Rheumatology Flashcards
when are anti-Ro antigens found?
Anti-Ro: Sjogren’s syndrome, SLE, congenital heart block
when are anti-la antigens found?
Anti-La: Sjogren’s syndrome
when are anti-jo 1 antigens found?
Anti-Jo 1: polymyositis
when are Anti-SCL-70 found?
Anti-SCL-70: diffuse cutaneous systemic
sclerosis
when are Anti-centromere found?
Anti-centromere: limited cutaneous systemic sclerosis
what is gout caused by?
-why does this happen?
Gout is a form of microcrystal synovitis caused by the deposition of monosodium urate monohydrate in the synovium. It is caused by chronic hyperuricemia (uric acid > 450 μmol/l) mostly due to ↓ renal execretion of UA (90%)
what causes exist for decreased excretion of uric acid?
Drugs - diuretics
CKD
Lead toxicity
what causes exist for increased production of uric acid?
Myeloproliferative/lymphoproliferative disorder
Cytotoxic drugs
Severe psoriasis
what is Lesch-Nyhan syndrome?
- what is this caused by?
- how is this inherited?
- what are the clinical features?
• Hypoxanthine-guanine phosphoribosyl transferase deficiency
• Inheritance = X-linked recessive
• Features: gout, renal failure, learning difficulties,
head-banging
Tophaceous gout
- what is this assoc. with?
- how do affected joints appear?
- what is this due to?
- what is seen on X-Ray?
- Associated with renal impairment and prolonged diuretics use.
- Affected joints are hot swollen and knobby appearance.
- Due to deposition of Na+ urate in skin and joint.
- X-ray: punched out bony cyst
what are drug causes of gout?
- Thiazides, furosemide
- Alcohol
- Cytotoxic agents
- Pyrazinamide
what is the acute management of gout?
• NSAIDs
• Intra-articular steroid injection
• Colchicine has a slower onset of action. (main side-effect is diarrhea and ↑ INR with warfarin)
• If the patient is already taking allopurinol it should be continued
• Rasburicase: is a recombinant version of a urate oxidase enzyme given in acute setting, it allows
allopurinol to be commenced without worsening of symptoms. Only used when other Rx can not be given
when is colchicine helpful in gout?
Colchicine is useful in patients with renal impairment who develop gout as NSAIDs are relatively contraindicated. BNF advises to ↓ the dose by up to 50% if creatinine clearance is less than 50 ml/min and to avoid if creatinine clearance is less than 10 ml/min.
when should prednisolone not be used in gout?
diabetic patients
when should allopurinol prophylaxis be started in gout?
- what is the initial dose?
- what is the aim level of uric acid?
- what should be used as ‘cover’?
Allopurinol prophylaxis
• Allopurinol should not be started until 2 weeks after an acute attack has settled.
• Initial dose of 100 mg od, with the dose titrated every few weeks to aim for a serum uric acid of
< 300 μmol/l
• NSAID or colchicine cover should be used when starting allopurinol
when should allopurinol be considered?
- Recurrent attacks - the British Society for Rheumatology recommend ‘In uncomplicated gout uric acid lowering drug therapy should be started if a second attack, or further attacks occur within 1 year’
- Tophi
- Renal disease
- Uric acid renal stones
- Prophylaxis if on cytotoxics or diuretics
what are lifestyle modifications for gout?
Lifestyle modifications
• ↓ alcohol intake and avoid during an acute attack
• Lose weight if obese
• Avoid food high in purines e.g. Liver, kidneys, seafood, oily fish (mackerel, sardines) and yeast
products
what is pseudogout?
Pseudogout is a form of microcrystal synovitis caused by the deposition of calcium pyrophosphate dihydrate in the synovium
what are the features of pseudogout?
Features
• Knee, wrist and shoulders most commonly affected
• X-ray: chondrocalcinosis (linear calcification of the articular cartilage)
• Joint aspiration: weakly-positively birefringent rhomboid shaped crystals
what are risk factors for pseudogout?
