MSK

Question 1

Describe the causes and common sites of compartment syndrome

Answer 1

Interstitial pressure within a closed fascial compartment resulting in microvascular compromise

Common sites – leg, forearm, thigh

Causes

> Increased internal pressure
> Trauma - fractures, entrapment, bleeding
> Muscle oedema / myositis
> Reperfusion - vascular surgery
> Intracompartmental administration of fluids / drugs

> Increased external compression
> Casts/bandages, full thickness burns
> Impaired consciousness / protective reflexes
» Drug / alcohol misuse
» Iatrogenic
» Positioning in theatre – lithotomy

> Combination

Question 2

What is the consequence of an untreated compartment syndrome in the arm?

Answer 2

Volkmann’s ischaemic contracture

Question 3

Describe the pathogenesis of compartment syndrome

Answer 3

External compression
> Swelling after injury + external compression
> Pressure increases and venous flow reduced but arterial inflow continues
> Pressure increases
> External compression removed leads to restoration of venous flow and pressure normalises

Non-expansile compartment
> Bleeding into compartment
> Increased compartment content
> Venous flow reduced but arterial inflow continues so pressure increases
> Ischaemia and permanent damage result

Question 4

Describe the pathophysiology of compartment syndrome, including later stages

Answer 4

Pressure within compartment exceeds pressure within capillaries – reduced blood flow

Muscles become ischaemic and develop oedema through increased endothelial permeability – vicious cycle

Autoregulatory mechanisms overwhelmed

Necrosis begins in the ischaemic muscles after 4 hours

Damaged muscles release myoglobin

Ischaemic nerves become neuropraxic

May recover if relieved early, permanent damage after 4 hours

Irreversible damage – loss of function, limb or life

Compromise of the arterial supply – late

Question 5

Describe the time scale associated with damage in compartment syndrome

Answer 5

1 hour
> Nerve conduction normal, muscle viable

4 hours
> Neuropraxis in nerves – reversible
> Reversible muscle ischaemia

8 hours
> Nerve axonotmesis and irreversible change
> Irreversible muscle ischaemia and necrosis

End stage limb changes
> Stiff fibrotic muscle compartments
> Impaired nerve function
> Clawing of limbs
> Loss of function

Question 6

Describe the clinical presentation of compartment syndrome

Answer 6

Pain out of proportion to that expected from the injury

Pain on passive stretching of the compartment

Pallor

Paraesthesia

Paralysis

Pulselessness

Question 7

Describe compartment pressure measurements used to determine whether compartment syndrome is present

Answer 7

Normal pressure: 0-4 mmHg, 10 mmHg with exercise

DBP-CP <30 mmHg
Where a patient may be hypotensive, e.g. after trauma, relating the compartment pressure to the diastolic blood pressure (DBP) is more accurate

CP > 30 mmHg
Abnormal with normal BP

Question 8

Describe the treatment for compartment syndrome

Answer 8

Open any dressings / bandages

> Reassess

> Observation (see if symptoms settle)
> Surgical release if no improvement or deterioration

> > > Fasciotomy

> > > > Full length decompression of all compartments - releases pressure

> > > > Excise any dead muscle

> > > > Leave wounds open

> > > > Repeat debridement every 48h until pressure down and all dead muscle excised

> > > > Outflow restored and pressure normalises

> > > > 48h delayed wound closure +/- plastic surgery or skin grafting

Late presentation
> Irreversible damage already present
> Fasciotomy will predispose to infection
> Non-operative treatment
> Splint in position of function
> Does not restore function but prevents clawing

Question 9

List the causes of acute monoarthritis

Answer 9

Infection

> Crystal-induced
> Gout
> Calcium pyrophosphate

Reactive (may be oligo-)

Haemarthrosis

Systemic rheumatic condition

Trauma

Question 10

Describe the pathogenesis of septic arthritis

Answer 10

Acute monoarthritis is septic until proven otherwise
> Usually involves knee
> Can involve any other joint or be polyarticular

Pathogenesis
> Bacteria enter joint and deposit in synovial lining
» Haematogenous spread
» Local invasion / inoculation

> Rapid entry into synovial fluid
> No basement membrane
> Close relationship to blood vessels

Question 11

List risk factors for septic arthritis

Answer 11

• Previous arthritis
• Trauma
• Diabetes
• Immunosuppression
• Bacteraemia
• Sickle cell anaemia
• Prosthetic joint

Question 12

Describe the findings of synovial fluid analysis in septic arthritis

Answer 12

Cell count > 50,000 wbcs/mm3
Differential >75% PMNs (polymorph neurophils)
Glucose: low
Gram stain: relatively insensitive test
Culture: positive
> Consider unusual pathogens in immunocompromised

Question 13

Describe the management of septic arthritis

Answer 13

Joint aspiration
> Daily or more frequently as needed

Antibiotics

Surgical intervention
> Only necessary if patient is not responding after 48h of appropriate therapy

Question 14

Describe polyarticular septic arthritis

Answer 14

More likely to be over 60 years

Average of 4 jonts
> Knee, elbow, shoulder and hip predominate

High prevalence of RA

Often without fever and leukocytosis

> Blood cultures are positive in 75%
Synovial fluid culture positive in 90%
Staph and strep most common

Poor prognosis

Question 15

List risk factors for gout

Answer 15

Modifiable
- Obesity
- Alcohol consumption
- High purine diet
- HFCS (high fructose corn syrup)

• Medications
  > Aspirin: reduces uric acid excretion
  > Diuretics
  > Cyclosporin
  > Pyrazinamide and ethambutol
  > Nicotinic acid

Non-modifiable
- Age
- Male gender
- Race
- Genetic factors
- Impaired renal function

Question 16

How is gout diagnosed?

