Rheumatology Flashcards
Ankylosing spondylitis: features
Ankylosing spondylitis features - the ‘A’s
Apical fibrosis
Anterior uveitis
Aortic regurgitation
Achilles tendonitis
AV node block
Amyloidosis
Ankylosing spondylitis is a HLA-B27 associated spondyloarthropathy. It typically presents in males (sex ratio 3:1) aged 20-30 years old.
Features
typically a young man who presents with lower back pain and stiffness of insidious onset
stiffness is usually worse in the morning and improves with exercise
the patient may experience pain at night which improves on getting up
Clinical examination
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
Other features - the ‘A’s
Apical fibrosis
Anterior uveitis
Aortic regurgitation
Achilles tendonitis
AV node block
Amyloidosis
and cauda equina syndrome
peripheral arthritis (25%, more common if female)
Ankylosing spondylitis investigation and management
Ankylosing spondylitis is a HLA-B27 associated spondyloarthropathy. It typically presents in males (sex ratio 3:1) aged 20-30 years old.
Investigation
Inflammatory markers (ESR, CRP) are typically raised although normal levels do not exclude ankylosing spondylitis.
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
Plain x-ray of the sacroiliac joints is the most useful investigation in establishing the diagnosis. Radiographs may be normal early in disease, later changes include:
sacroiliitis: subchondral erosions, sclerosis
squaring of lumbar vertebrae
‘bamboo spine’ (late & uncommon)
syndesmophytes: due to ossification of outer fibers of annulus fibrosus
chest x-ray: apical fibrosis
If the x-ray is negative for sacroiliac joint involvement in ankylosing spondylitis but suspicion for AS remains high, the next step in the evaluation should be obtaining an MRI. Signs of early inflammation involving sacroiliac joints (bone marrow oedema) confirm the diagnosis of AS and prompt further treatment.
Spirometry may show a restrictive defect due to a combination of pulmonary fibrosis, kyphosis and ankylosis of the costovertebral joints.
Management
The following is partly based on the 2010 EULAR guidelines (please see the link for more details):
encourage regular exercise such as swimming
NSAIDs are the first-line treatment
physiotherapy
the disease-modifying drugs which are used to treat rheumatoid arthritis (such as sulphasalazine) are only really useful if there is peripheral joint involvement
the 2010 EULAR guidelines suggest: ‘Anti-TNF therapy should be given to patients with persistently high disease activity despite conventional treatments’
research is ongoing to see whether anti-TNF therapies such as etanercept and adalimumab should be used earlier in the course of the disease
Rheumatoid arthritis: antibodies
Rheumatoid factor
Rheumatoid factor (RF) is a circulating antibody (usually IgM) which reacts with the Fc portion of the patients own IgG.
RF can be detected by either
Rose-Waaler test: sheep red cell agglutination
Latex agglutination test (less specific)
RF is positive in 70-80% of patients with rheumatoid arthritis, high titre levels are associated with severe progressive disease (but NOT a marker of disease activity)
Other conditions associated with a positive RF include:
Sjogren’s syndrome (around 100%)
Felty’s syndrome (around 100%)
infective endocarditis (= 50%)
SLE (= 20-30%)
systemic sclerosis (= 30%)
general population (= 5%)
rarely: TB, HBV, EBV, leprosy
Anti-cyclic citrullinated peptide antibody
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 a sensitivity similar to rheumatoid factor (around 70%) with a much higher specificity of 90-95%.
NICE recommends that patients with suspected rheumatoid arthritis who are rheumatoid factor negative should be test for anti-CCP antibodies.
