Rheumatology Flashcards
cytoplasmic inclusions on muscle biopsy1st line treatment of osteoporosis?
alendronate
2nd line treatment of osteoporosis if unable to tolerate alendronate due to upper GI side effects?
risedronate/ etidronate
3rd line treatment of osteoporosis if cannot take bisphosphonates?
Strontium Ralenate (dual action: promotes differentiation from pre-osteoblast to osteoblast + inhibits osteoclasts) or Raloxifene (Selective oestrogen receptor modulator)
what e.g. is a once only oral bisphosphonate?
ibandronate
denosumab?
human monoclonal antibody: anti-RANK ligand -> inhibits maturation of osteoclasts
what protein is defective in Marfans?
fibrillin-1
autosomal dominant- defect in FBN1 gene on chr 15
oral + genital ulcers + anterior uveitis + thrombophlebitis?
Behcet’s syndrome
classic triad of Behcet’s syndrome?
oral ulcers + genital ulcers + anterior uveitis
Features of Behcets?
- oral + genital ulcers - anterior uveitis - thrombophlebitis +/- DVT - arthritis - neuro involvement e.g. aseptic meningitis - GI: abdo pain, diarrhoea - erythema nodosum *presumed autoimmune-mediated inflammation of arteries and veins
What HLA is assoc w Behcets?
HLA-B51 (a split antigen of HLA B5)
Diagnosis of Behcets?
clinical: no definitive test - positive pathergy test is suggestive (ie. puncture site following needle prick becomes inflamed with small pustule forming)
what joints are most commonly implicated in osteoarthritis?
carpometacarpal + DIP joints
What are Heberden’s and Bouchard’s nodes?
Heberden: DIPJ Bouchard: PIPJ result of osteophyte formation.
features of osteoarthritis?
- usually bilateral - provoked by movement, relieved by resting - stiffness: Worse after long periods of inactivity (only lasts few mins) - Heberdens + Bouchards - squaring of the thumbs
What T score suggests osteoporosis? vs osteopenia?
> -1.0 = normal
-1.0 to -2.5 = osteopaenia
< -2.5 = osteoporosis
most useful investigation in diagnosis of Ankylosing spondylitis?
Plain x-ray of the sacroiliac joints
features of ankylosing spondylitis on X-ray?
- 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
Ix of choice if X-ray is negative for Ank spondylitis but clinical suspicion remains high?
MRI: Signs of early inflammation involving sacroiliac joints (bone marrow oedema) confirm the diagnosis
1st line mx of Ank Spond?
NSAIDs + exercise / physio
What management should be considered in persistently high disease activity in Ank Spond despite conventional treatment?
Anti-TNF therapies e.g. etanercept / adalimumab
mix of SLE + Systemic sclerosis + myositis?
mixed connective tissue disease ie. Sharp’s syndrome
what antibody is most sensitive for mixed connective tissue disease?
anti-U1 RNP antibodies RNP = ribonucleoprotein
most common features of mixed connective tissue disease?
- Raynaud’s often precedes (occurs in 90%) - polyarthralgia/ arthritis - myalgia - dactylitis - other dermatological (e.g. photosensitive rash), oesophageal dysfunction, respiratory, haematological, cardiac, renal, neuropsych features
osteogenesis imperfecta - abnormality in what?
type 1 collagen - which is main component of the organic part of bone + skin & tendons
Disorder in type 5 collagen?
Ehlers-Danlos syndrome - Type 5 collagen found in cell surfaces, hair, placentas
Type 4 collagen mutations cause?
Alpert’s syndrome, Goodpasture’s *defect in basal lamina
Defect in type 2 collagen?
Chondrodysplasias - type 2 collagen is main component of cartilage
Defect in type 3 collagen?
can lead to a type of Ehlers-Danlos *not the classic type Type 3 collagen is main component of reticular fibres
features of osteogenesis imperfecta?
- fractures following minor trauma - blue sclera - deafness 2dry to osteosclerosis - dental imperfections
Ca/ Phosphate/ PTH/ Alk Phos results in osteogenesis imperfecta?
usually all normal
common causes of drug-induced lupus?
