Rheumatology - Monoarthropathy - OA, Septic arthritis, Gout Flashcards
List diseases that cause monoarticular symptoms
Septic arthritis: Bacterial, Mycobacterial, Lyme disease…etc
Crystal deposition diseases:
- Gout
- Pseudogout
- Hydroxyapatite
- Calcium oxalate
Trauma:
- Fracture
- ACL/ PCL tear
- Hemarthrosis
Others:
- OA
- Juvenile idiopathic arthritis
- Coagulopathy
- Avascular necrosis of bone
List polyarticular diseases that sometimes present with monoarticular onset
RA
JIA
Viral arthritis
Spondyloarthritis (SpA)
- Reactive arthritis
- Psoriatic arthritis
- IBD associated arthritis
Ddx the most likely cause of monoarticular pain over minutes, hours/days, weeks
Pain in Seconds/ minutes: Fracture, Hemarthrosis
Hours to days: Septic arthritis, Crystal deposition disease
Weeks: Inflammatory arthritis/ SpA, Indolent infection (TB), Osteoarthritis
Ddx most likely causes of articular pain with recurrent acute attacks
Crystal arthritis: e.g. gout, pseudogout, hydroxyapatite, calcium oxalate
Inflammatory arthritis syndromes
Ddx most likely causes of articular pain with immunosuppression
Septic arthritis
Osteonecrosis
First-line investigations for mono-articular pain
Synovial fluid aspiration and analysis:
- Gross appearance
- Microscopy
- Microbiology
Blood:
- CBC with diff.
- ESR
- Serum uric acid level
- Prothrombin and Partial thromboplastin time
- ANA, ACPA, autoimmune markers
Microbiology: Blood, urine, other sample culture
Others: Arthroscopy, X-ray of joint and contralateral side, Synovial biopsy, Other imaging
Indications of synovial fluid aspiration and analysis
Clinical suspicion of:
- Infection
- Crystal deposition disease
- Hemarthrosis
- Differentiate inflammatory and non-inflammatory arthritis
List all tests done on synovial fluid analysis
Gross appearance
- Color
- Turbidity
- Viscosity
Microscopy
- Wet films
- Cell stains and differential counts
- Polarized light
Microbiology
- Gram stain
- Culture
- Special stains: ZN stains, Fungal stains
Interpret the following profile of synovial fluid
High viscosity
Straw- yellow color
Transparent
WBC: 200-2000
PMN: <25%
Non-inflammatory arthritis/ Normal/ OA
Interpret the following profile of synovial fluid
Viscosity Low
Yellow color
Translucent
WBC: 2000-75000
PMN: >50%
Inflammatory arthritis e.g. RA, crystal deposition diseases
Interpret the following profile of synovial fluid
Variable viscosity, sometimes low, sometimes high
Variable color
Opaque
WBC >100,000
PMN: >75%
Septic arthritis
Interpret following synovial fluid analysis
Low viscosity
Red color
Slightly turbid
WBC: <200
PMN: <25%
Haemarthrosis
Describe the function of polarized light microscopy on synovial fluid
Birefringent crystal in fluid alters vector of plane polarized light
Birefringence detected by color shift to blue (Positive) or yellow (Negative) when long axis of crystal is aligned with optical axis of the first order red compensator
Blue when parallel to optical axis of red compensator = Calcium pyrophosphate
Yellow (negative) when parallel to optical axis = Monosodium urate
Arthroscopy
Functions
Indication
Functions
- Diagnostic: directly visualize articular surface, assess cartilage damage, take synovial biopsy
- Therapeutic: Debridement of damaged cartilage, remove loose bodies, pain relief
Indications:
- Pain relief
- Inflammatory arthritis needing synovial biopsy
- Remove fractured cartilage/ loose bodies
Septic arthritis
- Typical onset
- Distribution
- Routes of infection
Abrupt onset of monoarticular pain
Typically at large weight bearing joints e.g. hip, knee
Routes of infection:
- Hematogenous
- From adjacent Osteomyelitis
- Adjacent soft tissue infection
- Diagnostic/ therapeutic procedure contamination
- Penetrating injury by puncture or cut
Risk factors of septic arthritis
Age under 5 or over 65
Medical:
- Chronic arthritic diseases e.g. RA, OA, Crystal deposition diseases…etc
- Chronic skin infections
- Chronic systemic diseases: SLE< DM, Malignancy, Immunocompromised…etc
Iatrogenic:
- Prosthetic joints
- Intra-articular injections or arthrocentesis
Social:
- Parenteral/ IV drug use
- STDs
Common causative bacteria for septic arthritis in:
Infant (<1 month)
Children <2 years old
Infants:
- Streptococcal agalactiae
- Gram negative bacilli e.g. E. coli
- Staph. aureus
Children:
- Hemophilus influenzae type B
Common causative bacteria of septic arthritis in:
