Pseudogout

Definition and nomenclature. Pseudogout is acute inflammatory arthritis caused by deposition of calcium pyrophosphate dihydrate (CPPD) crystals in articular cartilage and fibrocartilage. The current terminology is "acute CPP crystal arthritis", with chondrocalcinosis denoting the radiographic calcification and CPPD disease the umbrella term. It is predominantly a disease of the elderly — prevalence rises steeply after 65 and chondrocalcinosis is present in a substantial minority of those over 80.

Causes and associations. Most cases are idiopathic and age-related, but a secondary cause must be sought in anyone presenting young or with florid disease. The classic associations — mnemonic "5 Hs" — are Hyperparathyroidism, Haemochromatosis, Hypophosphatasia, Hypomagnesaemia and Hypothyroidism; add Wilson's disease, gout, osteoarthritis, and previous joint trauma or meniscectomy. Attacks are precipitated by acute illness, surgery (especially parathyroidectomy), trauma, dehydration, myocardial infarction, stroke and intra-articular hyaluronate injection — which is why pseudogout so often appears in an already unwell hospitalised older patient.

Clinical presentations — it has more than one face. (a) Acute pseudogout — a hot, swollen, painful joint, most often the knee, then the wrist, developing over days rather than hours, frequently with fever and a raised white cell count and CRP, so it convincingly mimics sepsis. (b) Chronic CPP crystal inflammatory arthritis — a symmetrical polyarthritis mimicking rheumatoid arthritis ("pseudo-rheumatoid"). (c) Osteoarthritis with CPPD — affecting unusual joints for osteoarthritis such as the metacarpophalangeal joints, wrist, elbow and shoulder. (d) Asymptomatic chondrocalcinosis — an incidental radiographic finding. (e) Crowned dens syndrome — CPPD around the odontoid peg presenting as acute neck pain, stiffness and fever, mimicking meningitis, polymyalgia rheumatica or giant cell arteritis in an older patient. In the elderly it also presents non-specifically as immobility, delirium, a fall or "off legs".

Diagnosis. Joint aspiration is essential, both to identify crystals and to exclude infection. CPP crystals are rhomboid or rod-shaped, weakly positively birefringent under polarised light — the mirror image of the needle-shaped, strongly negatively birefringent urate crystals of gout. Synovial fluid is inflammatory with 2,000–50,000 white cells/mm³; always send Gram stain and culture. Radiographs show chondrocalcinosis — linear or punctate calcification of the knee menisci and hyaline cartilage, the triangular fibrocartilage of the wrist, and the symphysis pubis — though its presence does not prove that CPPD is causing this attack. Ultrasound shows hyperechoic bands within hyaline cartilage. Screen for secondary causes: calcium, phosphate, magnesium, alkaline phosphatase, PTH, ferritin and transferrin saturation, and TSH.

The critical differential remains septic arthritis, and it may coexist. Pseudogout in an older adult reproduces every feature of sepsis — fever, a hot swollen joint, leucocytosis and a high CRP — and crystals in the fluid do not exclude infection. Aspirate, culture, and if there is any doubt treat empirically for sepsis while awaiting results. Other differentials: gout, acute osteoarthritic flare, haemarthrosis in an anticoagulated patient, cellulitis, reactive arthritis and, for the polyarticular form, rheumatoid arthritis and polymyalgia rheumatica. Carpal tunnel syndrome is common in older adults and can be confused with gout, rheumatoid arthritis or pseudogout.

Management. There is no therapy that removes CPP crystals — this is the essential contrast with gout, where urate-lowering therapy is curative. Treatment is therefore anti-inflammatory and supportive. Acute attack: joint aspiration alone is often therapeutic; then intra-articular corticosteroid for a single joint, which is the preferred first choice in the older adult; or short-course NSAIDs with gastroprotection if renal function, blood pressure and gastrointestinal history permit; or low-dose colchicine; or oral prednisolone 30–35 mg for 5 days for polyarticular disease. Add rest, ice and analgesia. Prophylaxis for recurrent attacks (three or more a year): low-dose colchicine 0.5 mg once or twice daily, dose-reduced for renal function. Treat any identified secondary cause — correcting hypomagnesaemia and treating hyperparathyroidism, haemochromatosis or hypothyroidism. Refractory chronic inflammatory disease may need hydroxychloroquine, methotrexate or an IL-1 inhibitor under specialist care. Physiotherapy and joint protection preserve function.

CPPD disease now has formal ACR/EULAR classification criteria (2023) and a defined role for imaging and IL-1 blockade. The 2023 ACR/EULAR classification criteria for calcium pyrophosphate deposition disease were the first for this condition: entry requires at least one episode of joint swelling, tenderness and pain in a peripheral joint, the presence of CPP crystals in synovial fluid is a sufficient criterion, and in their absence a weighted score combines clinical features, age, associated metabolic disease and — importantly — imaging evidence of chondrocalcinosis on radiograph, ultrasound or dual-energy CT. The practical consequences are three. First, ultrasound has become a validated, bedside, radiation-free way to demonstrate crystal deposition — useful in a frail patient in whom aspiration is difficult. Second, the criteria formally recognise crowned dens syndrome, which matters because it is a treatable mimic of meningitis and of giant cell arteritis in older adults. Third, IL-1 inhibition (anakinra) is increasingly used for acute attacks in patients in whom NSAIDs, colchicine and steroids are all contraindicated — a situation that is common in multimorbid older patients with chronic kidney disease and heart failure. The unchanged core message remains: there is still no crystal-dissolving therapy, so management is anti-inflammatory plus treatment of the underlying metabolic cause.