Rheumatology Flashcards
1
Q
List 6 causes of secondary osteoarthritis
A
- Haemachromatosis
- Wilson’s disease
- Ehler’s-Danlos syndrome
- Diabetes
- Alkaptonuria
- Previous injury
- Congenital joint disorders
2
Q
How does joint involvement differ between OA and RA?
A
Involvement of the DIP joint is highly suggestive of OA or psoriatic arthritis, although may occur in RA
RA is more likely to be symmetric
3
Q
What are Heberden’s nodes and when are they found?
A
Pain and nodular thickening on the dorsal sides of the distal interphalangeal joints
OA
4
Q
What are Bouchard’s nodes and when are they found?
A
Pain and nodular thickening on the dorsal sides of the proximal interphalangeal joints
OA
5
Q
What is hallux rigidus and when is it found?
A
Arthrosis of the first metatarsophalangeal joint characterised by hypertrophy of the sesamoid bones
OA
6
Q
List four radiological signs of OA
A
1. Irregular joint space narrowing
2. Subchondral sclerosis
Dense area of bone (visible on x-ray) just below the cartilage zone of a joint, formed due to a compressive load on the joint
3. Osteophytes
4. Subchondral cysts
Fluid-filled cysts that develop at the surface of a joint due to local bone necrosis induced by the joint stress of osteoarthritis
7
Q
Which HLA alleles are associated with RA?
A
HLA-DR4, HLA-DR1
8
Q
What are 3 environmental triggers for RA?
A
Smoking
Infection
Silica dust
Mineral oils
9
Q
What is a pannus?
A
Growth of granulation tissue from the inflamed synovium into the joint space
Characteristic of RA
10
Q
How does a pannus cause joint disease?
A
Production of proteinases → destruction of cartilage and ECM
The pannus is composed of inflammatory cells
11
Q
What is a swan neck deformity?
A
PIP hyperextension and DIP flexion
12
Q
What is a Boutonniere deformity?
A
PIP flexion and DIP hyperextension
13
Q
What is trigger finger?
A
Stenosing flexor tenosynovitis
Flexor tendon catches when it glides through a stenotic sheath at the first annular (A1) pulley
(associated with RA and diabetes)
14
Q
What is a hammer toe?
A
MTP and DIP hyperextension, PIP hyperflexion
A sign of motor neuropathy but can also develop after trauma or rheumatoid arthritis. DM is the most common cause
15
Q
What is the major complication of RA in the cervical spine?
A
Atlanto-axial subluxation → cervical spinal cord compression
16
Q
What is the triad of Felty syndrome?
A
Arthritis, splenomegaly, neutropenia
A severe subtype of seropositive RA
17
Q
When is the peak incidence of RA?
A
Ages 20-50
May occur at any age
18
Q
Name 4 spondyloarthropathies
A
- Ankylosing spondylitis
- Psoriatic arthritis
- Reactive arthritis
- Arthritis of IBD
19
Q
Reactive arthritis most commonly follows which infections?
A
Enteric - Salmonella, Shigella, Campylobacter
Genitourinary e.g. Chlamydia, mycoplasma
20
Q
Which connective tissue disease is strongly associated with temporal arteritis?
A
Polymyalgia rheumatica
21
Q
What are gout crystals composed of?
A
Monosodium urate monohydrate
22
Q
What is pseudogout?
A
Calcium pyrophosphate deposition disease
23
Q
What are the differences found on laboratory between monosodium urate and calcium pyrophosphate crystals?
A
Monosodium urate - negative birefringent and needle-shaped
Calcium pyrophosphate - positive birefringent and rhomboid-shaped
24
Q
Genetic defects impede what process in Ehlers-Danlos syndrome
A
Collagen synthesis
25
What are 3 clinical features of Ehlers-Danlos syndrome?
1. Hyperextensible skin
2. Joint hypermobility
3. Easy bleeding (tissue fragility affecting vasculature)
26
What is tenosynovitis?
Inflammation of a tendon and its sheath
27
What is the classic triad of reactive arthritis?
Urethritis
Conjunctivitis
Arthritis
28
What is the most specific test for RA?
Anti-citrullinated peptide antibodies (ACPA)
AKA anti-cyclic citrullinated peptide (anti-CCP)
95% specific
(RF is 85% specific)
29
What are these?
Tophi
30
Name 4 common causative agents in viral arthritis
1. Parvovirus B19
2. HBV
3. HCV
4. Rubella
5. HIV
31
What are 3 clinical tests which can be used in the diagnosis of ankylosing spondylitis?
