Rheumatoid Arthritis Flashcards
What is rheumatoid arthritis?
RA is a chronic systemic inflammatory disease, characterised by a symmetrical, deforming, peripheral polyarthritis.
RA = synovial disease characterised by synovitis
RA increases the risk of CVS disease 2-3 fold
Who does RA affect?
Women > men [3:1]
Higher risk in smokers
Peak onset : 5-6th decade
What is the aetiology (genetics, enviromental, autoantibodies) of rheumatoid arthritis?
Genetics:
=> Increased risk in 1st degree relative
=> HLA/DR4 assoc. with increased severity
Environment:
=> Smoking ± bronchial stress causes increased risk of RA with HLA-DR4 (acts synergistically)
Autoantibodies:
=> Rheumatoid factor - autoantibodies to the Fc portion of IgG in 80% of RA - specific but not sensitive
=> Anti-citrulinated peptide antibodies (ACPA) more sensitive and specific for RA
What is immunological basis of rheumatoid arthritis?
Synovitis in RA occurs due to overproduction of TNF-a => joint destruction
=> overproduction of TNF-a is driven by T & B lymphocytes
=> TNF-a stimulates IL-6
Dysfunction of cells => synovitis
- Synovial cells : produce pro-inflammatory cytokines
- Osteoclasts : bone & cartilage destruction
- Synovial B-cells : autoantibodies => IgM & IgG RF most common
Is IgM RF diagnostic of RA and why?
No, RF is not diagnostic of rheumatoid arthritis - presence of RF does not confirm diagnosis of rheumatoid arthritis, nor does absence of RF exclude rheumatoid arthritis.
RF => useful in prognosis for rheumatoid arthritis
What is the significance of anti-citrulinated peptide antibodies (ACPA)?
ACPA present with RF in rheumatoid arthritis.
Better predictors of RA.
ACPA + RF => even more specific rheumatoid arthritis
What is the clinical presentation of RA?
~70% RA presents with:
=> progressive, symmetrical, peripheral polyarthritis
=> swollen, painful & stiff small joints of the hands and feet, eventually larger joints
=> worse in morning
=> evolves over weeks / months
=> between 30-50 years
~15% RA presents with:
=> sudden onset over few days
=> severe widespread, symmetrical, polyarticular involvement
=> in elderly
What are the signs & symptoms of early RA?
Inflammation but no joint damage
Pain & stiffness of small joints of hands & feet
=> swollen MCP, PIP, wrist or MTP joints
=> DIP is always spared in RA
Often symmetrical
Pain & stiffness worse in the morning
90% = polyarticular ; 10% = monoarticular
Tenosynovitis
Bursitis
Sleep disturbances + fatigue
Restricted movements + muscle wasting
What are the signs & symptoms of late RA?
Joint damage + deformity
Ulnar deviation
Subluxation of wrist & fingers
Boutoniere & swan neck deformities of fingers
Z-deformity of thumb
Rupture of hand extensor tendons
Larger joints involved i.e. hip / knee
What are the other 5 types of presentations of RA?
- Palindromic: monoarticular attacks lasting 24-48h => 50% progresses to other types of RA
- Transient: self-limiting, lasts <12months, no permanent joint damage. Seronegative for IgM RF and ACPA
- Remitting: several years of active RA but then remits, minimal damage
- Chronic persistent: typical form
=> may be sero+ve or -ve for RF
=> relapsing / remitting course over several years
=> sero+ve and ACPA patients develop greater joint damage & long term disability
=> need early, more aggressive treatment with DMARD - Rapidly progressive: leads rapidly to severe joint damage + disability
=> sero+ve & ACPA = high incidence of systemic complications & difficult to treat
What are the factors predicting a poor prognosis for progression in early RA?
Older age
Female sex
Symmetrical small joint involvement
Morning stiffness >30mins
> 4 swollen joints
Smoking
Co-morbidity
High CRP
+ve RF and ACPA
What are the differential diagnosis of RA?
Postviral arthritis i.e. rubella, hepatitis B
Seronegative spondyloarthropathies
Polymyalgia rheumatica
Acute nodal osteoarthritis (PIP, DIP joints involved)
What are the complications of RA?
Septic arthritis
Amyloidosis - risk in uncontrolled RA but rare
*RA 2nd most common cause of amyloidosis
More than 6 points is the cut off for diagnosing RA.
