Inflammatory arthritis Flashcards
What is the definition of rheumatoid arthitis?
Insidious (v slow onset so as not be noticed), symmetrical arthritis, with swollen and painful joints > 6 weeks
Autoimmune rheumatic diseases - name 6
RA Seronegative spondylo-arthropaties Chronic arthritis in childre SLE Systemic sclerosis Sjogren's syndrome
RA - female:male ratio?
3:1
What age does RA normally begin?
20-50
Generally young adults. Premenopausal women.
What is the evidence for the immune system’s role in RF
Identification of RF (an anti IgG AB present in >80% patients). Most of these ABs are IgM subtype. High levels of RF associated with RA.
How is FR linked to prognosis?
High elves of FR = worse prognosis
Other than RF, what else is normally raise in RA?
Anti - CCP
Inflammation signs - raised ESR, CRP, (platelets)
What is anchor treatment for RA?
Methotrexate
Consider sensitivity and specificity re. RF vs anti-CCP
Anti-CCP is v specific (if you have it, you definitely have RA), but less sensitive (found in 60% patients, while 75% patients with RA have RF present)
4 hand deformities associated with RA?
Swan neck deformity (finger - DIP hyperflexed, PIP hyperextended)
Boutonnier (DIP hyperextended, PIP flexed)
Z thumbs
Ulnar deviation
What is a clinical skin feature of RA? NB - v rare
Vasculitic lesions
Clinical eye feature of RA?
Scleritis/uveitis
Lung feature of RA? (4)
Fibrosing alveolitis
Effusions
Pleuritis
Caplan’s syndrome - occurs when there is: RA + pneumoconiosis (occupational restrictive lung disease) = intrapulmonary nodules
What can be found on the bony prominences in RA?
Rheumatoid nodules (inflammatory granulomatous lesions, espec subcutaneous)
Where else can rheumatoid nodules occur? (not on bony prominences)
Lung pleura (Caplan’s?)
What time of day is RA stiffness worst?
Morning
Which joints are most commonly affected in RA (pain and swelling)?
MCP, POP, MTP, wrists, ankles, elbows.
Disorder of the blood associated with RA?
Vasculitis
XR features of RA?
Erosion at the margins of a joint
Bone not covered by cartilage
Decr joint space
Soft tissue inflammation
High percentage of RA patients is associated with which particular genetics?
HLA-DR4 subtype
What is Felty’s syndrome? Triad? Which genotype is it associated with? Which extra-articular manifestation is is particularly associated with?
Aggressive complication of RA. Triad of RA, splenomegaly and neeutropenia
HLA-DR4 (an aggressive RA genotype)
Vasculitis
RA therapy against which immune cells has proved effecctive?
T cells
B cells
Which cytokine has proved pivotal in RA, both directly and indirectly?
TNF
MHC polymorphism is related to which kind of immune cell?
T cellss
RA susceptible individual tend to be at risk of what more generally?
Persistant inflammation
Deposits of __ trigger free radical production and so are important in RA pathogenesis
Iron
5 main categories of current treatments?
NSAIDs Steroids DMARDs Anti - cytokines (e.g. anti TNF) Anti CD20
Which sorts of joints tend to be affected in RA?
Small joints
Systemically, what is often foudn in RA?
Blood?
Lymph?
Anaemia
Lymphadenopathy
What is the effect of NSAIDs on prognosis?
None. But good for symptom relief (better than opiates and paracetamol)
Most common polyarthropathy in UK? What percentage of adults affected?
RA
1%
Which of the COX enzymes is inducible? Which compound does COX act on? What is its stimulus? What does it cause?
COX - 2
Arachidonic acid
Inflammatory stim –> inflammation via positive feedback
How do NSAIDs act pharmacologically?
Inhibit COX enzymes
What is the reason for the main side effects of NSAIDs?
- GI (ulcers, haemorrhage etc)
- Renal (nephrotoxicity etc)
Inhibit production of prostaglandins
GI: PGs inhibit gastric acid production os have protective effect on mucosa
Renal: PGs cause renal vasodilatation —> creatinine clearance
How often is the hip involved in rheumatoid arthiritis?
Rarely
What feature is unique to RA compared to other inflammatory arthritises?
Nodules:
- dermis, periosteum (pressure sites), lungs, heart
What lifestyle habit is associated with incr RA risk?
Smoking
How do B cells make rheumatic factor, despite it being an autoantibody?
T cell help
What diagnosis (RA is a differential), should you consider first when a young woman presents with symmetrical synovitis of pip and MCP?
SLE
What sort of presentation has the worst prognosis?
Gradual
4 big side effects of methotrexate? What should you do to prevent some of these? Who must you be very careful about giving it to?
