Rheumatology JC082: Painful Red Joint: Monoarthropathy, Gouty Arthritis, Septic Arthritis, Haemarthrosis Flashcards
DDx of Monoarthritis
記: Septic, Crystal, Inflammatory (monoarthritis presentation), OA, Trauma
- ***Septic arthritis
- Bacterial
- Mycobacterial
- Lyme disease (mimic septic arthritis but it is a Borrelia infection) - ***Crystal arthritis
- Gout
- CPPD (Pseudogout: Calcium pyrophosphate deposition disease)
- Hydroxyapatite deposition disease
- Calcium oxalate deposition disease - ***Trauma
- Fracture
- ACL / PCL tear
- Haemarthrosis - Others
- **OA
- Juvenile idiopathic arthritis (JIA)
- Coagulopathy
- Avascular necrosis of bone
- **Monoarticular presentation of polyarticular disease (e.g. RA, SpA, PsA)
DDx of Polyarticular diseases
記: Inflammatory
Occasionally present with monoarticular onset
1. RA
2. JIA
3. Viral arthritis
4. Spondyloarthritis (SpA) (inflammation in spine + joints)
- Reactive arthritis (ReA)
- Psoriatic arthritis (PsA)
- IBD-associated arthritis
History taking of Monoarticular problem
- ***Onset of Pain
- second / min: Fracture, Internal derangement
- over several hours / 1-2 days: Infection, Crystal arthritis
- over days - weeks: Inflammatory arthritis syndromes, Indolent infection, OA - Joint overused / damaged, recently / past
- Traumatic causes
- OA - ***Previous acute attacks of self limiting arthritis
- Crystal arthritis
- Inflammatory arthritis syndromes - Treatment with immunosuppressive agents (e.g. steroid, cytotoxic agent)
- Infection
- ***Osteonecrosis - History of ***bleeding disorders / treatment with anti-coagulants
- Haemarthrosis
***Investigations of Monoarticular problem
- ***Synovial fluid analysis
- Appearance
- Microscopy
- Microbiology - CBC
- ***ESR
- Biochemistry (including Serum ***uric acid level)
- ***PT, aPTT
- ***Cultures of blood, urine, other possible primary sites of infection
- ***Serological tests for ANA, RF, ACPA
- Radiograph of joint + contralateral joint (for comparison)
- ***Arthroscopy
- ***Synovial biopsy
- Other imaging studies (USG, CT, MRI)
Synovial fluid analysis
USG-guided knee joint aspiration
Indications:
1. Infection
2. Crystal arthritis
3. Haemarthrosis
4. Differentiating inflammatory from non-inflammatory arthritis
Examination
1. Appearance
- Colour
- Turbidity
- Viscosity
- Microscopy
- **Cell stains + counts
- Wet films
- **Polarised light - Microbiology
- Gram stain
- Culture
- Special techniques e.g. ZN stain, Fungal stain
***Classification of Synovial effusions
- Non-inflammatory (Normal / OA)
- Viscosity: High
- Colour: Straw to yellow
- Clarity: Transparent
- WBC: 200-2000
- PMN leukocytes: <25% - Inflammatory (RA / Crystal)
- Viscosity: ***Low
- Colour: Yellow
- Clarity: Translucent / Turbid
- WBC: 2000-75000
- PMN leukocytes: >50% often - Septic
- Viscosity: Variable
- Colour: Variable
- Clarity: **Opaque
- WBC: **>100000 often
- PMN leukocytes: ***>75% - Haemarthrosis
- Viscosity: ***Low
- Colour: Bloody
- Clarity: Blood-like
- WBC: similar to blood level
- PMN leukocytes: similar to blood level
Polarised microscopy
Monosodium urate monohydrate (Gout): **Needle shaped, **Negative birefringence
Calcium pyrophosphate dihydrate (Pseudogout): **Rhomboid shaped, **Positive birefringence
Birefringent crystal (colour shift of crystal) altering the vector of plane polarised light —> allow it to be seen at microscope eye piece
Unpolarised light
—> Polariser
—> Light resolved into rays on a vertical axis
—> Crystal
—> Light rays twisted to a horizontal plane by crystal
—> Analyser (a red compensator to filter out background polarised light so can only see diffracted light from crystals)
—> Align crystal to axis of Analyser
—> Only rays vibrating in a horizontal axis allowed through
—> Can be seen by eye
Birefringence can be detected by a colour shift to blue (positive) or yellow (negative) when the long axis of crystal is aligned with the optical axis of a first order red compensator
