Rheumatology 2 Flashcards
who does Psoriatic arthritis present?
can be symmetric polyarthritis (very similar to rheumatoid arthritis) - 30-40% of cases
Asymmetrical oligoarthritis - typical affacts hands and feet (20-30%)
Sacroilitis
DIP joint disease
arthritis mutilans (severe deformity fingers/hand, ‘telescoping fingers’)
Psoriatic skin lesions
Periarticular disease - tenosynovitis and soft tissue inflammation resulting in:
enthesitis: inflammation at the site of tendon and ligament insertion e.g. Achilles tendonitis, plantar fascitis
tenosynovitis: typically of the flexor tendons of the hands
dactylitis: diffuse swelling of a finger or toe
nail changes
pitting
onycholysis
investigations for Psoriatic arthropathy
X-ray
often have the unusual combination of coexistence of erosive changes and new bone formation
periostitis
‘pencil-in-cup’ appearance
management of Psoriatic arthropathy?
treatment is similar to that of rheumatoid arthritis (RA). However, the following differences are noted:
mild peripheral arthritis/mild axial disease may be treated with ‘just’ an NSAID, rather than all patients being on disease-modifying therapy as with RA
if more moderate/severe disease then methotrexate is typically used as in RA
use of monoclonal antibodies such as ustekinumab (targets both IL-12 and IL-23) and secukinumab (targets IL-17)
apremilast: phosphodiesterase type-4 (PDE4) inhibitor → suppression of pro-inflammatory mediator synthesis and promotion of anti-inflammatory mediators
has a better prognosis than RA
what crystals are seen in pseudo gout?
Pseudogout is a form of microcrystal synovitis caused by the deposition of calcium pyrophosphate dihydrate crystals in the synovium.
Risk factors for Pseudogout?
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 cartilage
management of pseudo gout?
aspiration of joint fluid, to exclude septic arthritis
NSAIDs or intra-articular, intra-muscular or oral steroids as for gout
How is Marfan’s inherited?
Marfan’s syndrome is an autosomal dominant connective tissue disorder.
what is the genetic abnormality in Marfan’s?
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 of Marfans?
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)
how does spinal stenosis present?
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
red flags in lower back pain?
Red flags for lower back pain
age < 20 years or > 50 years
history of previous malignancy
night pain
history of trauma
systemically unwell e.g. weight loss, fever
What is Dural Ectasia?
Dural ectasia affects around 60% of patients with Marfan’s syndrome. It may cause lower back pain associated with neurological problems such as bladder and bowel dysfunction.
causes of septic arthritis in adults?
most common organism overall is Staphylococcus aureus
in young adults who are sexually active, Neisseria gonorrhoeae is the most common organism (disseminated gonococcal infection)
the most common cause is hematogenous spread
this may be from distant bacterial infections e.g. abscesses
in adults, the most common location is the knee
investigations for septic arthritis?
synovial fluid sampling is obligatory
this should be done prior to the administration of antibiotics if necessary
may need to be done under radiographic guidance
shows a leucocytosis with neutrophil predominance
gram staining is negative in around 30-50% of cases
fluid culture is positive in patients with non-gonococcal septic arthritis
blood cultures: the most common cause of septic arthritis is hematogenous spread
joint imaging
management of septic arthritis?
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 4-6 weeks)
patients are typically switched to oral antibiotics after 2 weeks
needle aspiration should be used to decompress the joint
arthroscopic lavage may be required
Ceftrixone for gonococcal arthritis
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
what is tumour necrosis factor?
Tumour necrosis factor (TNF) is a pro-inflammatory cytokine with multiple roles in the immune system.
acting mainly in a paracrine fashion:
activates macrophages and neutrophils
acts as costimulator for T cell activation
key mediator of bodies response to Gram negative septicaemia
similar properties to IL-1
anti-tumour effect (e.g. phospholipase activation)
what secretes tumour necrosis factor?
It is secreted mainly by macrophages
what is osteomalacia?
