Week 11 MSK Flashcards
Types of joint disorders
Infection (septic arthritis)
Inflammatory (reactive arthritis)
Crystal arthropathy (Gout, pseudo gout)
Degenerative (OA)
Septic arthritis
- Bacterial infection of joint
- Synovium inflamed with fibrin exudation and neutrophil polymorphs
- Medical emergency
Clinical features: Sudden onset, fever, swollen, hot joint, loss of function, mostly hips or knees, usually one joint
Causes: Staph. aureus, neisseria gonorrhoea, haemophilus influenzae (children)
- If have loss of cartilage can cause secondary OA
- Pott’s disease: TB from spine
Risk factors: steroids, biologics, RA, joint prosthesis, IV drug abuse, sexually active
Investigations:
Bloods - FBC, CRP
Blood culture
Joint aspirate - for microbiology culture
Treatment
IV antibiotics
Drainage
Types of SA
Lyme disease (due to borrelia burgdoferi)
Brucellosis
Sphyilitc arthritis
Crystal arthropathy - Gout
Includes Gout and pseudogout
Gout:
- Inflammatroy arthritis due to excess levels of uric acid
- Urate cystals deposited in joint (tophi)
Acute gout: deposition stimualtes acute inflammatory reaction
Chronic gout: tophi formation
Clinical features: Acute onset (<24 hours), swelling, erythema, tenderness of involved joint, big toe
Investigations:
- Synovium fluid aspirate: negatively birefringent
needle shaped crystals on polarised microscope
- Urate levels
X-ray
Primary - hyperuricaemia due to genetic predisposition e.g. Lesch Nyhan syndrome
Secondary - high uric acid due to myeloproliferative disorder, thiazides, chronic renal disease
Risk factors: obesity, age, alcohol, diabetes, HTN, diuretics
Management
Short term:
NSAIDs
Cholchicine (inhibits IL-1, chemotactic factor. Statins should be stopped)
Corticosteroids
Long-term:
Lifestyle factors (though not enough)
Urate lowering therapy:
Allopurinol (xanthine oxidase inhibitor - reduces production of uric acid)
Risks: SJS/TEN, hepatitis, vasculitis
Rasburicase (recombiant uric oxidase - metabolises urc acid in blood)
- effective but risk of anaphylaxis with repeated doses
Crystal arthropathy - pseudo gout
Deposition of calcium pyrophosphate
Synvoium (pseudo gout)
Cartilage (chondrocalcinosis)
Clinical features: Acute onset (<24 hours), swelling, erythema of joint
Acute (acute inflammatory arthritis) or Chronic (mimics OA or RA)
Primary or secondary (hyperparathyroidism and haemochromatosis)
Investigations
Aspiration: positively birefringent rhomboid shaped crystals
X-ray
Serum calcium and parathyroid hormone
Management
NSAIDs
Colchicine
Intra-articular joint corticosteroids
Joint aspiration (reduce pain and swelling)
Reactive arthritis
Defintion: Sterile, inflammatory arthritis that occurs after infections, usually GI or genitourinary
- Salmonella, Shigella, Chlamydia trachomatis
Clinical features: Onset days/weeks post infection, asymmetrical lower limb arthritis
Assoc. symptoms:
Classic triad (not needed for diagnosis): conjunctivitis, non-gonococcal urethritis, post infectious arthritis (can’t see, pee or climb a tree)
Risk factors:
Male, HLA-B27, previous GI or chlamydial infection
Signs:
- Dactylitis (swollen digits)
- Enthesitis (inflammation of entheses - where tendons insert into bone)
- Keratoderma blenorrhagica (“blenno: mucousy, “rrhagia” discharge) - yellow, waxy lesion usually on palms, soles
Complications
- Aortic regurgitation, aortitis
Management
- Usually self-limiiting (can last up to 6 mnths)
- NSAIDs
- Intra-articular steroids
Enteropathic (IBD) arthritis
Form of reactive synovitis that’s assoc with IBD
Asymmetrical lower limb arthritis. enthesitis
Treatment
- Treat bowel disease
- NSAIDs
Definition, Presentation, Risk factors, Investigations, Treatment of OA vs RA
Definition: Degnerative joint disease characterised by loss of articular cartilage
Commonest form of arthritis
Risk factors: female, age (more common in elderly), obesity
Primary: Wear and tear
Secondary: Trauma, avascular necrosis, other arthropathies e.g. RA, Paget’s disease, haemachromotosis
Pathophysiology:
Loss of balance between cartilage production and breakdown causing loss of articular cartilage and:
- irregular cartilage surface
- articulation of bone on bone causing thickening of subarticular bone (eburnation)
- ostephytes forms - due to bone trying to repair itself producing cartilagenous outgrowths which calcifiy
- loss of joint space leading to deformity
- immbolity of joint
Macroscopically: loss of articular cartilage with eburantion of surface, subarticular cysts, osoteophytes, sclerosis (thickening of subchondral bone)
Clinical presentation: characterised by joint pain, stiffness (morning <30 mins) and loss of function, usually hip or knee
Clinical examination: pain (worse on movement, better with rest) muscle wasting, limited ROM, joint deformity, antalgic gait
Investigations
X-Ray: Joint space narrowing, osteophytes, subchondral sclerosis, bony cysts
(Subarticular cysts due to raised intraarticular cysts)
Synvoium becomes hyperplastic, mild inflammation, bony detritus (broken down material)
Bloods:
FBC (normal), CRP/ESR (normal) , RF/Anti-CCP (negative), Ca2+, phosphate, Alk phos (normal)
Secondary OA due to gout - high levels uric acid, or due to Paget’s - high Alk Phos
Treatment:
Analgesics
Physiotherapy
Reducing load - weight loss, walking stick
Surgical:
- arthrodesis (fusion of bones. Considered in young pts where joint replacement would be expected to fail as demands are higher)
- joint replacement (weigh up benefits of pain relief and improved function, against risks of surgery)
- excision arthroplasty (affected jointis removed and space is filled with fibrous tissue)
RA
Definition:
Multisystem autoimmune disease characterised by chronic, symmetrical polyarthritis
Risk factors:
HLA-DR4, smoking, infections (TB, EBV), hormones
Affects 1% population, usually middle aged, female 3:1
Pathophysiology:
- IgM and IgA directed against Fc portion of IgG - forms large immune complexes. Synovitis occurs, immune cells (macrophages, T cells, plasma cells) invade normally acellular synovium. Immune cells secrete cytokines which activate enzymes in synovium.