Answer 16

Aspirate of synovial fluid

> Birefringent rods (needle-shaped) under polarising microscope being phagocytosed

Question 17

Describe the clinical presentation of gout

Answer 17

Podagra – gout of first metatarsophalangeal joint, acutely painful, even bedding is painful

History of gout flares or hyperuricaemia

Raised serum uric acid (sUA) between attacks

Can drop acutely as uric acid is mobilised

Question 18

Describe the differential diagnosis for gout

Answer 18

Septic arthritis

CPPD – calcium pyrophosphate crystal deposition (pseudogout)
> Less commonly first MTP
> Most commonly seen in knee, wrist and shoulder
> Crystals are rhomboid shaped

Question 19

Describe the treatment of gout

Answer 19

Acute attacks: relieve pain and reduce inflammation
> Non-pharmacological: cold packs
> NSAIDs / Coxibs / Colchicine / Corticosteroids

Long-term: prevent further acute attacks, prevent joint damage, eliminate tophi

> Lifestyle modifications

> > Diet
> Reduce purine intake
> Reduce fructose-containing drinks
> Include skimmed milk, low fat yogurts, vegetable protein and cherries every day

> > Weight loss
> 1kg/month - avoid crash diets
> Avoid high protein diets

> > Moderate exercise

> > Reduce alcohol intake

Urate lowering therapies

> Allopurinol
> Xanthine oxidase inhibitor
> Start 100mg increase in 100mg steps every 4 weeks til target or max 900mg daily

> Febuxostat
> 80mg with option to increase to 120mg after 4 weeks if not at target urate
> More potent xanthine oxidase inhibitor
> Not nephrotoxic

Question 20

What are the indications for treatment of gout?

Answer 20

Recurring attacks - >2/12

Tophi

Chronic gouty arthritis

Renal impairment (eGFR <60ml/min)

History of urolithiasis

Diuretic therapy use

Primary gout starting at a young age (under 40)

Very high serum urate >500 micromol/L

Question 21

Describe the pathogenesis of reactive arthritis

Answer 21

Seronegative spondyloarthropathy
> Seronegative for rheumatoid factor
> Strong association with HLA-B27
» Increased likelihood of developing ReA and persistence

ReA develops soon after infection occurs elsewhere in the body
> Viable organism cannot be recovered from a joint – not a true septic arthritis

May involve cross-reactivity between bacterial antigen and joint tissues leading to a perpetuating Th2 cell-mediated response

Persistence of antigenic material (heat shock proteins) due to failed clearance possibly due to polymorphism of toll-like receptors

Question 22

Describe the groups of bacteria which can cause reactive arthritis

Answer 22

SARA (sexually acquired reactive arthritis)
> Following infection with Chlamydia trachomatis

> Other GU organisms have been implicated
> Neisseria gonorrhoea
> Mycoplasma genitalium
> Ureplasma urealyticum

> Lymecycline may be used
> 70% self-limiting, most disease mild and short-lived

Enteric infections
> Salmonella
> Shigella
> Yersinia
> Campylobacter
> Clostridium

Question 23

Describe the clinical features of a reactive arthritis

Answer 23

Acute onset usually 2-6 weeks post-infection

Warm, swollen, tender joints, usually lower limb

Systemically unwell

Elevated inflammatory markers and malaise

Triad of arthritis, conjunctivitis and urethritis

70% will resolve in 3-12 months, 50% will recur

Lower limb asymmetric oligoarthritis

Dactylitis – sausage digits

Enthesopathy – Achilles tendonitis, plantar fasciitis

Inflammatory back pain

Extra-articular features
> Conjunctivitis, iritis, keratitis, episcleritis
> Keratoderma blennorrhagica and nail dystrophy
> Urethritis, prostatitis, cystitis, cervicitis
> Circinate balanitis
> Stomatitis, diarrhoea
> Rarely cardiac involvement with aortitis

Question 24

Describe the investigations and management of reactive arthritis

Answer 24

Investigations
> Joint aspiration to exclude sepsis
> Swabs – urethral, cervical
> Screen for other related infections
> Inflammatory markers – ESR, CRP
> Chlamydia serology
> HLA-B27 for prognostic not diagnostic reasons

Management
> Mild – NSAID and simple analgesia
> Moderate – NSAID, joint aspiration and corticosteroid injection
> Severe or prolonged – refer rheumatology for consideration of DMARD
» Sulphasalazine, methotrexate, anti-TNF alpha

Referrals
> Joint effusions should be aspirated to exclude sepsis
> Ophthalmology if uveitis
> Rheumatology referral indicated if symptoms unrelieved by NSAIDs or joint effusions evident

Question 25

Describe the factors influencing fracture healing

Answer 25

Type of bone > Long bones take longer to heal Mechanism of injury > High energy injuries > Take longer as energy is transferred to bone and soft tissue destruction ensues Closed or open fracture > Open fractures are prone to infection, can impair healing

Question 26

Describe indirect fracture healing

Answer 26

Callus formation > Fracture haematoma and inflammation > Blood from broken vessels forms a clot > 6-8h after injury > Swelling and inflammation with removal of dead bone/tissue cells at fracture site Fibrocartilagenous (soft) callus > 3 weeks > New capillaries organise fracture haematoma into granulation tissue – procallus > Fibroblasts and osteogenic cells invade procallus > Make collagen fibres which connect ends together > Chondrocytes begin to produce fibrocartilage Bony (hard) callus > After 3 weeks and lasts 3-4 months > Osteoblasts make woven bone Bone remodelling > Osteoclasts and osteoblasts remodel woven bone into compact bone and trabecular bone Management > A degree of movement is desirable to promote tissue differentiation > Excessive movement disrupts the healing tissue and affects all cellular differentiation

Question 27

Describe direct fracture healing

Answer 27

Unique artificial surgical situation Relies upon reduction and compression of bone ends – anatomical reduction Fracture stable – absolute stability – no movement under physiological load Mechanism > No callus > Cutting cones across fracture site > Direct formation of bone via osteoclastic resorption and osteoblastic formation

