Rheumatoid Arthritis Flashcards
What is rheumatoid arthritis?
an autoimmune condition that causes inflammation of the synovial lining of the joints, tendon sheaths and bursa
it is an inflammatory arthritis
it mostly affects the joints, but can affect other organ systems such as the skin and lungs
What type of arthritis is RA and why?
symmetrical polyarthritis
- it tends to be symmetrical and affects multiple joints (> 5 on each side)
What does inflammation of the tendons increase the risk of?
inflammation of the tendons increases the risk of tendon rupture
Who tends to be affected by RA?
- 3 times more common in women
- can present at any age, but usually develops in middle age
- family history increases the risk
Is RA genetic or environmental?
- it is an autoimmune condition that is usually triggered by a combination of genetic + environmental factors
- environmental factors can cause modification of our own antigens
e.g. someone with HLA-DR1 or DR-4 may develop RA after being exposed to something in the environment (e.g. cigarette smoke)
What joints are commonly affected by RA?
it tends to affect the small joints, such as:
- proximal interphalangeal (PIP) joints
- metacarpophalangeal (MCP) joints
- metatarsophalangeal (MTP) joints
- cervical spine
- wrist / ankle
as the disease worsens, it begins to affect large joints, such as:
- shoulders
- knees
- ankles
- elbows
RA rarely ever affects the DIPs - if these are swollen, it is more likely to be OA
What is meant by a RA flare?
- occurs when there is a sudden worsening of symptoms
- affected joints become warm, swollen, red and painful
What is a Baker (popliteal) cyst and why does it occur?
- a one-way valve can form within the knee joint
- fluid from the swollen knee fills the semi-membranous bursa
- the synovial sac becomes so swollen that it bulges posteriorly into the popliteal fossa
- this creates a synovial fluid-filled cyst
What are the genetic associations of RA?
HLA-DR4:
* this gene is often present in RF positive patients
HLA-DR1:
* this gene is occasionally present in RA patients
What are the 2 main autoantibodies associated with RA?
- rheumatoid factor (RF)
- anti-CCP antibodies
anti-CCP = cyclic citrullinated peptide antibodies
What is rheumatoid factor and how does it play a role in arthritis developing?
- IgM autoantibody
- it targets the Fc portion of the IgG antibody
- this causes activation of the immune system against the patients own IgG, causing systemic inflammation
RF is present in around 70% of RA patients
How are anti-CCP antibodies more specific to RA than RF?
- anti-CCP autoantibodies are more sensitive and specific to RA than RF
- they pre-date the development of RA
- the presence of anti-CCP autoantibodies gives an indication that the patient will develop RA at some point
these autoantibodies target citrullinated proteins
What are the 3 key symptoms associated with RA?
it presents as a symmetrical distal polyarthropathy with joint:
- pain
- swelling
- stiffness
What is the onset of RA like?
Which joints tend to be affected?
- the onset can be rapid (i.e. overnight) or take months to years
- typically, there is pain + stiffness in the small joints of the hands and feet
- larger joints such as the knees, shoulders and elbows can also be affected
When does the pain associated with RA tend to be worse?
- the pain is worse after rest and improves with activity
- stiffness is worse in the morning (or after periods of inactivity)
- morning stiffness usually lasts > 30 minutes
this is different to OA, in which pain is worse on activity and improves with rest
What are the systemic symptoms associated with RA?
- fatigue
- weight loss / loss of appetite
- flu-like illness
- muscle aches / weakness
What is meant by palindromic rheumatism?
- there are self-limiting short episodes of inflammatory arthritis
- these involve pain, stiffness and swelling affecting only a few joints
- they tend to last 1-2 days and then completely self resolve
What is a concerning finding in palindromic rheumatism?
- the presence of anti-CCP or RF
- this indicates that it is likely to progress to full RA
What is meant by atlantoaxial subluxation?