Osteomalacia describes softening of the bones secondary to low vitamin D levels that in turn lead to decreased bone mineral content. If this occurs in growing children it is referred to as rickets, with the term osteomalacia preferred for adults.
causes of osteomalacia?
vitamin D deficiency
malabsorption
lack of sunlight
diet
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
Investigations for osteomalacia?
bloods
low vitamin D levels
low calcium, phosphate (in around 30%)
raised alkaline phosphatase (in 95-100% of patients)
x-ray
translucent bands (Looser’s zones or pseudofractures)
Treatment for Osteomalacia?
vitamin D supplmentation
a loading dose is often needed initially
calcium supplementation if dietary calcium is inadequate
Investigations for gout?
Uric acid
NICE recommends measuring uric acid levels in suspected gout (i.e. in the acute setting)
a uric acid level ≥ 360 umol/L is seen as supporting a diagnosis
if uric acid level < 360 umol/L during a flare and gout is strongly suspected, repeat the uric acid level measurement at least 2 weeks after the flare has settled
Synovial fluid analysis
needle shaped negatively birefringent monosodium urate crystals under polarised light
XR
USS - double contour sign may be seen - a hyperechoic, irregular band over the superficial margin of the joint cartilage, produced by deposition of monosodium urate crystals on the surface of the hyaline cartilage, which increases the interface of the cartilage surface, reaching a thickness similar to the subchondral bone.
radiological features of gout?
Radiological features of gout include:
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
Features of reactive arthritis?
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)
what is apremilast used for and what is the mechanism of action?
seronegative spondyloarthropathy psoriatic arthritis.
phosphodiesterase type-4 (PDE4) inhibitor → suppression of pro-inflammatory mediator synthesis and promotion of anti-inflammatory mediators
what is Paget’s disease?
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.
predisposing factors of Paget’s disease?
increasing age
male sex
northern latitude
family history
clinical features of Paget’s disease?
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
Investigations for Pagets disease?
Raised ALP
Calcium and phosphate are normal
other markers of bone turnover include
procollagen type I N-terminal propeptide (PINP)
serum C-telopeptide (CTx)
urinary N-telopeptide (NTx)
urinary hydroxyproline
x-rays
osteolysis in early disease → mixed lytic/sclerotic lesions later
skull x-ray: thickened vault, osteoporosis circumscripta
bone scintigraphy
increased uptake is seen focally at the sites of active bone lesions
Management of Paget’s disease?
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 of Pagets disease?
deafness (cranial nerve entrapment)
bone sarcoma (1% if affected for > 10 years)
fractures
skull thickening
high-output cardiac failure
what is avascular necrosis of the hip ?
Avascular necrosis (AVN) may be defined as death of bone tissue secondary to loss of the blood supply. This leads to bone destruction and loss of joint function. It most commonly affects the epiphysis of long bones such as the femur.
causes of avascular necrosis of the hip?
long-term steroid use
chemotherapy
alcohol excess
trauma
Investigations for avascular necrosis of the hip?
plain x-ray findings may be normal initially
osteopenia and microfractures may be seen early on
collapse of the articular surface may result in the crescent sign
MRI is the investigation of choice
it is more sensitive than radionuclide bone scanning
how is osteomyelitis sub classified?
haematogenous 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
non-haematogenous 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
What is the common cause of osteomyelitis?
Staph. aureus is the most common cause except in patients with sickle-cell anaemia where Salmonella species predominate
investigations and treatment for osteomyelitis?
Investigations
MRI is the imaging modality of choice, with a sensitivity of 90-100%
Management
flucloxacillin for 6 weeks
clindamycin if penicillin-allergic
management of gout?
Acute management - NSAIDs or Colchicine
Urate lowering therapy
Allopurinol is first line
the second-line agent when allopurinol is not tolerated or ineffective is febuxostat (also a xanthine oxidase inhibitor)
refractory cases - uricase can be used
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
when is crate lowering therapy recommended in gout?
