Week 11 - Musculoskeletal Flashcards
1
Q
What is the purpose of a tendon?
A
Transmits force from muscle to achieve movement
2
Q
Describe the structure of a tendon?
A
- Parallel collagen fibrils with tenocytes
- Surrounded by paratenon / tendon sheath
3
Q
How does the tendon get its nutrition?
A
Largely avascular, nutrition via paratenon
4
Q
What are 3 results of chronic tendon injury over use (repetitive loading)?
A
- Degeneration, disorganisation of collagen fibres
- Increased cellularity
- Little inflammation
5
Q
Describe tendinopathy?
A
Loss of balance between micro damage from overuse & reparative mechanisms
6
Q
List 7 risk factors for tendinopathy?
A
- Age
- Chronic Disease
- Diabetes, Rheumatoid Arthritis
- Adverse Biomechanics
- Repetitive Exercise
- Recent increase in activity
- Quinolone Antibiotics
7
Q
Describe the pathology of tendinopathy?
A
- Deranged collagen fibres / Degeneration with a scarcity of inflammatory cells
- Increased vascularity around the tendon
- Failed healing response to micro tears
8
Q
List the 3 inflammatory mediators released in tendinopathy?
A
- IL-1
- Nitric Oxide
- Prostaglandins
9
Q
What do the released inflammatory mediators cause in tendinopathy?
A
- Apoptosis
- Pain
- Provoke degeneration through release of matrix metalloproteinas
10
Q
List 8 common tendinopathies?
A
- Achilles Tendinopathy
- Rotator cuff tendonitis
- Tennis Elbow (Lateral epicondylitis)
- Golfers Elbow (Medial epicondylitis)
- Patella Tendinopathy
- Hamstring tendonitis
- Adductor tendonitis
- Plantar fasciitis
11
Q
List the 5 clinical features of Tendinopathy?
A
- Pain
- Swelling
- Thickening
- Tenderness
- Provocative tests
12
Q
What are 3 ways to diagnose Tendinopathy?
A
- X-ray
- Ultrasound
- MRI- Tendinopathy best seen on T1
13
Q
List the 9 non-operative treatment for Tendinopathy?
A
- NSAID’s
- Activity modification
- Physiotherapy
- GTN patches
- PRP injection
- Prolotherapy- irritant injection, dextrose
- Extracorporeal Shockwave Therapy
- Topaz- radiofrequency coblation
- Steroid injection
14
Q
Describe the physiotherapy intervention for Tendinopathy?
A
- Eccentric loading
- Contraction of the musculotendinous unit whilst it elongates
- Beneficial in approx 80%
15
Q
Describe the GTN patch intervention for Tendinopathy?
A
- ¼ patch 125 mcg
- Vasodilator, Increases local perfusion
- Takes up to 12 weeks to see effects
16
Q
What is the side effect of GTN patch intervention for Tendinopathy?
A
Headaches
17
Q
Describe Extra Corporeal Shockwave Therapy for Tendinopathy?
A
- 3 weekly treatments
- Approx 75% improve
18
Q
Describe the operative treatment for Tendinopathy?
A
- Debridement
- Excision of diseased tissue
- Possible to debride 50% of tendon without loss of function
- Tendon transfers
19
Q
What is the outcome for Tendinopathy?
A
- Most will improve over time with activity modification
- Most non-operative measures improve symptoms in 70-80% over 1-2 years
- Surgical treatment effective in approx 80% if non-operative methods fail
20
Q
What is the definition of compartment syndrome?
A
Elevated interstitial pressure within a closed fascial compartment resulting in microvascular compromise
21
Q
What are the 3 common sites for compartment syndrome?
A
- Leg
- Forearm
- Thigh
22
Q
How severe is compartment syndrome?
A
Orthopaedic Emergency causing loss of function, limb or life
23
Q
Describe the pathophysiology of compartment syndrome?
A
- Pressure within the compartment exceeds pressure within the capillaries
- Reduced local blood flow
- Reduced tissue perfusion
24
Q
Describe the muscular effect of compartment syndrome?
A
- Muscles become ischemic & develop oedema through increased endothelial permeability
- Necrosis begins in the ischaemic muscles after 4 hours
25
What happens to the ischaemic nerves in compartment syndrome?
- Become neuropraxic
| - This may recover if relieved early, permanent damage may result after as little as 4 hours
26
What happens in late compartment syndrome?
Compromise of the arterial supply
27
What is the equation for Local Blood Flow (LBF)?
LBF = (Pa – Pv)/R
28
List the 6 pathophysiological outcomes for compartment syndrome?
1. Decreased perfusion
2. Muscle ischaemia & swelling
3. Increased permeability- fluid leaks into interstitial space
4. Increased pressure
5. Autoregulatory mechanisms overwhelmed
6. Muscle necrosis and myoglobin release
29
Describe the effect of 1hr ischaemia in compartment syndrome?
Nerve conduction normal, Muscle viable
30
Describe the effect of 4hr ischaemia in compartment syndrome?
- Neuropraxia in nerves, reversible
| - Reversible Muscle ischaemia
31
Describe the effect of 8hr ischaemia in compartment syndrome?
- Nerve axonotmesis & irreversible change
| - Irreversible muscle ischaemia & necrosis
32
List the 4 end stage features of compartment syndrome?
1. Stiff fibrotic muscle compartments
2. Impaired nerve function
3. Clawing of limbs
4. Loss of function
33
What are the 2 different causes of compartment syndrome?
1. Internal pressure
| 2. External compression
34
List the 5 types of internal pressure causing of compartment syndrome?
1. Trauma- fractures, entrapment
2. Bleeding
3. Muscle oedema / myositis
4. Intracompartmental administation of fluids / drugs
5. Re-perfusion- vascular surgery
35
List the 4 types of external compression causing compartment syndrome?
1. Impaired consciousness / protective reflexes (drug / alcohol misuse, Iatrogenic)
2. Positioning in theatre- lithotomy
3. Bandaging / casts
4. Full thickness burns
36
List the 6 clinical features of compartment syndrome?
1. Pain out of proportion to that expected from the injury
2. Pain on passive stretching of the compartment
3. Pallor
4. Parathesia
5. Paralysis
6. Pulselessness
37
List the 3 signs & symptoms of compartment syndrome?
1. Swelling
2. Shiny Skin
3. Autonomic Responses- sweating, tachycardia
38
Describe the pulses in compartment syndrome?
Pulses present (until late stages) unless associated vascular injury
39
What occurs later in compartment syndrome?
Parasthesia & paralysis as the deep nerves affected
40
How is the majority of compartment syndrome diagnosed?
Clinically
41
What is the normal & exercise compartment pressure?
- Normal pressure 0-4 mmHg
| - Exercise pressure 10mmHg
42
Describe the urgent treatment of compartment syndrome?
- Open any constricting dressings / bandages
- Reassess
- Surgical release
- Later wound closure
- Skin grafting / Plastic surgery input
43
Describe the surgical release in compartment syndrome?
- Full length decompression of all compartments
- Excise any dead muscle
- Leave wounds open
- Repeat debridement until pressure down & all dead muscle excised
44
How many compartments does the forearm have?
3 (extensor, flexor, mobile wad of three)
45
How many compartments does the leg have?
4 (deep posterior, anterior, lateral, superficial posterior)
46
How many compartments does the thigh have?
3 (anterior, adductor, posterior)
47
List the 6 peri-operative things to monitor/treat in compartment syndrome?
1. Adequate hydration
2. Fluid loss
3. Monitor & regulate electrolytes (K+)
4. Correct acidosis
5. Myoglobinuria
6. Renal function
48
Describe the 4 factors of a late compartment syndrome presentation diagnosis?
1. Irreversible damage already present
2. Fasciotomy will predispose to infection
3. Consider non-operative treatment
4. Splint in position of function
49
List the 4 signs & symptoms of septic arthritis?
1. Pain
2. Fever
3. Swollen joint
4. Loss of function
50
List 3 causative organisms of septic arthritis?
1. Staphylococcus aureus
2. Neisseria gonorrhoea
3. Haemophilus influenzae (children)
51
What 2 things give you an increased risk of septic arthritis?
1. Steroids
| 2. Rheumatoid arthritis
52
What are the 5 routes in which bacteria can reach the joint and cause septic arthritis?
1. Haematogenous
2. Dissemination from osteomyelitis
3. Spread from an adjacent soft tissue infection
4. Diagnostic or therapeutic measures
5. Penetrating damage by puncture or trauma
53
What are the 4 investigations for septic arthritis?
1. Joint aspirate- microbiology for gram stain & culture
2. Blood culture
3. FBC- leucocytosis
4. X-ray is of no value
54
Describe the synovium in septic arthritis?
Inflamed with fibrin exudation & numerous neutrophil polymorphs
55
How do you treat septic arthritis?
Antibiotics immediately IV
56
How can you get secondary osteoarthritis with septic arthritis?
When articular cartilage is lost
57
What is important in septic arthritis & why?
Tuberculosis- blood spread from focus elsewhere, usually spine (Potts disease), hip, knee, tubular bones of hands
58
What are 3 other specific types of septic arthritis?
1. Lyme disease- borrelia burgdoferi
2. Brucellosis
3. Syphilitic arthritis- congenital & acquired
59
What are the 2 types of crystal arthropathy?
1. Gout
| 2. Pseudogout
60
Describe crystal arthropathy?
- Excess levels of uric acid
| - Leads to deposition of urate crystals in joints or soft tissue (tophi)
61
Describe acute gout?
Precipitation in joint stimulates acute inflammatory process
62
What is the main factor of chronic gout?
Tophi formation
63
How is gout diagnosed?
By aspirate- negatively birefringent needle shaped crystals on polarized microscopy
64
What are 2 other tests you would do for gout?
Serum urate levels & U&Es
65
Describe primary gout?
Hyperuricaemia due to genetic predisposition eg Lesch-Nyhan syndrome
66
Describe secondary gout?
High uric acid due to myeloproliferative disorder (PCRV), leukaemia treated by chemo, thiazides, chronic renal disease
67
What is the general rule for uric acid levels?
Higher in older people, obesity, high alcohol consumption, high protein diet, diabetes mellitus
68
What is the main type of drug for managing gout?
NSAIDs- high doses rapidly reduce pain & swelling
69
What are 2 alternatives of NSAIDS for managing gout?
1. Colchicine
| 2. Corticosteroids
70
What are the 2 treatments if gout attacks are repeated?
1. Allopurinol- xanthine oxidase inhibitor
| 2. Uricosuric agent (probenecid)- increases secretion of uric acid into urine
71
Describe Pseudogout?
- Calcium pyrophosphate crystal deposition
- Synovium (pseudogout)
- Cartilage & extra-articular tissues (chondrocalcinosis)
72
What are the 2 different types of Pseudogout?
1. Acute or Chronic
| 2. Primary or Secondary (hyperparathyroidism, haemochromatosis)
73
Describe the appearance of Pseudogout on aspiration?
Positively birefringent rhomboid shaped crystals
74
What are 3 ways to manage Pseudogout?
1. Aspiration helps reduce the pain & swelling
2. NSAIDs
3. Colchicine
75
What is reactive arthritis?
- Sterile synovitis which occurs following an infection
| - Preceding illness usually a urethritis or diarrhoeal
76
List 4 trigger organisms for reactive arthritis?
1. Salmonella
2. Shigella
3. Yersinia
4. Chlamydia trachomatis
77
What is reactive arthritis associated with?
HLA B27 (75%)
78
Describe the clinical features of reactive arthritis?
- Acute, asymmetrical lower limb arthritis
- More common in men
- Days to weeks post infection
79
List 6 other clinical signs of reactive arthritis?
1. Enthesitis (eg plantar fasciitis)
2. Sacroiliitis
3. Spondylitis
4. Anterior uveitis
5. Conjunctivitis
6. Keratoderma blenorrhagica
80
How do you manage reactive arthritis?
- Little evidence that treating the triggering infection alters the course of the disease
- Pain control: NSAIDs, intra-articular steroids
81
Describe the prognosis of reactive arthritis?