- occurs in the cervical spine
- the axis (C2) and odontoid peg shift within the atlas (C1)
- this results in instability and increased mobility between C1 and C2
- caused by local synovitis and damage to the ligaments and bursa around the odontoid peg of the axis and atlas
What is the major risk associated with atlantoaxial subluxation?
When is this particularly important?
- subluxation can result in spinal cord compression - this is an EMERGENCY
- particularly important if a patient is having general anaesthetic and requiring intubation
- MRI scans can visualise changes in these areas as part of pre-op assessment
What will it feel like when palpating around a joint affected by RA?
- palpation of the synovium around affected joints gives a “boggy” feeling
- this is related to inflammation and swelling
What are the 4 key findings in the hands of someone with RA?
- Boutonnieres deformity
- swan neck deformity
- ulnar deviation of the fingers at the MCP joint
- Z shaped deformity of the thumb
What is swan neck deformity?
- hyperextension at the PIP joints
- flexion at the DIP joints
What is Boutonnieres deformity?
- flexion of the PIP joints
- hyperextension of the DIP joints
What are the 5 most significant extra-articular manifestations of RA?
rheumatoid nodules:
* occur at pressure points (e.g. elbow)
- rarely occur in the lungs, heart + sclera
anaemia
increased risk of atherosclerosis:
* and associated risk of MI / stroke
interstitial lung fibrosis:
* also called Caplan’s syndrome
pleural effusions:
* presents with progressive SOB
What are rheumatoid nodules?
- firm lumps that develop under the skin
- usually occur near the affected joints
What is Caplan’s syndrome?
- pulmonary fibrosis with pulmonary nodules
- it involves swelling and scarring of the lungs
- it occurs in people with RA that have been exposed to dust from coal or silica
What is bronchiolitis obliterans?
inflammation causing small airway destruction
- inflammation in the small airways causes them to become scarred, resulting in permanent narrowing
What is Felty’s syndrome?
- a triad of RA, neutropenia and splenomegaly
- this results in repeated infections
neutropenia = decreased WCC
What mnemonic is used to remember the components of Felty’s syndrome?
SANTA
S - splenomegaly
A - anaemia
N - neutropenia
T - thrombocytopenia
A - arthritis (rheumatoid)
What is secondary Sjögren’s (Sicca) syndrome?
- an autoimmune condition which affects parts of the body that produce fluids
- most commonly dry mouth, dry eyes, fatigue and MSK pain
- also affects salivation / tear production
What are other possible extra-articular manifestations of RA?
- anaemia of chronic disease
- episcleritis / scleritis
- cardiovascular disease
- lymphadenopathy
- carpal tunnel syndrome
- amyloidosis
How is RA diagnosed?
the diagnosis is mostly clinical in patients presenting with a symmetrical polyarthropathy affecting the small joints +
- check rheumatoid factor (RF)
- if RF negative, check anti-CCP antibodies
- check inflammatory markers - CRP & ESR
- XR of hands and feet
What X-ray changes would you expect to see in RA?
- joint destruction + deformity
- soft tissue swelling
- periarticular osteopenia
- bony erosions
What is periarticular osteopenia?
- there is a lower-than-normal bone mass in the region surrounding the joint
- it is the earliest radiographic sign of RA
When should a patient be referred to a specialist?
- anyone with persistent synovitis
- even if they have negative RF, anti-CCP and inflammatory markers
URGENT REFERRAL:
- if it the small joints of the hands / feet are involved
- if multiple joints are involved
- symptoms present for > 3 months
What diagnostic score is used to determine whether a patient has RA?
patients are scored based on:
- the joints involved (more and smaller joints score higher)
- serology (RF + anti-CCP)
- inflammatory markers (ESR + CRP)
- duration of symptoms (more or less than 6 weeks)
a score of 6 or more indicates a diagnosis of RA
Diagnostic criteria come from the American College of Rheumatology (ACR) / European League Against Rheumatism (ELAR) from 2010
What is the DAS28 score and what is it used for?
