Rheumatology 2

Question 1

where does Psoriatic arthritis present?

Answer 1

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

Question 2

investigations for Psoriatic arthropathy

Answer 2

X-ray
often have the unusual combination of coexistence of erosive changes and new bone formation
periostitis
‘pencil-in-cup’ appearance

Question 3

management of Psoriatic arthropathy?

Answer 3

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

Question 4

what crystals are seen in pseudo gout?

Answer 4

Pseudogout is a form of microcrystal synovitis caused by the deposition of calcium pyrophosphate dihydrate crystals in the synovium.

Question 5

Risk factors for Pseudogout?

Answer 5

haemochromatosis
hyperparathyroidism
low magnesium, low phosphate
acromegaly, Wilson’s disease

Question 6

Features of pseudo gout?

Answer 6

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

Question 7

management of pseudo gout?

Answer 7

aspiration of joint fluid, to exclude septic arthritis
NSAIDs or intra-articular, intra-muscular or oral steroids as for gout

Question 8

How is Marfan’s inherited?

Answer 8

Marfan’s syndrome is an autosomal dominant connective tissue disorder.

Question 9

what is the genetic abnormality in Marfan’s?

Answer 9

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.

Question 10

features of Marfans?

Answer 10

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)

Question 11

how does spinal stenosis present?

Answer 11

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

Question 12

red flags in lower back pain?

Answer 12

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

Question 13

What is Dural Ectasia?

Answer 13

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.

Question 14

causes of septic arthritis in adults?

Answer 14

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

Question 15

investigations for septic arthritis?

Answer 15

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

Question 16

management of septic arthritis?

Answer 16

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

Question 17

SLE in pregnancy?

Answer 17

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

Question 18

what is tumour necrosis factor?

Answer 18

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)

Question 19

what secretes tumour necrosis factor?

Answer 19

It is secreted mainly by macrophages

Question 20

what is osteomalacia?

Answer 20

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.

Question 21

causes of osteomalacia?

Answer 21

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

Question 22

features of osteomalacia?

Answer 22

bone pain
bone/muscle tenderness
fractures: especially femoral neck
proximal myopathy: may lead to a waddling gait

Question 23

Investigations for osteomalacia?

Answer 23

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)

Question 24

Treatment for Osteomalacia?

Answer 24

vitamin D supplmentation
a loading dose is often needed initially
calcium supplementation if dietary calcium is inadequate

Question 25

Investigations for gout?

Answer 25

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.

Question 26

radiological features of gout?

Answer 26

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

Question 27

Features of reactive arthritis?

Answer 27

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)

Question 28

what is apremilast used for and what is the mechanism of action?

Answer 28

seronegative spondyloarthropathy psoriatic arthritis. phosphodiesterase type-4 (PDE4) inhibitor → suppression of pro-inflammatory mediator synthesis and promotion of anti-inflammatory mediators

Question 29

what is Paget's disease?

Answer 29

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.

Question 30

predisposing factors of Paget's disease?

Answer 30

increasing age male sex northern latitude family history

Question 31

clinical features of Paget's disease?

Answer 31

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

Question 32

Investigations for Pagets disease?

Answer 32

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

Question 33

Management of Paget's disease?

Answer 33

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

Question 34

complications of Pagets disease?

Answer 34

deafness (cranial nerve entrapment) bone sarcoma (1% if affected for > 10 years) fractures skull thickening high-output cardiac failure

Question 35

what is avascular necrosis of the hip ?

Answer 35

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.

Question 36

causes of avascular necrosis of the hip?

Answer 36

long-term steroid use chemotherapy alcohol excess trauma

Question 37

Investigations for avascular necrosis of the hip?

Answer 37

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

Question 38

how is osteomyelitis sub classified?

Answer 38

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

Question 39

What is the common cause of osteomyelitis?

Answer 39

Staph. aureus is the most common cause except in patients with sickle-cell anaemia where Salmonella species predominate

Question 40

investigations and treatment for osteomyelitis?

Answer 40

Investigations MRI is the imaging modality of choice, with a sensitivity of 90-100% Management flucloxacillin for 6 weeks clindamycin if penicillin-allergic

Question 41

management of gout?

Answer 41

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

Question 42

when is crate lowering therapy recommended in gout?

Answer 42

- 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

Question 43

lifestyle modifications in gout?

Answer 43

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

Question 44

what type of collagen does Ehlers-Danlos syndrome affect? How is it inherited?

Answer 44

Ehler-Danlos syndrome is an autosomal dominant connective tissue disorder that mostly affects type III collagen.

Question 45

What are the features and complications of Ehler-Danlos syndrome?

Answer 45

elastic, fragile skin joint hypermobility: recurrent joint dislocation easy bruising aortic regurgitation, mitral valve prolapse and aortic dissection subarachnoid haemorrhage angioid retinal streaks

Question 46

what is cANCA and pANCA associated with?

Answer 46

cANCA = granulomatosis with polyangiitis; pANCA = eosinophilic granulomatosis with polyangiitis + others

Question 47

Common findings in ANCA associated vasculitis?

Answer 47

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

Question 48

mechanism of action of methotrexate?

Answer 48

Methotrexate is an antimetabolite that inhibits dihydrofolate reductase, an enzyme essential for the synthesis of purines and pyrimidines. It is reversible inhibition

Question 49

markers of elevated bone turnover?

Answer 49

procollagen type I N-terminal propeptide (PINP) serum C-telopeptide (CTx) urinary N-telopeptide (NTx) urinary hydroxyproline

Question 50

what is familial Mediterranean fever?

Answer 50

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.

Question 51

How is familial mediterranean fever inherited?

Answer 51

AR

Question 52

features of familial mediterranean fever inherited?

Answer 52

attacks typically last 1-3 days pyrexia abdominal pain (due to peritonitis) pleurisy pericarditis arthritis erysipeloid rash on lower limbs

Question 53

management of familial mediterranean fever inherited?

Answer 53

colchicine may help

Question 54

what predisposes to gout?

Answer 54

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

Question 55

what is osteopetrosis?

Answer 55

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

Question 56

blood tests in osteopetrosis?

Answer 56

calcium, phosphate and ALP are normal

Question 57

osteoporosis Pagets Osteopetrosis osteoclast function ???

Answer 57

Pagets: Increased Osteoclast Osteoporosis : Increased osteoclast Osteopetrosis : Reduced osteoclast

Question 58

Drugs causing gout?

Answer 58

diuretics: thiazides, furosemide ciclosporin alcohol cytotoxic agents pyrazinamide

Question 59

what is mixed connective tissue disease?

Answer 59

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.

Question 59

what is undifferentiated connective tissue disorder?

Answer 59

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.

Question 60

How does mixed connective tissue disease present?

Answer 60

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

Question 61

Investigations for mixed connective tissue disorder?

Answer 61

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

Question 62

L3 nerve root compression features?

Answer 62

Sensory loss over anterior thigh Weak hip flexion, knee extension and hip adduction Reduced knee reflex Positive femoral stretch test

Question 63

L4 nerve root compression features?

Answer 63

Sensory loss anterior aspect of knee and medial malleolus Weak knee extension and hip adduction Reduced knee reflex Positive femoral stretch test

Question 64

L5 nerve root compression features?

Answer 64

Sensory loss dorsum of foot Weakness in foot and big toe dorsiflexion Reflexes intact Positive sciatic nerve stretch test

Question 65

S1 nerve root compression features?

Answer 65

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

Question 66

what are poor prognostic features in RA?

Answer 66

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