Flashcards in Clinical (Weeks 1+2) Deck (183):
1
What genes are associated with a susceptibility to RA?
HLA DR4
HLA DR1
2
What cells invade the synovium in RA?
Macrophages
Fibroblasts
Multinucleated giant cells
3
What is the basic process behind RA?
1. Synovial expansion
2. Invasion of bone
3. Erodes bone and cartilage
4
Articular symptoms of RA?
Joint pain
Morning stiffness
Joint swelling
5
Extra-articular manifestations of RA
Respiratory:
- Effusions
- Fibrosis
- Nodules
Rheumatoid nodules on extensor surfaces
Ocular involvement:
- Keratoconjunctivitis
- Episcleritis
- Uveitis
- Nodular scleritis
Increased CVS morbidity and mortality
6
What hand joint is not affected by RA?
DIP
7
What pattern of joint involvement is seen in RA?
Symmetrical
8
How is RA defined by the EULAR/ACR Classification?
Synovitis in >/=1 joint
Absence of better diagnosis
Achievement of >/=6/10 of:
- Number and site of affected joints (0-5)
- Serological abnormality (0-3)
- Increased CRP/ESR (0-1)
- Symptom duration (0-1)
9
What is the best autoantibody to test for to aid in the diagnosis of RA?
Anti-CCP (Cycli citrullinated peptide) Antibody
10
Does a patient need to be Rheumatoid Factor positive (RhF) to have RA?
No
11
What chronic haematological change may be seen in RA?
Anaemia
12
What x-ray changes are seen in RA?
Osteopaenia:
- Loss of joint space
- Periarticular erosions
Soft tissue swelling
13
What late complications can be seen in RA?
Infection
Cervical myelopahy secondary to:
- Atlanto-axial/Subaxial subluxation
ILD
Peripheral neuropathy
14
What comorbidities is RA associated with?
Severe infections
CVS mortality
Lymphoma
15
What genetic factor is a poor prognostic factor in RA?
HLA DR4 positive
16
How soon must treatment be begun in RA to prevent irreversible damage?
Within 3 months
17
What are the principles of RA treatment?
DMARDs
Steroids to cover lag phase
Frequent reviews
18
Give examples of DMARDs and when they might be used?
1st line - Methotrexate
2nd line and in pregnancy - Sulphasalazine
Hydroxychloroquine
Leflunamide
19
What four approaches to biologic therapy can be used in RA and give examples of drugs in each class?
TNF-alpha inhibition:
- Infliximab
- Adalimumab
- Etanercept
B cell depletion:
- Rituximab
Disruption of T cell co-stimulation:
- Abatecept
Interleukin inhibition:
- Anankira (IL-1)
- Tocilizumab (IL-6)
(Jak-2 inhibitors)
20
What is the pathogenesis of OA?
Loss of matrix (Collagen ii with chondrocytes embedded)
Cytokine release:
- IL-1
- TNF-alpha
- Metalloproteinases
- Prostaglandins from chondrocytes
Surface fibrosis and attempted repair -> Oestophytes
21
How are localised and generalised idiopathic OA defined
Localised:
- Hands
- Feet
- Knee
- Hip
- Spine
Generalised is >/= 3 sites involved
22
What are some secondary causes of OA?
Previous injury
RA
Genetic
Acromegaly
Crystal arthropathy
Perthes
SUFE
23
Risk factors of OA
Age
Female
Obesity
Job
Injury/Sports
24
When is pain typically present in OA?
During exercise
25
How long does morning stiffness last in OA?
Less than 30 minutes
26
What might be found on examination of a patient with OA?
Crepitus
Bony enlargements
Joint tenderness and effusion
27
What can lumbar spine OA result in?
Spinal stenosis
28
Where does hip OA pain radiate to?
Groin/back
29
OA at what site can result in genu valgum and a Baker's cyst?
Knee
30
What are some features of OA in the hand?
Heberden's nodes (DIP OA)
Bouchard's nodes (PIP OA)
Thumb base squaring (CMC OA)
31
Sterotypical x-ray features of OA?
