Rheumatology & Internal Medicine & Family Medicine
Pseudogout (chondrocalcinosis — CPPD deposition disease)
Pseudogout - the clinical term for the acute arthritic crisis of calcium pyrophosphate dihydrate deposition disease (CPPD) - is a microcrystalline arthropathy caused by the precipitation and deposition of calcium pyrophosphate dihydrate (CPPD) crystals in the articular cartilage, menisci, tendons, bursae and synovium of many joints, which can then be released into the synovial fluid, triggering an intense neutrophil-mediated acute inflammatory reaction - a clinical picture resembling a gout attack, but involving crystals of a distinct chemical nature (calcium pyrophosphate vs. monosodium urate) and with a different joint distribution (knee ++ vs. metatarsophalangeal ++ in gout). The modern terminology recommended by EULAR (2023) refers to this entity as CPPD disease, with its clinical forms: acute CPPD arthritis (old pseudogout) + asymptomatic chondrocalcinosis (radiological deposits without inflammation) + chronic CPPD arthropathy (accelerated degenerative joint damage). Chondrocalcinosis - a radiological term describing the calcification of articular cartilage visible on standard radiography - is the pathognomonic sign of CPPD disease, visible in particular in the knees (meniscal fibrocartilage + hyaline cartilage), wrist (triangular cartilage + lunotriquetral ligament + carpal bone), symphysis pubis, intervertebral discs and hip. The prevalence of chondrocalcinosis increases sharply with age - from 7 % in the 60-70 age group to 50 % after the age of 80 - making CPPD a very frequent cause of acute monoarthritis in the elderly, often misdiagnosed and mistakenly treated as rheumatic fever or septic arthritis.
Pathophysiology and risk factors
- Mechanism of CPPD crystal formation: local elevation of inorganic pyrophosphate (PPi) in articular cartilage → PPi precipitation with calcium as CPPD crystals → deposits in the cartilaginous matrix + fibrocartilage + synovium + release of crystals into synovial fluid during trauma + infectious episodes + surgery → phagocytosis by neutrophils → activation of the NLRP3 inflammasome → IL-1β secretion → acute inflammation + same pathway as for monosodium urate crystals in gout
- Metabolic risk factors — to systematically look for: Primary hyperparathyroidism (hypercalcemia → excess calcium for CPPD crystal precipitation) + hereditary hemochromatosis (iron overload → inhibition of phosphatases that normally degrade PPi → PPi accumulation) + chronic hypomagnesemia (magnesium normally inhibits CPPD crystallization — its deficiency favors precipitation) + hypothyroidism (reduced PPi degradation) + Wilson's disease + hypophosphatasia (alkaline phosphatase deficiency → PPi accumulation)
- Aging — principal risk factor: Aging reduces chondrocytic pyrophosphatase activity and alters cartilage matrix composition, leading to progressive PPi accumulation, CPPD deposition, and the vast majority of radiologically evident chondrocalcinosis cases are age-related with no identifiable metabolic cause.
