Rheumatology (Autoantibodies, DMARDs, Joint conditions) Flashcards
autoantibodies for RA
rheumatoid factor
anti-CCP (higher specificity)
autoantibodies for SLE
Presence of
- ANA - high sensitivity, not very specific
- Anti-dsDNA (more specific)
- Anti- Ro and Anti- La
During flare
- Raised ESR (normal CRP)
- decreased C3 and C4
Autoantibodies in Sjorgrens syndrome
- rheumatoid factor (RF) positive in around 50% of patients
- ANA positive in 70%
- anti-Ro (SSA) antibodies in 70% of patients with PSS
- anti-La (SSB) antibodies in 30% of patients with PSS
autoantibodies for systemic sclerosis
anti-Scl-70
anti-centromere
autoantibodies for granulomatosis with polyangiitis (Wegener’s granulomatosis)
Cytoplasmic ANCA (c-ANCA)
autoantibodies for eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
p-ANCA
autoantibodies for primary sclerosing cholangitis
p-ANCA
classification of DMARDS
Conventional DMARDS - broad immunosuppressive effects
- methotrexate
- sulfalazine
- hydroxychloroquine
Biologic DMARDs- genetically engineered proteins that target specific parts of the immune system
- TNF inhibitors e.g. infliximab
- B cell inhibitors e.g. rituximab
- Interleukin inhibitors
- T-cell inhib inhibitors
Targeted synthetic DMARDS- target specific immune system componenents
- Janus kinase inhibitors
- JAK1 and JAK2 inhibots
- Phosphodiesterase type 4-inhibitor
patients on DMARDs should seek immediate help if they have signs of
Blood disorders whose features may include:
* Sore throat
* Fever
* Bruising
* Mouth ulcers
Liver toxicity whose features may include:
* Nausea, vomiting, or abdominal discomfort
* Dark urine
Respiratory effects such as:
* Shortness of breath
Methotrexate
MOA
- antifolate
Dosing
- given once a week
- prescribed with folic acid and taken on different days to the methotrexate dosea
Contraindication
- pregnancy or trying for pregnancy (men and women)
- active infections
- do not breastfeed
Adverse reaction
- anorexia
- N and V
- diarrhoea
- mouth ulcers
- pneumonitis
- pulmonary fibrosis
- liver damage sich as hepaitits, cirrhosis or fibrosis
Monitoring
Pre-treatment screening:
* Pregnancy must be excluded before treatment
* Patients should have FBC, U&Es, and LFTs done before treatment
Monitoring:
* FBC, U&Es, LFTs every 1-2 weeks until therapy stabilised
* Then FBC, U&Es, and LFTs every 2-3 months
sulfalazine
MOA
- It metabolises into 5-aminosalicylic acid (5-ASA) which appears to play a bigger role in its therapeutic effect.
Contraindications
- Salicylate hypersensitvity
Interactions
- concomitnant use with azathiprine may cause bone marrow suppression
Adverse effects
- nausea
- oral ulcerrs
- myelosuppression
- Oligospermia
- SJS and TEN
- cough
- intersititial lung disease
Monitoring
* FBC including white cell differential and platelet count, U&Es, and LFTs must be done initially and monthly during the first 3 months
* After 12 months, monitoring may be stopped
hydroxychloroquine
MOA
- not fully understood
Contraindications
- known hypersensitivity
- eye problems
Interactions
- Hydroxychloroquine prolongs the QT interval, avoid using it with any drugs that prolong the QT interval e.g. amiodarone, clarithromycin, citalopram etc.
Adverse effects
* Photosensitive skin rashes
* Nausea
* Dyspepsia
* Diarrhoea
* Headaches
* Hair loss
* Tinnitus
* Visual problems – retinopathy
Monitoring
- Baseline ophthalmological examination (fundus photography and spectral domain optical coherence tomography) and annually following
Pregnancy and breastfeeding
- May be used in pregnancy if needed
- May be used if breastfeeding, small amounts may be present in milk
Biologic DMARDs
Adverse effects
- The main adverse effect is that anti-TNF medication can reactivate latent tuberculosis as TNF-α is needed to maintain the latent state.
Monitoring
- FBC, U&Es, and LFTs at 3-4 months, then every 6 months
- Lipids 4-8 weeks after starting treatment
If indicated: assessment for hepatitis B, hepatitis C, tuberculosis, or HIV
Osteoarthritis (OA)
is a degenerative joint disorder whose prevalence increases with age. It’s also known as the “wear and tear” of joints.
