General Flashcards
What are the features of adhesive capsulitis?
external rotation is affected more than internal rotation or abduction
both active and passive movement is affected
patients typically have a painful freezing phase, an adhesive phase and a recovery phase
bilateral in up to 20% of patients
the episode typically lasts between 6 months and 2 years
What is the association with adhesive capsulitis?
Diabetes mellitus
What are the features of ANCA positive vasculitis?
renal impairment
- caused by immune complex glomerulonephritis → raised creatinine, haematuria and proteinuria
respiratory symptoms
- dyspnoea
- haemoptysiis
systemic symptoms
- fatigue
- weight loss
- fever
vasculitic rash: present only in a minority of patients
ear, nose and throat symptoms
sinusitis
What investigations should be completed in ANCA positive vasculitis?
urinalysis for haematuria and proteinuria
bloods:
urea and creatinine for renal impairment
full blood count: normocytic anaemia and thrombocytosis may be seen
CRP: raised
ANCA testing (see below)
chest x-ray: nodular, fibrotic or infiltrative lesions may be seen
Vasculitis caused by cANCA?
granulomatosis with polyangiitis
Vasculitis caused by pANCA?
eosinophilic granulomatosis with polyangiitis + others (see below)
What ANCA can be used to monitor disease levels?
cANCA
Target of cANCA autoantibody?
Serine proteinase 3 (PR3)
Target of pANCA autoantibody?
myeloperoxidase (MPO)
Other conditions associated with pANCA?
Ulcerative colitis (70%)
Primary sclerosing cholangitis (70%)
Anti-GBM disease (25%)
Crohn’s disease (20%)
Features of ankylosing spondylitis?
Young man
Insidious onset
Improves with exercise
Pain at night
Worse when getting up
Clinical features of 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
What are the other features of ankylosing spondylitis?
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)
Features of antiphosphlipid syndrome
venous/arterial thrombosis
recurrent fetal loss
livedo reticularis
thrombocytopenia
prolonged APTT
other features: pre-eclampsia, pulmonary hypertension
Why does antiphospholipid syndrome have a paradoxical rise in APTT?
ex-vivo reaction of the lupus anticoagulant autoantibodies with phospholipids involved in the coagulation cascade
Associations of antiphospholipid syndrome?
SLE
Autoimmune disorders
Lymphoproliferative disorders
Management of antiphospholipid syndrome?
Primary propylaxis
1. Low dose aspirin
Secondary prophylaxis
1. initial venous thromboembolic events: lifelong warfarin with a target INR of 2-3
2. recurrent venous thromboembolic events: lifelong warfarin; if occurred whilst taking warfarin then consider adding low-dose aspirin, increase target INR to 3-4
3. arterial thrombosis should be treated with lifelong warfarin with target INR 2-3
Causes of avscular necrosis of the hip?
long-term steroid use
chemotherapy
alcohol excess
trauma
Features of avascular necrosis of the hip?
Death of bone tissue secondary to loss of the blood supply
initially asymptomatic
pain in the affected joint
Investigation findings for avascular necrosis of hip?
Osteopenia and microfractures may be seen early on. Collapse of the articular surface may result in the crescent sign
Best imaging modality for avscular necrosis?
MRI is the investigation of choice. It is more sensitive than radionuclide bone scanning
What is the mechanism of azathioprine?
metabolised to the active compound mercaptopurine, a purine analogue that inhibits purine synthesis.
What test should be done before starting azathiprine?
thiopurine methyltransferase (TPMT) test
What are the adverse effects of azathioprine?
bone marrow depression
- consider a full blood count if infection/bleeding occurs
nausea/vomiting
pancreatitis
increased risk of non-melanoma skin cancer
Can azathioprine be used in pregnancy ?
Yes
What is the classic triad of bechets ?
Oral ulcers
Gential ulcers
Anterior uveitis
What is the HLA type of bechets?
HLA B 51
more specifically HLA B51, a split antigen of HLA B5
Features of bechets?
classically: 1) oral ulcers 2) genital ulcers 3) anterior uveitis
thrombophlebitis and deep vein thrombosis
arthritis
neurological involvement (e.g. aseptic meningitis)
GI: abdo pain, diarrhoea, colitis
erythema nodosum
What are the adverse effects of bisphsophonates?
oesophageal reactions: oesophagitis, oesophageal ulcers (especially alendronate)
osteonecrosis of the jaw
increased risk of atypical stress fractures of the proximal femoral shaft in patients taking alendronate
acute phase response: fever, myalgia and arthralgia may occur following administration
hypocalcaemia: due to reduced calcium efflux from bone. Usually clinically unimportant
What is the mechanism of bisphonsates
Inhibits osteoclasts
Osteoporosis: Calcium Phosphate ALP PTH ?
All normal
Osteomalacia: Calcium Phosphate ALP PTH ?
Decreased calcium
Decreased phosphate
Increased ALP
Increased PTH
Primary Hyperthyroidism : Calcium Phosphate ALP PTH ?
Increased calcium
Decreased phosphate
Increased ALP
Increased PTH
Chronic kidney disease ( Secondary hyperparathyroidism) : Calcium Phosphate ALP PTH ?
Decreased calcium
Increased phosphate
Increased ALP
Increased PTH
Paget’s disease: calcium, phosphate, ALP ,PTH?
Normal Calcium
Normal phosphate
Increased ALP
Normal PTH
What is osteopetrosis?
