Osteoarthritis & Chronic Inflammatory Arthritis Flashcards

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1
Q

Impact of Arthritis

A
  • 1 out of 5 US adults carries diagnosis of arthritis (52 million)
    • Most common is osteoarthritis (degenerative)
    • Other forms : RA, lupus, gout
  • 2/3 individuals with arthritis are <65 yo
  • More common among women (26%) vs men (19%)
  • $128 billion in medical expenditures/lost earnings in 2003
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2
Q

Osteoarthritis (OA)-aka Degenerative Arthritis-General (1/2)

A
  • Characterized by DEGENERATION (wear and tear) of articular cartilage
    • **Distinct from an inflammatory arthritis
    • Chondrocytes of articular cartilage respond to biomechanical and biologic stresses in way that results in breakdown of matrix
  • Most common type of arthritis
  • Classified as primary or secondary
    • Primary most common
    • secondary-see with trauma (knee or shoulder)
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3
Q

Secondary OA

A
  • several ways to develop
    • **trauma
    • inflammatory arthritis
    • dysplastic and hereditary conditions
    • Kashin-Bek dz
    • bone disorders
    • metabolic and endocrine disorders
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4
Q

Osteoarthritis (OA)-aka Degenerative Arthritis-General (2/2)

A
  • Seen most commonly in persons >65 yo
  • Radiographic changes
    • >45 yo: knee 37%, hip 27%, hands >90%
    • Most with radiographic changes have few sx
  • **Symptomatic OA (lower #s)
    • >45 yo: 17% knee, 9% hip
  • Lifetime risk of symptomatic OA of knee: 66%
    • Higher with obesity and risk factors
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5
Q

OA/DA: Pathogenesis-RF

A
  • *Age=strongest RF*
  • Obesity most associated with OA of the knee but may contribute to hip & hand
    • Leptin may have influence on chondrocytes
  • Chronic repetitive impact loading
    • Long term weight bearing sports
  • Genetic factors (if gma has bony nodules)
    • Many have family history, especially finger involvement in women
  • Jt dysplasia increases risk for hip OA
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6
Q

Nml Morphology (3+1 main players)

A
  • Specialized connective tissue
    • Collagen, proteoglycans, water, chondrocytes
  • Collagen: Mostly type II collagen
    • Distributes compressive forces
    • Tethers cartilage to subchondral bone
    • Dissipates weight bearing force, protecting soft tissue & subchondral bone
  • Proteoglycans=cushion
    • Aggrecan: high fixed negative charge allows for retention of water
  • Chondrocytes mediate turnover of matrix components
    • Sparsely scattered
    • Chondrocytes influenced by factors ie) GF, cytokines, physical stimuli
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7
Q

OA/DA Morphology

A
  • Articular cartilage
    • Loss of homogeneity, disruption & fragmentation of surface
  • Deeper layers of cartilage invaded by capillaries from calcified cartilage
  • Chondrocytes which are normally isolated cells now proliferate & cluster
  • Osteophytes form (bone spurs)
  • **Early OA: WATER content of diseased cartilage INCREASES & cartilage swells
  • Increase in both anabolic (build up) & catabolic (break down) activity
    • Eventually, anabolic cannot keep up with catabolic activity
    • Degradative enzymes released by chondrocytes
    • Matrix less structurally sound & less organized; cannot withstand forces
  • Causes for biochemical & metabolic changes not fully understood
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8
Q

OA/DA Clinical Characteristics

A
  • Localized joint pain
  • Stiffness
  • Worse with weight bearing-after activity or at the end of the day
  • Better with rest
  • Very little morning stiffness (diff from other)
  • Distal & Proximal interphalangeal joints
    • Heberdens & Bouchards nodes
  • Knees, Hips, Cervical & lumbar spine
  • Joint crepitus-crunching
  • Swelling not common
  • Bony enlargement
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9
Q