BM suppression - PANCYTOPAENIA (so must monitor v closely)
Mouth ulcers (Rx folic acid)
Tetarogenic - is actually an abortificant, so be careful with woomen of repro age
Pneumonitis
Hydroxychloroquine is another DMARD used in RA, main side effect?
Retinal damage
Other main DMARD (not methotrexate) used to treat RA?
Sulphasalazine
Sulphasalazine:
1 common SE
1 rare (but serious side effect)
1 SE in males
Nausea
Neutropaenia
Azoospermia
How do you achieve best effects with DMARDs?
Use a combo of the 3 big ones
If combo of DMARDs doesnt work, what is the first biological you would try? Give an example.
Anti TNFa drug e.g. Infliximab
2nd line biological? How does it work?
Rituximab. Deplete B cells.
What is the big risk of biologicals? (there are lots, just name one that you should screen for/consider prophylaxis of)
Reactivation of TB
When are steroids useful in RA?
Serious complication (eg vasculitis) Low dose while introducing DMARDs Flares that need rapid resolution
Before being started on biologicals, a patient needs:
__ occasions of active disease, __ month(s) apart
Not responded to at least __ DMARDs for __ months
2
1
2
6
When is RA stiffness worst?
Morning
5 features of seronegative spondyloarthropathies
- where does it affect (3)
- antibodies?
- genetics?
Axial inflammation (spinal and sacroiliac) Assymetrical peripheral arthritis Inflammation of enthesis Absence of RF (seronegative) Strong association with HLA - B27
5 seronegative spondyloarthropathies
Ankylosing spondylitis Psoriatic arthritis Reactive arthritis Post-dysenteric reactive arthritis Enteropathic arthritis
Who does ankylosing spondylitis mainly affect? (age, sex)
Young adults
Men (more frequent and more severe)
How do AS patients present present history wise?
Increasing pain and morning stiffness in the lower back and buttocks
What does inspection of the spine reveal in AS?
Loss of lumbar lordosis and increased kyphosis
Limitation of lumbar spine mobility in both sagittal and frontal planes.
How do you demonstrate reduced spinal flexion?
Schober test - mark made at 5th lumbar spinous process and 10cm above, on bending forward, the distance should increase to >15cm in normal individuals
Ankylosing spondylitis
Articular:
- foot features (2)
- chest features. Why? (2)
Extra articular:
- eyes
- heart
- lungs
Achilles tendinitis, plantar fasciitis
Tenderness around chest wall (and also pelvis). Reduced chest expansion due to involvement of costovertebral joint
Anterior uveitis
Aortic incompetence and cardiac conduction defects
Apical lung fibrosis
What do each of the following tests reveal in ankylosing spondylitis?
- bloods
- MRI
Raised ESR and CRP
Sacroiliitis before it is seen on X-ray
Ankylosing spondylitis xray
Erosion and ___ of the margins of the ___ joint –> ___ (immobility and consolidation of the joint)
Spinal column - blurring of the upper or lower vertebral rims at the thoracolumbar junction caused by an ___ at the insertion of the ___ ___.
This heals with new bone resulting in bony spurs (___).
Progressive calcification of the ___ ___ and ___ eventually produce ‘___ ___’.
Sclerosis Sacroiliac Ankylosis Enthesitis Intervertebral ligaments Syndesmophytes Interspinous ligaments Syndesmophytes Bamboo spine
What is a syndesmophyte?
A bony growth originating inside a ligament
At what point does ankylosing spondylitis become irreversible?
Syndesmophyte formation
Drugs for ankylosing spondylitis:
- pain, when are they taken?
- methotrexate: where is it helpful and also not helpful?
- most effective drug class for treating both spinal and peripheral joint inflammation?
NSAIDs, at night
Helpful for peripheral arthritis but not spinal disease
TNFalpha blocking drugs
In what percentage of patients with psoriasis does arthritis occur? What feature of psoriasis is particularly associated with arthritis?
20%
Nail disease
4 types of psoriatic arthritis?
Asymmetrical involvement of the small joints of the hand, incl distal interphalangeal joints
Symmetrical seronegative polyarthritis resembling RA
Arthritis mutilans, severe form with destruction of small hand and foot bones
Sacroiliitis - unilateral or bilateral
What do the following investigations reveal in psoriatic arthritis?
- bloods
- Xrays
Nothing really, ESR often normal
‘Pencil in cup’ deformity in IPJs
Why do ‘pencil in cup’ deformities come about?
Bone erosion - pointy appearance
Articulating bone = concave
How do you treat psoriatic arthritis?
- normally
- local synovitis
- severe cases
NSAIDs and analgesia
Intra-articular corticosteroid injections
Methotrexate or anti TNFalphas
What is reactive arthritis? What precedes it? What drives it?
A sterile synovitis following a GI infection or STI
Bacterial antigens persist in the inflamed synovium
What can cause the GI infections that precede reactive arthritis? (4 organisms)
Shigella, Salmonella, Yersinia, Campylobacter
What STIs can precede reactive arthritis?