- Family/hereditary forms: ANKH gene mutations (gene regulating pyrophosphate transport out of chondrocytes) → early-onset familial chondrocalcinosis (before 55 years of age) + autosomal dominant transmission + investigate chondrocalcinosis in a subject Under 55 years old with no metabolic cause
- Triggers of acute crises: Joint trauma + surgery (including remote surgery - parathyroidectomy ++ due to sudden calcium drop) + acute intercurrent illness (infection + myocardial infarction) + transfusion or infusion (hemodilution)
Clinical forms
| Clinical form | Presentation and preferred locations | Features and frequency |
|---|---|---|
| Acute arthritis with CPPD (pseudogout) | Acute monoarticular arthritis + sudden onset within hours + intense pain + swelling + warmth + localized redness + joint effusion + knee ++ (50 % of attacks — unlike gout, which preferentially affects the 1st metatarsophalangeal joint) + wrist + ankle + hip + elbow + shoulder + bilateral or polyarticular involvement possible in 10–20 % of attacks | Duration of crisis: 5 to 21 days (longer than a typical gout attack) + often triggered by trauma or intercurrent illness + possible fever (38–38.5 °C) + diagnosis by joint aspiration + CPPD crystals |
| Asymptomatic chondrocalcinosis | CPPD deposits visible on standard X-ray without any arthritis or joint symptoms + incidental finding on a standard X-ray or joint ultrasound + very common in the elderly (> 50 % after 80 years) + no treatment necessary | Often incidental on knee X-ray, pubic symphysis X-ray, and wrist X-ray. Clinical monitoring and metabolic workup if the subject is young (< 60 years old). |
| Chronic arthropathy with CPPD | Accelerated chronic degenerative arthropathy affecting unusually affected joints by primary osteoarthritis (wrists + metacarpophalangeal joints ++ + elbows + shoulders) + with or without superimposed acute flares + can mimic rheumatoid polyarthritis (finger involvement + wrists + morning stiffness) or atypical diffuse osteoarthritis | May precede or accompany acute crises + wrist osteoarthritis + MCP osteoarthritis in an elderly man → consider hemochromatosis + Haglund's arthropathy (severe joint destruction in some forms) + symptomatic treatment only |
| Rheumatoid-like form | Chronic arthritis with CPPD affecting multiple joints (wrists + MCPs + knees) + morning stiffness + joint swelling + systemic signs (elevated ESR + CRP) → can mimic rheumatoid arthritis + negative RF and anti-CCP + CPPD crystals in synovial fluid + chondrocalcinosis on X-ray | 5–10 % of CPPD disease presentations + differential diagnosis of RA in the elderly + do not treat with methotrexate + respond better to colchicine and hydroxychloroquine |
Diagnosis
- Joint aspiration + synovial fluid analysis — reference examination: inflammatory fluid (cloudy appearance + leukocytosis > 2,000 WBC/mm³ + neutrophil predominance > 75 %) + identification of CPPD crystals on compensated polarized light → rhomboid or rod-shaped crystals + weakly positive birefringence (distinguishes from monosodium urate crystals, which are strongly birefringent and needle-shaped) + aspiration is MANDATORY to confirm the diagnosis and rule out septic arthritis (emergency) — radiographic chondrocalcinosis is not sufficient to confirm an acute CPPD flare
- Standard radiography — chondrocalcinosis: Linear or punctate calcifications of articular cartilage (hyaline and fibrocartilaginous) + knees: meniscal calcifications (especially the medial meniscus) + femorotibial cartilage + wrist: triangular fibrocartilage calcifications + ligaments + pubic symphysis + intervertebral discs (calcifying discopathy) + hip + shoulder (rotator cuff)
- Joint ultrasound visualize CPPD deposits as intra-cartilaginous hyperechoicities (in the middle of the cartilage layer - unlike hydroxyapatite deposits which are superficial) + detect joint effusion + guide aspiration + more sensitive than radiography for early cartilage deposits
- High-resolution scanner (DECT — Dual Energy CT): allows for the chemical characterization of crystalline deposits + distinguishes CPPD crystals (calcium) from urate crystals (sodium urate) + useful if synovial fluid analysis under polarized light is inconclusive or if aspiration is not feasible + limited availability
- Systematic metabolic workup for chondrocalcinosis in individuals under 60 years of age: Calcium level + PTH (primary hyperparathyroidism) + magnesium level (hypomagnesemia) + ferritin + transferrin saturation (hemochromatosis) + TSH (hypothyroidism) + alkaline phosphatase + phosphate level (hypophosphatasia) + copper level + ceruloplasmin (Wilson's disease)
ℹ️
Pseudogout and septic arthritis can have identical clinical presentations (acute monoarthritis with fever, swelling, and redness). Differentiating them without joint aspiration is impossible and potentially dangerous. Untreated septic arthritis can destroy the joint within days. Joint aspiration with synovial fluid analysis (leukocytosis, crystals, bacterial culture) is mandatory for any acute febrile monoarthritis, even if chondrocalcinosis is known and visible on X-ray, as a joint superinfection can coexist with CPPD crystals.
