Rheumatoid arthritis

Question 1

RA prevalence and peak onset (decades)

Answer 1

1% of population
Peak onset 30-60 y.o.

Question 2

Characteristics of RA

Answer 2

Systemic autoimmune disease characterised by:
- autoantibody production
- synovial inflammation and hyperplasia

Question 3

RA Pathogenesis

Answer 3

a reasonable hypothesis is that the genetic predisposition to RA involves a propensity to autoimmune responses, but that repeated exposure to environmental agents is ultimately responsible for tipping the balance from subclinical autoimmunity to diseases such as RA

Question 4

Genetic factors for RA:
- anti-CCP positive disease
- negative disease

Answer 4

CCP positive - HLA-DRB101, -04, -15, CTLA4, STAT4
CCP negative - HLA-DRB103, -*13, IRF5, STAT4

Question 5

Environmental factors for RA

Answer 5

3 mucosal sites involved: lungs, oral mucosa, GI tract

Smoking - dose dependent
Gum disease - PADI (peptidyl arginase deaminase) by Porphyromonas gingivalis

Question 6

Antibodies in RA

Answer 6

Rheumatoid factor
Anti-CCP
Anti-PAD4
Anti-CarP

Question 7

Rheumatoid factor
- what are they against
- sensitivity
- specificity
- effect on disease severity

Answer 7

RF
- Ab against Fc portion of IgG Ab
- present in 75% of RA
- moderate specificity at low titre, high specificity at high titre
- more likely to have severe disease, extra-articular manifestations and higher cardiovascular risk

Question 8

What other conditions are associated with rheumatoid factor positivity?

Answer 8

Sjogrens (75-95%)
Cryoglobulinaemia
SLE
Chronic infections (HBV and HCV)
Cancer

Question 9

Anti-CCP
- what are they against
- sensitivity
- specificity
- effect on disease severity

Answer 9

Associated with higher disease severity
95% specificity
Citrullination is the post-translational conversion of peptidylarginine to peptidylcitrulline

Question 10

What is the process occurring in the synovium of RA?
Inflammatory cells and mediators involved

Answer 10

hypertrophic, villous appearance with thickening of synovial layer with sublayer infiltrated with inflammatory cells. Over time this develops a pannus which erodes bone at the cartilage - pannus junction.

In synovium: dendritic cells interact with Fibroblast-Like Synoviocytes and macrophages (plus osteoclasts, T and B cells): produce cytokines, growth and differentiation.
Key cytokines include TNF, IL-17A, IL-17F, IL-1 a + B, IL-6, BLyS + April, RANK /RANK-L

Question 11

Clinical features of RA
Onset
acute
intermediate
chronic / insidious

Answer 11

Acute 15%
Intermediate 20%
Chronic / insidious onset in the majority 65%

Question 12

Clinical features
Joints involved
Joints spared

Answer 12

Usually small joints of the hands first
Larger joints often involved later in disease
Spares DIPs

Question 13

What is RS3PE syndrome?

Answer 13

Remitting, seronegative, symmetrical synovitis with pitting edema syndrome:
- seronegative, responds to glucocorticoids

Question 14

RA typical hand / finger deformities

Answer 14

Hands and wrists:
Wrist synovitis
Swan neck deformity
Boutonniere deformity
Flail interphalyngeal joint

Question 15

RA typical foot involvement

Answer 15

Hindfoot synovitis: ankle and subtalar involvement resulting in pronation and eversion of foot, arch collapse
Subluxation of metatarsal heads “walking on marbles”
36% have involvement of feet prior to hands
5th MTP is often first site to develop erosions

Question 16

Extra-articular RA involvement

Answer 16

Rheumatoid nodules
Vasculitis (small and medium vessels)
Ulcers
Neutrophillic dermatosis
Episcleritis
Scleritis
Perilimbal ischaemic ulcers
Secondary Sjogren syndrome

Question 17

Pulmonary RA features

Answer 17

Pleural effusiuons - exudate, low glucose
Pleuritis
Nodules that can mimic cancer
Cricoarytenoid arthritis
Interstitial lung disease
Bronchiectasis
Cryptogenic organising pneumonia

Question 18

Cardiovascular RA features

Answer 18

Premature atherosclerosis
Comparable to that with diabetes mellitus
Risk 2x fold higher than general population
TNFi and Mtx may modify this risk
Pericarditis and pericardial effusion
Arrhythmias
Myocarditis
Heart failure (usually HFpEF)
Cardiac nodules

Question 19

GI and Renal RA features

Answer 19

Secondary sjogrens
Xerostomia
Gastritis or PUD (from NSAIDS or steroids)
Stomatitis, mucositis (from Mtx)
Glomerulonephritis (mesangioproliferative)
Proteinuria
Treatment related kidney disease

Question 20

Haematologic features of RA

Answer 20

Lymphadenopathy
Felty syndrome (usually long standing, sero+, nodular, deforming RA. Splenomegaly, leukopaenia but also lower limb ulceration, hyperpigmentation, bone marroy hyperplastic suppressed by ongoing inflammation.
Lymphoma
Amyloidosis
Cryoglobulinaemia
Large granular lymphocyte syndrome

Question 21

Radiographic features of RA

Answer 21

Periarticular soft tissue swelling
Juxta-articular osteoporosis
Marginal erosions
Joint space narrowing
Symmetric involvement
Deformities

XR
US and MRI - greater sensitivity than examination alone.

Question 22

RA classification criteria

Answer 22

At least one joint swelling and synovitis not better explained by another condition

And score of 6 or more out of 10 from the following categories:
A. Joint involvement
B. Serology
C. Acute phase reactants (CRP/ESR)
D. Duration (more or less than 6 weeks)

Question 23

Treatment for RA

Answer 23

Symptoms: NSAIDs
Prednisolone for bridging
DMARDs:
MTX, Sulfasalazine, leflunomide, tofacitinib
TNFi, CD20i, IL-6Ri, T-cell co-stimulation inhibitor, JAK inhibitor