Loss of joint space
Osteophyte formation
Subchondral sclerosis
Subchondral cysts
(LOSS)
32
Define the grades of OA according to the Kellgren-Lawrence scale?
Grade 0:
- No findings
Grade 1:
- Minute osteophytes
Grade 2:
- Definite osteophytes
- Unimpaired joint space
Grade 3:
- Definite osteophytes
- Moderate loss of joint space
Grade 4:
- Definite osteophytes
- Severe space loss and sclerosis
33
What are the main non-pharmacological treatments of OA?
Physiotherapy
Weight loss
Exercise
34
What pharmacological treatments are prescribed in OA?
Analgesia:
- Paracetamol
- Topicals
NSAIDs
Pain modulators:
- TCAs
- Gabapentin
35
What intra-articular medications can be used in OA?
Steroids
Hyaluronic acid
36
Surgical treatments of OA
Arthroscopic washout
Soft tissue trimming
Joint replacement
37
What causes gout?
Uric acid crystals
38
Is gout more common in men or women?
Men
39
What results in increased urate production?
Enzyme defects
Psoriasis
Haemolytic disorders
Alcohol
High purine diet (red meat, seafood)
40
What results in decreased urate excretion?
Renal impairment
Volume depletion
Hypothyroidism
Diuretics
Cytotoxics
41
True or false; Blood uric acid can be normal in acute gout?
True
42
What joint is the most common site of acute gout?
1st MTP (Podagra)
43
What is chronic tophaceous gout associated with?
Diuretics
44
What is the best diagnostic investigation for gout?
Polarised microscopy:
- Negatively birefringent
- Needle shaped crystals
45
What appearance will gout show on x-ray?
Erosive arthritis features
46
How do we treat an acute flare of gout?
NSAIDs
Steroids
Colchicine
47
How can we prevent gout?
Xanthine oxidase inhibitors:
- Allopurinol
- Febuxostat
48
How do we use allopurinol?
Start 2-4 weeks after acute
Continue use during future acute flares
Titrate dose up until serum urate
49
What causes psuedogout?
Deposition of calcium pyrophosphate crystals
50
What does pseudogout cause?
Calcinosis:
- Deposition of calcium in cartilage and soft tissue
- No inflammation
51
How does pseudogout appear on polarised micropscopy?
Mildly positive birefringement
Envelope-shaped crystals
52
What is pseudogout associated with?
Hyperparathyroidism
Hypothyroidism
Amyloidosis
Haemochromatosis
Gout
Trauma
Ageing
Haemosiderosis
53
A 54 year old female prevents with reduced shoulder movement, that is painful and tender to touch. There is hydroxyapatite in the synovial fluid. How would we treat this?
Milwaukee shoulder:
- NSAIDs
- Intra-articular steroids
- Physiotherapy
- Arthroplasty
54
How could we differentiate between soft tissue rheumatism and fibromyalgia?
Fibromyalgia is a more generalised pain
Soft tissue rheumatism is confined to one site
55
What genetic syndromes are associated with joint hypermobility?
Marfan's
Ehlers Danlos
56
How do we measure joint hypermobility?
Modified Beighton Score
57
When do we treat joint hypermobility?
If there is arthralgia or permature OA
58
What is the female to male ratio in SLE?
F:M is 9:1
59
What does SLE stand for?
Systemic Lupus Erythematosus
60
What populations is SLE most common in?
Asians
African-Americans
Afro-Caribbeans
Hispanic Americans
61
What population is SLE least common in?
African blacks
62
What is the environmental aetiology of SLE?
Smoking
UV light
Silica dust
63
What infection can trigger SLE?
EBV
64
Order these steps in the pathogenesis of SLE:
- B+T cells stimulated
- Loss of immune regulation
- Autoantibodies made
- Increase in defective apoptosis
- Immune complexes
- Nuclear material persists -> Acts as autoantigens
- Autoimmunity due to extended exposure to nuclear and intraceullar proteins
1. Loss of immune regulation
2. Increase in defective apoptosis
3. Nuclear material persists -> Acts as autoantigens
4. Autoimmunity due to extended exposure
5. B+T cells stimulated
6. Autoantibodies made
7. Immune complexes
65
Where do the immune complexes in SLE gather and what does this cause?