Pannus (tissue made of fibrous vascular connective tissue) is formed which destroys cartilage and bone.
Clinical features:
Synovitis of any joint, symmetrical, PIP joints of fingers, wrists, elbows, knees, morning stiffness (>30mins) - better as day goes on
- Pain, erythema, swelling, fatigue, weight loss
Late signs:
Boutonniere deformity joints nearest knucle (PIP) flexion (bent towards palm) and DIP hyperextension (bent away))
Swan neck deformity
Extra-articular features:
- lungs: pleural effiusions (due to inflammation and rubbing)
- cardiac: pericarditis, vasculitis
- skin: rhematoid nodule
- Felty’s syndrome (triad of RA, splenomegaly, neutropenia)
- higher risk of malignancy (as chronic inflammation leads to higher cell turnover)
Invstigations:
Bloods - FBC (low HB)
Blood film:
- normocytic normochromic anaemia of chronic disease
- pts who take NSAIDs can have IDA from upper GI bleeding
- pts with Felty’s syndrome (RA+spenomegaly) can have haemolytic anaemia
ESR/CRP (high)
LFT (elevated Alk phos. gamma GT during acute flare ups)
ANA (exclude SLE, may be postive in 20% RA pts)
RF (IgM against Fc portion of IgG) - 70% sensitive
Anti-CCP (anti-cyclic citrullinated peptide) - more sen and specific
Complement (normal. Exclude SLE, vasculitis)
Immunuglobulins: increased IgA and IgG but normal IgM
Xray (LESS): loss of joint space, erosions, soft tissue swelling, soft bone (osteopenia)
US
MRI: bone marrow oedema
DAS-28 (disease activity score) in 28 joints
Treatments:
NSAIDs: symptomatic
1nd line: DMARDS - sulfasalazine, methotrexate
Corticosteroids
Biologics: anti-TNF (infliximab), Anti CD20 (B cell) (rituximab)), Anti-IL6 (tociluzumab), anti CTLA4 ((T cell) (Abatacept)
Physio: maintains movement, prevents muscle atrophy
OT: adaption to pt’s lifestyle and housing improves long-term outlook
Podiatry: shoe wear alteration, good feet hygeiene as feet almost always involved
Surgical:
tendon repair
joint replacement - esp for knee
joint fusion - ankles and wrist (last resort)
Tendinopathy
General term that describes tendon degeneration characterised by pain, swelling, impaired performance
Tendinitis (inflammation of tendon)
Tendinosis (degenerative)
Tenosynovitis (inflammation of tendon sheath)
Tendinopathy can also be:
Insertional (damage where tendon attaches to bone)
Non-insertional (damage to damage itself)
What is a tendon, what does it do?
- Attaches muscle to bone
- Transmits force from muscle to to achieve movement
- Made up mostly of parallel collagen fibres with tenocytes. Surrounded by paratenon (e.g. achilles tendon) or tendon sheath (e.g. fingers)
- Mostly avascular, receives nutrition from tendon sheath/paratenon. So slow to heal.
Pathologyof tedinopathy
Repetitive loading/over use leads to chronic tendon injury: - Degeneration and disorganisation of collagen fibres
- Increased vasuclarity around tendon (as body tried to heal it)
- Increased cellularity
- Little inflammation
- Inflammatory mediators released - NO, prostoglandins, IL-1 which causes pain, degeneration by release of matrix mellanoproteinases
- Failed healing mechanisms in repsonse to micro damage
Risk factors of tendinopathy
Age, chronic disease, diabetes, RA, repetitive exercise, quinolones (ciprofloxacin)
Common tendinopathies
Achilles tedinopathy
Tennis elbow (lateral epicondylitis)
Golfers elbow (medial epicondylitis)
Clinical features of tedinopathy
Pain
Swelling
Thickening of tendon
Tenderness
Provocative tests - pain elciited, when ask pt to contract muscle
Diagnosis of tedinopathy
Ultrasound (can see shape of tendon, neovascularisation)
MRI (tedinopathy best seen on T1 weighted MRI)
Management of tedinopathy
Non-operative
NSAIDs
Physiotherapy - eccentric loading (contract of musculotedinous junction whilst it elongates)
GTN patches - vasodilator (increases local perfusion)
PRP (plalelet rich plasma) injections
Prolotherapy - inject irritant (dextrose) to stimulate a bit of damage, which stimulateshealing
Extracoporeal shockwave therapy - breaks down calcifcation, and causes little areas of trauma to stimualate healing
Steroid inejections
Operative treatment
Debridement - excise diseased tissue. Can debride 50% without loss of function.
Compartment syndrome: definition
Increased interstitial pressure in a closed fascial compartment leading to decreased perfusion of tissue
- Leg, forearm, thigh
- Orthopeadic emergency (loss of function/life)
Causes of compartment syndrome
Increased interstitial pressure:
- trauam: bleeding
- muscle oedema
- administration drugs/fluids
Increased external compression:
- Impaired conciousness (loss of protective reflexes e..g moving aorund)
- Positioning in theatre - lithotomy
- Bandaging
Pathophysiology of compartment syndrome
- Pressure in compartment beomes greater than the pressure in capillaries
- Leads to decreased blood flow, muscles become ischaemic and develop oedema (through increased endothelial permeability) - leads pressure
- Necrosis starts after 4 hours of muscles being ischaemic, and myoglobin released (toxic esp. to kindeys)
- Ischaemic nerves become neuropraxic (blockage of nerve conduction )
- Loss of function
Increased pressure leads to reduced blood flow due to Local Blood Flow (LBF)=(Pa-Pv)/R
(difference between between arterial and venous pressure, divided by peripheral resistance)
leading to reduced tissue perfusion
Clinical significance of timely management of compartment syndrome
1 hr - muscle viable, nerve conduction normal
4 hrs - muscle ischaemia (reversible) neuropraxis in nerves (reversible)
8hrs - muscle necrosis, nerve axonotmesis (damage to axon, irreversible)
End-stage
- Stiff, fibrotic muscle compartments
- Nerve damage
- Clawing of limbs
- Loss of function
Clinical features of compartment syndrome
Pain - out of proportion to injury
- Pallor
- Parathesia
- Pulselessness
- Paralysis
- Pershingly cold
Diagnosis compartment syndrome
Mostly clinical diagnosis
Site: Leg, forearm, thigh
- Swelling, shiny skin, autonomic repsonses (tachycardia)
If patient has impaired consiousness:
- compartment pressure measurement: Compare compartment pressure (CP) to diastolic BP: if <30mmHg than it is diagnostic, or if CP alone is >30mmHg
Management compartment syndrome
Open restricting bandages
Peri-operative:
- fluids, monitor electrolytes, correct acidosis, renal function
Surgical release - decompression across all compartments, excise dead muscle, wound closure/skin graft
Describe the normal function and structure of bone
Function: Movement, protection, support, stores Ca and phosphate
Structure:
Cortical bone (compact/tubular):
- Outer layer
- Slow turnover rate/metabolic activity
- High Young’s modulus (resistane to tension and bending)
Cancellous bone (spongy/trabeculae):
- Fills centre of bone
- Higher turnover rate, undergoes remodelling
- Lower Young’s Modulus
Anatomy of bone
Diaphysis - main shaft
Epiphysis - ends of the bone
Metaphysis - between diaphysis and epiphysis
Physis (growth plate): feature of children’s bones
- repsonsible for skeletal growth, allows remodelling after fracture, blood supply to physis damaged then will lead to stopping growth
Understand the process of indirect and direct bone healing
Indirect bone healing (secondary, via callus formation) - formation of bone via callus formation to restore skeletal continuity
- IRR (inflammation, repair and remodelling)
1. Fracture haematoma and inflammation (6-8 hours after)
- Blood (from broken blood vessel) forms clot
- Swelling and inflammation occur.
