Rheumatoid Arthritis Flashcards
rheumatoid arthritis (RA) - defined
*a chronic autoimmune disease marked by inflammation and destruction of multiple synovial joints
*causes symmetric, inflammatory joint destruction and deformation of the joints, usually fingers, wrists, and feet
rheumatoid arthritis (RA) - epidemiology
*1% of adults; prevalence increases with age
*female predominant (2:1)
*age on onset: 40-60s
rheumatoid arthritis (RA) - genetic risk factors
*genetic component (monozygotic twin concordance rate = 12-15%), but does not explain all of it
*shared epitope: HLA-DR4 = increased risk,, especially combined with SMOKING
rheumatoid arthritis (RA) - environmental risk factors
*SMOKING = increased risk (esp. with HLA-DR4 epitope)
*bacteria (normal flora; esp poor dental hygiene)
*viruses
rheumatoid arthritis (RA) - pathogenesis
*synovial inflammation → hypertrophy of synovial lining, forming a pannus (inflamed granulation tissue) → triggers inflammation cascade
*type III hypersensitivity reaction
features of inflammatory arthritis
*morning stiffness > 1 hour
*improves with activity
*worsens with rest
note - RA classically has inflammatory arthritis
features of non-inflammatory arthritis
*morning stiffness < 30 min
*worsens with activity
*improves with rest
note - osteoarthritis classically has non-inflammatory arthritis
contrast inflammatory vs. non-inflammatory arthritis
*morning stiffness:
-inflammatory: > 1 hour
-noninflammatory: < 30 min
*effects of activity/rest:
-inflammatory: improves with activity, worsens with rest
-noninflammatory: worsens with activity, improves with rest
rheumatoid arthritis (RA) - clinical presentation
*INLAMMATORY joint pain (morning stiffness > 1 hour, improves with activity, worsens with rest)
*SYMMETRIC involvement
*most commonly involves:
-small joints of the hands, wrists, ankles, feet
-specifically, MCPs & PIPs but spares DIPs
-spares the spine (except for cervical spine C1/C2)
classic joints in the hands that are affected by rheumatoid arthritis
*disease affects:
1. MCPs (metacarpophalangeal joints) - located where the metacarpal meets the proximal phalange
2. PIPs (proximal interphalangeal joints)
*disease SPARES the DIPs (distal interphalangeal joints)
rheumatoid arthritis (RA) - physical exam findings
*swelling, warmth, and erythema at the joints in classic patterns: boggy, synovitis
* Boutonniere deformity (PIP flexion with DIP hyperextension)
*Swan neck deformity (DIP flexion with PIP hyperextension)
rheumatoid arthritis (RA) - C1/C2 (atlantoaxial) subluxation
*misalignment between the first and second cervical vertebrae in the neck
*sx include occipital headache or neck pain, upper extremity numbness and tingling, and muscle weakness of the arms
*can occur in long-standing seropositive, erosive disease
*important to consider with intubation, etc
rheumatoid arthritis (RA) - extra-articular manifestations: SKIN
-
rheumatoid nodules:
-extensor surfaces of the elbows; seen on hands as well
-need to differentiate from a tophus
-pathology: fibrinoid central necrosis with palisading histiocytes -
vasculitis:
-leukocytoclastic vasculitis, small vessel vasculitis, medium vessel vasculitis
-pyoderma gangrenosum
histology findings of rheumatoid nodules
*fibrinoid central necrosis with palisading histiocytes
rheumatoid arthritis (RA) - extra-articular manifestations: HEMATOLOGIC
-
anemia of chronic disease/chronic inflammation:
-result of IL-6’s influence on hepcidin - Fetty’s Syndrome (splenomegaly, neutropenia, infections, non-healing ulcers)
Felty’s Syndrome in RA
*rheumatoid arthritis PLUS characteristic features:
1. splenomegaly
2. leukopenia (neutropenia < 2000)
3. infections & non-healing ulcers
*risk factors: positive RF, nodules, extra-articular disease
*treatment: treat the underlying RA
rheumatoid arthritis (RA) - ADDITIONAL extra-articular manifestations:
*eyes: episcleritis, scleritis, uveitis
*heart: pericarditis
*lung: PLEURAL DISEASE (low glucose)
rheumatoid arthritis (RA) - diagnosis
- clinical symptoms & physical exam: duration and distribution, classic inflammatory symptoms, tender and swollen joints
- labs: RF, anti-CCP, elevated ESR and CRP
- imaging: hand films, foot films, imaging modalities
note - anti-CCP (citrullinated peptide) antibodies are the most SPECIFIC for RA
x-ray findings in RA
*periarticular osteopenia
*marginal erosions
*symmetric joint space narrowing
*follows same pattern as swollen/painful joints
rheumatoid arthritis (RA) - poor prognostic indicators
*high titer RF, positive anti-CCP