Older children, adults, elderly, chronically ill
Staphylococcus auerus
Gram negative bacilli (chronically ill, elderly)
Neisseria gonorrhoeae (disseminated), Chlamydia trachomatis (reactive) (sexually active)
Common causative bacteria of septic arthritis in:
Prosthetic infection
Skin infection
IV drug users
Gas forming infection
Prosthetic: Staphylococcal aureus
Skin/ soft tissue infection: Streptococcal infection
IV DU: Gram negative bacilli, Pseudomonas aeruginosa, Staphylococcal aureus
Gas forming/ foul smelling; Anaerobes e.g. Clostridium difficile, Clostridium perfringens
Red flag features and approach/ first-line investigations to septic arthritis
Clinical Features:
- Fever
- Acute onset of hot, swollen and tender joint with restricted movement
Investigations:
- Synovial fluid aspiration for microbiology: Negative gram smear or culture does not exclude sepsis
- Blood culture, CBC, ESR, CRP
- Electrolyte, RFT, LFT (detect end-organ damage, antibiotic use)
- Imaging: X-ray and MRI
Promptly treat with antibiotics only AFTER joint aspiration
Empirical antibiotics treatment for septic arthritis (typical organisms)
First-line: IV Flucloxacillin - 2g, 4 doses/ day
Penicillin-allergy:
- IV Clindamycin 450-600mg QDS or
- IV 2nd/ 3rd gen. cephalosporin
Empirical antibiotics treatment for septic arthritis caused by:
- Gram-negative sepsis
- MRSA
- Gonoccocus or meningococcus
- Gram-negative sepsis: IV 2nd/ 3rd gen. cephalosporin
- MRSA: IV Vancomycin + IV 2nd/3rd gen. cephalosporin
- Gonoccocus or meningococcus: IV Ceftriaxone
What conditions are associated with gram negative or MRSA spetic arthritis
Gram-negative: Elderly with chronic illness, Recurrent UTI, Recent abdominal surgery
MRSA: recent inpatient care, Leg ulcers, Nursing home residents, Long-term catheter insertion
Which patient groups cannot be given empirical antibiotics for septic arthritis
IV Drug users
ITU/ ICU patients with known colonization of other organs
Surgical treatment options for septic arthritis
Acute: Arthroscopy
Delayed or chronic: Open arthrotomy
Repeat surgical debridement until infection is controlled
Intrinsic crystalline particles in crystal deposition diseases
- Monosodium Urate monohydrate
- Calcium Pyrophosphate Dihydrate CPPD
- Calcium phosphate compounds e.g. hydroxyapatite, tricalcium phosphate, calcium oxalate
- Lipids: Cholesterol, lipid crystals, Charcot-Leyden phospholipase crystals
- Cystine
- Xantine, Hypoxanthine
- Protein precipitates e.g. cryoglobulins
Extrinsic crystalline particles in crystal deposition disease
Synthetic corticosteroids
Plant thorns - Semi crystalloid cellulose e.g. blackthorn, rose thorn, dried palm fronds
Sea-urchin spines - Crystalline calcium carbonate
Gout
- Demographics
- Joint distribution
- Presentations
- Diagnostic Ix
Demographics
- M:F = 8:1
- 30-60 years old
Joint distribution
- First MTP in 20%
Presentations
- Acute gouty arthritis with systemic upset
- Intercritical gout
- Chronic tophaceous gout
Diagnostic Ix: Urate crystals in synovial fluid aspiration
Compare the presentation between acute, intercritical and chronic tophaceous gout
Acute: Monoarticular pain with systemic upset, Pruritus and desquamation of overlying skin
Intercritical: Asymptomatic between attacks, frequency and duration increases, becomes polyarticular
Chronic tophaceous gout: Late stage, continuous arthritis with superimposed acute attacks
Areas affected by chronic tophaceous gout
Tophi in periarticular tissues, Helix of ear, Tendon sheaths
Late stage: Larynx. tongue, heart
Gout
Associated diseases
Causes of hyperuricaemia
Associated diseases:
- Obesity
- Alcoholism
- Type IV hyperlipoproteinemia
- Impaired glucose tolerance
- Ischemic heart disease
- Hypertension
Pathogenesis:
- Dietary excess of uric acid +/- Overproduction of urate Under-excretion of urate
Outline the production and excretion cycle of uric acid
Causes of overproduction of uric acid
Primary hyperurecaemia
- Idiopathic
- HGPRT deficiency - cannot convert hypoxanthine to xanthine
- PRPP synthase superactivity - cannot convert 5-phosphoribosyl 1-pyrophosphate to PRPP glutamine
Secondary hyperurecaemia
- Excessive purine intake
- Myeloproliferative/ lymphoproliferative diseases/ Hemolytic diseases - increase cell breakdown
- Psoriasis
- Glycogen storage diseases type 1,3,5,7
Causes of under-secretion of uric acid