- 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
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 type of collagen does Ehlers-Danlos syndrome affect?
How is it inherited?
Ehler-Danlos syndrome is an autosomal dominant connective tissue disorder that mostly affects type III collagen.
What are the features and complications of Ehler-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 is cANCA and pANCA associated with?
cANCA = granulomatosis with polyangiitis; pANCA = eosinophilic granulomatosis with polyangiitis + others
Common findings in ANCA associated 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
mechanism of action of methotrexate?
Methotrexate is an antimetabolite that inhibits dihydrofolate reductase, an enzyme essential for the synthesis of purines and pyrimidines.
It is reversible inhibition
markers of elevated bone turnover?
procollagen type I N-terminal propeptide (PINP)
serum C-telopeptide (CTx)
urinary N-telopeptide (NTx)
urinary hydroxyproline
what is familial Mediterranean fever?
Familial Mediterranean Fever (FMF, also known as recurrent polyserositis) is an autosomal recessive disorder which typically presents by the second decade. It is more common in people of Turkish, Armenian and Arabic descent.
How is familial mediterranean fever inherited?
AR
features of familial mediterranean fever inherited?
attacks typically last 1-3 days
pyrexia
abdominal pain (due to peritonitis)
pleurisy
pericarditis
arthritis
erysipeloid rash on lower limbs
management of familial mediterranean fever inherited?
colchicine may help
what predisposes to gout?
Decreased excretion of uric acid
drugs*: diuretics
chronic kidney disease
lead toxicity
Increased production of uric acid
myeloproliferative/lymphoproliferative disorder
cytotoxic drugs
severe psoriasis
Lesch-Nyhan 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
what is osteopetrosis?
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
blood tests in osteopetrosis?
calcium, phosphate and ALP are normal
osteoporosis
Pagets
Osteopetrosis
osteoclast function ???
Pagets: Increased Osteoclast
Osteoporosis : Increased osteoclast
Osteopetrosis : Reduced osteoclast
Drugs causing gout?
diuretics: thiazides, furosemide
ciclosporin
alcohol
cytotoxic agents
pyrazinamide
what is mixed connective tissue disease?
Mixed connective tissue disease (MCTD, Sharp’s syndrome) is a rare, heterogeneous, multi-system autoimmune disorder. It is a distinct clinical entity, but features of systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and myositis may all be present. It is associated with anti-U1 ribonucleoprotein (RNP) antibodies.
what is undifferentiated connective tissue disorder?
Undifferentiated connective tissue disease refers to syndromes in which features of one or more ‘classical’ connective tissue disease may be present, but do not meet diagnostic criteria. Anti-U1 RNP is absent.
How does mixed connective tissue disease present?
Raynaud’s phenomenon often precedes other symptoms and occurs in 90% of cases
Polyarthralgia/arthritis
Myalgia
‘Sausage fingers’(dactylitis)
Dermatological: photosensitive rash, scleroderma-like changes, alopecia
Oesophageal dysfunction
Respiratory: pleuritis, pulmonary hypertension, interstitial lung disease
Haematological: anaemia, lymphadenopathy, splenomegaly, rarely TTP
Cardiac: pericarditis, pericardial effusion, accelerated coronary artery disease
Renal: glomerulonephritis (tends to be milder than SLE)
Neuropsychiatric: seizures, mood disturbance
Investigations for mixed connective tissue disorder?
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
L3 nerve root compression features?
Sensory loss over anterior thigh
Weak hip flexion, knee extension and hip adduction
Reduced knee reflex
Positive femoral stretch test
L4 nerve root compression features?
Sensory loss anterior aspect of knee and medial malleolus
Weak knee extension and hip adduction
Reduced knee reflex
Positive femoral stretch test
L5 nerve root compression features?
Sensory loss dorsum of foot
Weakness in foot and big toe dorsiflexion
Reflexes intact
Positive sciatic nerve stretch test
S1 nerve root compression features?
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 are poor prognostic features in RA?
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
