Rheumatology - Polyarthritis - OA, RA, SpA Flashcards
List causes of polyarthritis
Non-inflammatory:
- OA
- Fibromyalgia
Inflammatory:
- RA
- Viral polyarthritis
- Infective: IE, rheumatic fever, bacterial polyarthritis, Lyme disease
- Connective tissue disease/ SLE
- Spondyloarthritis (SpA): Ankylosing spondylitis, Psoriatic arthritis, Reactive arthritis, IBD-related arthritis
- Crystal deposition disease: Gout, Pseudogout, Lipid, Calcium…etc
Most likely cause of polyarticular pain in this profile:
Young age
Insidious onset
symmetrical arthritis involving small and large joints in upper and lower limbs
Spares DIP
Morning stiffness that resolves after some time
Rheumatoid arthritis
Most likely cause of polyarticular pain in this profile:
Old age
symmetrical polyarthralgia affecting DIP, PIP, 1st CMCJ, weight-bearing joints and neck
Insidious onset
Typically (at least initially) associated with movement and resolved with rest
Osteoarthritis
Most likely cause of polyarticular pain in this profile:
Acute onset of monoarticular pain with recurrent attacks
Affects distal > proximal joints in a migratory/simultaneous pattern
Systemic upset, fever during acute attacks
Overlying skin is pruritic
Gout
Most likely cause of polyarticular pain in this profile:
Young age, insidious onset
Wide distribution of peripheral and axial joints affected, asymmetrical
Associated with back pain, psoriasis, uveitis and other widespread S/S
Spondyloarthritis
Differentiate mono, oligo and polyarthritis/ -arthalgia
1= mono
2-4 = oligo
≥5 joints = poly
Rheumatoid arthritis
Joints affected by RA
Classical deformities in chronic cases
Classically symmetrical arthritis involving small and large joints in upper and lower limbs
Classically starts in MCP, PIP, wrists and MTP joints and spares DIP joint
Eventually spread to involve multiple peripheral joints ± atlantoaxial joint (C1/2), cricoarytenoid
Deformities: swan neck/Boutonierre deformity, Z thumb, rheumatoid nodules
Spondyloarthritis
Joints affected
Extra-articular features
Axial form: SI joint and other interarticular joints
Peripheral form: asymmetrical oligoarthritis (LL>UL), DIP not spared
Extra-articular:
- enthesitis, dactylitis (sausage digits due to tendinitis)
- anterior uveitis, conjunctivitis/urethritis (in reactive arthritis)
- psoriasis (in PsA)
- IBD (in IBD-associated SpA)
Viral polyarthritis
Causative pathogens
Joints affected
- Common associations: hep B and C, EBV, parvovirus B19, Dengue virus, rubella, HIV
- Symmetrical, small joint arthritis ± rash and prodromal illness → usually self-limiting ≤6w
Outline history taking approach for polyarthritis
- Inflammatory vs non-inflammatory pain?
- Pain localized to joint or extra-articular?