Arthroscopy
Allow direct visualisation of arterial surface
Diagnostic:
- Assess degree of cartilage damage
- ***Synovial biopsy for equivocal cases
Therapeutic:
- ***Debride damaged cartilage
- Remove loose bodies
- Provide a short period of pain relief
Septic arthritis
- Most sinister type of monoarthritis —> ***Rheumatologic emergency
- Quick diagnosis + Aggressive treatment
- Bacterial infections esp. Gram +ve organisms can destroy joint cartilage within a few days (***very short time)
—> need prompt + proper treatment to avoid permanent structural damage
Clinical presentation:
- **Abrupt onset
- Monoarticular involving large **weight bearing joints
Route of infection:
1. Haematogenous
2. Adjacent osteomyelitis
3. Adjacent soft tissue infection
4. Iatrogenic (e.g. diagnostic / therapeutic procedures like joint aspiration)
5. Penetrating damage by puncture / cutting
Causative agents:
1. Bacterial
2. Mycobacterial
3. Fungal
4. Viral
Risk factors:
1. **Extreme of age (<5, >65)
2. **Chronic arthritic syndromes
- RA
- Crystal arthritis
- Severe OA
- Charcot joint
- Haemarthrosis
3. **Prosthetic joints
4. **Intra-articular injection / arthrocentesis
5. **Parenteral drug user
6. **STD
- localised gonococcal disease —> disseminate to cause joint disease
7. Chronic skin infections
8. Chronic systemic illness
- DM, SLE, malignancy, immunocompromised state
Acute bacterial arthritis
Children >2 years + adults
- **Streptococcus
- **Staphylococcus aureus
Special consideration
- Infant < 1month: **GBS, **Gram -ve bacilli (e.g. E. coli), Staphylococcus aureus
- Children <2 years: **Hib
- Elderly / chronically ill: **Gram -ve bacilli
- Sexually active young adults: **N. gonorrhoeae (particular of disseminated gonococcal infection, usually polyarticular)
- IVDU: Gram -ve bacilli, Pseudomonas aeruginosa, **Staphylococcus aureus
- Late prosthetic joint infection: Staphylococcus aureus
- Skin / soft tissue infection: Streptococcal
- Foul smelling / gas forming: ***Anaerobes e.g. C. difficile
General approach to Septic arthritis
- High level of suspicion
- acute history of ***hot, swollen, tender joints with restriction of movement - Prompt + appropriate treatment
- if suspicion is high, treat even in absence of fever but only after joint aspiration
- Negative gram smear / culture does NOT exclude sepsis - Involve OT surgeons
Investigations of Septic arthritis
- Synovial joint aspiration + Culture (most important)
- fluid sent fresh for relevant stains + culture
- **prior to antibiotic therapy
- **warfarin not CI for needle aspiration
- if hip joint involved —> always do imaging-guided joint aspiration - ***Blood culture always be taken
- CBP, ESR, CRP
- Electrolytes, Baseline LRFT
- detect end-organ damage
- guide antibiotic choice - Plain X-ray
- MRI (most appropriate where required)
- also sensitive in detecting ***osteomyelitis
Treatment of Septic arthritis
**Parenteral antibiotic
- mainstay of treatment
- different initial **empirical antibiotic cover for different patient groups until positive culture / sensitivity
- in doubt, consult microbiologist
Patient group:
1. No risk factors for atypical organisms
- **Flucloxacillin 2g QDS IV
- **Clindamycin 450-600mg QDS IV or 2nd / 3rd gen ***Cephalosporin IV
- High risk of Gram -ve sepsis (elderly, frail, recurrent UTI, recent abdominal surgery)
- 2nd / 3rd gen ***Cephalosporin IV - MRSA risk (known MRSA, recent inpatient, nursing home resident, leg ulcers, catheters)
- ***Vancomycin IV + 2nd / 3rd gen Cephalosporin IV - Suspected gonococcus / meningococcus
- ***Ceftriaxone IV - IVDU
- Discuss with microbiologist - ITU patients, known colonisation of other organs (e.g. cystic fibrosis)
- Discuss with microbiologist
Surgical management by OT surgeon
1. Confirm diagnosis by examination of joint aspirate
2. **Urgent joint irrigation / **debridement
