Rheumatoid Arthritis (RA) Flashcards
Immunopathogenesis of RA
- RF produced by RA synovium (B cells)
- RF’s fix complement
- Complement consumed in RA joint; recruit PMN’s
- Anti-cyclic citrullinated peptides
RA Pathophysiology
HLA-DRB 4 alleles and DRB 1
Pathologic changes in joints precedes synovitis in RA patients 5-10 years
Infiltration of leukocytes, cytokines and macrophages act as antigen presenting cells to activate T cells
“B” lymphocytes produce autoantibodies, cytokines (TNF alpha, IL-1, IL6), proinflammatory cytokines synovial proliferation, increase synovial fluid, leads to “pannus” that invades cartilage and bone.
the pannus invades and erode the cartilage
RA treatment
- Begin NSAID for pain control
- Early use of DMARD
- May need low dose of steroid for a few weeks
- Monitor progress and toxicity
why is RA important?
- Significant mortality (inc. CAD, HF due to endothelial damage from chronic inflammation)
- Frequently disables patients
mortality associated with RA
infection
renal disease
GI disease
heart disease
malignancy
2010 RA Classification Criteria
Joint involvement:
1 large joint = 1 pt
2-10 large joints = 2 pt
1-3 small joints = 2 pt
4-10 small joints = 3 pt
> 10 joints (at least 1 sm) = 5 pt
Score > 6/10 = definite RA
Serology (at least 1 test +)
Neg. RF & neg. anti - CCP = 0
Low + RF or low + ACCP = 2
High + RF or high + ACCP = 3
Acute phase reactants (at least 1 test needed)
Normal CRP & normal ESR = 0
Abn CRP or abn ESR = 1
Articular Manifestations of RA
diarthrodial synovial joint
starts in hands and feet; MCP, PIP, MTP / spares DIP
- Swan neck (hyperextension of PIP joints)
- Boutonniere (button hole deformity) (hyperflexion of PIP joints)
- Feet - MTP
- Wrist – radial deviation; synovial proliferation may compress the median nerve; carpal tunnel syndrome
- Knees – Bakers cyst; popliteal – rupture painful differential diagnosis is VTE
- Neck - C1 – C2 May subluxation
Later larger joints
C1 – C2 / Not the rest of the axial spine
Inc. risk osteoporosis
Morning stiffness > one (1) year
Extra-Articular Manifestations
More common in RF positive or Anti-CCP positive
Skin – subcutaneous nodules; extensor surface of forearm
Pyroderma Gangrenosum-Tender reddish purple papule; leads to necrotic, non-healing ulcer
Rheumatoid Vasculitis-Purpura, petechial, splinter hemorrhages, digital infarct (look at toes)
Extra‐articular manifestation of RA due to a secondary Sjogrens (Show‐gren) Syndrome (keratoconjunctivitis sicca)
keratoconjunctivitis sicca-dry eys, dry mouth
- Ro/SS-a, La/SS-B (both associated with salivary gland involvement)
- Schirmers test
- Slit-lamp exam
Treatment:
- Lubrication with artificial tears
- Oral hygiene, encourage water
why important?: 35% of the RA patients are predisposed to Sjogren’s (majority are female)
Sjogren’s Syndrome
Sicca symptoms include dry eyes, dry mouth, vaginal dryness and tracheo-bronchial dryness
Primary Sjogren’s Syndrome is associated w/SS-A (Ro) and SS – B (La) + antibodies
Treated sx Anti–Inflammatory & Immunosuppressive
Autoimmune Exocrinopathy
Feltys Syndrome
Triad:
Rheumatoid arthritis
splenomegaly
Neutropenia (<2000)
RF and anti-CCp positive
Atlantoaxial subluxation (C1-C2) due to erosion of odontoid process; peripheral neuropathy and cervical myelopathy
- General – Life long disease process without known cure
- Use consultant (Rheumatologist), PT, OT
- Articular rest (red, warm, swollen?, put it to rest)
- “Treat to Target”
– treat early to prevent irreversible cartilage and bone damage
• Goal is disease remission as soon as possible; possible in 50% of patients if treated early
NSAID (first-line)
- Pain relief
- Does not halt disease progression/not disease modifying
- Can use with DMARD’s
- GI toxicity
- Inhibits COX enzymes / PGE2, promotes renal sodium exertion
corticosteroids
“Bridge Therapy”, “Flares Therapy with corticosteroids
DMARDS - Disease Modifying Anti-Rheumatic Drugs start 3-6 months standard of care
2 Groups – Non-biologics (conventional) & Biologics
- Non-biologics – Methotrexate – inhibits folic acid/give supplemental folic acid
- Recommended as first DMARD for RA/once a week
- Monitor lab (CBC, LFT’s (liver function tests), Creat) q 4 – 8 weeks
- Toxicity – hepatic, myelosuppression, pulmonary
- Don’t give during pregnancy
other non-biologic DMARDs
Hydroxychloroquine (Plaquenil and Chloroquine)
- Need F/U with ophthalmologist (macular damage to retina, blurred vision, halos, photophobic)
- Can use with Methotrex and sulfasazine (Azulfidine)
safe for pregnancy
Leflunomide
Pyrimidine antagonist
Rapid excretion with cholestyramine
Don’t use when pregnant
GI/hepatic toxicity/teratogenic!!
Sulfasalazine
Monitor WBC
Can use with methotrexate
Safe in those who are pregnant
Toxicities of all biologics
Inc. risk of infection
TNF alpha is pro-inflammatory cytokine in RA pathogenesis.
- Stimulates synovial cell proliferation and collagenase/destroy cartilage
- Increase inflammation
Anti-TNF Agents
- Etanercept (Enbrel)
- Infliximab (Remicade)
- Adalimumab (Humira)
- Rituximab (Rituxan; depletes B cells)
Managing RA
- Define extent of joint and extra-articular involvement
- Full dose of NSAID
- Early use of DMARD – methotrexate 3-6 month window
- Add a biologic agent
- Low does steroids – flares/bridge
- Adequate pain management
- Monitor progress/toxicity
