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
Osteoporosis management
Osteoporosis management
Advancing age and female sex are significant risk factors for osteoporosis. Prevalence of osteoporosis increases from 2% at 50 years to more than 25% at 80 years in women.
There are many other risk factors and secondary causes of osteoporosis. We’ll start by looking at the most ‘important’ ones - these are risk factors that are used by major risk assessment tools such as FRAX:
history of glucocorticoid use
rheumatoid arthritis
alcohol excess
history of parental hip fracture
low body mass index
current smoking
Other risk factors
sedentary lifestyle
premature menopause
Caucasians and Asians
endocrine disorders: hyperthyroidism, hypogonadism (e.g. Turner’s, testosterone deficiency), growth hormone deficiency, hyperparathyroidism, diabetes mellitus
multiple myeloma, lymphoma
gastrointestinal disorders: inflammatory bowel disease, malabsorption (e.g. Coeliac’s), gastrectomy, liver disease
chronic kidney disease
osteogenesis imperfecta, homocystinuria
Medications that may worsen osteoporosis (other than glucocorticoids):
SSRIs
antiepileptics
proton pump inhibitors
glitazones
long term heparin therapy
aromatase inhibitors e.g. anastrozole
Investigations for secondary causes
If a patient is diagnosed with osteoporosis or has a fragility fracture further investigations may be warranted. NOGG recommend testing for the following reasons:
exclude diseases that mimic osteoporosis (e.g. osteomalacia, myeloma);
identify the cause of osteoporosis and contributory factors;
assess the risk of subsequent fractures;
select the most appropriate form of treatment
The following investigations are recommended by NOGG:
History and physical examination
Blood cell count, sedimentation rate or C-reactive protein, serum calcium,
albumin, creatinine, phosphate, alkaline phosphatase and liver transaminases
Thyroid function tests
Bone densitometry ( DXA)
Other procedures, if indicated
Lateral radiographs of lumbar and thoracic spine/DXA-based vertebral imaging
Protein immunoelectrophoresis and urinary Bence-Jones proteins
25OHD
PTH
Serum testosterone, SHBG, FSH, LH (in men),
Serum prolactin
24 hour urinary cortisol/dexamethasone suppression test
Endomysial and/or tissue transglutaminase antibodies (coeliac disease)
Isotope bone scan
Markers of bone turnover, when available
Urinary calcium excretion
So from the first list we should order the following bloods as a minimum for all patients:
full blood count
urea and electrolytes
liver function tests
bone profile
CRP
thyroid function tests
Osteoporotic Treatment
NICE guidelines were updated in 2008 on the secondary prevention of osteoporotic fractures in postmenopausal women.
Key points include
treatment is indicated following osteoporotic fragility fractures in postmenopausal women who are confirmed to have osteoporosis (a T-score of - 2.5 SD or below). In women aged 75 years or older, a DEXA scan may not be required ‘if the responsible clinician considers it to be clinically inappropriate or unfeasible’
vitamin D and calcium supplementation should be offered to all women unless the clinician is confident they have adequate calcium intake and are vitamin D replete
alendronate is first-line
around 25% of patients cannot tolerate alendronate, usually due to upper gastrointestinal problems. These patients should be offered risedronate or etidronate (see treatment criteria below)
strontium ranelate and raloxifene are recommended if patients cannot tolerate bisphosphonates (see treatment criteria below)
Treatment criteria for patients not taking alendronate
Unfortunately, a number of complicated treatment cut-off tables have been produced in the latest guidelines for patients who do not tolerate alendronate
These take into account a patients age, theire T-score and the number of risk factors they have from the following list:
parental history of hip fracture
