Calcium Pyrophosphate Deposition Disease (CPPD)
Patients younger than 55 years with chondrocalcinosis (CC) should be evaluated for a familial form or metabolic diseases associated with CPPD.
Chronic CPPD should be considered in any elderly patient with symptoms suggesting seronegative rheumatoid arthritis or polymyalgia rheumatica.
Chronic CPPD should be considered in any patient with diffuse osteoarthritis (OA) in atypical joints such as the metacarpophalangeal joints (MCPs), wrists, elbows, and shoulders.
The mnemonic ABC (Alignment Blue Calcium) is useful for remembering the color of a CPPD crystal parallel to the first-order red compensator when viewing synovial fluid by polarized light microscopy.
Calcium pyrophosphate dihydrate is a calcium salt (Ca2P2O2·2H2O) that in crystalline form (called CPP crystals) is deposited in cartilage and other articular tissues, leading to a variety of clinical manifestations. CPPD is the preferred umbrella term for all presentations related to CPP crystal deposition. Other terms such as CPPDD/CPDD (calcium pyrophosphate dihydrate deposition disease) are the same as CPPD.
CPPD-associated arthritis is the third most common cause of inflammatory arthritis, occurring in 3.4% of adult patients. However, it can present in a number of different ways. It should be considered in the diagnosis of any acute or chronic mono-, oligo-, or polyarticular inflammatory or noninflammatory arthritis occurring in patients over the age of 55 years. If it occurs in a patient aged <55 years, then familial forms, certain metabolic diseases (hyperparathyroidism, hemochromatosis, hypomagnesemia, dialysis-dependent renal failure, others), and/or a history of joint trauma/meniscectomy need to be considered.
Acute CPP crystal arthritis (pseudogout) is an acute arthritis caused by release of CPP crystals from the cartilage or synovium into the joint space. CPP crystals can interact with cell membranes, causing nonspecific activation of signal transduction pathways and inducing the release of prostaglandins, leukotrienes, and cytokines. The CPP crystals also interact with Toll-like receptor 2 on cells, which engulfs the CPP crystals. The crystals interact with the intracellular NLRP3 (cryopyrin) inflammasome, resulting in caspase-1 activation and IL-1 and IL-18 release, which causes intense inflammation of the joint. CXCL8 stimulates ingress of neutrophils into the joint, which is critical in triggering crystal-induced inflammation and the resultant synovitis. Symptoms of acute pseudogout are the same as for any acute arthritis, with rapid onset of pain and swelling. Physical examination reveals warmth, swelling with effusion, tenderness, and limited motion of the involved joint(s). Overlying erythema may simulate cellulitis. Occasionally systemic symptoms such as malaise and fever will also raise suspicion of infection (pseudoseptic arthritis).