1
Q
List three features seen in tendinopathy.
A
- degeneration, disorganisation of collagen fibres
- increased cellularity
- little inflammation
2
Q
List some risk factors of tendinopathy.
A
age, chronic disease, DM, RA, adverse biomechanics, repetitive exercise, quinolone antibiotics
3
Q
Describe the pathology of tendinopathy. (4 points)
A
- deranged collagen fibres/degeneration with a scarcity of inflammatory cells
- increased vascularity around tendon
- failed healing response to micro tears
- inflammatory mediators released IL-1, NO, PG’s - cause apoptosis, pain and provoke degeneration through release of MMPs
4
Q
Lateral epicondylitis is commonly known as?
A
tennis elbow
5
Q
What is another name for medial epicondylitis?
A
golfers elbow
6
Q
What are the clinical features of tendinopathy?
A
pain, swelling, thickening, tenderness, provocative tests
7
Q
List some non-operative treatment options for tendinopathy.
A
NSAIDS, physiotherapy, GTN patches, extra corporeal shockwave therapy - common ones
8
Q
Discuss how physiotherapy is beneficial in tendinopathy.
A
eccentric loading - contraction of the musculotendinous unit whilst it elongates - beneficial in 80%
9
Q
Discuss the operative treatment options for tendinopathy.
A
- debridement
- excision
- tendon transfers
10
Q
What is compartment syndrome?
A
elevated interstitial pressure within a closed fascial compartment resulting in microvascular compromise
11
Q
What are the common sites of compartment syndrome?
A
leg, forearm, thigh
12
Q
What causes compartment syndrome?
A
- increased internal pressure e.g. bleeding, swelling, iatrogenic infiltration
- increased external compression e.g. casts/bandages, full thickness burns
13
Q
Describe the pathophysiology of compartment syndrome.
A
continuous cycle of increased pressure, increased venous pressure, reduced blood flow, ischaemia, muscle swelling, increased permeability
14
Q
Over time, what are the effects of ischaemia in compartment syndrome?
A
irreversible nerve and muscle damage
ischaemia
15
Q
List some clinical features of compartment syndrome.
A
- pain - out of proportion to that expected from the injury
- pain on passive stretching of the compartment
- pallor
- parasthesia
- paralysis
- pulselessness
16
Q
How might you use compartment pressure measurement in the diagnosis of compartment syndrome?
A
A pressure higher than 30 mmHg of the diastolic pressure in conscious or unconscious person is associated with compartment syndrome
17
Q
How might you treat compartment syndrome?
A
- open any constricting dressings/bandages
- reassess
- surgical release
- later wound closure
- skin grafting/plastic surgery input
18
Q
What is the commonest form of primary bone tumour?
A
myeloma
19
Q
Where do secondary tumours in bone usually arise?
A
bronchus, breast, prostate, kidney, thyroid
20
Q
Name two childhood secondary bone tumour origins.
A
neuroblastoma, rhabdomysosarcoma
21
Q
What are the effects of metastases on bone?
A
- often asymptomatic
- bone pain
- bone destruction
- long bones - pathological fracture
- hypercalcaemia
- spinal metastatic effects
22
Q
List some effects of spinal metastases.
A
- vertebral collapse
- spinal cord compression
- nerve root compression
- back pain
23
Q
What is the best imaging technique for metastatic bone disease?
A
PET CT
24
Q
What is the mechanism of destruction in bone tumours?
A
- osteoclasts, not tumour cells
- stimulated by cytokines from tumour cells
- inhibited by bisphosphonates
25
Where do sclerotic metastases of bone originate from?
- prostatic carcinoma
- breast carcinoma
- carcinoid tumour
26
Renal and thyroid carcinomas typically lead to which type of bone metastases?
solitary
27
Monoclonal proliferation of which type of cell leads to myeloma?
plasma cells
28
Discuss the impact of renal impairment caused by myeloma.
- precipitated light chains in renal tubules - Bence Jones protein in urine
- hypercalcaemia
- amyloidosis
29
Discuss the impact of marrow replacement caused by myeloma
- pancytopenia
- anaemia
- leukopenia: infections
- thrombocytopenia: haemorrhage
30
Name 3 benign primary bone tumours.
- osteoid osteoma
- chondroma
- giant cell tumour
31
Name 3 malignant primary bone tumours.
- osteosarcoma
- chondrosarcoma
- Ewing's tumour
32
List four clinical features of osteoid osteoma.
- M:F 2:1
- any bone, especially long bones
- pain - worse at night, relieved by aspirin
- sympathetic synovitis - juxta-articular tumours
33
What is an osteoid osteoma?
a small, benign osteoblastic proliferation
34
What is an osteosarcoma?
a malignant tumour whose cells form osteoid or bone
35
What are the two commonest sites of osteosarcoma?
metaphysis of long bones e.g. around knee
| early lung metastases
36
Define Paget's disease.