- Usually self limited, lasts up to 6 months
| - May be chronic
82
What complication can occasionally occur in reactive arthritis?
Cardiac complications eg aortic regurgitation, aortitis & amyloidosis
83
What is Enteropathic arthritis?
Form of reactive synovitis seen in association with UC & Crohn’s disease
84
Describe the appearance of Enteropathic arthritis?
Asymmetrical lower limb arthritis
85
How do you treat Enteropathic arthritis?
Treatment of the bowel disease & NSAIDs
86
Describe Osteoarthritis?
- Degenerative joint disease
- Commonest form of arthritis
- Middle aged/elderly
- Weightbearing joints ie. hip, knee
87
Describe the pathology of osteoarthritis?
Disorder of articular cartilage
88
Describe primary generalised osteoarthritis?
Multiple joints, hands
89
Describe secondary osteoarthritis?
Fracture, previous sepsis, RA, osteonecrosis, CDH, steroids, chronic overuse, gout, haemochromatosis, ochronosis, peripheral neuropathy
90
List 4 X-ray features of osteoarthritis?
1. Loss of joint space
2. Osteophytes
3. Subchondral cysts
4. Subchondral Sclerosis
91
What are the 2 main clinical symptoms of osteoarthiris?
1. Pain
| 2. Stiffness
92
Describe the synovium in osteoarthritis?
Hyperplastic, mild inflammation, bony detritus
93
What is the diagnostic criteria used for septic arthritis?
- Kocher Criteria for SA hip in children
| - Modified Newman
94
Describe the 4 points of the Modified Newman criteria for septic arthritis?
1. Isolation of pathogenic organism from affected joint
2. Isolated of pathogenic organism from another source (blood) in context of a hot red joint suspicious of sepsis
3. Typical clinical features & turbid joint fluid in the presence of previous antibiotic treatment &
4. Postmortem/ pathological features suspicious of septic arthritis
95
List the 9 risk factors of septic arthritis?
1. Rheumatoid/OA & other inflammatory arthritides
2. Biologic disease-modifying anti-rheumatic drugs (bDMARDs)
3. Joint prosthesis/surgery
4. Low socioeconomic status
5. IV drug abuse
6. Alcoholic liver disease
7. Diabetes
8. Previous IA corticosteroid injection
9. Cutaneous infection/ulcers
96
What are 4 differentials for an acute hot joint?
1. Septic Arthritis
2. Crystal arthropathy
3. Trauma/Haemarthrosis
4. Early presentation of polyarthropathy (RA/PsA/AS/ReA)
97
What 4 populations have a higher risk of gram negative bacteria causing septic arthritis?
1. Children
2. Elderly
3. Immunocompromised
4. IV drug users
98
What increasing number of septic arthritis cases are there?
ESBL cases
99
How may <30 day arthroplasty be managed?
- Debridement
- Exchange of PE liners & prolonged IV antibiotics
- >1 month almost always need full explant to cure
100
What is the duration of antibiotics for treating septic arthritis?
- IV for up to 2 weeks or until signs improve
- Orally for 4 weeks
- If prosthetic joint, duration is usually longer (6+ weeks IV then oral suppressive therapy)
101
What are the medical & surgical treatments for septic arthritis?
1. Medical- closed needle aspirations
| 2. Surgical- arthrotomy, arthroscopy
102
Describe the triad in reactive arthritis (ReA)?
1. Post-infectious arthritis
2. Non-gonococcal urethritis
3. Conjunctivitis
103
What type of people are more prone to reactive arthritis & why?
20-40 year Caucasians, probably due to the higher HLA-B27 frequency
104
For gout management what is the serum uric acid (SUA) aim?
<300 using urate lowering therapy
105
What are the PROS & CONS of Febuxostat in gout management?
- PROS: can use in renal failure
| - CONS: more expensive than Allopurinol
106
What are the 2 side effects of Febuxostat (gout treatment)?
1. LFT abnormalities
| 2. Increased cardiovascular events
107
Give 3 examples of drugs used in the long term management of gout?
1. Allopurinol- Xanthine Oxidase inhibitor
2. Febuxostat- Xanthine Oxidase inhibitor
3. Rasburicase- recombinant urate oxidase given IV
108
What is the active metabolite in Allopurinol?
Oxypurinol, which is excreted renally
109
Describe Rasburicase in long term gout management?
Effective & rapid at lowering SUA, but limited by antigenicity & progressive risk of anaphylaxis esp with repeated doses
110
What are the 2 main functions of bone?
1. Structural- support, protection, movement
| 2. Mineral storage- calcium, phosphate
111
Describe cortical bone?
- Compact or tubular bone
- Slow turnover rate / metabolic activity
- Higher Young’s modulus & resistance to torsion & bending
112
What % of bone is made up of cortical bone?
80%
113
Describe cancellous bone?
- Spongy or trabecular bone
- Higher turnover rate & undergoes greater remodelling
- Lower Young’s modulus & is more elastic
114
What are the 2 types of bone matrix?
1. Organic (40%)
| 2. Inorganic (60%)
115
What are the 4 cells in bone?
1. Osteoprogenitor
2. Osteocyte
3. Osteoblast
4. Osteoclast
116
Describe the function of osteoblast bone cells?
Produce new bone under the influence of parathyroid hormone
117
Describe the function of osteocyte bone cells?
- 90% of the cells in mature bone
| - Maintain extracellular calcium levels
118
Describe the function of osteoclast bone cells?
Resorb bone
119
List the 6 chemicals present in the organic matrix of bone?
1. Collagen (mainly type I)
2. Mucopolysaccharides
3. Non-collagenous proteins
4. Proteoglycans
5. Growth factors
6. Cytokines
120
List the 2 chemicals present in the inorganic matrix of bone?
1. Calcium hydroxyapatite
| 2. Calcium phosphate
121
Describe the 3 part structure of bone?
1. Diaphysis (shaft)
2. Epiphysis (end)
3. Metaphysis (transitional flared area between diaphysis & epiphysis)
122
What is Physis?
- Unique feature of childrens’ bone
| - Responsible for skeletal growth
123
What does Physis allow for?
Remodelling of angular deformity after fracture
124
What will happen if the physeal blood supply is damaged?
Will lead to growth arrest (either partial or complete)
125
What are the 2 types of fracture healing?
1. Indirect healing (Secondary via callus formation)
| 2. Direct healing (Primary)
126
Describe the "fracture haematoma & inflammation" stage of indirect fracture healing?
- Blood from broken vessels forms a clot
- 6-8 hours after injury
- Swelling & inflammation to dead bone cells at fracture site
127
Describe the "Fibrocartilage (SOFT) callus" stage of indirect fracture healing?
- Lasts about 3 weeks
- New capillaries organise fracture hematoma into granulation tissue - ‘procallus’
- Fibroblasts & osteogenic cells invade procallus
- Make collagen fibres which connect ends together
- Chondrocytes begin to produce fibrocartilage
128
Describe the "Bony (HARD) callus" stage of indirect fracture healing?
- After 3 weeks & lasts about 3-4 months
| - Osteoblasts make woven bone
129
Describe the "Bone remodelling" stage of indirect fracture healing?
- Osteoclasts remodel woven bone into compact bone & trabecular bone
- Often no trace of fracture line on X-rays
130
What are the 4 stages of indirect fracture healing?
1. Haematoma +Inflammation
2. Soft Callus
3. Hard Callus
4. Remodelling
131
Describe direct fracture healing?
- Unique ‘artificial’ surgical situation
- ‘Direct formation of bone via osteoclastic absorption & osteoblastic formation, without the process of callus formation, to restore skeletal continuity’
132
What does direct fracture healing rely on?
Compression of the bone ends
133
Describe the strength of direct fracture healing?
Fracture stable with no movement under physiological load
134
What is the appearance of direct fracture healing?
- No callus
- Cutting cones cross fracture site
- Lay down new osteones directly
135
What must bones have in order to heal?
A blood supply
136
What are the 2 types of bone blood supply?
1. Endosteal- inner 2/3rds
| 2. Periosteal- outer 1/3rd
137
What are 2 ways bone blood supply can be injured?
1. Fracture
| 2. Surgery
138
List the 4 fractures what are prone to problems with union or necrosis (bone death) because of potential problems with blood supply?
1. Proximal pole of scaphoid fractures
2. Talar neck fractures
3. Intracapsular hip fractures
4. Surgical neck of humerus fractures
139
List 8 patient factors that leads to inhibition of fracture healing?
1. Increasing age
2. Diabetes
3. Anaemia
4. Malnutrition
5. Peripheral vascular disease
6. Hypothyroidism
7. Smoking
8. Alcohol
140
List 3 medications that lead to inhibition of fracture healing?
1. NSAIDs
2. Steroids
3. Bisphosphonates
141
Describe how NSAIDs can lead to inhibition of fracture healing?
- Reduce local vascularity at fracture site
- Reduction in healing effect independent of blood flow
- Mainly animal studies, some surgeons avoid use post-operatively
142
What type of NSAIDS inhibit fracture healing more?
COX 2 NSAIDS inhibit fracture healing more than non-specific NSAIDS
143
What is the magnitude of NSAID effect on fracture healing related to?
Duration of treatment
144
Describe how bisphosphonates inhibit fracture healing?
- Inhibit osteoclastic activity
- Delay fracture healing as a result
- Long half life
145
List 4 things that can be seen on radiographs?
1. Trauma
2. Arthritis
3. Congenital
4. Tumour
146
List 2 things seen on computed tomography (CT) ?
1. Bone detail
| 2. Complex fractures
147
List 5 things seen on Ultrasound (US)?
1. Small superficial lumps
2. Tendons
3. Joints
4. Ligaments
5. Synovitis
148
What is nuclear medicine & PET scanning good for detecting?
Cancer staging
149
What is Magnetic Resonance Imaging (MRI) good for assessing?
Gold standard for assessing diseases of joints, soft tissues, bones
150
What is DEXA scanning good for detecting/monitoring?
Osteoporosis
151
Give 3 examples of guided interventional procedures?
1. CT or US guided biopsy
2. Drainage
3. Radiofrequency ablation
152
Describe the different density and how anatomy is seen on Xray?
- Air= black
- Fat= dark grey
- Water (muscle)= grey
- Bone= white
153
List the 10 different types of fractures?
1. Displaced
2. Angulated
3. Rotated
4. Overriding
5. Distracted
6. Comminuted
7. Compound
8. Transverse
9. Oblique
10. Spiral
154
What are the 2 types of joint fractures?
1. Extra articular
| 2. Intra-articular
155
Describe the appearance of a supracondylar fracture on X-ray?
Malunion will result in the classic 'gunstock' deformity due to rotation or inadequate correction of medial collapse
156
What can posterolateral displacement of the of the distal fragment in a supracondylar fracture be associated with?
Injury to the neurovascular bundle which is displaced over the medial metaphyseal spike
157
Describe the prognosis of nerve injury due to a Supracondylar fracture?
Almost always results in neuropraxis that resolves in 3-4 months
158
Describe the appearance of vascular injury due to a Supracondylar fracture?
Usually results in a pulseless but pink hand
159
What sign needs exploration in a Supracondylar fracture?
Pulseless & white hand after reduction
160
What important structure is located around the supracondylar area?
Brachial artery which could result in a loss of blood supply to the distal forearm
161
What is the most common location for a femoral fracture?
Neck of femur
162
List 6 different femoral fractures?
1. Subcapital neck fracture
2. Transcervical neck fracture
3. Intertrochanteric fracture
4. Subtrochanteric fracture
5. Fracture of the greater trochanter
6. Fracture of the lesser trochanter
163
What 2 femoral fractures are at a risk of damaging the intracapsular vascular supply?
1. Subcapital neck fracture
| 2. Transcervical neck fracture
164
What is pathophysiology of Paget's disease of bone?
Increased bone turnover- osteoclastic & osteoblastic activity either monostotic or polyostotic
165
Describe the population most affected by Paget's disease of bone?