1. Reduced chest expansion
2. Mennell sign: tenderness to percussion and pain on the displacement of the sacroiliac joints
3. FABER test: Flexion, ABduction, External Rotation provoke pain in the ipsilateral hip
4. Reduced spinal mobility
32
What is this radiological finding?
Syndesmophytes in AS "bamboo spine"
Bony growth originating inside a ligament
33
What is this radiological finding?
Sclerosis of the vertebral ligaments
AS "dagger sign"
34
Which drug is used in RA if methotrexate is contraindicated or not tolerated?
Leflunomide
35
List 4 management options for ankylosing spondylitis
**1. Physical therapy**
2. NSAIDs e.g. indomethacin
3. TNF-alpha inhibitors (do not alter disease progression)
4. Intra-articular glucocorticoids
5. DMARDs for peripheral arthritis (no axial effects)
6. Surgery
36
3/5 features are required for a diagnosis of psoriatic arthritis.
What are these 5 features?
1. Evidence of psoriasis
2. Psoriatic nail dystrophy
3. **Negative rheumatic factor**
4. Dactylitis
5. Radiologic signs
37
What are 3 treatment options for psoriatic arthritis?
1. NSAIDs (mild)
2. DMARDs (moderate to severe)
3. Physical therapy
38
What are the features of CREST syndrome?
C - calcinosis cutis
R - Raynaud's phenomenon
E - Esophageal hypomotility
S - Sclerodactyly
T - Telangiectasia
(form of systemic sclerosis)
39
Which test is used to measure tear production?
What is a normal result?
Schirmer's test
Normal: \>15mm after 5 minutes (Sjogren \<5mm)
40
What is the triad for disseminated gonococcal infection?
1. Polyarthralgia
2. Tenosynovitis
3. Dermatitis
41
How does disseminated gonococcal infection present if it is not the clinical triad?
Purulent gonococcal arthritis
Abrupt inflammation in up to 4 joints (commonly kees, ankles and wrists)
42
Calcification of synovia and cartilage on ultrasound is characteristic of which disease?
Pseudogout
43
What is the tetrad for HSP?
1. Palpable purpura
2. Arthritis/arthralgia
3. GI symptoms
4. Renal disease
44
Which purpura characteristically has elevated platelets?
HSP
45
List the 5 major criteria for rheumatic fever
1. Arthritis (migratory polyarthritis primarily involving large joints)
2. Carditis
3. Sydenham chorea
4. Subcutaneous nodule
5. Erythema marginatum
46
List the 4 minor criteria for rheumatic fever
1. Aseptic monoarthritis or polyarthralgia
2. Fever
3. Elevated acute phase reactants (ESR/CRP)
3. Prolonged PR interval
47
What combination of major and minor criteria is required for diagnosis of rheumatic fever?
2 major
1 major + 2 minor
3 minor (if recurrent)
ALL + plus evidence of preceding Group A streptococcus infection
48
What is serum sickness?
Type III hypersensitivity reaction in response to anti-toxin or anti-venom administration
49
What is a serum sickness-like reaction?
Reaction clinically identical to serum sickness in response to medications
Pathogenesis unclear
50
Name 3 conditions people with Sjogren's are at an increased risk of developing? (one must be non-rheumatological)
1. B cell lymphoma
2. MALT (mucosa-associated lymphoid tissue) lymphoma
3. SLE
4. RA
51
What is the triad for septic arthritis?
1. Fever
2. Joint pain
3. Restricted range of motion
52
What is a normal white cell count in synovial fluid?
\< 200/mm3 (cmm)
53
Synovial fluid containing a range of how many white cells is suggestive of non-inflammatory arthritis?
200 - 2000/mm3 (cmm)
54
Above a threshold of how many white cells in synovial fluid is inflammatory arthritis highly likely?
\>2000/mm3 (cmm)
55
What is empiric antibiotic therapy for septic arthritis?
Flucloxacillin
56
List 5 DDx for migratory polyarthritis
1. Gonococcal arthritis
2. Rheumatic fever
3. Sarcoidosis
4. Systemic lupus erythematosus
5. Lyme disease
6. Bacterial endocarditis
7. Whipple's disease
57
List 4 causes of symmetrical polyarthritis
1. Rheumatoid arthritis
2. SLE
3. Polymyalgia rheumatica
* (autoimmune connective tissue diseases)*
4. Viral arthritis
58
What are 2 **highly specific** tests for SLE?
Anti-dsDNA
Anti-Sm
59
Which antibody test is most sensitive for SLE?
ANA (93% sensitive)
60
For which diseases is a positive ANA most sensitive?