Condition were bone harden
All bone markers are normal
What are features of an osteoma?
Benign tumour
Benign overgrowth
Typically seen on skull
Associated with Gardner’s syndrome (a variant of familial adenomatous polyposis, FAP)
What are the features of an osteochrondroma?
Benign tumour
cartilage-capped bony projection on the external surface of a bone
What are the features of a giant cell tumour?
Benign tumour
occurs most frequently in the epiphyses of long bones
X-ray shows a ‘double bubble’ or ‘soap bubble’ appearance
What is the most common primary malignant bone cancer?
Osteosarcoma
Features of osteosarcoma?
Most common primary malignant tumour
Seen frequently at metaphysis
x-ray shows Codman triangle (from periosteal elevation) and ‘sunburst’ pattern
mutation of the Rb gene significantly increases risk of osteosarcoma (hence association with retinoblastoma)
other predisposing factors include Paget’s disease of the bone and radiotherapy
Features of ewing’s sarcoma?
Malignant tumour
frequently in the pelvis and long bones. Tends to cause severe pain
associated with t(11;22) translocation which results in an EWS-FLI1 gene product
x-ray shows ‘onion skin’ appearance
Features of chondrosarcoma?
malignant tumour of cartilage
most commonly affects the axial skeleton
more common in middle-age
What are the features of carpal tunnel syndrome?
weakness of thumb abduction (abductor pollicis brevis)
wasting of thenar eminence (NOT hypothenar)
Tinel’s sign: tapping causes paraesthesia
Phalen’s sign: flexion of wrist causes symptoms
What are the two eponymous named tests for carpal tunnel?
Tinel’s sign: tapping causes paraesthesia
Phalen’s sign: flexion of wrist causes symptoms
Causes of carpal tunnel syndrome?
idiopathic
pregnancy
oedema e.g. heart failure
lunate fracture
rheumatoid arthritis
Management of carpal tunnel?
Flexor retinaculum division
Features of cubital tunnel syndrome?
Tingling and numbness of the 4th and 5th finger which starts off intermittent and then becomes constant.
Over time patients may also develop weakness and muscle wasting
Pain worse on leaning on the affected elbow
What is de quervains tenosynovitis?
condition in which the sheath containing the extensor pollicis brevis and abductor pollicis longus tendons is inflamed
What are the features of de quervain’s tenosynovitis?
pain on the radial side of the wrist
tenderness over the radial styloid process
abduction of the thumb against resistance is painful
What test can be done to confirm de quervain’s tenosynovitis?
Finkelstein’s test: the examiner pulls the thumb of the patient in ulnar deviation and longitudinal traction. In a patient with tenosynovitis this action causes pain over the radial styloid process and along the length of extensor pollisis brevis and abductor pollicis longus
What is denosumab ? - what is it used in? - what is its mechanism?
human monoclonal antibody that prevents the development of osteoclasts by inhibiting RANKL
What are the features of dermatomyositis?
symmetrical, proximal muscle weakness and characteristic skin lesions
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
Autoantibodies associated in dermatomyositis?
antibodies against histidine-tRNA ligase (also called Jo-1)
antibodies to signal recognition particle (SRP)
anti-Mi-2 antibodies
Other features of dermatomyositis?
proximal muscle weakness +/- tenderness
Raynaud’s
respiratory muscle weakness
interstitial lung disease: e.g. Fibrosing alveolitis or organising pneumonia
dysphagia, dysphonia
Most specific antibody for dermatomyositis?
anti-Mi-2 antibodies are highly specific for dermatomyositis, but are only seen in around 25% of patients
Other investigation findings on dermatomyositis?
elevated creatine kinase
EMG
muscle biopsy
ANA positive in 60%
anti-Mi-2 antibodies are highly specific for dermatomyositis, but are only seen in around 25% of patients
anti-Jo-1 antibodies are not commonly seen in dermatomyositis - they are more common in polymyositis where they are seen in a pattern of disease associated with lung involvement, Raynaud’s and fever
Features of discoid lupus?
erythematous, raised rash, sometimes scaly
may be photosensitive
more common on face, neck, ears and scalp
lesions heal with atrophy, scarring (may cause scarring alopecia), and pigmentation
very rarely progresses to systemic lupus erythematosus
characterised by follicular keratin plugs and is thought to be autoimmune in aetiology
Management of discoid lupus?
topical steroid cream
oral antimalarials may be used second-line e.g. hydroxychloroquine
avoid sun exposure
Most common cause of drug induced lupus?
Most common causes
procainamide
hydralazine
Less common causes
isoniazid
minocycline
phenytoin
What is the antibody profile in drug induced lupus?
ANA positive in 100%, dsDNA negative
anti-histone antibodies are found in 80-90%
anti-Ro, anti-Smith positive in around 5%
Features of ehler’s danlos syndrome?
elastic, fragile skin
joint hypermobility: recurrent joint dislocation
easy bruising
aortic regurgitation, mitral valve prolapse and aortic dissection
subarachnoid haemorrhage
angioid retinal streaks
What are the features of lateral epicondylitis?
pain and tenderness localised to the lateral epicondyle
pain worse on resisted wrist extension with the elbow extended or supination of the forearm with the elbow extended
episodes typically last between 6 months and 2 years. Patients tend to have acute pain for 6-12 weeks
What are the features of medial epicondylitis?
pain and tenderness localised to the medial epicondyle
pain is aggravated by wrist flexion and pronation
symptoms may be accompanied by numbness / tingling in the 4th and 5th finger due to ulnar nerve involvement
What are the features of radial tunnel syndrome?
compression of the posterior interosseous branch of the radial nerve
symptoms are similar to lateral epicondylitis making it difficult to diagnose
however, the pain tends to be around 4-5 cm distal to the lateral epicondyle
symptoms may be worsened by extending the elbow and pronating the forearm
Features of cubital tunnel syndrome?
initially intermittent tingling in the 4th and 5th finger
may be worse when the elbow is resting on a firm surface or flexed for extended periods
later numbness in the 4th and 5th finger with associated weakness
Features of olecranon bursitis?
