Rheumatoid Arthritis (RA) Flashcards
Define Rheumatoid Arthritis (RA).
A chronic, systemic, inflammatory AUTOIMMUNE disorder of the synovial joints, causing a SYMMETRICAL POLYARTHRITIS
Describe the epidemiology of RA.
- 2 to 3 times more common in women.
- Approximately 1% of the population affected.
- Prevalence increased in smokers.
Describe the usual onset of RA.
Aged 30-50.
Rapid, within a year.
Describe the aetiology of RA.
Auto-antibodies e.g. RF and anti-CCP lead to a defective cell mediated immune response.
Give 5 risk factors for RA.
- Gender
- Women - especially pre-menopausal = risk 3x greater (suggests role of sex hormones - oestrogen?) - FHx
- Genetics
- HLA DR4 (a gene often present in RF positive patients)
- HLA DR1 (a gene occasionally present in RA patients) - Smoking
- Obesity
Describe the disease process behind RA.
- Chemoattractants in the joint recruit inflammatory cells
- B/T cells + neutrophils infiltration
- Production of cytokines (IL-1,2,4,6,8 + TNF-a) by T cells = inflammation.
- Overproduction of TNF-a
- Synovitis -> proliferation -> pannus formation -> pannus destroys articular cartilage and subchondral bone.
= inflammation at the synovial membrane
= damage to soft tissue and cartilage
= damage to bone
Give 5 symptoms of RA.
- Early morning + cold-environment stiffness (>60 mins).
- Pain that eases with use.
- Swelling.
- Systemic symptoms e.g. fatigue, weight loss, flu like illness, muscles aches + weakness
- Extra-articular involvement.
Describe the character of the pain from RA.
Morning stiffness >60 mins.
Pain is accompanied by stiffness.
Give 5 signs of RA.
- Symmetrical.
- Deforming.
- Polyarthropathy.
- Erosion on X-ray.
- 80% are RF positive.
Describe the pattern of joints affected by RA.
Symmetrical.
Small and large joints on both sides.
>3 affected, hands usually involved.
What joints tend to be affected in RA?
- MCP.
- PIP.
- MTP.
- Wrist.
Give 5 key signs in the hands for RA.
- Z shaped deformity to the thumb
- Swan neck deformity (hyperextended PIP with flexed DIP)
- Boutonnieres deformity (hyperextended DIP with flexed PIP)
- Ulnar deviation of the fingers at the knuckle (MCP joints)
- Piano key deformity of the wrist
Which joint is almost never affected in RA?
Distal interphalangeal joints (DIP)
- If you come across enlarged painful distal interphalangeal joints, this is most likely to be Heberden’s nodes due to osteoarthritis.
If you were examining the hands of someone with RA, give 5 things you might expect to see.
- DIP not affected
- Hurts to squeeze the joints
- Joints are warm
- Ulnar deviation
- Cannot make a fist
- Z thumb
- Swan neck deformity
What systemic features are present in RA?
- Elbow and lung nodules
- Vasculitis
- Pericarditis
- Carpal tunnel
- Sjorgen’s
- Raynaud’s
- Lymphadenopathy
- Fever, myalgia, malaise, fatigue
RA extra-articular involvement: describe the effect on soft tissues.
- Nodules.
- Bursitis.
- Muscle wasting.
RA extra-articular involvement: describe the effect on the eyes.
- Dry eyes.
- Scleritis (severe pain, can’t look at bright lights)
- Episcleritis (non severe mild redness of eyes)
RA extra-articular involvement: describe the neurological effects.
- Sensory peripheral neuropathy.
- Entrapment neuropathies e.g. carpal tunnel syndrome.
- Instability of cervical spine.
RA extra-articular involvement: describe the haematological effects.
- Palpable lymph nodes.
- Splenomegaly.
- Anaemia.
RA extra-articular involvement: describe the pulmonary effects.