SLE (93%)
Systemic sclerosis/scleroderma (85%)
61
What is the most specific antibody test for systemic sclerosis?
Anti-Scl-70
| (anti-topoisomerase)
62
Which two antibodies are together most sensitive for Sjogren syndrome?
Anti-Ro/SSA
Anti-LA/SSB
*60-80% of patients are positive for one or both antibodies*
63
What is the most sensitive antibody for mixed connective tissue disease?
Anti-U1 RNP
64
Anti-cytoplasmic antigens (ANCAs) are typical in which group of diseases?
Vasculitis
65
Which antibody test can be used to assess disease activity in SLE?
Anti-dsDNA
66
Enthesitis is found in which group of diseases?
Spondyloarthropathies
67
Parotid gland enalrgement is found in which connective tissue disorder?
Sjorgren's syndrome
68
List 4 foods which can lower serum uric acid
1. Dairy products
2. Soybeans
3. Vegetable sources of protein
4. Cherries
5. Vitamin C
6. Coffee
69
What are the two most common causes of avascular necrosis?
Glucocorticoid use
Excessive alcohol use
70
How does inflammation/infection affect the viscosity of synovial fluid?
Decreases
Proteolytic enzymes released in inflammation decreases the viscosity
71
What is the treatment for polymyalgia rheumatica?
Low-dose oral glucocorticoid e.g. prednisolone
## Footnote
*RA does not respond rapidly to low-dose corticosteroids*
72
What is mixed connective tissue disease?
Overlapping symptoms of systemic sclerosis, systemic lupus erythematosus and polymyositis
73
What is polymyositis?
Inflammatory myopathy affecting the proximal skeletal muscles
74
What is dermatomyositis?
Inflammatory myopathy that presents similarly to polymyositis, with the addition of skin involvement
75
Which two joints are most affected by polymyositis/dermatomyositis?
Hip
Shoulder
76
What are two characteristic cutaneous manifestations of dermatomyositis?
1. Gottron papules (extensor surface of the hands)
2. Helitrope rash (erythematous rash on the upper eyelids)
77
What condition are these characteristic of?
Dermatomyositis
Gottron's papules
78
What condition is this characteristic of?
Dermatomyositis
Heliotrope rash
79
What is the difference between limited and diffuse cutaneous systemic sclerosis?
Limited (CREST) - Raynaud's precedes other symptoms, skin involvement limited to the hands, fingers and face
Diffuse - widespread skin findings, extracutaneous organ manifestations
80
What are 4 extracutaneous manifestations of diffuse systemic sclerosis?
1. Arthralgia and myalgia
2. Dysphagia and reflux (oesophageal dysmotility)
3. Constipation, bloating, gas (small bowel dysmotility)
4. Pulmonary hypertension
5. Interstitial lung disease
6. Prerenal kidney failure (collagen deposits in renal arterioles)
81
Which antibodies are most specific for limited SSc?
Anti-centromere antibodies (ACA)
82
Which antirheumatic drug may cause a reactivation of latent TB?
TNF alpha inhibitors
## Footnote
*TNF alpha plays a key role in containing TB within granulomas*
83
What is the most specific antibody for SLE?
Anti-Smith
84
Name 3 TNF-alpha antagonists used in rheumatology
1. Adalimumab
2. Etanercept
3. Infliximab
85
List 6 adverse effects of methotrexate
1. Gastrointestinal (stomatitis, nausea, diarrhoea, bleeding)
2. Rash
3. Hepatotoxicity
4. Interstitial pneumonitis and pulmonary fibrosis
5. Bone marrow suppression
6. Nephrotoxicity
7. Increased risk of lymphoproliferative disorders
8. Teratogenicity
9. Alopecia
86
What are contraindications to methotrexate use?
Significant liver or kidney disease
Heavy alcohol intake
Pregnancy
Lactation
87
Name 4 conventional synthetic disease-modifying antirheumatic drugs (csDMARDs)
1. Methotrexate
2. Leflunomide
3. Hydroxychloroquine
4. Sulfasalazine
5. Cyclosporine
6. Azathioprine
88
What is the mechanism of cyclosporine?
Calcineurin inhibitor
Inhibits T cell activation (prevents production of IL-2 and other cytokines which stimulate T cell proliferation and differentiation)
89
Name 3 classes of biologic disease-modifying antirheumatic drugs (bDMARDs)
1. TNF-alpha inhibitors e.g. adalimumab
2. Janus kinase inhibitors e.g. tofacitnib
3. B cell depletors e.g. rituximab
4. Selective T cell costimulation modulator e.g. abatecept
5. Interleukin-1 receptor antagonist e.g. anakinra
90
Why are NSAIDs used for acute gout?