- male
- female (2 organisms)
Urethritis (non-specific)
Cervicitis - Chlamydia trachomatis or Ureaplasma urealyticum
Which joints are particularly affected in reactive arthritis? what pattern?
Lower limb joints
Asymmetrical
What to the skin lesions in reactive arthritis resemble?
Psoriasis
What other features are there with reactive arthritis?
- eyes
- enthesitis (2)
- ___ syndome
- spine?
Anterior uveitis
Achilles tendonitis, plantar fasciitis
Reiter’s
Sacroiliitis and spondylitis
What is the triad found with Reiter’s syndrome
Urethritis, reactive arthritis, conjunctivitis
Reactive arthritis:
- bloods
- synovial fluid?
ESR raised in acute stage
Sterile but with high neutrophil count
What is normally use to treat reactive arthritis (2)?
If the infection persists?
In cases that relapse (they normally don’t) (3)
NSAIDs, local corticosteroid injection,
ABx
Methotrexate/sulphasalazine and antiTNFa
What conditions is enteropathic arthritis associated with?
Ulcerative colitis/Chrohn’s. Normally parallels activity of the IBD.
Which joints does enteropathic arthritis affect? (2 options)
- large joint mono arthritis
OR - asymmetrical oligo-arthritis
What is gout caused by?
Hyperuricaemia and intra-articular sodium urate crystals
Who does gout affect?
- gender? age?
10x more common in men than women
Rarely before young adulthood (if it does occur, generally due to enzyme deficiency)
Rarely in pre-menopausal females
How does hyperuricaemia come about?
Overproduction of uric acid or renal undexcretion
Where does uric acid come from?
Breakdown of purines
4 different gout syndromes?
Acute gout
Chronic polyarticular gout
Chronic tophaceous gout
Urate renal stone formation
What can precipitate an attack of acute gout? (4)
Dietary excess
Alcohol excess
Dehydration
Diuretic
Where does gout normally begin?
Big toe
What is the most important condition to rule out in monoarthritis?
Septic arthritis
What colour are tophi?
They are found particularly in the skin and around joints, which body parts are affected particularly?
White
Fingers, ear, Achilles’ tendon
What does joint fluid microscopy reveal in gout affected joints?
Needle shaped crystals which are negatively birefringent under polarized light
When does serum urate levels determined gout diagnosis? What is the problem generally using serum urate levels?
When plasma levels are in lower half of normal range
When urate crystalises during an acute attack, the serum plasma level is often normal
What is first line gout treatment? 2nd line? And?
NSAIDs
Colchine
Cortiocosteroids
What are problems with using Colchine and what are its side effects?
Narrow therapeutic window
Side effects - diarrhoea, abdo pain, multiorgan failure
How do you prevent future gout attacks?
Reduce serum uric acid levels
- obese patients should lose weight
- alcohol consumption reduced
- drugs like thiazides and salicylates should be withdrawn
3 example of purine riich foods?
Offal
Fish/shellfish
Spinach
What main drug is given to prevent future gout? How does it work?
Allopurinol
Reduces serum urate levels by inhibiting xanthine oxidase (enzyme involved in xanthine oxidase
When you start someone on allopurinol, why do you give them NSAIDs and Colchine for 4 weeks before and after?
Allopurinol can trigger an acute attack
What is pseudogout?
Deposition of calcium pyrophosphate dihydrate (CPPD) in articular cartilage and periarticular tissue.
Why does pseudogout resemble gout?
Shedding of crystals into the joint –> acute synovitis
How is pseudogout different from gout in terms of who gets it?
More common in elderly women
How is pseudogout diff from gout in terms of where it affects?
Knee or wrist
What conditions is gout associated with in young people?(4)
Haemochromoatosis
Hyperparathyroidism
Wilson’s disease
Alkaptonuria (black/brown depostion in cartilage etc)
What does joint fluid microscopy of pseudogout show?
Small brick-shaped pyrophosphate crystals which positively birefringent under polarized light
What is key xray finding of pseudogout? What is it?
Chondrocalcinosis.
That is the deposition of CDDH crystals
What might blood results show in pseudogout?
Raised WBC count
What is treatment of pseudogout?
Joint aspiration with NSAIDs or colchine
Injection of local corticosteroids
Why does gout start in the big toe? (2)
MTPJ - lots of pressure (so more prone to osteoarthritis), coldest part of body
Why is gout so hot?
It is NEUTROPHILIC inflammation
Why is gout more common in men? (2)
Boozing (and meat)
Testosterone poss has an effect
Why is gout systemic?
It is caused by urate in the blood
Which drugs impair excretion of uric acid (2)?
Thiazide diuretics
Low dose aspirin