Question 28

Describe the general blood supply to a bone

Answer 28

Skeleton receives 5-10% cardiac output Endosteal supply > Inner 2/3 > Nutrient artery > High pressure Periosteal supply > Outer 1/3 > Capillaries from muscle attachments > Low pressure Metaphyseal-epiphyseal vessels > Ends of long bone > Separate in children, connected in adults

Question 29

Describe the blood supply to the femoral neck

Answer 29

Metaphyseal-epiphyseal system > Medial + lateral circumflex arteries >> Branches of profunda femoris >> Form an extracapsular arterial ring at the base of the femoral neck Ascending cervical vessels (aka retinacular vessels) pass up the femoral neck and form a subsynovial ring at the base of the femoral head > Epiphyseal branches from this ring supply the femoral head itself Other vessels (less extensive) > Branch of obturator artery (via ligamentum teres); more predominant in children > Branches from nutrient artery through diaphysis

Question 30

Describe femoral fractures

Answer 30

Certain types of fracture can cause disruption, particularly to cervical retinacular vessels e.g. displaced intracapsular neck of femur fractures > Problems with bone healing and avascular necrosis

Question 31

Describe fractures that cause problems with blood supply

Answer 31

Fractures > Femoral neck fractures Surgery > Surgical fixation of fractures e.g. intramedullary nail used to fix a long bone fracture – temporary damage to endosteal blood supply Certain fractures are prone to problems with union because of potential problems with blood supply > Proximal pole of scaphoid fractures > Talar neck fractures > Intracapsular hip fractures > Surgical neck of humerus fractures

Question 32

List factors that may inhibit fracture healing

Answer 32

Patient factors > Increasing age > Diabetes > Anaemia > Malnutrition > Peripheral vascular disease > Hypothyroidism > Smoking > Alcohol Medication > NSAIDs (especially COX-2 inhibitors) > Reduce local vascularity at fracture site > Additional reduction in healing effect independent of blood flow > Steroids (inhibit osteoblasts) > Bisphosphonates >> Inhibit osteoclastic activity – inhibit bone remodelling >> Recognised bisphosphonate associated fractures (subtrochanteric femoral fractures) >> Delay fracture healing as a result >> Long half-life

Question 33

Describe avascular necrosis and its consequences

Answer 33

AVN / osteonecrosis > Bone infarction – tissue death caused by an interruption of the blood supply – near a joint Can cause > Infarction of sub-chondral bone > Collapse of the joint and end stage arthritis Osteonecrosis is most common in the hip Pathophysiology - Interruption to blood flow - Extraosseous e.g. trauma - Intraosseous e.g. microcirculation from sickle cell - Increased extravascular pressure e.g. steroid-induced fat cell hypertrophy Early stages > Necrosis always involves the medullary bone first > Cortex – collateral blood supply > Articular cartilage spared – receives nutrition from synovial fluid Later stages > If bone does not remodel, microdamage does not get repaired and the mechanical properties of the bone are impaired > Subchondral bone weakens and collapses > Joint surface becomes irregular and no longer smooth > Further damage to surrounding articular cartilage – arthrosis

Question 34

List risk factors for avascular necrosis

Answer 34

Risk factors: AS IT GRIPS Collapse Happens > Alcohol abuse > Steroids / sickle cell disease > Idiopathic > Trauma (especially joint dislocation) > Gaucher's disease / Gout > Rheumatoid / radiation > Infection / inflammatory arthritis > Pancreatitis / pregnancy > SLE / smoking > Chronic renal failure / chemotherapy / Caisson disease (decompression sickness) > Hyperlipidaemia

Question 35

Describe the clinical presentation and examination of avascular necrosis

Answer 35

Asymptomatic Pain – infarction or arthritis Hip (AVN femoral head) > Groin pain > Worsens with weight bearing and motion > Less commonly thigh and buttock pain Rest pain Night pain Clinical examination > Physical exam findings >> Pain on joint movement >> Limp >> Restricted motion > Hip (AVN femoral head) >> Limitation in internal rotation and abduction

Question 36

Describe the changes seen on X-ray in avascular necrosis

Answer 36

Early > Mild density changes followed by sclerosis / cystic areas Later > Subchondral radiolucency > "Crescent sign" precedes subchondral collapse > Loss of sphericity and collapse of the femoral head > Joint-space narrowing and degenerative changes > AVN is bilateral in 55% of cases

Question 37

Describe the treatment of avascular necrosis

Answer 37

Depends on stage of disease at presentation Reduce risk > Use minimum effective dose of systemic corticosteroids Early symptoms > Partial weight bearing > Bisphosphonates? Intervention > Aimed at trying to reperfuse and heal infarcted region >> Core decompression +/- bone graft >> Vascularised bone graft >> Stem cell therapy > Healing phase >> Creeping substitution – dead bone is replaced by new bone > If subchondral collapse or arthrosis >> Total joint replacement – hip replacement surgery

Question 38

What is Kienbock's disease?

Answer 38

AVN of the lunate bone

Question 39

Describe the composition of bone matrix

Answer 39

Organic (40%) > Type I collagen (90%) > Also type V, XI collagen > Mucopolysaccharides > Bone-specific proteoglycans > Non- collagenous matrix proteins – osteonectin, osteopontin > Responsible for tensile strength Inorganic (60%) > Calcium hydroxyapatite: calcium + phosphorus (also sodium & potassium) > Responsible for compressive strength

Question 40

Describe the different types of cells found in bone

Answer 40

Osteoprogenitor - stem cells Osteoblasts – bone-forming cells > Derived from mesenchymal stem cells through osteoprogenitor cells > Produce new bone matrix > Contain abundant ER and mitochondria > After laying down new bone, 3 main fates >> Osteocyte – 90% of bone population >> Bone lining cell >> Apoptosis Osteocytes – mature bone cells Osteoclasts – bone-resorbing cells > Large multinucleated cells > Ruffled border > Abundant mitochondria and lysosomes (contain acid phosphatase)