They have uricosuric effects at high doses
91
Why is aspirin use a risk factor for gout?
Inhibits uric acid excretion
92
What is the mechanism of colchicine?
Anti-inflammatory
NOT analgesic, but can reduce pain due to less inflammation
93
A patient with gout initiates a new medication and develops diarrhoea. Which drug is most likely to have this effect?
Colchicine
Near 100% with high doses
94
What is the mechanism of allopurinol?
What effect does it have on uric acid?
Xanthine oxidase inhibitor
Reduces uric acid production
95
List 2 notable side effects of allopurinol
1. Hypersensitivity syndrome (rash, fever, nephritis, hepatitis, eosinophilia)
2. Toxic epidermal necrolysis/Steven-Johnson syndrome
3. GI intolerance
4. Neutropenia, thrombocytopenia
96
Why has allopurinol traditionally been avoided during acute attacks of gout?
The frequency of acute flares increases in the first months of allopurinol use
BUT do not discontinue during acute attacks
97
What is the mechanism of febuxostat?
Xanthine oxidase inhibitor
Used when allopurinol is not tolerated
98
What is the mechanism of rituximab?
CD-20 monoclonal antibody
Binds to and lyses B cells (not plasma cells - does not significantly lower immunoglobulin levels, but inhibits the formation of new IgM antibodies)
*Used for RA*
99
Anti-histone antibodies are suggestive of which disease?
Drug-induced lupus
100
Anti-Jo-1 antibodies are suggestive of what?
Idiopathic inflammatory myopathies
Polymyositis, dermatomyositis
101
Name 2 calcineurin inhibitors
Cyclosporine
Tacrolimus
*Inhibits IL-2 and other cytokines which normally stimulate T cell proliferation and differentiation*
102
What is the major adverse effect of cyclosporine?
Nephrotoxicity
103
How does antiphospholipid syndrome lead to a hypercoagulable state?
Antibodies form complexes with anticoagulant proteins e.g. protein C, S, antithrombin III
Antibodies activate platelets and vascular endothelium
→ hypercoagulable state → increased risk of thrombosis and embolism
104
What are the clinical features of antiphospholipid syndrome?
C - clotting (arterial and venous)
L - livedo reticularis
O - obstetric problems
T - thrombocytopenia
105
Which ophthalmological condition is associated with rheumatoid arthritis?
Episcleritis
106
Which alleles are associated with SLE?
HLA-DR2 and HLA-DR3
107
Which antibodies are associated with drug-induced lupus?
Anti-histone
## Footnote
*anti-dsDNA is not associated with drug-induced lupus*
108
What are 3 poor prognostic markers in SLE?
1. High serum anti-dsDNA
2. Fall in complement (CH50, C3, C4)
3. Diagnosis before 25
4. Renal, vascular or neurological involvement
5. Low C1q (lupus nephritis)
109
Which medication is used in all patients with lupus?
Hydroxychloroquine or chloroquine
110
Which medications most commonly cause drug-induced lupus?
Sulfa drugs (drugs containing a sulfonamide group)
+ hydralazine, isoniazid, phenytoin, TNF-alpha inhibitors
111
Which organs are unaffected in drug-induced lupus but affected by idiopathic SLE?
Oral mucosa
Brain
Kidneys
112
What is the prognosis for drug-induced lupus erythematosus?
Remission after discontinuation
113
How are complement levels affected by SLE?
Low C3 and C4
114
What is the most important prognostic factor for SLE?
Lupus nephritis
(immune complex-mediated glomerulonephritis)
115
Which two autoantibodies are most strongly associated with antiphospholipid syndrome?
Anticardiolipin
Lupus anticoagulant
116
How does lupus anticoagulant influence aPTT
In vitro (lab) → prolonged aPTT
In vivo (body) → short aPTT
117
Which laboratory test does the presence of anticardiolipin autoantibodies alter?
False positive syphilis (cardiolipin is used for syphilis testing)
118
What is behcet syndrome?
Systemic vasculitis that can affect arteries and veins of all sizes
119
What is the classic triad of behcet syndrome?
1. Painful mouth ulcers
2. Painful genital ulceration
3. Uveitis
120
What is unique about the vegetations in Libman-Sacks endocarditis?
Sterile
On both sides of the valve
Vegetations are easily dislodged and embolisation is common
Emboli are particularly large
121
Which drug is used for gout if allopurinol is not tolerated?
Febuxostat
122
What are 5 extra-cutaneous manifestations of SLE?