alcohol intake of 4 or more units per day
rheumatoid arthritis
It is very unlikely that examiners would expect you to have memorised these risk tables so we’ve not included them in the revision notes but they may be found by following the NICE link. The most important thing to remember is:
the T-score criteria for risedronate or etidronate are less than the others implying that these are the second line drugs
if alendronate, risedronate or etidronate cannot be taken then strontium ranelate or raloxifene may be given based on quite strict T-scores (e.g. a 60-year-old woman would need a T-score < -3.5)
the strictest criteria are for denosumab
Supplementary notes on treatment
Bisphosphonates
alendronate, risedronate and etidronate are all licensed for the prevention and treatment of post-menopausal and glucocorticoid-induced osteoporosis
all three have been shown to reduce the risk of both vertebral and non-vertebral fractures although alendronate, risedronate may be superior to etidronate in preventing hip fractures
ibandronate is a once-monthly oral bisphosphonate
Vitamin D and calcium
poor evidence base to suggest reduced fracture rates in the general population at risk of osteoporotic fractures - may reduce rates in frail, housebound patients
Raloxifene - selective oestrogen receptor modulator (SERM)
has been shown to prevent bone loss and to reduce the risk of vertebral fractures, but has not yet been shown to reduce the risk of non-vertebral fractures
has been shown to increase bone density in the spine and proximal femur
may worsen menopausal symptoms
increased risk of thromboembolic events
may decrease risk of breast cancer
Strontium ranelate
‘dual action bone agent’ - increases deposition of new bone by osteoblasts (promotes differentiation of pre-osteoblast to osteoblast) and reduces the resorption of bone by inhibiting osteoclasts
concerns regarding the safety profile of strontium have been raised recently. It should only be prescribed by a specialist in secondary care
due to these concerns the European Medicines Agency in 2014 said it should only be used by people for whom there are no other treatments for osteoporosis
increased risk of cardiovascular events: any history of cardiovascular disease or significant risk of cardiovascular disease is a contraindication
increased risk of thromboembolic events: a Drug Safety Update in 2012 recommended it is not used in patients with a history of venous thromboembolism
may cause serious skin reactions such as Stevens Johnson syndrome
Denosumab
human monoclonal antibody that inhibits RANK ligand, which in turn inhibits the maturation of osteoclasts
given as a single subcutaneous injection every 6 months
initial trial data suggests that it is effective and well tolerated
Teriparatide
recombinant form of parathyroid hormone
very effective at increasing bone mineral density but role in the management of osteoporosis yet to be clearly defined
Hormone replacement therapy
has been shown to reduce the incidence of vertebral fracture and non-vertebral fractures
due to concerns about increased rates of cardiovascular disease and breast cancer it is no longer recommended for primary or secondary prevention of osteoporosis unless the woman is suffering from vasomotor symptoms
Hip protectors
evidence to suggest significantly reduce hip fractures in nursing home patients
compliance is a problem
Falls risk assessment
no evidence to suggest reduced fracture rates
however, do reduce rate of falls and should be considered in management of high risk patients
Pagets disease of the bone
Paget’s disease is a disease of increased but uncontrolled bone turnover. It is thought to be primarily a disorder of osteoclasts, with excessive osteoclastic resorption followed by increased osteoblastic activity. Paget’s disease is common (UK prevalence 5%) but symptomatic in only 1 in 20 patients. The skull, spine/pelvis, and long bones of the lower extremities are most commonly affected.
