2. Definition
• Chronic inflammatory disorder of unknown
aetiology characterized by Symmetric
Polyarthritis (MC form of Chronic inflammatory
arthritis)
2
3. Epidemiology
• 0.5-1% of Adult pop
• Asia & Africa – Low prevalence = 0.2-0.4%
• F > M = 2-3:1
• Estrogen TNF α Enhance immune response
3
4. Genetics
• 1st Degree Relative
• HLA DRB1 gene MHC 2 β chain Shared Epitope(SE)
• Carriers of SE allele Anti-CCP Ab production worse
outcome
• High Risk Alleles = 0401
• Moderate Risk Alleles = 0101 4040 0901 1001
• GWAS position of 11,71,74 of HLA-DRB1 ; 9 of HLA-B
; 9 of HLA-DPB1
• PTNP22 gene Anti-CCP positive disease Europe
• PADI4 gene Asian pop.
• APOM East Asian pop. inc. risk of Dyslipidemia too
• Micro RNA miR146a/miR155
4
5. Environmental factors
• Cigarette smoking-> Anti-CCP AB positive cases
• EBV
• Peridontitis Porphyromonas gingivialis
PAD( peptidy arginine deiminase) enzyme
Cirtullination of arginine Ab against citrulline
Anti-CCP Ab
5
6. PATHOGENESIS
• GENETICS + ENVIRONMENT FACTORS
• Modification of our own Ag
• Citrullination in Type 2 collagen and Vimentin
• APC detecting citrullinated cells as Foreign Ag
• Cd4+ T cells B cells Plasma cells Ig production
• T cells IFNγ and IL 17 Macrophages TNFα ,
IL 1 , IL6 Synovial cell proliferation & PANNUS
• Inflammatory cytokines T cells RANK L
Osteoclasts Resorption lacunae of bone
• Ab RF & Anti-CCP Immune complexes
Complement activation Inflammation
• Chronic Inflammation Angiogenesis 6
32. Measurement of Disease Progression
• To determine the progression of RA, patients are categorized by clinical and
radiologic criteria into 4 stages, as follows:
• Stage I (early RA) – No destructive changes observed upon radiographic
examination; radiographic evidence of osteoporosis is possible
• Stage II (moderate progression) – Radiographic evidence of periarticular
osteoporosis, with or without slight subchondral bone destruction; slight cartilage
destruction is possible; joint mobility is possibly limited, but no joint deformities
are observed; adjacent muscle atrophy is present; extra-articular soft tissue lesions
(e.g., nodules and tenosynovitis) are possible
• Stage III (severe progression) – Radiographic evidence of cartilage and bone
destruction in addition to periarticular osteoporosis; joint deformity (e.g.,
subluxation, ulnar deviation, or hyperextension) without fibrous or bony
ankylosis; muscle atrophy is extensive; extra-articular soft tissue lesions (e.g.,
nodules, tenosynovitis) are possible
• Stage IV (terminal progression) – Presence of fibrous or bony ankylosis, along
with criteria of stage III 32
33. TREATMENT
33
• ACR 20,50,70 Improvement Criteria = Clinical trials
• DAS 28 - Disease Activity Score 28 joint
• SDAI - Simplified Disease Activity Index
• CDAI - Clinical Disease Activity Index
• RAPID3 – Routine Assessment of Patient Index Data 3
• PAS
• PAS Ⅱ
• Continuous measures of disease activity
35. NSAIDs
• Adjunctive agents in Rx of RA
• Non selective COX1 &COX 2 Inhibition
S/E:
• Chronic Gastritis
• Peptic ulcer disease
• CRF
35
36. DMARDs
• Conventional = Mtx, HCQs, Sulfasalazine, Leflunomide
• Not in Use = Minocycline, Gold salts, Penicillamine,
Azathioprine, Cyclosporine
• Delayed onset of action = 6-12 weeks
• Slow/prevent Structural progression of RA
• Mtx = Methotrexate = Benchmark of efficacy
• HCQs = not TRUE DMARD = doesn’t delay
radiographic progression
used in early & mild disease / Adjunctive Rx in combo
with other DMARDs
36
37. Glucocorticoids
1. Low to Moderate doses Rapid disease control
before onset of fully effective DMARD therapy
2. 1-2 week burst of Glucocorticoids Acute flare
3. Low dose Prednisone = 5-10mg/d Inadequate
response to DMARDs
4. High doses Steroids > 10mg/day Prednisone Severe
Extra Articular C/F ILD
5. One/Few Joints IntraArticular Inj. Triamcinolone
acetonide Exclude Infection Mimic Flare
S/E:
• Osteoporosis Bisphosphonate – Primary Prevention
• PUD 37
40. Biologics
Anti -TNF agents:
• Infliximab = Chimeric Monoclonal Ab
• Adalimumab & Golimumab = Humanized monoclonal Ab
• Etanercept = TNF Receptor 2 binding to Fc portion of IgG1
• Certolizumab = Pegylated Fc free fragment binding to TNFα
Can be used as Monotherapy
S/E:
• Serious Bact. Inf.
• Oppurtunistic fungal inf.
• Reactivation of Latent TB
C/I:
• Chronic Hep B
• Class 3/4 Heart Failure 40
46. Treatment of EA C/F
• RA-ILD
• Rx with High Dose Steroids +
Immunosuppressants = Azathioprine,
Mycophenolate mofetil, Rituximab
• Aggressive Mx of early disease Prevent
Occurrence
• Other C/F Underlying RA Rx covers
46
47. ACR 2015 Rx Guidelines
• Early (<6 months of disease duration)
• Established(>6months)
Physical therapy :
• Dynamic strength training
• Physical activity = 30 min of moderately intensity activity most
days a week
• Foot Orthotic = Painful valgus deformity
• Wrist Splints
Surgery:
• Knee, Hip, Shoulder, Elbow = Total joint arthroplasty
• Silicone implants MCP arthroplasty
• Arthrodesis & Total wrist Arthroplasty
47
48. Pregnancy:
• 75% = Improvement of symptoms
• Flare Glucocorticoids Low dose
• HCQs & Sulfasalazine = Safest DMARDs
• Mtx & Leflunomide Category X
• Biologics = Avoided
• Elderly:
• > 60 yrs
• Less aggressive Rx with less drug toxicity
• NSAIDs = decline in renal function
• Mtx = Avoided in S.Cr > 2mg/dl
48