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Rheumatology > Rheumatoid arthritis > Flashcards

Rheumatoid arthritis Flashcards

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
Q

Which biologics can be used in pregnancy and breastfeeding?

A

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)

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26
Q

Baracitinib (JAKi) use in RA

A

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

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27
Q

Upadacitinib (JAKi)

A

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

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28
Q

Do they stay on biologics forever?

A

Likely

Very hard to get them off it

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29
Q

Biologics pre-op

A

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

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30
Q

Hep C

Which biologic to choose?

A

Etanercept

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31
Q

Untreated chronic hep B

Which biologic to choose?

A

No biologic recommended

32
Q

Treated solid malignancy <5 years or treated
melanoma
Which biologic to choose?

A

Rituximab

33
Q

Treated solid malignancy >5 years

Which biologic to choose?

A

Any biologic

34
Q

Is combination therapy better in RA?

A

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
Q

Main cause of reduced life expectancy in RA

A

Increased cardiovascular risk (from uncontrolled inflammation)

36
Q

Risk factors for developing RA

A

Genetic factors
HLADRB1
Smoking
Peridontal disease

37
Q

Main cytokines involved in RA

A

TNF-alpha
IL1
IL6
IL17

Pro-inflammatory
Activate synovial fibroblasts, osteoclasts –> bone and cartilage damage

38
Q

Pattern of joint involvement in RA

A

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
Q

Radiology findings of RA

A

Periarticular soft tissue swelling (joint effusion, tenosynovitis)

Juxta-articular osteoporosis

Bone erosions

Joint space narrowing

Deformities in advanced disease - subluxation

40
Q

When is prednisolone useful in RA?

A

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
Q

Rituximab AEs

A

Infection (especially if low Ig)
Infusion reaction
Reduced response to vaccine
Reactivation of hep B

42
Q 
Treatment for RA
1st line
2nd line
3rd line
Remission phase
A

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
Q

Which bDMARD is best in RA?

A

Similar efficacy despite different MOA

Always combine with MTX!

44
Q

What do you expect RF and HLAB27 to be in seronegative spondyloarthritis?

A

RF negative

HLAB27 positive

45
Q

Features of inflammatory back pain

A

Onset <45 years

> 3 consecutive months

Alternating buttock pain

Awaken at night particularly 2nd half of night, improves on arising

Responds to NSAIDs

46
Q

Axial spondyloarthritis clinical features

A

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
Q

Diagnostic criteria for AS (ACAS classification criteria)

A

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
Q

What’s the difference between non-radiographic axial spondyloarthropathy vs AS?

A

Spectrum of the same disease

85% Non-radiographic axial spondyloarthropathy will eventually progress to AS

49
Q

…% of HLAB27+ will develop AS

A

5%

50
Q

…% of AS has HLAB27+

A

> 90%

51
Q

What imaging should you do in suspected AS?

A

Xray (takes months-years to evolve)
Sacro-iliac joints
Cervical, thoraco-lumbar spine

MRI

52
Q

Management of AS

A

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
Q

How to qualify for biological therapy (2nd line) in AS?

A

Must have trialled 12/52 NSAIDs and exercise

54
Q

Do people need to have psoriasis to have psoriatic arthritis?

A

No

55
Q

Clinical features of psoriatic arthritis

A

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
Q

RF and CCP in Psoriatic arthritis

A

Negative

57
Q

Management of psoriatic arthritis

A

NSAIDs

csDMARDs - MTX, sulfasalazine, lefluonamide

Anti-TNF - infliximab, adalimumab, etanercept, golimumab, certolizumab

Anti-IL17 - secukinumab, ixekizumab

Anti-p40 subunit IL12/23 - ustekinumab

58
Q

Causes of reactive arthritis

A

Genito-urinary infection - chlamydia trachomatis

GI infection - girardia, salmonella, campylobacter, yersinia

59
Q

Reactive arthritis clinical presentation

A 
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
Q

Treatment of IBD associated spondyloarthritis

A

NSAIDs

DMARDs e.g. sulfasalazine; peripheral disease only, not axial

Anti-TNF

Controlling bowel disease

61
Q

Ab associated with SLE

A 
ANA
dsDNA
Anti-histone
Anti-SM (most specific)
Low C3/C4
62
Q

Ab associated with Sjogren’s

A

Anti-Ro
Anti-La
ANA

63
Q

Ab associated with mixed CT disease

A

Anti-RNP

64
Q

Ab associated with scleroderma

A

ANA
Anti-Scl70 (diffuse)
Anti-centromere (limited)
RNA polymerase III (renal crisis)

65
Q

Ab associated with myositis

A

ANA
Anti-Jo1 (anti-synthetase syndrome)
Anti-HMG Co-A reductase ab (statin induced ISMN)

66
Q

Ab associated with RA

A

RF
Anti-CCP

don’t repeat testing
Not markers of disease activity

67
Q

Ab associated with GPA

A

c-ANCA (PR3)

68
Q

Ab associated with MPA

A

p-ANCA (MPO)

69
Q

Ab associated with EGPA

A

p-ANCA (MPO)

70
Q

What is the one drug that men trying to conceive should avoid?

A

Cyclophosphamide

71
Q

Is tacrolimus and cyclophosphamide safe in pregnancy?

A

Yes

72
Q

Are TNFi safe in pregnancy?

A

Yes

The only biologics that are safe

73
Q

Should you continue csDMARDs and bDMARDs peri-op?

A

Continue csDMARDs e.g. MTX

Hold bDMARDS e.g. rituximab

74
Q

In mild SLE, should you hold rheumatic medications peri-op?

A

Yes

Hold 1/52 before surgery

75
Q

In severe SLE, should you hold rheumatic medications peri-op?

A

No

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Rheumatology (5 decks)

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