- Onset/ triggers? e.g. conjunctivitis in SpA
- Acute or chronic:
Acute: Crystals, reactive, septic, viral
Chronic, SpA, RA, OA, Connective tissue diseases… - Joints: mono-, oligo- or polyarthritis
- Spatial pattern: symmetrical vs asymmetrical, large or small joints, axial or peripheral
- Temporal pattern: Migratory or additive or intermittent
Features of inflammatory joint pain
→ Early morning stiffness: lasts >30min after waking (classical in RA)
→ Swelling, heat, redness in joints
→ Better with gentle exercise and worse with rest
Ddx symmetrical vs asymmetrical polyarthritis
Symmetrical:
RA, SLE, OA
Asymmetrical:
Psoriatic SpA
Axial SpA
Peripheral SpA
Ddx polyarthritis with migratory, additive and intermittent patterns
Migratory pattern: symptoms present in certain joints for a few days then remit, only to reappear in other joints
- rheumatic fever, gonococcal arthritis and SLE-associated arthritis
→ Additive pattern: symptoms begin in some joints and persist with subsequent involvement of other joints
- RA and SLE
→ Intermittent pattern: repetitive attacks of acute polyarthritis with complete remission between attacks
- RA, polyarticular gout and palindromic rheumatism
Rheumatoid arthritis
Extra-articular features and asso. S/S
Constitutional or systemic symptoms: weight loss, fatigue, anaemia of chronic disease ± Felty syndrome
Musculoskeletal: osteopenia/osteoporosis, muscle weakness, steroid-related myopathy, carpal tunnel syndrome
Skin: digital ulcers,Rheumatoid nodules (20-35%): common on pressure points
Eye: Episcleritis, Scleritis
RA-related ILD, lung nodules and pericarditis
Rheumatoid vasculitis
Hepatosplenomegaly
SLE
Extra-articular features
Constitutional or systemic symptoms: fever, weight loss, myalgia, fatigue, anaemia of chronic disease
Cutaneous lupus: buttery fly rash (acute), annular/papulosquamous (subacute), discoid rash, scarring alopecia
Raynaud’s phenomenon, Lupus vasculitis
GI: oral/mucosal ulcers, protein-losing enteropathy, Hepatitis
Lupus nephritis
Serositis (pericarditis, pleuritis),
ILD and pulmonary hypertension
Cerebral lupus, and thromboembolic stroke
Eye: keratoconjunctivitis sicca, episcleritis/scleritis/uveitis
Haematological: haemolytic/NcNc anaemia, APS, Lymphadenopathy and hepatosplenomegaly
SpA
Extra-articular features
Dactylitis (sausage digits)
Enthesitis: common at insertion of Achilles tendon
Psoriatic changes: skin psoriasis, nail pitting, dystrophy
Uveitis (a/w most types of SpA), IBD (in IBD-associated SpA), urethritis/conjunctivitis (in reactive arthritis)
Vasculitis-caused polyarthritis
Extra-articular features
Constitutional or systemic symptoms: fever, fatigue, weight loss, arthralgia
Livedo reticularis: non-blanching palpable purpuric rash at dependent areas or pressure sites
Nail fold erythema, splinter haemorrhages
palmar/finger pulp vasculitis- digital ulcers/gangrene
Renal and pulmonary involvement
First-line investigations for polyarthritis
□ CBC/L/RFT
□ ESR/CRP
□ Serum urate
□ ANA, anti-ENA, C3/4 if suspicious for SLE
□ Rheumatoid Factor, anti-CCP if suspicious for RA
□ HLA-B27 if suspicious for SpA
□ Plain XR of affected joint: as mainstay
□ Other imaging:
→ USG: guide aspiration and injections, detect synovitis
→ MRI: for neurological complications, other Cx
→ Bone scan for inflammatory activity
→ CT scan for structural complications, eg. pseudoarthrosis, ILD
Radiological features of OA, RA joints
→ OA: subchondral cyst, osteophytes, ↓joint space, subchondral sclerosis
→ RA: marginal erosion, ↓joint space, soft tissue swelling, osteoporosis
Radiological features of SLE, SpA joints
→ SLE: typically non-erosive (osteoporosis, soft tissue swelling with normal joint spaces)
→ SpA: SI joint sclerosis, spinal marginal syndesmophytes or parasyndesmophytes
Joints affected by chronic tophaceous gout
Site: extensor surface of fingers, hands, forearm, elbows, Achilles tendons, helix of ear
OA
Typical joints affected
Single or multiple joint OA