*multiple joint involvement
*erosions on X-rays
*extra-articular manifestations
*sustained elevation of acute phase reactants
*low SES/education level
*poor functional level
*HLA-DR4 shared epitope (although we do not check this)
rheumatoid arthritis (RA) - treatment overview
- disease-modifying anti-rheumatic drugs (DMARDs):
-methotrexate
-hydroxychloroquine
-sulfasalazine
-leflunomide - biologic DMARDs:
-TNF alpha inhibitor
-IL6 inhibitor
-CTLA4
-JAK inhibitors
methotrexate - MOA, uses
*MOA: folic acid analog that competitively inhibits dihydrofolate reductase → decreased dTMP → decreased DNA synthesis
*first-line therapy for RA
-takes 6 to 8 wks to start working (prednisone helps in the interim)
glucocorticoids - MOA
*inhibit phospholipase A2 via inhibition of NF-KB
*prevents formation of arachidonic acid
*arachidonic acid breaks down into leukotrienes, prostaglandins, thromboxanes
methotrexate - ADEs
*hepatotoxicity (cannot drink alcohol)
*oral ulcers, hair loss (folic acid helps)
*myelosuppression (folic acid helps)
*PULMONARY FIBROSIS
*teratogenic
*monitor labs every 3 months
*note - we use in smaller doses in RA than in chemo; helps decrease side effects
hydroxychloroquine in RA
*brand name = Plaquenil
*antimalarial (presumed through TLR inhibition, raising pH of lysosome)
*good safety profile
* retinal toxicity with high dose, long term use
*safe in pregnancy
*benefit in 3-6 months
*monitor: yearly eye exams
sulfasalazine in RA
*anti-inflammatory from aspirin-like properties (“aspirin with a sulfa group”)
*ADEs: myelosuppression, hepatotoxicity, G6PD deficiency
*safe in pregnancy
*benefit in 6-8 weeks
*monitor labs every 3 months
biologic therapy for RA - overview
*works better in combination with non-biologic DMARDs (methotrexate)
*universally expensive
*infection in universally the biggest risk
*cannot combine biologic therapies together
naming of biologic therapies: -mab
*monoclonal antibody
naming of biologic therapies: -ximab
*chimeric monoclonal antibody
*ex: infliximab, rituximab
naming of biologic therapies: -zumab
*humanized monoclonal antibody
*ex: certolizumab
naming of biologic therapies: -mumab
*fully humanized monoclonal antibody
*ex: adalimumab, golimumab
naming of biologic therapies: -cept
*fusion protein
*ex: etanercept, abatacept
innate immune system - review
*first line defense
*recognizes conserved features (shared molecular patterns) of pathogens by germ-line encoded receptors
*stimulates adaptive immunity and influences the type of adaptive response
adaptive immune system - review
*requires clonal expansion of effector cells (several days) for clearance of pathogens
*pathogen-specific recognition through recombined receptors
*“remembers” pathogens for rapid response to future infections
TNF-alpha inhibitors - overview
*first-line biologic therapy for RA
*contraindications: demyelinating diseases, CHF (esp. classes 3/4)
*examples:
-infliximab
-etanercept
-adalimumab
-certolizumab pegol
-golimumab
note - must screen for TB prior to initiating tx, due to risk of reactivation
TNF-alpha inhibitors - ADEs
*infections (URIs)
*TB reactivation - screen prior to initiation
*drug-induced lupus
*hold medication for infection, surgery
association between TNF inhibitors and tuberculosis
*need TNF to support the granuloma in TB
*once you inhibit TNF-alpha, cannot maintain granuloma → release of walled-off granuloma → reactivation of TB
*ex TB screening test: interferon-gamma release assay (aka Quantiferon)
association between TNF inhibitors and malignancy
*pts with RA are already at an increased risk for malignancy
*only significantly increased association: non-melanomatous skin cancer
rituximab
*anti-CD20 (B cell target)
*used to treat: RA, cancer, vasculitis, lupus, etc
*vaccinate prior to starting therapy (need B cells to create antibody)
abatacept
*fusion protein of CLTA4 (aka CD80/86; T cell target)
*inhibits the necessary secondary signal for T cell activation
tocilizumab
*IL-6 inhibitor
*indications: RA, GCA (temporal arteritis), COVID
*ADEs: infection, increase in lipids, bowel perforation
*caution in pts with diverticulitis
JAK kinase inhibitors
*inhibits JAK-STAT pathway
*ex: toficitinib, upadacitinib
*oral therapy
*ADEs: cytopenias, infection, elevated LFTs, bowel perforation
treatment regimen for rheumatoid arthritis
*START with METHOTREXATE, with prednisone to help with sx until methotrexate kicks in
*next steps vary depending on patient preference, insurance regulations, fiscal implications
*frequent visits to monitor