Risk factors • Hyperparathyroidism • Hypothyroidism • Hemochromatosis • Acromegaly • ↓ magnesium, ↓ phosphate • Wilson's disease
what investigations are indicated in pseudogout?
Investigations:
• Transferrin saturation (may indicate hemochromatosis, a recognised cause of pseudogout)
• Aspiration of joint fluid, to exclude septic arthritis and show weakly-positively birefringent brick shaped crystals
what is the treatment for pseudogout?
NSAIDs or intra-articular, intra-muscular or oral steroids as for gout
what is the peak onset of rheumatoid arthritis?
-what is the female:male ratio?
-how prevalent is this in the UK
what HLA is this assoc with?
Epidemiology
• Peak onset = 30-50 years, although occurs in all age groups
• ♀:♂ ratio = 3:1
• Prevalence in UK = 1%
• Some ethnic differences e.g. High in native Americans
• Associated with HLA-DR4 (especially felty’s syndrome)
what criteria is used for the diagnosis of rheumatoid arthritis?
American College of Rheumatology criteria
• Requires 4 of the following 7 criteria
• Sensitivity = 92%, specificity = 89%
1. Morning stiffness > 1 hr (for at least 6 weeks)
2. Soft-tissue swelling of 3 or more joints (for at least 6 weeks)
3. Swelling of PIP , MCP or wrist joints (for at least 6 weeks)
4. Symmetrical arthritis
5. Subcutaneous nodules
6. Rheumatoid factor positive
7. Radiographic evidence of erosions or periarticular osteopenia
what antibody should patients who have suspected rheumatoid arthritis and are rheumatoid factor negative be tested for?
Anti-cyclic citrullinated peptide antibody may be detectable up to 10 years before the development of rheumatoid arthritis. It may therefore play a key role in the future of rheumatoid arthritis, allowing early detection of patients suitable for aggressive anti-TNF therapy. It has sensitivity similar to rheumatoid factor (70-80%, see below) with a much higher specificity of 90-95%.
NICE recommends that patients with suspected rheumatoid arthritis who are rheumatoid factor negative should be tested for anti-CCP antibodies.
what are early x-ray findings in rheumatoid arthritis?
Early x-ray findings
• Loss of joint space (seen in both RA and osteoarthritis)
• Juxta-articular osteoporosis
• Soft-tissue swelling
what are late x-ray findings in rheumatoid arthritis?
Late x-ray findings
• Periarticular erosions (osteopenia and osteoporosis)
• Subluxation
what is key in the pathophysiology of rheumatoid arthritis?
Rheumatoid arthritis - TNF is key in pathophysiology
what are poor prognostic features of rheumatoid arthritis?
Poor prognostic features • Rheumatoid factor positive • Poor functional status at presentation • HLA DR4 • X-ray: early erosions (in < 2 years) • Extra articular features e.g. Nodules • ♀sex • Insidious onset • Anti-CCP antibodies
what respiratory complications exist in rheumatoid arthritis?
• Respiratory: pulmonary fibrosis, pleural effusion, pulmonary nodules, bronchiolitis obliterans,
methotrexate pneumonitis, pleurisy
what ocular complications exist in rheumatoid arthritis?
Ocular: keratoconjunctivitis sicca (most common), episcleritis, scleritis, corneal ulceration,
keratitis, steroid-induced cataracts, chloroquine retinopathy
what endocrine complication exists in RA?
• Osteoporosis
what cardiac complications exist in RA?
ISCHEMIC heart disease: RA carries a similar risk to T2DM
what systemic complications exist in RA?
Increased risk of infections
what psych. complications exist in RA?
• Depression
what syndromes are assoc with RA?
- Felty’s syndrome (RA + splenomegaly + low white cell count)
- Amyloidosis
what organism predisposes patients to RA?
Proteus mirabilis is a (G-ve rod), causes UTI → predisposes susceptible patients to RA
what is the general treatment combination for RA?