Disease Activity Score
- based on the assessment of 28 joints
- points are given for swollen joints, tender joints and ESR/CRP result
- used to monitor disease activity and response to treatment
What is the Health Assessment Questionnaire (HAQ) and when do NICE recommend it is used?
- it measures functional ability
- it is recommended to be used at diagnosis to monitor response to treatment
Which patients with RA are more likely to have a worse prognosis?
- younger onset
- male patients
- having more joints & organs affected
- RF AND anti-CCP present
- bone erosions on XR
What treatment is often given to patients with RA at their first presentation?
- a short course of steroids can be used at first presentation and during flare ups to quickly settle the disease
- NSAIDs / COX-2 inhibitors can be effective
- these must be co-prescribed with PPIs due to the risk of GI bleeding
What is the overall aim of treatment for RA?
How is its effectiveness monitored?
- the aim is to induce remission or get as close to remission as possible
- DAS28 and CRP are used to monitor treatment
- the dose of medication is reduced to the “minimal effective dose” that controls the disease
What is the first-line treatment for RA?
monotherapy with one of:
- methotrexate
- sulfasalazine
- leflunomide
- in very mild disease, hydroxychloroquine is considered
these are all forms of disease modifying anti-rheumatic drugs (DMARDs)
What is second-line treatment for RA?
the use of 2 DMARDs in combination:
- methotrexate
- sulfasalazine
- leflunomide
What is the third line treatment for RA?
methotrexate + biologic
this is usually a TNF inhibitor
What is the fourth line treatment for RA?
methotrexate + rituximab
rituximab = anti-CD20
What DMARDs are used in pregnancy?
Why must different drugs be used?
- hydroxychloroquine and sulfasalazine are considered in pregnancy
- pregnant women tend to have an improvement in symptoms during pregnancy
- thought to be due to naturally higher production of steroid hormones
What are the most commonly used anti-TNF biologics?
- adalimumab
- infliximab
- etanercept
What is the most serious side effect associated with all biologics?
IMMUNOSUPPRESSION
- patients are prone to serious infections
- there can also be reactivation of dormant infections - such as TB and hepatitis B
When does surgery play a role in the management of RA?
the use of DMARDs and biologics means that patients are less likely to progress to the stage in which they need surgery
How is methotrexate taken?
What must be co-prescribed with it?
- taken once a week as an injection or tablet
- folic acid 5mg must also be taken once a week, on a different day to methotrexate
What are the most significant side effects associated with methotrexate?
- mouth ulcers / mucositis
- liver toxicity
- bone marrow suppression & leukopenia (low WCC)
- teratogenic (must be avoided in men and women prior to conception)
What are the most significant side effetcs of leflunomide?
- teratogenic
- bone marrow suppression & leukopenia
- mouth ulcers / mucositis
- liver toxicity
- rashes
- raised BP
- peripheral neuropathy
it is an immunosuppressant that interferes with the production of pyrimidine (part of DNA & RNA)
What are the side effects associated with sulfasalazine?
- bone marrow suppression
- temporary male infertility (reduced sperm count)
it is safe in pregnancy but adequate folic acid supplementation is required
What are the side effects associated with hydroxychloroquine?
- nightmares
- reduced visual acuity (macular toxicity)
- liver toxicity
- skin pigmentation
typically used as an anti-malarial medication that interferes with toll-like receptors
How do anti-TNF drugs work?
- tumour necrosis factor (TNF) is a cytokine involved in stimulating inflammation
- blocking TNF reduces inflammation
What are the most serious side effects associated with anti-TNF medications?
- vulnerability to serious infections + sepsis
- reactivation of TB and hepatitis B
How does rituximab work?
- it is a monoclonal antibody that targets the CD20 protein on the surface of B cells
- it causes destruction of B cells
What are the most serious side effects associated with rituximab?
- vulnerability to severe infections + sepsis
- night sweats
- thrombocytopenia
- peripheral neuropathy
- liver / lung toxicity