In blood vessel walls:
- Skin
- Kidneys
Complement release -> Neutrophils release enzymes
Damage to basement membrane results
66
Are complement levels high or low in SLE?
Low
67
What are some of the distinguishing cutaneous features of SLE?
Photosensitivity
Malar 'butterfly' rash:
- Spares labial-nasal fold
Discoid LE
Subacute cutaneous lupus
68
What deforming arthropathy can be seen in SLE?
Jaccoud's arthritis
69
What pulmonary features can be present in lupus?
Pleurisy -> Pleuritis
Effusion
PE
Pulmonary hypertension
Fibrosis (diffuse) -> ILD
70
What cardiac features can be present in SLE?
Pericarditis
Cardiomyopathy -> MI
Libman-Sachs endocarditis
71
What haematological conditions can be seen in lupus?
Lymphadenopathy
Leukopaenia
Anaemia
Thrombocytopaenia
72
Why are patients with lupus more susceptible to infections?
Decreased complement
Impaired cell mediated immunity
Defective phagocytosis
Poor Ab response
73
What is the most specific autoantibody in lupus?
Anti-double stranded DNA antibody (Anti-DNA)`
74
What other antibodies can also be present in SLE?
Anti-ENA:
- Anti-Ro
- Anti-Sm
- Anti-RNP
Anti-ANA
75
What autoantibody is associated with the cutaneous manifestations and congenital heart block and neonatal LE?
Anti-Ro
76
What autoantibody is associated with the CNS manifestations in SLE?
Anti-Sm
77
What is prescribed to every SLE patient?
NSAIDs
Simple analgesia
Hydroxychloroquine
78
How is hydroxychloroquine effective in SLE?
Reduces arthritis
Reduces cutaneous and constituional symptoms
79
A patient with severe disease and diffuse glomerulonephritis presents to A&E. There is extensive organ involvement and they are known to have SLE. What steroids would we prescribe?
High dose prednisolone:
- 1mg/kg/day IV
80
What classes as a small dose of steroids in SLE and what can this treat?
15mg prednisolone daily
Rashes, arthritis and serositis
81
What immunosuppressant used in SLE is safe in pregnancy?
Azathioprine
82
How do we define mild SLE?
Cutaneous and MSK involvement only
83
How do we treat mild SLE?
HCQ
Topical steroid
NSAIDs
84
How do we treat moderate SLE?
Oral steroids
Azathioprine
Methotrexate
85
How do we define severe SLE?
Renal, CNS and severe Haem involvement
86
How do we treat severe SLE?
IV steroids
Cyclophosphamide
Rituximab
87
A 29 year old woman presents with a purple mottled discolouration on her lower limbs. She has suffered from migraines for the past year. She has noted that she has bruised easily and has suffered regular nosebleeds. She also suffered a miscarriage at 28 weeks.
Anti-Phospholipid syndrome
88
What features in a patient's history may suggest anti-phospholipid syndrome?
Pregnancy loss with no explanation 10-34 weeks
3 losses with no explanation
89
Having at least one of the following, on two occasions >/= 12 weeks apart is diagnostic of what:
- Positive anti-cardiolipin Ab
- Lupus anticoagulant activity
- Anti-Beta2-glycoprotein
Anti-Phospholipid syndrome
90
What is the treatment of anti-phospholipid syndrome?
Lifelong warfarin
If pregnancy loss:
- Aspirin and heparin during pregnancy
91
A patient presents with a swelling in front of her left ear. She notes eye and mouth dryness for the last 5 months. She has been feeling very fatigued.
Sjogren's syndrome
92
What causes Sjogren's syndrome?
Lymphocyte infiltration of exocrine glands
93
What is the name given to the ocular dryness cause by Sjogren's?
Keratoconjunctivitis sicca
94
What is the diagnostic test of Sjogren's?