In 2018 NICE updated their rheumatoid arthritis guidelines. They now recommend DMARD monotherapy +/- a short-course of bridging prednisolone. In the past dual DMARD therapy was advocated as the initial step.
Flares
flares of RA are often managed with corticosteroids - oral or intramuscular
Methotrexate:
- what needs to be monitored?
- what side effect does this cause?
Methotrexate is the most widely used DMARD. Monitoring FBC & LFTs is essential due to the risk of myelosuppression and liver cirrhosis. Other important side-effects include pneumonitis
which 2 DMARDs can be used in pregnancy?
• Sulfasalazine
• Hydroxychloroquine
Azathiopurine can be used if sulfasalazine and hydroxychloroquine are not controlling
what RA therapy is absolutely contraindicated in pregnancy?
Methotrexate and NSAIDs are absolutely contraindicated
when are TNF-inhibitors indicated in RA?
The current indication for a TNF-inhibitor is an inadequate response to at least two DMARDs including methotrexate
anti-TNF: Etanercept
- administration
- adverse effect
Etanercept: subcutaneous administration
can cause demyelination, risks include reactivation of tuberculosis
anti-TNF: Infliximab
- administration
- adverse effect
Infliximab: intravenous administration, risks include reactivation of
tuberculosis
anti-TNF: adalimumab
-administration
Adalimumab: subcutaneous administration
when should anti-TNF meds be stopped prior to surgery?
Stop 2-4 weeks before any major surgery
what is rituximab:
- how is this given?
- what reaction is common?
- Anti-CD20 monoclonal antibody, results in B-cell depletion
- Two 1g intravenous infusions are given two weeks apart
- Infusion reactions are common
what is abatacept?
-how is this given?
- Fusion protein that modulates a key signal required for activation of T lymphocytes
- Leads to ↓ T-cell proliferation and cytokine production
- Given as an infusion
- Pulmonary fibrosis
- Pleural effusion
- Pulmonary nodules
- Bronchiolitis obliterans
- Complications of drug therapy e.g. Methotrexate pneumonitis
- Pleurisy
- Caplan’s syndrome - massive fibrotic nodules with occupational coal dust exposure
- Infection (possibly atypical) secondary to immunosuppression
are all complications of
Rheumatoid arthritis
what is adult still’s disease?
Adult Still’s Disease: is a form of rheumatoid arthritis typically affects 16-35 year olds
what are clinical features of adult still’s disease?
- what blood tests are raised?
- RF? ANA?
- Arthralgia
- Fever (noticeable at afternoon and evening)
- Elevated serum ferritin
- Rash: salmon-pink, maculopapular, pruritic
- Pyrexia
- Lymphadenopathy
- RF and ANA negative (but ANA 25% positive). ↑ ESR and CRP
- Leukocytosis and thrombocytosis
what is the management of adult still’s disease?
Management:
• NSAIDs
• Steroids
• Methotrexate
what is mandatory in all patients with a hot swollen joint?
Joint aspiration is mandatory in all patients with a hot, swollen joint to rule out septic arthritis. If
this was excluded then intra-articular or system steroid therapy may be considered
what is the most common organisms overall and in young adults who are sexually adults that causes septic joint?
- Most common organism overall is Staphylococcus aureus
- In young adults who are sexually active Neisseria gonorrhea should also be considered
- WBC > 50 x 109/L or > 75% of baseline – neutrophils
what is the management for septic joint?
• Synovial fluid should be obtained before starting treatment
• Intravenous antibiotics which cover gram-positive cocci are indicated. The BNF currently
recommends flucloxacillin + fusidic acid or clindamycin if penicillin allergic
• Antibiotic treatment is normally be given for several weeks (BNF states 6-12 weeks)
• Needle aspiration should be used to decompress the joint
• Surgical drainage may be needed if frequent needle aspiration is required
what is the most common site of hand osteoarthritis?
trapeziometacarpal joint (base of thumb) is the most common site of hand osteoarthritis
what is the management of osteoarthritis?