2. Fibrocartilage (soft) callus (lasts 3 weeks)
- New capillaries allow haematoma to become granulation tissue (procallus)
- Fibrobalsts form collagen, which join ends together
- Chrondroblasts form fibrocartilage
3. Bony (hard) callus (lasts 3 months)
- Osteoblasts form woven bone
4. Bone remodelling
- Osteoclasts remodel woven bone into coritcal and spongy bone
- No fracture line on X-ray
Direct bone healing (primary)
- Artifical surgical situation
- Direct formation of bone, without callus formation to restore skeletal continuity
- No callus formed
- Lead by formation of cutting cones (osteoclasts at front (resorption) followed by osteoblasts to lay down new bone
- Leads to formation of osteons
Bone blood supply
- Bone must have blood supply to heal
- Endosteal (nutrient artery) supplies inner 2/3rds
- Periosteal supplies outer 1/3rd
Understand factors which compromise blood supply to bone
Surgical factors (iatrogenic)
Anatomical factors
- some fractures are prone to necrosis due to problems in blood supply
e. g. proximal pole of scaphoid, talar neck, intracapsular hip, surgical neck of humerus fractures
Patient factors
- Age, diabetes, hypothyroidism, malnutrition
Medication
- NSAIDs (esp. those that inhibit COX2)
- Steroids
- Bisphosphonates (inhibits osteoclast activity. Delays fracture healing)
Composition of bone
ECM and cells (osteoprogenitor cells, osteocytes, osteoblasts, osteoclasts)
ECM is organic (40%) and non-organic salts (60%
Organic: collagen I
Non-organic salts: hydroxyapatite crystals (Ca and phosphate)
Know the types of tumours which affect the bones and their demographics
Primary bone tumours: rare
- Myeloma: commonest primary bone tumour
Secondary bone tumours: common
- Metastatic carcinoma: lung, prostate, thyroid (follicular) kidney, breast (LP Thomas Knows Best)
- Childhood: neuroblastoma, rhabdomyosarcoma
Long bones, vertebrae usually affected as have good blood supply
The clinical presentation of bone tumours and their management
Effects of metastases:
- Often aysmptomatic
- Bone pain
- Bone destruction
- Pathological fractures
Spinal metastases: vertebral collpase, spinal cord compression, nerve root compression
- hypercalcaemia
Management:
PET-CT: Anatomical and metabolic data
Differentials of acute hot joint
- Septic arthritis
- Crystal arthropathy
- Trauma
- Early presentation of polyarthropathy e.g. RA
Histology of bone
(A) Compact bone organised into osteons (Haverisan systems) - concentric lamellae (rings of calcified matrix where osteocytes are embedded in)
(B) Spongy bone: Arranged in trabeculae, with spaces between filled with bone marrow. White spaces is meduallary cavity (haemapoeitc marrow)
(D) Immature osteoprogenitor cells forms osteoblasts (mononuclear) which form osteoid
Osteoclasts (multi nucleated giant cells)
2 different types of metastasis
Lytic (bone is destroyed) or sclerotic
Lytic:
More common e.g. in lung cancer
Tumour activates cyotkines which activate osteoclasts
Inhibited by bisphosphonates
Sclerotic:
New bone is formed due to tumour cells
e.g. prostate, breast
looks whiter (sclerotic) on Xray
Solitary bone metastases
Renal and thyroid carcinomas
Often long survival as can be surgically removed
Myeloma
Commonest malignant primary bone tumour
Monoclonal proliferation of plasma cells
Plasmacytoma (single tumour) or multiple myeloma
Clnical effects:
CRAB
hyperCalcaemia
Renal infsufficiency
Anaemia (Pancytopenia ((as occurs in bone marrow) - Anaemia, leucopenia (decreased WBCs) and thrombocytopenia (decreased platelets)
Bone Lytic lesions
Diagnosis:
Immunoglobulin excess
- Increased CRP
- Urine/Serum electrophoresis - monoclonal band
- Immunoglobulin light chain (normally have both kappa and lambda light chains produced. In myeloma, only one type of light chain is produced)
FBC: normocytic normochromic anaemia
Ca2+
Bone marrow aspirate and biopsy: plasma cell infiltrate >10%
Histology myeloma
Sheets of malignant plasma cells (nucleus that looks like clockface, clear cytoplasm (Hoff), variation in nuclear size)
Primary bone tumours
Benign
- Osteoid osteoma
- Enchrondroma
- Osteocartilagenous exostosis
Malignant
- Osteosarcoma
- Chrondrosarcoma
- Ewing’s tumour
Osteoid osteoma
Benign tumour of osteoblasts surrounded by rim of reactive bone
Common in adolescnece
Any bone esp. diaphysis of long bones
If tumours near joint (juxta-articular tumours) - sympathetic synovitis
Presentation: Pain worse at night, relieved by aspirin
Radiology: nidus (network of osteoblasts, woven bone) surrounded by sclerotic bone
Osteosarcoma
Malignant proliferation of osteoblasts
Metaphysis of long bone
- Teenagers, or less commonly elderly
Presentation: pain, swelling, inability to move limb
Natural history:
Aggressive
Commonly metastasise to lungs
Risk factors: Paget’s disease of bone
Paget’s disease
Type of osteosarcoma
- Excessive bone turnover
- Increased osteoclasts, body tried to compensate by increasing osteoblast activity, so weak bone formed
- vertebrae, pelvis, skull
- usually lytic
- common in elderly
Clinical features: bone pain, deformity, bowing of legs, pathological fractures, high cardiac output failure (as lots of blood goes to the bones)
Enchondroma
Benign tumour of cartilage, usually arises in medulla
Mostly in hands and feet, long bones
Usually asymptomatic in long bones
Hands - swelling, pathological fracture
Osteocartilagenous exostosis (osteochondroma)
Most common benign tumour of bone
Benign outgrowth of cartilage on surface of bone
Common in adolescence
Arises from lateral projection of from growth plate
Complications:
- In Multiple diaphyseal aclasis (AD form) - multiple tumours, can form into malignant chondrosarcoma in cartilage cap
Chondrosarcoma
De novo (primary) or from endochondroma or exostosis (secondary)
Malignant cartilage forming tumour, usually arises in medulla
Mostly middle aged/elderly
Shoulder girdle, ribs, pelvis
Better prognosis than osteosarcoma
Management:
Surgery, not chemo/radiotherapy
Ewings sarcoma
Malignant proliferation of poorly differentiated cells derived from neuroectoderm (small, round, blue cell tumour)
