Rheumatology JC083: Multiple Joint Pain: Rheumatoid Arthritis, Osteoarthritis, The Concept Of Spondyloarthritis Flashcards
Arthropathy classification
Inflammatory arthritis (persistent inflammation —> cause joint destruction):
1. RA
- Rheumatism
- Undifferentiated arthritis
- CT disease / SLE (minimal inflammation)
- Jaccoud’s arthropathy - Spondyloarthritis
- AS
- Psoriatic arthritis
- IBD-related
- Reactive arthritis - Crystal arthritis
- Gout
- Pseudogout
Non-inflammatory arthritis:
1. OA
2. Fibromyalgia
Clinical features of different arthritis: History taking
RA:
- younger age
- **insidious onset
- **polyarthritis
- **small hand joints (MCP, PIP) —> subluxation + ulnar deviation over MCP joint
- sparing DIP joints
- **early morning stiffness >=30 mins
Spondyloarthritis:
- younger age
- **insidious onset
- mono / polyarthritis
- **any joint can be involved
- **psoriasis (DIP joint with onycholysis), IBD, STD / dysentery, uveitis
- **back pain
- family history
Osteoarthritis:
- **insidious onset
- **weight bearing joints, DIP joints (nodal OA)
- older age
Gout:
- **acute onset
- 1st MTP joint involvement (any joint can be involved after MTP joint)
- usually **self-limiting
- sometimes ***fever
P/E of arthritis
- Monoarthritis
- Gout
- OA
- Spondyloarthritis - ***Polyarthritis
- RA (symmetrical small hand joints) - Oligoarthritis (a few joints)
- Spondyloarthritis (e.g. Psoriatic arthritis) - ***Symmetrical
- RA - Asymmetrical
- Spondyloarthritis (sometimes can mimic RA as symmetrical)
Osteoarthritis (OA)
- Commonest non-inflammatory arthritis
- Prevalence ↑ steeply with age (75% women >=65 yo)
- Primary vs Secondary OA
***Primary (JC Surgery Upper limb painful conditions):
- Wear + Tear
***Secondary:
- Post-traumatic
- Post-inflammation (e.g. Post-RA, Post-Psoriatic arthritis)
- Post-infection
Sites:
- Weight bearing joints: Knee, Hips, Spine
- **CMC joint (wrist)
- **DIP joint
- Trapeziometacarpal joints
—> >=3 joints involved —> ***Generalised OA
P/E:
- **Crepitus
- **Minimal swelling
Imaging features:
- Loss of joint space (loss of cartilage)
- Osteophyte (marginal, abnormal bone proliferation)
- Subchondral cyst
- Subchondral sclerosis (sclerosed area: dead bone)
- **Preserved bone density (vs RA)
- **Synovial hypertrophy
- Thickened capsule
- Joint deformity
(From JC Surgery Upper limb painful conditions:
Clinical features:
1. Pain on loading, relieved by rest
3. Stiffness, Swelling
4. Osteophytes —> Heberden’s nodes (DIP) + Bouchard’s nodes (PIP) —> may block movement / loss of ROM
5. Deformity / Instability of joint
6. Diminished grip + pinch strength —> unable to perform ADL
Radiological changes:
1. Loss of joint space (vs Widening of joint space in RA initially)
2. Osteophyte
3. Subchondral sclerosis
4. Subchondral cysts)
Rheumatoid arthritis (RA)
- Commonest autoimmune inflammatory polyarthritis
- found in all races
Epidemiology:
- 1-2% in Caucasians
- 0.3-0.4% in Chinese
- Rare in blacks
- Peak age of onset: **35-55 yo
- **F:M = 3:1
Pathology:
- Synovial **proliferation (thickening) + **inflammation
- Insidious onset
Site (44 Joint count):
1. Appendicular
- ***hands / feet: MCP + PIP (earliest changes in 2nd + 3rd MCP + 3rd PIP) (DIP rare)
- wrists, elbows, knees, ankles, shoulders, hips
- Axial skeleton
- apophyseal + atlantoaxial joints of ***cervical spine (esp. C1, C2 joints)
Features:
Disease activity:
1. Pain
2. **Swelling
3. **Stiffness (morning)
4. Functional limitation
Investigations:
1. Clinical:
- **DAS (disease activity) score
—> Swollen joint count
—> Tender joint count
—> ESR / CRP
—> Global assessment of health
- Swollen joint count
- Duration of stiffness
2. **CRP / ESR
3. USG
4. MRI
5. ***Extra-articular features (e.g. rheumatoid nodules, pulmonary fibrosis, amyloidosis, neuropathy)
Disease damage:
1. Pain
2. Less swelling
3. Deformity