- disorder of excessive bone turnover
- increased osteoclasis, increased bone formation, structurally weak bone
- disorganised bone architecture
37
Where is Paget's disease common?
vertebrae, pelvis, skull, femur
38
List some clinical features of Paget's disease.
- bone pain
- bowing of long bones
- pathological fracture
- osteoarthritis
- deafness
- spinal cord compression
- high cardiac output
- Paget's sarcoma - lytic
- age > 40
- M > F
39
Name 3 cartilaginous tumours.
- enchondroma
- osteocartilaginous exostosis
- chondrosarcoma
40
What is an enchondroma?
lobulated mass of cartilage within medulla
41
Where does enchondroma affect? And what are the symptomatic features?
hands - swelling, pathological fracture
feet
long bones - often asymptomatic
42
What is an osteocartilaginous exostosis?
benign outgrowth of cartilage with endochondral ossification, probably derived from growth plate (metaphysis of long bones)
43
When is osteocartilaginous exostosis common?
adolescence
44
Is chondrosarcoma primary or secondary?
Both
primary - de novo
secondary - pre-existing enchondroma or exostosis
45
What sites are chondrosarcomas usually found?
axial skeleton, pelvis, ribs, shoulder girdle, proximal femur and humerus
46
What is a chondrosarcoma?
a cancer composed of cells derived from transformed cells that produce cartilage
47
What is Ewing's sarcoma?
a malignant small, round, blue cell tumour. It is a rare disease in which cancer cells are found in the bone or in soft tissue
48
At what age does Ewing's sarcoma peak?
5-15 years
49
Where does Ewing's sarcoma affect?
```
long bones (diaphysis or metaphysis)
flat bones of limb girdles
```
50
Name 3 common sites for Ewing's sarcoma to metastases to.
lung, bone marrow, bone
51
What are the three basic steps in indirect fracture healing?
inflammation
repair
remodeling
52
Define indirect fracture healing.
formation of bone via a process of differential tissue formation until skeletal continuity is restored
53
Give more detail about the inflammatory process in indirect fracture healing.
- fracture haematoma forms from broken vessels
- 6-8 hours after injury
- swelling and inflammation to dead bone cells
54
Describe fibrocartilage callus formation in fracture healing.
- lasts about 3 weeks
- new capillaries organise fracture haematoma into granulation tissue - 'procallus'
- fibroblasts and osteogenic cells invade procallus
- make collagen fibres which connect ends together
- chondrocytes begin to produce fibrocartilage
55
Describe bony callus formation in fracture healing.
- after 3 weeks and lasts about 3-4 months
| - osteoblasts make woven bone
56
Discuss bone remodeling in relation to indirect fracture healing.
- osteoclats remodel woven bone into compact bone and trabecular bone
- often no trace of fracture line on X-rays
57
Define direct fracture healing.
'direct formation of bone via osteoclastic absorption and osteoblastic formation, without the process of callus formation, to restore skeletal continuity'
- unique 'artificial' surgical situation
- relies upon compression of bone ends
- cutting cones cross fracture site
58
Briefly describe the blood supply of bone.
- endosteal - inner 2/3rds
| - periosteal - outer 1/3rds
59
Which fractures are prone to problems with union or necrosis because of problems with blood supply?
- proximal pole of scaphoid fractures
- talar neck fractures
- intracapsular hip fractures
- surgical neck of humerus fractures
60
List some patient factors which inhibit fracture healing.
increasing age, diabetes, anaemia, malnutrition, peripheral vascular disease, hypothyroidism, smoking, alcohol
61
Name some medications which inhibit fracture healing.
NSAIDs, steroids, bisphosphonates
62
Describe how NSAIDs inhibit fracture healing.
- reduce local vascularity at fracture site
- additional reduction in healing effect independent of blood flow
- specifically COX-2 inhibitors
63
Describe how bisphosphonates inhibit fracture healing.
- inhibit osteoclastic activity
| - delay fracture healing as a result
64
List potential fractures of the femoral neck.
- subcapital
- transcervical
- intertrochanteric
- subtrochanteric
- fracture of greater trochanter
- fracture of less trochanter
65
What is the hallmark sign of degenerative bone disease?
bone production
66
What is the hallmark sign of inflammatory joint disease?
periarticular erosions
67
What is the hallmark of depositional bone disease?
periarticular soft tissue masses
68
On X-ray how can you tell the difference between an active and old bone erosion?
```
active = ill-defined
old = well-defined
```
69
What are the X-ray features of primary degenerative arthritis?