OA commonly affected joints
- Knee
- Hip
- PIP and DIP
- the spine (lumbar and cervical regions)
OA Risk Factors & Associations
- > 50yrs
- Female sex
- Family history of OA
- Obesity
- Physically demanding occupation
- Sports
- Trauma/injury
- Hypermobility
presentation of OA
worse on activity and relieved with rest
- morning stiffness that lasts <30 mins
- history of long term physical labour
- PIP and DIP joints affacted (spares MCP joint)
- localised tnederness over joint line
- Knee locking or giving way
- Bony deformity
- active and passive range of movement may be reduced and painful
OA signs on examiantion
- Squaring of the base of the thumb (first carpometacarpal joint) is a sign of hand OA
- In advanced knee OA: new bone formation causes bony swellings around the knee joint
- Enlargement of the DIP joints – Heberden nodes
- Enlargement of the PIP joints – Bouchard nodes
- There may be palpation of crepitus during movement of the joint
- There may be small effusions
- There may be joint line tenderness
- Patients may have an abnormal gait
x-ray findings for OA
LOSS
- Loss of joint space
- Osteophytes
- Subchondral sclerosis
- Subchondral cysts
OA vs RA
- Usually a symmetrical small joint polyarthritis affecting the MCP and PIP joints and may spare the DIP joints
- RA is associated with prolonged morning stiffness (>30 minutes)
- Joint pain and stiffness are worse with rest and improve with movement
- There can also be evidence of systemic upset, such as fatigue, low mood, and fever
Management of OA
First line
- Weight loss if appropriate
- Muscle strenghthening
- Paracetamol and topical NSAIDs for OA of the hand or knee
Second line
- Oral NSAID/COX-2 inhibitor + PPI
Third line
- Intra-articular corticosteorid injections
Fourth line
- Joint replacement surgery - appropriate if OA having significant impact on QoL
RA
is an autoimmune disorder characterised by inflammation of the synovial membrane leading to joint swelling, tenderness, warmth, and stiffness. This can also lead to destruction of the surrounding tissues and the joint. RA may also have extra-articular disorders.
Risk Factors for RA
- Family history
- Smoking
- HLA-DR4 or HLA-DR1
presentation of RA
RA typically presents with an insidious onset (generally over months) of symmetrical polyarthritis (arthritis affecting both sides equally) affecting the small joints of the hand and feet.
Pain
- worse with rest and improve with exercise
- prolonged moring stiffness >1 hour
Joint erythema and warmth
* Metacarpophalangeal (MCP) - positive MCP squeeze test
* Proximal interphalangeal (PIP)
* Metatarsophalangeal (MTP)
Joint swelling
- boggy or squishy around joint
Additional
* Rheumatoid nodules – hard swellings over extensor surfaces
* Extra-articular features (vasculitis or eye, lung, or heart involvement)
* Systemic upset (fever, fatigue, weight loss, night sweats, malaise)
RA signs on examination
- ‘Boggy’ swellings around joints
- Swan neck deformity – late-stage sign
- Boutonniere’s deformity – late-stage sign
- Ulnar deviation due to MCP inflammation
- Rheumatoid nodules on extensor surfaces of tendons
extra articular features of RA
vasculitis or eye, lung, or heart involvement)
investigations for RA
Autoantibodies
Rheumatoid factor (RF):
* High sensitivity, but around 1/3 of patients are RF-negative
Anti-cyclic citrullinated peptide (anti-CCP) antibody:
* High specificity, positive in around 80% of people with RA
Imaging
X-ray of the hands and feet – in all patients with RA:
* Helps with diagnosis and determination of disease severity
* May show loss of joint space, juxta-articular osteoporosis, soft tissue swelling, periarticular erosions, or subluxation
Other investigations to consider are:
C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR):
* Non-specific markers of inflammation
Full blood count, urea and electrolytes, and liver function tests:
* Guides treatment and identifies comorbidities
XRAY finding RA
LESS
L – loss of joint space
E – erosions
S – soft tissue swelling
S – soft bones (osteopenia)
when diagnosing RA what needs to be ruled out
septic arthritis
management of RA in primary care
Consider offering an NSAID and proton pump inhibitor while awaiting a rheumatology appointment for symptomatic relief.