Swelling over the posterior aspect of the elbow
What is associated with an anti-Ro antibody?
Sjogren’s syndrome
SLE
congenital heart block
What is associated with an anti-la antibody?
Sjorgan’s syndrome
What is associated with anti-Jo antibody?
Polymyositis
What is associated with anti-Scl70 antibody?
Diffuse cutaneous systemic sclerosis
What is associated with anti-centromere antibody?
Limited cutaneous systemic sclerosis
What is familial mediterian fever?
Autosomal recessive
Features - attacks typically last 1-3 days
pyrexia
abdominal pain (due to peritonitis)
pleurisy
pericarditis
arthritis
erysipeloid rash on lower limbs
Management of familial mediterian fever?
Colchicine
Drug causes of gout?
diuretics: thiazides, furosemide
ciclosporin
alcohol
cytotoxic agents
pyrazinamide
aspirin
Joints typically affected in gout?
1st metatarsophalangeal (MTP) joint
ankle
wrist
knee
What are the radiological features of gout?
joint effusion is an early sign
well-defined ‘punched-out’ erosions with sclerotic margins in a juxta-articular distribution, often with overhanging edges
relative preservation of joint space until late disease
eccentric erosions
no periarticular osteopenia (in contrast to rheumatoid arthritis)
soft tissue tophi may be seen
What is gout ?
deposition of monosodium urate monohydrate in the synovium.
Acute management of gout?
- NSAIDs or colchicine are first-line
2 Gastroprotection
Consider steroids if colchicine is contraindicated
Urate lowering therapy
When should rate lowering therapy be used in gout?
Should be started after first bout 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
Does not need to be started after 2 weeks post flare. Can start whenever
Dose of allopurinol in gout?
100 mg
What can be tried in refractory cases of hyperuricaemia and gout?
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
Lifestyle modifications in gout?
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
What drug changes should be made to a patient’s drug list?
stop thiazides
Lorsartan has a uricosuric action and may be particularly suitable for the many patients who have coexistent hypertension
Vitamin C may also reduced uric acid
Risk factors the reduced uric acid secretion?
drugs*: diuretics
chronic kidney disease
lead toxicity
Risk factors the increased uric acid secretion?
myeloproliferative/lymphoproliferative disorder
cytotoxic drugs
severe psoriasis
Features of lesch nyman syndrome?
hypoxanthine-guanine phosphoribosyl transferase (HGPRTase) deficiency
x-linked recessive therefore only seen in boys
features: gout, renal failure, neurological deficits, learning difficulties, self-mutilation
Features of greater trochanteric pain syndrome?
pain over the lateral side of hip/thigh
tenderness on palpation of the greater trochanter
Mechanism of greater trochanteric pain syndrome?
repeated movement of the fibroelastic iliotibial band
Features of osteoarthritis?
Pain exacerbated by exercise and relieved by rest
Reduction in internal rotation is often the first sign
Features of inflammatory arthritis?
Pain in the morning
Systemic features
Raised inflammatory markers
Features of meralgia parasthetica?
Caused by compression of lateral cutaneous nerve of thigh
Typically burning sensation over antero-lateral aspect of thigh
Features of avascular necrosis ?
Symptoms may be of gradual or sudden onset
May follow high dose steroid therapy or previous hip fracture of dislocation
Features of 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
Features of transient idiopathic osteoporosis?
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
Features of developmental dysplasia of the hip?
Often picked up on newborn examination
Barlow’s test, Ortolani’s test are positive
Unequal skin folds/leg length
Features of transient synovitis of the hip ?
Typical age group = 2-10 years
Acute hip pain associated with viral infection
Commonest cause of hip pain in children
What is Perthes disease?
degenerative condition affecting the hip joints of children, typically between the ages of 4-8 years. It is due to avascular necrosis of the femoral head
10% are bilateral
What are the features of perthes disease?
hip pain: develops progressively over a few weeks
limp
stiffness and reduced range of hip movement
x-ray: early changes include widening of joint space, later changes include decreased femoral head size/flattening
Features of slipped upper femoral epiphysis?
Typical age group = 10-15 years
More common in obese children and boys
Displacement of the femoral head epiphysis postero-inferiorly
Bilateral slip in 20% of cases
May present acutely following trauma or more commonly with chronic, persistent symptoms
What is juvenile idiopathic arthritis?
Preferred to the older term juvenile chronic arthritis, describes arthritis occurring in someone who is less than 16 years old that lasts for more than three months. Pauciarticular JIA refers to cases where 4 or less joints are affected. It accounts for around 60% of cases of JIA
Features of juvenile idiopathic arthritis?
joint pain and swelling: usually medium sized joints e.g. knees, ankles, elbows
limp
ANA may be positive in JIA - associated with anterior uveitis
Features of septic arthritis?