- narrowed joint space
- osteophytes
- subchondral sclerosis/cysts
70
Where is excessive wear and tear most common?
hips and knees
71
List the common causes of secondary degenerative arthritis.
trauma, infection, avascular necrosis, calcium pyrophosphate dihydrate deposition (CPDD) disease, RA, haemophilia
72
What causes CPDD disease?
idiopathic or associated with hyperparathyroidism and haemochromatosis
73
What impact does CPDD have on articular cartilage? And which bones does it most commonly affect?
calcification
- triangular fibrocartilage of wrist
- knee, hip, shoulder
- symphysis pubis
74
Describe the clinical features of CPDD.
- sudden onset of pain/fever
- tender, swollen, red joint
- may mimic septic arthritis
75
Which organisms commonly cause infectious arthritis?
staph, strep, TB
76
Which joints does infectious arthritis commonly affect?
- fingers from bites
- feet in diabetes
- hips in total hip replacements
77
Describe the clinical features of a infectious arthritis joint.
- soft tissue swelling
- destruction of cartilage/bone
- rapid loss of joint space
- +/- periosteal reaction
- osteoporosis
- later subluxation, OA, fusion
78
What are the radiographic findings in discitis?
- normal 1-3 weeks
- end-plate erosion
- disc space narrowing
- bone destruction
- paravertebral mass
- late - sclerosis
- ankylosis
79
What is the newest classification for RA?
presence of bilateral wrist, MCP or PIP joint enhancement on MRI and leads to a more accurate diagnosis of early RA
80
Describe a RA joint.
- soft tissue swelling
- synovitis
- effusion
- erosions and cysts
- joint space narrowing
- secondary degenerative changes
- bone marrow oedema
81
How do sero-negative inflammatory arthropathies differ from RA?
- negative rheumatoid factor
- normal bone density
- periostitis
- ankylosis (fusion)
- asymmetrical pattern
82
What gene is positive in sero-negative inflammatory arthropathies?
HLA-B27
83
List 4 causes of sero-negative inflammatory arthropathy.
Psoriatic arthritis
Ankylosing spondylitis
Inflammatory bowel disease
Reactive arthritis
84
Discuss the clinical features of psoriatic arthritis.
- usually skin and nail changes
- DIP joints of hands > feet
- pencil in cup deformity
- resorption of distal phalanges
- M=F, young adults
85
What is the other name for reactive arthritis?
Reiter's syndrome
86
Discuss the clinical features of reactive arthritis including extra-articular manifestations.
- M > F
- 20-40 yrs
- asymmetrical oligoarthritis
- lower limb and sacroiliac joint
- dactylitis, enthesitis, bursitis
- circinate balanitis
- keratoderma blennorrhagicum
- mouth ulcers
87
What organisms cause reactive arthritis?
chlamydia, salmonella, shigella
88
What illnesses go in hand with reactive arthritis to form a triad?
- urethritis
| - conjuncitivitis
89
Who does ankylosing spondylitis commonly affect?
- M:F 3:1
- 20-40 yrs
- HLA B27 +ve
90
Describe the clinical features of AS?
- low back pain
- stiffness
- bilateral sacro-illiitis
- squaring of vertebral bodies
- peripheral large joint arthritis
91
What is gout?
sodium urate crystal induced synovial inflammation
92
Who does gout usually affect?
elderly males, hereditary, young age suspect renal disease or myeloproliferative disorder
93
What are the radiographic features seen in gout?
- para-articular erosions
- sharply marginated with sclerotic rims
- overhanging edges
- no joint space narrowing till late
- little or no osteoporosis
- soft tissue swelling
- tophi not usually calcified
94
What is osteonecrosis?
avascular necrosis - refers to bone infarction near a joint
95
Where is osteonecrosis most common?
hip and shoulder
96
What are the consequences of osteonecrosis?
- pain from infarction
| - death of subchondral bone can lead to collapse of the joint surface and end stage arthritis
97
Describe how osteonecrosis present with particular focus on femoral head.
- often asymptomatic and found on imaging
- pain - either from infarction or arthritis
- groin pain that worsens with weight-bearing and motion
- rest pain 2/3
- night pain 1/3
98
Osteonecrosis accounts for what percent of total hip replacement?
10
99
What is the peak age of prevalence for avascular necrosis?
40-50
100
What is the prevalence of osteonecrosis in sickle cell anaemia?
10
101
Discuss the pathophysiology of osteonecrosis.
- decreased intraosseous blood flow
- ischaemia
- bone necrosis
102
What can cause decreased blood flow in osteonecrosis? (4 points)
1. Blood vessel disruption e.g. trauma
2. Intraluminal obliteration e.g. fat microemboli and thrombosis
3. Increased marrow pressure e.g. adipocyte hypertrophy and bone oedema
4. Cytotoxicity
103
List factors which lead to poor outcome of osteonecrosis.
- extensive
| - heavy loads
104
What happens to cause the necrotic cancellous bone to collapse?
- osteoclasts resorb the necrotic trabeculae while remaining ones serve as scaffolding for deposition of new bone
- 'creeping substitution' may not be fast enough
105
What is the crescent sign seen in osteonecrosis?
subchondral radiolucency which precedes subchondral collapse
106
Discuss what is seen in imaging in late stages of AVN.
