From the Guidelines
Pseudogout is primarily caused by calcium pyrophosphate crystal deposition (CPPD) in joint tissues, which forms when calcium combines with pyrophosphate in the joint, leading to inflammation and symptoms similar to gout. Several factors increase the risk of developing pseudogout, including aging (most common in people over 60), joint trauma, genetic predisposition, and metabolic conditions like hyperparathyroidism, hemochromatosis, hypomagnesemia, and hypophosphatasia 1. Unlike gout, which involves uric acid crystals, pseudogout specifically involves calcium pyrophosphate crystals. The condition often affects larger joints such as knees, wrists, shoulders, and ankles.
Some key points to consider in the management of pseudogout include:
- Optimal treatment requires both non-pharmacological and pharmacological modalities, tailored according to clinical features, general risk factors, and the presence of a predisposing metabolic disorder 1
- For acute CPP crystal arthritis, treatment comprises application of ice or cool packs, temporary rest, joint aspiration, and intra-articular injection of long-acting glucocorticosteroids (GCS) 1
- Oral non-steroidal anti-inflammatory drugs (NSAIDs) with gastroprotective treatment and/or low-dose colchicine may be used for acute CPP crystal arthritis, although their use is often limited by toxicity and comorbidity, especially in older patients 1
- Prophylaxis against frequent recurrent acute CPP crystal arthritis can be achieved with low-dose oral colchicine or low-dose oral NSAID with gastroprotective treatment if indicated 1
Managing underlying metabolic disorders is essential for long-term control of pseudogout, as conditions like hyperparathyroidism, hemochromatosis, or hypomagnesemia should be treated if detected 1. The crystal formation occurs because aging cartilage releases more pyrophosphate, which then combines with calcium in the joint fluid, creating the inflammatory crystals that trigger the immune response and subsequent joint pain and swelling. Treatment typically includes NSAIDs like ibuprofen or naproxen for acute attacks, joint aspiration to remove fluid, and corticosteroid injections for severe cases, with colchicine used for prevention in recurrent cases 1.
From the Research
Cause of Pseudogout
The cause of pseudogout is associated with the deposition of calcium pyrophosphate dihydrate (CPPD) crystals in the joints 2, 3.
- CPPD crystal deposition irritates the innate immune system, leading to an inflammatory response 3.
- The synovial fluid contains activated inflammatory macrophages and neutrophil granulocytes, which play a role in the inflammatory response 3.
- Human neutrophils engulf CPPD crystals and form large amounts of neutrophil extracellular traps (NETs) in vitro, releasing proinflammatory cytokines such as IL-1β and IL-8 3.
- The formation of NETs is dependent on various signaling pathways, including the ERK/MEK signaling pathway, heat shock protein 90, PI3K, and an intact cytoskeleton 3.
- Proinflammatory cytokines, such as TNF-α, GM-CSF, and IL-1β, increase NET release by the crystals, contributing to the inflammatory conditions observed in CPPD crystal-driven synovitis 3.