline
What is the role of immune complexes in RA?
Immune complexes activate the complement system and cause inflammation
What are the three different ways that RA can cause bone loss?
Focal erosions
Periarticular osteoporosis
Generalised osteoporosis in skeleton
How does cartilage loss occur in RA?
inflammatory cytokines (ILs and TNFa) stimulate the production of proteases which break down cartilage
Describe the pathophysiology of RA (up to pannus formation)
- T-cells enter the joint and recruit macrophages.
- Macrophages secrete TNF-a, IL1, IL6
- Cytokines stimulate synovial proliferation and pannus formation and angiogenesis (allows more inflammatory cells/markers into joint)
- Pannus erodes into bone and cartilage
How is bone eroded in RA?
T cells are stimulated to display RANK-Ligand, which binds to RANK on osteoclasts.
Stimulates osteoclasts to break down bone
How is cartilage broken down in RA?
Activated synovial cells secrete proteases
What are immune complexes formed by in RA?
RF and anti-CCP bind to their targets and form immune complexes
What is the role of immune complexes in RA?
Activate the complement system and cause inflammation of the joint
What is RF?
Rheumatoid factor = IgM antibody which binds to Fc (constant portion) in altered IgG antibodies
What is citrullination in RA?
Amino acid arginine is changed into citrulline in certain proteins such as vimentin and type 2 collagen
What does anti-CCP bind to?
citrullinated peptides
What sites (joints) are commonly affected in RA?
Hands, knees, feet, ankles
What are the signs of RA in the hands?
- Boutonniere
- Swan neck
- Z-thumb
- Ulnar deviation
Where can RA present (extra-articular)?
- Neuro
- Lungs
- Heart
- Kidneys
- Skin
- Eyes
- Haem
What are the neuro manifestations of RA?
- Peripheral neuropathies
- Entrapment neuropathies
- Cervical instability
What can occur as a result of cervical instability in RA?
- Atlanto-axial subluxation
2. Cervical myelopathy
Give two entrapment neuropathies
Carpal tunnel
Tarsal tunnel
What are the RA manifestations in the lungs?
- Pleural effusion
- Interstitial lung disease
- Caplan’s syndrome
- Rheumatoid nodules
- Small airways disease
What are the RA manifestations in the heart?
Pericardial rub
Pericardial effusion
Pericarditis
What are the RA manifestations in the kidney?
Amyloidosis (presents with proteinuria)
Analgesic nephropathy
What is amyloid?
Acute phase protein
What are the soft tissue manifestations in RA?
- Rheumatoid nodules
- Bursitis
- Muscle wasting
- Tenosynovitis
What are the haematological manifestations of RA?
- Felty syndrome
2. Anaemia
What is Felty syndrome?
seropositive RA + neutropaenia + splenomegaly
What anaemias can occur as a result of RA?
- Normocytic normochromic (chronic disease)
- Iron deficiency anaemia
- Haemolytic anaemia (rare)
- Anaemia occurring as part of a pancytopaenia
What are the eye manifestations of RA?
Scleritis
Episcleritis
Necrotising scleritis
Sicca, sjogren’s
What are some consequences of RA vasculitis?
- Nailbed infarcts
- Mononeuritis multiplex
What can occur as a result of mononeuritis multiplex in RA?
wrist drop
foot drop
How is RA treated?
Methotrexate
Steroids
Cyclophospamide
Mycophenolate
NSAIDs
Biologics:
Infliximab
adalimumab
tocilizumab
What are the XR findings in RA?
LESS
Loss of joint space
Erosions
Soft tissue swelling
Soft bones
How is RA treated?
- DMARDs - Methotrexate is gold standard
- NSAIDs for pain
- Steroids while waiting for DMARDs to work
- Biologics
a. TNF-a blockers are first line
Infliximab, etanercept, adalimumab
b. Rituximab
c. IL-blockers
Tocilizimab, anakinra
d. T cell activation blockers
Abatacept
Give 3 examples of a TNF-a blocker
Infliximab
Etanercept
Adalimumab
Give an example of a B cell blocker
Rituximab (CD20)
Stops production of RF
Give two examples of IL blockers
Tocilizumab
Anakinra
Give an example of a T cell activation blocker
Abatacept
Blocks T cells
no activation of macrophages and B cells
Who does ank spond mainly affect
men 20-30s
how does ank spond present
- lower back/buttock pain and stiffness, worse in morning, relieved by exercise
- back pain at night, relieved by waking up
what would you see on clinical examinaton of ank spond
- reduced lateral flexion
- reduced forward flexion - schober’s test, <5cm extension
- reduced chest expansion
What are the other features of ank spond (A features)?