Acute hip pain associated with systemic upset e.g. pyrexia. Inability/severe limitation of affected joint
Adverse effect of hydroxychloroquine?
bull’s eye retinopathy - may result in severe and permanent visual loss
Most common bacteria to cause a psoas abscess?
Haematogenous spread of bacteria
Staphylococcus aureus: most common
Secondary causes of psoas abscess?
Crohn’s (commonest cause in this category)
Diverticulitis, colorectal cancer
UTI, GU cancers
Vertebral osteomyelitis
Femoral catheter, lithotripsy
Endocarditis
intravenous drug use
What is the specific test to investigate for a psoas abscess?
Lie the patient on the normal side and hyperextend the affected hip. This should elicit pain as the psoas muscle is stretched.
What is the specific test to investigate for a psoas abscess?
Lie the patient on the normal side and hyperextend the affected hip. This should elicit pain as the psoas muscle is stretched.
What are the features of chondromalacia patellae?
Softening of the cartilage of the patella
Common in teenage girls
Characteristically anterior knee pain on walking up and down stairs and rising from prolonged sitting
Usually responds to physiotherapy
Features of Osgood scatter disease?
Seen in sporty teenagers
Pain, tenderness and swelling over the tibial tubercle
features of Osteochondritis dissecans
joint condition in which bone underneath the cartilage of a joint dies due to lack of blood flow. This bone and cartilage can then break loose, causing pain and possibly hindering joint motion
Pain after exercise
Intermittent swelling and locking
What are the features of patellar subluxation?
Medial knee pain due to lateral subluxation of the patella
Knee may give way
What is langerhans call histiocystosis?
rare condition associated with the abnormal proliferation of histiocytes. It typically presents in childhood with bony lesions.
Features of lagerhands Histiocytecystosis
bone pain, typically in the skull or proximal femur
cutaneous nodules
recurrent otitis media/mastoiditis
tennis racket-shaped Birbeck granules on electromicroscopy
What are the features of lateral epicondylitis?
pain and tenderness localised to the lateral epicondyle
pain worse on wrist extension against resistance with the elbow extended or supination of the forearm with the elbow extended
episodes typically last between 6 months and 2 years. Patients tend to have acute pain for 6-12 weeks
what should be considered when consenting a women for leflunomide ?
Very long half life
Very teratogenic
Adverse effects of leflunomide?
gastrointestinal, especially diarrhoea
hypertension
weight loss/anorexia
peripheral neuropathy
myelosuppression
pneumonitis
Red flags in back pain?
age < 20 years or > 50 years
history of previous malignancy
night pain
history of trauma
systemically unwell e.g. weight loss, fever
Features of spinal stenosis?
Usually gradual onset
Unilateral or bilateral leg pain (with or without back pain), numbness, and weakness which is worse on walking. Resolves when sits down. Pain may be described as ‘aching’, ‘crawling’.
Relieved by sitting down, leaning forwards and crouching down
Clinical examination is often normal
Requires MRI to confirm diagnosis
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
Peripheral arthritis (25%, more common if female)
Features of peripheral arterial disease?
Pain on walking, relieved by rest
Absent or weak foot pulses and other signs of limb ischaemia
Past history may include smoking and other vascular diseases
Features of L3 nerve root compression?
Sensory loss over anterior thigh
Weak quadriceps
Reduced knee reflex
Positive femoral stretch test
Features of L4 nerve root compression?
Sensory loss anterior aspect of knee
Weak quadriceps
Reduced knee reflex
Positive femoral stretch test
Features of L5 nerve root compression?
Sensory loss dorsum of foot
Weakness in foot and big toe dorsiflexion
Reflexes intact
Positive sciatic nerve stretch test
Features of S2 nerve root compression?
Sensory loss posterolateral aspect of leg and lateral aspect of foot
Weakness in plantar flexion of foot
Reduced ankle reflex
Positive sciatic nerve stretch test
What is lumbar spinal stenosis?
spinal stenosis is a condition in which the central canal is narrowed by tumour, disk prolapse or other similar degenerative changes.
What are the features of lumbar spinal stenosis?
Neuropathic pain
Claudication symptoms - position element
- sitting better than standing
- Pain worse working downhill
Best test to diagnose lumbar spinal stenosis?
MRI
What causes disk bulging?
Loss of water content
Loss of proteoglycan
increased stress transfer to the posterior facet joints, which accelerates cartilaginous degeneration, hypertrophy, and osteophyte formation
Management of lumbar spinal stenosis?
Laminectomy
Genetics of Marfan’s syndrome?
Autosomal dominant
FBN1 mutation
Chromosome 15
Protein fibrillin 1
Features of Marfan’s syndrome?
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
Eyes
- Upward lens dislocation
- Blue sclera
-myopia
dural ectasia (ballooning of the dural sac at the lumbosacral level)
Leading cause of death in Marfan’s syndrome?
Aortic things
beta-blocker/ACE-inhibitor therapy
What is Mcardle’s disease?
autosomal recessive type V glycogen storage disease
caused by myophosphorylase deficiency
this causes decreased muscle glycogenolysis
Feature of Mcardl’e disease?
muscle pain and stiffness following exercise
muscle cramps
myoglobinuria
low lactate levels during exercise
What does the lateral cutaneous nerve arise from?