OA: Xrays and Labs

A
  • Xrays
    • Decreased joint space
    • Subchondral sclerosis (bones start touching) & cysts
    • Osteophytes (spurs)
    • ***xray findings may not always be proportionate to pain
  • Labs
    • No useful tests
    • Not inflammatory
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10
Q

OA/DA: Early and Late Stages

A
  • losing the dark line (joint space) and joint connections starting to get misaligned
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11
Q

OA/DA Management

A
  • No cure
  • Manage risk factors: physical therapy, exercise, weight loss, dietary measures
    • Quadriceps strengthening in knee OA
  • Pharmacologic (pain control)
    • Acetaminophen, Nonsteroidal anti-inflammatory drugs & other analgesics
    • Intra-articular steroid injections in selected cases
  • Sx: Jt replacement (especially knees, hips-large jts)
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12
Q

RA General

A
  • Systemic
  • Chronic (>6wks, some infections can mimic-Parvovirus B19)
  • Inflammatory
  • Autoimmune-WBC attacks jts
  • Primarily involves jts but can affect extra-articular organs
    • Lungs (interstitial lung disease, pleural effusion)
    • Anemia of chronic disease
    • Eyes (episcleritis, scleritis)
    • Skin (vasculitis), soft tissue (rheumatoid nodules)
    • Heart (pericarditis)
    • CNS v. rarely (pachymeningitis), peripheral neuropathy (v. severe)
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13
Q

RA-Epidemiology and RF

A
  • Prevalence: 1%
  • 5 times more common in women vs men (duh, a.i. dz)
  • Peak incidence 2nd-5th decade of life
  • Genetic risk factors: HLA-DRB1 locus (MHC-Class 2)
    • Genetic susceptibility
  • Environmental risk factors
    • Potential triggers: infectious (P gingivalis and others)
      • Prevalence of periodontal disease 2 fold amongst RA
    • Smoking: anti-CCP Ab (cyclic citrullinated peptide)-MAKE MORE!
      • Relative risk 1.4 for developing RA compared to nonsmokers
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14
Q

**RA vs. OA/DA**

A
  • Inflammatory (swelling) VS. OA/DA-no swelling
  • Prolonged morning stiffness VS. OA/DA: limited morning stiffness
  • Systemic manifestations VS. OA/DA: localized symptoms
  • Joints involved:
    • PIPs, MCPs, wrists VS OA/DA: PIPs, DIPs, CMCs
  • Lumbar spine not involved VS. DA lumbar spine commonly involved
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15
Q

Morphology: RA vs. OA

A
  • sides, where synovium joins up with bone-inflamm is fom jt space lining
  • RA:**eroding cartilage
  • OA/DA: **bony spur; more evenly thoughout
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16
Q

RA Pathogenesis

A
  • (over) Activation of CD4+ helper T cells
    • Environmental trigger in genetically predisposed individual
  • T and B cell responses to self-Ag
    • Activated CD4+ helper T cells, TH17 cells, B lymphocytes & plasma cells, macrophages
    • Inflamed synovium
    • ***Increase in inflammatory cytokines:
      • IL1, IL6, TNF, IL8, IL17, IFN gamma
  • Fibroblasts, chondrocytes, synovial cells respond to pro-inflammatory milieu
    • Destructive enzymes: collagenase, stromelysin, elastase, PGE2
  • **Osteoclast response
    • Increased expression of **RANKL (receptor activator of nuclear factor kB ligand)
    • Osteoclast activation leading to bone erosions
      • want to get to the pt before the bony erosions happen
17
Q

RA Morphology: Pannus Formation (5-LEDTV)

A
  • Chronic papillary synovitis
  • Synovial cell hyperplasia & proliferation: THICKENED=pannus
  • Perivascular inflammatory cell infiltrates: DENSE
    • CD4+ T cells, plasma cells, macrophages
  • Angiogenesis: VASCULAR
  • Neutrophils & organizing fibrin on synovial surface: LAYERED
  • Increased osteoclast activity: ERODED
    • arrows on the X-ray
18
Q