o Predilection for hands (PIP/ DIP/ 1st CMC/ 1st MCP), knee, hip and apophyseal (facet) joints of lower cervical and lower lumbar spine
Generalized OA
o Defined as OA at spinal or hand joints and in at least 2 other joint areas/ 3 joints, presence of Heberden’s nodes and Bouchard’s node
Differentiate primary vs secondary OA
Primary OA
o Idiopathic and related to genetics
Secondary OA
o Secondary to abnormal mechanical forces or previous joint insult
o Predisposing conditions including trauma (fracture), rheumatoid arthritis, avascular necrosis, Paget’s disease of bone
OA
Demographics
Risk factors
Demographics: >40 years old, female predominant
RF: Age Obesity Trauma Occupational usage (Farmer’s hip)/ Heavy weight-lifting Recreational usage (Footballer’s knee)
OA
Pathogenesis of articular damage
Articular cartilage
• Loosening of collagen network and loss of extracellular matrix in cartilage
- Proliferation of chondrocytes and swelling of cartilage
- Production of matrix metalloproteinases (MMP) and pro-inflammatory cytokines
- Chondrocytes death leading to cartilage loss and joint space narrowing
OA
Pathogenesis of bone changes
• Osteophyte formation
o Bone spurs or outgrowths form at joint margins often at insertion site of tendons and ligaments attempt to stabilized the joints
• Subchondral sclerosis
o Thickening of subchondral bone due to increased production of collagen that is improperly mineralized attempt to support framework beneath cartilage
• Subchondral cysts
o Cartilage damage transmit pressure of synovial fluid to bone
o Extravasation of fluid into subchondral bone to form subchondral cysts
OA
Pathogenesis of synovium and soft tissue damage
Synovium
• synovial inflammation (synovitis) or synovial hypertrophy
Soft tissues
• joint capsule, ligaments and menisci (in knees) are commonly affected with disruption of extracellular matrix and loss of cells
» Thickening of joint capsule, ligaments and menisci tearing
• Periarticular muscles and nerves are also affected
SOCRATES for OA joint pain
- Site: Affects one or few joints at a time
- Onset: Insidious onset with slow progression over years
- Character: Sharp or dull aching pain
- Associated symptoms: Stiffness, swelling, decrease ROM
- Time course: Intermittent
- Exacerbating factor: Joint use
- Relieving factor: Resting
- Severity: Variable in intensity
OA
S/S
Joint pain
Joint tenderness, stiffness (late afternoon, evening)
Joint swelling and deformity
Joint instability: Giving away or buckling sensation
Locomotor restriction
• Reduced active and passive movement
• Due to marginal osteophytes, capsular thickening, synovial hyperplasia and effusion
Describe the hand joint deformities in OA
Heberden’s nodes: Bony articular nodules at DIP joint
Bouchard’s nodes: Bony articular nodules at PIP joint
Lateral deviation of interphalangeal joints +/- instability (Characteristic)
Radial subluxation and adduction at thumb base
Describe the knee pain and deformities a/w OA Knee
Pain: Patellofemoral or tibiofemoral joint are MOST commonly affect
Deformities: fixed flexion or varus deformity
Quadriceps weakness and wasting
Instability and feeling of giving way associated with falls
Range of motion
• Reduced active and passive movement
• Coarse crepitation on joint movement
Describe the hip pain and deformities a/w OA hip
Pain: Anterior groin, or upper thigh pain; Distal radiation causing thigh or knee pain
Deformities: external rotation, adduction and fixed flexion in end-stage
Thigh muscle weakness and wasting
Shortening of affected extremity, +ve Trendelenburg test
Range of motion
• Reduced active and passive movement
• Coarse crepitation on joint movement
Describe the spinal pain a/w OA spine
Location of pain
• Localized lumbar pain
• Radiation to buttocks, groin, thigh and ends above knees
Nature of pain
• Exacerbated by activity such as exercise, lumbar spine extension, rotatory motion or when sitting and standing
Ddx OA
Specialized test for OA
RA
Psoriatic arthritis (dactylitis with nail changes, DIP involvement)
Gout and pseudogout (Crystalline arthritis)