Treatment
- Acute crisis - NSAIDs (nonsteroidal anti-inflammatory drugs): naproxen 500 mg x 2/day + indomethacin 25–50 mg x 3/day + ibuprofen 600 mg x 3/day + treatment for 7 to 14 days depending on the duration of the attack + first line if no contraindication (kidney failure + anticoagulants + active gastric ulcer) + systematic gastroprotection (PPI)
- Acute attack - colchicine: 1 mg at the first symptoms → 0.5 mg 1 hour later → then 0.5 mg twice daily until resolution + alternative to NSAIDs or in combination + also effective in preventing recurrences (colchicine 0.5–1 mg daily continuously in patients with frequent attacks) + side effects: diarrhea + nausea
- Acute crisis — intra-articular corticosteroid infiltration: methylprednisolone 40–80 mg intra-articular + or triamcinolone 20–40 mg intra-articular + after aspiration of inflammatory fluid + rapid and very effective treatment + indicated if contraindications to NSAIDs and colchicine + or if large joint with abundant effusion (knee) + drainage + injection in the same session
- Treatment of the metabolic cause: Normalization of serum calcium (parathyroidectomy if primary hyperparathyroidism → crisis reduction) + magnesium supplementation if hypomagnesemia (frequency reduction of crises) + hemochromatosis treatment (phlebotomies → reduction of tissue deposits + improvement of arthropathy) + hypothyroidism treatment
- Chronic form and prophylaxis of relapses: Colchicine 0.5–1 mg/day long-term → reduction in attack frequency + hydroxychloroquine (Plaquenil® 200 mg × 2/day) for the pseudo-rheumatoid form + no treatment equivalent to allopurinol for gout that would dissolve already deposited CPPD crystals + treatment of the deposits themselves is not currently possible
Situations requiring rapid medical consultation
Consult a doctor within the next few hours if a joint (knee + wrist + ankle) suddenly becomes painful, swollen, warm, and red. Acute crystal-induced arthritis (pseudogout or gout) and septic arthritis have similar presentations, and only joint aspiration can differentiate them. Septic arthritis is a surgical emergency that can destroy a joint in 24 to 48 hours without treatment. Never treat acute monoarthritis with NSAIDs or colchicine alone without first ruling out infectious arthritis.
For the assessment of radiological chondrocalcinosis in individuals under 60 years of age (screening for treatable metabolic causes), the treatment of an acute pseudogout attack, and rheumatological management, Clinique Omicron offers medical consultations at its service points in Quebec and via telemedicine. To make an appointment, visit cliniqueomicron.ca.
Consult at Clinique Omicron
Clinique Omicron's doctors and Nurse Practitioners (NPs) evaluate acute microcrystalline arthropathies (pseudogout + gout), perform or prescribe diagnostic joint aspiration, prescribe NSAIDs + colchicine treatment or corticosteroid injection depending on the context, prescribe metabolic testing to rule out a treatable cause in young patients, and refer to rheumatology for chronic relapsing or pseudo-rheumatoid forms. Consultations are available at several service points in Quebec and via telemedicine. To book an appointment, visit cliniqueomicron.ca.
The content of this page is for informational purposes only and does not substitute for the advice of a physician or rheumatologist. Any acute monoarthritis should undergo joint aspiration to exclude infectious arthritis before being treated as crystal-induced arthritis.
Omicron Clinic
Need to consult a doctor?
Treatment within 24-48 hours. In-clinic or telemedicine, anywhere in Quebec.
Insurance receipts. 7j/7. No family doctor required.