Children
Long bones (Diaphysis), pelvis
Early metastases to lungs, bone marrow
Repsonds well to chemo/radio
Investigations:
Stain: CD99
Molecular genetics/karyotyping: chromosomal translocation 11:22
Management:
Chemotherapy/radiotherapy
Describe the vasculitides by vessel size and immune-pathology
Primary vasculitidies - group of autoimmune disorders characterised by inflammation of blood vessels
- Normally blood vessels of skin, nerves, kidneys, lungs
Classified by vessel size:
Large vessel vasculitis e.g. Temporal Giant cell arteritis, Takayasu arteritis
Medium vessel vasculitis e.g. Kawasaki disease, polyarteritis nodosa
ANCA-associated small vessel vasculitis e.g.
Granulomatosis with polyangiitis (GPA), Microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis (Churg Strauss)
Immune complex small vessel vasculitis e.g. IgA vasculitis (Henoch-Schonlein pupura)
Giant cell artertitis
Systemic vasculitis that affects aorta and major branches
>50 years old.
More common in females, caucasians
Clinical presentation: subacute temporal headache, visual symptoms (due to ischaemia of optic nerves), jaw claudication (pain upon chewing), polymyalgia rheumatica (pain and stiffness of msucles esp. shoudlers and hip)
Clinical examination findings:
Thickening and loss of pulse of temporal artery
Complications:
Blindness, vascular aneuryms, CVA
Investigations:
ESR (increased)
Temporal artery biopsy (TAB):
- gold standard for diagnosis
- Infiltration of mononuclear cells (macropahges, lymphocytes) into vessel wall. Granulotamous inflammation. Multinucleated giant cells seen but absence doesn’t exlcude a diagnosis
Affects arteries segmentally - skip lesions, so requires long sample of blood vessel
Temporal artery ultrasound
MRI
PET-CT
Management:
Start corticosteroids if clinical suspiscion, dont wait for investigations (due to risk of visual loss)
Prednisolone for 1 month
Methylprednisolone (if visual symptoms)
Aspirin
Corticosteroid sparing therapy in pts with relapse:
- Methotrexate
- Tocilizumab (IL-6 inhibitor)
Cutaenous vasculitis
Small vessel vasculitis
Pathology: leukocytoclastic (damage due to infiltrating neutrophils) vasculitis
Differentials:
Drugs, infection (HCV, HBV), secondary RA, malignancy,
- Henoch Schonlein pupura is a subtype of cutaneous vasculitis
Henoch Schonlein pupura (IgA vasculitis)
Small vessel vasculitis due to IgA complex deposition
- Most common vasculitis in children, most under 10
- Triggered by streptococcal sore throat
- Usually self-limiting
Presentation - characterised by 4 features: pupuric (non-blanching), abdominal pain, arthritis, glomerulonephritis
Complications: GI bleeding, IgA nephropathy
Investigations
- Exclude secondary causes - history, examination, immunology (RF, ANA, ANCA), virology (Hep B/C)
- Urinalysis (assess renal involvement)
Treatment:
Self limiting
- Analgesics
- Corticosteroids complications e.g. abdominal pain, testicular torsion
Granulomatosis with polyangiitis (Wegener’s granulomatosis)
ANCA-associated small vessel vasculitis
Characterised by granulotamous necrotising inflammatory lesions involving upper (nasopharyngeal) and lower respiratory tract, kidneys
Presentation: Classical triad of upper (sinusitis otitis media )and lower respiratory tract (haemoptysis, lung nodules) and pauci-immune glomerulonephritis (haematuria)
- Constitutional symptoms: fever, weight loss, fatigue
Other symptoms:
Conjuctivitus, ulcers in oral mucosa, pupura
Investigations
ANCA (anti-neutrophil cytoplasmic antibodies) : tested by 2 methods -
- indirect immunofluorescence: p or cANCA staining pattern (cytoplasmic or peri-nuclear anit-neutrophil cytoplasmic anitbody)
- ELISA: proteinase 3 (PR3) or myeloperoxidase antigens (MPO)
cANCA + PR3: Granulomatosis with polyangiitis
pANCA + MPO: MPA (microscopic polyangiitis) or Churg Strauss syndrome
Postive ANCA by indirect immunofluorescence but -ve PR3/MPO ELISA - no significance
Management
- Prednisolone AND
Severe disease: rituximab (anti- B cell biologic)
Moderate disease: Methotrexate
Remission maitenance: methotrexate, azothioprine
Clinical presentation of rheumatoid arthritis, its epidemiology and demographics
Chronic inflammatory condition, affects 1% population
- Usually 50s, female 3:1
Risk factors:
HLA-DR4, smoking, infection (TB), hormonal
Pathophysiology:
- Synovitis occurs, immune cells invade normally acellular synovium, forming pannus
Pannus (hyperplastic, invasive, granulation tissue) formation leads to breakdown of cartilage, erosions, reduced function
Clinical features:
Synovitis of any joint, symmetrical, usually hands and feet
- Pain, erythema, swelling, fatigue, weight loss
Late signs:
Boutonniere deformity (joints nearest knucle (PIP) bent towards palm whilst DIP is bent back)
Swan neck deformity
Extra-articular features: lungs e.g. pleural effiusions (due to inflammation and rubbing), cardiac e.g. pericarditis, vasculitis, higher risk of malignancy (as chronic inflammation leads to higher cell turnover)
Invstigations:
FBC, U&Es, LFT, ESR/CRP
- RF (autoantibody against Fc portion of IgG) - 60% sens, 80% spec
- anti-CCP (anti-cyclic citrullinated peptide) - 60% sens, 90% spec
Xray: soft tissue swelling, joint space narrowing, erosions
US
MRI: bone marrow oedema
DAS-28 (disease activity score) in 28 joints
Differential diagnosis of patients presenting with new inflammatory arthritis
OA
SLE
Psoriatic arthritis
Reactive arthritis
jUnderstand the relevant pharmacological management (DMARDS, steroids, NSAIDS and biologic drugs) monitoring requirements, screening and some side effects
Appreciate the range of MOA of the biologic drugs, special precautions, vaccination issues, malignancy and infection risks
1st line: DMARDS (and NSAIDs, corticosteroid)
Methotrexate (dihydrofolate reducatase inhibitor)
Side effects: GI upset, liver toxicity, BM supression
Contra-indicated: pregnancy, infection, antibiotics
- Sulfasalazine
- Anti-inflammtory effects
Side effects: GI upset, rash, bone marrow supression. Can be used in pregnancy.
