Describe the causes and common sites of compartment syndrome
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
What is the consequence of an untreated compartment syndrome in the arm?
Volkmann’s ischaemic contracture
Describe the pathogenesis of compartment syndrome
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
Describe the pathophysiology of compartment syndrome, including later stages
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
Describe the time scale associated with damage in compartment syndrome
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
Describe the clinical presentation of compartment syndrome
Pain out of proportion to that expected from the injury
Pain on passive stretching of the compartment
Pallor
Paraesthesia
Paralysis
Pulselessness
Describe compartment pressure measurements used to determine whether compartment syndrome is present
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
Describe the treatment for compartment syndrome
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
List the causes of acute monoarthritis
Infection
> Crystal-induced
> Gout
> Calcium pyrophosphate
Reactive (may be oligo-)
Haemarthrosis
Systemic rheumatic condition
Trauma
Describe the pathogenesis of septic arthritis
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
List risk factors for septic arthritis
- Previous arthritis
- Trauma
- Diabetes
- Immunosuppression
- Bacteraemia
- Sickle cell anaemia
- Prosthetic joint
Describe the findings of synovial fluid analysis in septic arthritis
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
Describe the management of septic arthritis
Joint aspiration
> Daily or more frequently as needed
Antibiotics
Surgical intervention
> Only necessary if patient is not responding after 48h of appropriate therapy
Describe polyarticular septic arthritis
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
List risk factors for gout
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
How is gout diagnosed?
Aspirate of synovial fluid
> Birefringent rods (needle-shaped) under polarising microscope being phagocytosed
Describe the clinical presentation of gout
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
Describe the differential diagnosis for gout
Septic arthritis
CPPD – calcium pyrophosphate crystal deposition (pseudogout)
> Less commonly first MTP
> Most commonly seen in knee, wrist and shoulder
> Crystals are rhomboid shaped
Describe the treatment of gout
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
What are the indications for treatment of gout?
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
Describe the pathogenesis of reactive arthritis
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
Describe the groups of bacteria which can cause reactive arthritis
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
Describe the clinical features of a reactive arthritis
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
Describe the investigations and management of reactive arthritis
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
Describe the factors influencing fracture healing
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
Describe indirect fracture healing
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
Describe direct fracture healing
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
Describe the general blood supply to a bone
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
Describe the blood supply to the femoral neck
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
Describe femoral fractures
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
Describe fractures that cause problems with blood supply
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
List factors that may inhibit fracture healing
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
Describe avascular necrosis and its consequences
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
List risk factors for avascular necrosis
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
Describe the clinical presentation and examination of avascular necrosis
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
Describe the changes seen on X-ray in avascular necrosis
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
Describe the treatment of avascular necrosis
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
What is Kienbock’s disease?
AVN of the lunate bone
Describe the composition of bone matrix
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
Describe the different types of cells found in bone
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)
Describe the structure of compact bone
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
Describe the structure of cancellous bone
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
Describe secondary bone tumours including clinical presentation
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
Describe myeloma
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)
Describe osteoid osteoma
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
Describe an enchondroma
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
Describe osteocartilagenous exostosis
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
Describe osteosarcoma
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
Describe chondrosarcoma
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
Describe Ewing’s sarcoma
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
Describe the pathophysiology of RA
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
Describe the signs and symptoms associated with rheumatoid arthritis
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
Describe Felty’s syndrome
Rare complication of RA
SANTA
> Splenomegaly
> Anaemia
> Neutropaenia
> Thrombocytopaenia
> Arthritis (Rheumatoid)
List the differential diagnoses for rheumatoid arthritis
Polyarticular gout
Psoriatic arthritis
Osteoarthritis
SLE
Describe the investigations used in the diagnosis for RA
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
Describe the classification criteria for RA
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
Describe the treatment of RA
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
Describe the mechanism of action, side effects and monitoring requirements of methotrexate
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
Describe the mechanism of action, side effects and monitoring requirements of sulphasalazine
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
Describe the mechanism of action, side effects and monitoring requirements of hydroxychloroquine
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
Describing the screening requirements, contraindications and monitoring required for biologic DMARDs
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
Describe the DAS28 scoring system
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
What is the HAQ used for in RA?
Health Assessment Questionnaire is used to assess function in RA
What are the criteria for the use of biologic agents in RA?
