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Rheumatoid arthritis Flashcards

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1
Q

ACR/EULAR 2010 criteria for RA

A

Number of joints involved. The more joints, the more points.

Serology
- RF, Anti-CCP

Acute phase reactant
- CRP, ESR

Duration of symptoms
≥6 weeks

A score of ≥6 = definite RA

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2
Q

Serology for RA

A

RF
Positive in 70% RA
Low specificity
More severe disease, more extra-articular complications e.g. nodules, vasculitis, lung

Anti-CCP
Specificity >90% 
Correlate with RF
Sensitivity 60-80%
Precede onset and an important predictor of development of RA 
More severe disease, ILD, CV disease
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3
Q

Extraarticular features of RA

7 organ systems

A

1) Skin
Rheumatoid nodules
Vasculitis - small and medium sized vessels; poor prognosis
Ulcers

2) Eyes
Episcleritis/scleritis
Secondary Sjogren’s syndrome

3) Lungs
Pleuritis/pleural effusion 
Pulmonary nodules +/- cavitation
ILD - NSIP, UIP 
Bronchiectasis
Cryptogenic organising pneumonia
4) Cardiovascular
Premature atherosclerosis/CVD/PVD
Pericarditis/pericardial effusion
Arrhythmias
Myocarditis
HFpEF
Cardiac nodules

5) Renal
Glomerulonephritis (usually mesangioproliferative)
Proteinuria

6) Liver
Liver nodules/hyperplasia
Portal fibrosis

7) Haem
Lymphadenopathy
Felty's syndrome - splenomegaly, leukopenia, LL ulceration, hyperpigmentation
Lymphoma
Amyloidosis
Cryoglobulinemia
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4
Q

What is the most important drug in RA?

A 
MTX
Everyone should get MTX unless there is 
- Mild, seronegative disease
- Renal impairment
- Liver disease
- High ETOH
- Lung disease

Concomitant folic acid
Subcut better than PO
Monitor FBC, Cr, LFTs

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5
Q

Does everyone with RA need treatment?

A 
YES
90% progressive disease
Damage occurs early with loss of BMD in first year 
Disability occurs early 
Spontaneous remission is rare
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6
Q

Vaccination for RA

A

Hep B
Pneumococcus
Annual fluvax
HPV

VZV recommended age >50

  • Shingrix available
  • Should be given before biologics or tofacitinib
  • Can give to patients on MTX and Arava

No live vaccines (yellow fever, MMR, BCG, Rubella) on biologics or MTX or Arava or Pred >10mg

*Vaccinate before they go on drugs

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7
Q

MTX lung disease

A

Fever, SOB, non-productive cough, pleuritic chest pain
Pulmonary crackles
Hypoxia, reduced DLCO
Acute interstitial and alveolar often bibasally

DDx: opportunistic infection

Mx: discontinue MTX, steroids
Majority recover completely

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8
Q

MTX and malignancy

A

Increased incidence of lymphoma

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9
Q

Stop MTX before surgery?

A

No

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10
Q

MTX hepatotoxicity associated with

A

Strong association with
ETOH
Preexisting liver disease
Renal insufficiency

Probable association
Duration
Cumulative disease
Obesity and diabetes

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11
Q

Lefulonamide MOA and efficacy in RA

A

Pyrimidine synthesis inhibitor –> kills T cells

Response rate similar to MTX
Takes 3/12 to work
Reduces joint damage

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12
Q

AE lefluonamide

A

Peripheral neuropathy - must cease drug. Need to do cholestyramine wash out.
Diarrhoea, hair loss
Pneumonitis

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13
Q

Criteria for biologics

A

Must have tried
MTX for 3/12
A second DMARD for 3/12

So can’t trial DMARD for at least 6/12

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14
Q

TNFi in RA

A

Completely turns off joint damage even if there is active disease (radiologically)
BUT TNFi has clinically the same effect as MTX

Any biologics + MTX work better than single therapy alone
When combined with MTX, all biologics/treatment specific DMARDs have similar efficacy when used as a first treatment strategy in early RA

Only 70% will get a good response
<50% will go into remission

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15
Q

What to do before starting TNFi?

A

Screen for latent TB, hep B, C, HIV

Vaccinate

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16
Q

How to do TB screening before TNFi?

A

Quantiferon gold
Mantoux

If patients come in with weight loss, feeling unwell after starting TNFi, they have TB until proven otherwise, even if quantiferon gold negative.