Schirmer test:
- Normal result is >10mm of water
95
Which of the following is not associated with Sjogren's?
- Lymphoma
- Arthralgia
- Raynaud's
- Pulmonary hypertension
- ILD
Pulmonary hypertension
96
What is pilocarpine
A parasympathomimetic used to increase salivation
97
What autoantibodies are associate with Sjogrens?
ANA
Anti-Ro
98
What is CREST syndrome and what does it stand for?
Limited Systemic Sclerosis
Calcinosis
Raynaud's
Esophageal dysmotility
Sclerodactyly (Hands)
Telangiectasias
99
How soon are skin changes seen in diffuse systemic sclerosis?
Within one year of Raynaud's (Trunk and limbs - Not just hands like in limited)
100
What organs can be involved in diffuse systemic sclerosis?
Renal
Pulmonary
GI
MSK
CVS
101
How do we treat systemic sclerosis?
Raynauds:
- Calcium channel blockers
- Iloprost
- Bosentan
Renal:
- ACE inhibitors
GI:
- PPIs
ILD:
- Cyclophosphamide
102
What autoantibodies are associated with each type of systemic sclerosis?
Limited - Anti-Centromere
Diffuse - Anti-Scl-70
103
What are the following major criteria of?
- Raynauds
- Arthralgia
- Myositis
- Sclerodactyly
- Pulmonary hypertension
- ILD
Mixed Connective Tissue Disease
104
Anti-RNP autoantibodies are seen in what condition?
Mixed Connective Tissue Disease
105
A 43 year old woman presents complaining of difficult climbing the stairs. You note a rash around her eyes and a rash over her scapulae. She has also noted difficulty swallowing.
Dermatomyositis
106
What is Gottron's sign and what is it seen in?
Erythematous scaling:
- Symmetrical
- Over MCP and IP joints
Seen in dermatomyositis
107
What malignancies are increased in polymyositis and dermatomyositis?
Ovarian
Breast
Gastric
Lung
Bladder
Colon
108
What features of a patient's PMHx may be present in polymyositis?
Diabetes
Thyroid disease
109
What autoantibodies are present in polymyositis/dermatomyositis?
ANA
Anti-Jo-1
110
What is seen in electromyography in polymositis patients?
Increased fibrillations
Abnormal motor potentials
Repetitive discharges
111
How is polymyositis treated?
Steroids
Azthioprine
Methotrexate
Ciclosporin
IV Ig
112
A 61 year old man presents with wrist, finger and leg weakness over the last month.
Inclusion body myositis
113
What is the difference in creatinin kinase levels between polymyositis and inclusion body myositis?
CK higher in PM
114
What will a muscle biopsy show in inclusion body myositis?
Inclusion bodies
115
A 73 year old woman presents with difficult climbing stairs and brushing her hair. She also notes morning stiffness that lasts about two hours. She says her symptoms improve throughout the day.
Polymyalgia Rheumatica
116
What is polymyalgia rheumatica associated with?
Giant cell arteritis
117
How do we treat polymyalgia rheumatica?
15mg prednisolone daily for 18 months
118
A patient presents with pain on chewing and vision problems. They have also experience a temporal headache and pain on brushing her hair.
Giant cell arteritis
119
What is the definitive diagnostic technique of GCA?
Temporal artery biopsy
(Also increased ESR/PV/CRP)
120
Treatment options for GCA
No vision problems:
- 40mg prednisolone
Vision problems:
- 60mg prednisolone
(for 2 years)
121
What CVS problems is GCA associated with?
Aortic aneurysm
Aortic dissection
122
What is the commonest cause of chronic MSK pain in women?
Fibromyalgia
123
Spondyloarthropathies are usually seen in individuals positive for what?
HLA-B27
124
What are the four subgroups of spondyloarthropathies?
Ankylosing spndylitis
Psoriatic arthritis
Reactive arthritis/Reiter's syndrome
Enteropathic arthritis
125
When is mechanical back pain worst?
On exertion
At the end of the day
126
When is inflammatory back pain worst?