3. Acute phase: **Arthroscopy
4. Delayed / Chronic cases: **Open arthrotomy
5. Repeated surgical debridement until infection under control
6. Be prepared for co-existing osteomyelitis
Crystalline particles in joint disease
Intrinsic:
1. **Monosodium urate monohydrate (most common)
2. **Calcium pyrophosphate dihydrate (most common)
3. Calcium phosphates
- acidic: brushite, monetite, **calcium oxalate
- basic: **hydroxyapatite, octacalcium phosphate, tricalcium phosphate
4. Lipids
- cholesterol
- lipid liquid crystals
- Charcot-Leyden (phospholipase) crystals
5. Cystine
6. Xanthine, hypoxanthine
7. Protein precipitates (e.g. cryoglobulins)
Extrinsic:
1. ***Synthetic corticosteroids
2. Plant thorns (semicrystalloid cellulose), esp. blackthorn, rose, dried palm fronds
3. Sea-urchin spines (crystalline calcium carbonate)
Clinical features of Gout
- Asymptomatic hyperuricaemia
- Acute gouty arthritis
- M:F = 8:1
- commonest age of onset: 30-60 yo
- initial presentation: **monoarticular
- 1st MTP joint affected first in 20%
- systemic upset common during acute stage (e.g. **low grade fever)
- pruritus + desquamation of overlying skin
- diagnosis: **Demonstration of UA crystal in joint
- serum UA level useful but **not diagnostic
(- may actually ***↓ during flare up) (check urate when gout attack subside: 4-6 weeks + other tests e.g. lipid profile, RFT, FG 1 week prior to FU to check for other associated conditions (SpC FM)) - Intercritical gout
- entirely asymptomatic in between attacks
- attacks getting ***more frequent
- may become polyarticular - Chronic tophaceous gout
- **tophi: hallmark
- tophi in periarticular tissues, **helix of ears, tendon sheaths
- rarely in larynx, tongue, heart
- in 60% of patients after 10 years of gout
X-ray:
- 1st MTP: ***punched out erosive lesion (characteristic of gout)
Clinical associations:
1. Obesity
2. **Heavy alcohol intake
3. **Type 4 hyperlipoproteinaemia (high TG contained in VLDL)
4. Impaired glucose tolerance
5. IHD
6. HT
Natural history of gout
Stage 1:
- Asymptomatic hyperuricaemia —> No arthritis
Stage 2:
- Acute gouty arthritis / Intercritical gout
- Duration: 1-2 weeks to 1 week-2 months
- Interval: 6 months-2 years to 2 weeks-4 months
- Number of joints involved: 1-2 to 4-5
Stage 3:
- Chronic gouty arthritis
—> Continuous arthritis + Superimposed acute attacks
—> Tophi
Progression from stage 1 to 2 variable: short / long
***Causes of hyperuricaemia
- Dietary excess
- Overproduction of urate
- Underexcretion of urate (>90%)
Balance of uric acid:
1. Dietary nucleotides, nucleoproteins (1/3)
- Production: Cellular nucleotides, nucleoproteins breakdown (2/3)
—> Purine (Adenine, Guanine)
—> Purine breakdown —> Uric acid - Excretion
- Gut excretion (bacterial degradation) (1/3)
- ***Renal excretion (10% of filter load) (2/3)
Urate in Kidney
- Glomerular filtration of all serum urate
- Proximal tubular resorption of 99% of filter load
- Resecretion of 50% of resorbed load
- Resorption of ~80% of resecreted urate
- Excretion of ~10% of all filtered load
Urate secretion / reabsorption are bidirectional
- Salicylate, Thiazide, Loop diuretic —> competitive substrate for secretion by transporter ABCG2, NPT1, NPT4, MRP4
- Penicillin, Cephalosporin, Methotrexate, Thiazide —> competitive substrate for secretion by transporter OAT1, OAT3
- Fructose, Pyrazinamide, Lactic acid, Nicotinic acid —> exchange for urate —> ↑ reabsorption of urate
**Probenecid, **Losartan: antagonise urate reabsorption by blocking URAT1 —> ***uricosuric effect
Overproduction of uric acid
Primary hyperuricaemia
1. **Idiopathic
2. Complete / Partial deficiency of **HGPRT (hypoxanthine-guanine phosphoribosyltransferase) —> ↑ Xanthine production
3. Superactivity of ***PRPP (phosphoribosyl pyrophosphate) synthetase —> ↑ Xanthine production
**Secondary hyperuricaemia (more common)
1. **Excessive purine consumption (e.g. heavy beer drinking)
