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Step 2 CK · Internal Medicine · Rheumatology

Acute Monoarthritis & Synovial Fluid Analysis

Tap first, read the fluid, and never let crystals talk you out of infection

Rheumatology·Crystal, Degenerative & Soft-Tissue Disorders·6 min read·9 high-yield points·Reviewed by Veli Bakalov, MD @HemeOncBuddy
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Approach to the acute hot joint

Framing. Acute monoarthritis, a single joint that becomes warm, swollen and painful over hours to days, is bacterial septic arthritis until proven otherwise. Infection can destroy cartilage within days, and mortality approaches 10%. The main alternatives are gout, calcium pyrophosphate deposition (CPPD), trauma or hemarthrosis, reactive and Lyme arthritis, and a first presentation of inflammatory arthritis.

Joint or periarticular? True synovitis causes an effusion and limits and hurts through the whole passive arc. Bursitis, tendinitis and cellulitis cause localized tenderness but largely spare passive motion.

  1. Arthrocentesiscell count with differential, Gram stain, culture, polarized-light crystal exam
  2. Blood culturesplus CBC and inflammatory markers; mucosal NAATs if gonococcal infection is possible
  3. Empiric antibioticsimmediately after the tap when infection is plausible, chosen by the Gram stain
  4. Drainageserial needle aspiration or arthroscopic or open washout
  5. Tailornarrow therapy to culture and susceptibility results

Timing. Aspirate before antibiotics, because prior antibiotics can sterilize cultures, but never let the tap delay therapy in a septic-appearing patient. The hip usually needs ultrasound or fluoroscopic guidance, therapeutic anticoagulation is generally not a contraindication, and suspected prosthetic joint infection goes to orthopedics.

Never pass the needle through cellulitis or other infected overlying skin: it can seed the joint. Use an alternate approach or ultrasound guidance.

Reading the synovial fluid

The WBC ladder. Normal fluid has fewer than 200 WBC/µL. The count, the neutrophil percentage and the gross appearance place fluid into broad categories, and the higher the count, the more likely infection becomes.

Synovial fluid categories
CategoryAppearanceWBC/µLTypical causes
NormalClear, viscous<200None
NoninflammatoryClear yellow, viscous<2000, few neutrophilsOsteoarthritis, trauma
InflammatoryCloudy yellow, low viscosity2000–50,000, mostly neutrophilsGout, CPPD, RA, spondyloarthritis, reactive and Lyme arthritis
SepticOpaque, purulentUsually >50,000, >90% neutrophilsBacterial infection
HemorrhagicBloody or brownVariableTrauma, anticoagulants, hemophilia, PVNS
Cutoffs are guides, not rules; the categories overlap.
>50,000/µLsynovial WBC that makes infection likely, especially with >90% neutrophils
<2000/µLnoninflammatory fluid (osteoarthritis, trauma)

Overlap. Early, gonococcal, partially treated or immunosuppressed septic joints can have fewer than 50,000 cells, and an intense gout flare can exceed 50,000. The diagnosis of infection rests on Gram stain and culture, not on the count alone.

Crystals and bacteria can coexist: a gouty or CPPD joint can also be infected. Gram stain and culture every hot joint, and treat empirically while cultures are pending when suspicion is high.

Crystal identification

Technique. Fresh fluid is examined under compensated polarized light; color depends on crystal orientation relative to the red compensator's slow axis.

Urate versus calcium pyrophosphate crystals
FeatureMonosodium urate (gout)Calcium pyrophosphate (CPPD)
ShapeNeedleRhomboid or rod
BirefringenceStrongly negativeWeakly positive
Color when parallelYellow (blue when perpendicular)Blue (yellow when perpendicular)
AbundanceNumerous, often inside neutrophilsSparse, easily missed
Typical jointsFirst MTP (podagra), midfoot, ankle, kneeKnee, wrist
ImagingPunched-out erosions with overhanging edges in chronic goutChondrocalcinosis of menisci, wrist triangular fibrocartilage, pubic symphysis
Mnemonic ABC: Aligned (parallel) + Blue = Calcium pyrophosphate.

Serum urate. Serum urate can be normal or even low during an acute flare, so it neither confirms nor excludes gout; seeing urate crystals is diagnostic. Recheck urate at least 2 weeks after the flare settles. Thiazide and loop diuretics raise urate and can precipitate flares. Once crystals are found and infection is unlikely, the flare is treated with an NSAID, colchicine or a glucocorticoid.