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17
Q

AE TNFi

A

Infections e.g. TB

Demyelination
- Avoid in those with MS 1st degree relatives

Malignancies
- Non-melanoma skin cancers, lymphoma (children)

Autoantibodies (ANA, dsDNA)
Drug-induced lupus

Hepatotoxicity

Uncommon
Vasculitis
Psoriasis
Sarcoidosis

Generally well tolerated
All work better with MTX

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18
Q

Abatacept MOA and use in RA

A

MOA: Ig binds to B7 (CD80/86) on APC so it can’t bind to CD28 on T cell = block constimulation

Only approved in combination with MTX
More effective in anti-CCP positive

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19
Q

Tocilizumab MOA and use in RA

A

Humanised anti-IL6 receptor antibody
Only biologic that is clinically more efficacious than MTX as monotherapy
Superior to TNFi as monotherapy but not better than TNFi + MTX

Consider after failure of multiple TNFi

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20
Q

AE Tocilizumab

A 
Increased infections including TB reactivation
Infusion reactions
Bowel perforation
Lipid elevations
Neutropenia
LFTs derangement

Can’t look at CRP! Will be normal even in sepsis.

More side effects than TNFi so we don’t go to this straight away

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21
Q

Rituximab MOA and use in RA

A

Anti-CD20 ab
Depletes B cells. Plasma cells spared.
Produces significant and sustained improvement in disease outcome for many months
Only available with MTX

Use in patients with malignancy or have failed TNFi
Useful in rheumatoid lung disease
Don’t use in hep B

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22
Q

JAK inhibitors AE

A 
Infection; reactivation of TB
Herpes zoster 
Cytopenias 
Hyperlipidaemia 
Malignancy
CV disease
Venous thromboses
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23
Q

JAK inhibitors MOA

A

Small molecules that inhibit JAK and ILD

JAK 1 inhibitor - helpful for RA
JAK 2 and 3 - side effects

More effective with MTX
Quick onset of action

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24
Q

Tofacitinib (JAKi) AEs

A

Dirty drug like tocilizumab (IL6 inhibition)

On top of class AEs there are

Transaminitis
Increased serum Cr
Bowel perforation (avoid in severe diverticulitis)

