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

Rheumatology 3 - Rheumatoid arthritis Flashcards

(46 cards)

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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?

Study These Flashcards
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?

Study These Flashcards
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?

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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?

Study These Flashcards
A

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

23
Q

What are significant causes of false +ve rheumatoid factor?

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

What is anti-CCP?

Study These Flashcards
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
What is the effect of smoking on CCP?
increases anti-CCP
26
What are genetic factors predisposing to RA?
HLADR4 PTPN22 STAT4 PADI
27
What are environmental triggers for RA?
EBC, CMV, Parvovirus, Barmah Forest, RR fever, foreign or auto antigen exposure
28
What is the most potent environmental factor?
SMOKING
29
What is an AE of MTX plus leflunomide?
Pneumonitis, peripheral neuropathy, transaminitis
30
Why is MTX the gold standard of therapy?
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
What are features of leflunomide?
``` 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
What immunological pathway blockade works in RA?
``` 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
What cell types does TNFa promote?
synoviocytes, chondrocytes and osteoclasts
34
Which TNFi is not cytolytic?
etanercept
35
What are key points of TNF blockade?
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
What are issues with TNF blockade?
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
What are pathologies that respond to TNF blockade?
Infections (bacterial) - staph/strep/pneumococcus Zoster! Chronic HSV (ophthalmic) Melanoma
38
What is the relationship between TNF blockade and malignancy?
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
What is the management of latent/active TB prior to TNFi commencement?
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
What is the effect of IL-6 in RA?
``` 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
What are precautions in IL-6R blockade
tocilizumab = Anti-IL6R Increased LFTs 11% esp with MTX Increased total and HDL cholesterol but decreased CRP - lower CV risk
42
What is the role of b-cell depletion in RF?
reduced rheumatoid factor by B-cells leads to reduced complement fixation and inflammation. RITUXIMAB is anti-CD20, measure CD19 to check levels
43
What is the role of abatacept in RA?
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
What is the role of tofacitinib in RA?
oral JAK3/1 inhibition, reduces signs and symptoms of RA as monotherapy - suppreses STAT1 dependent genes
45
What patients with RA require aggressive treatment of OP?
CRP/ESR high at baseline/in spite of therapy high swollen joint count persistent inflammatory symmetrical arthrtitis (PISA) RhF/anti-CCP high erosions
46
What patients should be selected for aggressive bDMARD therapy?
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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