L2 / L3
What diseases are present in mixed connective tissue disease?
SLE
Systemic sclerosis
Myositis
What antibody is associated with mixed connective tissue disease?
anti-U1 ribonucleoprotein (RNP) antibodies
Features of mixed connective tissue disease?
Raynaud’s phenomenon often precedes other symptoms and occurs in 90% of cases
Polyarthralgia/arthritis
Myalgia
‘Sausage fingers’(dactylitis)
Investigation findings in mixed connective tissue disease?
Exclude other connective tissue disease/vasculitis
Bloods FBC: anaemia, leucopenia, thrombocytopenia, U+E: renal impairment, CRP/ESR raised
ANA (usually) positive, anti Ds-DNA and scleroderma-specific antibodies (e.g. Anti-Scl70) are negative
Anti-U1 RNP (an extractable nuclear antigen, ENA), must be positive*.
Organ-specific investigations, e.g. ECG, echo, CT chest, MRI brain
Mechanism of mycophenolate mofatile?
inhibits inosine monophosphate dehydrogenase, which is needed for purine synthesis
as T and B cells are particularly dependent on this pathway it can reduce the proliferation of immune cells
Features of myopathy?
symmetrical muscle weakness (proximal > distal)
common problems are rising from chair or getting out of bath
sensation normal, reflexes normal, no fasciculation
Causes of myopathy?
inflammatory: polymyositis
inherited: Duchenne/Becker muscular dystrophy, myotonic dystrophy
endocrine: Cushing’s, thyrotoxicosis
alcohol
What are Heberden’s nodes?
Painless nodes (bony swellings)
Heberden’s nodes at the DIP joints
Seen in osteoarthritis?
What are Bouchard’s nodes?
Bouchard’s Nodes at the PIP joints
Painless bony swellings
Management of osteoarthritis?
paracetamol and topical NSAIDs are first-line analgesics. Topical NSAIDs are indicated only for OA of the knee or hand
Genetics of osteogenesis imperfecta?
autosomal dominant
abnormality in type 1 collagen due to decreased synthesis of pro-alpha 1 or pro-alpha 2 collagen polypeptides
Features of osteogenesis imperfecta?
presents in childhood
fractures following minor trauma
blue sclera
deafness secondary to otosclerosis
dental imperfections are common
Investigation findings in osteogenesis imperfecta?
adjusted calcium, phosphate, parathyroid hormone and ALP results are usually normal in osteogenesis imperfecta
What is osteomalacia?
softening of the bones secondary to low vitamin D levels
Causes of osteomalacia?
vitamin D deficiency
chronic kidney disease
drug induced e.g. anticonvulsants
inherited: hypophosphatemic rickets (previously called vitamin D-resistant rickets)
liver disease: e.g. cirrhosis
coeliac disease
Features of osteomalacia?
bone pain
bone/muscle tenderness
fractures: especially femoral neck
proximal myopathy: may lead to a waddling gait
Features of haematogenous spread osteomyelitis?
results from bacteraemia
is usually monomicrobial
most common form in children
vertebral osteomyelitis is the most common form of haematogenous osteomyelitis in adults
risk factors include: sickle cell anaemia, intravenous drug user, immunosuppression due to either medication or HIV, infective endocarditis
Features of non-haematogenous spread osteomyelitis?
results from the contiguous spread of infection from adjacent soft tissues to the bone or from direct injury/trauma to bone
is often polymicrobial
most common form in adults
risk factors include: diabetic foot ulcers/pressure sores, diabetes mellitus, peripheral arterial disease
Most common bacteria to cause osteomyelitis
staph aureus
Sickle cell: salmonella
Most common bacteria in sickle cell to cause osteomyelitis?
Salmonella
Best imaging to diagnose osteomyelitis?
MRI
Management of osteomyelitis?
Flucloxacillin 6 weeks
Clindamycin in penicillin allergic
Features of osteoPETrosis?
also known as marble bone disease
rare disorder of defective osteoclast function resulting in failure of normal bone resorption
results in dense, thick bones that are prone to fracture
bone pains and neuropathies are common.
calcium, phosphate and ALP are normal
stem cell transplant and interferon-gamma have been used for treatment
Causes of osteoporosis?
history of glucocorticoid use
rheumatoid arthritis
alcohol excess
history of parental hip fracture
low body mass index
current smoking
What is a T score for osteoporosis ?
T score: based on bone mass of young reference population
Z score is adjusted for age, gender and ethnic factors
What do T scores mean?
T score
> -1.0 = normal
-1.0 to -2.5 = osteopaenia
< -2.5 = osteoporosis
T score of -1.0 means bone mass of one standard deviation below that of young reference population
Management of osteoporosis according to T score?
T score Management
Greater than 0 Reassure
Between 0 and -1.5 Repeat bone density scan in 1-3 years
Less than -1.5 Offer bone protection
Pathophysiology of Paget’s disease?
uncontrolled bone turnover. It is thought to be primarily a disorder of osteoclasts, with excessive osteoclastic resorption followed by increased osteoblastic activity
What is the stereotypical presentation of Paget’s disease?
older male with bone pain and an isolated raised ALP
Markers of increased bone turnover?
procollagen type I N-terminal propeptide (PINP)
serum C-telopeptide (CTx)
urinary N-telopeptide (NTx)
urinary hydroxyproline
Xray findings in Paget’s disease?
osteolysis in early disease → mixed lytic/sclerotic lesions later
skull x-ray: thickened vault, osteoporosis circumscripta
Complication of Paget’s disease/
deafness (cranial nerve entrapment)
bone sarcoma (1% if affected for > 10 years)
fractures
skull thickening
high-output cardiac failure
Management of Paget’s disease?
bisphosphonate (either oral risedronate or IV zoledronate)
calcitonin is less commonly used now
What is polyarteritis nodosa/
medium-sized arteries with necrotizing inflammation leading to aneurysm formation. PAN is more common in middle-aged men and is associated with hepatitis B infection.
