What are the causes of pseudogout?

Causes of Pseudogout

Pseudogout is primarily caused by calcium pyrophosphate dihydrate (CPPD) crystal deposition in joints, with several metabolic conditions, aging, and genetic factors serving as underlying causes.

Primary Causes

• Aging: Advanced age is the most common risk factor for pseudogout, with prevalence increasing significantly in patients over 60 years 1

• Metabolic and endocrine disorders:

  • Primary hyperparathyroidism - a significant association that can both trigger pseudogout attacks and be revealed by them 2
  • Hemochromatosis (iron overload) - can lead to CPPD crystal deposition 3
  • Hypomagnesemia - significantly associated with pseudogout during parenteral nutrition 1
  • Hypophosphatasia - can contribute to CPPD crystal formation 4

• Genetic factors: Some forms of CPPD deposition disease have familial patterns, suggesting genetic predisposition 4

Secondary Causes and Triggers

• Chronic kidney disease: Patients with chronic renal failure have higher incidence of chondrocalcinosis (15.8% in patients over 60), predisposing them to pseudogout 5

• Rapid changes in calcium levels:

  • Post-parathyroidectomy hypocalcemia - can trigger acute pseudogout attacks 6
  • "Hungry bone syndrome" following parathyroid surgery 6

• Joint trauma: Physical injury to affected joints can precipitate acute attacks 3

• Surgery: Surgical procedures, especially those affecting calcium metabolism, can trigger pseudogout attacks 3, 6

• Acute medical events:

  • Infections - can precipitate pseudogout episodes 3
  • Vascular events - associated with triggering attacks 3

Pathophysiological Mechanisms

• CPPD crystal formation: Occurs in articular cartilage, leading to chondrocalcinosis visible on imaging 1

• Crystal shedding: Relative hypocalcemia (such as after parathyroidectomy) can stimulate crystal shedding into synovial fluid, precipitating acute attacks 2

• Inflammasome activation: CPPD crystals activate the NALP-3 inflammasome of the innate immune system, triggering inflammatory cascades 4

Clinical Manifestations

• Chondrocalcinosis: Radiographic evidence of cartilage calcification, particularly in fibrocartilage of wrists, knees, and pubic symphysis 1

• Periarticular calcification: Calcification of tendons, ligaments, and joint capsules is common 1

• Pyrophosphate arthropathy: A progressive, destructive form of osteoarthritis affecting approximately one-third of patients 3

Important Considerations

• Always investigate for underlying metabolic disorders in patients presenting with pseudogout, especially if they are younger than typical presentation age 3, 2

• Pseudogout may be the first clinical manifestation of an undiagnosed metabolic condition like hyperparathyroidism 2

• The clinical presentation can mimic septic arthritis, requiring joint aspiration and crystal identification for definitive diagnosis 6, 5

• Patients with a history of pseudogout undergoing parathyroid surgery should be monitored for post-operative attacks, typically occurring on or after the second day following surgery 2