- Age >40 years
| - M>F
166
What is the aetiology of Paget's disease of bone?
- Unknown
- Viral?
- Racial predilection
167
What is raised in Paget's disease of bone?
Alkaline phosphatase (ALP)
168
What are the 2 complications of Paget's disease of bone?
1. Fracture deformity
| 2. Rarely sarcoma
169
What imaging sign is coherent with Paget's disease of bone?
Blade of grass sign- lucent leading edge in a long bone seen during the lytic phase
170
What can osteoarthritis look like on X ray?
Avascular necrosis
171
What is the hallmark for degenerative arthritis?
Bone production
172
What is the hallmark for inflammatory arthritis?
Periarticular erosions
173
What is the hallmark for depositional arthritis?
Periarticular soft tissue masses (gout & amyloid)
174
Give 3 examples of reactive bone formation?
1. Sub-chondral sclerosis
2. Osteophytosis
3. Periostitis
175
What are the 2 locations for bone erosions?
1. Peri-articular
| 2. Para-articular
176
What are the 2 appearances of bone erosions?
1. Ill-defined= active
| 2. Well defined= old
177
What are 2 symmetrical joint space narrowing signs?
1. Erosions
| 2. Soft tissue swelling
178
What are 2 asymmetrical joint space narrowing signs?
1. Osteophytes
| 2. Sclerosis
179
What are the 2 categories of Joint Space narrowing?
1. Inflammatory
| 2. Degenerative
180
Describe the 2 different types of inflammatory joint space narrowing?
- 1 Joint: infection
| - >1 Joints: Rheumatoid arthritis, seronegative spondyloarthropathy
181
Describe the 2 different types of degenerative joint space narrowing?
- Typical osteoarthritis
| - Atypical osteoarthritis: trauma, crystal depositions, neuropathic, haemophilia
182
What is Atypical osteoarthritis defined as?
Unusual distribution, severity or age
183
What is the distal signs of seronegative spondyloarthropathy?
Bony proliferation
184
What is the proximal signs of rheumatoid arthritis?
No bony proliferation
185
Describe Primary Degenerative Arthritis?
- Intrinsic degeneration of articular cartilage
| - Excessive wear and tear, commonly in hips & knees
186
What are the 3 X-ray features of Primary Degenerative Arthritis?
1. Narrowed joint space
2. Osteophytes
3. Subchondral sclerosis / cysts
187
Describe primary degenerative arthritis in the hands?
- DIP, PIP & 1ST MCP joints
- Sclerosis
- Marginal osteophytes
188
What is secondary degenerative arthritis?
Another process destroys articular cartilage
189
What are 3 ways to recognise secondary degenerative arthritis?
1. Atypical locations
2. Atypical appearance
3. Atypical age
190
What are 6 common causes of secondary degenerative arthritis?
1. Trauma
2. Infection
3. Avascular Necrosis
4. Calcium pyrophosphate dihydrate disease (CPPD)
5. Rheumatoid arthritis
6. Haemophilia
191
What are 4 uncommon causes of secondary degenerative arthritis?
1. Haemachromatosis
2. Acromegaly
3. Ochronosis
4. Wilson’s disease
192
What can any arthritis end up as?
Degenerative arthritis
193
What are 3 features of Rheumatoid Arthritis with secondary degenerative changes?
1. Loss of joint space
2. Mild subarticular sclerosis
3. Lack of osteophytes
194
What are the 2 causes of Calcium Pyrophosphate Dihydrate Deposition Disease (CPPD)?
1. Idiopathic
| 2. Associated with Hyperparathyroidism & Haemachromatosis
195
Describe the appearance of Calcium Pyrophosphate Dihydrate Deposition Disease (CPPD)?
- Symmetrical
- Similar to osteoarthritis but unusual distribution
- Calcification of articular cartilage (Chondrocalcinosis)
- Triangular fibrocartilage of wrist, knee, hip, shoulder & symphysis pubis
196
What are the 3 clinical signs & symptoms of Calcium Pyrophosphate Dihydrate Deposition Disease (CPPD)?
1. Sudden onset of pain / fever
2. Tender, swollen, red
3. May mimic septic arthritis
197
What are the 4 types of inflammatory arthritis?
1. Infection
2. Rheumatoid (seropositive) arthritis
3. Seronegative arthropathies
4. Other Connective tissue diseases
198
What are 4 examples of inflammatory Seronegative arthropathies?
1. Psoriatic arthritis
2. Reactive arthritis
3. Ankylosing spondylitis
4. Inflammatory bowel disease
199
What are 2 examples of connective tissue diseases causing inflammatory arthritis?
1. Systemic Sclerosis (scleroderma)
| 2. Systemic lupus erythematosis
200
What is infectious arthritis usually due to?
Staph, Strep, TB from local injury or surgery
201
Describe infectious arthritis?
- Destruction of cartilage & cortex
- Tends to affect 1 joint (monoarticular)
- Fingers from bites, Feet in diabetes
- Hips with total hip replacements
202
List 6 clinical signs of infectious arthritis?
1. Soft tissue swelling
2. Destruction of cartilage/bone
3. Rapid loss of joint space
4. +/- periosteal reaction
5. Osteoporosis
6. Later subluxation, OA, fusion
203
What is the normal duration of discitis?
1-3 weeks
204
List the 5 radiographic findings of discitis?
- End-plate erosion
- Disc space narrowing
- Bone destruction
- Paravertebral mass
- Ankylosis
205
What is a radiographic finding in LATE discitis?
Sclerosis
206
Who is more commonly affected by rheumatoid arthritis?
2F:1M, middle aged
207
What is rheumatoid arthritis?
Erosive arthropathy
208
List the 6 common skeletal locations affected by rheumatoid arthritis?
1. Hands
2. Feet
3. Elbows
4. Knees
5. Hips
6. Cervical spine
209
What does the newer classification of rheumatoid arthritis include?
Presence of bilateral wrist, MCP or PIP joint enhancement on MRI & leads to a more accurate diagnosis of early RA
210
List the 6 parts of the rheumatoid arthritis old criteria (4/6 needed for diagnosis)?
1. Morning stiffness
2. > 2 joints
3. Hand & wrist joints
4. Rh Nodules
5. RF positive
6. XR changes
211
What are the 9 clinical features of rheumatoid arthritis?
1. Hyperaemia
2. Soft tissue swelling
3. Synovitis
4. Effusion
5. Bone marrow oedema
6. Erosions, cysts
7. Joint space narrowing
8. Secondary degenerative changes
9. Loose bodies
212
What are the 2 types of MRI to show joint changes?
1. STIR (Short TI Inversion Recovery)
| 2. T1W contrast
213
What is better at showing joint changes- MRI or X-ray?
MRI
214
Describe the genetics of Sero-negative inflammatory arthropathies?
- Negative rheumatoid factor
| - Positive HLA-B27
215
In what 4 ways does Sero-negative inflammatory arthropathies differ from rheumatoid arthritis?
1. Normal bone density
2. Periostitis
3. Ankylosis (fusion)
4. Asymmetrical pattern
216
Who is more prone to Psoriatic arthritis?
- M = F
| - Young adults
217
Describe the features of psoriatic arthritis?
- Usually skin & nail changes
- DIP joints of hands>feet
- Pencil in cup deformity
- Resorption of distal phalanges
218
Who is more prone to reactive arthritis (Reiter's syndrome)?
- M > F
- 20 – 40yrs
- White > black
219
What are the 5 clinical signs/features of reactive arthritis (Reiter's syndrome)?
1. Urethritis
2. Arthritis (50%)
3. Conjunctivitis
4. Periostitis
5. Enthesopathy
220
What are 2 common skeletal locations for reactive arthritis (Reiter's syndrome)?
1. Lower limb
| 2. Sacroiliac joint
221
When does reactive arthritis (Reiter's syndrome) occur?
1-3 weeks after infection
222
Who is more prone to Ankylosing spondylitis?
- 3M:1F
| - 20-40yrs
223
What are the 6 clinical signs/features of Ankylosing spondylitis?
1. Low back pain
2. Stiffness
3. Bilateral sacro-iliitis- symmetrical
4. Squaring of vertebral bodies
5. Bamboo spine
6. Peripheral large joint arthritis
224
What is the positive genetic factor for Ankylosing spondylitis?
HLA B27 +ve
225
What are the 3 main spinal features of Ankylosing spondylitis?
1. Romanus lesions
2. Bamboo spine
3. Spinal fractures
226
Who is more prone to gout?
- Elderly males
| - Hereditary
227
List the 3 clinical features of gout?
1. Olecranon bursitis common
2. Para-articular erosions
3. Soft tissue mass
228
List 4 skeletal locations of gout?
1. 1st foot MTP joint
2. Knee
3. Hand
4. Elbow
229
List the 7 radiographic features of gout?
1. Para-articular erosions
2. Sharply marginated with sclerotic rims
3. Overhanging edges
4. No joint space narrowing till late
5. Little or no osteoporosis
6. Soft tissue swelling
7. Tophi not usually calcified
230
What 2 things should you suspect in a young person with gout?
1. Renal disease
| 2. Myeloproliferative disorder
231
What 4 things does crystal deposition in gout induce?
1. Inflammation
2. Idiopathic
3. Enzyme defects
4. Secondary to myeloproliferative disorders.
232
Describe the progression of gout?
Several years before X-ray changes occur, cartilage OK until late
233
What is rhyme for reactive arthritis (Reiter's syndrome)?
Can’t see, can’t pee and can’t climb a tree!
234
What are the 4 causes of reactive arthritis (Reiter's syndrome)?
1. Chlamydia
2. Salmonella
3. Shigella
4. UTI's
235
What 3 joint pathologies light up with MRI dye (T1W contrast, STIR)?
1. Bone marrow oedema
2. Soft tissue swelling
3. Erosion
236
What hand joints are typically affected in rheumatoid arthritis?
All of the joints apart from the distal joints
237
What are 3 types of bone tumours & how common are they?
1. Secondary tumours in bone: very common
2. Myeloma: commonest primary bone tumour
3. Primary bone tumours: rare
238
How common is secondary tumours in bone?
60% of patients dying of cancer
239
Give 5 locations of metastatic carcinomas causing secondary bone tumours?
1. Bronchus
2. Breast
3. Prostate
4. Kidney
5. Thyroid (follicular)
240
What are 2 childhood malignancies causing secondary bone tumours?
1. Neuroblastoma
| 2. Rhabdomyosarcoma
241
Which bones are more prone to tumours?
Those with good blood supply- long bones, vertebrae
242
What are the 6 effects of metastases?
1. Often asymptomatic
2. Bone pain
3. Bone destruction
4. Long bones: pathological fracture
5. Spinal metastases: vertebral collapse, spinal cord compression, nerve root compression, back pain
6. Hypercalcaemia
243
What is the benefit of combining PET & CT?
Anatomical detail can now be achieved as well as functional data
244
What are the 2 types of bone metastasis?
Lytic & Sclerotic
245
Describe the mechanism of bone destruction?
- Osteoclasts, not tumour cells
| - Stimulated by cytokines from tumour cells
246
What is bone destruction inhibited by?
Bisphosphonates
247
Where is sclerotic metastasis typically from in males & females?
- Males: prostate cancer
| - Females: breast cancer
248
What is the less common origin of sclerotic metastases?
Carcinoid tumour
249
What is the main feature of Sclerotic metastases?
Reactive new bone formation, induced by tumour cells
250
What are the 2 typical origins of solitary bone metastases?
Renal & thyroid carcinomas
251
What is the prognosis of solitary bone metastases?
- Often long survival
| - Surgical removal often valuable
252
Describe a Myeloma?
- Monoclonal proliferation of plasma cells
| - Solitary (plasmacytoma) or multiple myeloma
253
List the 3 clinical effects of Myelomas?
1. Bone lesions
2. Marrow replacement
3. Immunoglobulin excess
254
Describe the bone lesions seen in myelomas?
- Punched out lytic foci
| - Generalised osteopenia
255
What are 2 consequences of marrow replacement in myeloma?