- loss of sphericity and collapse of femoral head
- joint space narrowing
- bone remodelling
107
List RF's of AVN.
- trauma
- corticosteroids
- alcohol abuse
- sickle cell disease
- bisphosphonates
108
What are the treatment option for AVN?
- partial weight bearing
- bisphosphates (undergoing trial)
- core decompression with or without bone graft in early stages
- replacement if bone collapse
109
What is RA?
a chronic autoimmune multisystem disease affecting any synovial joint
hallmark is synovial but multiple extra-articular manifestations
110
Discuss the aetiology of RA.
- HLA-DR4
- smoking
- infection
- hormonal
111
Describe the pathophysiology of RA.
- synovitis = immune cells invading a normally acellular synovium in the form a of pannus
- release of TNF, IL-1 and IL-6 causing inflammation and destruction
112
What is a pannus in relation to RA?
hyperplastic, invasive tissue leading to cartilage breakdown, erosions and reduced function
113
Name some clinical features of RA.
- synovitis
- symmetrical
- early = MCPs/PIPs/wrists
- inflammatory = pain, erythema, swelling
- fatigue, weakness, fever, weight loss, anoxeria
114
What are the classic joint features seen in late stage RA?
- boutonniere
- swan neck
- Z thumb
- volar subluxation of wrist
- ulnar deviation digits
- radial deviation wrists
- piano key ulnar head
115
Describe some of the extra-articular manifestations of RA.
- pleural effusions
- mononeuritis multiplex
- anaemia
- thrombocytosis
- lung fibrosis and nodules
- muscle wasting
116
Which investigations would you undertake in a patient with suspected RA?
FBC, U&Es, LFT, ESR/CRP, RF, ACPA, ANA
117
What is rheumatoid factor? What is its role in investigating RA?
- autoantibody against Fc portion of IgG
| - part of assessment, not diagnostic
118
What is ACPA?
Anti–citrullinated protein antibody - linked with smoking (increases citrullination) - predictor of worse prognosis, more erosions and resistant disease
119
Discuss the imaging techniques useful in RA and what they show.
- XR: Loss of joint space, Erosions, Soft tissue swelling, Soft bones (osteopenia)
- USS: synovitis and erosions
- MRI: bone marrow oedema
120
What non-pharmacological treatments are available for RA?
OT, PT, podiatrists, dietitians
121
Discuss the pharmacological medications available in RA including symptomatic and disease modifying.
- symptomatic: NSAIDs, analgesia
| - DMARDs: glucocorticoids, methotrexate, sulfasalazine, anti-TNF (infliximab), anti-CD20, anti-IL6
122
Which DMARD is a dihydrofolate reductase inhibitor?
methotrexate
123
What must be given alongside MTX?
folic acid
124
What is MTX contraindicated?
pregnancy, infection, on antibiotics
125
What are common side effects of sulfasalazine?
GI, rashes, BM
126
In what case is sulfasalazine indicated over MTX?
pregnancy
127
Etanercept, inflixumab and adalimumab are examples of which type of biologic therapy?
anti-TNF
128
What are the side effects of anti-TNF therapy?
TB, infection, MS, CHF
129
What is the mechanism of rituximab?
anti-CD20
130
List 3 side effects of rituximab.
infection, PML, hypogammaglobulinaemia
131
Name an anti-IL6 therapy.
tocilizumab
132
In which populations is SLE most common?
afro-caribbean, south asian, mexican
133
List the clinical SLICC criteria used in diagnosis of SLE.
- acute cutaneous lupus e.g. malar rash
- chronic cutaneous lupus e.g. classic discoid rash
- oral ulcers
- non-scarring alopecia
- synovitis
- serositis
- renal dysfunction
- neurological: seizures, pyschosis
- haemolytic anaemia
- leucopenia
- thrombocytopenia
134
List the immunological SLICC criteria used in diagnosis of SLE.
- high ANA
- > x2 anti-asDNA
- antiphospholipid (lupus anticoagulant)
- low complement
- +ve direct Coomb's test
135
How is SLE diagnosed from SLICC? (2 points)
- 4 of criteria including one from each section
| - biopsy proven nephritis compatible with SLE and with ANA or anti-dsDNA antibodies
136
Describe the common features in the clinical presentation of SLE.
- constitutional symptoms
- cutaneous manifestations
- arthralgia and arthritis
137
Name 3 MSK manifestations of SLE.
- AVN
- fibromyalgia
- osteoporosis
138
What % of people with SLE will develop ESFR in 10 years?
20
139
List some pulmonary manifestations of SLE.
- pleural effusions
- acute pneumonitis
- diffuse alveolar haemorrhage
- pulmonary hypertension
140
List some CV manifestations of SLE.
