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Delta Med - Rheumatology > Rheumatology 3 - Rheumatoid arthritis > Flashcards

Rheumatology 3 - Rheumatoid arthritis Flashcards

1
Q

What is the pathogenesis of RA?

A

Environmental factors (smoking, gut biome, periodontis), epigenetic modification and susceptibility genes lead to altered post-transcriptional reguation - leading to self protein citrullination.

This leads to loss of tolerance - ACPA, RF

Transitions to arthritis with synovitis, structural damage and exacerbation of coexisting conditions.

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2
Q

What are features found in RA on joints?

A

Pannus formation
Synovitis
Bone erosion
Cartilage degradation with joint space narrowing

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3
Q

What are genetic risk factors for RA?

A

DRB1
STAT4
PADI
PTPN22

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4
Q

What are environmental risk factors for RA?

A

Smoking
Periodontitis
Gut dysbiosis
Anti-CCP (enolase)

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5
Q

What are inflammatory mediators involved in RA?

A

TNF, IL1, IL6 (macrophages)
IL-2, IFN (lymphocytes)
IL-12, IL-15, IL-18 (drive towards Th1 lymphocytes)
IL-17 (Th17 lymphocytes)

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6
Q

What are other mediators implicated in joint destruction?

A

PG, COX (inflammation, swelling)
RANKL (bone damage)
MMP, Aggrecanase (cartilage loss)

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7
Q

What cell types are most involved in RA pathogenesis?

A 
Macrophage
T-cell
Synovial fibroblast
B-cells
PMN (in fluid mainly)

Driven by IL-1, TNF, IL-6

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8
Q

What is a feature of Treg cells in RA?

A

Fox P3 +ve

Fox P3 inhibits differentiation to Th1, Th2, Th17

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9
Q

What cytokines drive t-cell expansion in RA?

A

IFN, IL-2

IL-12, IL-15, IL-18, IL-17

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10
Q

What cytokines drive leucocyte trafficking in RA?

A

IL-1, TNF, IL-8, MCP, MIP

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11
Q

What cytokines drive local inflammation and damage in RA?

A

IL-1, IL6, TNF

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12
Q

What is the cause of bone erosion in RA?

A

Mediated by Osteoclasts
Macrophages are potential OCs
Inflammatory milieu drives osteoclast activity
CKs TNF, IL-1, IL-6 are important

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13
Q

What is meant by cytokine disequilibrium in RA?

A

INcreased TNF and IL-1, vs soluble TNF receptor, IL-10 and IL-1 receptor antagonist

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14
Q

What proporotion of RA patients are seronegative?

A

1/3

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15
Q

How is a Dx of RA made?

A 
Small joints
symmetrical
6 weeks duration
Arm stiffness for 1 hour
RhF or anti-CCP
Nodules
Erosions
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16
Q

What is the feature of small joint involvement in RA?

A

DIP joints are spared, with fixed deformity and erosion/destruction

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17
Q

How are small joints differently involved in SLE?

A

DIP joints are spared, but deformity is passively correctible and there is minimal destruction

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18
Q

How is small joint involvement different in gout vs RA?

A

gout has involvement of the DIPJ, with tophi and large, marginal punched out lesions

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19
Q

How is small joint involvement different in psoriatic arthritis vs RA?

A

Nail changes are common, DIP joints are NOT spared and there is erosion and new bone formation with pencil in cup appearance

20
Q

How is small joint involvement different in OA?

A

DIP joints are not spared, there are heberden’s nodes and there are osteophytes, and juxta-articular sclerosis

21
Q

What is rheumatoid factor?

A

autoantibody (usually IgM) - against Fc of IgG
+ve RF and arthritis is not specific for RA

RF is associated with Rheumatoid nodules, vasculitis and worse prognosis

22
Q

What are 3 causes of high titre RF and Sn for each?

A

RA - 70-90%
Sjogren’s - 75-95%
Cryoglobulinaemia - 40-100%

23
Q

What are significant causes of false +ve rheumatoid factor?

A 
Hep B or C
Bacterial endocarditis
TB
Syphilis
Viral infection
Sarcoidosis
IPF
PBC
Malignancy
24
Q

What is anti-CCP?

A 
highly specific for RA (90%)
highly predictive of RA in asymptomatic and undifferentiated patients
Sn = 70%
Marker of severe erosive disease
Not for marker of severe disease
25
Q

What is the effect of smoking on CCP?

