Pseudogout: Pathogenesis and clinical findings
Authors: Usama Malik Yan Yu* Reviewers: Jennifer Au Stephanie Nguyen Martin Atkinson* * MD at time of publication
Familial chondrocalcinosis
Overactivity of the NTPPPH enzyme and mutations in the ANKH gene,↑ pyrophosphate production
Hyperparathyroidism
↑ levels of parathyroid hormone produced, ↑ gut Ca2+ absorption
Hemochromatosis
Clearance of calcium pyrophosphate dihydrate (CPPD) crystals from joints is inhibited by iron
Hypomagnesia
The relative absence of magnesium impairs pyrophosphatase activity, reduces pyrophosphate breakdown
Hypophosphatasia
Defective mineralization of calcium and phosphorous in bones
Idiopathic (vast majority of cases)
Mechanism unknown
↑ serum concentrations of Ca2+ or Pyrophosphate
Enhanced mineralization in chondrocytes (cells that make cartilage)
Abbreviations
• NTPPPH nucleoside triphosphate
pyrophosphohydrolase
• CPPD – Calcium Pyrophosphate
Dihydrate
Notes:
• There are different types of calcium pyrophosphate crystal deposition (CPPD) disease. This slide only covers “pseudogout”.
• Pyrophosphate (PPi) = 2 phosphate molecules = P2O74−
• Pyrophosphate is made from the breakdown of Adenosine triphosphate (ATP): ATP -> AMP + PPi
Once in cartilage, high levels of either calcium ions or pyrophosphate can result in them binding together, forming CPPD crystals
Aggregated CPPD crystals shed into synovial fluid
Neutrophils enter joint to phagocytose the crystals and release pyrophosphatase enzyme
Repeated crystal precipitation into joint space over time (subacute process)
CPPD crystals collect on collagen fibers in articular cartilage
Chondrocalcinosis, seen on high-resolution ultrasound and/or x-ray
CPPD crystals exhibit unique properties on polarizing microscopy
Inflammatory cascade
Positively birefringent (crystals appear blue parallel to axis of polarizer)
PAINFUL, warm, swollen joint (sudden onset)
↑ C-reactive protein (CRP); erythrocyte sedimentation rate (ESR)
Knees and wrist subjected to more trauma over a person’s lifetime
Knee > Wrist >>> any other joint affected
Wearing down of joint cartilage over time
Rapidly progressive osteoarthritis (see osteoarthritis slide)
Subchondral sclerosis & cysts, joint space narrowing, and osteophytes seen on x-ray
bone loss, hemarthrosis
Nerve damage over time
“Charcot-like” joint: severe weightbearing to areas that joint destruction/deformity,
Painless joint
Lack of sensation can cause tolerate it poorly
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
Published February 16, 2020 on www.thecalgaryguide.com