RA X-rays

A
  • periauticular osteopenia-darker due to osteoclast activation
  • bone is getting thinner as it gets closer to joints
  • on right, not seeing bones that were previously seperated by bone spaces in wrist
19
Q

RA Diagnosis

A
  • Clinical Diagnosis
    • Chronic, symmetrical, inflammatory polyarthritis
    • Extra-articular manifestations may occur
      • Rheumatoid nodules, Interstitial lung disease
        • nodule: in area where theres lots of trauma/friction (elbows, hands)
        • area of fibrinoid necrosis (ctr) surrounded by palisading histiocytes (arrows)
  • Blood tests
    • Rheumatoid factor
      • Auto-Abs against Fc portion of normal polyclonal IgG
      • IgM, IgG, or IgA
    • Anti-CCP Ab-increased in smokers
    • Elevated inflammatory markers (sedimentation rate, C-reactive protein-made by liver)
  • X-rays
    • Erosions and peri-articular osteoporosis
  • Synovial fluid
    • Inflammatory (look for elevated #wbc), low glucose, nonspecific
20
Q

RA Tx (1/2)

A
  • Try to get to the root of the inflamm
  • NSAIDS
    • Often not enough as monotherapy
  • Corticosteroids (prednisone)
    • As a bridge
    • Too many SE to use as monotherapy
  • DMARDS (disease modifying anti-rheumatic drugs)
    • Mainstay longterm tx
    • Mostly immunosuppressive
  • Non-biologic DMARDs
    • Methotrexate (immunosuppresive)
    • Leflunomide
  • Also, biologic….
21
Q

RA Tx-2/2: Biologics

A
  • decreases the rate of the deformities-much more aggressive and immunosuppressive
  • aims for those stupid IL that are causing all the trouble
  • Anakinra
    • Anti-IL1
  • *****Etanercept, Adalimumab, Infliximab-most effective, and have the most data
    • Anti-TNF alpha
  • Tocilizumab
    • Anti-IL 6
  • Abatacept
    • CTLA4 agonist
    • Blocks CD28 co-stimulation of T cells
  • Rituximab-also used for NHL chemo and SLE
    • Anti-CD20
    • Causes destruction of B cells
  • Tofacitinib (oral)
    • JAK1 and 3 inhibitor
    • Janus associated kinase
    • Blocks signaling for inflammatory cytokines
22
Q

Seronegative Spondylo-Arthropathies: General

A
  • Ankylos = Greek for “bent,” fusion (**can get fusion of the spine)
  • Spondylos = Greek for “vertebral disk”
  • Group of inflammatory arthritides (cousin to RA) which primarily involve ankylosing of the spine
    • Inflammatory back pain
    • Improves with exercise, not relieved by rest
  • Different pattern of joint involvement compared to RA
    • Oligoarticular (<3), assymetric, more large joints involved
    • Axial involvement: sacroiliitis (upper buttock pain, worse in the morning, associated with stiffness)
      • “bamboo spine” (not seen in RA)
    • Enthesitis = inflammation of tendon insertions (not seen in RA)
      • Ex: achilles tendon
  • Extra-articular manifestations
    • Uveitis (not seen in RA)
    • GU tract (in reactive)
    • skin (in psoriatic)
    • GI tract (in IBD associated)
23
Q

Seronegative Spondylo-Arthropathies: Umbrella

A
  • Psoriatic arthritis
    • peripheral psoriatic arthritis in 15-30% pts with psoriasis
    • over spondyloarthritis in 10% of pts with psoriatic arthritis
  • Ankylosing spondylitis-bamboo spine, fusion
  • Inflammatory Bowel Disease (IBD) related-Crohns or UC (5-10%)
  • Reactive Arthritis
    • triad: cant pee, cant see, cant climb a tree
      • nongonococcal urethritis, conjunctivitis, arthritis
      • though many only have arthritis
    • more temporary: self-limiting over 4-12 mo
      • 10-20% develop chronic
    • Keratoderma blennorhagica (pic)
    • follows certain enteric infections and STI
  • usually from infections
  • Formerly known as Reiter Syndrome
  • Undifferentiated spondyloarthropathy-less specific
24
Q