- **Subluxation (partial dislocation) (C1, 2, MCP, ulnar deviation, carpal bone fusion) / **Dislocation
- **Tendon rupture
4. **Secondary OA
5. Functional limitation
6. Post-inflammatory ***hyperpigmentation of joints
Investigations:
1. X-rays
2. CT (not useful to assess activity ∵ cannot see degree / amount of inflammation —> but can see bone destruction / deformity)
3. Extra-articular features (e.g. rheumatoid nodules, pulmonary fibrosis, amyloidosis, neuropathy)
Signs:
1. **Swan neck deformity (rupture of extensor tendon at DIP level —> unopposed flexion at DIP)
2. **Boutonniere deformity (rupture of extensor tendon at PIP level —> unopposed flexion at PIP)
3. **Mallet finger
4. MCP ulnar deviation
5. Z-thumb (SpC Revision)
6. Extra-articular features
- **Eyes: scleritis, keratoconjunctivitis
- Pleura: effusion
- **Lung: fibrosis, nodules
- LN: reactive lymphadenopathy
- **Pericardium: effusion
- Spleen: splenomegaly (Felty syndrome (self notes))
- **Gut, Kidney: amyloidosis
- **BM: anaemia of chronic disease, thrombocytosis (if severe inflammation)
- Muscle: wasting (common, ∵ disuse atrophy)
- Skin: thinning, ulceration (∵ vasculitis)
- ***Nervous system: peripheral neuropathy (∵ vasculitis)
Pathogenesis of RA (from MSS15)
Causes:
- Genetics
- Environment (smoking, bacteria, dust / silica)
—> trigger inflammation in mucosal sites e.g. gums, lungs, gut - Autoimmune
1. Activation of immune system
—> minor trauma **↑ expression of citrullinated proteins in normal healthy joints (joint: second hit)
—> osteoclasts express enzyme that also **↑ citrullination of collagen 2 in cartilage leading to attack by AutoAb
—> ***APCs + dendritic cells presenting citrullinated proteins (post-translational modification of proteins) to immune system
- AutoAb formation (can be detected before disease onset)
- CD4 Th cells
—> initiate response by reacting with an agent to produce cytokines
—> stimulate ***macrophages (through IFNγ), Th17 (through IL17) - Macrophage infiltration
—> with release of TNFα + IL1 (intensity of infiltration correlates with disease activity and radiological progression)
—> 1. stimulate synovial cells to produce **enzymes that destroy cartilage
—> 2. +ve feedback between TNFα and factors by fibroblasts: chemotactic for **monocytes
—> 3. AutoAb to citrullinated peptide (CCP) - Rheumatoid factor
—> serum IgM / IgA AutoAb that bind to Fc IgG (antibody against Fc portion of IgG)
—> Immune complex formation
End result:
**Acute **destructive **inflammatory **synovitis
—> AutoAb against citrullinated vimentin (structural filament in fibroblasts): **cross reactive with other citrullinated antigen
—> lead to osteoclast-dependent **bone destruction
***Diagnosis of RA (ACR-EULAR classification criteria)
Diagnosis: Clinical features
ACR-EULAR classification criteria (only ***helps to diagnose disease, NOT diagnostic)
Target population:
- >=1 joint with definite clinical synovitis (swelling)
- with synovitis not explained by another disease
***記: Joint involvement, Serology, Acute-phase reactant, Duration
Categories A-D (***>=6/10 needed for classification of patient as definite RA):
A. Joint involvement:
- 1 large joint
- 2-10 large joints
- 1-3 small joints (+/- large joints)
- 4-10 small joints (+/- large joints)
- >10 joints (>=1 small joints)
B. Serology (**RF, **ACPA: both specific for RA, RF can be elevated in chronic inflammation / infection, ACPA more specific)
- Negative RF + Negative ACPA
- Low-positive RF / Low-positive ACPA
- High-positive RF / High-positive ACPA
C. Acute-phase reactant
- Normal CRP + Normal ESR
- Abnormal CRP / Abnormal ESR
D. Duration of symptoms
- <6 weeks
- >=6 weeks
Rheumatoid factor
- AutoAb (IgM) against IgG
- ***Not sensitive (many RA patients do not have RF, many false negative) —> Rmb: Clinical features more important than markers!!!