- pericarditis
- myocarditis
- valvular abnormalities
- coronary heart disease
- risk of MI x50
141
Name some neuropsychiatrc manifestations of SLE.
headache, anxiety, seizures, demyelinations, GBS, mononeuritis
142
List some haematological manifestations of SLE.
- anaemia of chronic disease
- autoimmune haemolytic anaemia
- thrombotic thrombocytopenic purpura
- leucopenia
- thrombocytopenia
143
What is the significance of ANA?
anti-nuclear antibody, often diagnostic of SLE
144
What are the three medications licensed as treatment for SLE in UK?
- steroids
- hydroxychloroquine
- belimumab
145
What is belimumab?
human monoclonal antibody that inhibits B-cell activating factor (BAFF)
146
What is the treatment for mild cutaneous SLE disease?
topical therapies, UVA/UVB sunblock
147
What is the treatment for mild MSK SLE disease?
NSAIDs, IA/IM steroid, low dose oral prednisolone
148
What is the treatment for mild serositis SLE disease?
NSAIDs, MTX
149
Discuss the treatment of moderate SLE.
treatment as per mild plus:
- oral prednisolone
- MTX
- immunosuppressants e.g. Azathioprine, Mycophenolic acid, ciclosporin, tacrolimus
- belimumab
150
Discuss the treatment of severe SLE disease.
treatment as per mild and moderate plus:
- high dose steroid
- DMARDs
- cyclophosphamide
- IV immunoglobulin therapy
- plasmapheresis
151
What are the primary vasculitides?
a group of autoimmune conditions characterised by inflammation of blood vessels
152
What systems can be affected by inflammation of blood vessels?
joints, skin, nerves, kidneys, lungs, ENT
153
What are the different types of vasculitis?
- large vessel vasculitis: giant cell arteritis, Takayasu's arteritis
- medium vessel vasculitis: polyarteritis nodosa, Kawasaski disease
- small: ANCA-associated (microscopic polyangiitis, granulomatosis with polyangiitis, eosinophilic granulomatosis), immune complex (HSP-IgA vasculitis, Goodpasture's disease)
154
Define giant cell arteritis.
systemic vasculitis that affects the aorta and its major branches
155
Describe the clinical presentation of giant cell arteritis.
- headache - temporal with tenderness, subacute onset, constant
- visual symptoms
- jaw claudication
- polymyalgia rheumatica symptoms
156
What are polymyalgia rheumatica symptoms?
subacute onset of shoulder and pelvic gridle stiffness and pain
157
What are the three main complications of temporal arteritis?
- visual loss
- large vessel vasculitis
- CVA
158
How is GCA typically diagnosed?
- clinical presentation
- clinical examination findings
- acute phase response: ESR/CRP
159
What are the clinical exam findings in GCA?
temporal artery assymetry, thickening, loss of pulsatility
160
Describe the gold standard diagnostic tool in GCA.
temporal artery biopsy:
| - positive if interruption of internal elastic lamina with infiltration of mononuclear cells in vessel
161
What are the treatment options for GCA?
- prednisolone 60mg for 1 month
- taper to 15mg by 12 weeks
- discontinue by 12-18 months
162
What is the DDx of cutaneous vasculitis?
idiopathic, drugs, infection, secondary RA/CTD/PBC, malignancy, manifestation of ANCA vasculitis
163
Describe the clinical features of Henoch Schonlein Purpura.
- classic purpuric rash esp. buttocks, thigh
- hives, confluent petechiae, ecchymoses, ulcers
- arthralgia/arthritis
164
List some complications of Henoch Schonlein Purpura.
- GI: pain, bleeding, diarrhoea
- renal: IgA nephropathy
- orchitis (inflammation of testicles)
165
Discuss the approach to management of HSP.
1. Exclude secondary causes
2. Assess extent of involvement - urinalysis
3. Often no treatment required - frequently self-limiting up to 16 weeks
166
Streptococcal sore throat can occasionally trigger which vasculitis?
HSP
167
Which group of vasculides have the most morbidity and mortality associated with it?
ANCA- associated small vessel vasculitis
168
Define granulomatosis with polyangiitis.
vasculitis characterised by granulomatous necrotising inflammatory lesions of the upper and lower respiratory tract and often a pauci-immune glomerulonephritis
169
Describe the triad of GPA disease.
1. Upper airway/ENT - rhinitis, sinusitis, chronic otitis media
2. Renal - pauci-immune glomerulonephritis
3. Lower respiratory - parenchymal nodules, alveolar haemorrhage
170
List some constitutional symptoms of GPA.
fatigue, weight loss, fever, sweats, myalgia, arthralgia, failure to thrive in elderly
171
What are ANCAs?
autoantibodies directed against the cytoplasmic constituents of neutrophils and monocytes
172
What are the two methods for testing ANCA?