If a flare of RA occurs, rule out septic arthritis, seek specialist advice and offer short-term glucocorticoid treatment, which may involve:
* Intra-articular glucocorticoid, intramuscular glucocorticoid, or oral glucocorticoids
secondary care management of RA
First line:conventional DMARD and short term prednisolone bridging therapy (oral, intramuscular or intra-articular) while waiting for cDMARD to take ffect (2-3 months)
- Methotrexate (+ folic acid)- must monitor FBC and LFT for risk of myelosuppression and liver cirrhosis or
- Sulfasalazie or
- Hydroxychloroquine
Second line: if inadequate response to at least 2 cDMARDS consider biologic DMARD
- TNF-inhibitors e.g. inflixamab
- B-cell inhibitor e.g. Rituximab
psoriatic arthritis
Psoriatic arthritis (PsA) is a seronegative inflammatory arthritis affecting joints and connective tissue and is associated with psoriasis of the skin or nails. PsA can occur without the presence of skin disease, or the rash may be difficult to notice.
PsA may affect the tendons surrounding the joints as well as the joints themselves. This can lead to swelling of the whole digit (dactylitis) or enthesitis (inflammation of the entheses, the sites where tendons or ligaments insert into the bone).
It is a progressive disorder ranging from mild synovitis to severe progressive arthropathy. Around 40-60% of patients with psoriatic arthritis develop erosive and deforming joint complications.
risk factors for psoriatic arthritis
- Psoriasis
- Family history of psoriatic arthritis
- HLA-B27
- Obesity
- Smoking
presentation of psoriatic arthritis
Monoarticular or oligoarticular joint involvement
Hand signs
- Pitting of nails
- Onycholysis
- Dactylitis - sausage-like swelling
Inflammatory joint pain:
- prolonged morning stiffness >30 mins
- better on exercise
- worse on prolonged rest
investigations for psoriatic arthritis
Investigations
X-ray of hands and feet:
- Shows erosions in DIP and periarticular new bone formation
- In advanced disease –“pencil in cup” deformity seen
Rheumatoid factor and anti-CCP:
- Rheumatoid factor may be positive or negative
- Anti-CCP is negative
If monoarthritis, synovial fluid aspiration and analysis:
- To exclude gout or septic arthritis
ESR/CRP:
- May be normal or elevated
Tests for metabolic syndrome:
- Patients with psoriatic arthritis have a higher risk of metabolic syndrome
management of psoriatic arthriits
Treatment is initiated by a rheumatology specialist.
The management of PsA is similar to rheumatoid arthritis except for the following difference:
- Limited peripheral joint disease: NSAID only, instead of offering all patients a disease-modifying antirheumatic drug (DMARD) as with rheumatoid arthritis
- As well as the DMARDs available for rheumatoid arthritis, monoclonal antibodies including ustekinumab and secukinumab are possible treatment options
septic arthritis
Any hot, swollen, acutely painful joint with restriction of movement is septic arthritis until proven otherwise, even in the absence of fever and irrespective of blood test and microbiology results.
Delayed diagnoses can lead to permanent joint damage and the resulting disability and mortality rates can be as high as 50%.
most common joints affected by septic arthritis
- Knee
- Hip
- Shoulder
- Ankle
- Elbow
- Wrist
pathophysiology of septic arthritis including pathogens
haematogenous spread
- Most common: Staph aureus
- Young sexually activate : Neisseria gonorrhoea
risk factors for septic arthritis
- OA/ RA
- Prosthetic joint
- > 80 yo
- IVDU
- HIV
- DM
- iImmunosupression
presentation of septic arthritis
single swollen joint with pain on active or passive movement
- hot, swollen, painful and restricted joint
- fever
- patient holds joint in position that maximises joint soace e.g. fully extended knee, hip abduced, flexed and externally roated
septic arthritis signs on examination
- Septic joints may be held in a position of maximum joint volume
- Joint effusions may be present
- Passive and active movement are limited and very painful
- Patients may not be able to weight-bear/walk
investigations for septic arthritis
Synovial fluid aspiration (except prostethic joints)
- ideally before starting antibiotics
- microscopy and gram stain
- culture and sensitivities
- WCC
Blood culture
- ideally before starting antibiotics - do not delya treatment arrnaging a blood culture
Bloods
FBC
- may show leukocytosis
CRP/ESR
- may be raised
UEs
- baseline
management of septic arthritis
Management
- If prosthetic joint involvement, immediately refer to orthopaedics to consider surgery
Immediate needle aspiration and blood cultures before giving antibiotics - IV antibiotics that cover Gram-positive cocci according to local hospital policy
- Flucloxacillin can be given
- Clindamycin can be given if the patient is allergic to penicillin
reactive arthritis
a seronegative arthropathy associated with inflammatory back pain, oligoarthritis, and extra-articular symptoms that usually occur 1-6 weeks after a gastrointestinal or urogenital infection. The organism cannot be recovered from the joint and is not present in it.