Question 41

Describe the structure of compact bone

Answer 41

Compact e.g. outer shaft of femur > Aka cortical bone > Mainly found in diaphysis of long bones > Lamellae (sheets) of bone matrix arranged concentrically around central neurovascular bundles forming Haversian systems/osteons > Between each layer of lamellae there are osteocytes, which lie in lacunae > Canaliculi are small channels derived from lacunae and allow communication between osteocytes > Larger perforating channels lie perpendicular to vessels – Volkmann's canals >> Allow perforating vessels to supply each osteon > Slow turnover rate and metabolic activity > Stronger and greater resistance to torsion and bending than cancellous bone

Question 42

Describe the structure of cancellous bone

Answer 42

Cancellous e.g. medullary cavity of femur Aka spongy bone 3 dimensional lattice / trabecular structure Trabeculae arranged along lines of mechanical stress Spaces between them allow perforation of blood vessels and house bone marrow Found in metaphysis and epiphysis of long bones Found centrally in cuboid bones e.g. tarsals, carpals Higher turnover rate than cortical bone Less dense and less strong than cortical bone

Question 43

Describe secondary bone tumours including clinical presentation

Answer 43

Metastatic carcinoma > Bronchus, breast, prostate, kidney, thyroid (follicular) Childhood > Neuroblastoma, rhabdomyosarcoma Bones with good blood supply – long bones, vertebrae – due to haematogenous spread Clinical presentation > Asymptomatic > Bone pain > Bone destruction > Long bones – pathological fracture > Spinal metastases – vertebral collapse, spinal cord compression, nerve root compression, back pain > Hypercalcaemia Types of bone mets - Lytic - Sclerotic > reactive new bone formation, induced by tumour cells > Caused by prostatic and breast carcinoma, carcinoid tumour - Solitary bone metastases > typically renal and thyroid carcinomas > Often long survival > Surgical removal often valuable

Question 44

Describe myeloma

Answer 44

Commonest primary bone tumour Monoclonal proliferation of plasma cells Solitary – plasmacytoma – or multiple myeloma Median age at diagnosis is 68; slightly more common in men Clinical effects > Punched out lytic bone lesions > Marrow replacement – anaemia, infections, bleeding > Immunoglobulin excess > Serum electrophoresis – monoclonal band > Urine – immunoglobulin light chains (Bence Jones protein)

Question 45

Describe osteoid osteoma

Answer 45

A small, benign osteoblastic proliferation Common, any age, especially adolescents M:F 2:1 Any bone, especially long bones, spine Pain, worse at night - relieved by aspirin Scoliosis Juxta-articular tumours > Sympathetic synovitis Treatment: radiofrequency ablation

Question 46

Describe an enchondroma

Answer 46

Lobulated mass of cartilage within medulla Common, any age >50% - hands and feet, long bones Often asymptomatic in long bones Hands – swelling, pathological fractures Low cellularity, often surrounded by plates of lamellar bone

Question 47

Describe osteocartilagenous exostosis

Answer 47

Benign outgrowth of cartilage with endochondral ossification Derived from growth plate Very common, usually in adolescence Uncommonly, multiple-diaphyseal aclasis – autosomal dominant Metaphysis of long bones, not cranio-facial Treatment – surgical resection

Question 48

Describe osteosarcoma

Answer 48

Malignant tumour whose cells form osteoid (unmineralised) or bone (mineralised) Age: peak 10-25, second peak in adulthood Site: metaphysis of long bones, 50% around knee Sex: male preponderance, 3:2 Presentation > Bone pain, swelling, pathological fracture > Often delayed presentation Spread > Highly malignant > Haematogenous spread > Early lung metastases > Modern survival: 50-60% Imaging > Lytic destructive lesion > Cortical destruction with soft tissue mass > Codman triangle: tumour extends out through the cortex, body responds by producing a neocortex, old cortex is lifted up, forming a triangle Treatment > Neoadjuvant chemotherapy > Wide local excision, limb sparing > Further chemotherapy +/- radiotherapy for local control

Question 49

Describe chondrosarcoma

Answer 49

De novo (primary) or from a pre-existing enchondroma or exostosis (secondary) Central, within the medullary canal or peripheral on bone surface 10% of malignant primary bone tumours; predominantly middle-aged and elderly Males:females, 2:1 Axial skeleton, pelvis, ribs, shoulder girdle, proximal femur and humerus Hands and feet are rare Presentation > Bone pain, swelling, pathological fracture, neurological symptoms Spread > Locally aggressive > Behaviour depends on histological grade (1-3) >> Grade 1 – 85% 5 year survival >> Grade 3 – 50% 5 year survival > Tend to recur rather than metastasise > IDH1 and IDH2 mutations Imaging > Popcorn calcifications > Lytic > May get cortical destruction with soft tissue mass Microscopic appearance > Pleomorphism – variation in size and shape > High mitotic activity > Hyperchromasia – dark nuclei

Question 50

Describe Ewing's sarcoma

Answer 50

Peak 5-15 years Long bones – diaphysis or metaphysis > Flat bones of limb girdles Highly aggressive – haematogenous spread and early metastases to lung, bone marrow and bone micrometastases 5 year survival: 60-70% Presentation: pain, swelling, night sweats, weight loss, fever X-ray > "Moth eaten" appearance > Lytic lesion > Periosteal new bone formation - "onion skinning" - layers Diagnosis via biopsy > Poorly differentiated small round blue cell tumour > CD99 positive Possible neural crest origin 90% show translocation between chromosomes 11 and 22 (EWSR1) - FiSH and PCR Treatment > Neoadjuvant chemotherapy – doxorubicin, cyclophosphamide, vincristine > Surgery – pathological assessment > Further chemotherapy +/- radiotherapy for local control

