Rheumatoid arthritis Flashcards
Common symptoms to rheumatoid diseases
Malaise, fatigue
myalgia
arthritis
anaemia
RA
Caused by rheumatoid factor ACPA (Anti cyclic citrullinated peptide antibody) Based on: Synovitis in at least 1 joint No alternative explaination ACR score >6
Incidence of RA ^with age until 75 and class 2 genes account for 40% of genetic susceptability
PAD -Peptidyl arginine deiminase
The enzyme converts arginine on peptide to citrulline
This leads to a citrullinated peptide which is an autoantigen
ACPA
Highly specific
Found upto 14 years beforehand
Accurate predictor of erosive and progressive disease
Signs and symptoms
Onset over weeks and months
Pained/stiff joints due to inflammatory synovitis
Swelling in small joints, sometimes also in large
Fatigue
Flu
Morning stiffness
Radiology evidence of RA
Soft tissue swelling Narrow joint space Less cartilage Juxta-articular erosion Large cystic erosion Deviation of carpus and ulnar digits Erosion of MTP foot joints atlantial axial subluxaation of neck
DAS28
Score <2.6=remission
score 1-3.2=low disease activity
Score >5.1=High disease activity
HAQDI scoring
Difficulty in performing various tasks
0-3 with
0=no difficulty and 3=cannot do
RA effect on QoL
Radio evidence of erosion in 0-2years 50% disabled in 5 years 50% max radio damage in 6 years 80% disabled in 20 years Life expectancy reduced by 3-18yrs due to commorbidities
Indicators of RA poor outcome
HLA-DRB1 gene
High CRP/ESR
ACPA/RF +ve
Triple therapy
Methotrexate, Sulfasalazine, Hydroxychloroquine
Methotrexate
Subs as folic acid interfering with tetrahydrofolate and purine synthesis
Effects rapid turnover cells: hair, immune and mucousal
7.5-25mg ONCE a week given as 2.5g tabs
6-8week onset
Dont use with pregnancy, sulfa antibiotics, alcohol
Hydroxychloroquine
Antimalarial with use for inflammatory arthritis. Increases cell pH and inhibits ability to degrade and process proteins
200-400mg daily
Onset in 6-12weeks
Photosensitivity may occur as well as rash, nausea, diarrhoea and difficulty reading
Sulfasalazine
Salacylic acid+sulfapyridine joined by azo bond
Sulfapyridone thought to be API but no one knows how it works
500mg daily=>500mg QDS
6-8 weeks onset
Monitoring to be done
AST/ALP/ALT/albumin
ESR/CRP
RF/ACPA
FBC and Cr
csDMARD
conventional synthetic DISEASE MODIFYING ANIT-RHEUMATIC DRUG
Leflunomide
Newer DMARD. Is a pro drug activated in GI/liver 10-20mg daily Inhibits pyrimidine synthesis Onset in 6-8weeks Avoid in pregnancy/alcohol
Rituximab (TNF)
B cell depleting anti CD20 antibody
Complement mediated cell lysis occurs
Leads to bcell apoptosis
Abatacept
Receptor made of CTLA 4 +FcR region of IgG
Stops interaction of CD80 on t cells
May use CD28 to inhibit lymphocyte activation and cause cell apoptosis
Other Biologics
Anakinra/tocilizumab: Inhibits interleukins
JAK inhibitors which block IL cytokine activity
Surgery
Synovectomy
arthroplasty
Spinal stablilisation
Causes of immunopathology
Following a mycobacterium or streptococcus infection
CD4+ T cells intiates and sustains disease by recognising collagen and cartilage as antigens
Lines of treatment
1st line- NSAIDS all have significant side effects
2nd line- DMARDS more severe toxicity but aims to improve disease state rather than symptomatic relief
DMARD mechanism
Inhibits macrophage activation
Inhibits cell proliferation
Inhibits inflammatory cytokines and RONS
Endogenous corticoids
Mineral-aldosterone, water/electrolyte homeostasis
Gluco- hydrocortisone/corticosterone
-carb/protein metab
-anti inflammatory+ immunosuppression
Deficiency cause addisons
excess causes cushings and conns syndrome
Glucocorticoids
Inhibits inflammation
Decrease cell extravasation and cell activation
Decrease synthesis of inflam mediators
IL 1 Effects
^synthesis of COX 2 and iNOS
^expression of ICAM/VCAM
^bone erosion through osteoclasts