Biologics
Anti-TNF: infliximab, entaracept,certolizumab (can be used in pregnancy)
- TB, infection risk, worsen MS symptoms
Anti CD20: rituximab
- Hypogammaglobulinaemia
Anti-IL6: tocilizumab
- Infections, high lipids
CTL4-Ig (comprises CTL4 linked with IgG): Abatacept (stops second signal needed for T cell activation)
JAK inhibitors: tofacitinib
Infections:
Increaseed risk e.g. TB, VZV
Vaccines:
- pts should be vaccinted against influenza and pneumococcal annually
Vaccines should be given before IL-6, CTLA4-Ig administered
Live vaccines avoided
X ray changes OA vs RA
OA:
(LOSS)
Loss of joint space
Osteophytes
Subchondral sclerosis
Subchondral cysts
RA:
(LESS)
Loss of joint space
Erosions
Soft tissue swelling
Soft bone (osteopenia)
Describe the presentation, pathology and management of OA
Presentation: pain, stiffness (esp. in morning), swelling, crepitus, deformity, nearby joint problems (e.g. hip OA can present with knee pain)
Pathology:
- Preotelytic breakdwon of cartilage due to increased production of enzymes e.g. matrix mellanoproteinases
- Proteoglycan and collagen fragments released into synovial fluid as disease progresses.
- Erosion to cartilage roughens surface of bone, and fibrillation narrows joint space
- Increased production of synovial mellanoproteinases, cytokines which diffuse back into cartilage to destroy soft tissue
Clinical Examination:
- General examination (include antalgic gait)
Systemic examination
Specific joint examintion (look/feel/move/special tests inc. leg length measurement)
Hip - pain on flexion and internal rotation, wasting of buttock muscles, limited ROM
Appreciate the clinical indications for joint replacement
Kellgren Lawrenece Stages of OA on radiographs
Stage 1 (Minor): If pt not predisposed to OA, no special treatment. Mainly weight loss, if obese will slow progression
Stage 2 (mild) - physiotherapy
Stage 3 (moderate) - NSAIDs, intra-articular steroid injections
Stage 4 (severe) - surgery: replacement (most common), realignment, excision, fusion
Understand the outcomes following joint replacement
Complications (total knee and hip replacement) - DVT/PE, infection, failure of procedure, revision
Specific to hip - dislocation, fracture, leg length discrepancy
Specific to knee - fracture, ligament or tendon damage
Presentation, diagnosis, investigation and management of SLE
Presentation:
Chronic multi-system autoimmune disorder, charcterised by deposition of antinuclear antibodies (autoanitbodies agianst nucleus) in tissues (skin, kidneys) leading to systemic inflammation.
- Mostly affects women in repdroductive years.
Most frequenlty affects skin, joints, kidneys.
Diagnosis:
ACR (American Collge of Rheumatology) critera: at least 4 criteria
Revised by SLICC requires: biopsy proven lupus nephritis with antinuclear antibodies or 4 classification with i clinical and 1 immunological.