1. Anaemia
| 2. Infections
256
Describe the immunoglobulin excess seen in myelomas?
- ESR > 100
- Serum electrophoresis: monoclonal band
- Urine: immunoglobulin light chains (Bence Jones protein)
257
What is the main histological feature of myelomas?
The light chains are a unbalanced ratio of either Kappa or Lambda
258
What are the 3 renal impairments caused by myeloma?
1. Myeloma kidney: precipitated light chains in renal tubules
2. Hypercalcaemia
3. Amyloidosis
259
What are the 4 consequences of marrow replacement in myelomas?
1. Complete pancytopenia
2. Anaemia
3. Leucopenia: infections
4. Thrombocytopenia: haemorrhage
260
Give 3 examples of benign primary bone tumours?
1. Osteoid osteoma
2. Chondroma
3. Giant cell tumour
261
Give 3 examples of malignant primary bone tumours?
1. Osteosarcoma
2. Chondrosarcoma
3. Ewing’s tumour
262
What are Osteoid osteoma's?
A small, benign osteoblastic proliferation
263
Describe the prevalence of Osteoid osteoma's?
- Common
- Any age especially adolescents
- M:F 2:1
264
What bones are affected in Osteoid osteoma's?
Any bone, especially long bones, spine
265
Describe the pain associated with Osteoid osteoma's?
- Worse at night
| - Relieved by aspirin
266
What clinical sign can Osteoid osteoma's cause?
Painful scoliosis
267
What is an osteosarcoma?
A malignant tumour whose cells form osteoid or bone
268
Who are more prone to osteosarcomas?
- Peak 10-25 years
| - 3M:2F
269
What is the common site for osteosarcomas?
- Metaphysis of long bones
| - 50% around knee
270
Describe the prognosis of osteosarcoma?
- 5 year survival: 15-20% pre-chemotherapy
| - Modern 5 year survival: 50-60%
271
Where can osteosarcomas spread to?
Early lung metastases
272
What is a bone sign of tumour?
Codman's triangle (raised periosteum from the bone)
273
Give 6 osteosarcoma variants that have a normal prognosis?
1. Osteoblastic
2. Chondroblastic
3. Fibroblastic
4. Telangiectatic
5. Small cell
6. Sclerotic
274
Give 3 osteosarcoma variants that have a worse prognosis?
1. Paget’s
2. Multifocal
3. Post-irradiation
275
Give 3 osteosarcoma variants that have a better prognosis?
1. Parosteal
2. Periosteal
3. Low grade central
276
Describe the bone in Paget's disease?
- Weak
| - Disorganised bone architecture
277
What 4 bones are commonly affected by Paget's disease?
1. Vertebrae
2. Pelvis
3. Skull
4. Femur
278
List the 7 consequences of Paget's disease?
1. Bone pain
2. Deformity- bowing of long bones
3. Pathological fracture
4. Osteoarthritis
5. Deafness (compressed 8th cranial nerve from thickened skull)
6. Spinal cord compression
7. High cardiac output- cardiac failure
279
What can extensive Paget's disease turn into?
Paget's sarcoma (aggressive)
280
Describe Paget's sarcoma?
- Usually lytic
| - Long bones > spine
281
Where does Paget's sarcoma metastasis to?
Early metastases to lung & bone
282
What is the prognosis for Paget's sarcoma?
Very poor
283
Give 2 examples of benign cartilaginous tumours?
1. Enchondroma
| 2. Osteocartilaginous exostosis
284
Give an example of malignant cartilaginous tumours?
Chondrosarcoma
285
What is a Enchondroma?
- Lobulated mass of cartilage within medulla
| - Low cellularity, often surrounded by plates of lamellar bone
286
What bones are locations are affected by Enchondroma?
>50% hands & feet, long bones
287
Describe the symptoms of long bones with Enchondroma?
Often asymptomatic
288
Describe the symptoms of hands with Enchondroma?
- Swelling
| - Pathological fracture
289
What is Osteocartilaginous Exostosis?
Benign outgrowth of cartilage with endo-chondral ossification
290
What is Osteocartilaginous Exostosis probably derived from?
Growth plate
291
Describe the prevalence of Osteocartilaginous Exostosis?
Very common, usually in adolescence
292
What is Osteocartilaginous Exostosis uncommonly?
Multiple-diaphyseal aclasis, autosomal dominant
293
What is the usual location of Osteocartilaginous Exostosis?
Metaphysis of long bones, not cranio-facial
294
What are the 2 types of Chondrosarcoma?
De novo (primary) or from a pre-existing enchondroma or exostosis (secondary)
295
What are the 2 locations of Chondrosarcoma?
Central within the medullary canal or peripheral on bone surface
296
What is the prevalence of Chondrosarcoma?
10% of malignant primary bone tumours
297
Who is more prone to Chondrosarcoma?
Males 2: females 1
298
List the 7 locations of Chondrosarcoma?
1. Axial skeleton
2. Pelvis
3. Ribs
4. Shoulder girdle
5. Proximal femur
6. Humerus
7. Hands & feet rare
299
What is the peak age for getting a Ewing’s sarcoma?
5-15 years
300
What are the 2 bone locations for Ewing’s sarcoma?
- Long bones (diaphysis or metaphysis)
| - Flat bones of limb girdles
301
Where do Ewing's sarcoma spread too?
Early metastases to lung, bone marrow & bone
302
Describe rheumatoid arthritis?
- Chronic multisystem disease
- Autoimmune
- Small joint preponderance but distal sparing
- Multiple extra-articular manifestations
303
What is the hallmark for rheumatoid arthritis?
Synovitis
304
Describe the epidemiology of rheumatoid arthritis?
- Females:males 3:1
- Clusters in families
- If 1st degree relative affected, 2-10x greater risk over population prevalence
- Recurrence risk highest for relatives of most severe patients
305
Describe the aetiology of rheumatoid arthritis?
- HLA-DR4 & other weaker genetic factors
- Genetic variations between ACPA+ve & -ve pts
- Shared epitope
- Smoking
- Epigenetics
- Infection
- Hormonal (pregnancy)
306
Describe smokings interaction with rheumatoid arthritis?
- Doubles risk among current smokers with 20-pack-year history
- APCA+ve mainly: Interaction with genetic risk can increase risk 20 fold
307
Describe the epigenetic associated with rheumatoid arthritis?
- DNA Methylation
- Histone PTMs
- Disease classification
308
What 3 infections are associated with rheumatoid arthritis development?
1. EBV
2. TB
3. Porphyromonas gingivalis
309
What is the pathophysiology of synovitis?
Immune cells invading a normally relatively acellular synovium in the form of a pannus
310
What is the pathophysiology of Pannus?
Hyperplastic, invasive tissue leading to cartilage breakdown, erosions & consequent reduced function
311
What is the pathophysiological difference between osteoporosis and rheumatoids?
- Osteoporosis: inside --> out
| - Rheumatoid: outside --> in
312
List the 8 clinical features of rheumatoid arthritis?
1. Synovitis
2. Pain
3. Erythema
4. Swelling
5. Early morning stiffness
6. Tenosynovitis
7. Bursitis
8. Carpal tunnel syndrome
313
List the 5 Constitutional symptoms of rheumatoid arthritis?
1. Fatigue
2. Weakness
3. Low grade fever
4. Weight loss
5. Anorexia
314
What joint are affected in rheumatoid arthritis?
- Small joints hands & feet early on
| - MCPs/PIPs/wrists
315
List 7 classical joint features of late rheumatoid arthritis?
1. Boutonniere
2. Swan neck
3. Z-thumb (Boutonniere of thumb)
4. Volar subluxation of wrist
5. Ulnar deviation digits
6. Radial deviation wrist
7. Piano Key ulnar head
316
What is a positive piano key sign in rheumatoid arthritis?
(a) The protruding ulna is found when the forearm is in full pronation
(b) Demonstrated by depressing the ulnar head. It springs back into position like a piano key
317
What is the respiratory extra-articular feature of rheumatoid arthritis?
Pulmonary fibrosis
318
What is the cardiac extra-articular feature of rheumatoid arthritis?
Pericarditis
319
What is the dermatological extra-articular feature of rheumatoid arthritis?
Vasculitis
320
What is the neurological extra-articular feature of rheumatoid arthritis?
Carpal tunnel
321
What is the haematological extra-articular feature of rheumatoid arthritis?
Anaemia of chronic disease
322
What are 7 blood tests that you would do to investigate rheumatoid arthritis?
1. FBC
2. U+Es
3. LFTs
4. ESR/CRP
5. RF
6. ACPA
7. (ANA)
323
What is rheumatoid factor?
- Autoantibody against Fc portion of IgG
| - Usually IgM against IgG, though can be any isotype
324
List 6 other conditions that have positive rheumatoid factor, apart from rheumatoid arthritis?
1. Systemic lupus erythematosus (SLE)
2. Subacute bacterial endocarditis (SBE)
3. Stevens-Johnson Syndrome (SJS)
4. TB
5. EBV
6. Healthy controls (esp elderly)
325
What is the relevance of rheumatoid factor in rheumatoid arthritis?
Part of assessment, not diagnostic
326
What is Anti-CCP/ACPA?
- Antibody that picks up those who may be RF negative
| - Predictor of worse prognosis, more erosions, resistant disease
327
What is Anti-CCP/ACPA linked to?
Smoking
328
What assessment is Anti-CCP/ACPA part of?
“Pre-RA”- highest risk of progression to RA
329
What 4 signs are X-rays good at detecting in rheumatoid arthritis?
1. Soft tissue swelling
2. Joint space narrowing
3. Erosions
4. Periarticular OP
330
What are USS good at detecting in rheumatoid arthritis?
More sensitive for synovitis & erosions
331
What are MRI's good at detecting in rheumatoid arthritis?
Bone marrow oedema
332
List 9 differentials for rheumatoid arthritis?
1. OA
2. SLE/other connective tissue disease
3. Polymyalgia rheumatica
4. Psoriatic arthropathy
5. Sponyloarthropathies
6. Reactive arthritis
7. Sarcoid
8. CPPD (calcium pyrophosphate)
9. Lyme’s
333
What is a typical clinical sign for Lupus?
Butterfly-shaped rash across the cheeks & bridge of the nose
334
What classification criteria is used for rheumatoid arthritis?
EULAR/ACR Diagnostic Criteria 2010
335
List the 3 non-pharmacological treatment of rheumatoid arthritis?
1. Occupational Therapist / Physiotherapist (mobility + preservation, work, walking aids)
2. Podiatrists (foot clinics, specialty foot assessment, footwear adjustments)
3. Other e.g. dieticians
336
List the 2 symptomatic pharmacological treatments for rheumatoid arthritis?
1. NSAIDs
| 2. Analgesia
337
List the 3 disease modifying (DMARDs) pharmacological treatments for rheumatoid arthritis?
1. Glucocorticoids (oral, IA, IM)
2. Methotrexate
3. Sulfasalazine
4. Leflunomide
5. Gold injections
6. Hydroxychloroquine
7. Biologics (anti-TNF, anti-CD20, anti-IL6, etc)
338
Describe Methotrexate?
- Anchor drug in multiple Rheum conditions
| - Dihydrofolate reductase inhibitor
339
What are the other actions of Methotrexate?
Anti-inflammatory targeting adenosine pathways
340
What dose of Methotrexate is usually given for rheumatoid arthritis?
7.5mg-25mg per week orally or s/c
341
List the 4 common & 3 serious side effects of Methotrexate?
- Common side effects: GI upset, hair, skin, rashes
| - Serious side effects: lungs/liver/Bone marrow suppression
342
What is a total contraindication for Methotrexate?
Pregnancy (need concomitant folic acid)
343
In what 2 scenarios would you withhold Methotrexate?
1. Infection
| 2. On Antibiotics (trimethoprim)
344
What is 5-ASA made up of?
Salazyopyrin & mesalazine
345
What are 3 conditions that you would use Sulfasalazine?
1. Rheumatoid arthritis
2. Seronegative spondyloarthropathies (SpA)
3. IBD
346
What dose of Sulfasalazine would you use for rheumatoid arthritis?