- Apical fibrosis
- Anterior Uveitis
- Aortic regurgitation
- Achilles Tendonitis (enthesitis)
- AV node block
- Amyloidosis
- And Cauda Equina
- Arthritis (peripheral, more common in females)
what is a key complication of ank spond
vertebral fractures
what are some other symptoms of ank spond aside from arthritis
aortitis enthesitis dactylitis anaemia heart block
what investigations for ank spond
- ESR, CRP might be raised, neg does not exclude
- XRay spine and sacrum - sacroillitis, bamboo
- MRI Spine - may show bone marrow oedema
what Xray changes would you see in ank spond
- sacroillitis
- squaring of vertebral bodies
- subchondral sclerosis and erosions
- syndesmophytes
- ossification of ligaments, tendons, and joints
- fusion of facet, sacroiliac, and costovertebral joints
how is ank spond managed
- encourage regular exercise, swimming, physiotherapy
- NSAIDs first line
- steroids during flares to control symptoms
- anti-TNF - etanercept/infliximab
- secukinumab - anti IL17
what type of anti interleukin is secukinumab against
anti-IL17
what might spirometry show in ank spond
restrictive picture:
- pulm fibrosis
- kyphosis
- ankylosis of costovertebral joints
what are some additional treatments for ank spond’s other features
stop smoking
bisphosphonates for osteoporosis
What scoring for ank spond
BASDAI
what is olecranon bursititis
inflammation of bursa, thickening of synovial membrane and increased synovial fluid production - leading to swelling
what causes bursitis
- friction from repetitive movements or leaning on the joint
- trauma
- inflammatory conditions - gout, RA
- infection - septic bursitis
how does bursitis present
swollen
warm
tender
fluctuant - fluid filled
what is an important differential diagnosis of bursitis
septic arthritis
how would septic arthritis differ from bursitis in presentation
septic arthritis - inflammation of whole joint, limited range of movement
how is bursitis investigated
aspiration of fluid if infection suspected
what do different bursa fluid colours indicate
pus - infection
straw-coloured - infection less likely
blood stained - trauma, inflammatory causes, infection
milky - gout/pseudogout
how is bursitis managed
rest ice compression analgesia - nsaids/paracetamol aspiration of fluid to relieve pressure steroid injections
how is septic bursitis managed
fluclox, clarithromycin second line
explain the pathophys of gout
deposition of monosodium urate crystals in synovium due to chronic hyperuricaemia
what can predispose to gout (decreased excretion of uric acid)
- diuretics
- CKD
- lead toxicity
what can predispose to gout (increased production of urate)
- purine-rich diet - gout and seafood, some alcohols
- cytotoxic drugs
- severe psoriasis
- myeloproliferative/lymphoproliferative disease
what x-linked recessive condition can predispose to gout
lesch-nyhan syndrome
how does gout present
painful, swollen, warm, erythematous joint
what can repeated untreated gout do to a joint
damage
what other risk factors for gout?
being male
obesity
alcohol
family history
what investigations for gout
- joint aspiration
- negatively birefringent needle-shaped crystals under polarised light
uric acid
- 2 weeks after acute flare
X ray joint
what would xray of gout look like
- joint effusion
- punched out erosions with sclerotic margins in a juxta-articular distribution, with overhanging edges
- lytic lesions in bone
- soft tissue tophi may be seen
what is a common side effect of colchicine
diarrhoea, dose dependent
what management of gout in acute flare
nsaids and colchicine, intra-articular or oral steroids can be used
when to start allopurinol for gout
after acute attack has settled, but should continue use throughout the attack
how does radiograph of gout differ to RA?
no periarticular osteopaenia in gout
what prophylaxis for gout
lifestyle mods - lose weight, hydration, decrease purine rich foods (meat seafood, yeast)
allopurinol
febuxostat
uricase
what medication can be given in htn and gout, and has a specific uricosuric action
losartan
which vitamin may decrease uric acid levels in serum
vit C
what are the extra-articular manifestations of RA
- rheumatoid nodules
- CV disease
- pulmonary fibrosis and nodules (caplan syndrome)
- bronchiolitis obilterans
- felty - RA neutropaenia splenomegaly
- secondary sjogren
- anaemia of chronic disease
- scleritis episcleritis
- lymphadenopathy
- carpal tunnel syndrome
- amyloidosis
what xr changes in ra
less loss of joint space erosions soft tissue swelling soft bones (osteopaenia)
what side effects of DMARDs
methotrexate - bone marrow suppression and leukopaenia, teratogenic
hydroxychloroquine - nightmares, retinopathy
sulfasalazine - reduced sperm count
leflunomide - HTN and peripheral neuropathy
biologics - reactivation of TB, Hep B
rituximab (CD20) - thrombocytopaenia, night sweats
what mgmt of ra in preg
hydroxychloroquine or sulfasalazine
what mgmt of RA
- dmards, steroids as bridging to help induce remission
- steroids oral, IM for flares
- 2 dmards combined
- methotrexate + antiTNF (infliximab etanercept adalimumab
- methotrexate + rituximab
what are some ocular manifestations of RA
- keratoconjunctivitis sicca
- scleritis, episcleritis
- keratitis
- corneal ulceration
iatrogenic:
- steroid induced cataracts
- chloroquine retinopathy
what investigation on joint fluid in suspected septic arthritis
- gram staining
- microscopy and culture and sensitivities
- crystal microscopy
what differentials in septic arthritis
- reactive arthritis
- gout
- pseudogout
- haemarthrosis
what are the complications of SLE
- CV disease
- infection
- anaemia of chronic disease
- pericarditis
- pleuritis
- interstitial lung disease - pulm fibrosis
- lupus nephritis
- neuropsychiatric - depres,anx, seizures, psychosis
- recurrent miscarriage
- VTE due to antiphospholipid syndrome
what type of hypersensitivity is lupus?
SLE = type 3 hypersensitivity
what type of hypersensitivity is antiphospholipid
anti-phospholipid = type 2 hypersensitivity
what are two complications of discoid lupus
development of SLE
squamous cell carcinoma
how does discoid lupus present
photosensitive rash
inflamed dry, scaly, crusty, patchy erythematous rash
hypo/hyperpigmented scars
alopecia if on scalp
how is discoid lupus diagnosed
skin biopsy
how is discoid lupus treated
suncream
topical steroids
intralesional steroid injections
hydroxychloroquine
what are the RFs for pseudogout
wilson's haemochromatosis hyperparathyroidism hypomagnesaemia, hypophosphataemia acromegaly
what treatment for pseudogout
nsaids, colchicine
intraarticular, IM, PO steroids
joint wash out (arthrocentesis) if severe
