Gout & Pseudogout

Acute gout flare: sudden onset, often overnight, peaking within 6-12 hours. The joint is intensely painful, hot, tense, shiny, and erythematous, and can mimic cellulitis. First presentations are typically monoarticular and around 50% involve the 1st MTP (podagra); other sites include the ankle, midfoot, knee, wrist, fingers, and olecranon bursa. Polyarticular gout occurs in chronic disease and the elderly. Flares are self-limiting in 1-2 weeks untreated. Low-grade fever is common; high fever with rigors raises concern for septic arthritis. Common precipitants: alcohol, purine-rich food, dehydration, acute illness, surgery, trauma, ULT initiation (mobilisation flare), and diuretic initiation.

Intercritical gout is asymptomatic, but crystals remain; without ULT, flares grow more frequent and become polyarticular. Chronic tophaceous gout features tophi over the ear helix, olecranon, fingers, Achilles, and 1st MTP, with chronic erosive joint destruction mimicking RA. Tophi may ulcerate and discharge chalky material.

Acute CPP crystal arthritis ('pseudogout') most commonly affects the knee (over 50%), in contrast to gout''s predilection for the 1st MTP. Other sites: wrist, ankle, shoulder. It predominantly affects the elderly and is often triggered by acute illness, surgery, or metabolic disturbance.

Chronic CPP inflammatory arthritis ('pseudo-RA'): symmetrical polyarthritis of wrists, MCPs, and knees with negative RF and anti-CCP, and chondrocalcinosis on X-ray.

OA at atypical joints (wrist, MCP, shoulder, patellofemoral) with chondrocalcinosis points to CPPD with or without haemochromatosis.

Crowned dens syndrome: acute neck pain and stiffness with raised inflammatory markers from CPP deposition around the odontoid; CT shows peri-odontoid calcification. Mimics meningitis, septic arthritis, and PMR/GCA in an elderly patient and responds to anti-inflammatory treatment.

NICE NG219 (2022) permits clinical diagnosis of gout in typical presentations. Aspiration is the reference standard when confirmation is needed, diagnosis is uncertain, or septic arthritis is in the differential.

Joint aspiration: send synovial fluid for crystal analysis under polarised light microscopy (MSU: needle-shaped, negatively birefringent; CPP: rhomboid, weakly positively birefringent), cell count (WCC >50,000/mm3 with neutrophil predominance suggests septic arthritis, with some overlap), Gram stain, and culture (always send - coexistence occurs). False-negative microscopy is recognised, particularly for CPP.

Serum urate: measure during the acute flare per NICE NG219. If elevated (>=360 micromol/L), supports the diagnosis. Urate can be falsely normal in up to 40% of flares because of inflammatory redistribution; if normal but gout is still clinically suspected, repeat at 2-4 weeks. A normal urate during a flare does NOT exclude gout. Serum urate is essential for guiding and monitoring ULT.

Other bloods: CRP/ESR, FBC, renal and liver function, lipid profile, and HbA1c (metabolic syndrome screening). CPPD metabolic screen in younger, atypical, recurrent, or severe disease: calcium and PTH (hyperparathyroidism), ferritin and transferrin saturation (haemochromatosis), magnesium, and ALP (hypophosphatasia).

Imaging:

• •X-ray gout: 'punched-out' erosions with overhanging sclerotic margins; preserved adjacent bone density; joint space preserved until late. Often normal in early disease.
• •X-ray CPPD: chondrocalcinosis (linear cartilage calcification - menisci, TFCC, symphysis pubis). Incidental chondrocalcinosis is common in the elderly and does not prove causation.
• •USS in gout: double-contour sign (hyperechoic line on the cartilage surface), tophi, and aspiration guidance.
• •Dual-energy CT (DECT): highly specific for MSU crystal deposition; useful in atypical or chronic disease (specialist centres).
• •CT: peri-odontoid calcification in crowned dens syndrome.

The 2015 ACR/EULAR classification criteria for gout combine clinical pattern, serum urate, and imaging (USS double-contour or DECT) into a weighted score for research and atypical cases.

NICE NG219 (2022) anchors UK practice. Gout management has two arms: the acute flare and urate-lowering therapy (ULT). There is no disease-modifying treatment for CPPD.

Acute gout flare - first-line options, chosen by comorbidity:

• •Colchicine 500 microg two to four times daily until the flare resolves. Start early. Dose-reduce in CKD (toxicity risk); significant interactions with macrolides and ciclosporin.
• •NSAIDs at maximum dose with PPI cover. Short course. Avoid in significant CKD, heart failure, peptic ulcer, or anticoagulation. Not aspirin (reduces urate excretion).
• •Corticosteroids: oral prednisolone 30-35 mg for 5 days (no taper), intra-articular injection (single accessible joint, diagnostic and therapeutic), or intramuscular triamcinolone when oral route is unsuitable or several joints are involved.
• •IL-1 inhibitors (anakinra) when NSAIDs, colchicine, and steroids are all contraindicated, not tolerated, or ineffective (specialist).
• •If already on ULT, continue it during the flare. NICE NG219 permits ULT initiation during a flare if flares are frequent, provided anti-inflammatory cover is established.