500mg-4g OD orally
347
What are the 2 common & 1 serious side effect of Sulfasalazine?
- Common side effects: GI upsets, rashes
| - Serious side effects: BM suppression
348
Can you use Sulfasalazine in pregnancy?
YES
349
Sulfasalazine is fine in infection unless _______?
Cytopenic
350
Give 5 examples of anti-TNF biologics?
1. Etanercept
2. Infliximab
3. Adalimumab
4. Golimumab
5. Certolizumab
351
What 4 conditions can be treated with Anti-TNF biologics?
1. TB
2. Infection
3. Multiple Sclerosis
4. Congestive heart failure
352
Give an example of an Anti-CD20 biologic?
Rituximab
353
What 3 conditions can be treated with Anti-CD20 biologic?
1. Infection
2. Progressive Multifocal Leukoencephalopathy
3. Hypogammaglobulinaemia
354
Give an example of an Anti-IL6 biologic?
Tocilizumab
355
What 3 conditions can be treated with Anti-IL6 biologic?
1. Minimal CRP
2. Infections
3. High lipids
356
Give an example of a CTLA4-Ig biologic?
Abatcept
357
What condition can be treated with CTLA4-Ig biologic?
Infection
358
Give 2 examples of JAK inhibitor biologics?
1. Tofacitinib
| 2. Baricitinib
359
What 3 conditions can be treated with JAK inhibitor biologics?
1. High lipids
2. Infections esp VZV
3. Reduced CRP
360
Describe the risk of infections with Biologics?
- Highest in first 6 months
| - Reduced thereafter but remains above risk with conventional DMARDs
361
List 4 infections that biologics put you in higher risk of getting?
1. TB
2. Varicella zoster
3. Opportunistic infections
4. Intracellular organisms (e.g. Listeria, Salmonella)
362
What should you determine before starting biologics?
Vaccine status
363
What should you ideally be vaccinated against before starting biologics?
Against influenza & pneumonoccal annually
364
What biologics can you give concurrent vaccines?
- Anti-TNF, IL6, CTLA4-Ig
| - Before Rituximab
365
What should you avoid when taking biologics?
Live vaccines
366
What 2 drugs make the response to vaccinations attenuated?
csDMARDs & biologics
367
Who is more prone to Systemic Lupus Erythematosus (SLE)?
- Commoner in Afro-Caribbean, South Asian, Mexican populations
- Female
- Diagnosed 40-50yrs
368
Describe the prognosis of Systemic Lupus Erythematosus (SLE)?
- High morbidity
- Average 25yrs premature death (infection, CVD, ESRF)
- 15yr survival ~85%
369
What are the 2 criteria for diagnosing Systemic Lupus Erythematosus (SLE)?
1. SLICC (2012)
| 2. Revised 1997 ACR
370
What are the 2 problems with the ACR criteria for diagnosing Systemic Lupus Erythematosus (SLE)?
1. Classification rather than diagnostic criteria
| 2. Subset of the clinical manifestations
371
Describe the SLICC criteria for Systemic Lupus Erythematosus (SLE)?
- Need at least 1 clinical & 1 serological manifestation
- Diagnosis possible with just biopsy proven Lupus Nephritis & positive immunology (ANA or Anti-DNA)
- Less specific
372
List the 3 common features of SLE clinical presentation?
1. Constitutional symptoms ie. fatigue
2. Cutaneous manifestations
3. Arthralgia (joint pains) & arthritis
373
How common are cutaneous lupus erythematosus (CLE) in SLE?
- Acute CLE 72%
- Subacute CLE 58%
- Discoid lupus 28%
- Discoid lupus confined to head/neck 6%
374
Do cutaneous manifestations mean a patient has lupus?
NO
375
Describe Jaccoud's arthropathy?
Deforming, non-erosive arthritis, occurring in 2-35% of SLE patients
376
What are 3 other musculoskeletal manifestations of systemic lupus Erythematosus (SLE)?
1. Avascular necrosis
2. Fibromyalgia overlaps- chronic concurrent pain concurrent
3. Osteoporosis- due to amount of steroid
377
How common are renal complications in systemic lupus Erythematosus (SLE)?
- 1/3-1/2 patients will have renal involvement
| - 20% will develop end stage renal failure in 10 years
378
How is renal function monitored in patients with SLE?
- Urinalysis, U&E, BP monitored at clinic
| - ds-DNA rise in titre can predict flares
379
What is helpful for diagnosis, prognosis and treatment of SLE?
Renal biopsy
380
List 6 pulmonary side effects of SLE?
1. Pleurisy
2. Pleural effusions
3. Acute pneumonitis
4. Diffuse alveolar haemorrhage
5. Pulmonary hypertension (rare)
6. Shrinking lung syndrome
381
List 5 cardiovascular side effects of SLE?
1. Pericarditis +/- effusion
2. Myocarditis
3. Valvular abnormalities
4. Coronary heart disease- high risk of morbidity & mortality long-term
5. Risk of MI 50x
382
List the 6 neuropsychiatric side effects of SLE?
1. Constant Headache
2. Anxiety & mood disorder
3. Seizure
4. Demyelination
5. Guillain-Barré syndrome
6. Mononeuritis
383
What 5 neuropsychiatric investigations would you do for SLE?
1. EEG
2. MRI
3. LP
4. Psychiatric evaluation
5. Anti-ribosomal P- associated with mood disorders
384
List the 6 uncommon gastrointestinal side effects of SLE?
1. Dysphagia
2. Reduced peristalsis
3. Peritonitis
4. Pancreatitis
5. Pseudo-obstruction
6. Lupus hepatitis- biopsy required
385
List the 7 haematological side effects of SLE?
1. Anaemia of chronic disease
2. Autoimmune haemolytic anaemia
3. Thrombotic thrombocytopenic purpura (TTP)
4. Leukopenia
5. Lymphadenopathy
6. Splenomegaly
7. Thrombocytopenia
Mild or ITP
386
Describe Antinuclear antibody (ANA) in SLE?
- Present in 95-98% of patients
| - SLE results due to activation of innate & adaptive immunity
387
What is Antinuclear antibody (ANA)?
Interaction of self antigens on or released by apoptotic cells
388
What % of healthy population have a positive ANA?
5% (sensitive but not specific)
389
When would you do Extractable nuclear antigen (ENA)?
If ANA positive, helpful to know which antigens affected
390
List 7 antibodies can ENA detect & what conditions do these correlate to?
1. Ro/La- SLE, Sjogrens
2. Ds-DNA- SLE
3. Sm- SLE
4. RNP- mixed connective tissue disease
5. Centromere- limited systemic scleroderma
6. Scl-70- diffuse systemic scleroderma
7. Histone- drug induced lupus
391
Describe the complements measured in active disease?
- C3 more specific
- C4 can be chronically low
- Trends more important than absolute numbers
- >90% negative predictive value
392
What are the 3 medications licensed in the UK for SLE?
1. Steroids
2. Hydroxychloroquine
3. Belimumab
393
What medications would you give to treat mild SLE?
1. Cutaneous disease- topical therapies, UVA/UVB sunblock
2. MSK- NSAIDS, IA/IM steroid, low dose oral prednisolone, Hydroxychloroquine +/- methotrexate
3. Serositis- NSAIDS, methotrexate
394
What medication would you give to treat moderate SLE?
Treatment as per mild disease plus:
1. Oral prednisolone (0.5mg/kg)
2. Methotrexate, Azathioprine, mycophenolate mofetil, Ciclosporin, Tacrolimus
3. Belimumab
395
What medication would you give for refractory SLE?
Rituximab
396
What medication would you give (additional to the mild/moderate medication) to treat severe SLE?
1. High dose steroid
2. DMARDs
3. B cell therapy
4. Cyclophosphamide
5. Intravenous immune globulin
6. Plasmapheresis
397
What are 5 adjunctive therapies would you give for SLE & why?
1. Topical lubricants for sicca symptoms
2. Fatigue management groups
3. Calcium channel blockers for Raynauds
4. Treatment of co-existent Fibromyalgia
5. Co-existent APLS: Anticoagulation in confirmed thromboembolic disease
398
What blood results are typical of Lupus (SLE)?
ESR is disproportionately elevated compared to CRP
399
What are the 11 clinical criteria in SLICC for SLE diagnosis?
1. Acute cutaneous lupus
2. Chronic cutaneous lupus
3. Oral or nasal ulcers
4. Non scarring alopecia
5. Arthritis
6. Serositis
7. Renal
8. Neurologic
9. Haemolytic anaemia
10. Leucopenia
11. Thrombocytopenia
400
What are the 6 immunological criteria in SLICC for SLE diagnosis?
1. ANA
2. Anti-DNA
3. Anti-Sm
4. Antiphospholipid antibodies
5. Low complement
6. Direct coombs (in absence of HA)
401
What are the 2 2017 guidelines for managing systemic lupus erythematosus (SLE)?
BSR & BHPR Guidelines
402
What are the 2 2012 guidelines for managing adult & paediatric lupus nephritis?
EULAR & ERA-EDTA Guidelines
403
What is the 2010 guideline for the management of systemic lupus erythematosus (SLE) with neuropsychiatric manifestations?
EULAR Guideline
404
What is primary vasculitides?
Group of autoimmune conditions characterised by inflammation of the blood vessels
405
What 6 blood vessels are typically affected by vasculitides?
1. Skin
2. Kidneys
3. Lungs
4. Joints
5. Nerves
6. ENT
406
What is the pathophysiological process of Vasculitis?
Genetic predisposition + environmental trigger --> Autoimmune reaction
407
Why is it important to talk about vasculitis?
- 30% mortality rate at 5yrs & 40% at 10 yrs
| - Its life & organ threatening but treatable with avoidance of end organ damage if diagnosed early
408
What are the 5 different types of Vasculitis?
1. Large vessel vasculitis
2. Medium vessel vasculitis
3. ANCA- associated small vessel vasculitis
4. Anti-GBM disease
5. Immune complex small vessel vasculitis
409
Give 2 examples of Large vessel vasculitis?
1. Takayasu arteritis
| 2. Giant cell arteritis
410
Give 3 examples of ANCA- associated small vessel vasculitis?
1. Microscopic polyangiitis
2. Granulomatosis with Polyangiitis (Wegener's)
3. Eosinophilic granulomatosis with Polyangiits (Churg-Strauss)
411
Give 2 examples of Medium vessel vasculitis?
1. Polyarteritis nodosa
| 2. Kawasaki disease
412
Give 3 examples of Immune complex small vessel vasculitis?
1. Cryoglobulinemic vasculitis
2. IgA vasculitis (Henoch-Schonlein)
3. Hypocomplementemic Urticarial vasculitis (Anti-C1q vasculitis)
413
What is the most commonly seen vasculitis?
Giant cell arteritis
414
Describe Giant Cell Arteritis?
Systemic vasculitis that affects the aorta & its major branches
415
What is the prevalence of Giant Cell Arteritis?
- Rare below age 50 years
| - Peak incidence 70-79 years
416
What population is at higher risk of Giant Cell Arteritis?
- Female 2-3: Male 1
- Highest in Caucasians from Northern Europe & Northern US
- Extremely uncommon in non-white populations
417
What are the 5 typical clinical presentations of Giant Cell Arteritis?
1. Headache
2. Visual symptoms
3. Jaw claudication in 50%
4. Polymyalgia rheumatica symptoms
5. Constitutional upset
418
Describe the typical headache of Giant Cell Arteritis?
- Temporal with tenderness
- Subacute onset
- Constant
- Little relief with analgesics
419
What is jaw claudication?
Pain on chewing which is relived by stopping mastication & can be a cause of weight loss & often as problematic as the headache
420
What are the Polymyalgia rheumatica symptoms seen in Giant Cell Arteritis?
Subacute onset of shoulder & pelvic girdle stiffness & pain, with no alternate diagnosis
421
What are the 3 complications of Giant Cell Arteritis?