Rheumatoid arthritis: x-ray changes
Early x-ray findings
loss of joint space
juxta-articular osteoporosis
soft-tissue swelling
Late x-ray findings
periarticular erosions
subluxation
Antiphospholipid syndrome
Antiphospholipid syndrome is an acquired disorder characterised by a predisposition to both venous and arterial thromboses, recurrent fetal loss and thrombocytopenia. It may occur as a primary disorder or secondary to other conditions, most commonly systemic lupus erythematosus (SLE)
A key point for the exam is to appreciate that antiphospholipid syndrome causes a paradoxical rise in the APTT. This is due to an ex-vivo reaction of the lupus anticoagulant autoantibodies with phospholipids involved in the coagulation cascade
Features
venous/arterial thrombosis
recurrent fetal loss
livedo reticularis
thrombocytopenia
prolonged APTT
other features: pre-eclampsia, pulmonary hypertension
Associations other than SLE
other autoimmune disorders
lymphoproliferative disorders
phenothiazines (rare)
Management - based on BCSH guidelines
initial venous thromboembolic events: evidence currently supports use of warfarin with a target INR of 2-3 for 6 months
recurrent venous thromboembolic events: lifelong warfarin; if occurred whilst taking warfarin then increase target INR to 3-4
arterial thrombosis should be treated with lifelong warfarin with target INR 2-3
Dermatomyositis
an inflammatory disorder causing symmetrical, proximal muscle weakness and characteristic skin lesions
may be idiopathic or associated with connective tissue disorders or underlying malignancy (typically ovarian, breast and lung cancer, found in 20-25% - more if patient older). Screening for an underlying malignancy is usually performed following a diagnosis of dermatomyositis
polymyositis is a variant of the disease where skin manifestations are not prominent
Skin features
photosensitive
macular rash over back and shoulder
heliotrope rash in the periorbital region
Gottron’s papules - roughened red papules over extensor surfaces of fingers
‘mechanic’s hands’: extremely dry and scaly hands with linear ‘cracks’ on the palmar and lateral aspects of the fingers
nail fold capillary dilatation
Other features
proximal muscle weakness +/- tenderness
Raynaud’s
respiratory muscle weakness
interstitial lung disease: e.g. Fibrosing alveolitis or organising pneumonia
dysphagia, dysphonia
Investigations
the majority of patients (around 80%) are ANA positive
around 30% of patients have antibodies to aminoacyl-tRNA synthetases (anti-synthetase antibodies), including:
antibodies against histidine-tRNA ligase (also called Jo-1)
antibodies to signal recognition particle (SRP)
anti-Mi-2 antibodies
This is a description of the typical skin changes seen in dermatomyositis, a connective tissue disease. In addition to the plaques on the knuckles (Gottron’s papules) and eyelids (heliotrope rash) there may be scaling of the scalp and changes to the nail beds and cuticles. There is inflammation of the proximal muscles causing weakness, but the skin changes often are the first presenting feature. Dermatomyositis is usually an autoimmune condition, in which case it is controlled with immunosuppressants, but may also be a paraneoplastic syndrome.
Systemic lupus erythematosus: features
Systemic lupus erythematosus (SLE) is a multisystem, autoimmune disorder. It typically presents in early adulthood and is more common in women and people of Afro-Caribbean origin.
General features
fatigue
fever
mouth ulcers
lymphadenopathy
Skin
malar (butterfly) rash: spares nasolabial folds
discoid rash: scaly, erythematous, well demarcated rash in sun-exposed areas. Lesions may progress to become pigmented and hyperkeratotic before becoming atrophic
photosensitivity
Raynaud’s phenomenon
livedo reticularis
non-scarring alopecia
Musculoskeletal
arthralgia
non-erosive arthritis
Cardiovascular
pericarditis: the most common cardiac manifestation
myocarditis
Respiratory
pleurisy
fibrosing alveolitis
Renal
proteinuria
glomerulonephritis (diffuse proliferative glomerulonephritis is the most common type)
Neuropsychiatric
anxiety and depression
psychosis
seizures
Drug-induced lupus
In drug-induced lupus not all the typical features of systemic lupus erythematosus are seen, with renal and nervous system involvement being unusual. It usually resolves on stopping the drug.
Features
arthralgia
myalgia
skin (e.g. malar rash) and pulmonary involvement (e.g. pleurisy) are common
ANA positive in 100%, dsDNA negative
anti-histone antibodies are found in 80-90%
anti-Ro, anti-Smith positive in around 5%
A woman with drug-induced lupus
Most common causes
procainamide
hydralazine
Less common causes
isoniazid
minocycline
phenytoin
Gottron’s papules, roughened red papules over the knuckles mainly, are seen in dermatomyositis
This patient may have dermatomyositis. She is describing muscle weakness with associated skin changes. Gottron’s papules are erythematous, keratotic macules overlying her interphalangeal joints and they are seen in dermatomyositis.
It is osteoarthritis that is linked to Bouchard’s and Heberden’s nodes. They present as painless swellings of the proximal and distal interphalangeal joints respectively.
Osler nodes and janeway lesions are associated with endocarditis and present as macular lesions on the palms. Osler nodes are painful and due to immune complex deposition whereas janeway lesions are painless and due to septic emboli.