What is polyartertitis nods associated with?
Hepatitis B
Feature of polyartertitis nodes?
fever, malaise, arthralgia
weight loss
hypertension
mononeuritis multiplex, sensorimotor polyneuropathy
testicular pain
livedo reticularis
haematuria, renal failure
perinuclear-antineutrophil cytoplasmic antibodies (ANCA) are found in around 20% of patients with ‘classic’ PAN
hepatitis B serology positive in 30% of patients
Features of polymyalgia rheumatic?
typically patient > 60 years old
usually rapid onset (e.g. < 1 month)
aching, morning stiffness in proximal limb muscles
weakness is not considered a symptom of polymyalgia rheumatica
also mild polyarthralgia, lethargy, depression, low-grade fever, anorexia, night sweats
Investigation findings of PMR?
raised inflammatory markers e.g. ESR > 40 mm/hr
note creatine kinase and EMG normal
If PMR does not respond to steroids, what should you consider?
Another diagnosis
Antibody associated with polymyositis?
anti-synthetase antibodies
anti-Jo-1 antibodies are seen in pattern of disease associated with lung involvement, Raynaud’s and fever
Definitive test for polymyositis?
muscle biopsy
Management of psoriatic arthritis?
monoclonal antibodies such as ustekinumab (targets both IL-12 and IL-23) and secukinumab (targets IL-17)
Presentation of psoriatic arthritis?
sacroiliitis
DIP joint disease (10%)
arthritis mutilans (severe deformity fingers/hand, ‘telescoping fingers’)
asymmetrical oligoarthritis: typically affects hands and feet (20-30%)
symmetric polyarthritis
Management of raynoids?
all patients with suspected secondary Raynaud’s phenomenon should be referred to secondary care
first-line: calcium channel blockers e.g. nifedipine
IV prostacyclin (epoprostenol) infusions: effects may last several weeks/months
HLA associated with reactive arthritis?
HLA B 27
Non-sti bacteria that cause reactive arthritis?
Shigella flexneri
Salmonella typhimurium
Salmonella enteritidis
Yersinia enterocolitica
Campylobacter
STI bacteria that cause reactive arthritis?
Chlamydia trachomatis
Features of reactive arthritis?
Features
time course
typically develops within 4 weeks of initial infection - symptoms generally last around 4-6 months
around 25% of patients have recurrent episodes whilst 10% of patients develop chronic disease
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)
What is relapsing polychondritis?
multi-systemic condition characterised by repeated episodes of inflammation and deterioration of cartilage.
can affect other parts of the body such as the nose and joints.
Features of relapsing polychondritis?
Ears: auricular chondritis, hearing loss, vertigo
Nasal: nasal chondritis → saddle-nose deformity
Respiratory tract: e.g. hoarseness, aphonia, wheezing, inspiratory stridor
Ocular: episcleritis, scleritis, iritis, and keratoconjunctivitis sicca
Joints: arthralgia
Less commonly: cardiac valcular regurgitation, cranial nerve palsies, peripheral neuropathies, renal dysfunction
Complications of rheumatoid arthritis?
respiratory: pulmonary fibrosis, pleural effusion, pulmonary nodules, bronchiolitis obliterans, methotrexate pneumonitis, pleurisy
ocular: keratoconjunctivitis sicca (most common), episcleritis, scleritis, corneal ulceration, keratitis, steroid-induced cataracts, chloroquine retinopathy
osteoporosis
ischaemic heart disease: RA carries a similar risk to type 2 diabetes mellitus
increased risk of infections
depression
Less common
Felty’s syndrome (RA + splenomegaly + low white cell count)
amyloidosis
Side effect of methotrexate ?
Myelosuppression
Liver cirrhosis
Pneumonitis
Side effect of sulfasalazine?
Rashes
Oligospermia
Heinz body anaemia
Interstitial lung disease
Side effect of leflunomide?
Liver impairment
Interstitial lung disease
Hypertension
Side effect of hydroxychlolquine?
Retinopathy
Corneal deposits
Side effect of prednisolone ?
Cushingoid features
Osteoporosis
Impaired glucose tolerance
Hypertension
Cataracts
Side effect of monoclonals ?
Reactivation of TB
What is rheumatoid factor?
Rheumatoid factor (RF) is a circulating antibody (usually IgM) that reacts with the Fc portion of the patients own IgG.
How can rheumatoid factor be detected?
Rose-Waaler test: sheep red cell agglutination
Latex agglutination test (less specific)
Antibody associated with rheumatoid arthritis?