Presentation:
Triad of fever, joint pain, and rash
Constiotional symtpms: fatigue, weight loss
Cutanous symptoms: butterfly shaped malar rash over cheeks and bridge of nose, discoid lupus (plaque-like rash that develops in sun exposed areas)
MSK symptoms: arthalgia (joint pain), arthritis (inflammatory), Jaccoud’s arthropathy (non-erosive, reversible conditions which occurs after bouts of arthritis)
Renal symptoms: Nephritic syndrome, Nephrotic syndrome
Resp: pleurisy, pleural effusions
Cardio: pericarditis, myocarditis, coronary heart disease
Avascular necrosis, fibromylagia, OP
Neuro: headache, anxiety
Gastro: dysphagia
Haemoatological: anaemia of chronic disease
Investigations:
Serum ANA (98% sesitive, but not specific)
ENA (extractable nuclear antibodies):
- Anti-dsDNA (confirms diagnosis SLE)
- Anti-Smith: (confirms diagnosis SLE)
- Anti-Ro and anti-LA: SLE, Sjogrens
Serum Complement (low due to activation of complement system)
Management:
- Hydroxychloroquine (1st line)
- Steroids
- Belimumab
Mild disease: topical therapies, sunblock for cuteanous symptoms
NSAIDs, IM steroids (MSK symptoms)
Moderate: treatment as mild+
- oral prednisolone, methotrexate, azothioprine, belumimab
Severe: treatment as mod+
- high dose steroid, cyclophosphamide (immuno suppressive), IV Ig (IV immunoglobulin), plasmapheresis
Adjunt therapy:
- Ca2+ blockers for Raynoads
- fatigue management groups
ENA (extractable nuclear antigens)
- Autoantibodies to these antibodies assoc with connective tissue disorders
Anti-dsDNA - SLE
Anti-smith - SLE
Anti-Ro/LA - SLE, Sjogrens
RNP - mixed CTD
Centromere - limited SScl (systemic sclerosis)
Scl-70 - diffuse SScl
Histone - drug induced lupus
Presentation, diagnosis, investigation and management of the systemic sclerosis (SScl) (scleroderma)
Multisystem autoimmune disease where fibroblasts are activated leads to deposition of collagen in tissues inc. blood vessels
- Usually middle aged females
Presentation: Raynaud’s phenomenon (most common), oedema of hands, thickened skin, ulcers on fingers
GI symptoms: dysphagia, malabsorption
Resp symptoms: pulmonary hypertension, respiratory failure
Investigations:
Serum ANA (90%)
Anti-DNA topoisomerase antibody
Centromere: limited SScl (systemic sclerosis)
Scl-70: diffuse SScl
FBC (microcytic anaemia, GI bleed), ESR/CRP, ECG (cardiac disease), CXR (lung disease)
Management:
Raynaud’s: Sidenafil (enothelin 1 receptor inhibitor) adjunct Ca+ channel blocker
Skin: Topical emoillient, corticosteroids, methotrexate
Presentation, diagnosis, investigation and management of myositis
Dermatomyositis: Chronic inflamation of skin and skeletal muscle with rash
In elderly, assoc. with malignancy e.g. gastric carcinoma
Clinical presentation
- painful, proximal muscle weakness,
- inflammation in muscle (biospy or MRI)
- elevation muscle enzymes
- characteristic EMG pattern
- Skin changes: rash of upper eyelids (heliotrope rash), malar rash, red papules on elbows
Investigations
Serum creatine kinase, myglobin (increased)
Serum ANA (90%)
Anti Jo-1 antibodies
ESR/CRP
EMG (muscle dysfunction)
Muscle biopsy (muscle necrosis)
Management
IV corticosteroids, adjunct creatinine
Polymyositis: chornic inflammation of skeletal muscles, doens’t involve skin
Presentation, diagnosis, investigation and management of Sjogren’s
Systemic autoimmune destruction of lacrimal and salivary glands. Lymphocyte mediated Type IV HS.
Presentation: dry eyes, mouth, throat, myalgias, arthalgias, renal disorders
Assoc. with RA
Investigations:
Schirmer’s test (quantitatively measures tears)
Anti-Ro and Anti-LA (Anti-Ro also in SLE)
Management:
Artificial tears
Ciclosporin eye drops (immunosuppressant)
Pilocarpine (Cholinergic drug - stimulates secretion of glands)
Drugs used in the treatment of vasculitis and the implications of these
Moderate:
- Mycophenolate (immunosuppressant)
Methotrexate
Risks: teratogen, hepatotoxicity
Severe:
- Cyclophosphamide (immunosuppressant)
Risks: infections, malignancy, infertility
- Rituximab (anti-B cell)
Risks: less risk of malignancy, no risk of infertility
Remission maintenance:
- Prevent relapse, lower drug toxicity, more prolonged therapy
- Methotrexate
- Azothioprine
Risks: BM supression, agranulocytosis
Describe common indications for immunosuppressant drugs and biologic therapies
Steroids are good immunosuppressants (rapid onset, easy to administer) however causes: weight gain, OP, hepatoxicity. Though does not cause BM suppression.
MOA: Binds to glucocorticoid receptors, activates anti-inflammatory transcription factors and inhibits pro-inflammatory transcription factors
Steroid sparing agents
Inhibitors DNA synthesis
- Methotrexate
- Azothoprine
Lymphocyte signalling inhibitors:
- Cyclosporin
- Tacrolimus
Biologics:
Therapeutic agents synthesised bioligcally rather than chemically
- Targets specific components of immune system, with minimal off-target effects
- Usually delivered parenteral
- Favourable side effect profile
Methotrexate
MOA:
Inhibits dihydrofolate reducatase (enzyme involved in tetrahydrofolate synthesis) and thymidylate synthetase - needed for DNA, RNA synthesis
- Leads to S-phase arrest in cell cycle
Indications:
1st line for RA. psoriatic arthritis
Giant cell ateritis
High dose: chemotherapeutic agent
Adverse effects: teratogen, hepatoxicity, BM suppression (increaed infections), pulmonary fibrosis
Clinical use:
Given once a week, with folic acid 4 days later
Normally orally
Pts need regular blood monitoring
Azathioprine
MOA: metabolised to 6-mercaptopurine which incoporates in DNA and RNA chains leading to termination of nucleic acid strands. Stops cell growth and metabolism
Preferential action on lymphocytes (as other cells have pruine salvage pathways)
Also inhibits T ell co-stimulation by interfering with CD28
Adverse effects: BM suppression (leukopenia, thrombocytopenia, increased infections), N&V, hepatitis
Clincal use:
- TPMT enzyme which reduces active metabolite (6-mercaptopurine). Without TPMT - accumulation of active metabolites causing severe toxicity
- Need to check TPMT acvitiy in pts (0.6% pts lack TPMT)
- Given orally
- Monitor bloods
Cyclosporin
Small molecule inhibitor of calicneurin, which leads to inhibition of signalling transduction from activated TCR. Leads to inhibition of T-cell activation
Indications:
Organ transplantation (liver, kidney)
Topically for skin, eye
Adverse effects:
Nephrotoxicity, Hypertension, Hepatotoxicity, does not cause BM suppression
Tacrolimus similar MOA, more potent
Clincal use:
- Given orally
- Drug interactions through CYP450
- Monitor bloods
Risks and common types of infection associated with these drugs
Immunosuppressants:
Effectiveness:
Not enough to control inflammatory disease if it progresses
Usually have slow rate onset, limiting use in acute severe conditions
Toxicity:
Even with low dose, has significant toxicities e.g. BM suppression, frequent infections
Biologics:
Adverse events:
Hypersensitivty, infusion reactions, mild GI toxicity
Infections not significantly higher than placebo
Infliximab (Anti-TNF): Increased risk of TB, salmonella, listeria (screen for latent TB)
Abatacept (AntiCD86 (T cell)): Increased risk of pneumonia, respiratory tract infections. Increased risk of TB but less than antiTNF
Rituximab (Anti-CD20 (B cell)): Increased generalised serious infections. Increased risk of Hep B (need to screen and prophylax)
Anti-IL1: increased of respiratory infections, pneumonia
Identify common fractures on X-Ray
Transverse: straight through bone
Oblique: oblque line through bone
Comminuted: more than 2 parts to fracture
Compound fracture: broken bone peirces skin
Angular fracture: Axis of bone displaced so distal pprtion of bone points at a diff direction
Overriding: proximal and distal fragments overlap
Intra-articular fractures vs Extra-articular fractures
Intra-articular fractures: fractures that involves a joint space, resulting in damage to cartilage. Higher risk of developing long term complications.