-conservative/non-pharmacological
-pharmacalogical 1st line and 2nd line
`
• All patients should be offered help with weight loss, given advice about local muscle
strengthening exercises and general aerobic fitness
• Paracetamol and topical NSAIDs are first-line analgesics. Topical NSAIDs are indicated only
for OA of the knee or hand
• Second-line treatment is oral NSAIDs/cox-2 inhibitors, opioids, capsaicin cream and intra-
articular corticosteroids. A proton pump inhibitor should be co-prescribed with either drug.
These drugs should be avoided if the patient takes aspirin
• Non-pharmacological treatment options include supports and braces, tens and shock absorbing
insoles or shoes
• If conservative methods fail then refer for consideration of joint replacement
what is reactive arthritis/reiter’s syndrome?
Reactive Arthritis is one of the HLA-B27 associated seronegative spondyloarthropathies. It encompasses Reiter’s syndrome, a term which described a classic triad of urethritis, conjunctivitis and arthritis following a dysenteric illness
The American College of Rheumatology now define reactive arthritis as an episode of peripheral arthritis lasting for greater than 1 month associated with urethritis/cervicitis or diarrhea
what are the clinical features of reiter’s syndrome?
• Typically develops within 4 weeks of initial infection - symptoms generally last around 4-6
months
• Arthritis is typically an asymmetrical oligoarthritis of lower limbs
• May present as monoarthritis e.g. Knee
• Symptoms of urethritis
• Eye: conjunctivitis (seen in 50%), anterior uveitis
• Skin: circinate balanitis (painless vesicles on the coronal margin of the prepuce), keratoderma
blenorrhagica (waxy yellow/brown papules on palms and soles)
what percentage of patients with reactive arthritis have recurrent episodes? what percentage develop chronic disease?
Around 25% (15-50%) have recurrent episodes whilst 10% (15-30%) develop chronic disease.
what percentage of HLA B27 positive patients will develop ankylosing spondylitis?
Ankylosing spondylitis develop in upto 50% of HLA B27 +ve patients
what two forms of reactive arthritis exist?
- Post-STI form much more common in men (e.g. 10:1)
* Post-dysenteric form equal sex incidence with better prognosis
what organisms are responsible for post-dysenteric reactive arthritis?
Organisms often responsible for post-dysenteric form • Shigella flexneri • Salmonella typhimurium • Salmonella enteritidis • Yersinia enterocolitica • Campylobacter
what organism is responsible for post-STI reactive arthritis?
Organisms often responsible for post-STI form
• Chlamydia trachomatis
what is the management of reactive arthritis?
- Symptomatic: analgesia, NSAIDs, intra-articular steroids
- Sulfasalazine and methotrexate are sometimes used for persistent disease
- Symptoms rarely last more than 12 months
what is palindromic arthritis?
Rare type of recurrent inflammatory arthritis that causes sudden inflammation in one or several joints (pain, swelling and erythema) followed by complete recovery with no permanent damage
what does palindromic arthrtis affect? how long does this last?
- Affects articular or periarticular areas, any joint could be affected but mostly large joints
- Lasts < 72 hours before recovering completely
what age of patient can be affected by palindromic arthritis?
♂=♀ - age 20-50 years.
what may palindromic arthritis progress to? what antibodies are present?
- May progress to RA: incidence of RA may ↑ when RF is present
- Anti-CCP and antikeratin antibodies (AKA) are present in a high proportion of patients
what is recent-onset arthritis?
Recent-Onset Arthritis can be due to parvovirus-induced arthritis
what is a risk factor for recent-onset arthritis?
• Exposure to children with recent febrile illness is known risk
who does recent-onset arthritis affect?
Affects ♀>♂ - mostly women with contact to children (at home or at work)
what joints are affected in recent-onset arthritis?
Small hands joints, wrists, elbows, hips, knees, and feet are each affected in > 50% of cases.
what antibody is strong evidence of parvovirus being a cause of recent-onset arthritis?