DAS-28 > 5.1
3 or more tender joints and 3 or more swollen joints
Failed trials of 2 DMARDs including methotrexate
Which DMARDs are used in the treatment of psoriatic arthritis?
- Methotrexate
- Sulphasalazine
- Leflunoomide
- Cyclosporin
- Hydroxychloroquine can flare psoriasis, so NOT used
Describe the disease assessment tools use in ankylosing spondilitis
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
Describe the clinical presentation of osteoarthritis
Synovial joints
> Degenerative disease
> Progressive loss of hyaline cartilage
Clinical presentation
> Pain
> Stiffness
> Loss of ROM
> Deformity
> Loss of function
> Reduced quality of life
Describe the risk factors for osteoarthritis
Modifiable
- Trauma
- Muscle weakness
- High impact activities
Non-modifiable
- Gender (females > males)
- Age
- Genetics
- Congenital
- Acquired
- Infection
- Dysplasia
- Slipped capital femoral epiphysis (SCFE)
- Perthes
Describe the examinations used in osteoarthritis
Inspection
- BMI
- Gait
- Leg length
- Scars
ROM
- Active
- Passive
Special tests
Describe the 4 features seen in an OA X-ray
Loss of joint space
Sclerosis
Subchondral cysts
Marginal osteophytes
Describe the management of OA
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
Describe the clinical presentation of SLE
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
What is Libman-Sacks endocarditis?
Non-bacterial endocarditis associated with SLE where there is an inflammatory change within the valve, leading to disintegration of valve
Describe renal monitoring in SLE
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
List the investigations used in SLE
EEG
MRI
LP
Psychiatric evaluation
Anti-ribosomal P: associated with mood disorders
ANA
Describe the significance of ANA, ENA and complement in the diagnosis of SLE
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
Describe the treatment of SLE
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
Describe adjunctive therapies used in SLE
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
Describe the scoring system used in the assessment of SLE
Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)
Scoring system used to assess disease activity
Low disease activity: SLEDAI <4
Remission: SLEDAI = 0
Describe the clinical features of scleroderma
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
Describe the classification criteria for systemic sclerosis
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
What are the disease mimics for systemic sclerosis?
Diabetic cheiroarthropathy
Generalised morphea
Eosinophilic fasciitis
Describe the treatment of systemic sclerosis
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
List the subtypes of idiopathic inflammatory myositis
Polymyositis
Dermatomyositis
Overlap syndromes
> Scleroderma / myositis overlap
Juvenile PM/DM
Drug-induced
Inclusion body myositis
> Males, >50s, degenerative distal disease
Describe the clinical manifestations associated with idiopathic inflammatory myositis
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
Describe the investigations used in idiopathic inflammatory myositis
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
Describe the treatment of idiopathic inflammatory myositis
Corticosteroids
> Prednisolone – 1mg/kg
Immunosuppression
> Methotrexate
> Tacrolimus
> Azathioprine
> Mycophenolate
IV immunoglobulins
Resistant disease
> Rituximab
> Cyclophosphamide
Describe primary and secondary Sjogren’s syndrome
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
Describe the test used in Sjogren’s syndrome
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
Describe the management of Sjogren’s syndrome
Artificial tears
Artificial saliva
Vaginal lubricants
Hydroxychloroquine – halts progression of disease
Describe the complications associated with Sjogren’s syndrome
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
List the different types of vasculitis
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)
Describe the clinical presentation of giant cell arteritis
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
Describe the complications of giant cell arteritis
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
Describe the diagnosis of giant cell arteritis
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
Describe the treatment of giant cell arteritis
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)
List the causes of cutaneous (small vessel) vasculitis
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
Describe the clinical presentation of Henoch-Schonlein Purpura (HSP)
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
Describe the complications associated with Henoch-Schonlein Purpura
GI
> Pain
> Bleeding
> Diarrhoea
> Intussusception (rare)
Renal
> IgA nephropathy
Urological
> Orchitis
CNS
> Very rare
Describe the treatment of Henoch-Schonlein Purpura
Often none required (self-limiting)
Corticosteroids for certain complications
> Testicular torsion
> GI disease
> Arthritis
Relapses in 5-10%, usually within 12 months
Describe the clinical presentation of Granulomatosis with Polyangiitis (GPA)
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
Describe the investigations used in Granulomatosis with Polyangiitis (GPA)
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
Describe the general treatment of vasculitis
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