Extra-articular fractures: fracture outside of the joint
Supracondylar fractures
If fracture heals in deformed position (malunion) results in gunstock deformity (part of it is deviated towards midline)
Mostly in children
Complications:
Nerve injury - neuroprxis which resolves
Vascular injury - pulseless but pink hand
Femoral neck fracture
Are intracapsular fractures:
Subcapital - femoral head
Transcervical - midportion of femoral neck
Basicervical - base of femoral neck
Can cause disruption of blood supply to femoral head (avascular necrosis)
Paget’s disease
Blade of grass sign (candle flame appearence)
Characteristic of lytic phase of Paget’s
How arthritis Xray changes can be classified
Degenerative - Bone production
Inflammatory - Periarticular erosions
Depositional - Periarticular soft tissue masses
OA radiography
Primary degenerative arthritis
Intrinsic degeneration of articular cartilage
Excessive wear and tear
Commonly in hips and knees
X ray features: (LOSS)
Loss of joint space
Osteophytes
Subschondral sclerosois
Subchondral cysts
Hands:
DIP, PIP, 1st MCP joint (whereas RA in PIP or MCP)
More common in females
Secondary degenerative arthritis
Another process destorys articular catilage
Atypical location, appearence age
Causes: Trauma, infection, any arthritis esp. RA, avascular necrosis
RA with secondary OA
Loss of joint space
Mild subarticular sclerosis
No osteophytes
Calcium Pyrophosphate dihydrate deposition disease (CPPD)/Pseudo gout
Idiopathic or associated with hyperparathyroidism or haemochromatosis
Symmetrical
Similar to OA but unusual distribution:
Calcification of articular cartilage (chondrocalcinosis) in knee, hip, shoulder, symphysis pubis
Classification of inflammatory arthritis
Infective/septic arthritis
Sero-positive (RA)
Sero-negative:
- psoriatic arthritis
- reactive arthritis
Ankylosing spondylitis
IBD
Other connective tissue diseases
- SLE
- Systemic sclerosis
RA radiography
- Symmetrical
X ray findings: (LESS)
- loss of joint space
- erosion
- soft tissue swelling
- soft bone (osteopenia)
Others:
- MCP ulnar deviation (swelling of MCP joint causes deviation to ulnar (little finger) side
- MCP joint erosions
Sero-negative inflammatory arthropathies
Heterogenous group of conditions that are RF negative with overlapping clinical manifestations and assoc HLA B27
Differs from RA:
- normal bone density
- periositis (inflammtion of membrane covering bone)
- asymmetrical
- ankylosis (fusion)
Psoriatic, reactive, ankylosing spondylitis, IBD
Psoriatic arthritis
Both male and female, young adults
Skin and nail changes
DIP joints of hands>feet
- Pencil in cup defomity (erosions and bone resorption giving appearence of pencil in a cup)
X ray features of Ankylosing spondylitis
Chronic, progressive inflammatory arthropathy which presents as low back pain and spinal stiffness which leads to spinal fusion
More common in young males
Complications: uvetitis, aortic regurgitation
Pathology:
Spinal joints affected
Inflammation starts in lumbar vertebral and sacroiliac joints and extends up (symmetrical)
Pathology starts at entheses (where ligments, tendons insert) causing enthesiopathy
Xray:
Romanus lesions (erosions in anterior and posteior vertebral bodies)
Bamboo spine (vertebral body fusion)
Spinal fractures (as vertebrae is rigid and fused together, brittle, more likely to fracture)
Anatomy of synovial joint (6 points)
- Bones which make contact with each other covered by articular cartilage ( type II collagen)
- Joint surrounded by connective tissue capsule which encloses the 3. joint cavity (contains synovial fluid)
- Inner surface of capsule and non-articular surfaces of bone is lined with synovial membrane which secretes synovial fluid
- Capsule supporte by ligamens which stabilise joint
- Joint allows wide range of movement
Histology of OA vs RA
OA
Microscopically:
Fissuring, flaking then full thickeness loss of articular cartilage
Subarticular cysts
Osteophytes at joint margins
Subchondral sclerosis
Histology:
Increased water content
Alteration in proteoglycans, collagen, binding of proteins to hyaluronic acid
Rate of DNA, collgen, proteoglycan synthesis increased
Detritus synovitis - bone and cartilage broken off from damaged joint and embedd into synovium causing villous hyperplasia and inflammation
RA
Histology:
Villous hypertrophy
Hyperplasia of synoival lining
Fibrin exudate
Chronic inflmmation - aggregrates of lymphoid cells and plasma cells
When ultrasound, MRI, CT and DXA scanning are indicated for arthritis)
US:
- shows joint and surrouding soft tissue, mostly those located near surface of skin e.g. hands, use them to guide difficult joint injections
MRI:
- shows detailed picture of bone and surrounding tissue (cartilage, ligaments) detects joint damage esp. spine, synovitis, bony erosions
CT: more detailed for bone and soft tissue, bony erosions
MRI/CT indicated to see SC and patients with subluxation (atlanto-axial subluxation in RA)
DXA:
- detects bone mineral density.