- indirect immunofluorescence which gives p/cANCA staining patterns
- ELISA for PR3/MPO
173
How useful is ANCA?
- diagnosis
- prognostic information
- assess response to treatment
- monitoring for early signs of relapse
174
Which ANCA result is suggestive of GPA?
cANCA with PR3
175
Which ANCA result is suggestive of MPA?
pANCA with MPO
176
How is vasculitis treated?
1. Remission induction - prednisolone + MTX (if moderate)/rituximab or cyclophosphamide (if severe) i.e. IMMUNOSUPPRESSION
2. Remission maintenance - prevent relapse, lower drug toxicites, more prolonged therapy: azathioprine, MTX
177
List some side effects of corticosteroids.
- weight gain and fluid retention
- glaucoma
- osteoporosis
- infection
- hypertension and hypokalaemia
- peptic ulcer, GI bleed
- psychological symptoms
178
What is the mechanism of action of corticosteroids?
Bind to glucocorticoid receptors. This causes up-regulation of a variety of anti-inflammatory mediators and down regulation of pro-inflammatory mediators. This provides immunosupression.
179
What is the mechanism of action of methotrexate?
Stops the action of the enzyme dihydrofolate needed for production of DNA.
180
List some adverse effects of methotrexate.
- GI: N&V, diarrhoea, hepatitis, stomatitis
- haematological: leukopenia
- others: frequent infection, PF
181
What are the main indications for MTX use?
- RA
- psoriasis and psoriatric arthropathy
- steroid sparing agent in GCA
182
Discuss the mechanism of action of azathioprine.
Disrupt DNA synthesis. Blocks purine synthesis mainly in lymphocytes.
183
What are some adverse effects of azathioprine?
- GI: N&V, diarrhoea, hepatitis, cholestasis
- haematological: leucopenia, thrombocytopenia
- frequent infections
184
How can toxicity develop when using azathioprine?
some individuals lack TPMP enzyme which is vital in reducing active drug in cells
185
When is azathioprine used in clinical practice?
- IBD e.g. ulcerative colitis, Crohn's disease
- myaesthenia gravis
- eczema
186
How does cyclosporin work?
- small molecule inhibitor of calcineurin
- effect of inhibiting signal transduction from activated TCR complex
- profound inhibition of T cell activation
187
List some adverse effects of cyclosporin.
nephrotoxicity, hypertension, hepatotoxicity, anorexia, lethargy, hirsutism, paraesthesia
188
What are the indications for cyclosporin use?
- usually given for organ transplantation
- inflammatory conditions
- used topically i.e. skin, eyes
189
What are the disadvantages of immunosuppressants?
- often insufficient to control inflammatory disease with subsequent progression
- significant toxicities
- bone marrow suppression
- frequent infections
190
What are some side effects of biologic therapies?
hypersensitivity reaction, infusion reactions, mild GI toxicity
191
There is an increased risk of TB infection with which biologic therapy?
anti-TNF - need to screen for latent TB before prescribing
192
Which therapies increase risk of pneumonia and respiratory tract infection?
abatacept (anti-CD86) and anti-IL1
193
Rituximab increased the risk of which infections?
- generalised increased risk of serious infection
| - hepatitis B reactivation
194
85% of Ewing's sarcoma are associated with translocation of which chromosomes?
11 and 22
195
In AVN of femoral head, which movements are particularly limited?
internal rotation and abduction
196
What is the name given to the disease causing avascular necrosis and collapse of the lunate bone in the wrist?
Kienbock's disease
197
What are the three key imaging findings in osteonecrosis?
1 subchondral collapse
2 bone remodelling
3 crescent sign
198
What are some of the risk factors to developing septic arthritis?
- RA and OA
- joint prosthesis/surgery
- IV drug abuse
- ALD
- diabetes
- cutaneous infections/ulcers
- chronic renal failure
199
What are the differentials of an acute hot, swollen, tender joint?
- septic arthritis
- crystal arthropathy
- trauma
- early presentation of polyarthropathy
200
What investigations should be carried out if septic arthritis is suspected?
joint aspirate, blood cultures, CRP, X-ray
201
How long should an antibiotic regimen be carried out in septic arthritis?
- 2 weeks IV
| - 4 weeks oral
202
Which joint is most commonly affected with gout?
MTP joint of big toe
203
List some factors which may precipitate an attack of gout.
trauma, surgery, infection, starvation, diuretics
204
What are the risk factors for developing gout?
- reduced urate excretion: elderly, impaired renal function, hypertension, metabolic syndrome
- excess urate production: diet, genetics, myelo/lympho-proliferative disorders, psoriosis
205
Polarised light microscopy is used to investigate synovial fluid. What is the main difference seen between gout and CPPD?
- gout = negatively birefringent crystals
| - CPPD = positively birefringent crystals
206
What are some of the risk factors to developing septic arthritis?