causes of reactve arthritis
Reactive arthritis is sometimes subdivided into two subgroups:
1) Post-enteric – the most commonly associated pathogens are:
* Campylobacter
* Salmonella
* Shigella
2) Post-venereal – typically following Chlamydia trachomatis infection
presentation of reactive arhtirits
“can’t see (eye involvement), pee (urethritis), or climb a tree (arthritis)”:
- Arthritis – usually an asymmetrical oligoarthritis affecting larger joints of the lower extremity
- Urethritis
- Eye involvement – conjunctivitis, anterior uveitis, episcleritis
- Skin involvement – circinate balanitis, keratoderma blennorrhagia
- Lower back pain
- Enthesitis (inflammation where a tendon inserts into the bone)
- Dactylitis (swelling of an entire digit)
Investigations for reactive arthritis
ESR and CRP:
* These are both increased
Anti-nuclear antibody (ANA):
* Negative
Rheumatoid factor (RF):
* Negative
Urogenital NAAT testing for Chlamydia trachomatis/Neisseria gonorrhoeae:
* Negative
Stool cultures:
* Negative
Plain x-rays:
* Sacroiliitis may be present
Arthrocentesis and synovial fluid analysis:
* Negative
Management of acute reactive arthritis:
1st line: NSAIDs e.g. naproxen/ibuprofen/diclofenac/indomethacin
2nd line: corticosteroids:
- Intra-articular if mono-/oligoarticular reactive arthritis
- Systemic steroids if many joints are affected or ocular manifestations present
If persistent or chronic reactive arthritis:
- Sulfasalazine
gout pathophysiology
Type of arthritis caused by deposition of monosodium urate crystals in and around joints
- associated with hyperuricaemia
- over time larger crystals can deposit in different regions fo the body leading to irregular nodules known as gouty tophi -> chronic joint damage
risk factors for gout
- Obesity
- Drugs – thiazides and loop diuretics
- Hypertension, coronary heart disease and heart failure
- Diabetes mellitus
- Chronic kidney disease
- High triglycerides
- Psoriasis
- Menopause
- Meat and seafood consumption
- Alcohol consumption
gout presentation
Gout typically presents acutely (over hours)
Acute severe joint pain, swelling, and warmth– may occur overnight
- Typical joints affected are in the feet, most cases occur in the first metatarsophalangeal joint (MTP) of the foot
- Usually monoarticular or oligoarticular (<5 joints)
- It may be polyarticular in older people
Gouty tophi may be present – these suggest longstanding, untreated gout
- They are seen on extensor surfaces of affected joints, Achilles tendons, dorsal hands and feet, and the helix of the ear
Investigations for gout
Arthrocentesis with synovial fluid analysis is diagnostic:
- Strongly negatively birefringent needle-shaped crystals under polarised light
Uric acid around 2 weeks after the attack resolves:
- This is because it may be falsely low or normal during attacks
Ultrasound scan which may show:
- Erosions
- Tophi
- Double contour lines
X-ray which may show:
- Periarticular erosions (may have a punched-out appearance or an overhanging edge)
management of active gout flare
1st line:
1) NSAIDs (e.g. naproxen/ibuprofen/diclofenac/celecoxib)
- Avoid if renal impairment/GI bleeds
2) or Colchicine if renal impairment - Common side effects are: diarrhoea, nausea, and vomiting
- Avoid if eGFR <10mL/minute/1.73m2
2nd line if NSAIDS of Colchicine contraindicated
- Prednisolone intra-articular or parenterally depending on the severity
- should be avoided if septic arthritis hasnt been excluded
If the patient is already taking allopurinol, this should be continued
chronic management of gout
Urate- lowering therapy
should be started around 2 weeks after attack
First line
* Allopurinol + suppressive therapy (“cover” therapy) e.g. colchicine, naproxen, ibuprofen, diclofenac
* If NSAIDs and colchicine are contraindicated, prednisolone may be considered
2nd line: febuxostat if allopurinol is not tolerated/ineffective + suppressive therapy
allopurinal monitoring
- When starting allopurinol, closely monitor patients for hypersensitivity
- This may manifest as multi-system failure, eosinophilia, and dermatitis
gout and patient advice
Patients should have lifestyle changes:
- Drinking alcohol responsibly
- Avoiding dehydration
- Reduction in the quantity of purine-based food consumption e.g. herring/sardines/liver/kidneys/oatmeal
- Reducing meat or seafood intake
- Weight reduction
- Regular exercise
- Smoking cessation
Pseudogout vs gout
pseudogout describes inflammation of joints caused by the deposition of calcium pyrophosphate crystals in articular and periarticular joints. It is another type of crystal arthropathy.