Indicated:
- Detect risk of OP (RA has increased risk of OP)
- Condition that leads to low bone density e.g. RA
Occasions when interventional radiology may be required for MSK diseases
Arthrocentesis - joint aspiration guided by US
Features of mechanical back pain
Acute back pain: most resolves
Chronic back pain: >3 months. Most due to wear and tear but can be due to: cancers, medical emergencies, treatable conditions
Back pain = symptom
- (97%) Non specific lower back pain
- (3%) Radiculopathy, spinal stenosis, spondylolisthesis, cauda equina, compression fracture
Non-specific back pain:
Onset, any age
Worsens with movement or prolonged standing
Better with rest
Early morning stiffness <30 mins
Causes:
Lumbar strain
- Most common
- Muscle spasms settle within 24-48hrs
Degenerative discs (spondylosis):
- increase with flexion, sneezing
Disc prolapse:
- more localised
- increased with extension
Treatment:
Education, promote self management
Physiotherapy
Analgesics
Acupuncture
Causes of back pain
Mechanical:
- (97%) Non specific lower back pain
- (3%) Radiculopathy, spinal stenosis, spondylolisthesis, cauda equina, compression fracture
Systemic:
- infection (e.g. discitis - infection of vertebral disc, usually staph. aureus)
- malignancy (LP Thomas Knows Best - Lungs, Prostate, Thyroid, Kidneys Breast)
- inflammatory (mostly in teens, symptom not a diagnosis)
Referred (no pathology in back):
- Aortic aneurysm
- Acute pancreatitis
Mechnical back pain - radiculopathy
Disc prolapse: Herniated nucleus pulposus
May be acute
Usually leg
Straight leg raise +ve
Treatment:
Resolves within 12 wks
NSAIDs
Epidural cortiosteroid injections
<10% need surgery (helps leg, not back pain)
Mechanical back pain - spinal stenosis
Anatomical narrowing of spinal canal
Presents with claudication of legs (too little blood flow - cramp)
- Worse with walking, rest in flexed position
- Xray, MRI
Cauda equina syndrome
Back pain emergency
Compresison of SC nerve roots (below SC (L1/L2))
Neuropathic symptoms:
- Bilateral sciatica
- Saddle anaesthesia
Bladder/bowel dysfunction
- Reduced anal tone
Mechincal back pain - spondylolisthesis
Slipping of vertebrae, usually at base
Asymptomatic in most
Pain may radiate to post. thigh
Increase with extension
Mechanical back pain - compression fracture
Sudden onset, severe
“belt” around chest, abdomen
Assoc OP
Investigations: Xray, DEXA
Treatment: Analgesia, calcitonin, vetebroplasty (cement), kyphoplasty (balloon)
‘Red flags’ for sinister causes of back pain to diagnose serious back pathology
New onset aged <16 or >50
Previous malignancy
Recent serious infection
Fever, weight loss
After signfiicant trauma
IV drug abuse, immunosupressed
Urinary retention
Non-mechanical pain (Worse at rest/night)
Signs:
Saddle anaethesia
Reduced anal tone
Generalised neurological deficit
Yellow signs:
Attitudes, Beliefs, Compensation, Diagnosis
Features of mechanical vs inflammatory back disease
Mechanical:
>40 years
Acute onset
Morning stiffness <30 mins
Exercise worsens pain
Rest imrpoves pain
May improve at night (due to rest)
Inflammatory:
<40 years
Onset: Insiduous
Morning stiffness >30 mins
Exercise improves pain
No improvement
May wake during night
Define spondylolisthesis, spondylosis and spinal stenosis
Spondylosis: OA of spine, degernation of disc or facet joints
Spondylolisthesis: slipping of vertebrae
Spinal stenosis: Anatomical narrowing of spinal canal
Describe the relevant diagnostic tests and treatments for axial spondyloarthritis
Diagnosis
Symptoms: inflammatory back pain, fatigue, enthesitis, extra-articular inflammation e.g. psoriasis, uveitis
Imaging
HLA-B27
CRP/ESR (usually normal)
Treatment:
Education, exercise phsyio
NSAIDs, biologics (TNF inhibitors, IL-17A inhibitors)
Juvenile arthritis
Disease of childhood onset, characterised by arthritis persisting for more than 6 weeks, no known cause. It is a clinical diagnosis.
Subtypes:
Oligoarticular
Up to 4 joints, usually one
Polyarticular
RF positive polyarthritis (RA in adults)
RF -ve
Systemic onset:
Systemic features+arthritis
- hepatosplenomegaly, pericarditis
Enthesitis related arthritis (Alkylosing spondylitis in adults)
Juvenile psoriatic arthritis - dactylitis (swelling of one joint)
Kawasaki disease
Medium vessel vasculitis
<4 years, asian children
Fever, conjunctivitis
Erythematous rash on palms and soles, strawberry tongue, mucositis (lips peel)
Coronary artery involved so risk of aneursym formation and MI
Juvenile dermatomyositis
Cutaneous signs:
Heliotrope rash: telangectasia on eyelids, rash across bridge of nose
Gottron’s papules: pale, red lesions over PIP and MCP joints
Nail fold changes e.g. megacapillaries
Calcinosis
Complications: vasculitis ulcers
Juvenile SLE
Neuro symptoms: Headache, depression, cognitive impairment
Renal disease
Diagnosis: ANA
Localised scleroderma
Linear or morphea (several patches occur)
Morphea: Leisons on trunk, abdomen, proximal limb. have purple halo
Linear: localised. Occur distally, band of discoloured skin. Growth of joint may be restricted.
Locaised scleroderma en coup de sabre: linear scleroderma which involves face. Ptosis, cataracts, scarring alopecia.
Localised scleroderma Parry Romberg sydnrome:
Changes in skull, reduced tongue development
Osteonecrosis (avascular necrosis) - Clinical presentation, pathophys, risk factors
Infarction of bone near a joint
Leads to death of subchrondral bone and lead to joint collapse and arthritis
Most common in hip, then shoulder
Clinical presentation:
Limp, tenderness, limited ROM
Pts with osteonecrosis of femoral head present with groin pain that worsens with movement. Limitation in internal rotation, abduction.
Pathophysiology:
- Necrosis involves medullary bone
- Leads to empty lacunae which are surrounded by necrotic adipocytes which rupture and release fatty acids
- FAs can bind to calcium and form insoluble Ca2+ soaps
- necrotic cancellous bone collapses
Risk factors:
History trauma
Corticosteroid use
Alcohol
Sickle cell
Osteonecrosis imaging
Crescent sign (subchoondral radiolucenecy)
Subchondral collapse
Joint space narrowing
Bone remodelling
How does osteonecrosis cause arthritis?
If bone dies, does not remodel
So micro-damage doesn’t get repaired
Subchrondral bone weakens and collapses
Joitn surface becomes irregular, causing damage
Prostatic breast - sclerotic
Lung - lytic lesions
Kidey, thyroid - solitary bone mets