- RA and OA
- joint prosthesis/surgery
- IV drug abuse
- ALD
- diabetes
- cutaneous infections/ulcers
- chronic renal failure
207
What are the differentials of an acute hot, swollen, tender joint?
- septic arthritis
- crystal arthropathy
- trauma
- early presentation of polyarthropathy
208
What investigations should be carried out if septic arthritis is suspected?
joint aspirate, blood cultures, CRP, X-ray
209
How long should an antibiotic regimen be carried out in septic arthritis?
- 2 weeks IV
| - 4 weeks oral
210
Which joint is most commonly affected with gout?
MTP joint of big toe
211
List some factors which may precipitate an attack of gout.
trauma, surgery, infection, starvation, diuretics
212
What are the risk factors for developing gout?
- reduced urate excretion: elderly, impaired renal function, hypertension, metabolic syndrome
- excess urate production: diet, genetics, myelo/lympho-proliferative disorders, psoriosis
213
Polarised light microscopy is used to investigate synovial fluid. What is the main difference seen between gout and CPPD?
- gout = negatively birefringent crystals
| - CPPD = positively birefringent crystals
214
What medications are currently available for acute gout attack?
- NSAIDs
- colchicine
- steroids
- RICE
215
How might an acute attack of gout be prevented?
- lifestyle changes
- allopurinol
- febuxostat (use in renal failure)
216
When should prophylaxis for acute gout attacks be considered?
> 1 attack in 12 months, tophi, renal stones
217
Describe the mechanism of action of allopurinol.
xanthine oxidase inhibitor
| Reduces synthesis of uric acid by competitively inhibiting xanthine oxidase. Reduces serum uric acid level.
218
What side effects are associated with allopurinol?
SJS/TEN, hepatitis, vasculitis, AKI
219
Describe the clinical criteria for diagnosis of rheumatoid arthritis.
```
A: Joint involvement
- 1 large joint = 0
- 2-10 large joints = 1
- 1-3 small joints = 2
- 4-10 small joints = 3
- >10 joints = 5
B: Serology
- -ve RF and -ve anti-CCP = 0
- low +ve RF or low +ve anti-CCP = 2
- high +ve RF or high +ve anti-CCP = 3
C: Acute phase reactants
- normal CRP and ESR = 0
- abnormal CRP or ESR = 1
D: Duration of symptoms
- <6 weeks = 0
- >6 weeks = 1
```
Scores =/> 6 are diagnostic
220
What is Sjogren's syndrome?
chronic inflammatory autoimmune disorder involving lymphocytic infiltration and fibrosis of exocrine glands
221
List some of the clinical features of Sjogren's syndrome.
- decreased tear production
- decreased salivation
- parotid swelling
- dry cough and dysphagia
222
What are some of the systemic signs of Sjogren's syndrome?
polyarthritis, Raynaud's, lymphadenopathy, vasculitis, peripheral neuropathy
223
Which other autoimmune conditions is Sjogren's syndrome associated with?
thyroid disease, autoimmune hepatitis, PBC
224
What investigations should you carry out in Sjogren's syndrome?
- Schirmer's test = conjunctival dryness
| - antibodies = anti-RO, anti-La, ANA, RF
225
What treatment is available for Sjogren's syndrome?
- hypromellose (artificial tears)
- frequent drinks
- NSAIDs for arthralgia
226
Describe the three main features of systemic sclerosis.
1. Scleroderma
2. Internal organ fibrosis
3. Microvascular abnormalities
227
Which plasma autoantibodies are present in limited systemic sclerosis?
ANA, anticentromere antibodies
228
Describe the skin distribution of both limited and diffuse systemic sclerosis.
- limited: face, hands, feet
| - diffuse: whole body
229
Which plasma autoantibodies may be positive in diffuse systemic sclerosis?
ANA, antitopoisomerase-1, anti-RNA polymerase
230
What is myositis?
rare conditions characterised by insidious onset of progressive symmetrical proximal muscle weakness and autoimmune mediated striated muscle inflammation, associated with myalgia +/- arthralgia.
231
What are some of the consequences of muscle weakness in myositis?
dysphagia, dysphonia, respiratory weakness
232
List the skin signs seen in dermatomyositis.
- macular rash
- lilac-purple rash on eyelids often with oedema
- nailfold erythema
- Gottron's papules
233
Name the tests that you would carry out in myositis.
- muscle enzymes in plasma: increased
- MRI: muscle oedema
- autoantibodies: anti-Mi2, anti-Jo1
234
What treatment is available for myositis?
- prednisolone
| - skin: hydroxychloroquine/topical tacrolimus
235
Define juvenile idiopathic arthritis.
disease of childhood onset characterised primarily by arthritis persisting for at least 6 weeks and currently having no known cause
236
Which eye disease often co-exists with oligoarthritis in children?
uveitis - screening by paediatric opthalmologist
237
What are the childhood equivalents of RA and AS?