CPPD in younger patients. Pseudogout is mainly a disease of older adults. CPPD before about age 55, or unusually florid polyarticular disease, should prompt a search for the 4 H's: hemochromatosis (ferritin, transferrin saturation), hyperparathyroidism (calcium, PTH), hypomagnesemia (serum magnesium) and hypophosphatasia (low alkaline phosphatase). Familial CPPD is another cause.

Bloody fluid and fat globules

Hemarthrosis. Bloody fluid suggests trauma (the ACL tear is the classic cause of acute traumatic knee hemarthrosis, and fractures are another), anticoagulant therapy, hemophilia or another coagulopathy, or pigmented villonodular synovitis (PVNS). Coagulation studies separate hemophilia (prolonged aPTT) from local causes.

PVNS. Also called tenosynovial giant cell tumor, this benign proliferative synovial neoplasm of young adults usually affects the knee and causes recurrent atraumatic brownish-bloody effusions. MRI shows nodular synovial thickening with hemosiderin that "blooms" as low signal. Treatment is synovectomy.

Lipohemarthrosis. Fat globules floating on bloody fluid mean marrow fat has entered the joint through an intra-articular fracture, such as of the tibial plateau. A cross-table lateral radiograph shows a fat–fluid level, and CT finds fractures that plain films miss.

Septic arthritis

Nongonococcal infection. S. aureus, including MRSA, is the most common cause, followed by streptococci; gram-negative rods affect older, immunosuppressed and injection-drug-using patients, and drug users also get Pseudomonas and sternoclavicular or sacroiliac infection. Risk factors include age over 80, RA, a prosthetic joint, diabetes, recent joint surgery or injection, and skin infection. The knee is involved in about half of cases and fever may be absent.

Disseminated gonococcal infection. Sexually active young adults, more often women, present with the triad of wrist and hand tenosynovitis, migratory polyarthralgia and a few painless vesiculopustules, or with purulent monoarthritis (often the knee) without skin lesions. Cultures are often negative, so NAATs of the urethra or cervix, pharynx and rectum make the diagnosis. Treat with ceftriaxone 1 g IV daily, stepping down after improvement to complete at least 7 days; add doxycycline if chlamydia is not excluded, and test for HIV and syphilis. Recurrent neisserial infection suggests terminal complement (C5–C9) deficiency.

Gonococcal versus nongonococcal septic arthritis
FeatureGonococcalNongonococcal
HostYoung, sexually activeOlder, RA, prosthesis, diabetes, injection drug use
PatternMigratory polyarthralgia, tenosynovitis, pustules; or purulent kneeSingle hot joint, often knee
DiagnosisCultures often negative; mucosal NAATsSynovial culture usually positive; blood cultures in about half
TreatmentCeftriaxone; surgery rarely neededVancomycin with or without a cephalosporin, plus drainage

Empiric antibiotics. Start IV therapy right after the tap and let the Gram stain choose it: gram-positive cocci call for vancomycin; gram-negative rods for a third-generation cephalosporin (ceftazidime or cefepime when Pseudomonas is a risk); and a negative Gram stain for vancomycin plus ceftriaxone. Narrow once cultures and susceptibilities return.

Drainage. Antibiotics alone are not enough: pus is removed by repeated needle aspiration or arthroscopic or open washout. Hip and prosthetic joints, loculated collections and failure to improve with serial aspiration require surgery. Follow effusion size and repeat synovial counts and cultures.

Other diagnoses to keep in mind

Lyme arthritis. In an endemic area, weeks to months after a tick bite, a large and relatively painless knee effusion appears, often recurring in episodes. The fluid is inflammatory, two-tier serology is positive at this stage, and treatment is 28 days of oral doxycycline, amoxicillin, or cefuroxime. Arthritis that persists after an oral course gets a second oral course or IV ceftriaxone for 2 to 4 weeks.

Reactive arthritis. An asymmetric lower-limb oligoarthritis follows enteric (Salmonella, Shigella, Campylobacter, Yersinia) or chlamydial infection by about 1–4 weeks, often in HLA-B27-positive patients, with conjunctivitis, urethritis or enthesitis.

Early inflammatory arthritis. Monoarthritis can be the first sign of RA, psoriatic arthritis or spondyloarthritis. Chronic monoarthritis with negative routine cultures calls for mycobacterial and fungal cultures or a synovial biopsy.