Gout management
Gout is a form of microcrystal synovitis caused by the deposition of monosodium urate monohydrate in the synovium. It is caused by chronic hyperuricaemia (uric acid > 450 µmol/l)
Acute management
NSAIDs or colchicine are first-line
the maximum dose of NSAID should be prescribed until 1-2 days after the symptoms have settled. Gastroprotection (e.g. a proton pump inhibitor) may also be indicated
colchicine* has a slower onset of action. The main side-effect is diarrhoea
oral steroids may be considered if NSAIDs and colchicine are contraindicated. A dose of prednisolone 15mg/day is usually used
another option is intra-articular steroid injection
if the patient is already taking allopurinol it should be continued
Indications for urate-lowering therapy (ULT)
the British Society of Rheumatology Guidelines now advocate offering urate-lowering therapy to all patients after their first attack of gout
ULT is particularly recommended if:
→ >= 2 attacks in 12 months
→ tophi
→ renal disease
→ uric acid renal stones
→ prophylaxis if on cytotoxics or diuretics
Urate-lowering therapy
allopurinol is first-line
it has traditionally been taught that urate-lowering therapy should not be started until 2 weeks after an acute attack, as starting too early may precipitate a further attack. The evidence base to support this however looks weak
in 2017 the BSR updated their guidelines. They still support a delay in starting urate-lowering therapy because it is better for a patient to make long-term drug decisions whilst not in pain
initial dose of 100 mg od, with the dose titrated every few weeks to aim for a serum uric acid of < 300 µmol/l. Lower initial doses should be given if the patient has a reduced eGFR
colchicine cover should be considered when starting allopurinol. NSAIDs can be used if colchicine cannot be tolerated. The BSR guidelines suggest this may need to be continued for 6 months
the second-line agent when allopurinol is not tolerated or ineffective is febuxostat (also a xanthine oxidase inhibitor)
in refractory cases other agents may be tried:
uricase (urate oxidase) is an enzyme that catalyzes the conversion of urate to the degradation product allantoin. It is present in certain mammals but not humans
in patients who have persistent symptomatic and severe gout despite the adequate use of urate-lowering therapy, pegloticase (polyethylene glycol modified mammalian uricase) can achieve rapid control of hyperuricemia. It is given as an infusion once every two weeks
Lifestyle modifications
reduce 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
Other points
consideration should be given to stopping precipitating drugs (such as thiazides)
losartan has a specific uricosuric action and may be particularly suitable for the many patients who have coexistent hypertension
increased vitamin C intake (either supplements or through normal diet) may also decrease serum uric acid levels
*inhibits microtubule polymerization by binding to tubulin, interfering with mitosis. Also inhibits neutrophil motility and activity
Gout: drug causes
Gout is a form of microcrystal synovitis caused by the deposition of monosodium urate monohydrate in the synovium. It is caused by chronic hyperuricaemia (uric acid > 0.45 mmol/l).
Drug causes
diuretics: thiazides, furosemide
ciclosporin
alcohol
cytotoxic agents
pyrazinamide
aspirin: it was previously thought that only high-dose aspirin could precipitate gout. However, a systematic review (see link) showed that low-dose (e.g. 75mg) also increases the risk of gout attacks. This obviously needs to be balanced against the cardiovascular benefits of aspirin and the study showed patients coprescribed allopurinol were not at an increased risk
Pseudogout
Pseudogout is a form of microcrystal synovitis caused by the deposition of calcium pyrophosphate dihydrate crystals in the synovium.
