Synovial fluid analysis

Four questions

*The single most informative test in any acute arthritis* - and the one most often omitted
Four questions, answered simultaneously
- Is it infected? - cell count, Gram stain, culture
- Is it crystal? - polarised light microscopy
- Is it inflammatory? - cell count and differential
- Is it blood? - haemarthrosis
Normal synovial fluid: <3.5 mL, clear, pale yellow, viscous (hyaluronan), <200 cells/microL, no crystals, glucose ~ serum

Septic arthritis incidence ~4-10 per 100,000/yr; *mortality ~10-15%, and joint destruction within days*
*Gram stain is positive in only ~30-50%* of culture-proven septic arthritis
Synovial culture positive in ~70-90%; blood cultures positive in ~50%
Crystals and infection coexist in up to 5% of septic joints - finding crystals never excludes sepsis

Inflammation -> inc vascular permeability -> protein-rich exudate + neutrophil influx
Hyaluronan is degraded by inflammation -> viscosity falls (the "string sign" is lost - fluid drips rather than strings)
Bacterial proteases and neutrophil elastase -> cartilage matrix degradation within 24-48 h - the reason septic arthritis is an emergency
Crystals
- Monosodium urate - needle-shaped, from supersaturated urate
- Calcium pyrophosphate dihydrate - rhomboid, from pyrophosphate metabolism in cartilage
- Basic calcium phosphate (hydroxyapatite) - not birefringent; needs alizarin red staining

*Aspirate BEFORE antibiotics or corticosteroid* - unless it would unacceptably delay treatment in a septic patient
*NEVER aspirate through overlying cellulitis* - seeds a sterile joint
Prosthetic joint: aspirate in theatre or under orthopaedic supervision
Send: cell count + differential, Gram stain, culture (inoculate blood-culture bottles as well), polarised light microscopy
- Add gonococcal and mycobacterial NAAT/culture, fungal culture where indicated
Two sets of blood cultures before antibiotics

WCC (cells/microL)	Category	Causes
<200	Normal
200-2,000	Non-inflammatory	OA, trauma, AVN, Charcot, hypothyroidism
2,000-50,000 (some report to 75,000)	Inflammatory	Crystal, RA, spondyloarthritis, reactive, viral, SLE - and early or partially treated SEPSIS
>50,000, neutrophils >90%	*SEPTIC until proven otherwise*	Bacterial; also severe crystal arthritis
Bloody	Haemarthrosis	Trauma, anticoagulation, haemophilia, PVNS, Charcot, tumour

*No cell count reliably excludes sepsis*
- Gout regularly exceeds 50,000; septic arthritis can present below 20,000 in the immunosuppressed, in gonococcal disease, in prosthetic joints and after partial antibiotic treatment
Prosthetic joints use much lower thresholds: >3,000/microL with >80% neutrophils suggests infection
Lipid droplets / fat globules = intra-articular FRACTURE

Appearance	Meaning
Clear, straw, viscous	Normal or non-inflammatory
Translucent yellow, reduced viscosity	Inflammatory
Opaque, purulent, thick	Septic
Bloody	Haemarthrosis
Blood with a supernatant fat layer	Intra-articular fracture
Milky white	Chylous, or heavy crystal load

	Monosodium urate (gout)	CPPD (pseudogout)
Shape	Needle-shaped	Rhomboid / rod
Birefringence	*NEGATIVELY birefringent*	*Weakly POSITIVELY birefringent*
Colour when parallel to the compensator axis	YELLOW	BLUE
Position	Often intracellular in an acute attack	Often extracellular

*Mnemonic: "ABC" - Aligned/parallel, Blue, Calcium (CPPD)***; urate is the opposite
Intracellular crystals confirm the crystal is causing THIS attack; extracellular crystals may be incidental
Basic calcium phosphate is non-birefringent - suspect it in Milwaukee shoulder and calcific periarthritis

*Synovial glucose, protein, LDH and "rheumatoid factor in fluid" add nothing* - do not order them
Synovial lactate and alpha-defensin are used in prosthetic joint infection algorithms, not native joints

>50,000 with neutrophil predominance, or a positive Gram stain
- Empirical IV antibiotics immediately after cultures - flucloxacillin, plus vancomycin if MRSA risk, severe sepsis or penicillin allergy; add Gram-negative cover in the elderly, IVDU or immunosuppressed
- Urgent orthopaedic referral for washout or serial aspiration - antibiotics alone do not clear a purulent native joint
- Ceftriaxone if gonococcal disease is possible (plus doxycycline, contact tracing, mucosal-site NAATs - joint fluid is often culture-negative)
Crystals seen, sepsis excluded -> NSAID, colchicine, or corticosteroid (intra-articular where a single accessible joint)
- *Do not start, stop or change urate-lowering therapy during a flare* - continue existing therapy
- CPPD -> symptomatic treatment, plus a metabolic screen if young or recurrent: calcium, PTH, magnesium, ferritin/transferrin saturation, ALP, TSH
Inflammatory, no crystals, no organism -> look for spondyloarthritis, RA, reactive, viral; treat empirically for sepsis while cultures are pending if the picture is at all septic
Non-inflammatory -> OA, trauma, internal derangement -> imaging, analgesia, physiotherapy
Haemarthrosis -> reverse anticoagulation, factor replacement in haemophilia, image for fracture, orthopaedic review

Septic arthritis - **Staphylococcus aureus commonest at all ages; streptococci; Gram negatives in the elderly, IVDU and immunosuppressed; gonococcus in young sexually active adults**
Prosthetic joint infection - coagulase-negative staphylococci, *Cutibacterium acnes*; different thresholds and pathway
Rheumatoid arthritis - *septic arthritis is commoner, often polyarticular, and routinely dismissed as "a flare"*
Gout - alcohol, diuretics, CKD, obesity, transplant drugs (ciclosporin)
CPPD - ageing; *in a younger patient screen for haemochromatosis, hyperparathyroidism, hypothyroidism, hypomagnesaemia, hypophosphatasia*
Haemophilia, anticoagulation, pigmented villonodular synovitis, Charcot joint
TB and fungal arthritis - indolent, monoarticular, immunosuppressed or endemic exposure

*Untreated septic arthritis destroys cartilage within days and causes irreversible joint damage in up to 40-50%* even when treated
Mortality ~10-15%, higher with polyarticular sepsis, age, RA and comorbidity
Repeat aspiration is used to follow response - falling cell count and sterile cultures
Crystal arthritis resolves over days to weeks with treatment; chondrocalcinosis on an old X-ray does not prove the current attack is CPPD
Culture-negative septic arthritis is common after prior antibiotics - *treat clinically; do not be reassured by a negative culture after antibiotics were given*

11 more sections, plus exam facts

Premium unlocks every note across every specialty, and the full exam fact library behind it.