2. **Myeloproliferative / Lymphoproliferative disorders
3. **Haemolytic diseases
4. ***Psoriasis
5. Glycogen storage diseases: type 1, 3, 5, 7
***Underexcretion of uric acid
Primary hyperuricaemia
1. ***Idiopathic
**Secondary hyperuricaemia
1. **Decreased renal function
2. **Metabolic acidosis (ketoacidosis / lactic acidosis)
3. Dehydration
4. **Diuretics
5. HT
6. ***Hyperparathyroidism
7. Drugs (cyclosporine, pyrazinamide, ethambutol, low-dose aspirin)
8. Lead nephropathy
Overproduction + Underexcretion of urate
- ***Alcohol use
- ***G6PD deficiency
- ***Fructose-1-phosphate-aldolase deficiency
***Management of gout
Objectives:
1. Rapid + safe pain relief
2. Prevent further attacks
3. Prevent formation of tophi / destructive arthritis
4. Address associated medical conditions
Drugs:
Acute attacks
1. ***Oral Indomethacin (widely used) (COX-1 selective)
- aspirin, salicylate should be avoided (↓ effect of uricosuric agents)
- ***COX-2 selective inhibitors (recent GI bleeding / high GI risk)
- Etoricoxib -
**Colchicine
- diagnostic + therapeutic value but narrow margin between therapeutic and doses
- but **slow onset of action - Steroid (2nd line)
- intra-articular / oral / parenteral (e.g. IM) - Anti-IL1 (2nd line)
- Anakinra, Canakinumab (injection)
Long term management (prevent recurrent attacks)
(SpC Medicine + Blue book: Initiate when
- **>=2 attacks within 1 year
- **Tophaceous disease
- **Coexistent / Past history of renal impairment
- **Urolithiasis)
1. **Allopurinol
- **Xanthine oxidase inhibitor
- usual dose: 300mg daily
- but higher dose may be used in severe cases, smaller dose in renal insufficiency
- SE: severe skin reaction: **SJS (HLA-B5801)
-
**Probenecid / Sulphinpyrazone
- **Uricosuric agents —> ↑ uric acid excretion
- CI in:
—> primary overproduction of uric acid
—> gross hyperuricosuria
—> evidence of urolithiasis
—> renal insufficiency - Febuxostat
- Selective Xanthine oxidase / Xanthine dehydrogenase inhibitor
- fewer severe skin reactions but relatively CI in ***liver impairment - Newer urate lowering drugs
- Pegloticase: recombinant uricase (Uricolytic agent) (changes urate to allantoin: more soluble than urate —> easier to excrete) (G6PD haemolysis)
- Lesinurad: URAT1 inhibitor —> ↓ reabsorption of urate from proximal tubules - Low purine diet (CL Lai)
- Avoid alcohol, shellfish (e.g. mussels), liver, tuna, salmon, mushrooms, strawberry - Avoid high fructose drink (e.g. soft drinks) (SpC FM)
Colchicine (From MSS21)
Clinical applications:
- ↓ inflammation during gouty attack
- prophylaxis of gout flare with urate-lowering therapy
MOA:
**Reduce phagocytosis of urate
1. Inhibit **Tubulin polymerization into microtubules
—> inhibit leukocyte migration and phagocytosis
2. Inhibit ***Leukotriene B4 formation
—> ↓ inflammatory response
Adverse effects (**inhibit cell division in fast-growing cells: GI tract):
- **Diarrhoea
- **N+V, **abdominal pain
- Hepatic necrosis, acute renal failure, DIC
- Seizures
- Hair loss
- ***Bone marrow depression
—> IV not accepted now
—> Lower dose recommended:
Acute relief: 1.2mg followed by 0.6mg after an hour
Prophylaxis: 0.6mg OD-TDS
—> ↓ dose / less frequent in hepatic / renal disease
Xanthine oxidase inhibitors DDI
Allopurinol / Febuxostat should NOT be co-prescribed with **Azathioprine
—> interfere with metabolism of Azathioprine (via **TPMT (SpC Medicine))
—> ↑ 6MP plasma level
—> potentially fatal blood ***dyscrasias
Careful monitoring of patients ***CBC if both drugs have to be prescribed
Principles of Long-term drug treatment of gout (e.g. Xanthine oxidase inhibitor, Uricosuric agents)
- NOT to be started until acute attack has completely subsided
- may exacerbate attack (Gout flare) - Co-administration with **prophylactic Colchicine / NSAID during first **3 months to prevent “breakthrough” attacks
- Serious toxic reactions may occur (although rare)