Predisposing factors
increasing age
male sex
northern latitude
family history
Clinical features - only 5% of patients are symptomatic
the stereotypical presentation is an older male with bone pain and an isolated raised ALP
bone pain (e.g. pelvis, lumbar spine, femur)
classical, untreated features: bowing of tibia, bossing of skull
raised alkaline phosphatase (ALP) - calcium* and phosphate are typically normal
other markers of bone turnover include: procollagen type I N-terminal propeptide (PINP), serum C-telopeptide (CTx), urinary N-telopeptide (NTx), and urinary hydroxyproline
skull x-ray: thickened vault, osteoporosis circumscripta
Indications for treatment include bone pain, skull or long bone deformity, fracture, periarticular Paget’s
bisphosphonate (either oral risedronate or IV zoledronate)
calcitonin is less commonly used now
Complications
deafness (cranial nerve entrapment)
bone sarcoma (1% if affected for > 10 years)
fractures
skull thickening
high-output cardiac failure
Polymyalgia rheumatica
Pathophysiology overlaps with temporal arteritis
histology shows vasculitis with giant cells, characteristically ‘skips’ certain sections of affected artery whilst damaging others
muscle bed arteries affected most in polymyalgia rheumatica
Features
typically patient > 60 years old
usually rapid onset (e.g. < 1 month)
aching, morning stiffness in proximal limb muscles (not weakness)
also mild polyarthralgia, lethargy, depression, low-grade fever, anorexia, night sweats
Investigations
ESR > 40 mm/hr
note creatine kinase and EMG normal
Treatment
prednisolone e.g. 15mg/od - dramatic response
Psoriatic arthropathy
Psoriatic arthropathy correlates poorly with cutaneous psoriasis and often precedes the development of skin lesions. Around 10-20% percent of patients with skin lesions develop an arthropathy with males and females being equally affected
Types*
rheumatoid-like polyarthritis: (30-40%, most common type)
asymmetrical oligoarthritis: typically affects hands and feet (20-30%)
sacroilitis
DIP joint disease (10%)
arthritis mutilans (severe deformity fingers/hand, ‘telescoping fingers’)
Management
should be managed by a rheumatologist
treat as rheumatoid arthritis but better prognosis
Raynauds
Raynaud’s phenomena may be primary (Raynaud’s disease) or secondary (Raynaud’s phenomenon)
Raynaud’s disease typically presents in young women (e.g. 30 years old) with bilateral symptoms.
Factors suggesting underlying connective tissue disease
onset after 40 years
unilateral symptoms
rashes
presence of autoantibodies
features which may suggest rheumatoid arthritis or SLE, for example arthritis or recurrent miscarriages
digital ulcers, calcinosis
very rarely: chilblains
Secondary causes
connective tissue disorders: scleroderma (most common), rheumatoid arthritis, SLE
leukaemia
type I cryoglobulinaemia, cold agglutinins
use of vibrating tools
drugs: oral contraceptive pill, ergot
cervical rib
Management
first-line: calcium channel blockers e.g. nifedipine
IV prostacyclin (epoprostenol) infusions: effects may last several weeks/months
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
Chronic fatigue syndrome
Diagnosed after at least 4 months of disabling fatigue affecting mental and physical function more than 50% of the time in the absence of other disease which may explain symptoms
Epidemiology
more common in females
past psychiatric history has not been shown to be a risk factor
Fatigue is the central feature, other recognised features include
sleep problems, such as insomnia, hypersomnia, unrefreshing sleep, a disturbed sleep-wake cycle
muscle and/or joint pains
headaches
painful lymph nodes without enlargement
sore throat
cognitive dysfunction, such as difficulty thinking, inability to concentrate, impairment of short-term memory, and difficulties with word-finding
physical or mental exertion makes symptoms worse
general malaise or ‘flu-like’ symptoms
dizziness
nausea
palpitations
Investigation
NICE guidelines suggest carrying out a large number of screening blood tests to exclude other pathology e.g. FBC, U&E, LFT, glucose, TFT, ESR, CRP, calcium, CK, ferritin*, coeliac screening and also urinalysis
Management
cognitive behaviour therapy - very effective, number needed to treat = 2
graded exercise therapy - a formal supervised program, not advice to go to the gym
‘pacing’ - organising activities to avoid tiring
low-dose amitriptyline may be useful for poor sleep
referral to a pain management clinic if pain is a predominant feature
Better prognosis in children
Reactive arthritis features
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 during the Second World War. Later studies identified patients who developed symptoms following a sexually transmitted infection (post-STI, now sometimes referred to as sexually acquired reactive arthritis, SARA).
Reactive arthritis is defined as an arthritis that develops following an infection where the organism cannot be recovered from the joint.