What are the 4 main components of the diagnostic criteria for RA?
a) Joint involvement 1 large joint = 0 points 2-10 large joints = 1 point 1-3 small joints = 2 points 4-10 small joints = 3 points >10 joints (at least 1 small joint) = 5 points
b) Serology
-ve RF and anti-CCP = 0 points
Low +ve RF or low +ve anti-CCP = 2 points
High +ve RF or high +ve anti-CCP = 3 points
c) Acute phase reactants
Normal CRP / ESR = 0 points
Abnormal CRP or ESR = 1 point
d) Duration of symptoms
>6 weeks = 1 point
What investigations are carried out if RA is suspected?
Bloods: Raised platelets, ESR, CRP
=> Anaemia of chronic disease
Serology:
=> RF +ve in 70% - high titre assoc. with severe disease, erosions & extra-articular disease
=> Anti-CCP - highly specific (98%) for RA + sensitive (70-80%) ; also predicts disease progression
X-rays:
=> Soft tissue rheumatoid nodules, juxta-articular osteopenia and reduced joint space
=> Later, bony erosion, subluxation, complete carpal tunnel destruction
MRI / Ultrasound:
=> Synovitis
=> Bone erosions
Aspiration of the joints
ANTI-CCP (Anti-cyclic citrullinated peptides) = ACPA (anti-citrullinated protein antibodies)
Both anti CCP and ACPA are the same/interchangeable
~40% of patients with RA experience non-articular features.
What are the non-articular features of RA?
- Subcutaneous Nodules:
=> Firm , intradermal nodules occuring over pressure points i.e. elbows, finger joints, achilles tendon
=> Lungs, cardiac, CNS, lymphadenopathy, vasculitis - Tenosynovitis of flexor tendons in the hand - stiffness
=> Bursitis
3. Lungs: => Pleural effusion => Interstitial lung disease => Small airway disease => Nodules
- CVS
=> Pericarditis / pericardial effusion
=> Endocarditis
=> Myocardial disease i.e. MI, IHD - CNS
=> Carpal tunnel syndrome
=> Peripheral neuropathy
6. Eye => Scleritis / episcleritis => Scleromalacia => Keratoconjunctivitis sicca => Sjögren's syndrome (dry eyes/mouth)
- Osteopororis
- Amyloidosis
- Splenomegaly (Felty syndrome)
- Anaemia
- Atlantoaxial subluxation may cause cervical cord compression
How do you manage RA?
- Early diagnosis & referral to rheumatologist
- Early use of DMARDs + biological agents => improves long term outcomes
- Steroids => rapidly reduce symptoms & inflammation
=> used in acute exacerbation
=> intra-articular steroids for rapid but short term effect
=> oral steroids for difficult symptoms - NSAIDs good for symptom relief but no effect on disease progression
- Surgery may help relieve pain, improve function and prevent deformity.
* paracetamol & weak opiates not effective
RA increases risk of cardiovascular/cerebrovascular disease
=> RA accelerates atherosclerosis
=> Manage risk factors of atherosclerosis
Smoking increases symptoms of RA
What are disease-modifying anti-rheumatic drugs (DMARDs)?
What are some side effects?
DMARDs = 1st line in RA and started within 3 months of persistent symptoms
=> 6-12 weeks for symptomatic relief
=> Combination of methotrexate, sulfasalazine and hydroxychloriquine (all types of DMARD) = best results
Side effects:
=> Immunosuppression - can be fatal with pancytopenia, increased risk of infection with atypical organisms, neutropenic sepsis
=> Methotrexate: pneumonitis, oral ulcers, teratogenic, hepatotoxicity
=> Sulfasalazine: rash, reduced sperm count, oral ulcers, GI upset
=> Hydroxychloroquine: retinopathy
Biologics are initiated by specialists when at least 2 DMARD trial has failed.
What are biological agents and when is it used in RA?
- TNF-a inhibitor i.e. infliximab => 1st line
- B-cell depletion i.e. rituximab
=> used in combination with methotrexate for active RA
=> when DMARD and TNF-a inhibitor failed - IL-1 & IL-6 inhibitor i.e. tocilizumab
=> used in combination with methotrexate
=> when TNF-a inhibitor has failed - Inhibitor of T-cell co-stimulation i.e. abatacept
=> active RA when DMARDs / TNF-a blocker failed
What are some side effects of biologics used in RA?
Severe infection
Reactivation of TB
Hepatitis B
Worsening HF
Hypersensitivity
Skin cancers
What is the mechanism of action of methotrexate?
Methotrexate is an antimetabolite, which inhibits enzyme dihydrofolate reductase, thus inhibiting the synthesis of the purines and pyrimidines necessary for nucleic acid synthesis.
=> Anti-inflammatory effects
Adenosine signalling in RA - increases adenosine levels and adenosine interaction with its extracellular receptors => an intracellular cascade is activated promoting an overall anti-inflammatory state