1. Visual loss
2. Large vessel vasculitis
3. CVA
422
Describe the visual loss complication in Giant Cell Arteritis?
- Irreversible
- 14-70% depending on the series
- Acute ischaemic optic neuropathy
- Sudden painless loss of vision, occasionally preceded by amaurosis fugax
423
Describe the large vessel vasculitis complication of Giant Cell Arteritis?
Vascular stenoses & aneurysms
424
Describe the CVA complication of Giant Cell Arteritis?
Obstruction or occlusion of internal carotid artery or vertebral arteries
425
What are the 4 steps to diagnosing giant cell arteritis?
1. Clinical presentation
2. Clinical examination- temporal artery asymmetry, loss of pulsatility
3. Acute phase response- ESR/CRP
4. Further investigations
426
What is the gold standard for diagnosing giant cell arteritis?
Temporal artery biopsy
427
Describe a positive Temporal artery biopsy for giant cell arteritis?
- Interruption of internal elastic laminae with mononuclear inflammatory cell infiltrate within vessel wall
- Multinucleated giant cells are typical (40-60%) but their absence does not exclude a diagnosis
428
Describe how giant cell arteritis affects vessels?
Focally & segmentally & not uniformly, therefore ‘skip lesions’ mean histological signs of inflammation may be missed in segments of arteries that are arteritis free
429
What are 3 other investigations for giant cell arteritis?
1. Temporal Artery USS
2. MRI
3. PET CT
430
What should you do if there is a strong clinical suspicion of giant cell arteritis?
Treat as the risk of visual loss is high!
- 1mg/ kg/ day prednisolone
- IV methylprednisolone if visual symptoms
- Aspirin 75mg daily (reduces ischaemic complications)
431
What is the treatment of giant cell arteritis?
- Maintain prednisolone 60mg for 1 month then taper to 15mg by 12 weeks
- Corticosteroid sparing therapy in patients with disease relapse on steroid sparing
432
What are the 3 corticosteroid sparing therapies for relapsing giant cell arteritis?
1. Mycophenolate Mofetil
2. Methotrexate
3. Tocilizumab (anti-IL6)
433
What 2 investigations are specifically important in confirming giant cell arteritis diagnosis?
Temporal artery biopsy &/or temporal artery USS
434
What are 6 differential diagnosis for cutaneous vasculitis?
1. Idiopathic
2. Drugs
3. Infection: HCV, HBV, gonococcus, meningococcus, staph
4. Secondary RA/ CTD/ PBC/ UC
5. Malignancy: haematological > solid organ
6. Manifestation of small/ medium vessel ANCA associated vasculitis
435
What is Henoch-Schönlein Purpura (HSP)?
Small vessel vasculitis
436
Who is more prone to Henoch-Schönlein Purpura (HSP)?
- More common in children, 2-11y
- Observed in adults, mean age 43y
- Male > Females
437
What is the prognosis of Henoch-Schönlein Purpura (HSP)?
- Frequently self limiting illness, 4-16 weeks
- Good overall prognosis
- Mortality 1-2%
438
List 6 clinical signs & symptoms of Henoch-Schönlein Purpura (HSP)?
1. Classic purpuric rash; buttocks, thighs >lower legs
2. Urticarial rash
3. Confluent petechiae
4. Ecchymoses
5. Ulcers
6. Arthralgia/ Arthritis (lower limb) in 75%
439
List the 4 complications of Henoch-Schönlein Purpura (HSP)?
1. Gastrointestinal disease- pain, bleeding, diarrhoea, rarely intussusception. More common in children
2. Renal disease- IgA nephropathy, more common in adults
3. Urological disease- orchitis
4. CNS disease
440
What are the 2 approaches to managing Henoch-Schönlein Purpura (HSP)?
1. Exclude secondary causes
| 2. Assess extent of involvement
441
List 4 ways to exclude secondary causes of Henoch-Schönlein Purpura (HSP)?
1. History: multisystem disease, recent infections, recent drugs, lifestyle
2. Examination
3. Immunology: RF, ANA, ANCA, PR3/ MPO
4. Virology
442
How would you assess the extent of involvement in Henoch-Schönlein Purpura (HSP)?
Urinalysis/ urine PCR
443
Describe the management of Henoch-Schönlein Purpura (HSP)?
- Often no treatment required
| - Corticosteroids if complicated by: testicular torsion, GI disease, arthritis
444
How effective are steroids in preventing renal disease in Henoch-Schönlein Purpura (HSP)?
Steroids do NOT prevent development or progression of renal disease
445
Describe the prognosis of Henoch-Schönlein Purpura (HSP)?
- Frequently self-limiting
| - Relapses in 5-10%, tends to occur within 12 months
446
What is Henoch Schönlein Purpura (HSP) occasionally triggered by?
Streptococcal sore throat
447
What are the 2 most significant complications of Henoch Schönlein Purpura (HSP)?
- GI disease (children)
| - Renal disease (children and adults)
448
What group of vasculitis tends to have the most morbidity & mortality?
ANCA associated vasculitis
449
What is Granulomatosis with polyangiitis (GPA) formerly known as?
Wegener’s granulomatosis
450
Describe the incidence of Granulomatosis with polyangiitis (GPA)?
- 2-12 per million population
| - Higher incidence in Northern European countries
451
What is Granulomatosis with polyangiitis (GPA) characterised by?
Granulomatous necrotising inflammatory lesions of the upper & lower respiratory tract & often a pauci-immune glomerulonephritis
452
What is the classic triad of disease for Granulomatosis with polyangiitis (GPA)?
1. Upper airway/ENT
2. Lower respiratory
3. Renal + constitutional symptoms
453
List the 5 upper airway diseases associated with Granulomatosis with polyangiitis (GPA)?
1. Rhinitis
2. Chronic sinusitis
3. Chronic otitis media
4. Saddle nose deformity
5. Nasal septal perforation
454
What is the renal disease associated with Granulomatosis with polyangiitis (GPA)?
(Rapidly progressive) pauci-immune glomerulonephritis
455
List the 2 lower respiratory diseases associated with Granulomatosis with polyangiitis (GPA)?
1. Parenchymal nodules +/- cavitation
| 2. Alveolar haemorrhage
456
List the 5 constitutional symptoms of Granulomatosis with polyangiitis (GPA)?
1. Fatigue
2. Weight loss
3. Fever/ sweats
4. Myalgia/ arthralgia
5. Failure to thrive in elderly
457
List the organ specific features of Granulomatosis with polyangiitis (GPA)?
1. Oral- ulcerations
2. Eye- pseudotumours, conjunctivitis
3. Skin- nodules on the elbow, purpura
4. Heart- pericarditis
5. Nose- stuffiness, nosebleeds, saddle nose
6. Lungs: cavities, bleeds, lung infiltrates
458
What is the 4 step approach to vasculitis care?
Make the correct diagnosis --> Assess disease severity --> Treat --> Assess disease activity & manage complications
459
In what 5 clinical situations would you consider the diagnosis of vasculitis?
1. Classical presentation (triad)
2. Constitutional symptoms
3. Multi-system disease (detailed systemic enquiry)
4. Repeated GP/ hospital attendances
5. Not behaving as expected ie. not responding to treatment
460
What is ANCA (immunology)?
Autoantibodies directed against the cytoplasmic constituents of neutrophils & monocytes
461
What are the 2 means of testing for ANCA?
1. Indirect immunofluorescence (gives p or cANCA)
| 2. ELISA for proteinase 3/ myeloperoxidase
462
In what 4 ways is ANCA helpful?
1. Diagnosis- as a screening tool it's unhelpful
2. Prognostic information
3. Assess response to treatment
4. Monitoring for early signs of relapse
463
What 2 positive immunology results are very suggestive of Granulomatosis with polyangiitis (GPA)?
cANCA & proteinase 3 (PR3)
464
What 2 positive immunology results are suggestive of microscopic polyangiitis or EGPA?
pANCA with a strong myeloperoxidase (MPO)
465
What 2 immunology results are not supportive of a ANCA-associated vasculitis?
Positive ANCA by indirect immunofluorescence but negative proteinase 3 (PR3)/ myeloperoxidase (MPO)
466
What are the 4 rules to Remission Induction in vasculitis?
1. Switch off vasculitis activity
2. Higher doses = higher toxicity
3. 3-6 months
4. Time pressure
467
What are the 3 drugs given to induce remission in severe vasculitis (life or organ threatening)?
1. Prednisolone +
2. Cyclophosphamide (oral/ IV)
2. Rituximab (anti- B cell biologic agent)
468
What are the 4 risks of Cyclophosphamide?
1. Infection
2. Cytopenias
3. Malignancy
4. Infertility
469
Describe the PROS of Rituximab for vasculitis?
- As effective as Cyclophosphamide
- Better for relapsing disease
- Safer for repeated treatment
- No risk of infertility
470
What are the 3 drugs given to induce remission in moderate vasculitis severity (not life or organ threatening)?
1. Prednisolone +
2. Methotrexate
3. Mycophenolate
471
What are 4 ways to maintain remission in systemic vasculitis?
1. Prevent relapse
2. Lower drug toxicities
3. More prolonged therapy (2+ years)
4. Supportive therapy
472
What are the 3 drugs options for systemic vasculitis remission maintenance?
1. Azathioprine
2. Methotrexate
3. Mycophenolate Mofetil (less good)
473
What is the main take home message about systemic vasculitis?
Its a rare potentially life/organ threatening disease but treatable (immunosuppression) when there is a timely diagnosis
474
Give 3 examples of things causing abnormal inflammation in the body?
1. Inflammatory arthropathies
2. Ulcerative colitis/Crohns
3. Psoriasis
475
Give 2 examples of things causing unwanted normal inflammation in the body?
1. Solid organ transplants
| 2. Bone marrow grafts
476
For what 3 reasons are steroids excellent immunosuppressants?
1. Rapid onset (within hours)
2. Easy to administer
3. Able to treat wide variety of inflammatory conditions
477
What are steroids limited by?
Intolerable adverse effects, esp at high dose
478
What are the 7 unwanted side effects of steroids?
1. Weight gain & fluid retention
2. Glaucoma
3. Osteoporosis
4. Infection
5. Hypertension & hypokalaemia
6. Peptic ulceration & GI bleed
7. Psychological/psychiatric symptoms
479
What are the 3 non-steroid immunosuppressant drugs which work by inhibiting DNA synthesis?
1. Methotrexate
2. Azathioprine
3. Mycophenolate
480
What are the 4 non-steroid immunosuppressant drugs which work by inhibiting lymphocyte signalling?
1. Cyclosporin
2. Tacrolimus
3. Sirolimus
4. Leflunomide
481
What is the role of methotrexate at high dose?
Cytotoxic Chemotherapeutic Agent
482
What is the role of methotrexate at low dose?
Immunosuppressant
483
What does methotrexate appear like structurally?
Folic acid
484
What is the mechanism of action of methotrexate?
- Dihydrofolate reductase
| - Thymidylate synthetase
485
What is Methotrexates effect on the cell cycle?
S-phase arrest (stops DNA replication)
486
What are 6 other actions of Methotrexate?
1. Folate antagonism
2. Adenosine signalling
3. Methyl donors
4. Eicosanoids & MMPs
5. Cytokines
6. Adhesion molecules
487
What are the 4 adverse effects of methotrexate?
1. GI toxicity- N/V, diarrhoea, hepatitis, stomatitis
2. Haematological- leukopenia
3. Frequency infections
4. Pulmonary fibrosis
488
What is given to reduce methotrexate toxicity?
Folic acid 5mg given 4 days after methotrexate
489
What are the 3 indications for methotrexate?
1. Rheumatoid arthritis
2. Psoriasis & psoriatic arthropathy
3. Steroid sparing agent in giant cell arteritis
490
Describe the clinical use of methotrexate?
- Once a week with folic acid usually 4 days later
- Normally orally but can be given s/c if significant GI toxicity
- Takes several weeks for effect to become apparent
491
What do patients on methotrexate need?
Regular monitoring bloods
492
Describe the progression of azathioprine breakdown in the body?
