STEPTRACKERMUSCULOSKELETAL | PATHOLOGY + BIOCHEMISTRY + PHARMACOLOGY | HIGH-YIELD REVIEW

Crystal & Infectious Arthritis

The hot swollen joint — tap it, look for crystals and count the cells.

FOCUS ON
Gout: monosodium urate, needle-shaped, negatively birefringent; big toe, after alcohol or a feast; tophi; underexcretion > overproduction. Pseudogout: CPPD, rhomboid, positively birefringent; knee, chondrocalcinosis; hemochromatosis, hyperparathyroidism. Septic arthritis: S aureus; gonococcus in sexually active young adults. Synovial WBC > 50,000 → treat as septic.
DISORDER
MECHANISM · CAUSE
FEATURES
CLUE · TREATMENT
Hyperuricemia — underexcretion
most common
↓ renal urate clearance
CKD, thiazide and loop diuretics, low-dose aspirin, alcohol, ketoacidosis, lead, cyclosporine
Normal urine uric acid
Hyperuricemia — overproduction
↑ purine turnover or synthesis
Tumor lysis, myeloproliferative disease, psoriasis, Lesch-Nyhan (HGPRT), PRPP synthetase overactivity, von Gierke
↑ urine uric acid
Acute gout
Urate crystals activate the NLRP3 inflammasome → IL-1β → neutrophils
Sudden very painful red swollen joint, often 1st MTP (podagra) at night; after alcohol, meat/seafood, fructose, dehydration, surgery
Needle-shaped, negatively birefringent (yellow when parallel)
Chronic tophaceous gout
Urate deposits surrounded by foreign-body giant cells
Tophi (ear, olecranon, Achilles, fingers); "rat-bite" erosions with overhanging edges; urate nephropathy, uric acid stones
Chalky white material
Gout — acute treatment
Stop inflammation
NSAIDs (indomethacin), colchicine (blocks neutrophil microtubules), glucocorticoids
Avoid NSAIDs in CKD
Gout — prevention
Lower uric acid
Allopurinol/febuxostat (xanthine oxidase), probenecid (uricosuric; ↑ stones), pegloticase (uricase)
Allopurinol + azathioprine/6-MP → toxicity · HLA-B*58:01 → SJS
Pseudogout (CPPD)
Calcium pyrophosphate crystals; older adults; hemochromatosis, hyperparathyroidism, hypomagnesemia, hypothyroidism, hypophosphatasia
Acute knee or wrist arthritis; chondrocalcinosis on X-ray
Rhomboid, weakly positively birefringent (blue when parallel)
Septic arthritis
Hematogenous or direct; S aureus most common; streptococci, gram-negatives (IVDU, elderly)
Single hot swollen joint (knee, hip in children), fever, can't move it
Synovial WBC > 50,000 neutrophils · drain + antibiotics
Disseminated gonococcal infection
N gonorrhoeae bacteremia in sexually active young adults
Migratory polyarthralgia, tenosynovitis (wrists, hands), scattered pustular skin lesions → or purulent monoarthritis
Ceftriaxone · culture all mucosal sites
Lyme arthritis
Borrelia burgdorferi (Ixodes tick); late stage
Intermittent large-joint (knee) monoarthritis months after erythema migrans
Doxycycline or ceftriaxone
Prosthetic joint infection
Biofilm on hardware
Early: S aureus · late: S epidermidis, Cutibacterium
Often needs revision

Mechanism — purines to gout

PurinesFood, cell turnover
→
Hypoxanthine → xanthine
→
Uric acidXanthine oxidase (allopurinol)
→
Urate crystalsCool, acidic joints
→
NLRP3 → IL-1βNeutrophil storm (colchicine)

Starting urate-lowering therapy can mobilize crystals and trigger flares — cover with colchicine or an NSAID.

Synovial fluid

TYPE
WBC/µL
% PMN
EXAMPLES
Normal
< 200
< 25%
—
Noninflammatory
200–2,000
< 25%
Osteoarthritis, trauma
Inflammatory
2,000–50,000
> 50%
Gout, pseudogout, RA, reactive
Septic
> 50,000
> 75%
Bacterial infection
Hemorrhagic
RBCs
—
Trauma, hemophilia

How it's tested

COMMON CONFUSIONGout: Negative birefringence, Needles. Pseudogout: Positive birefringence, Polygonal/rhomboid. Yellow-parallel = urate; blue-parallel = CPPD.
THE TRAPCrystals don't rule out infection — gout and septic arthritis can coexist. Very high WBC means culture and treat for infection anyway.
YOUR APPROACHHot joint → aspirate → cell count, Gram stain, culture, crystals → cause → acute treatment → long-term prevention (urate lowering, treat hemochromatosis, partner treatment).

If you see… think…

Middle-aged man, red hot big toe after a night of beer and steak → gout
Needle-shaped crystals, yellow when parallel to the compensator → monosodium urate
Gout flare after starting hydrochlorothiazide → diuretic-induced hyperuricemia
Chalky nodules on the ear helix → tophi
Boy with self-biting, dystonia and gout → Lesch-Nyhan (HGPRT)
Older woman with knee arthritis and rhomboid crystals → pseudogout (CPPD)
Young man with CPPD arthritis and bronze skin → hemochromatosis
Synovial WBC 85,000, mostly neutrophils → septic arthritis
Sexually active woman with wrist tenosynovitis and pustules → disseminated gonococcal infection
Hiker with recurrent knee swelling months after a bull's-eye rash → Lyme arthritis