Question 51

Describe the pathophysiology of RA

Answer 51

Genetic predisposition > Multiple genes involved – HLA-DR4 Environmental trigger > Infection – viral, bacterial > Smoking Changes > Cytokine production > Activation of macrophages, neutrophils > Propagation of inflammatory response >> Pro-inflammatory cytokines: TNF-alpha, IL-6 > Leads to pannus formation >> Inflammatory tissue invading and taking over normal synovial tissue of joint > Synovial fibroblast activation and further cytokine release > Activation of osteoclasts – erosion of bone > Neutrophils release free radicals – NO – leading to cardiovascular and systemic effects

Question 52

Describe the signs and symptoms associated with rheumatoid arthritis

Answer 52

Symptoms - Pain - Stiffness - Early morning stiffness - Joint gelling - Swelling - Differentiates between osteoarthritis - Small joints more affected than large joints - Symmetrical pattern of joint involvement - Persistent Signs - Synovitis - Boggy swelling and tenderness of joints - Deformity > Swan neck > Boutonniere > Z-thumb - Rheumatoid nodules

Question 53

Describe Felty's syndrome

Answer 53

Rare complication of RA SANTA > Splenomegaly > Anaemia > Neutropaenia > Thrombocytopaenia > Arthritis (Rheumatoid)

Question 54

List the differential diagnoses for rheumatoid arthritis

Answer 54

Polyarticular gout Psoriatic arthritis Osteoarthritis SLE

Question 55

Describe the investigations used in the diagnosis for RA

Answer 55

Laboratory - Non-specific > CRP/ESR > FBC > Bone/urate Specific - Immunology > Rheumatoid factor >> IgM antibody directed against Fc portion of IgG antibody >> Also found in SLE, Sjogren's, PBC, hepatitis B & C, bacterial endocarditis, increasing age > CCP antibody >> Inflammation leads to cellular damage >> Enzymatic process leads to the conversion of arginine residues to citrulline >> Alteration of shape creates a foreign antigen from self – anti-citrullinated cyclic peptide antibodies Imaging - Plain radiograph > First changes >> Peri-articular osteopenia >> Soft tissue swelling > Late changes >> Erosion >> Joint destruction >> Subluxation, dislocation – ulnar deviation Ultrasound - Synovitis > Thickening of synovium – synovial hypertrophy > Fluid in joint is dark > Doppler detects signal within joint space > Degree of blood flow correlates with degree of synovitis

Question 56

Describe the classification criteria for RA

Answer 56

EULAR 2010 Classification Criteria > Joint involvement: number of joints, large or small joints > Serology: RF, ACPA > Acute phase reactants: CRP, ESR > Duration of symptoms: >6 weeks

Question 57

Describe the treatment of RA

Answer 57

Reduce inflammation > NSAIDs – ibuprofen, naproxen, diclofenac > COX-2 inhibitors e.g. etoricoxib > Steroids >> Oral e.g. prednisolone >> Intramuscular – depomedrone (methylprednisolone) or Kenalog (triamcinolone acetonide) >> Intra-articular – depomedrone or Kenalog Maintain joint function - cDMARDs – first line, within 3 months of symptom onset > Methotrexate > Sulphasalazine > Hydroxychloroquine -bDMARDs > Anti-TNF: etanercept, adalimumab > B cell depleter: rituximab > IL-6 blocker: tocilizumab > IL-17 blocker: secukinumab > IL-23 blocker: ustekinumab > JAK inhibitor: baricitinib > T cell inhibitor: abatacept

Question 58

Describe the mechanism of action, side effects and monitoring requirements of methotrexate

Answer 58

Folate antagonist (requires folate replacement) Once weekly Side effects > rash > nausea > mouth ulcers > abnormal bloods > diarrhoea > headaches > rare – pneumonitis Monitoring requirements: FBC / LFTs / U&Es, ESR Contraindicated in pregnancy

Question 59

Describe the mechanism of action, side effects and monitoring requirements of sulphasalazine

Answer 59

Immunomodulatory, several actions including against folate, T and B cells Daily – pill burden Side effects > dizziness > abdominal pain > colour change of urine (bright yellow or orange) > tinges sweat and tears Monitoring requirements – FBC, U&Es, LFTs Safe in pregnancy

Question 60

Describe the mechanism of action, side effects and monitoring requirements of hydroxychloroquine

Answer 60

Blocks toll-like receptors on plasmacytoid dendritic cells thus reducing DC activation Daily – most benign DMARD Side effects – headache, nausea, muscle pain, rash Monitoring requirements – ocular (retinopathy) Safe in pregnancy

Question 61

Describing the screening requirements, contraindications and monitoring required for biologic DMARDs

Answer 61

Screening > Viral hepatitis and HIV (including anti-core antibody) > Varicella > CXR and IGRA (TB) > Vaccination – infuenza, pneumococcal, COVID-19 Contraindications > Active infection > Active or latent TB > Pregnancy (for some of the biologics) > Malignancy > Diverticular disease (IL-6) Monitoring > Infections > Malignancy (especially skin) > Bloods (FBC, LFTs) > Awareness with vaccination

Question 62

Describe the DAS28 scoring system

Answer 62

Disease Activity Score (DAS) 28 - measures overall disease activity in RA Composite score derived from 4 measures > Number of swollen joints > Number of tender joints > Measure ESR/CRP > Measure global assessment of health Scores >5.1 - active disease - 2x minimum for eligibility of biologic therapies - Drop of at least 1.2 points for continuation of treatment >3.2 - <5.1 - moderate disease <3.2 - low disease activity <2.6 - remission

Question 63

What is the HAQ used for in RA?

Answer 63

Health Assessment Questionnaire is used to assess function in RA

Question 64

What are the criteria for the use of biologic agents in RA?

Answer 64

DAS-28 > 5.1 3 or more tender joints and 3 or more swollen joints Failed trials of 2 DMARDs including methotrexate

Question 65

Which DMARDs are used in the treatment of psoriatic arthritis?