With rest
In the morning - Stiffness
127
What are some common features that all spondyloarthropathies present?
Sacroiliac and spine involvement
Enthesitis:
- Inflammation at tendon insertion
> Achilles tendinitis
> Plantar fasciitis
Dactylitis:
- 'Sausage digits' (Inflammation of the whole digit)
128
What is the typical joint pattern in spondyloarthropathies?
Oligoarticular
Asymmetric
Mainly lower limb
129
What sites are commonly by extra-articular manifestations in spondyloarthropathies?
Eyes:
- Anterior uveitis
- Conjunctivitis
Mucous membranes
130
Sacroiliitis is the hallmark of what spondyloarthropathy?
Ankylosing spondylitis
131
Is ankylosing spongylitis more common in men or women?
Men
132
What are the Modified New York Criteria for Ankylosing Spondylitis?
1. Limited lumbar movement
2. Lower back pain for 3 months:
- Improves with exercise
- Not relieved by rest
3. Reduced chest expansion
4. Bilateral (Grade 2-4) sacroiliitis on x-ray
5. Unilateral (Grade 3-4) sacroiliitis on x-ray
Define as AS is criterion 4 or 5 plus 1,2 or 3
133
Why is ankylosing spondylitis called the 'A' disease?
Axial arthritis
Anterior uveitis
Aortic regurgitation
Amyloidosis/IgA Nepropathy
Achilles tendonitis
plAntar fasciitis
134
What is the main examination test for ankylosing spondylitis?
Modified Schober's Test:
- 5cm line below posterior superior iliac crest
- 10cm line above PSIC
- Ask patient to bend forward
- Normal distance >/= 20cm
- Less than 18cm is AS
135
What x-ray features are seen in ankylosing spondylitis?
Sacroilitis
Syndesmophytes:
- Bony growths from within ligaments
- Bridge intervertebral disc
- Result in a late 'Bamboo spine' on AP view
136
Treatment of ankylosing spondylitis
Physiotherapy
NSAIDs
DMARDs if peripheral joint involvement
Anti-TNF (If BASDAI >4)
Surgery
137
Does a patient need to have psoriasis to suffer from psoriatic arthritis?
No
138
What nail features are seen in psoriatic arthritis?
Pitting
Onycholysis
139
What is the most severe subgroup of psoriatic arthritis?
Arthritis mutilans (aggressive and destructive)
140
What is the hallmark x-ray feature of psoriatic arthritis?
'Pencil-in-cup' appearance of DIP
141
What common infections result in reactive arthritis?
GU:
- Chlamydia
GI:
- Salmonella
- Shigella
- Yersinia
142
What is Reiter's syndrome?
Can't see, can't pee, can't bend the knee:
- Uveitis
- Urethritis
- Arthritis
143
How do we treat reactive arthritis?
Steroids
DMARDs
144
True of false; The joint aspirate in reactive arthritis is not sterile?
False. It is usually sterile
145
What mucocutaneous features can be seen in reactive arthritis?
Keratoderma blennorrhagicum:
- Vesiculopustular
- Yellow/brown
- Soles and palms
Circinate balantis:
- Painless
- Serpiginous dermatitis
- Glans penis
Painless oral ulcers
Hyperkeratotic nails
146
A 29 year old man presents with loose stools with mucus present. He has noticed weight loss over the last 6 months. The sole of his left foot is very painful. There are some painful ulcers on his buccal surfaces. He has noticed his knees and lower back have been stiff and painful when he is at rest.
IBD with enteropathic arthritis
147
What will an USS of an enteropathic arthritis show?
Synovitis
Tenosynovitis
148
What can trigger a secondary vasculitis?
Infection
Drugs
Toxins
Inflammatory conditions
Cancer
149
Give two examples of large-vessel vasculitidies
Takayasu arteritis
GCA
150
Give two examples of medium-vessel vasculitidies
Polyarteritis nodosa
Kawasaki disease
151
What two categores can small-vessel vasculitidies be divided into? Give examples of each
Immun-complex mediated:
- Henoch-Schonlein vasculities (IgA)
- Cryoglobulinaemic vasculitis
- Hypocomplementeric urticarial vasculitis
ANCA-Associated (AAV):
- Microscopic polyangiitis
- GPA (Wegener's)
- EGPA (Churg-Strauss)
152
What populations are large-vessel vasculitidies most common in?