Detection of IgM antibody, produced only in early disease, is a marker of recent infection and
therefore strong evidence in favor of parvovirus being the cause of recent-onset arthritis.
what HLA is ankylosing spondylitis assoc. with?
- who does this present in?
- how is this inherited?
- is HLA-? of use in making diagnosis?
Ankylosing spondylitis is a HLA-B27 associated spondyloarthropathies. It typically presents in ♂s (sex ratio 5:1) aged 20-30 years old. It has polygenic inheritance.
HLA-B27 is of little use in making the diagnosis as it is positive in:
• 90% of patients with ankylosing spondylitis
• 10% of normal patients
what are the clinical features of ankylosing spondylitis?
- Typically a young man who presents with lower back pain and stiffness
- Stiffness is usually worse in morning and improves with activity
- The patient may experience pain at night which improves on getting up
- Peripheral arthritis (25%, more common if ♀)
what are the ‘A’s of ankylosing spondylitis?
- Apical fibrosis (CXR)
- Anterior uveitis
- Aortic regurgitation
- Achilles tendonitis
- A V node block
- Amyloidosis
- And cauda equina syndrome
what is seen on examination in ankylosing spondylitis?
• Reduced lateral flexion
• Reduced forward flexion - Schober’s test - a line is drawn 10 cm above and 5 cm below the
back dimples (dimples of Venus). The distance between the two lines should increase by more
than 5 cm when the patient bends as far forward as possible
• Reduced chest expansion
↓ Lateral flexion of the lumbar spine is one of the earliest signs of ankylosing spondylitis. There tends to be a loss of lumbar lordosis and an accentuated thoracic kyphosis in patients with ankylosing spondylitis
what is the most useful investigation for diagnosis and monitoring of ank spond?
X-ray of the sacro-iliac joints is the most useful investigation for diagnosis and monitoring, but changes may not be seen for many years after the onset of symptoms
what is seen on x-rays sacroiliac joints and spine in ank spond?
X-rays are often normal early in disease, later changes include:
• Sacroilitis: subchondral erosions, sclerosis
• Squaring of lumbar vertebrae
• ‘Bamboo spine’ (late & uncommon)
what is seen in CXR in ank spond?
- CXR: apical fibrosis
what may be seen on spirometry in a patient with ank spond?
Spirometry may show a restrictive defect due to a combination of pulmonary fibrosis, kyphosis and ankylosis of the costovertebral joints
what is the management of ankylosing spondylitis?
• NSAIDs
• Physiotherapy
• Sulphasalazine may be useful if there is peripheral joint involvement - doesn’t improve spinal
mobility
• TNF-α blockers such as etanercept and adalimumab are increasingly used. This approach for
severe ankylosing spondylitis was supported by NICE in 2008
what are common features of seronegative spondyloarthropathies?
• Associated with HLA-B27
• Rheumatoid factor negative - hence ‘seronegative’
• Peripheral arthritis, usually asymmetrical
• Sacroilitis
• Enthesopathy: e.g. Achilles tendonitis, plantar fasciitis
• Extra-articular manifestations: uveitis, pulmonary fibrosis (upper zone), amyloidosis, aortic
regurgitation
list four seronegative spondyloarthropathies
- Ankylosing spondylitis
- Psoriatic arthritis
- Reiter’s syndrome (including reactive arthritis)
- Enteropathic arthritis (associated with IBD)
what is pseudoxanthoma elasticum?
Pseudoxanthoma Elasticum is an inherited condition (usually autosomal recessive) characterized by an abnormality in elastic fibers
what are the features of pseudoxanthoma elasticum?
Features
• Retinal angioid streaks
• ‘Plucked chicken skin’ appearance - small yellow papules on the neck, antecubital fossa and
axillae
• Cardiac: mitral valve prolapse, ↑ risk of ischemic heart disease
• Gastrointestinal hemorrhage
low levels of ? have been shown to be assoc with increased risk of developing SLE
Low levels of C4a and C4b have been shown to be associated with ↑ risk of developing systemic lupus erythematous