Seronegative Spondylo-Arthropathies: Epidemiology

A
  • 346 - 1,310 per 100,000 among persons 25 years and older in US
  • HLA B27
    • Allele of MHC I (or HLA Class I)
    • 90% of white pts with AS, 50% of AA with AS
    • 60-70% in psoriatic or IBD related spondyloarthropathy
    • 7-9% of healthy pop
      • ​therefore, use this test cautiously
  • Typically age 16-30 years (younger age group than RA)
25
Q

Seronegative Spondylo-Arthropathies: Path Theory 1/2

A
  • Arithrogenic theory AKA “Molecular Mimicry
  • **Yersinia, Shigella, Salmonella, Campylobacter, Chlamydia
26
Q

Seronegative Spondylo-Arthropathies: Path Theory 2/2

A
  • Misfolding & dimerization hypothesis
  • Unrelated to antigen presentation
  • Tendency to misfold & form dimers
    • Leads to inappropriate stimuli & inflammation
  • Homodimers
    • TNF a induction
    • Direct activation of NK cells, dendritic cells & CD4 T cells
    • CD4 T cells then produce IL-17 + IL-23 (vs. IL1,6, TNF a)
27
Q

Seronegative Spondylo-Arthropathies: Path Factors

A
  • TNF a plays a role
    • Similar to RA
  • IL-17, IL-23, TH 17 cells also play a substantial role
    • Different from RA
  • ***IL- 17
    • Important role in defense against extracellular bacteria
    • Dysregulated expression leads to joint destruction
      • Increase in proinflammatory cytokines
      • Increase in metalloproteinase
      • Increase in RANKL activity
  • IL-23
    • Strongly overexpressed in gut of AS patients
    • Promotes highly specific entheseal inflammation
28
Q

Seronegative Spondylo-Arthropathies: Sacroilitis

A
  • Granulation tissue from inflammation erodes through bone & cartilage into joint cavity
  • Synovial hypertrophy
  • Infiltration of subsynovium: macrophages, lymphocytes, plasma cells
  • Advanced disease:
    • Erosion of bone
    • Cartilage fusion (loss of joint space)
    • Sclerosis (increased whiteness) in para-articular bone
  • Osteoblast activation eventually leads to replacement of cartilage by new bone->AKA ankylosis
29
Q

Spinal Ankylosis

A
  • Two important processes:
      1. Spinal inflammation
      1. Spinal ankylosis
  • Inflammation at vertebral corners & subsequent development of syndesmophytes
  • Evidence for link between both
    • But also evidence that osteoproliferation may not be completely dependent on inflammation
30
Q

Syndesmophytes

A
  • Sclerosis & squaring of vertebral corners
  • Syndesmophytes leading to complete briding ossification
31
Q

Seronegative Spondylo-Arthropathies: Diagnosis

A
  • Inflammatory back and/or buttock pain
  • Chest wall pain
    • due to costo-sternal jt (ribs joining sternum)
  • Enthesitis (ie Achilles tendon, plantar fascia)
  • Dactylitis: sausage shaped swelling of digit caused by flexor tenosynovitis-ENTIRE finger (not just jt)
  • Extra-articular: uveitis (25-30% of pts)
  • Sacroiliitis on imaging (MRI or xray)
32
Q

Seronegative Spondylo-Arthropathies: Tx

A
  • Education & Physical Therapy
  • NSAIDs
    • Limitations, especially with underlying IBD
  • Oral DMARDS (dz modifying anti-rheumatic drugs)
    • Sulfasalazine, methotrexate
  • Biologic Therapies
    • ***Anti-TNF a–cant use the other antis that RA uses
      • Adalimumab, Etanercept, Infliximab
    • Anti-IL 23/ IL 12
      • Ustekinumab
    • Anti-IL17 in development
      • Ixekizumab, Sekukinumab (clinical trials in psoriasis)