Anti-cyclic citrullinated peptide antibody
Features of rheumatoid arthritis?
swollen, painful joints in hands and feet
stiffness worse in the morning
gradually gets worse with larger joints becoming involved
presentation usually insidiously develops over a few months
positive ‘squeeze test’ - discomfort on squeezing across the metacarpal or metatarsal joints
Poor prognostic feautres of anti-rheumatoid?
rheumatoid factor positive
anti-CCP antibodies
poor functional status at presentation
X-ray: early erosions (e.g. after < 2 years)
extra articular features e.g. nodules
HLA DR4
insidious onset
Xray findings in rheumatoid arthritis?
Early x-ray findings:
loss of joint space
juxta-articular osteoporosis
soft-tissue swelling
Late x-ray findings
periarticular erosions
subluxation
Features of rickets?
aching bones and joints
lower limb abnormalities:
in toddlers genu varum (bow legs)
in older children - genu valgum (knock knees)
‘rickety rosary’ - swelling at the costochondral junction
kyphoscoliosis
craniotabes - soft skull bones in early life
Harrison’s sulcus
Risk factors of rickets?
dietary deficiency of calcium, for example in developing countries
prolonged breastfeeding
unsupplemented cow’s milk formula
lack of sunlight
Function of supraspinatous?
aBDucts arm before deltoid
Most commonly injured
Function of infraspinatous?
Rotates arm laterally
Function of Teres minor?
aDDucts & rotates arm laterally
Function of subscapularis?
aDDuct & rotates arm medially
What is the associated risk with sjorgen’s syndrome?
Lymphoid malignancy
Most prevalent antibody in sjorgens?
rheumatoid factor (RF) positive in nearly 50% of patients
ANA positive in 70%
anti-Ro (SSA) antibodies in 70% of patients with PSS
anti-La (SSB) antibodies in 30% of patients with PSS
Investigation findings sjorgens?
rheumatoid factor (RF) positive in nearly 50% of patients
ANA positive in 70%
anti-Ro (SSA) antibodies in 70% of patients with PSS
anti-La (SSB) antibodies in 30% of patients with PSS
Schirmer’s test: filter paper near conjunctival sac to measure tear formation
histology: focal lymphocytic infiltration
also: hypergammaglobulinaemia, low C4
Features of still’s disease?
arthralgia
elevated serum ferritin
rash: salmon-pink, maculopapular
pyrexia
typically rises in the late afternoon/early evening in a daily pattern and accompanies a worsening of joint symptoms and rash
lymphadenopathy
rheumatoid factor (RF) and anti-nuclear antibody (ANA) negative
Cautions and adverse effects of sulfasalazine?
Cautions
G6PD deficiency
allergy to aspirin or sulphonamides (cross-sensitivity)
Adverse effects
oligospermia
Stevens-Johnson syndrome
pneumonitis / lung fibrosis
myelosuppression, Heinz body anaemia, megaloblastic anaemia
may colour tears → stained contact lenses
Can sulfasalazine be used in pregnancy and feeding?
Yes
Pathophysiology of SLE?
autoimmune disease: SLE a type 3 hypersensitivity reaction
associated with HLA B8, DR2, DR3
thought to be caused by immune system dysregulation leading to immune complex formation
immune complex deposition can affect any organ including the skin, joints, kidneys and brain
Features of SLE??
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
Antibodies in SLE?
99% are ANA positive
this high sensitivity makes it a useful rule out test, but it has low specificity
20% are rheumatoid factor positive
anti-dsDNA: highly specific (> 99%), but less sensitive (70%)
anti-Smith: highly specific (> 99%), sensitivity (30%)
also: anti-U1 RNP, SS-A (anti-Ro) and SS-B (anti-La)
What antibody is used to monitor SLE?
anti-dsDNA titres can be used for disease monitoring (but note not present in all patients)
Management of SLE?
Hydoxychloroquine
Basics
NSAIDs
sun-block
If organ involvement prednisolone
Risk of SLE in pregnancy?
risk of maternal autoantibodies crossing the placenta
leads to a condition termed neonatal lupus erythematosus
neonatal complications include congenital heart block
strongly associated withanti-Ro (SSA) antibodies
Features of limited cutanous 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
Features of 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
patients with renal disease should be started on an ACE inhibitor
poor prognosis
Examples of TNF inhibitors?
infliximab: monoclonal antibody, IV administration
etanercept: fusion protein that mimics the inhibitory effects of naturally occurring soluble TNF receptors, subcutaneous administration
adalimumab: monoclonal antibody, subcutaneous administration
golimumab: subcutaneous administration
adverse effects of TNF blockers include reactivation of latent tuberculosis and demyelination
What is pseudo gout associated with?
haemochromatosis
hyperparathyroidism
low magnesium, low phosphate
acromegaly, Wilson’s disease
Features of pseudo gout?
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 cartilag
Management of pseudo gout?
aspiration of joint fluid, to exclude septic arthritis
NSAIDs or intra-articular, intra-muscular or oral steroids as for gout
Discoid lupus management?
- Topical steroids
- Hydoxychloroquine
If allergic to aspirin, what other drugs is it likely you are allergic to?
Sulfasalazine
What is crest syndrome?
Limited systemic sclerosis
What disease is most strongly associated with raynoids?
Systemic sclerosis
Most specific antibodies for SLE?
Smith
DsDNA
Management of stills disease?
- Steroids
- Anti TN F - e.g. etanercept
- Ankaria - IL1
What sort of monoclonal is anakira?
IL-1
Features of trochanteric bursitis?
tenderness over the greater trochanter, a mildly raised CRP, and a lack of systemic symptoms
treated with physiotherapy, anti-inflammatory drugs, and cortisol injections.
