In patients presenting with acute calcium pyrophosphate arthritis, manifestations are similar to acute urate arthropathy with joint edema, erythema, and tenderness.[3] Up to 50% of these patients may also present with a low-grade fever.[1] The most commonly affected joint is the knee, but other weight-bearing joints may also be affected, including hips and shoulders.[11]

A subset of patients present with chronic CPP arthritis, often with waxing and waning episodes of non-synchronous, inflammatory arthritis affecting multiple non-weight bearing joints such as wrists and MCP joints, resembling rheumatoid arthritis.[1]

Clinicians should suspect crystal deposition disease in elderly patients presenting with acute degenerative arthritis in weight-bearing joints.[9] The elderly population will commonly run a milder course.[12] Some patients will present acute flares after traumatic injuries.[4]

After an appropriate physical examination, patients suspected to have calcium pyrophosphate deposition disease should undergo arthrocentesis for synovial fluid analysis, in addition to radiography of the involved joints.[13]

Diagnostic confirmation may be via the presence of rhomboid crystals in the synovial fluid aspirate visualized under polarized microscopy. These crystals typically present positive birefringence.[4]

While imaging findings consistent with chondrocalcinosis support the diagnosis of CPPD, its absence does not rule it out.[14] Early signs may be evidenced through ultrasound (US) as cartilage abnormalities. Joint cartilage calcification, known as chondrocalcinosis, may be visualized through radiographic imaging.[9][14][15]

Previous studies have demonstrated the usefulness of magnetic resonance imaging (MRI), particularly gradient-echo sequences, for the evaluation of calcium pyrophosphate crystal deposition burden in joint cartilage.[16]

The treatment for patients with calcium pyrophosphate deposition disease is based on decreasing inflammation and stabilizing any underlying metabolic disease that may predispose to calcium pyrophosphate crystal deposition. In patients with acute flares, with the involvement of one or two joints, the treatment of choice is usually joint aspiration and intra-articular glucocorticoid administration, unless contraindicated.[4][17]

For patients presenting with acute inflammation involving three or more joints, the treatment is typically systemic, often with nonsteroidal anti-inflammatory drugs (NSAIDs). Patients with contraindications for NSAIDs may receive treatment with colchicine or systemic glucocorticoids.[1]

Joint aspiration should only be performed after septic arthritis has been ruled out or considered unlikely. In patients presenting with signs and symptoms suggestive of septic arthritis, the recommendation is to defer glucocorticoid administration until synovial fluid cultures are negative.[1][4]

Other measures include the application of ice packs and joint rest with restriction of weight-bearing to decrease further inflammation. Patients with recurrent episodes of acute CPP arthritis may receive daily low-dose colchicine.[4]

While several medications decrease serum urate levels and prevent urate crystal formation, there is no current therapy directly targeting CPP crystal deposition. Hence, the treatment of CPPD relies on treating predisposing metabolic diseases, soft tissue inflammation, and symptomatology.[9]

As discussed above, calcium pyrophosphate deposition disease has different phenotypes. Therefore, the differential diagnosis should be based on the clinical presentation and may include gout, rheumatoid arthritis, ankylosing spondylitis, and erosive osteoarthritis.[4]

The intra-articular radiological calcification seen in patients with CPPD is characteristic. In knee x-rays, chondrocalcinosis presents as a thin dense intraarticular opacification that runs parallel and separated from the bone cortex or as a calcifying opacification in the menisci.[12][15]

Diagnosis of CPPD presumed in patients with the symptomatic joint disease who present the characteristic radiological findings of chondrocalcinosis.[12] As discussed, several imaging modalities may present characteristic findings of CPPD, including x-ray, US, or MRI.[9] When needed, definite diagnosis is achieved by polarizing light microscopy of synovial fluid, showing the presence of CPP crystals.[12][15]

Acute calcium pyrophosphate arthritis is generally self-limited, and the inflammation usually resolves within days to weeks of treatment.[1]

Patients with chronic CPP inflammatory arthritis may present overlapping manifestations with rheumatoid arthritis, such as morning stiffness, localized edema, and decreased range of motion. Some patients also present tenosynovitis with carpal or cubital tunnel syndrome.[11] Multiple joints are commonly involved, and the episodes of inflammation may present in a nonsynchronous, waxing, and waning clinical course lasting several months.[7][8]

Patients with underlying joint comorbidities, such as osteoarthritis, have an increased risk for acute CPP arthritis. When deposited, CPP crystals activate the immune system, promoting inflammation and fibrocartilage injury.[1]

The molecular structure of calcium pyrophosphate has the potential of triggering inflammatory responses.[9] The presence of chondrocalcinosis has associations with the degradation of menisci and synovial tissue.[16]

Rarely, patients may present with palpable nodules or masses that resemble gout tophi after several episodes of acute CPP crystal arthritis. These nodules localize in the periarticular tissue and represent CPP crystal accumulations within the synovium and adjacent soft tissue; they may lead to further degradation of the affected joint.[18]

A subset of patients may present with spinal involvement, occasionally causing clinical manifestations such as spine stiffness and bony ankylosis resembling ankylosing spondylitis. Some individuals may have clinical manifestations similar to diffuse idiopathic skeletal hyperostosis (DISH) with calcification of the posterior longitudinal ligament leading to spinal cord compression symptoms.[19][20]

Patients with chondrocalcinosis or previous episodes of acute calcium pyrophosphate arthritis will benefit from knowing that certain conditions carry associations with arthritic flares, including surgical procedures or trauma.[4] Individuals who present at a younger age with CPPD may receive screening for underlying metabolic abnormalities such as hyperparathyroidism or hemochromatosis. Obtaining an adequate family history is also necessary.[21]

Chondrocalcinosis is a relatively common imaging finding in asymptomatic patients. Studies have described a higher prevalence of these findings in late adulthood without gender predilection.[22] Furthermore, although chondrocalcinosis correlates with osteoarthritis, studies suggest that the risk of both diseases increases independently with age, meaning that chondrocalcinosis may develop without osteoarthritis.[23] Asymptomatic older patients may not require further workup or therapy for an isolated finding of chondrocalcinosis.

Due to a broad range of clinical manifestations, calcium pyrophosphate deposition disease should be considered in patients presenting with signs and symptoms suggestive of rheumatoid arthritis or ankylosing spondylitis.[24]

A number of specialists use the high-resolution US in the evaluation of patients with crystal arthropathies, as it may provide useful findings to help differentiate CPPD from other conditions such as gout. Chondrocalcinosis presents earlier in the US than in plain films. This modality may also find use in patients with symptomatic arthropathies of unclear etiology, or with inconclusive results in the fluid aspirate. Additionally, it could potentially decrease the need for using more expensive imaging modalities such as MRI.[16][25][26]