- Pleural effusions
- Fibrosing alveolitis
- Pneumoconiosis (Caplan’s syndrome, especially in miners)
- Pulmonary nodules, pulmonary fibrosis
- Interstitial lung disease
- Bronchiectasis
RA extra-articular involvement: describe the effects on the heart.
- Pericardial rub.
- Pericardial effusion.
RA extra-articular involvement: describe the effect on the kidneys.
Amyloidosis.
What investigations might you do in someone who you suspect has rheumatoid arthritis?
- Bloods for inflammatory markers; ESR and CRP will be raised.
- Test for anaemia.
- Test for RF and anti-CCP.
What would the lab findings be in RA?
- Rheumatoid factor - RhF +ve
- Anti-cyclic citrullinated peptide - Anti-CCP +ve
= highly specific for RA - Inflammatory markers - Raised CRP + Raised ESR
- FBC -> Normochromic normocytic ANAEMIA
What is rheumatoid factor?
An antibody against the Fc portion of IgG.
What would be the radiological findings in RA on a X-ray?
LESS:
Loss of joint space, Erosions, Soft bone, Swelling of soft tissue.
SPADES:
S - Soft tissue swelling
P - Peri-articular osteoporosis + erosions
A - Absent osteophytes
D - Deformity
E - Erosions (late feature)
S - Subluxation (joint space narrowing; late feature)
What is the diagnostic criteria for RA?
Need 4 out of 7:
- Morning stiffness >1h.
- 3+ joints affected.
- Arthritis in hand joints.
- Symmetrical.
- Rheumatoid nodules.
- RhF+ve.
- Radiological changes.
Describe the treatment for RA.
- Pain management - NSAIDs.
- DMARDs.
- Biological agents.
- Steroids - for flare ups
Management of rheumatoid arthritis requires the early introduction of DMARDS, often in combination with short courses of steroids, before escalation to biological drugs if disease activity persists.
Treatment of RA 1: Pain management with NSAIDs.
Pain management:
* NSAIDs e.g. IBUPROFEN and COX inhibitors e.g. ASPIRIN - relieve joint pain & stiffness - does not slow disease progression
- PARACETAMOL with/without opioid e.g. CODEINE or
DIHYDROCODEINE - weak opioids for additional pain relief
Treatment of RA: Corticosteroids.
- Short-term managements of flare ups in adults:
- Oral corticosteroids e.g. ORAL PREDNISOLONE have many side
effects - IM injection of depot for those waiting for DMARDs to work e.g.
METHYLPREDNISOLONE (IM) - Intra-articular injection - semicrystalline steroid (rapid but short-lived effect)
Treatment of RA 2: DMARDs.
Disease-Modifying Anti-Rheumatic drugs (DMARDs):
* Inhibit inflammatory cytokines - thereby suppress immune system and thus carry risk of INFECTION
* Used early to reduce inflammation and slow development of joint erosions and irreversible damage
* Take 6 weeks to start working
* All have serious side effects = so monitoring with blood tests is required
Give 3 examples of DMARDs.
- Oral Methotrexate
- Oral Sulfasalazine
- Oral Leflunomide
Which is the gold standard DMARD drug to use for RA?
Oral Methotrexate
How does methotrexate work as a treatment for RA?
Inhibits dihydrofolate reductase, which converts dietary folic acid to tetrahydrofolate (FH4), which is required for DNA and protein synthesis.
Lack of FH4 prevents cellular replication.
Also has anti-inflammatory and immunosuppressive effects.
Mediated by IL-6 and -8 and TNF-alpha.
When can methotrexate not be used in RA?
IN pregnancy!!
It is teratogenic (harmful to pregnancy) and needs to be avoided prior to conception in mothers and fathers.
Give some side effects of oral methotrexate (DMARD).
Nausea, mouth ulcers, diarrhoea, abnormal LFTs,
neutropenia, thrombocytopenia, renal impairment
What aminosalicylate is a treatment option for RA and how does it work?
