Osteoarthritis & Chronic Inflammatory Arthritis Flashcards
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
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)
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
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
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
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
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
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
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
10
Q
OA/DA: Early and Late Stages
A
- losing the dark line (joint space) and joint connections starting to get misaligned
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)
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)
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
- Potential triggers: infectious (P gingivalis and others)
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
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
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)
- Rheumatoid nodules, Interstitial lung disease
- 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)
-
Rheumatoid factor
-
X-rays
- Erosions and peri-articular osteoporosis
-
Synovial fluid
- Inflammatory (look for elevated #wbc), low glucose, nonspecific
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
- triad: cant pee, cant see, cant climb a tree
- usually from infections
- Formerly known as Reiter Syndrome
- Undifferentiated spondyloarthropathy-less specific
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:
- Spinal inflammation
- 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)