Most common: procainamide hydralazine
less common: isoniazid minocycline phenytoin
most sensitive antibodies for drug induced lupus?
anti-histone abs (in 80-90%) *ANA+ (100%), dsDNA -ve, anti Ro/ Smith +ve in 5%
xray changes in rheumatoid arthritis?
Early x-ray findings: - loss of joint space - juxta-articular osteoporosis - soft-tissue swelling Late x-ray findings: - periarticular erosions - subluxation
most specific antibodies for dermatomyositis?
anti-Mi-2 antibodies
most specific antibodies for polymyositis?
anti-Jo1 antibodies
Management of dermatomyositis?
prednisolone
anti-La antibodies?
Sjogrens
Anti-Ro antibodies?
Sjogrens, SLE, Congenital Heart block
SEs of bisphosphonates?
oesophageal reactions: ulcer/ oesophagitis osteonecrosis of the jaw increased risk atypical stress #s of proximal femoral shaft acute phase response: fever, myalgia, arthralgia following administration hypoCa: reduced ca efflux from bone, usually clincally unimportant
management of vit D deficiency?
Oral Vit D loading then maintenance
features of Antiphospholipid syndrome?
recurring fetal loss, venous/ arterial thrombosis
- livedo reticularis
- thrombocytopenia
- prolonged APTT
- pulmonary HTN, pre-eclampsia
primary thromboprophylaxis in antiphospholipid syndrome?
low dose aspirin
secondary thromboprophylaxis in antiphospholipid syndrome?
lifelong warfarin w target INR 2-3 to start
what type of hypersensitivity reaction is SLE?
type 3 immune complex dysregulation -> immune complex formation -> deposition can affect any organ (skin, joints, kidney, brain)
SLE assoc w which HLA?
HLA B8, DR2, DR3
SE of raloxifene?
increased risk of VTE may worsen menopausal symptoms
raloxifene and risk of breast ca?
decreases risk
causes of decreased excretion of uric acid? thus predisposing to gout
drugs: diuretics CKD lead toxicity Lesch-Nyhan syndrome
Gout: causes of increased production of uric acid?
myeloproliferative/ lymphoproliferative disorders cytotoxics severe psoriasis
IBD drugs: which are safe to use in pregnancy?
azathioprine, mesalazine and sulfasalazine (w folic acid) safe to use in pregnancy and breastfeeding
SE of Azathioprine?
bone marrow suppression N+V pancreatitis
azathioprine increases risk of what type of ca?
non melanoma skin cancer
azathioprine may interact w which drug?
allopurinol - lower doses of azathioprine should be used if taking allopurinol
management of methotrexate toxicity?
folinic acid
What medication may interact with methotrexate to increase the risk of methotrexate toxicity secondary to reduced excretion?
high dose aspirin
what antibody is found in polyarteritis nodosa?
assoc w p-ANCA perinuclear-antineutrophil cytoplasmic abs
what infection is assoc w polyarteritis nodosa?
hep B
CK and EMG findings in polymyalgia rheumatica?
Normal! Pts may have raised inflammatory markers e.g. ESR>40
features of pseudoxanthoma elasticum?
- 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
- GI haemorrhage
most common organism causing iliopsoas abscess?
staph aureus
most common secondary cause of iliopsoas asbcess?
crohns disease
examination findings of iliopsoas abscess?
hyperextension of hip -> pain as psoas muscle is stretched
ask pt to lift thigh against hand -> pain due to contraction of psoas muscle
ix of choice for iliopsoas abscess?
CT abdomen
management of iliopsoas abscess?
abx
percutaneous drainage initial approach
surgery if: failure of percutaneous draining/ presence of another intra-abdo pathology which requires surgery
when are topical NSAIDs indicated in osteoarthritis?
for OA of knee/ hand
what antibody titre can be used for disease monitoring of SLE?
anti-dsDNA titres
what is the major target within the cell of p-ANCA?
myeloperoxidase
what is the main target within the cell for cANCA?
proteinase-3
What is the minimum steroid intake a patient should be taking before they are offered osteoporosis prophylaxis?
equivalent of pred 7.5mg or more for 3 months or longer
proximal myopathy + mechanic hands + interstitial lung disease?
anti-synthetase syndrome
SE of hydroxychloroquine?