Septic arthritis
Specialized test: Thomas Test
First-line investigations for OA
Biochemical tests:
1. Inflammatory markers
• ESR and CRP to exclude inflammatory joint disease
- Autoimmune antibodies to r/o RA
• Rheumatoid factor (RF)
• Anti-cyclic citrullinated peptide (Anti-CCP) - Synovial fluid aspiration
• Usually non-inflammatory or mildly inflammatory with < 2000 WBC/mm3 with predominance in mononuclear cells
Imaging:
1. X-ray of joints
- USG: Detection of synovial inflammation, effusion and osteophytosis
OA
Treatment options
Medical:
- Acetaminophen (paracetamol) (APAP)
- NSAIDS, Example: Naproxen/ Diclofenac/ Ibuprofen
- COX-2 inhibitors, Example: Celecoxib/ Rofecoxib/ valdecoxib
- Intraarticular glucocorticoids
Surgical:
- Osteotomy: realignment of joint
- Total joint arthroplasty (replacement)
RA
Demographics
Risk factors
M:F - 1:3
Peak age of onset: 35-55
Risk factors:
- Genetic: MHC II (HLA-DR4 as major susceptibility haplotype), PTPN22, CD40L, CTLA4
- Smoking (induce airway enzymes that increase citrullination of proteins in inflamed tissues)
- Pregnancy-related: nulliparity, post-partum flare
RA
Two-hit pathogenesis
First hit (pre-RA): → Citrullination: normal self proteins become citrullinated by peptidyl arginine deiminase (PAD)
→ Mucosal inflammation: presentation of citrullinated (and other) auto-antigens to CD4+ cells → production of autoAb against various modified antigens (esp ACPA, RF)
Second hit (immune activation): sudden ↑expression of modified antigens in joint → Presentation of Ag to CD4+ T cells (Th1 and Th17)>> Interaction with B cells for AutoAb and MQ
→ Resultant cytokine elaboration (TNF, IL-1, IL-6) act on local cells in joint: chondrocyte death, Fibroblast proliferation, Osteoclast activation…etc
RA
Pathogenesis of pannus formation, osteopenia, and rheumatoid nodule formation
Cytokine production by B cells and MQ:
- Formation of pannus (inflammatory granulation tissue) → proliferates within joint and under cartilage → local joint destruction, fibrous or bony ankylosis
- Local osteoclast activation → bony location and periarticular osteopaenia
- Rheumatoid nodules: central area of fibrinoid material surrounded by palisade of proliferating mononuclear cells
RA
Typical joints involved
symmetrical peripheral polyarthritis → Hand: MCP, PIP, wrist → UL: elbow, shoulder → LL: MTP, ankle, knees, hip → Axial: C-spine (esp AAJ), cricoarytenoid
RA Hand deformities
PIPJ
MCPJ
Palm
Wrist
PIPJ:
- Swan neck deformity
- Boutonniere deformity
- Mallet finger
- Z deformity of thumb
MCPJ and palm:
→ Volar (palmar) subluxation
→ Ulnar deviation of fingers
→ Bow string sign: prominent tendon in extensor compartment
Wrist:
→ Late: radial deviation, dorsal subluxation/dislocation of ulna and distal RUJ
→ Carpal tunnel syndrome:
RA
Cutaneous changes
→ Raynaud phenomenon
→ Rheumatoid nodules on pressure points
→ Rheumatoid vasculitis changes: digital infarcts, periungual telangiectasiae
Explain the pathophysiology of Swan neck and Boutonniere deformities seen in RA
Swan neck deformity: lax volar plate ± FDS rupture → unopposed extensor force → PIPJ hyperextended, DIPJ flexed
Boutonniere deformity: broken central slip of extensor tendon → ‘button-like’ dorsal herniation of PIPJ → PIPJ flexed, DIPJ hyperextended
RA lower limb deformities
Feet, Knee, Hip
Feet:
→ MTP Joint erosion: lateral deviation, plantar subluxation of metatarsal heads - ‘cock up’ deformity
→ Ankle:
- Arthritis: diffuse swelling around talotibial joint
- Tarsal tunnel syndrome: heel pain, toe paraesthesia
Knee: similar to OA
→ Genu valgus
→ Baker’s cyst (rupture = pain)
→ Restriction of ROM, Quadriceps atrophy
→ Knee effusion
Hip: similar to OA
→ Restricted ROM, pain in groin, thigh, low back or referred to knee
RA arm deformities - elbow, shoulder
Elbow:
→ Loss of extension
→ Joint effusion/synovitis
→ Ulnar compressive neuropathy due to elbow synovitis
→ Rheumatoid nodule
Shoulder:
→ Frozen shoulder: due to capsulitis of glenohumeral joint
→ Rotator cuff injury, shoulder dislocation