Risk factors
haemochromatosis
hyperparathyroidism
acromegaly
low magnesium, low phosphate
Wilson’s disease
Features
knee, wrist and shoulders most commonly affected
joint aspiration: weakly-positively birefringent rhomboid-shaped crystals
x-ray: chondrocalcinosis
in the knee this can be seen as linear calcifications of the meniscus and articular cartilage
Management
aspiration of joint fluid, to exclude septic arthritis
NSAIDs or intra-articular, intra-muscular or oral steroids as for gout
Hip pain in adults
The table below provides a brief summary of the potential causes of hip pain in adults
Condition
Features
Osteoarthritis
Pain exacerbated by exercise and relieved by rest
Reduction in internal rotation is often the first sign
Age, obesity and previous joint problems are risk factors
Inflammatory arthritis
Pain in the morning
Systemic features
Raised inflammatory markers
Referred lumbar spine pain
Femoral nerve compression may cause referred pain in the hip
Femoral nerve stretch test may be positive - lie the patient prone. Extend the hip joint with a straight leg then bend the knee. This stretches the femoral nerve and will cause pain if it is trapped
Greater trochanteric pain syndrome (Trochanteric bursitis)
Due to repeated movement of the fibroelastic iliotibial band
Pain and tenderness over the lateral side of thigh
Most common in women aged 50-70 years
Meralgia paraesthetica
Caused by compression of lateral cutaneous nerve of thigh
Typically burning sensation over antero-lateral aspect of thigh
Avascular necrosis
Symptoms may be of gradual or sudden onset
May follow high dose steroid therapy or previous hip fracture of dislocation
Pubic symphysis dysfunction
Common in pregnancy
Ligament laxity increases in response to hormonal changes of pregnancy
Pain over the pubic symphysis with radiation to the groins and the medial aspects of the thighs. A waddling gait may be seen
Transient idiopathic osteoporosis
An uncommon condition sometimes seen in the third trimester of pregnancy
Groin pain associated with a limited range of movement in the hip
Patients may be unable to weight bear
ESR may be elevated
Hydroxychloroquine
Hydroxychloroquine is used in the management of rheumatoid arthritis and systemic/discoid lupus erythematosus. It is pharmacologically very similar to chloroquine which is used to treat certain types of malaria.
Adverse effects
bull’s eye retinopathy - may result in severe and permanent visual loss
recent data suggest that retinopathy caused by hydroxychloroquine is more common than previously thought and the most recent RCOphth guidelines (March 2018) suggest colour retinal photography and spectral domain optical coherence tomography scanning of the macula
baseline ophthalmological examination and annual screening is generally recommened
A contrast to many drugs used in rheumatology, hydroxychloroquine may be used if needed in pregnant women.
Monitoring
the BNF advises: ‘Ask patient about visual symptoms and monitor visual acuity annually using the standard reading chart’
Hypersensitivity
Hypersensitivity
The Gell and Coombs classification divides hypersensitivity traditionally divides reactions into 4 types:
Type
Mechanism
Examples
Type I - Anaphylactic
Antigen reacts with IgE bound to mast cells
- Anaphylaxis
- Atopy (e.g. asthma, eczema and hayfever)
Type II - Cell bound
IgG or IgM binds to antigen on cell surface
- Autoimmune haemolytic anaemia
- ITP
- Goodpasture’s syndrome
- Pernicious anaemia
- Acute haemolytic transfusion reactions
- Rheumatic fever
- Pemphigus vulgaris / bullous pemphigoid
Type III - Immune complex
Free antigen and antibody (IgG, IgA) combine
- Serum sickness
- Systemic lupus erythematosus
- Post-streptococcal glomerulonephritis
- Extrinsic allergic alveolitis (especially acute phase)
Type IV - Delayed hypersensitivity
T-cell mediated
- Tuberculosis / tuberculin skin reaction
- Graft versus host disease
- Allergic contact dermatitis
- Scabies
- Extrinsic allergic alveolitis (especially chronic phase)
- Multiple sclerosis
- Guillain-Barre syndrome
In recent times a further category has been added:
Type V
Antibodies that recognise and bind to the cell surface receptors.
This either stimulating them or blocking ligand binding
Septic arthritis
Septic arthritis
raised WCC
Management
synovial fluid should be obtained before starting treatment
intravenous antibiotics which cover Gram-positive cocci are indicated. The BNF currently recommends flucloxacillin 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
arthroscopic lavage may be required
Overview
most common organism overall is Staphylococcus aureus
in young adults who are sexually active Neisseria gonorrhoeae should also be considered
in adults, the most common location is the knee
The Kocher criteria for the diagnosis of septic arthritis:
fever >38.5 degrees C
non-weight bearing
raised ESR
Kocher’s criteria is used to assess the probability of septic arthritis in children
Importance: 68
Kocher’s criteria is used to assess the probability of septic arthritis in children using 4 parameters:
Non-weight bearing - 1 point
Fever >38.5ºC - 1 point
WCC >12 * 109/L - 1 point
ESR >40mm/hr
The probabilities are calculated thus:
0 points = very low risk
1 point = 3% probability of septic arthritis
2 points = 40% probability of septic arthritis
3 points = 93% probability of septic arthritis
4 points = 99% probability of septic arthritis
This girl scores 0, and with a history of recent viral infection, the likely culprit is transient synovitis.