Primary: idiopathic
Secondary:
- Poor renal function
- Metabolic acidosis
- Dehydration, Diuretics
- Hypertension
- Hyperparathyroidism
- Drugs: Cyclosporine, Pyrazinamide, Ethambutol, Salicylate
- Lead nephropathy
Gout
Acute treatment options
Pain relief and acute management
- NSAID (avoid aspirin or salicylates)
- COX-2 selective inhibitors - Etoricoxib
- Colchicine
- Steroids
- Anti-IL1 injection: Anakinra, Canakinumab
Describe the molecular pathway for urate crystals to trigger inflammatory response and articular damage
Signal 1 = innate immune response against pathogen
TLR at plasma membrane activated > NF-kB pathway > inflammasome response
Signal 2 = monosodium urate crystal > engulfed by macrophage > inflammasome > capase 1 to cleave pro-IL1 to IL1 > Release IL1 to extracellular space > draw more WBC to site of infection (chemotactic factor) for inflammatory response + fever
Gout
Long-term management objective and drug options
Prevent recurrent attacks, formation of tophi and articular damage
Prophylaxis: Colchicine or NSAID for 3 months to prevent breakthrough attacks
Xanthine oxidase inhibitors: (C/I Azathioprine, synergistic toxicity)
- Allopurinol
- Febuxostat (for impaired kidney function, C/I liver dysfunction)
Uricosuric agents:
- Probenecid, benzbromarone
- Sulphinpyrazone
Urate lowering agents:
- Pegloticase (recombinant uricase)
- Lesinurad: URAT1 inhibitor
C/I uricosuric agents
Primary overproduction of urate
Gross hyperuricosuria
Urolithiasis
Renal insufficiency
Toxic S/E of drugs for long-term Gout control
TEN and vasculitis - Allopurinol
Nephrotic syndrome - Probenecid
Hepatitis and BM suppression - Hypouricaemic drugs
Indications for hypourcaemic agents (allopurinol, rasburicase…etc)
Indications for hypouricaemic drugs:
- Recurrent acute attacks
- Tophi, chronic joint damage
(Contraindications for uricosuric agents)
* Renal disease
* Young patient with hyperuricaemia
* Family history of renal and heart disease
* Primary purine overproduction and under-secretion
Pseudogout/ Chondrocalcinosis
Demographics
Joints affected
Crystal
Demographics: Elderly, M:F = 1.4:1
Joint: Knee most common
Calcium Pyrophosphate - Rhomboid crystals
Pseudogout
Causes
Hereditary
Idiopathic (elderly)
Metabolic diseases:
- Hyperparathyroidism
- Haemachromatosis
- Hypothyroidism
- Gout
- Hypomagnesemia
- Hypophosphatasia
Pseudogout
Treatment options
Majority asymptomatic - no Tx
Supportive measures: ice pack, immobilization, joint rest
Joint aspiration + intra-articular glucocorticoid injection
Systemic anti-inflammatory drug if >2 joints involved:
- Choice: NSAIDs (caution on C/I in elderly), colchicine (first 24h), oral steroids
Haemarthrosis
Common causes
Symptoms
Diagnostic Ix
Tx
Causes:
- Trauma
- Hemophilia
- Acquired hemophilia
- Anti-platelet or anti-coagulants
S/S: Pain, swelling, stiffness (non-specific)
Diagnostic Ix: Arthrocentesis
Tx: Underlying cause
Xanthine oxidase inhibitor
Examples
MoA
S/E
D/D interactions
allopurinol and febuxostat
Initiation: start only after resolution of flare
MoA: block xanthine oxidase = increase conversion of hypoxanthine into xanthine into uric acid for urine excretion
S/E: rash, leukopenia/thrombocytopenia, diarrhoea (3-5%), xanthine stones, severe cutaneous reactions, DRESS syndrome
Uricosuric agents
Examples
MoA
Indications
S.E
probenecid, benzbromarone
MoA: inhibit PCT urate-anion exchangers → ↓urate reabsorption → ↑↑urate excretion
Indication: impaired urate excretion, used in combination with XOI for refractory to monotherapy
S/E: rash, precipitation of gout flare, GI intolerance, urate stone formation
Probenecid S/E = Precipitation of gout, Rash, Obstruction (urate stone), Bowels (GI upset)
Recombinant uricase
Examples
MoA
S/E
eg. pegloticase (for gout), rasburicase (for TLS, not for gout)
→ MoA: enzyme that catalyzes conversion of urate into more soluble allantoin for excretion
S/E: may develop Ab vs pegloticase → ↓therapeutic response → limiting factor for long-term treatment
Radiological features of pseudogout
→ Chondrocalcinosis: irregular faint punctate/linear
radiodensities in articular cartilage
→ Degenerative changes: subchondral cysts, osteophytes, ↓joint space
→ Other features in specific joints:
- MCPJ: squared off bone ends and hook-like MPCJ
- Wrist: isolated/unusually extensive radiocarpal joint narrowing
- PFJ: severe space degeneration
