Rheumatoid arthritis Flashcards
RA prevalence and peak onset (decades)
1% of population
Peak onset 30-60 y.o.
Characteristics of RA
Systemic autoimmune disease characterised by:
- autoantibody production
- synovial inflammation and hyperplasia
RA Pathogenesis
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
Genetic factors for RA:
- anti-CCP positive disease
- negative disease
CCP positive - HLA-DRB101, -04, -15, CTLA4, STAT4
CCP negative - HLA-DRB103, -*13, IRF5, STAT4
Environmental factors for RA
3 mucosal sites involved: lungs, oral mucosa, GI tract
Smoking - dose dependent
Gum disease - PADI (peptidyl arginase deaminase) by Porphyromonas gingivalis
Antibodies in RA
Rheumatoid factor
Anti-CCP
Anti-PAD4
Anti-CarP
Rheumatoid factor
- what are they against
- sensitivity
- specificity
- effect on disease severity
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
What other conditions are associated with rheumatoid factor positivity?
Sjogrens (75-95%)
Cryoglobulinaemia
SLE
Chronic infections (HBV and HCV)
Cancer
Anti-CCP
- what are they against
- sensitivity
- specificity
- effect on disease severity
Associated with higher disease severity
95% specificity
Citrullination is the post-translational conversion of peptidylarginine to peptidylcitrulline
What is the process occurring in the synovium of RA?
Inflammatory cells and mediators involved
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
Clinical features of RA
Onset
acute
intermediate
chronic / insidious
Acute 15%
Intermediate 20%
Chronic / insidious onset in the majority 65%
Clinical features
Joints involved
Joints spared
Usually small joints of the hands first
Larger joints often involved later in disease
Spares DIPs
What is RS3PE syndrome?
Remitting, seronegative, symmetrical synovitis with pitting edema syndrome:
- seronegative, responds to glucocorticoids
RA typical hand / finger deformities
Hands and wrists:
Wrist synovitis
Swan neck deformity
Boutonniere deformity
Flail interphalyngeal joint
RA typical foot involvement
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
Extra-articular RA involvement
Rheumatoid nodules
Vasculitis (small and medium vessels)
Ulcers
Neutrophillic dermatosis
Episcleritis
Scleritis
Perilimbal ischaemic ulcers
Secondary Sjogren syndrome
Pulmonary RA features
Pleural effusiuons - exudate, low glucose
Pleuritis
Nodules that can mimic cancer
Cricoarytenoid arthritis
Interstitial lung disease
Bronchiectasis
Cryptogenic organising pneumonia
Cardiovascular RA features
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
GI and Renal RA features
Secondary sjogrens
Xerostomia
Gastritis or PUD (from NSAIDS or steroids)
Stomatitis, mucositis (from Mtx)
Glomerulonephritis (mesangioproliferative)
Proteinuria
Treatment related kidney disease
Haematologic features of RA
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
Radiographic features of RA
Periarticular soft tissue swelling
Juxta-articular osteoporosis
Marginal erosions
Joint space narrowing
Symmetric involvement
Deformities
XR
US and MRI - greater sensitivity than examination alone.
RA classification criteria
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)
Treatment for RA
Symptoms: NSAIDs
Prednisolone for bridging
DMARDs:
MTX, Sulfasalazine, leflunomide, tofacitinib
TNFi, CD20i, IL-6Ri, T-cell co-stimulation inhibitor, JAK inhibitor