Features
typically develops within 4 weeks of initial infection - symptoms generally last around 4-6 months
arthritis is typically an asymmetrical oligoarthritis of lower limbs
dactylitis
symptoms of urethritis
eye: conjunctivitis (seen in 10-30%), anterior uveitis
skin: circinate balanitis (painless vesicles on the coronal margin of the prepuce), keratoderma blenorrhagica (waxy yellow/brown papules on palms and soles)
Around 25% of patients have recurrent episodes whilst 10% of patients develop chronic disease
‘Can’t see, pee or climb a tree’
Rheumatoid arthritis drug side-effects
The table below lists some of the characteristic (if not common) side-effects of drugs used to treat rheumatoid arthritis:
Drug
Side-effects
Methotrexate
Myelosuppression
Liver cirrhosis
Pneumonitis
Sulfasalazine
Rashes
Oligospermia
Heinz body anaemia
Interstitial lung disease
Leflunomide
Liver impairment
Interstitial lung disease
Hypertension
Hydroxychloroquine
Retinopathy
Corneal deposits
Prednisolone
Cushingoid features
Osteoporosis
Impaired glucose tolerance
Hypertension
Cataracts
Gold
Proteinuria
Penicillamine
Proteinuria
Exacerbation of myasthenia gravis
Etanercept
Demyelination
Reactivation of tuberculosis
Infliximab
Reactivation of tuberculosis
Adalimumab
Reactivation of tuberculosis
Rituximab
Infusion reactions are common
NSAIDs (e.g. naproxen, ibuprofen)
Bronchospasm in asthmatics
Dyspepsia/peptic ulceration
Rheumatoid arthritis: prognostic features
A number of features have been shown to predict a poor prognosis in patients with rheumatoid arthritis, as listed below
Poor prognostic features
rheumatoid factor positive
poor functional status at presentation
HLA DR4
X-ray: early erosions (e.g. after < 2 years)
extra articular features e.g. nodules
insidious onset
anti-CCP antibodies
In terms of gender there seems to be a split in what the established sources state is associated with a poor prognosis. However both the American College of Rheumatology and the recent NICE guidelines (which looked at a huge number of prognosis studies) seem to conclude that female gender is associated with a poor prognosis.
Septic arthritis
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
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
Rotator cuff muscles
SItS - small t for teres minor
Supraspinatus
Infraspinatus
teres minor
Subscapularis
Muscle
Notes
Supraspinatus
aBDucts arm before deltoid
Most commonly injured
Infraspinatus
Rotates arm laterally
teres minor
aDDucts & rotates arm laterally
Subscapularis
aDDuct & rotates arm medially
Sjogren’s syndrome
Sjogren’s syndrome is an autoimmune disorder affecting exocrine glands resulting in dry mucosal surfaces. It may be primary (PSS) or secondary to rheumatoid arthritis or other connective tissue disorders, where it usually develops around 10 years after the initial onset. Sjogren’s syndrome is much more common in females (ratio 9:1). There is a marked increased risk of lymphoid malignancy (40-60 fold).
Features
dry eyes: keratoconjunctivitis sicca
dry mouth
vaginal dryness
arthralgia
Raynaud’s, myalgia
sensory polyneuropathy
recurrent episodes of parotitis
renal tubular acidosis (usually subclinical)
Investigation
rheumatoid factor (RF) positive in nearly 100% 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
Schirmer’s test: filter paper near conjunctival sac to measure tear formation
histology: focal lymphocytic infiltration
also: hypergammaglobulinaemia, low C4
Management
artificial saliva and tears
pilocarpine may stimulate saliva production
Raynaud’s
Raynaud’s phenomena may be primary (Raynaud’s disease) or secondary (Raynaud’s phenomenon)
Raynaud’s disease typically presents in young women (e.g. 30 years old) with bilateral symptoms.