RA cervical spine deformities
Cricoarytenoid joint involvement:
□ Hoarseness
□ Inspiratory stridor if severe
Cervical spine involvement:
□ Subluxation: most commonly at atlanotoaxial joint (C1/2)
□ Apophyseal joint (neck stiffness, pain)
C1/2 subluxation S/S:
- Pain, stiffness of the neck
- Radiculopathy → radicular pain
- Cervical cord compression → cervical myelopathy emergency
Cervical subluxation in RA
S/S
Diagnostic Ix
Tx
S/S:
→ Neck pain radiating to occiput due to upper cervical root involvement
→ Clumsiness, abnormal gait (cervical myelopathy)
→ Spastic quadriparesis, sensory and sphincter disturbance in late stages
Ix: AP + lateral X-ray of C-spine with flexion and extension views
→ Anterior subluxation: typically defined by anterior atlantodens interval (AADI) ≥4mm
Tx:
- Avoid high-impact exercise, wear stiff collar brace, neuropathic pain relief
- Urgent surgery for cord decompression
Rheumatoid nodules
- Sites of involvement
Joint sites at pressure/friction points, eg. olecranon, sacrum, Achilles tendon, toes
Pulmonary (<1%): commonly occur at subpleural area, interlobular septa
- Asymptomatic or a/w pleural effusion, PTX, haemoptysis
Cardiac: commonly occur at myopericardium, valvular structure
Name 2 serum autoantibodies for RA
Confounding/ false positives
Compare sensitivity and specificity
Purpose of measuring these antibodies
Rheumatoid factor (RF): IgM autoantibody against IgG (anti-IgG IgM autoAb)
- Not sensitive or specific
- High titre is more specific for diagnosis
- High titre = Poor prognosis
- Confounding: Sjogren’s syndrome, Chronic infection, SLE, Normal individuals
Anti-citrullinated protein (anti-CCP, ACPA): Ab to citrullinated proteins
- Low sensitivity but high specificity to RA
- Allow early diagnosis of RA, positive before symptoms
- Predict progressive and erosive disease
Radiological features of RA
→ Soft tissue swelling and wide joint space due to synovial inflammation by effusion
→ Juxta-articular osteoporosis due to hyperemia and disuse
→ Joint space narrowing due to cartilage destruction by pannus
→ Periarticular erosion due to pannus destruction of unprotected bone at insertion of joint capsule
Outline the ACR/ EULAR guideline for clinical diagnosis of RA
Name one scoring system for assessing RA activity and treatment response
DAS28 score for assessing disease activity, response to Tx and need for biologics
List medical treatment options for RA
1st, 2nd, 3rd and 4th line
1st-line:
Methotrexate + Corticosteroids
NSAIDs, COX-2 inhibitors
2nd-line:
Conventional Disease-Modifying Anti-Rheumatic Drugs (DMARDs) e.g. azathioprine, sulphasalazine, hydroxychloroquine
3rd-line: Biologics
Anti-TNF agent e.g. etanercept, adlimumab
4th-line: More biologics Anti-IL6r: tocilizumab Anti-CD20: rituximab Co-stimulation blockade: abatacept Anti-IL1r: anakinra
Surgical treatment options for RA
Synovectomy: removal of inflamed synovium for pain relief, prevention of tendon rupture
Arthrodesis: artificial induction of joint ossification/ fusion
Re-alignment osteotomy: removal of parts of bone to restore alignment and stability
Joint replacement/ Total joint arthroplasty
SpA
List all the common features shared by these inflammatory joint diseases
Asymmetrical oligoarthritis with sacroiliitis, spondylitis and LL > UL involvement
HLA-B27-associated with tendency for familial aggregation
RF- and anti-CCP negative
Prominent extrasynovial inflammation/ extra-articular features including
→ Dactylitis and enthesitis
→ Mucosal inflammation: conjunctivitis, buccal ulceration, urethritis, prostatitis, IBD
→ Others: anterior uveitis, aortic root fibrosis (AR, conduction defects), erythema nodosum
Compare the traditional and newer classification of SpA
HLA-B27 and the pathogenesis of SpA
- Arthritogenic peptide hypothesis: HLA-B27 ‘sees’ certain microbial peptide similarly as self-peptides →cause autoreactivity in CD8+ T cells
- Propensity to form homodimers/ multimers to activate T cells, APCs, NK cells for autoreaction