Juvenile idiopathic arthritis (JIA) is more likely to give a polyarticular presentation with systemic features, including fever and rashes.
There is no indication of psoriasis in the presentation, making psoriatic arthritis unlikely.
Osteochondritis dissecans occurs when small segments of articular cartilage and bone come loose into the joint due to reduced blood supply. It tends to present in older children with a more insidious onset.
Radial tunnel syndrome presents similarly to lateral epicondylitis however pain is typically distal to the epicondyle and worse on elbow extension/forearm pronation
Importance: 54
Radial tunnel syndrome can be difficult to distinguish from lateral epicondylitis as both conditions present with lateral elbow pain. Radial tunnel syndrome however typically presents with tenderness distal to the common extensor origin in comparison to lateral epicondylitis where there is pain over the common extensor origin. It is most common in gymnasts, racquet players and golfers who frequently hyperextend at the wrist or carry out frequent supination/pronation. Patients can also complain of hand paraesthesia or aching at the wrist.
Cubital tunnel syndrome patients experience tingling and numbness in the 4th and 5th finger.
In olecranon bursitis, there would be presence of swelling over the posterior elbow.
Cervical radiculopathy would cause a burning pain radiating from shoulder to fingers. There may be reduced cervical range of motion or pain as clues in the history.
Marfan’s syndrome
Marfan’s syndrome is an autosomal dominant connective tissue disorder. It is caused by a defect in the FBN1 gene on chromosome 15 that codes for the protein fibrillin-1. It affects around 1 in 3,000 people.
Features
tall stature with arm span to height ratio > 1.05
high-arched palate
arachnodactyly
pectus excavatum
pes planus
scoliosis of > 20 degrees
heart: dilation of the aortic sinuses (seen in 90%) which may lead to aortic aneurysm, aortic dissection, aortic regurgitation, mitral valve prolapse (75%),
lungs: repeated pneumothoraces
eyes: upwards lens dislocation (superotemporal ectopia lentis), blue sclera, myopia
dural ectasia (ballooning of the dural sac at the lumbosacral level)
The life expectancy of patients used to be around 40-50 years. With the advent of regular echocardiography monitoring and beta-blocker/ACE-inhibitor therapy this has improved significantly over recent years. Aortic dissection and other cardiovascular problems remain the leading cause of death however.
Osteoarthritis diagnosis
Osteoarthritis diagnosis
NICE recommend that we can diagnose osteoarthritis clinically without the need for investigations if:
patient is > 45 years
has exercise related pain
no morning stiffness or morning stiffness lasting > 30 minutes
Osteoarthritis of the hands usually occurs as part of nodal osteoarthritis (a form of osteoarthritis that is usually genetic).
It results in the formation of:
Heberden’s nodes - swelling of the distal interphalangeal joints.
Bouchard’s nodes - swelling of proximal interphalangeal joints
No treatment is needed for these.
Source: http://www.arthritisresearchuk.org/arthritis-information/conditions/osteoarthritis/which-joints-are-affected/hands.aspx
Pyogenic granuloma is a bright red/blood crusted lesion that usually occurs follow trauma. It is more common in children.
A ganglion is subcutaneous, cystic lesion of the joint or synovial sheath of a tendon. It most commonly occurs at the wrist.
A sebaceous cyst is a round, mobile cyst with a characteristic central punctum
Osteoarthritis: x-ray changes
X-ray changes of osteoarthritis
decrease of joint space
subchondral sclerosis
subchondral cysts
osteophytes forming at joint margins
Osteoarthritis: management
NICE published guidelines on the management of osteoarthritis (OA) in 2014
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 NSAIDs and COX-2 inhibitors. 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 the role of glucosamine?
normal constituent of glycosaminoglycans in cartilage and synovial fluid
a systematic review of several double blind RCTs of glucosamine in knee osteoarthritis reported significant short-term symptomatic benefits including significantly reduced joint space narrowing and improved pain scores
more recent studies have however been mixed
the 2008 NICE guidelines suggest it is not recommended
a 2008 Drug and Therapeutics Bulletin review advised that whilst glucosamine provides modest pain relief in knee osteoarthritis it should not be prescribed on the NHS due to limited evidence of cost-effectiveness