bulls eye retinopathy - might result in severe and permanent visual loss
baseline exam + annual screening recommended
management of patients at risk of corticosteroid- induced osteoporosis?
if pt is >65 OR had fragility fracture in the past
offer bone protection ie. bisphosphonates
management of patients at risk of corticosteroid-induced osteoporosis?
offer bone density scan
if T score bone protection
if between 0 and -1.5 -> repeat bone density scan in 1-3 years
MOA of mycophenolate mofetil?
inhibits inosine-5-monophosphate dehydrogenase which is needed for purine synthesis
- > reduces lymphocyte production
- > used in organ transplant to preven rejection/ autoimmune conditions
sjogrens - increased risk of which malignancy?
lymphoid (40-60 fold)
osteoporosis in males - check what hormone level?
testosterone
- testosterone deficiency
muscle pain and stiffness following exercise, cramps, myoglobinuria, low lactate levels during exercise
McArdle’s disease
- autosomal recessive type V glycogen storage disease
- caused by myophosphorylase deficiency
allergy to which other classes should caution you to starting sulfasalazine?
aspirin, sulphonamides
SEs of sulfasalazine?
- oligospermia
- Stevens-Johnson syndrome
- pneumonitis / lung fibrosis
- myelosuppression, Heinz body anaemia, megaloblastic anaemia
- may colour tears → stained contact lenses
key features of relapsing polychondritis?
ears: auricular chondritis, hearing loss, vertigo
nasal: saddle nose deformity
Resp tract: e.g. wheeze/ stridor/ hoarseness
ocular: episcleritis/ scleritis/ iritis
arthalgia
less commonly: cardiac valvular regurg, cranial n palsies, peripheral neuropathies, renal dysfunction
What is the greatest predictor of future thrombosis in patients with anti-phospholipid syndrome?
Lupus anticoagulant
Lupus anticoagulants have an odds ratio for thrombosis 5 to 16 times higher than controls.
most useful characteristic sign of gout on US?
double contour sign
- a hyperechoic, irregular band over the superficial margin of the joint cartilage, produced by the deposition of monosodium urate crystals on the surface of the hyaline cartilage
most common cardiac abnormality of Marfans syndrome?
aortic root dilatation
what management might you start in Adult onset stills disease if symptoms persist despite initial management?
anti IL1 e.g. anakinra
/ TNF therapy
or methotrexate
monitoring while pt is on leflunomide (a DMARD)?
FBC/ LFTs and BP
topical NSAIDs used for OA of..?
knees/ hand
ank spond, what type of pulmonary fibrosis?
apical
Which one of the following cells secretes the majority of tumour necrosis factor in humans?
macrophages
lens dislocation in Marfans’s?
UP
MOA of azathioprine?
inhibits purine synthesis
osteopetrosis - dysfunction in?
defective osteoclast function -> failure of normal bone resorption
-> results in dense, thick bones that are prone to fracture
aka Marble bone disease
features of osteopetrosis?
bone pain/ neuropathies common
prone to fractures
Ca, PO4, ALP normal
stem cell transplant and IFN-gamma have been used for treatment
Pseudogout associated factors?
increasing age
haemochromatosis
hyperparathyroidism
low magnesium, low phosphate
acromegaly, Wilson’s disease
Ehlers-Danlos: what type of collagen is affected?
type 3 collagen
complications of Paget’s disease?
deafness (cranial nerve entrapment)
bone sarcoma (1% if affected for > 10 years)
fractures
skull thickening
high-output cardiac failure
SEs of TNFa inhibitors e.g. etanercept/ infliximab?
reactivation of TB
etanercept: can cause demyelination
which anti-TB medication causes drug induced SLE?
isoniazid
pathophysiology of discoid lupus erythematous?
- benign disorder, rarely progresses to SLE
- characterised by follicular keratin plugs
- autoimmune aetiology
Radial tunnel syndrome vs Lateral epicondylitis?