- **Toxic epidermal necrolysis + Vasculitis (Allopurinol)
- **Nephrotic syndrome (Probenecid)
- Hepatitis, ***BM suppression (both)
—> carefully monitor - Hypouricaemic agents considered when (Xanthine oxidase inhibitor / Uricosuric agents)
- **Recurrent + troublesome acute attacks
- **Evidence of tophi / chronic joint damage
- In presence of renal disease
- Young patient, high urate level, family history of renal / heart disease
- Evidence of primary purine overproduction + underexcretion
Pitfalls on gout
- High serum urate + arthritis =/= Gout
- Arthritis but low serum urate =/= Not gout
- defined by deposition in joint
- may not always be associated with hyperuricaemia - Great toe arthritis =/= gout
- ***hallux rigidis / hallux valgus more common - Allopurinol not indicated in all gout cases
- proper diet change, adequate hydration, reduction in alcohol consumption —> allopurinol may not be needed
Calcium pyrophosphate deposition disease (CPPD)
Aka **Chondrocalcinosis, **Pseudogout
- present in 6% of individuals >72 yo
- M:F = 1.4:1
- incidence ↑ with age
- incidence of symptomatic disease ~50% of gout
Clinical presentation:
1. Asymptomatic (most patients)
2. May mimic gout, RA, OA, septic arthritis, rarely ankylosing spondylitis (CPPD crystals deposit in intervertebral discs)
3. ***Knees most commonly affected
(From MSS15:
2 presentations:
1. Acute synovitis (mimic gout)
- ***Pseudogout
- Superimposed on chronic arthropathy
- elderly women
- Chronic pyrophosphate arthropathy (mimic OA)
- unlike OA commonly affect Radiocarpal, Glenohumeral, Midtarsal joints (**Atypical joints)
- Deposition of **rhomboidal CPP crystals (different crystal shape than urate crystal) from cartilage into joint space
(Normally:
- ATP from cells –> pyrophosphate + AMP; pyrophosphate –> inorganic phosphate by alkaline phosphatase
- under influence of growth promoting factors pyrophosphate complexes with Ca to form crystals)
X-ray:
Calcification of knee cartilage (Chondrocalcinosis) + Menisci
CPPD often **associated with OA
- OA contains replicating / damaged cells which **release ATP
- changes in cartilage matrix also interfere with growth factors (trigger Ca + pyrophosphate —> CPP crystal))
Causes of CPPD disease
- ***Hereditary
- Sporadic (***Idiopathic)
- Probable metabolic disease associations
- **Hyperparathyroidism
- Haemachromatosis
- **Hypothyroidism
- Gout
- HypoMg
- Hypophosphatasia
- Ageing
Treatment of CPPD disease
- Asymptomatic
- NOT require treatment - Acute attacks
- **Treat as per gout (milder than gout)
- NSAIDs, COX-2 inhibitors, Colchicine
- Thorough **aspiration may be effective - NOT possible to remove CPPD crystals once deposited in cartilage
- Treatment of underlying associated disease may NOT improve long term prognosis
Haemarthrosis
Causes:
1. **Trauma
2. **Congenital Haemophilia (Factor 8 / 9 deficiency)
3. Acquired Haemophilia (AutoAb)
3. Drugs (Warfarin, Heparin)
S/S:
1. Pain
2. Swelling
3. Stiffness
Diagnosis:
- Arthrocentesis (i.e. Joint aspiration)
—> Viscosity: Low
—> Colour: Bloody
—> Clarity: Blood-like
—> WBC: similar to blood level
—> PMN leukocytes: similar to blood level
Treatment:
- Treat underlying cause
Summary
Acute monoarthritis:
- Semi-emergency
- ***Septic arthritis until proven otherwise
Important investigations:
- Joint aspiration with synovial fluid analysis for **WBC, **Gram’s stain, **culture, **crystal
- Bacterial septic arthritis should be treated promptly with antibiotics according to culture sensitivity
- Surgical intervention indicated in some patients —> always get OT surgeon informed
- Acute crystal deposition arthritis: treated symptomatically with NSAIDs, Corticosteroid, Colchicine
- Implement long term prevention treatment in patients with recurrent attacks of gouty arthritis
- Definitive diagnosis of Haemarthrosis: Joint aspiration —> Treatment: treat underlying cause