- ***Specific but less than Anti-CCP (SpC Revision)
- ***Not correlate with disease activity
- High levels in RA —> ***Poor prognosis (∵ more joint damage in shorter time)
Causes:
1. RA
2. **Sjögren’s syndrome
3. **Chronic infection / Lymphoma
4. Elderly, ***Healthy individuals
ACPA / Anti-CCP
- Anti-cyclic citrullinated peptide Ab
- **Low sensitivity, **High specificity (>90% with positive clinical features)
- ***Not correlate with disease activity
- Predict **progressive + **erosive disease —> need to treat aggressively
- Specificity further improves when screened together with RF (if both positive —> high chance of RA)
***Radiological features of RA
-
**Soft tissue swelling + **Widened joint space (Initial stage)
- synovial inflammation + effusion - ***Juxta-articular osteoporosis (osteopenia next to affected joint)
- hyperaemia + disuse -
**Joint space narrowing
- destruction of **cartilage by ***Pannus (aggressive macrophage- and fibroblast-like mesenchymal cells, macrophage-like cells and other inflammatory cells that release collagenolytic enzymes) -
**Peri-articular erosions
- Pannus destruction of unprotected **bone at insertion of joint capsule
(- vs Juxta-articular erosions: Gout)
Spondyloarthritis (SpA)
Umbrella term: spectrum of disease
Axial SpA:
- AS (Prototype, with radiological sacroilitis)
- Psoriatic arthritis
- IBD-related SpA
- Reactive arthritis
- Undifferentiated SpA
Peripheral SpA:
- No spine / axial joints involved
Clinical features:
- **Spondylitis (inflammation of spine)
- **Peripheral arthritis (inflammation of peripheral joints)
- **Enthesitis (Archilles tendinitis, plantar fasciitis, chest wall tendons)
- **Anterior uveitis
- ***Aortitis
- Associated with HLA-B27
- Other associated features: Psoriasis (scaly plaques, onycholysis, dactylitis (sausage finger), IBD, Dysentery, STD
Pathognomonic findings of Axial SpA:
- **Inflammation + **Osteodestruction + ***Osteoproliferation
—> Final stage of AS: severe kyphosis of thoracic + cervical spine
P/E of Spondyloarthritis
- ***Modified Schober (spinal mobility)
- 5cm below imaginary line between PSIS + 10 cm above (i.e. 15cm apart)
- bend forward
- ↑ >=5 cm: normal - Lateral spinal flexion
- standing distance between finger and floor —> bend sidewards —> mark new distance
- no reference values - Occiput to Wall / Tragus to Wall
- max effort to move head against wall —> measure distance - Cervical rotation
- rotate neck maximally to side —> goniometer to measure angle - Intermalleolar distance
- separate legs as far as possible —> measure distance between 2 medial malleoli
(6. Chest expansion
- normal chest expansion >=5cm (CL Lai))
(7. **Question mark deformity (ascending fusion from SI joint from caudal to cranial) —> compensate by **knee flexion + ***hip extension to look up —> treatment: osteotomy to break bones up and bring spine up straight) (From SC044)
***HLA-B27
- a Gene
- 8-9% Caucasian carrying HLA-B27 gene (***lower in Asians)
- Positive in ***90-95% AS patients
- Positive in 46-75% Axial SpA patients
- ***Not sensitive / specific in SpA diagnosis
- Have prognostic value —> **Only those with HLA-B27 will have higher chance to progress to AS (*spinal fusion + new bone formation)
3 theories:
1. Peptide presentation: B27 presenting an “arthritogenic” / “enthesitogenic” peptide to CD8+ T cells (i.e. direct T cell attack cells presenting B27 gene)
2. Misfolding: B27 heavy chain tends to misfold during synthesis in the ER —> provoke ER stress response —> cytokine secretion (e.g. IL23) —> joint inflammation
3. Cell surface markers: B27 expressed on cell surface as dimers / multimers —> engage receptors on T cells, NK cells, APCs —> affect their functioning
***AS: Modified New York classification criteria
MUST have AS radiological criteria + 1 clinical criteria
- Clinical criteria
- low back pain + stiffness **>=3 months (improve with exercise, not relieved by rest)
- limitation of motion of **lumbar spine in both sagittal + frontal planes
- limitation of ***chest expansion relative to normal values corrected for age / sex -
**Radiological criteria (MUST)
- **Sacroiliitis: grade >2 bilaterally / grade 3-4 unilaterally
- erosion / fusion of SI joint
- grade 2: normal joint space
- grade 3: **narrowed / **widened joint space
- grade 4: ***fused completely
***Disease diagnosis of SpA
- ***MNY criteria
OR - ***ASAS classification criteria for axSpA (incorporate MRI: detect inflammation before joint damage)
- ***Axial criteria:
- Sacroiliitis on imaging + >=1 SpA feature
or
- HLA-B27 + >=2 SpA features - ***Peripheral criteria:
- Arthritis / Enthesitis / Dactylitis + other SpA feature
X-ray sacroiliitis:
- takes years for X-ray changes
- delay in diagnosis: up to 6-11 years