Azathioprine --> 6-Mercaptopurine --> Hypoxanthine --> TIMP --> Adenosine monophosphate
493
Describe how the body deals with Azathioprine?
- Converted within cells into a nucleoside analog
| - Incorporated into DNA & RNA chains leading to termination of nucleic acid strands
494
What effect does Azathioprine have on the body?
- Cell growth & metabolism halts
| - Preferential action of lymphocytes as other cells have purine salvage pathway
495
What is the effect of azathioprine given at too low a dose?
Prevents immune responses through cytotoxic effect
496
What other action dose azathioprine have on the immune system?
Inhibits T-cell co-stimulation through interference with CD28
497
What are the 3 adverse effects of azathioprine?
1. GI- N/V, diarrhoea, hepatitis, cholestasis
2. Haematological- leukopenia, thrombocytopenia
3. Frequent infections
498
Describe the metabolism of azathioprine in the body?
TPMT enzyme vital in reducing active drug in cells, around 0.2-0.6% of individuals lack TPMT
499
What happens if an individual is lacking TPMT & is on azathioprine?
Without TPMT there is accumulation of the most active metabolites of azathioprine within cells & development of severe toxicity
500
What is necessary before starting a patient on azathioprine?
Checking TPMT activity prior to treatment
501
What are the 4 indications for azathioprine?
1. Ulcerative colitis
2. Crohn's disease
3. Myaesthenia gravis
4. Eczema
502
Describe the clinical use of azathioprine?
- Orally on a daily basis
| - Effects take several weeks to become evident
503
What do patients on azathioprine need?
To monitor bloods on a monthly basis
504
What is Cyclosporin?
Small molecule inhibitor of calcineurin
505
What are the 2 effects of Cyclosporin?
1. Inhibiting signal transduction from the activated TCR complex
2. Profound inhibition of T-cell activation
506
List the 6 adverse effects of Cyclosporin?
1. Nephrotoxicity
2. Hypertension
3. Hepatotoxicity
4. Anorexia & lethargy
5. Hirsutism
6. Paraesthesia
507
What does Cyclosporin NOT cause?
Bone marrow suppression
508
What class of drugs have a similar mechanism of action to Cyclosporin?
Tacrolimus (FK506)
509
Describe the PROS & CONS of Tacrolimus (FK506)?
- CONS: More potent
| - PROS: Very similar use to cyclosporin but may be a little better tolerated
510
What are the 3 indications for cyclosporin?
1. Organ transplantation
2. Inflammatory conditions
3. Topically ie. skin or eye
511
Describe the clinical use of cyclosporin?
- Orally on a daily basis
- Dose established using therapeutic drug monitoring
- Main drug interactions through cytochrome P450 enzymes
512
What are the 2 effectiveness disadvantages of immunosuppressants?
1. Often insufficient to control inflammatory disease with subsequent progression
2. Usually slow rate of onset limiting usefulness in acute severe disease
513
What are the 3 toxic disadvantages of immunosuppressants?
1. Even at low dose, they have significant toxicities
2. Bone marrow suppression
3. Frequent infections
514
What is biologic therapy?
Therapeutic agents synthesised biologically rather than chemically synthesized small molecules
515
What are the 2 benefits of biology therapies?
1. Able to target specifically designated components of the immune system
2. With minimal off target effects
516
Describe the administration of biologic therapies?
Usually parenteral route
517
What are the 3 adverse effects of biologics?
1. Hypersensitivity reactions
2. Infusion reactions
3. Mild GI toxicity
518
Describe the infection side effect of biologic therapies?
- Much less frequent with most biologics than anticipated
| - Infectious complications have not been significantly higher than placebo in clinical trials
519
Describe the infection risks of Anti-TNF biologic therapy?
- Risk of TB, particularly disseminated TB
- Need to screen for latent TB before prescribing
- Also increased risk of salmonella & listeria
520
Describe the infection risks of Rituximab (anti-CD20) biologic therapy?
- Generalised increased risk of serious infection
| - High risk of hepatitis B reactivation. Need to screen & prophylax if necessary
521
Describe the infection risk of Abatacept (anti-CD86) biologic therapy?
- Risk of pneumonia & respiratory tract infection
| - Risk of TB but less than anti-TNF
522
Describe the infection risk of anti-IL1 biologic therapy?
Increased risk of respiratory tract infection & pneumonia
523
What do patients on anti-TNF biologic therapy often have?
Defective granuloma formation & disseminated disease
524
How do you screen for latent TB prior to anti-TNF treatment?
- Use an interferon gamma release assay (IGRA)
| - Treat for latent TB if required
525
What are the 6 burdens of back pain?
1. Financial- work
2. >50% have insomnia
3. Emotional stress
4. Relationship breakdowns
5. Severe emotional distress for partners
6. Limitations in fulfilling family tasks
526
What do 7% of people with back pain have?
Chronic back pain => 3months
527
What is the most common chronic back pain?
"Mechanical” “wear-& tear”
528
What are the 3 differential diagnosis of back pain?
1. Medical & surgical emergencies
2. Life-threatening cancers
3. Treatable conditions
529
What is difficult to determine in back pain?
Source- ligaments, facet joints, paravertebral muscles & fascia, discs, spinal nerve roots (all implicated as pain generators)
530
What are the 3 broad differential causes of back pain?
1. Mechanical (97%)- non-specific low back pain (NSLBP)
2. Systemic- Infection, Malignancy, Inflammatory
3. Referred (i.e. no pathology in back)
531
Describe Non-specific low back pain (NSLBP)?
- Onset at any age, variable rate
- Generally worsens with movement or prolonged standing
- Better with rest
- Early morning stiffness <30 min
532
What are the 4 causes of Non-specific low back pain (NSLBP)?
1. Lumbar strain/sprain
2. Degenerative discs/facets joints
3. Disc prolapse, spinal stenosis
4. Compression fractures
533
Describe Lumbar strain/sprain causing Non-specific low back pain (NSLBP)?
- Most common
| - Muscle spasms usually settle 24-48 hrs
534
Describe degenerative disc disease ("spondylosis") causing non-specific low back pain (NSLBP)?
- Many: asymptomatic disc disease
| - Increase with flexion, sitting, sneezing
535
Describe degenerative facet joint disease causing non-specific low back pain (NSLBP)?
- More localised
| - Increase with extension
536
List 6 management techniques for non-specific low back pain (NSLBP)?
1. Keep diagnosis under review
2. Reassurance
3. Education- promote self-management
4. Exercise programme & physiotherapy
5. Analgesics (avoid opiates)
6. Acupuncture
537
What are the 3 managements to avoid in non-specific low back pain (NSLBP)?
1. Injections
2. Traction
3. Lumbar supports
538
Describe the presentation of a disc prolapse (herniated nucleus pulposus)?
- May be acute, increase cough
- Typically leg > back pain “sciatica” “radiculopathy”
- Leg pain with dermatomal distribution
- Straight-leg raising test +ve
- Reduced reflexes
539
Describe the prognosis of disc prolapse (herniated nucleus pulposus)?
Most resolve spontaneously within 12wks
540
Describe the treatment of disc prolapse (herniated nucleus pulposus)?
- Wait with investigations: MRI (x-ray)
- <10% need surgery (helps leg, not back pain)
- Surgery better outcomes at 6 weeks than conservative
- But no clear benefit at 1 year
541
Describe a prolapsed disc?
Part of the softer middle disc bulges through the fibrous outer ring & presses on the nerve as it leaves the spinal cord
542
Describe Spinal Stenosis (anatomical narrowing of the spina canal)?
- Congenital &/or degenerative
- Worse walking, rest in flexed position
- Natural history variable, includes improvement (30:30:30%)
543
What does Spinal Stenosis often present with?
Claudication in legs/calves
544
What are the 2 investigations for Spinal Stenosis?
1. X-ray
| 2. MRI
545
Would you perform surgery for Spinal Stenosis?
Surgery generally high risk
546
Give an example of back pain emergency?
Cauda equina
547
Where does the spinal cord end?
L1/2
548
What are the 2 types of signs/symptoms for Cauda Equina?
1. Neuropathic symptoms- Bilateral sciatica, Saddle anaesthesia
2. Bladder or bowel dysfunction- reduced anal tone
549
What is usually the cause of caudal equina?
Large prolapsed disc
550
What is Spondylolisthesis?
“Slip” of one vertebra on the one below
551
Describe the prevalence of Spondylolisthesis?
3-6% population = pars interarticularis defect, asymptomatic in most
552
Describe the presentation of Spondylolisthesis?
- Pain may radiate to posterior thigh
| - Increase with extension
553
What does Spondylolisthesis rarely need?
Surgery if severe
554
Who often gets a compression fracture?
Elderly
555
Describe the presentation of a compression fracture?
- Often sudden onset, severe
- Radiates in “belt” around chest/abdomen
- Most pain settles in 3/12; chronic mechanical & kyphosis
556
What is a compression fracture associated with?
Osteoporosis
557
What are the 2 investigations for compression fracture?
1. X-ray
| 2. DEXA
558
What are the 2 treatments for compression fractures?
1. Conservative (analgesia)
| 2. Vertebroplasty (cement) or kyphoplasty (balloon)
559
What are the 5 areas of referred pain in the back?
1. Aortic aneurysm
2. Acute pancreatitis
3. Peptic ulcer disease (duodenal)
4. Acute pyelonephritis/ Renal colic
5. Endometriosis/gynae
560
What are the 3 systemic causes of back pain?
1. Infection- discitis, osteomyelitis, epidural abscess
2. Malignancy
3. Inflammatory
561
Describe the presentation of infective discitis?
- Fever (may be PUO), weight-loss
| - Constant back pain: rest, night pain
562
What are the 3 risk factors for developing infection discitis?
1. Immunosuppressed
2. Diabetes
3. IV drug use
563
What are the 4 investigations for infective discitis?
1. Bloods: FBC, ESR, CRP, blood cultures
2. X-ray (end-plate/vertebral destruction)
3. MRI
4. Radiology-guided aspiration
564
What is the most common organism for infective discitis?
Staph aureus
565
What is the combination treatment for discitis?
IV antibiotics ± surgical debridement
566
What 5 malignancies commonly metastasis to bone?
1. Lung
2. Prostate
3. Thyroid
4. Kidney
5. Breast
567
Describe the typical presentation of malignancy?
- Onset age >50 yrs
- Constant pain, often worse at night
- Systemic symptoms, primary tumour signs & symptoms
568
What are 3 investigations for bone malignancy?
1. X-ray (lytic/destructive)
2. MRI
3. Bone scan
569
Describe the typical presentation of inflammatory back pain (IBP)?
- Onset <45 years (often teens)
- Early morning stiffness >30mins
- Back stiff after rest & improves with movement
- May wake 2nd half night, buttock pain
570
What are 3 vital clues for chronic inflammatory back pain (IBP)?
Associated conditions (~1%), inflammatory symptoms (~10-15%) or family history
571
What are the 3 examinations for back pain?
1. Back
2. Neurology
3. Abdomen
572
What 2 imaging would you do for back pain?
1. MRI
| 2. X-ray
573
When would you check bloods for back pain?
If suspect infective/inflammatory, myeloma screen
574
List 10 red flag symptoms for back pain?
1. New onset age <16 or >50
2. Following significant trauma
3. Previous malignancy
4. Systemic = fevers/rigors, general malaise, weight loss
5. Previous steroid use
6. IV drug abuse, HIV or immunosuppressed
7. Recent significant infection
8. Urinary retention
9. Non-mechanical pain (worse at rest “night pain”)
10. Thoracic spine pain
575
List 5 red flag signs for back pain?
1. Saddle anaesthesia
2. Reduced anal tone
3. Hip or knee weakness
4. Generalised neurological deficit
5. Progressive spinal deformity
576
Describe the 7 parts to the bio-psycho-social model in patients likely to develop chronicity?