Answer 65

- Methotrexate - Sulphasalazine - Leflunoomide - Cyclosporin - Hydroxychloroquine can flare psoriasis, so NOT used

Question 66

Describe the disease assessment tools use in ankylosing spondilitis

Answer 66

BASDAI – Bath Ankylosing Spondilitis Disease Activity Index > Gold standard for measuring and evaluating disease activity > Major symptoms >> Fatigue >> Spinal pain >> Areas of localised tenderness – enthesis >> Morning stiffness duration >> Morning stiffness severity >> Scale from 1 to 10; 4 or greater – suboptimal control of disease BASFI – Bath Ankylosing Spondilitis Functional Index > Assess function, from easy to impossible e.g. putting on socks/tights without aid BASMI – Bath Ankylosing Spondilitis Metrology Index > Measures spinal mobility > Series of measurements carried out by physiotherapists

Question 67

Describe the clinical presentation of osteoarthritis

Answer 67

Synovial joints > Degenerative disease > Progressive loss of hyaline cartilage Clinical presentation > Pain > Stiffness > Loss of ROM > Deformity > Loss of function > Reduced quality of life

Question 68

Describe the risk factors for osteoarthritis

Answer 68

Modifiable - Trauma - Muscle weakness - High impact activities Non-modifiable - Gender (females > males) - Age - Genetics - Congenital - Acquired - Infection - Dysplasia - Slipped capital femoral epiphysis (SCFE) - Perthes

Question 69

Describe the examinations used in osteoarthritis

Answer 69

Inspection - BMI - Gait - Leg length - Scars ROM - Active - Passive Special tests

Question 70

Describe the 4 features seen in an OA X-ray

Answer 70

Loss of joint space Sclerosis Subchondral cysts Marginal osteophytes

Question 71

Describe the management of OA

Answer 71

Non-operative management - Analgesia > Paracetamol > 1st line opiate > NSAIDs > Topical - Lifestyle modification > Weight loss > Exercise program / physiotherapy > Corticosteroid injection > Viscoelastic injection (hyaluronic acid) > Glucosamine / chondroitin supplements > Possible stem cell therapy Operative management > Arthroscopic debridement > Joint preserving osteotomy > Focal resurfacing > Full joint resurfacing (hip) > Partial joint arthroplasty (knee) > Total joint arthroplasty

Question 72

Describe the clinical presentation of SLE

Answer 72

Constitutional symptoms > Avascular necrosis – seen outwith steroid use > Fibromyalgia > Osteoporosis Renal > ESRF Pulmonary > Pleurisy > Pleural infections > Acute pneumonitis > Diffuse alveolar haemorrhage > Pulmonary hypertension > Shrinking lung syndrome Cardiovascular > Pericarditis +/- effusion > Myocarditis > Valvular abnormalities > Coronary heart disease – high risk of morbidity & mortality - 50x risk of MI Neuropsychiatric > Headache – unremitting severe headache > Anxiety and mood disorder > Seizure > Demyelination > GBS > Mononeuritis multiplex Gastrointestinal (uncommon) > Dysphagia > Reduced peristalsis > Peritonitis > Pancreatitis > Pseudo-obstruction > Lupus hepatitis – biopsy required Haematological > Anaemia of chronic disease > Autoimmune haemolytic anaemia > Thrombotic thrombocytopaenic purpura (TTP) >> Microangiopathic haemolytic anaemia (MAHA) >> Low platelets >> Fever >> Neuro / renal involvement – check aPLS antibodies > Leukopaenia > Can have associated lymphadenopathy and splenomegaly > Thrombocytopaenia – mild or ITP Cutaneous manifestations: butterfly rash Arthralgia and arthritis > Non-erosive arthropathy; usually does not cause deformity > Exception – Jaccoud's arthropathy - due to tendon involvement

Question 73

What is Libman-Sacks endocarditis?

Answer 73

Non-bacterial endocarditis associated with SLE where there is an inflammatory change within the valve, leading to disintegration of valve

Question 74

Describe renal monitoring in SLE

Answer 74

Some patients will develop ESRF Renal impairment typically presents within 1-2 years Urinalysis, U&Es, BP monitored at clinic ds-DNA – rise in titre can predict flares Renal biopsy – gold standard for diagnosing lupus nephritis Also useful for prognosis and treatment

Question 75

List the investigations used in SLE

Answer 75

EEG MRI LP Psychiatric evaluation Anti-ribosomal P: associated with mood disorders ANA

Question 76

Describe the significance of ANA, ENA and complement in the diagnosis of SLE

Answer 76

Antinuclear antibody (ANA) > Present in 95-98% of patients > SLE results due to activation of innate and adaptive immunity > Interaction of self-antigens on or released by apoptotic cells Extractable nuclear antigen (ENA) > If ANA positive, helpful to know which antigens are affected > Ro/La - SLE, Sjogrens > Ds-DNA – SLE > Sm – SLE > RNP – mixed CTD > Centromere – limited SScl > Scl-70 – diffuse SScl > Histone – drug-induced lupus Complement > Complement consumption in active disease >> C3 more specific >> C4 can be chronically low

Question 77

Describe the treatment of SLE

Answer 77

Steroids Hydroxychloroquine > First-line treatment for lupus > Used in all severities and types of lupus > Useful in treating skin disease and joint pain, cardiovascular protective effects Belimumab > Monoclonal antibody that inhibits B cell activating factor (BAFF) aka B lymphocyte stimulator (BLyS) Azathioprine > Non-teratogenic Mycophenolate > Teratogenic > Good for renal manifestations Methotrexate > Teratogenic > Good for joint problems Calcineurin inhibitors > Cyclosporin, Tacrolimus Cyclophosphamide > Life-threatening manifestations or refractory disease Rituximab > Life-threatening manifestations or refractory disease