A

increases anti-CCP

26
Q

What are genetic factors predisposing to RA?

A

HLADR4
PTPN22
STAT4
PADI

27
Q

What are environmental triggers for RA?

A

EBC, CMV, Parvovirus, Barmah Forest, RR fever, foreign or auto antigen exposure

28
Q

What is the most potent environmental factor?

A

SMOKING

29
Q

What is an AE of MTX plus leflunomide?

A

Pneumonitis, peripheral neuropathy, transaminitis

30
Q

Why is MTX the gold standard of therapy?

A

Effective in 75% of patients
Flare with drug discontinuation
Improved mortality
MTX lung rare in practice - monitor LFT/UEC/Creat/FBC
Folinic acid rescue if sepsis and leucopenia

31
Q

What are features of leflunomide?

A 
Inhibits pyrimidine biosynthesis
Can be combined with SZP/HCQ or MTX
Pancytopenia/transaminitis/pneumonitis
Cholestyramine rescue if sepsis and leucopenia
Diarrhoea in 20% (most common AE)
32
Q

What immunological pathway blockade works in RA?

A 
TNF-a
IL-1
Il-6
costim
B-cell depletion
JAK kinase blockade
IL-12/23 blockade

CD4 T-cell depletion does not work

33
Q

What cell types does TNFa promote?

A

synoviocytes, chondrocytes and osteoclasts

34
Q

Which TNFi is not cytolytic?

A

etanercept

35
Q

What are key points of TNF blockade?

A

rapid onset - 1-2 weeks (60% of patients respond)
no difference in efficacy between agents
acceptable toxicity (Infection, TB risk, demyelination, lymphoma)
? induction of remission - BEST study w infliximab

36
Q

What are issues with TNF blockade?

A

TB
Congestive heart failure - NYHA Class III or above
De-myelinating disease (? optic neuritis/demyelinating conditions)
Lymphoma
Lupus like syndrome or ANA/dsDNA
Cancer in the last 5 years

37
Q

What are pathologies that respond to TNF blockade?

A

Infections (bacterial) - staph/strep/pneumococcus
Zoster!
Chronic HSV (ophthalmic)
Melanoma

38
Q

What is the relationship between TNF blockade and malignancy?

A

SIR around 1.0 with Lymphoma
No definite increase in risk of solid tumours
Increased skin cancer (melanoma and non-melanoma)
No TNFi if cancer in last 5 years

39
Q

What is the management of latent/active TB prior to TNFi commencement?

A

Latent - Quant gold+ve
- isoniazid for 4-6 weeks pre therapy, continue for 9 months (high rate abnormal LFTs with isoniazid)
Active TB
- pulm or non-pulmonary
- treat with std chemo
- should have at least 2 months of therapy before commenting TNFi

40
Q

What is the effect of IL-6 in RA?

A 
activation of autoreactive T-cells
Increase in RF
Hyper-gammaglobulinaemia
Leukocytosis
Anaemia
Thrombocytosis
Activation of osteoclasts
Induction of MMPs
Increase in acute phase proteins
Hypoalbuminaemia
Amyloidosis
Induction of VEGF
41
Q

What are precautions in IL-6R blockade

A

tocilizumab = Anti-IL6R
Increased LFTs 11% esp with MTX
Increased total and HDL cholesterol but decreased CRP - lower CV risk

42
Q

What is the role of b-cell depletion in RF?

A

reduced rheumatoid factor by B-cells leads to reduced complement fixation and inflammation.
RITUXIMAB is anti-CD20, measure CD19 to check levels

43
Q

What is the role of abatacept in RA?

A

blocks costimulation of T-cells by binding to B7, interrupting CD28-b7 interaction
CTLA-4 blockade significant improves S+Sx and QoL in addition to MTX

44
Q

What is the role of tofacitinib in RA?

A

oral JAK3/1 inhibition, reduces signs and symptoms of RA as monotherapy - suppreses STAT1 dependent genes

45
Q

What patients with RA require aggressive treatment of OP?

A

CRP/ESR high at baseline/in spite of therapy
high swollen joint count
persistent inflammatory symmetrical arthrtitis (PISA)
RhF/anti-CCP high
erosions

46
Q

What patients should be selected for aggressive bDMARD therapy?

A

Failed non biologic dmard
Cant tolerate non-biologic dmard
Persistently elevated ESR/CRP
Persistently elevated joint count

Delta Med - Rheumatology (3 decks)

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