ULT indications: offer to patients with multiple or troublesome flares, tophi, chronic gouty arthritis, CKD stages 3-5, or diuretic therapy that cannot be stopped. NICE NG219 encourages discussion with all patients after diagnosis.

First-line ULT: NICE NG219 offers EITHER allopurinol OR febuxostat as first-line.

• •Allopurinol (xanthine oxidase inhibitor): start low (100 mg daily; 50 mg if eGFR <30) and titrate every 2-4 weeks to target. Specifically preferred in patients with major established cardiovascular disease.
• •Febuxostat (non-purine xanthine oxidase inhibitor): also first-line, more potent than allopurinol 300 mg, no renal dose adjustment required. Use cautiously in pre-existing major cardiovascular disease (the CARES trial raised CV safety concerns; NICE permits use with discussion of CV risk).

Target serum urate is less than 360 micromol/L. Consider a lower target of less than 300 micromol/L to speed reduction in total body urate, particularly useful in tophaceous disease.

Allopurinol safety: stop the drug and seek prompt advice if a rash develops (rare allopurinol hypersensitivity syndrome with SJS/TEN, hepatitis, renal failure). Consider HLA-B*5801 testing before starting in patients of Han Chinese, Thai, or Korean ancestry due to higher allele prevalence and hypersensitivity risk. Allopurinol with azathioprine or mercaptopurine is a high-risk interaction (both metabolised by xanthine oxidase); reduce azathioprine by approximately 75% or use an alternative.

Flare prophylaxis during ULT initiation: colchicine 500 microg once or twice daily until target urate is reached, often several months. Low-dose NSAID or low-dose oral corticosteroid are alternatives. Prophylaxis is essential because crystal mobilisation provokes flares.

Uricosurics (specialist): benzbromarone, probenecid, lesinurad - increase renal urate excretion when xanthine oxidase inhibitors are insufficient or not tolerated.

Lifestyle (per NICE NG219): NICE notes insufficient evidence that any specific diet significantly lowers urate. Advise a healthy balanced diet, weight reduction in obesity, reduced alcohol (particularly beer), and adequate hydration. Dietary modification alone rarely reaches target urate - ULT is almost always needed. Manage cardiovascular risk aggressively (metabolic syndrome, hypertension, CKD, diabetes): losartan (uricosuric) is preferred for hypertension in gout; fenofibrate has uricosuric benefit for dyslipidaemia. Review thiazide and loop diuretics where alternatives exist.

CPPD: no drug dissolves CPP crystals. Acute CPP arthritis is managed with joint aspiration (diagnostic and therapeutic), NSAIDs, colchicine, or corticosteroids - same principles as acute gout. Chronic CPP inflammatory arthritis: low-dose colchicine for prophylaxis; methotrexate or hydroxychloroquine for refractory disease (specialist, limited evidence).

Acute flare: rest, elevation, and ice for comfort; resume normal activity as the flare resolves.

Exercise does not provoke gout flares. Regular exercise supports weight management, cardiovascular fitness, and metabolic health. For CPPD with associated OA, follow OA rehabilitation principles (NICE NG226).

Weight management: obesity is a major modifiable risk factor; modest sustained loss (5-10%) reduces serum urate and flare frequency. Avoid crash diets - rapid weight loss can mobilise urate and paradoxically provoke flares.

Patient education is critical for ULT adherence: many patients stop ULT when well or after a mobilisation flare, mistaking it for harm. Explain that ULT dissolves crystal deposits over months, that mobilisation flares are expected and prevented with prophylactic colchicine, and that lifelong treatment is usually needed with regular urate monitoring to confirm target is reached. For chronic tophaceous gout affecting the feet, appropriate footwear, podiatry input, and orthotic assessment are useful.

• •NICE NG219 (Gout: diagnosis and management, 2022) - the definitive UK guideline; clinical diagnosis in typical cases, allopurinol OR febuxostat first-line, target urate less than 360 micromol/L (consider less than 300 for tophaceous disease), ULT initiation during a flare permitted if frequent flares.
• •2015 ACR/EULAR classification criteria for gout - weighted score combining clinical pattern, serum urate, and imaging (USS double-contour or DECT); used in research and atypical presentations.
• •CARES trial (febuxostat vs allopurinol) - raised cardiovascular safety concerns for febuxostat; NICE permits use with discussion of CV risk and prefers allopurinol when major CV disease is established.
• •EULAR recommendations for CPPD - inform UK practice as there is no NICE guideline; symptomatic management only; screen for metabolic causes in younger or atypical disease.

• •1st MTP (podagra) is the classic gout joint; the knee is most affected in pseudogout.
• •Measure serum urate during the acute flare; falsely normal in up to 40%.
• •Target serum urate less than 360 micromol/L on ULT; less than 300 with tophi.
• •Allopurinol with azathioprine: reduce azathioprine ~75% or switch agent.
• •HLA-B*5801 testing before allopurinol in Han Chinese, Thai, or Korean ancestry.
• •Febuxostat has a CV safety signal (CARES); use cautiously in established CV disease.