- RA = rheumatoid factor positive polyarthritis
| - AS = enthesitis related arthritis
238
What is an enthesis?
insertion of tendon, ligaments, joint capsule, fascia to bone
239
How does Kawasaki disease present in young children and babies?
aneurysm formation in medium to large sized arteries, high fever, mucositis, conjunctivitis, arthritis, red palms
240
What are some of the causes of non-specific low back pain?
- lumbar strain/sprain
- degenerative discs/facet joints
- disc prolapse, spinal stenosis
- compression fractures
241
What is a vertebral disc prolapse and how might it present clinically?
- herniated nucleus pulposus
- acute lower back pain
- worse when coughing
- leg > back pain 'sciatica'
- leg pain = dermatomal distribution
242
In which cause of back pain is the straight leg test positive?
disc prolapse
243
What is spinal stenosis and how does it present?
- anatomical narrowing of spinal canal
| - 'claudication' in legs/calves - worse walking, rest in flexed position
244
What are the red flag symptoms of cauda equina syndrome?
- bilateral sciatica
- saddle anaesthesia
- bladder or bowel dysfunction
- reduced anal tone on PR
245
What is spondylolisthesis?
when one of the vertebrae slips out of place
246
Where does pain from a vertebral compression fracture usually radiate?
in 'belt' around chest/abdomen
247
What treatments are available for vertebral compression fractures?
- analgesia
- vertebroplasty
- kyphoplasty
248
Describe sources of referred pain to the back.
- aortic aneurysm
- acute pancreatitis
- peptic ulcer disease
- acute pyelonephritis/renal colic
- endometriosis
249
What are the symptoms of infective discitis?
constant back pain, fever, weight loss
250
What investigations should you carry out if suspecting infective discitis?
- FBC, ESR, CRP
- blood cultures
- radiology-guided aspiration
251
What is the most common pathogen to cause infective discitis?
staph aureus
252
What is the distinguishing feature between vertebral infection and malignancy on X ray?
- infection = damage to both sides
| - malignancy = only one side
253
What are the classical features of inflammatory back pain?
- onset < 45 years
- early morning stiffness >30 mins
- back stuff after rest and improves with movement
- waking during night with buttock pain
254
What are the red flag symptoms of back pain?
new onset age <16 or >50, trauma, previous malignancy, fever/rigors, malaise, weight loss, previous steroid use, IV drug use, HIV, immunosuppression, recent infection, urinary retention, non-mechanical pain
255
What are the red flag signs of back pain?
saddle anaesthesia, reduced anal tone, hip or knee weakness, generalised neurological deficit, progressive spinal deformity
256
What is the criteria for diagnosis of ankylosing spondylitis?
1. Clinical criteria
a) low back pain and stiffness > 3 months which improves with exercise, but is not relieved by rest
b) limitationof motion of the lumbar spine
c) limitation of chest expansion relative to normal
2. Radiological criterion
- sacroiliitis grade =/> 2 bilaterally or grade 3-4 unilaterally
Definite AS if radiological criterion is associated with at least 1 clinical criterion.
257
What is ankylosing spondylitis and which gene mutation is commonly associated with it?
- chronic inflammatory condition of the spine and sacroiliac joints of unknown aetiology
- HLA B27
258
What is the difference between radiography axSpA and AS?
- radio: X-ray +ve sacro-ilitis
| - AS: X-ray +ve sacro-ilitis and/or spinal changes
259
What are some of the features of spondyloarthritis?
- axial arthritis - inflammatory back pain
- fatigue
- enthesitis
- dactylitis
- ankylosis/new bone formation
- osteoporosis
- extra-articular: psoriasis, uveitis, IBD, aortic valve incompetence, oral ulcers
260
Discuss the ASAS classification criteria for axial SpA.
1. Sacroilitis on imaging plus >/= 1 SpA feature
OR
2. HLA-B27 plus >/= other SpA features
261
In which people groups are axSpA and AS most common?
- onset < 45 years
- mainly 15-35
- AS = mainly male
- axSpA = equal gender
262
Discuss what is seen in MRI and X-ray in AS.
- MRI: inflammation (bone marrow oedema), erosions, sclerosis, ankylosis
- X-ray: joint space narrowing, sclerosis, erosion, ankylosis, syndesmophytes
263
Which cytokines are associated with enthesitis and axSpA?
IL-23, IL-17
264
What are the treatment options for axSpA?
- exercise, physiotherapy
- NSAIDs
- TNFa inhibitors
- IL17 inhibitors
- surgery
265
Differentiate between the X-ray signs seen in RA and OA.
RA: Loss of joint space, Erosions, Soft tissue swelling, Soft bone (osteopenia)
OA: Loss of joint space, Osteophytes, Subchondral sclerosis, Subchondral cysts
Phase 3
flashcards
Decks in class (10)
# Cards