- similar presentation
- Radial tunnel syndrome: pain tends to be around 4-5cm distal to the lateral epicondyle
- symptoms may be worsened by extending the elbow and pronating the forearm
- compression of posterior interosseous branch of the radial nerve
most common cause of death in sustemic sclerosis?
respiratory involvement
(80%)
- interstitial lung disease and pulmonary arterial hypertension
causes of avascular necrosis of hip?
long-term steroid use
chemotherapy
alcohol excess
trauma
what autoantibody is most likely to be positive in dermatomyositis?
ANA
- positive in 60%
Anti-Mi-2 only seen in ~25%
1st step management of Rheumatoid arthritis?
DMARD monotherapy (most often methotrexate) +/- short course of bridging prednisolone
Rheumatoid arthritis: monitoring response to treatment?
CRP + DAS28 score to monitor disease activity
Features of polyarteritis nodosa?
fever, malaise, arthralgia
weight loss
hypertension
mononeuritis multiplex, sensorimotor polyneuropathy
testicular pain
livedo reticularis
haematuria, renal failure
- pANCA +ve in 20%, Hep B +ve in 30%
Dural ectasia in Marfan’s syndrome?
dural ectasia = ballooning of the dural sac at the lumbosacral lvl
may cause lower back pain associated with neurological problems such as bladder and bowel dysfunction.
Features of McArdle’s disease?
- decreased muscle glycogenolysis. auto recessive. myophosphorylase deficiency.
muscle pain and stiffness following exercise
muscle cramps
myoglobinuria
low lactate levels during exercise
pathophysiology of Langerhans cell histiocytosis?
abnormal proliferation of histiocytes
typically presents in childhood with bony lesions
Features of Langerhans cells histiocytosis?
bone pain, typically in the skull or proximal femur
cutaneous nodules
recurrent otitis media/mastoiditis
tennis racket-shaped Birbeck granules on electromicroscopy
main target of pANCA?
myeloperoxidase (MPO)
main target of cANCA?
serine proteinase 3 (PR3)
Mx of discoid lupus erythematous?
1st line: topical steroid cream
oral antimalarials may be used second-line e.g. hydroxychloroquine
avoid sun exposure
poor prognostic features of Rheumatoid arthritis?
rheumatoid factor +, 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
Which biochemical marker (other than alk phos) could be tested to support a diagnosis of Paget’s disease of the bone?
serum/ urine hydroxypoline (raised)
- markers of bone turnover
What is used for disease monitoring of SLE?
- ESR
- C3/4 = low
- anti-dsDNA titres
Autoantibodies in adult onset Still’s disease?
rheumatoid factor and ANA
are NEGATIVE
- its a diagnosis of exclusion
Features of adult onset Still’s disease?
arthralgia
raised ferritin
macpap, salmon-pink rash
pyrexia: typically rises late afternoon
lymphadenopathy
mx of familial mediterranean fever?
colchicine may help
what conveys poor prognosis in polymyositis?
interstitial lung disease
- major risk factor for premature death
Features of Polymyositis?
proximal muscle weakness +/- tenderness
Raynaud’s
respiratory muscle weakness
interstitial lung disease: e.g. fibrosing alveolitis or organising pneumonia
dysphagia, dysphonia
Wegeners/ Granulomatosis with polyangiitis: treatment of choice?
cyclophosphamide and streroids
what type of GN does Churg-strauss (Eosinophilic GPA) usually cause?
focal segmental glomerulosclerosis
What renal abnormalities are associated with Henoch-Schonlein purpura?
glomerular IgA deposition
- usually managed with NSAIDs. if severe: steroids
Ankylosing spondylitis: earliest sign on X-ray
sacroiliitis: subchondral erosions and sclerosis
Antiphospholipid syndrome: what autoantibodies are associated?
anti-cardiolipin
lupus anticoagulant
anti-B2 glycoprotein 1
most common type of psoriatic arthropathy at presentation?
peripheral asymmetric oligoarthropathy
Sjogren’s syndrome: what medication can stimulate saliva production?
pilocarpine
Features of Familial Mediterranean Fever?
- auto recessive
- attacks lasting 1-3 days
- pyrexia
- abdo pain (due to peritonitis)
- pleurisy
- pericarditis
- arthritis
- erysipeloid rash on lower limbs
Features of Scheuermann’s disease?
usually affects 13-16yo
- affects normal ossification of ring epiphyses of several thoracic vertebrae
- Vertebrae narrower anteriorly -> Kyphosis
Gout: prophylaxis in those where allopurinol is not tolerated?
febuxostat
(also a xanthine oxidase inhibitor)
Gout: what are other prophylactic medications in refractory cases?