Factors suggesting underlying connective tissue disease
onset after 40 years
unilateral symptoms
rashes
presence of autoantibodies
features which may suggest rheumatoid arthritis or SLE, for example arthritis or recurrent miscarriages
digital ulcers, calcinosis
very rarely: chilblains
Secondary causes
connective tissue disorders: scleroderma (most common), rheumatoid arthritis, SLE
leukaemia
type I cryoglobulinaemia, cold agglutinins
use of vibrating tools
drugs: oral contraceptive pill, ergot
cervical rib
Management
first-line: calcium channel blockers e.g. nifedipine
IV prostacyclin (epoprostenol) infusions: effects may last several weeks/months
Systemic sclerosis
This patient has Sclerodactyly and Raynaud’s phenomenon. Telangiectasia can also be seen on the hands. She therefore has the RST of CREST syndrome, or more accurately limited cutaneous systemic sclerosis.
Systemic sclerosis is a condition of unknown aetiology characterised by hardened, sclerotic skin and other connective tissues. It is four times more common in females.
There are three patterns of disease:
Limited cutaneous systemic sclerosis
Raynaud’s may be first sign
scleroderma affects face and distal limbs predominately
associated with anti-centromere antibodies
a subtype of limited systemic sclerosis is CREST syndrome: Calcinosis, Raynaud’s phenomenon, oEsophageal dysmotility, Sclerodactyly, Telangiectasia
Diffuse cutaneous systemic sclerosis
scleroderma affects trunk and proximal limbs predominately
associated with scl-70 antibodies
the most common cause of death is now respiratory involvement, which is seen in around 80%: interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH)
other complications include renal disease and hypertension
poor prognosis
Scleroderma (without internal organ involvement)
tightening and fibrosis of skin
may be manifest as plaques (morphoea) or linear
Polymyalgia rheumatica
Pathophysiology
overlaps with temporal arteritis
histology shows vasculitis with giant cells, characteristically ‘skips’ certain sections of affected artery whilst damaging others
muscle bed arteries affected most in polymyalgia rheumatica
Features
typically patient > 60 years old
usually rapid onset (e.g. < 1 month)
aching, morning stiffness in proximal limb muscles (not weakness)
also mild polyarthralgia, lethargy, depression, low-grade fever, anorexia, night sweats
Investigations
ESR > 40 mm/hr
note creatine kinase and EMG normal
Treatment
prednisolone e.g. 15mg/od - dramatic response
Temporal arteritis
Temporal arteritis is large vessel vasculitis which overlaps with polymyalgia rheumatica (PMR). Histology shows changes which characteristically ‘skips’ certain sections of affected artery whilst damaging others.
Features
typically patient > 60 years old
usually rapid onset (e.g. < 1 month)
headache (found in 85%)
jaw claudication (65%)
visual disturbances secondary to anterior ischemic optic neuropathy
tender, palpable temporal artery
around 50% have features of PMR: aching, morning stiffness in proximal limb muscles (not weakness)
also lethargy, depression, low-grade fever, anorexia, night sweats
Investigations
raised inflammatory markers: ESR > 50 mm/hr (note ESR < 30 in 10% of patients). CRP may also be elevated
temporal artery biopsy: skip lesions may be present
note creatine kinase and EMG normal
Treatment
high-dose prednisolone - there should be a dramatic response, if not the diagnosis should be reconsidered
urgent ophthalmology review. Patients with visual symptoms should be seen the same-day by an ophthalmologist. Visual damage is often irreversible
Osteomalacia
Basics
normal bony tissue but decreased mineral content
rickets if when growing
osteomalacia if after epiphysis fusion
Types
vitamin D deficiency e.g. malabsorption, lack of sunlight, diet
renal failure
drug induced e.g. anticonvulsants
vitamin D resistant; inherited
liver disease, e.g. cirrhosis
Features
rickets: knock-knee, bow leg, features of hypocalcaemia
osteomalacia: bone pain, fractures, muscle tenderness, proximal myopathy
Investigation
low 25(OH) vitamin D (in 100% of patients, by definition)
raised alkaline phosphatase (in 95-100% of patients)
low calcium, phosphate (in around 30%)
x-ray: children - cupped, ragged metaphyseal surfaces; adults - translucent bands (Looser’s zones or pseudofractures)
Treatment
calcium with vitamin D tablets
Polymyalgia rheumatica
Pathophysiology
overlaps with temporal arteritis
histology shows vasculitis with giant cells, characteristically ‘skips’ certain sections of affected artery whilst damaging others
muscle bed arteries affected most in polymyalgia rheumatica
Features
typically patient > 60 years old
usually rapid onset (e.g. < 1 month)
aching, morning stiffness in proximal limb muscles (not weakness)
also mild polyarthralgia, lethargy, depression, low-grade fever, anorexia, night sweats
Investigations
ESR > 40 mm/hr
note creatine kinase and EMG normal
Treatment
prednisolone e.g. 15mg/od - dramatic response
Reactive arthritis: features
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 during the Second World War. Later studies identified patients who developed symptoms following a sexually transmitted infection (post-STI, now sometimes referred to as sexually acquired reactive arthritis, SARA).