1. Myalgia
2. Serositis (pleuritis, pericarditis)
3. Nephritis
4. Libman-Sacks endocarditis
5. Pneumonitis
6. Interstitial lung disease
7. Oesophagitis
8. Hepatitis
9. Pancreatitis
10. Raynaud's phenomenon
11. Thromboembolism
12. Seizures
13. Personality changes
14. Autoimmune haemolytic anaemia
123
What is the mechanism of anakinra?
Interleukin-1 receptor antagonist
124
What is the role of environmental antigens in the pathophysiology of RA?
Cause modification (e.g. citrullation) of proteins (e.g. type II collagen)
*Susceptibility genes predispose someone to view these modified proteins as antigenic*
125
Why does RA accelerate osteoporosis?
Inflammatory cytokines increase RANKL expression on T cells --\> T cells bind to RANK on osteoclasts
126
What is the sensitivity and specificity of rheumatoid factor for RA?
Sensitivity: 70%
Specificity: 85%
127
What is the sensitivity and specificity of anti-CCP for RA?
Sensitivity: 67% (RF is better)
Specificity: 95%
128
What type of hypersensitivity reaction is RA?
III
129
What type of hypersensitivity reaction is reactive arthritis/Reiter's syndrome?
Type III
130
Which group is most affected by reactive arthritis?
Young men
20-40
M \> F post-urethral
M=F post-enteric
131
What is TNF-alpha?
A cytokine involved in inflammatory and immune responses and in the pathogenesis of rheumatoid arthritis, psoriasis and inflammatory bowel disease
132
What causes a pleural friction rub in RA?
Inflammation of the pleura secondary to a systemic inflammatory state
133
Which feature best distinguishes a malar rash from rosacea?
The butterfly rash spares the nasolabial folds
134
Why may patients with lupus exhibit livedo reticularis?
Thrombosis → blockage of the venous or arteriolar system → increased discoloured deoxygenated blood + venular dilation
135
When are biologic DMARDs indicated?
Moderate or severe disease activity after 3 months of csDMARD therapy
## Footnote
*Do not cease csDMARD*
136
What is the sensitivity of ANA in lupus?
93% (very sensitive)
137
What is the sensitivity of anti-dsDNA and anti-Sm antibodies in SLE?
Anti-dsDNA: 70% (prognostic plus associated with renal disease)
Anti-Sm: 30% (but highly specific)
138
Which antibodies are extractable nuclear antigens (ENA)?
Anti-Sm (SLE)
Anti-U1-RNP (MCTD)
Anti-Ro (Sjogren)
Anti-La (Sjogren)
139
What are the radiological features of RA?
Loss of joint space
Erosions
Soft tissue swelling
Soft bones (osteopenia)
(LESS)
140
How is the incidence of reactive arthritis affected by gender?
Post-enteric: equal
Post-urethritis: M \> F
141
What are the classic pathology findings of myocardial tissue in rheumatic heart disease?
Aschoff bodies (granuloma of rheumatic inflammation)
Antischkow cells (large, elongated cells found in Aschoff bodies)
142
How does ankylosing spondylitis affect males and females differently?
Male to female; 3:1
143
What are the ocular manifestations of reactive arthritis?
Conjunctivitis
Iritis
144
What are 3 risk factors for pseudogout
1. Joint trauma
2. Haemachromatosis
3. Gout
4. Hyperparathyroidism
5. Hypophosphatemia/hypomagnesemia
* Most commonly idiopathic*
* Damaged cartilage releases an enzyme, nucleoside triphosphate pyrophosphohydrolase which leads to CPPD crystal formation*
145
4/11 features are required for a diagnosis of lupus
Name as many of these 11 as you can
146
What ANA titre is considered positive?
1:160
147
Which arthritis' may present with DIP involvement?
AS
Psoriatic arthritis
OA
Sarcoidosis
148
How do calcineurin inhibitors work?
Inhibit T cell activation (prevents the production of IL-2 and other cytokines which stimulate T cell proliferation and differentiation)
149
How does rituximab affect B cells/plasma cells?
Binds to and lyses B cells (not plasma cells - does not significantly lower immunoglobulin levels, but inhibits the formation of new IgM antibodies)
CD-20 monoclonal antibody
Used for RA
150
Bull's eye maculopathy is associated with which rheumatological drug?
Hydroxychloroquine
151
Which antibodies are elevated in drug-induced lupus?
Anti-histone
152
How are acute gout attacks managed?
1. NSAIDs
2. Colchicine if contraindicated
3. Glucocorticoids (oral or intra-articular)