Pathophysiology of ankylosing spondylitis ?
Syndesmophytes (ossification of outer fibres of annulus fibrosus) are a feature of ankylosing spondylitis
What cell mostly secretes TNF?
Macrophages
How sensitive is ANA for SLE?
95%
What is the minimum steroid intake a patient should be taking before they are offered osteoporosis prophylaxis?
equivalent of 7.5mg 3 months or more for 3 months
Features of pseudoxanthoma elastic?
Autosomal recessive
retinal angioid streaks
‘plucked chicken skin’ appearance - small yellow papules on the neck, antecubital fossa and axillae
cardiac: mitral valve prolapse, increased risk of ischaemic heart disease
gastrointestinal haemorrhage
Double contour sign?
Gout
Management of Pagets?
Bisphophonates
Radiograph findings for ankylosing spondylitis?
subchondral erosions, sclerosis
and squaring of lumbar vertebrae
What is antisynthase syndrome ?
Dermatomyostitis / Polymyositis
Bone pain, tenderness and proximal myopathy (→ waddling gait) → ?
osteomalacia
Features of mixed connective tissue disease?
anti-RNP
R Raynoud
N swollen hands with No synovitis
P Pain in muscle and joints
elevated creatinine kinase
What are the features of drug induced lupus?
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%
What causes osteoporosis/.
Lck of osteoclast function
Most useful marker to monitor SLE?
Anti-DsDNA
Looser’s zones x-ray?
osteomalacia
DMARDS used in rheumatoid arthritis?
methotrexate
pneumonitis
sulfasalazine
leflunomide
hydroxychloroquine
Initial management in rheumatoid arthritis?
recommend DMARD monotherapy +/- a short-course of bridging prednisolone
when should anti TNF be used in rheumatoid arthritis?
current indication for a TNF-inhibitor is an inadequate response to at least two DMARDs including methotrexate
what malignancies associated with shortens?
lymphoid
How to differentiate between GPA and relapsing polychondritis?
eatures of saddle-nose deformity and ocular involvement can be seen in GPA however as it affects the blood vessels, involvement of the ears/hearing is not associated with the condition.
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
Non-sti causes of reactive arthritis?
Shigella flexneri
Salmonella typhimurium
Salmonella enteritidis
Yersinia enterocolitica
Campylobacter
Medication to help produced saliva?
Pilocarpine
Diagnosis of giant cell arteritis/?
- Age >50 y/o
- New onset localised headache
- Temporal artery tenderness or decreased pulsation
- ESR >50mm/hr
- Temporal artery biopsy positive
What drug is considered the anchor drug for SLE?
Hydroxychloroquine
What are poor prognostic signs for anti-Jo 1?
Interstital lung disease
Risk factors for osteoporosis?
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
What type of antibody is rheumatoid factor?
Rheumatoid factor is an IgM antibody against IgG
Why do CREST patients develop malabsorption?
vergrowth of the sclerosed small intestine
What are the Ottawa ankle rules?
Bony tenderness at the lateral malleolar zone (from the tip of the lateral malleolus to include the lower 6 cm of posterior border of the fibular)
Bony tenderness at the medial malleolar zone (from the tip of the medial malleolus to the lower 6 cm of the posterior border of the tibia)
inability to walk four weight bearing steps immediately after the injury and in the emergency department
Use of raloxifene in osteoporosis?
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
Side effect of TNF alpha monoclonals?
Reactivation of TB
What are the features of temporal arteritis?
typically patient > 60 years old
usually rapid onset (e.g. < 1 month)
headache (found in 85%)
jaw claudication (65%)
vision testing is a key investigation in all patients
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
What is the type of visual loss in temporal arteritis?
anterior ischemic optic neuropathy
Radiological features of rickets?
Widening of joints
Features of dural ecstasies in Marfan’s syndrome?
dural ectasia (ballooning of the dural sac at the lumbosacral level)
What is the function of fibrillar, how is it affected in Marfan’s?
Wrap around elastin
Defectin fibrillar in marfans
Management of ankylosing spondylitis?
- Exercise +NSAID
- anti-TNF drugs are currently only used for patients with severe ankylosing spondylitis which has failed to respond to NSAIDs.
Trimethoprim + Methotrexate?
methotrexate and trimethoprim containing antibiotics may cause bone marrow suppression and severe or fatal pancytopaenia
Why does rickets cause excess non-mineralised osteoid?
Rickets can present as widening of the wrist joints due to an excess of non-mineralized osteoid at the growth plate
Anti-TNF therapy in ankylosing spondylitis will not improve…?
Radiological progression
Collagen affect in Ehler’s danlos syndrome?
Type III collagen
What Antiphospholipid antibody is associated with thrombosis?
Lupus anticoagulant
Xray findings for ankylosing spondylitis?
Ankylosing spondylitis - x-ray findings: subchondral erosions, sclerosis
and squaring of lumbar vertebrae
When to offer rate lowering therapy in gout?
IMMEDIATELY
What is the risk factorsd for lung cancer?
asbestos - increases risk of lung ca by a factor of 5
arsenic
radon
nickel
chromate
aromatic hydrocarbon
cryptogenic fibrosing alveolitis
Smoking
Definition of pulmonary hypertension?
Pulmonary artery pressure >25 or > 30 if exercising
WHat drug can precipitate churg struass?
Leukotriene receptor antagonists may trigger eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