153
What are large-vessel vasculitidies characterised by?
Granulomatous infiltration of vessel walls
154
What are common examination findings in large-vessel vasculitidies?
Carotid bruit
BP difference at extremities
Claudication
Carotodynia
Hypertension
155
What lesions are seen in temporal artery biopsies in GCA patients?
Skip lesions
156
What might MRI/CT scans show in GCA patients?
Vessel wall thickening
Stenosis
Aneurysm
Increased metabolism
157
What populations is Kawasaki disease seen in?
Kids younger than 5 years old
158
What is the most concerning complication of Kawasaki disease?
Coronary Aneurysm
159
What types of lesions are seen in polyarteritis nodosa and where are they typically found?
Necrotising lesions
Located at vessel bifurcations
160
What body sites do medium-vessel vasculitidies tend to affect?
Skin
Gut
Kidneys
161
What infection is medium-vessel vasculitidies associated with?
Hep B
162
A 40 year old man presents complaining of regular nosebleeds and mouth ulcers. He also says he has experienced periods of deafness.
GPA
163
In what populations is GPA most common in?
Northern Europeans
Males
35-55 year olds
164
What ENT features are seen in GPA?
Sinusitis
Nasal crusting
Epistaxis
Mouth ulcers
Sensorineural defects
Otitis media
Deafness
'Saddle nose'
165
What other systems are affected by GPA?
Renal:
- Necrotising glomerulonephritis
CNS:
- Mononeuritis multiplex
- Sensorimotor polyneuropathy
- CN palsies
Ophthalmology:
- Conjunctivitis/Uveitis
- CN ii vasculitis
- Proptosis
166
A 41 year old man presents which shortness of breath and a runny nose. On examination you note wheeze and expiratory rhonchi.
EGPA/Churg-Strauss
167
On blood testing, what would expect in EGPA?
Increased peripheral blood eosinophil count
168
True or false: Mononeuritis multiplex is common in EGPA?
True
169
What are the two types of ANCA and what staining patterns are seen?
Cytoplasmic ANCA (c-ANCA):
- Uniform staining
- No interlobular accentuation
Perinuclear ANCA (p-ANCA):
- Perinuclear staining
- Nuclear expansion
170
What conditions are associated with each kind of ANCA?
c-ANCA:
- GPA (Wegener's)
p-ANCA:
- EGPA (Churg-Strauss)
- Microscopic polyangiitis
171
What is PR3?
The specific c-ANCA antigen seen in GPA
172
What is MPO and what is it more positive in, EGPA or MPA?
Myeloperoxidase (p-ANCE antigen)
MPA
173
How do we classify localised AAV?
Upper or lower respiratory tract disease
174
How do we classify early systemic AAV?
Without organ or life threatening disease
175
How do we classify generalised AAV?
Renal disease (Creatinine
176
How do we classify systemic AAV?
Renal disease (Creatine > 500micrograms/dL)
Other vital organ failure
177
How do we classify refractory AAV?
Progressive disease
Unresponsive to steroids and cyclophosphamide
178
How do we treat localised and early systemic AAV?
Methotrexate/Azathioprine
Plus steroids
179
How do we treat generalised and systemic AAV?
1st line:
- Cyclophosphamide + steroids
OR
- Rituximab + steroids
Plasma exchange if creatinine > 500
180
How do we treat refractory AAV?
IV Ig + Rituximab
181
A 5 year old boy presents with a purple rash on his lower limbs and buttocks. He has been complaining of "on and off" abdominal pain. His mother noticed some blood in his stool. Two weeks ago he had a URTI.
Henoch-Schonlein Purpura
182
What infections can precede Henoch-Schonlein purpura?
URTI
Pharyngeal
GI
183