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25
Which biologics can be used in pregnancy and breastfeeding?
TNFi Best data is with certoluzimab (don't cross placenta) But try and avoid in 3rd trimester because then the baby shouldn't have live vaccines (6 month rotavirus, MMR, varicella)
26
Baracitinib (JAKi) use in RA
Baracitinib + MTX is the most potent combination we have Better than TNFi + MTX JAK1 and 2 inhibitor Not much pregnancy data Increased thromboses Mild increase creatinine and lipids
27
Upadacitinib (JAKi)
Upadacitinib + MTX is the other most potent combination we have Better than TNFi + MTX JAK 1 inihibitor Not much pregnancy data Mild increase in creatinine and lipids
28
Do they stay on biologics forever?
Likely | Very hard to get them off it
29
Biologics pre-op
Cease 1-2 treatment cycles prior E.g. Etanercept 2 weeks, adalimumab 2-4 weeks Restart when wounds healed Rituximab when B cells normal Minor surgery no need for cessation
30
Hep C | Which biologic to choose?
Etanercept
31
Untreated chronic hep B | Which biologic to choose?
No biologic recommended
32
Treated solid malignancy <5 years or treated melanoma Which biologic to choose?
Rituximab
33
Treated solid malignancy >5 years | Which biologic to choose?
Any biologic
34
Is combination therapy better in RA?
YES MTX + SSZ + HCQ better than SSZ + HCQ or MTX alone But these days if ineffective on 2 csDMARDS for 6/12, we go to biologics (probably 50% will need biologics)
35
Main cause of reduced life expectancy in RA
Increased cardiovascular risk (from uncontrolled inflammation)
36
Risk factors for developing RA
Genetic factors HLADRB1 Smoking Peridontal disease
37
Main cytokines involved in RA
TNF-alpha IL1 IL6 IL17 Pro-inflammatory Activate synovial fibroblasts, osteoclasts --> bone and cartilage damage
38
Pattern of joint involvement in RA
Morning stiffness +++ Symmetrical, bilateral Small joints affected first MCP, PIP (spares DIP; affected in p`soriatic arthritis, OA) C spine (atlanto-axial subluxation; C1-C2 instability) Wrist synovitis/radial deviation of wrist and ulnar deviation of fingers at MCPs/CTS Swan neck deformity Boutonniere deformity Hindfoot and forefoot synovitis/MTPs affected ("walking on marbles")
39
Radiology findings of RA
Periarticular soft tissue swelling (joint effusion, tenosynovitis) Juxta-articular osteoporosis Bone erosions Joint space narrowing Deformities in advanced disease - subluxation
40
When is prednisolone useful in RA?
Useful to give pred for a few weeks (maximum 4-5/12) for bridging until DMARD efficacy reached (4-6/52 usually), or for flares
41
Rituximab AEs
Infection (especially if low Ig) Infusion reaction Reduced response to vaccine Reactivation of hep B
42
``` Treatment for RA 1st line 2nd line 3rd line Remission phase ```
1st line: MTX and short-term glucocorticoid 2nd line: Continue csDMARD and add a bDMARD/tsDMARD 3rd line: Use other bDMARD or tsDMARD in combination with existing csDMARD Move down the ladder until target reached. Once in remission phase, consider weaning therapy or spacing out treatments more.
43
Which bDMARD is best in RA?
Similar efficacy despite different MOA Always combine with MTX!
44
What do you expect RF and HLAB27 to be in seronegative spondyloarthritis?
RF negative | HLAB27 positive
45
Features of inflammatory back pain
Onset <45 years >3 consecutive months Alternating buttock pain Awaken at night particularly 2nd half of night, improves on arising Responds to NSAIDs
46
Axial spondyloarthritis clinical features
Axial features - Inflammatory back/buttock pain (sacroiliitis), restriction in spinal movement Extra-axial features - Peripheral arthritis (asymmetric, oligoarthritis of LL, enthesitis) Extra-articular features - Anterior uveitis (unilateral) - IBD, psoriasis, apical fibrosis, AR
47
Diagnostic criteria for AS (ACAS classification criteria)
Sacroilitis on imaging and ≥1 SpA feature HLAB27 and ≥2 SpA features SpA features - Inflammatory back pain - Arthritis - Enthesitis (heel) - Uveitis - Psoriasis - Crohn's/colitis - Good response to NSAIDs - HLAB27 - Elevated CRP
48
What's the difference between non-radiographic axial spondyloarthropathy vs AS?
Spectrum of the same disease 85% Non-radiographic axial spondyloarthropathy will eventually progress to AS
49
...% of HLAB27+ will develop AS
5%
50
...% of AS has HLAB27+
>90%
51
What imaging should you do in suspected AS?
Xray (takes months-years to evolve) Sacro-iliac joints Cervical, thoraco-lumbar spine MRI
52
Management of AS
Back pain and stiffness 1st line: NSAIDs (minimum 12 weeks), non-pharmacological tx 2nd line: TNF-alpha blocker or IL-17 blocker (Secukinumab) Peripheral arthritis 1st line also includes local steroids, DMARDs (MTX, sulfasalazine)
53
How to qualify for biological therapy (2nd line) in AS?
Must have trialled 12/52 NSAIDs and exercise
54
Do people need to have psoriasis to have psoriatic arthritis?
No
55
Clinical features of psoriatic arthritis
Asymmetric oligoarthritis (most common)/monoarthritis/polyarthritis DIP and PIP joints Can also have spondyloarthritis like AS Dactylitis (sausage digits) Nail disease (pitting, onycholysis, nail plate crumbling) Arthritis mutilans (complete destruction of involved joint --> looks like a telescope) Enthesitis (achilles tendon, plantar fascia)
56
RF and CCP in Psoriatic arthritis
Negative
57
Management of psoriatic arthritis
NSAIDs csDMARDs - MTX, sulfasalazine, lefluonamide Anti-TNF - infliximab, adalimumab, etanercept, golimumab, certolizumab Anti-IL17 - secukinumab, ixekizumab Anti-p40 subunit IL12/23 - ustekinumab
58
Causes of reactive arthritis
Genito-urinary infection - chlamydia trachomatis GI infection - girardia, salmonella, campylobacter, yersinia
59
Reactive arthritis clinical presentation
``` Classic triad (Reiter's syndrome): arthritis, urethritis, conjunctivitis = can't see, can't pee, can't climb a tree ``` Asymmetric, oligoarticular, lower limb Enthesitis Dactylitis Sacro-ilitis
60
Treatment of IBD associated spondyloarthritis
NSAIDs DMARDs e.g. sulfasalazine; peripheral disease only, not axial Anti-TNF Controlling bowel disease
61
Ab associated with SLE
``` ANA dsDNA Anti-histone Anti-SM (most specific) Low C3/C4 ```
62
Ab associated with Sjogren's
Anti-Ro Anti-La ANA
63
Ab associated with mixed CT disease
Anti-RNP
64
Ab associated with scleroderma
ANA Anti-Scl70 (diffuse) Anti-centromere (limited) RNA polymerase III (renal crisis)
65
Ab associated with myositis
ANA Anti-Jo1 (anti-synthetase syndrome) Anti-HMG Co-A reductase ab (statin induced ISMN)
66
Ab associated with RA
RF Anti-CCP don't repeat testing Not markers of disease activity
67
Ab associated with GPA
c-ANCA (PR3)
68
Ab associated with MPA
p-ANCA (MPO)
69
Ab associated with EGPA
p-ANCA (MPO)
70
What is the one drug that men trying to conceive should avoid?
Cyclophosphamide
71
Is tacrolimus and cyclophosphamide safe in pregnancy?
Yes
72
Are TNFi safe in pregnancy?
Yes | The only biologics that are safe
73
Should you continue csDMARDs and bDMARDs peri-op?
Continue csDMARDs e.g. MTX Hold bDMARDS e.g. rituximab
74
In mild SLE, should you hold rheumatic medications peri-op?
Yes | Hold 1/52 before surgery
75
In severe SLE, should you hold rheumatic medications peri-op?
No | Continue

Rheumatology (5 decks)

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