Question 78

Describe adjunctive therapies used in SLE

Answer 78

Topical lubricants for sicca symptoms Fatigue management groups Calcium channel blockers for Raynauds Treatment of co-existent fibromyalgia CVS risk Osteoporosis risk Co-existent APLS (autoimmune lymphoproliferative syndrome) > Anticoagulation in confirmed thromboembolic disease

Question 79

Describe the scoring system used in the assessment of SLE

Answer 79

Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Scoring system used to assess disease activity Low disease activity: SLEDAI <4 Remission: SLEDAI = 0

Question 80

Describe the clinical features of scleroderma

Answer 80

Aka systemic sclerosis (SScl) Mainly affects women aged 30-50 Skin thickening > Initially appears as non-pitting oedema of hands and feet > Progresses to skin tightness > Sclerodactyly (involvement of fingers) > Contracture > Calcinosis > Telangiectasia Progressive fibrosis Vascular disease > Raynaud's: severe disease with digital ulcers and auto amputations Musculoskeletal > Arthralgia > Myalgia > Inflammatory arthritis and inflammatory myositis less common > Tendon friction rubs GI > Oesophageal dysmotility > GORD > Small bowel hypomobility with bacterial overgrowth > Hypomobility of large bowel with constipation > Pancreatic insufficiency Respiratory > Interstitial lung disease > Organising pneumonia > Pulmonary hypertension Renal > Scleroderma renal crisis >> Hypertension >> Progressive renal failure >> MAHA >> Seizures >> Encephalopathy Cardiac > Arrhythmias > Pericardial effusions > Myocardial fibrosis

Question 81

Describe the classification criteria for systemic sclerosis

Answer 81

ACR/EULAR 2013 classification criteria Skin thickening of the fingers extending proximal to the metacarpophalangeal joints If not present, 7 other domains; score >9 in keeping with SScl > Skin changes > Fingertip lesions > Telangiectasia > Abnormal nail fold capillaries > Pulmonary arterial hypertension and/or ILD > Raynaud's phenomenon > SScl-related auto antibodies >> Anti-centromere antibodies: limited variant systemic sclerosis (CREST sydrome) >> Anti-Scl-70 in diffuse variant systemic sclerosis Limited variant SScl > Distal skin involvement – fingers, toes > Skin calcification > Telangiectasia > Raynaud's > Anti-centromere positive > Late incidence of pulmonary arterial hypertension (PAH) Diffuse variant SScl > Proximal skin involvement and trunk > Raynaud's > Early organ involvement >> ILD, PAH >> Renal failure >> Myocardial disease >> GI involvement

Question 82

What are the disease mimics for systemic sclerosis?

Answer 82

Diabetic cheiroarthropathy Generalised morphea Eosinophilic fasciitis

Question 83

Describe the treatment of systemic sclerosis

Answer 83

Cutaneous > Moisturiser > Methotrexate > Laser therapy for telangiectasia Musculoskeletal > Analgesia > Methotrexate Raynaud's > Calcium channel blockers – first-line > ACEi / fluoxetine > Sildenafil > Iloprost Pulmonary > Mycophenolate > Cyclosporin > Lung transplant > Stem cell transplant GI > Prokinetics > PPI/ H2 antagonist > Cyclical antibiotics > Laxatives Cardiac > Immunosuppressive > PPM if required Renal > ACEi

Question 84

List the subtypes of idiopathic inflammatory myositis

Answer 84

Polymyositis Dermatomyositis Overlap syndromes > Scleroderma / myositis overlap Juvenile PM/DM Drug-induced Inclusion body myositis > Males, >50s, degenerative distal disease

Question 85

Describe the clinical manifestations associated with idiopathic inflammatory myositis

Answer 85

Symmetrical, proximal muscle weakness > Upper arms, thighs Myalgia only in <50% Respiratory / diaphragm involvement > Can lead to respiratory failure Oesophageal involvement > Can lead to swallowing difficulties Rarely, face and neck involvement Distal disease unusual – can occur in IBM Systemic > Overlap syndromes > CTD > Antisynthetase syndromes Malignancy > Association with DM > PM Non-specific symptoms > Weight loss > Fevers > Fatigue Cutaneous > Does not occur in polymyositis > Dermatomyositis >> Can precede muscle involvement >> Gottrons papules – red/purple papules over MCP/PIPJ >> Heliotrope rash often with periorbital oedema >> Macular eruption – shawl sign, V sign >> Calcinosis, more common in children

Question 86

Describe the investigations used in idiopathic inflammatory myositis

Answer 86

Creatine kinase (CK) > In the thousands > Significantly higher figures suggest alternative causes EMG MRI of muscles Muscle biopsy – gold standard Myositis specific antibodies Tumour screening if symptoms / red flags

Question 87

Describe the treatment of idiopathic inflammatory myositis

Answer 87

Corticosteroids > Prednisolone – 1mg/kg Immunosuppression > Methotrexate > Tacrolimus > Azathioprine > Mycophenolate IV immunoglobulins Resistant disease > Rituximab > Cyclophosphamide

Question 88

Describe primary and secondary Sjogren's syndrome

Answer 88

Autoimmune condition that affects the exocrine glands Symptoms > Dry mucous membranes e.g. dry mouth, dry eyes and dry vagina Primary Sjogren's > This condition occurs in isolation Secondary Sjogren's > Occurs related to SLE or rheumatoid arthritis > Associated with anti-Ro and Anti-La antibodies

Question 89

Describe the test used in Sjogren's syndrome

Answer 89

Schirmer Test Inserting a folded piece of filter paper under the lower eyelid with a strip hanging out over the eyelid This is left in for 5 minutes and the distance along the strip that becomes moist is measured Tears should travel 15mm in a healthy young adult Less than 10mm is significant

Question 90

Describe the management of Sjogren's syndrome

Answer 90

Artificial tears Artificial saliva Vaginal lubricants Hydroxychloroquine – halts progression of disease