Sulfasalazine - DMARD.
Releases 5-ASA, which has anti-inflammatory and immunosuppressive effects.
Give some side effects of oral sulfasalazine (DMARD).
Nausea, skin rashes, mouth ulcers, neutropenia,
thrombocytopenia, abnormal LFTs
Give some side effects of oral leflunomide (DMARD).
Diarrhoea, neutropenia, thrombocytopenia, alopecia,
hypertension
What are the 4 types of biological agents that can be given for RA?
- TNF-a blockers
- B-cell inhibitors
- Interleukin blockers
- T cell activation blockers
What is the 1st-line biological agent treatment?
TNF-a blockers, given alongside methotrexate
- Adalimumab
- Infliximab
- Golimumab
- Certolizumab pegol
- Etanercept
Give an example of a B-cell blocker as a biological agent for RA treatment. What are its side effects?
RITUXIMAB (IV):
* Monoclonal antibody that targets CD20 on B cells
* Side effects: hypo/hypertension, skin rash, nausea, pruritus,
back pain
* Used in those who have failed to respond to anti-TNF agents
Side effects:
1. Vulnerability to severe infections and sepsis
2. Night sweats
3. Thrombocytopenia (low platelets)
4. Peripheral neuropathy
5. Liver and lung toxicity
Give an example of an Interleukin blocker as a biological agent for RA treatment. What are its side effects?
- TOCILIZUMAB:
* Monoclonal antibody that binds to IL-6 cytokine before it
reaches target receptor
* IL-6 & -1 are the most important in joint inflammation
* Used alongside METHOTREXATE - ANAKINRA:
* Monoclonal antibody that is a IL-1 antagonist
Give an example of a T cell activation blocker as a biological agent for RA treatment. What are its side effects?
ABATACEPT:
* Blocks T cell activation which thus means macrophages and
B cells cannot be activated thus reducing inflammation
Which RA treatment requires regular pregnancy tests in women of child-bearing age and why?
Methotrexate - it’s a folic acid antagonist, risk of neural tube defects is high.
Key side effects for RA medications:
1. Methotrexate
2. Leflunomide
3. Sulfasalazine
4. Hydroxychloroquine
5. Anti-TNF medications
6. Rituximab
TOM TIP: There are a lot of side effects to remember for your exams. Many of them are shared between medications. Try to remember the unique ones as these are more likely to be tested:
Methotrexate: Bone marrow suppression and leukopenia and highly teratogenic
Leflunomide: Hypertension and peripheral neuropathy
Sulfasalazine: Male infertility (reduces sperm count)
Hydroxychloroquine: Nightmares and reduced visual acuity
Anti-TNF medications: Reactivation of TB or hepatitis B
Rituximab: Night sweats and thrombocytopenia
What test is used to monitor the disease progression of RA + its response to treatment?
DAS28 Score (the Disease Activity Score):
- Based on the assessment for 28 joints
- Points are given for:
1. Swollen joints
2. Tender joints
3. ESR/CRP result
4. The patients ‘assessment of global health’ (0-100)
What factors would indicate a worse prognosis?
The following features are associated with a worse prognosis:
- High ESR/CRP
- Early erosions on X-rays
- High tender or swollen joint counts
- Positive anti-CCP or rheumatoid factor
List some key differences between RA and OA.
Outline the NICE guideline for DMARD use for RA.
- Mono therapy - methotrexate, leflunomide, Sulfasalazine, hydroxychloroquine
- Dual therapy - 2x DMARDs
- Methotrexate + biological agent - usually TNF inhibitor (main ones: adalimumab, infliximab, Etanercept)
- Methotrexate + Rituximab (Anti-CD20)
Which 2 DMARDs cannot be used during pregnancy?
- Methotrexate
- Leflunomide
Both = Teratogenic!!
Name 1 life-threatening complication of RA.
Felty Syndrome.
Triad:
1. RA
2. Granulocytopenia
3. Splenomegaly
