Crystal Arthritis & Gout Management
Needle vs rhomboid crystals, the target of 6, and why allopurinol waits
Two crystals, two arthritides
Framework. Gout (monosodium urate, MSU) and pseudogout (calcium pyrophosphate deposition, CPPD) both cause an acute inflammatory monoarthritis that can mimic septic arthritis. Polarized light microscopy of the synovial fluid separates them.
| Feature | Gout (MSU) | Pseudogout (CPPD) |
|---|---|---|
| Crystal shape | Needle | Rhomboid |
| Birefringence | Negative | Positive |
| Parallel to compensator | Yellow | Blue |
| Typical joints | First MTP (podagra), midfoot, ankle, knee | Knee, wrist |
| Imaging | Punched-out erosions with overhanging edges; tophi | Chondrocalcinosis |
| Long-term therapy | Urate lowering | No urate lowering; treat any underlying cause |
Gout: pathophysiology, flares and diagnosis
Supersaturation. Above about 6.8 mg/dL, urate supersaturates and deposits as MSU crystals. Roughly 90% of hyperuricemia comes from renal UNDERexcretion and 10% from overproduction (myeloproliferative disease, tumor lysis, Lesch-Nyhan syndrome). Most hyperuricemic people never develop gout, and asymptomatic hyperuricemia is not treated.
Podagra. The classic first attack strikes the first metatarsophalangeal joint, often overnight: red, hot, swollen and exquisitely tender. Untreated, attacks become more frequent, polyarticular and chronic.
Triggers. Purine-rich food (red meat, organ meat, shellfish), alcohol (beer more than spirits), high-fructose drinks, dehydration, and thiazide or loop diuretics. Starting OR stopping urate-lowering therapy can also precipitate a flare by shifting urate.
Thiazides and low-dose aspirin raise urate; losartan and fenofibrate are mildly uricosuric, so losartan is a sensible antihypertensive in gout.
Diagnosis. Arthrocentesis is definitive: needle-shaped, negatively birefringent MSU crystals, often inside neutrophils, with synovial WBC in the inflammatory range (about 2,000–50,000/μL). Send Gram stain and culture too, because crystals and infection can coexist. Serum uric acid can be NORMAL during an acute attack, so it cannot rule gout in or out; recheck it after the flare settles.
Tophi. Firm nodular urate deposits of longstanding gout collect at the helix of the ear, the olecranon bursa, the Achilles tendon and the finger pads. They signal chronic under-treatment and are themselves an indication for urate-lowering therapy.
Treating the acute flare
| Agent | Use | Cautions |
|---|---|---|
| NSAIDs (e.g., indomethacin) | Full dose early, then taper | CKD, peptic ulcer disease, heart failure, anticoagulation |
| Colchicine | Best within 24 hours of onset | Renal or hepatic impairment; CYP3A4 and P-glycoprotein inhibitors; diarrhea |
| Glucocorticoids | Oral, or intra-articular for one or two joints | Preferred in CKD, where NSAIDs and colchicine are risky; exclude infection before injecting |
Do NOT start allopurinol in the middle of a flare by traditional teaching, but CONTINUE it if the patient already takes it. The 2020 ACR guideline does allow starting urate-lowering therapy during a flare under anti-inflammatory cover; stopping ongoing therapy is never correct.
Colchicine pharmacology. Colchicine inhibits microtubule polymerization, blocking neutrophil chemotaxis and NLRP3 inflammasome activation. Diarrhea and GI upset are dose-limiting, and overdose causes myelosuppression. It also treats familial Mediterranean fever and recurrent pericarditis.
Long-term urate lowering
Indications. Start urate-lowering therapy (ULT) for tophi, radiographic damage from gout, or 2 or more flares per year (ACR 2020). After a first flare, start it only with CKD stage 3 or worse, serum urate above 9 mg/dL, or urolithiasis. CKD or hyperuricemia without gout flares is not an indication. Titrate to a serum urate target UNDER 6 mg/dL (under 5 with tophi). ULT is lifelong.
- Acute flareNSAID, colchicine or steroid
- Do not stop ULTcontinue allopurinol if already on it
- Start ULTfor 2 or more flares a year, tophi or radiographic damage, classically once the flare settles
- Titrate to urate under 6with colchicine prophylaxis for 3–6 months
| Drug | Mechanism | Key points |
|---|---|---|
| Allopurinol | Xanthine oxidase inhibitor | First line; start low and titrate; HLA-B*58:01 predicts SJS/TEN, so screen Southeast Asian and African American patients first |
| Febuxostat | Non-purine xanthine oxidase inhibitor | Option in allopurinol allergy; cardiovascular mortality signal (CARES trial), so switch to another agent with a CVD history or a new CV event |
| Probenecid | Uricosuric | Underexcreters with good renal function; avoid with kidney stones |
| Pegloticase | Recombinant uricase | Refractory tophaceous gout; avoid in G6PD deficiency (hemolysis) |
Xanthine oxidase inactivates 6-mercaptopurine, so allopurinol plus azathioprine or 6-MP causes dangerous marrow toxicity.
Prophylaxis. When starting ULT, co-prescribe low-dose colchicine (or an NSAID) for 3–6 months, because mobilizing urate paradoxically triggers flares.
Pseudogout (CPPD disease)
Presentation. Typically an older adult with an acutely swollen knee or wrist. Radiographs show chondrocalcinosis, linear calcification of cartilage in the knee, wrist and pubic symphysis, and aspiration shows rhomboid, positively birefringent crystals.
Secondary causes. Hemochromatosis, hyperparathyroidism, hypomagnesemia and hypophosphatasia. Work up young or recurrent CPPD with iron studies, calcium and PTH, magnesium and alkaline phosphatase.
Treatment. Treat flares like acute gout with NSAIDs, colchicine or glucocorticoids after excluding infection; there is no urate-lowering equivalent.