Question 91

Describe the complications associated with Sjogren's syndrome

Answer 91

Eye problems – conjunctivitis, corneal ulcers Oral problems – dental cavities, candida infections Vaginal problems – candidiasis, sexual dysfunction Rare > Pneumonia and bronchiectasis > Non-Hodgkins lymphoma > Peripheral neuropathy > Vasculitis > Renal impairment

Question 92

List the different types of vasculitis

Answer 92

Large vessel vasculitis > Takayasu arteritis > Giant cell arteritis Medium vessel vasculitis > Polyarteritis nodosa > Kawasaki disease Immune complex small vessel vasculitis > Cryoglobulinemic vasculitis > IgA vasculitis (Henoch-Schonlein) > Hypocomplementaemic urticarial vasculitis (anti-C1q) vasculitis ANCA-associated small vessel vasculitis > Microscopic polyangiitis > Granulomatosis with polyangiitis (Wegener's) > Eosinophilic granulomatosis with Polyangiitis (Churg-Strauss)

Question 93

Describe the clinical presentation of giant cell arteritis

Answer 93

Systemic vasculitis that affects the aorta and its major branches > Aka temporal arteritis Clinical presentation > Headache >> Temporal headache with tenderness >> Subacute onset >> Constant >> Little relief with analgesics Visual symptoms Jaw claudication - sore to eat or talk Polymyalgia rheumatica symptoms Constitutional upset > General malaise > Weight loss > Non-specific fatigue > Night sweats

Question 94

Describe the complications of giant cell arteritis

Answer 94

Visual loss > GCA major cause of irreversible visual loss > Acute ischaemic optic neuropathy > Sudden painless loss of vision, occasionally preceded by amaurosis fugax Large vessel vasculitis > Vascular stenoses and aneurysms CVA > Obstruction or occlusion of internal carotid artery or vertebral arteries

Question 95

Describe the diagnosis of giant cell arteritis

Answer 95

Temporal artery biopsy > Gold standard > Interruption of internal elastic laminae with mononuclear inflammatory cell infiltrate within vessel wall > Multinucleated giant cells are typical but their absence does not exclude a diagnosis Other investigations > Temporal artery USS > MRI > PET-CT

Question 96

Describe the treatment of giant cell arteritis

Answer 96

If strong clinical suspicion – treat > 1 mg / kg / day prednisolone (maximum 60mg) > Aspirin 75mg daily (reduces ischaemic complications) Established diagnosis > Maintain prednisolone 60mg for 1 month > Taper to 15mg by 12 weeks > Aim to discontinue steroids by 12-18 months Corticosteroid-sparing therapy in patients with disease relapse on steroid sparing > Mycophenolate mofetil > Methotrexate > Tocilizumab (anti-IL-6)

Question 97

List the causes of cutaneous (small vessel) vasculitis

Answer 97

Idiopathic Drugs: commonest cause Infection > HCV, HBV > Gonococcus > Meningococcus > HIV Secondary RA / CTD / PBC / UC Malignancy > Haematological > solid organ Manifestation of small / medium vessel ANCA-associated vasculitis

Question 98

Describe the clinical presentation of Henoch-Schonlein Purpura (HSP)

Answer 98

Aka IgA vasculitis, small vessel vasculitis Infections can be trigger More common in children: 2-11y; observed in adults, mean age 43y Males > females Frequently self-limiting illness, 4-16 weeks - good overall prognosis Presentation > Cutaneous vasculitis >> Classic purpuric rash; buttocks and thighs > lower legs >> Urticarial rash >> Confluent petechiae >> Ecchymoses >> Ulcers > Arthralgia, lower limb arthritis

Question 99

Describe the complications associated with Henoch-Schonlein Purpura

Answer 99

GI > Pain > Bleeding > Diarrhoea > Intussusception (rare) Renal > IgA nephropathy Urological > Orchitis CNS > Very rare

Question 100

Describe the treatment of Henoch-Schonlein Purpura

Answer 100

Often none required (self-limiting) Corticosteroids for certain complications > Testicular torsion > GI disease > Arthritis Relapses in 5-10%, usually within 12 months

Question 101

Describe the clinical presentation of Granulomatosis with Polyangiitis (GPA)

Answer 101

Aka Wegener's granulomatosis Granulomatous necrotising inflammatory lesions of the upper and lower respiratory tract Pauci-immune glomerulonephritis Presentation – classic triad of disease Upper airway / ENT > Rhinitis > Chronic sinusitis > Chronic otitis media > Saddle nose deformity > Nasal septal perforation Lower respiratory > Parenchymal nodules +/- cavitation > Alveolar haemorrhage Renal > Rapidly progressive pauci-immune glomerulonephritis Constitutional symptoms > Fatigue > Weight loss > Night sweats > Fever > Myalgia / arthralgia > Failure to thrive in elderly

Question 102

Describe the investigations used in Granulomatosis with Polyangiitis (GPA)

Answer 102

Immunology - ANCA > Autoantibodies directed against the cytoplasmic constituents of neutrophils and monocytes > 2 means of testing >> Indirect immunofluorescence >> ELISA for PR3/MPO > 2 types >> cANCA (cytoplasmic ANCA – high levels of PR3) - associated with GPA >> pANCA (peripheral ANCA – high MPO) - associated with MPA Pathology

Question 103

Describe the general treatment of vasculitis

Answer 103

Remission induction > Switch off vasculitis activity > Higher doses – higher toxicity > 3-6 months > Time pressure > Agents >> Prednisolone >> Cyclophosphamide >>> Risks – infection, cytopaenias, malignancy, infertility >> Rituximab: anti-B cell biologic agent >>> as effective as cyclophosphamide >>> Safer for repeated treatments – less malignancy >>> No risk of infertility >> Methotrexate >> Mycophenolate Remission maintenance > Prevent relapse > Lower drug toxicities > More prolonged therapy – 2+ years > Agents >> Azathioprine >> Methotrexate >> Rituximab