1) Psuedogout
- positively birefringent rhomboid-shaped crystals under polarised light
- calcium pyrophosphate
2) Gout
- negatively birefringent needle shaped
- monosodium urate crystals
Risk Factors for psuedogout
- Increasing age
- Family history
- Dehydration
- Haemochromatosis
- Hyperparathyroidism
- Hypomagnesaemia
- Hypophosphataemia
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Pseudogout presentation
typically presents acutely (over hours) or sometimes overnight with redness and swelling in a joint. Features include:
- Pain, redness, and swelling of the knee, wrist, and shoulders
- It may present as a sudden worsening of osteoarthritis (OA) or features of OA occurring in less typical joints (e.g. OA does not tend to affect the shoulders)
investigations for pseudogout
Investigations
Arthrocentesis with synovial fluid analysis:
* Positively birefringent rhomboid-shaped crystals under polarised light are diagnostic
X-ray of affected joints:
* May show linear calcifications of the meniscus and articular cartilage
Serum calcium:
* To screen for hyperparathyroidism
Iron studies:
* To screen for haemochromatosis
Serum magnesium:
* To screen for hypomagnesaemia
management of psuedogout
- NSAIDs (unless contraindicated) + paracetamol
- Consider adding PPI
- Colchicine (if NSAIDs contraindicated) + paracetamol
- Intra-articular corticosteroids
ankylosing spondylitis
chronic, seronegative arthritis which affects the spine (sacroillitis and spondylitis- axial skeleton)
risk factors for ankylosing spondylitis
- HLA-B27 presence
- Family history of AS
- Male sex
presentation of AS
Suspect AS in a patient aged 20-30 with an insidious onset of lower back pain. Features include:
Inflammatory joint pain:
- Pain and stiffness improve with movement and are worse with rest
- Prolonged morning stiffness (usually >1 hour)
- There may be pain at night that wakes the patient up
Enthesitis
- Achilles tendonitis, tibial tuberosity enthesitis, plantar fasciitis
- Dactylitis – swelling of a digit (sausage like swelling)
Peripheral arthritis – there may be involvement of lower limb joints
Fatigue
Extra-articular features and complications:
- Anterior uveitis
- Apical lung fibrosis
AS signs on examination
- Loss of lumbar lordosis
- Schober’s test positive
The examiner marks the L5 spinous process and marks 10cm above and 5cm below this point. The examiner then asks the patient to bend forward as far as possible and measures the distance between the two points. A distance of <20cm is positive. - Dyspnoea
May be due to spinal kyphosis leading to lung expansion limitation - Kyphosis
- Tenderness at the sacroiliac joint
investigations for AS
Pelvic x-ray:
- Shows sacroiliitis
- Vertebral bodies may become squared
- Syndesmophytes (bony-bridges) may form between adjacent vertebrae
- In late disease, there may be a complete fusion of the vertebral column – bamboo spine
Chest x-ray:
- This may show apical fibrosis
- If spirometry is performed this shows a restrictive defect
MRI performed if the x-ray does not show signs:
- May show early signs of inflammation (e.g. bone marrow oedema)
management of AS
All patients should be encouraged to exercise regularly.
Adults with pain with or without stiffness
- 1st line: NSAIDs + physiotherapy
Adults with pain with or without stiffness unresponsive to 2 different NSAIDs
- **1st line: **TNF-inhibitors e.g. infliximab+ physiotherapy and continue NSAID
patient advice for AS
- Patients should keep active and perform regular stretches
- Patients should use NSAIDs when they have inflammatory back pain symptoms
- Patients should be aware of iritis and when to seek help
briefly describe Felty syndorme
Complication of RA
Triad of:
- Rheumatoid arthritis
- Neutropenia
- Splenomegaly
Pathophysiology
- Unclear
- Inflammation may lead to splenomegaly.
- Splenomegaly may contribute to increased recycling of neutrophils leading to neutropenia.
Presentation
- Increased susceptibility to infection due to neutropenia
- Splenomegaly – may manifest as left upper quadrant pain
- Hepatomegaly may also be seen
- RA and its severe features (e.g. joint deformity)
Ankylosing spondylitis features - the ‘A’s
- Apical fibrosis
- Anterior uveitis
- Aortic regurgitation
- Achilles tendonitis
- AV node block
- Amyloidosis