- uricase
- pegloticase (polyethylene glycol modified mammalian uricase) > given as an infusion once every two weeks
in which group of patients would you start alendronate before DEXA scan confirms osteoporosis?
in adults ≥75 with fragility #
Perthes disease: management?
- keep the femoral head within the acetabulum: cast, braces
- If < 6 years: observation
- Older: surgical management with moderate results
- Operate on severe deformities
scleroderma renal crisis causing hypertensive emergency: mx?
oral ACEi
- aim gradual reduction of blood pressure at a rate of 10-15 mmHg per day
most definitive way of confirming the diagnosis of primary Sjogren’s syndrome?
Salivary gland biopsy
- will show focal lymphocytic sialadenitis
management of methotrexate if pt develops new oral ulceration?
hold MTX + discuss with rheum
Fibromyalgia: pharmacological therapies?
pregabalin, duloxetine, amitriptyline
Ix of Paget’s disease that reflects increased bone turnover?
Serum C-telopeptide (CTx) - useful in monitoring disease progression or treatment efficacy Others: - procollagen type I N-terminal propeptide (PINP) - urinary N-telopeptide (NTx) - urinary hydroxyproline
Features of familial Mediterranean fever aka recurrent polyserositis?
more common in people of Turkish, Armenian and Arabic descent Attacks lasting 1-3 days: - fever - abdo pain (peritonitis) - Pleurisy - pericarditis - arthritis - erysipeloid rash on lower limbs
Mx of familial Mediterranean fever aka recurrent polyserositis?
Colchicine
Features of jaccouds arthropathy?
‘reversible’ joint deformities such as swan neck, thumb subluxation, ulnar deviation, ‘boutonniere’ and hallux valgus + NO articular erosions on XR
Rheumatoid arthritis: When is a third agent required?
starting of biologic therapy when the patient has been on at least 2 DMARDs, including methotrexate > with two DAS 28 scores of > 5.1 at least one month apart
What ix will lead to diagnosis of polyarteritis nodosa?
Angiography Ie renal angiogram
Tx of choice in SLE?
Hydroxychloroquine
Tx to consider in SLE if f internal organ involvement e.g. renal, neuro, eye?
prednisolone, cyclophosphamide
What autoantibody is assoc with high risk of scleroderma renal crisis?
anti-RNA polymerase III
What antibodies are assoc with high risk of pulmonary hypertension in systemic sclerosis?
anti-U3-RNP
What autoantibodies are assoc with Systemic sclerosis assoc myositis?
anti-PM-Scl
Management of stills disease?
1st line: NSAIDs (to manage fever, joint pain, serositis) - trial for at least 1 wk before adding steroids if symptoms persist, the use of methotrexate, IL-1 or anti-TNF therapy can be considered
Steroid sparing agent for management of giant cell arteritis?
Methotrexate
First line management of adult onset stills disease?
NSAIDs first
First line management of adult onset stills disease?
NSAIDs first
Medications to treat LUPUS nephritis?
Mycophenolate mofetil
Ocular features in ehler Danlos?
angioid retinal streaks
Muscle biopsy: Endomysial lymphocytic infiltrates that invade nonnecrotic muscle fibres
Polymyositis
Muscle biopsy: Perimysial inflammation of lymphocytes and parafascicular atrophy
Dermatomyositis
Muscle biopsy: cytoplasmic inclusions
Inclusion body myositis
Features of Langerhans cell histiocytosis ? (abnormal proliferation of histiocytes)
- bone pain, typically in the skull or proximal femur 2. cutaneous nodules 3. recurrent otitis media/mastoiditis 4. tennis racket-shaped Birbeck granules on electromicroscopy
first line tx of psoriatic arthropathy?
Same as rheumatoid arthritis Ie DMARD like methotrexate
What medication might precipitate a scleroderma renal crisis?
Steroids
Ankylosing spondylitis: cardiac abnormalities?
AV node block Aortic regurgitation
