24th February 2025

Calcium pyrophosphate dihydrate deposition (CPPD) disease

Overview of CPPD disease

Previously known as pseudogout, as the historic name suggests, calcium pyrophosphate deposition disease is similar to gout in its pathophysiology, clinical presentation and management. The deposition of calcium pyrophosphate (CPP) crystals may be asymptomatic and inconsequential. If symptoms occur, they can vary from an acute, self-limiting synovitis in an unwell hospitalised patient, to a chronic process causing inflammation and chondrocalcification in locations such as the spinal column causing arthropathy. The varying severity of symptoms related to crystal deposition is very similar to hydroxyapatite deposition disease, though this predominantly affects the tendons, characteristically of the shoulder.

The incidence rises with advancing age, and if it occurs in those less than 50 years of age, then an underlying metabolic cause should be explored. It is associated with hyperparathyroidism, haemochromatosis and Wilson’s disease, as well as hypomagnesaemia and hypophosphataemia. An isolated flare can be triggered by acute illness, the post-surgery state (especially post-parathyroidectomy), in trauma and upon initiation of levothyroxine.

Signs and symptoms of CPPD disease

The signs and symptoms are as per that of gout; they are clinically impossible to differentiate without needle aspiration of the affected joint. That being said, as a general rule, the joints affected in CPPD disease are typically larger joints, such as the knees, whilst gout typically involves the smaller joints, such as the toes and fingers.

Investigation of CPPD disease

The diagnosis is typically suspected based on the history and examination. Much like gout, the diagnosis can usually be confirmed by needle aspiration of synovial fluid during a flare, showing positively birefringent rhomboid-shaped crystals on microscopy. X-rays and ultrasound may identify calcium deposits. As with gout, other differential diagnoses should be excluded.

Management of CPPD disease

Management of acute CPPD disease is similar in rationale to gout. Supportive measures can help, and the mainstay is with anti-inflammatory agents. Colchicine is also used as prophylaxis in chronic CPPD disease. The optimal management of any underlying metabolic conditions is vital. The anti-IL-1𝛃 drugs such as anakinra can be used in refractory acute flares, and DMARDs such as methotrexate and hydroxychloroquine in chronic resistant disease.