- Misfolding and autophagy: intracellular misfolding may lead to high ER stress → activates autophagy pathway by cytokine secretion
4 spinal mobility tests for SpA
Modified Schober Test - For spinal flexion
Lateral spinal flexion test
Occiput to wall and tragus to wall test
Cervical rotation test with Goniometer
Role of HLA-B27 measurement in SpA
Drawbacks of HLA-B27 as a diagnostic indicator
- Highly suggestive of Ankylosing spondylitis (90-95% positive)
- Used as Prognosis indicator
- Screening tool in inflammatory back pain
- Otherwise Not sensitive or specific enough to diagnose SpA
- Occurs in 9% of normal Caucasians (high false positive rate)
Ddx SpA based on the following:
- Symmetric sacroillitis
- Upper limb involvement before lower limb
- Not associated with enthesitis
- Not associated with dactylitis
- No cutaneous involvement
Symmetric sacroilitis - AS or IBD-associated SpA
Upper limb involvement first: Psoriatic arthritis
No enthesitis: IBS-associated SpA
No Dactylitis or skin involvement: AS
Outline the clinical diagnostic criteria for Ankylosing spondylitis
Modified New York criteria
Clinical: (At least 1)
- Lower back pain and stiffness for >3 months, improves with exercise and not relieved by rest
- Limited lumbar spine motion in sagittal and frontal plane
- Limited chest expansion compared to normal
Radiological: (Must be present)
Sacroilitis: grade >2 bilaterally or grade 3-4 unilaterally
Name one classification for diagnosis of Axial SpA
SpA Diagnosis: ASAS Classification criteria for SpA
Name one classification for Peripheral SpA
ASAS classification criteria for peripheral SpA (2011)
Name one index for disease severity of SpA
SpA Disease severity: Bath AS Disease Activity Index (BASDAI)
Radiological features of SpA
□ Squaring of vertebral bodies (early): loss of normal concavity of anterior border
□ Shiny corner sign (early): reactive sclerosis due to inflammatory erosions at superior and inferior endplates
□ Syndesmophytes and parasyndesmophytes (late): paravertebral ossification parallel to spine
□ Bamboo spine (late): occurs with complete ankylosis of vertebral bodies
Radiological features of sacroiliitis
Plain XR: erosions with loss of clear white line, ankylosis, changes in joint width, sclerosis
MRI: subchondral/periarticular BM oedema
Treatment options for SpA
Lifestyle modifications
1st line, 2nd line
adjunctive treatment for extra-articular complications
General measures:
→ Patient education
→ Stretching exercise and physiotherapy
→ Smoking cessation
Pharmacological treatment:
→ NSAIDs or COX-2 inhibitor as first line
→ Biologics: Anti-TNF or anti-IL-17A as second line
Adjunctive treatment:
→ DMARDs (eg. sulphasalazine)
→ Local glucocorticoid injections for enthesitis and dactylitis
→ Steroid eyedrops for anterior uveitis
→ Joint surgery
Reactive arthritis/ Reiter’s syndrome
Clinical features
Preceding conditions
Clinical features: triad of urethritis + reactive arthritis + conjunctivitis 1-4 weeks after infection
- Acute asymmetric oligoarthritis in LL first
- Enthesitis: Achilles tendinitis, plantar fasciitis
- Circinate balanitis (20-50%): starts at vesicles on coronal margin of prepuce and glans
- Conjunctivitis (50%)
- Oral ulcers and nail dystrophy
Preceding infection: bacterial dysentery (Salmonella, Shigella, Yersinia, Campylobacter, C. difficile) and chlamydial urethritis
Psoriatic arthritis
- Clinical presentation
→ Psoriasis
→ Arthritis: variable pattern
→ Enthesitis (35%) and dactylitis (~50%)
→ Nail changes: pitting, onycholysis, subungual hypekeratosis, horizontal ridging
→ Uveitis and conjunctivitis
→ Associated metabolic syndrome, eg. overweight, DM, HTN, hyperlipidaemia, hyperuricaemia
Difference between psoriatic arthritis and RA
Difference from rheumatoid arthritis: RA has non of the extra-articular features specific to SpA, esp. nail changes to psoriasis
→ Presence of psoriasis
→ Nail dystrophy: onycholysis, pitting, ridging etc
→ Pattern of joint involvement: spondylitis, sacroiliitis, DIPJ involvement
→ Enthesitis and dactylitis