1. Attitudes- towards current problem
2. Beliefs- misguided belief that they have something serious
3. Compensation- payment for an accident/ RTA?
4. Diagnosis - Inappropriate communication, patients misunderstanding
5. Emotions- depression/ anxiety
6. Family- over bearing or under supportive
7. Work relationship
577
What 2 conditions is chronic inflammatory back pain usually due to?
1. Ankylosing spondylitis (AS)
| 2. Non-radiographic Axial Spondyloarthritis (axSpA)
578
What does a diagnosis of Ankylosing spondylitis (AS) need?
X-ray damage
579
What is the criteria for Ankylosing spondylitis (AS) diagnosis?
Modified New York criteria for Ankylosing Spondylitis
580
Describe the spectrum of Axial Spondyloarthritis (axSpA)?
- Non-radiographic axSpA: x-ray negative
- Radiographic axSpA: x-ray positive sacro-iliitis
- X-ray positive sacro-iliitis &/or spinal changes
581
What are the 4 concepts of spondyloarthritis?
1. Enthesitis & dactylitis
2. Axial involvement
3. New bone formation/ Ankylosis
4. Extra-articular manifestations
* Heterogeneity*
582
Describe the ASAS classification criteria for Axial Spondyloarthritis (axSpA)?
In patients with =>3 months back pain and age at onset <45 years: Sacroiliitis on imaging + =>SpA feature OR
HLA-B27 + =>2 other SpA features
583
Who gets Axial Spondyloarthritis (axSpA) and Ankylosing spondylitis (AS)?
- Onset <45 years
- Many in late teens-early adulthood 15-35years
- AS = mainly male
- axSpA = 1:1 gender split
584
List the 5 symptoms of Axial Spondyloarthritis (axSpA)?
1. Inflammatory back pain
2. Fatigue
3. Arthritis in other joints: hips, knees
4. Enthesitis: Achilles tendon, plantar fasciitis
5. Inflammation outside joints = extra-articular (uveitis, psoriasis, IBD, osteoporosis)
585
What is the recommended imaging for Axial Spondyloarthritis (axSpA)?
X-rays: pelvis AP films (not sacroiliac joint (SIJ))
586
What are 3 features of lumbar spine films in anklosing spondylitis?
1. Sclerosis (shiny corners)
2. Syndesmophytes & spondylophytes
3. Bridging Syndesmophytes
587
What are 5 causes of a positive MRI showing bone marrow oedema of sacro-iliac joints?
1. Chronic low back pain = 21%
2. Postpartum = 63%
3. Healthy = 23%
4. Recreational runners = 30-35%
5. Elite ice hockey players = 41%
588
What are the 2 associated features of Ankylosing spondylitis (AS) and Axial Spondyloarthritis (axSpA)?
1. Family history of AS/axSPA
| 2. Extra-articular: psoriasis, colitis, uveitis
589
What are the 2 other investigations for Ankylosing spondylitis (AS) and Axial Spondyloarthritis (axSpA)?
1. HLA-B27 status
| 2. CRP/ESR (*usually normal*)
590
Describe the genetic involvement of Ankylosing spondylitis (AS) and Axial Spondyloarthritis (axSpA)?
- HLA-B27+ >75% AS vs 8% Caucasian population
- Lots of other mutations = overlap with other diseases
- IL-23R, Th17 response
591
Describe the 2 environmental involvements of Ankylosing spondylitis (AS) and Axial Spondyloarthritis (axSpA)?
1. Infection
| 2. Microbiome in gut and skin
592
What pathway is implicated in enthesitis & Axial Spondyloarthritis (axSpA)?
IL-23/-17 pathway
593
What are the 6 non-pharmacological treatment options for Axial Spondyloarthritis (axSpA)?
1. Education
2. Exercise
3. Physical therapy
4. Rehabilitation
5. Patient associations
6. Self help groups
594
What are the 4 pharmacological interventions for Axial Spondyloarthritis (axSpA)?
1. NSAIDS
2. Biologics (TNF inhibitors, IL-17A inhibitors)
3. Analgesics
4. Surgery
595
What are 6 reasons why someone with Axial Spondyloarthritis (axSpA) or Ankylosing spondylitis (AS) should stop smoking?
1. Higher rates of AS
2. Higher disease activity
3. Worse physical function
4. Poorer quality of life
5. More x-ray progression
6. Less likely to respond to biologics
596
What 5 things happen to the joint in arthritis/arthrosis?
1. Gets destroyed
2. The surface becomes eroded
3. Cartilage wears away
4. Osteophytes may form
5. Subchondral changes happen
597
Describe the pathology of cartilage breakdown in arthritis/arthrosis?
Proteolytic breakdown of the cartilage matrix from an increased production of enzymes, such as metalloproteinases
598
What is released as the arthritis/arthrosis disease progresses?
Proteoglycan & collagen fragments released into the synovial fluid & erosion to the cartilage roughens surface & fibrillation which narrows the joint space
599
What destroys the soft tissue around the knee in arthritis/arthrosis?
Increased production of synovial metalloproteinases, cytokines & TNF that can diffuse back into the cartilage
600
List the 11 clinical presentations of arthritis/arthrosis?
1. Pain
2. Stiffness
3. Swelling
4. Clicks/crepitus
5. Deformity
6. Mobility
7. Walking/support/Instability
8. Night sleep
9. Functioning
10. Normal activities
11. Recreational Activities
601
List the 9 underlying causes of secondary osteoarthritis?
1. Other Joint problems
2. Nearby Joint problems
3. Systemic problems
4. Back Problems
5. Long term medicines
6. Allergies- Metals
7. Family history
8. Treatment history/previous surgeries
9. Social history/Personal Habits
602
What are the 5 examinations for arthritis/arthrosis?
1. General Examination – include Gait
2. Systemic Examination
3. Specific Joint Examination
4. Look/Feel/Move/Special Tests
5. Neuro Vascular Status Distally
603
What are the 4 investigations for joint problems (arthritis/arthrosis) and underlying pathology?
1. Radiographic
2. Blood
3. Urine
4. Aspirate
604
What are the 5 stages of osteoarthritis on radiographs according to the Kellgren Lawrence classification?
1. Grade 0: no radiographic features of OA are present
2. Grade 1: doubtful joint space narrowing (JSN) & possible osteophytic lipping
3. Grade 2: definite osteophytes & possible JSN on anteroposterior weight-bearing radiograph
4. Grade 3: multiple osteophytes, definite JSN, sclerosis, possible bony deformity
5. Grade 4: large osteophytes, marked JSN, severe sclerosis & definite bony deformity
605
Describe the management of stage 1 (minor) osteoarthritis?
- If patient is not predisposed to OA, no treatment
- Lifestyle considerations: regular exercise & weight loss
- Supplements: glucosamine & chondroitin
- Prophylactic surgery: controversial & not recommended
606
What may the future hold for osteoarthritis management?
Genetic therapy/biological treatments
607
Describe the management of stage 2 (mild) osteoarthritis?
- Physiotherapy
- Strict regimen of exercise & strength training for increased joint stability & weight loss
- Braces, knee supports or shoe inserts
- Analgesia as required
- Prophylactic surgery: controversial & not recommended
608
Describe the management of stage 3 (moderate) osteoarthritis?
- NSAIDs/pain-relief therapies
- If methods are not effective stronger pain medicine (codeine & oxycodone)
- Physical therapy, Brace, Acupuncture, heat/cold therapy, massage, local anti-inflammatory gels
- Intra-articular injections of steroid/hyaluronic acid
- Some consider prophylactic realignment surgery
609
Describe the management of stage 4 (severe) osteoarthritis?
- Analgesia, physical therapy, weight loss, use of NSAIDs, Brace, Acupuncture, heat/cold therapy, massage, local anti-inflammatory gels
- Surgery
610
What are the 4 types of surgery for stage 4 (severe) osteoarthritis?
1. Realignment
2. Replacement (most common)
3. Excision
4. Fusion
611
What are the 3 different knee replacements?
1. Total Knee Replacement
2. Unicompartmental
3. Patello femoral replacement
612
What are the 2 basic principles of joint replacements?
1. Take away the diseased surface
| 2. Replace with artificial material that needs to stick to bone
613
List the 9 different materials for joint replacements?
1. Titanium
2. Molybdenum
3. Vanadium alloys
4. Cobalt Chrome alloys
5. Ultra High Molecular weight
6. Polyethylene
7. Ceramics
8. Coated implants: Porous/Hydroxyapatile/Tantalum
9. Polished implants
614
What are the 4 modes of fixation for joint replacements?
1. Uncemented- usually coated
2. Cemented- usually polished
3. Hybrid- Cup Uncemented, Stem Cemented
4. Reverse hybrid- Cup Cemented, Stem Uncemented
615
Describe the uncemented mode of fixation for joint replacement?
- Primary fixation by Pressfit
| - Secondary by Bone growth
616
Describe the cemented mode of fixation for joint replacement?
Primary and Secondary fixation with Cement (Polymethyl methacrylate)
617
What are the 9 steps to a joint replacement surgical procedure?
1. Positioning
2. Exposure
3. Bone preparation
4. Implantation
5. Reduction
6. Assessment
7. Closure
8. Post op checks
9. Rehabilitation
618
What are the 4 parts to the post op rehabilitation of joint replacement?
1. Mobilisation
2. Discharge
3. Home Exercise Program
4. Removal of clips/sutures if needed
619
What are the 4 parts to the modern early recovery program for joint replacements?
1. Preop Education
2. Preop Exercise
3. Joint School- Physiotherapist, Occ therapist, Discharge planning
4. Minimal soft tissue dissection surgery
620
How long is the modern early recovery program for joint replacements?
2 weeks to 1-4days
621
What are the 10 advantages for total hip replacement (THR)?
1. Cup- Orientation
2. Stem- Orientation
3. Assessment
4. More Insight
5. May better surgical technique
6. MIS / Patient demands
7. Better Anatomic Positioning ? Long term Results
8. Consistency with planning
9. Leg Length & Offset
10. Reduces the Ceramic on ceramic noise
622
List the 10 general complications associated with total knee & total hip replacements?
1. DVT/PE
2. Infection
3. Neuro vascular damage
4. Swelling & Stiffness
5. Non/Partial relief/recurrence
6. Anaesthetic problems
7. Renal, Gastric, respiratory, cardiac
8. Cerebral compromise
9. Death
10. Failure of procedure
623
List the 5 specific complications for a hip replacement?
1. Dislocation
2. Fracture
3. Leg length discrepancy
4. Hip noise
5. Implant breakage/failure
624
List the 6 specific complications for a knee replacement?
1. Stiffness
2. Fracture
3. Ligament or tendon damage
4. Kneeling difficulty
5. Failure
6. Dissatisfaction rates (10% - 20%)
625
What are the aims in hip arthroplasty?
To achieve a stable, well functioning hip with well balanced tissues that lasts for ever
626
What are the 6 important components in a hip arthroplasty?
1. Component fixation
2. Bearing surfaces
3. Leg length
4. Offset
5. Centre of rotation
6. Orientation of cup & femur
627
What are the 5 operative steps in a total knee replacement?
1. Exposure
2. 3 Bony cuts
3. Soft tissue balancing: ROM, Collateral balancing (Medio Lateral soft tissue release), Patellar tracking
4. Assessment
5. Closure
628
What are the 3 bony cuts for a total knee replacement?
1. Distal femoral
2. Rotational femoral (AP)
3. Proximal Tibial
629
What 4 things can incorrect alignment , position and rotation of the prosthesis can lead to?
1. Compromised function
2. Abnormal wear
3. Premature loosening
4. Patellofemoral problems
630
List the 9 roles computer navigation has in knee arthroplasty?
1. Well Proven
2. Component alignment in all the 3 planes
3. Contact stress reduction
4. Reduced fat embolism
5. Reduced Blood loss
6. MIS Surgery
7. Kinematics
8. Soft tissue releases
9. Longivity
631
What are the 5 factors in a joint replacement which gives the lowest risk?
1. Surgeon > 7yr experience
2. Does >75 cases / yr
3. Use any implant in top group
4. Unconstrained, Cemented
5. Effective Infection Control