Reactive arthritis is defined as an arthritis that develops following an infection where the organism cannot be recovered from the joint.
Features
typically develops within 4 weeks of initial infection - symptoms generally last around 4-6 months
arthritis is typically an asymmetrical oligoarthritis of lower limbs
dactylitis
symptoms of urethritis
eye: conjunctivitis (seen in 10-30%), anterior uveitis
skin: circinate balanitis (painless vesicles on the coronal margin of the prepuce), keratoderma blenorrhagica (waxy yellow/brown papules on palms and soles)
Around 25% of patients have recurrent episodes whilst 10% of patients develop chronic disease
‘Can’t see, pee or climb a tree’
Temporal arteritis
Temporal arteritis is large vessel vasculitis which overlaps with polymyalgia rheumatica (PMR). Histology shows changes which characteristically ‘skips’ certain sections of affected artery whilst damaging others.
Features
typically patient > 60 years old
usually rapid onset (e.g. < 1 month)
headache (found in 85%)
jaw claudication (65%)
visual disturbances secondary to anterior ischemic optic neuropathy
tender, palpable temporal artery
around 50% have features of PMR: aching, morning stiffness in proximal limb muscles (not weakness)
also lethargy, depression, low-grade fever, anorexia, night sweats
Investigations
raised inflammatory markers: ESR > 50 mm/hr (note ESR < 30 in 10% of patients). CRP may also be elevated
temporal artery biopsy: skip lesions may be present
note creatine kinase and EMG normal
Treatment
high-dose prednisolone - there should be a dramatic response, if not the diagnosis should be reconsidered
urgent ophthalmology review. Patients with visual symptoms should be seen the same-day by an ophthalmologist. Visual damage is often irreversible
Vitamin D supplementation
Vitamin D supplementation has been a hot topic for a number of years now. The muddied waters are now slightly clearer following the release of the following:
2012: letter by the Chief Medical Officer regarding vitamin D supplementation
2013: National Osteoporosis Society (NOS) release UK Vitamin D guideline
The following groups should be advised to take vitamin D supplementation:
all pregnant and breastfeeding women should take a daily supplement containing 10µg of vitamin D
all children aged 6 months - 5 years. Babies fed with formula milk do not need to take a supplement if they are taking more than 500ml of milk a day, as formula milk is fortified with vitamin D
adults > 65 years
‘people who are not exposed to much sun should also take a daily supplement’ e.g. housebound patients
Testing for vitamin D deficiency
The key message is that not many people warrant a vitamin D test. The NOS guidelines specify that testing may be appropriate in the following situtations:
patients with bone diseases that may be improved with vitamin D treatment e.g. known osteomalacia or Paget’s disease
patients with bone diseases, prior to specific treatment where correcting vitamin deficiency is appropriate e,g, prior to intravenous zolendronate or denosumab
patients with musculoskeletal symptoms that could be attributed to vitamin D deficiency e.g. bone pain ?osteomalacia
Patients with osteoporosis should always be given calcium/vitamin D supplements so testing is not considered necessary. People who are at higher risk of vitamin D deficiency (see above) should be treated anyway so again testing is not necessary.
