Calcium pyrophosphate deposition

What is calcium pyrophosphate deposition or pseudogout?¹²

Previously known as pseudogout, calcium pyrophosphate deposition disease (CPPD) is an inflammation of joints caused by the deposition of calcium pyrophosphate (CPP) crystals in articular and periarticular tissues.

How common is calcium pyrophosphate deposition?(Epidemiology)³⁴

• Calcium pyrophosphate deposition is common in the elderly. Half of adults develop radiographic changes typical of CPPD by the age of 80.

• 30-50% of patients with CPPD are over the age of 85.⁴

• Most cases of CPPD are non-familial but mutations in the ANK human gene (ANKH) have been demonstrated in some families.⁵

• Due to the low sensitivity of conventional radiography, it is likely that the prevalence of CPPD is underestimated.

CPPD is associated with:⁴⁶⁷

• Dehydration.

• Intercurrent illness.

• Previous surgery or trauma to the joint.

• A history of gout.

• Family history of CPPD.

• Osteoarthritis.

• Primary hyperparathyroidism.

• Haemochromatosis.

• Hypophosphatasia.

• Hypomagnesaemia.

Calcium pyrophosphate symptoms³⁴

CPPD is often asymptomatic, with only radiographic changes of chondrocalcinosis.

Calcium pyrophosphate deposition may cause an acute or chronic arthritis:

Acute CPP crystal arthritis (or pseudogout):

• Acute onset of monoarticular or oligoarticular arthritis.

• The knee is the most commonly involved joint, followed by the wrist.

• Acute attacks of CPPD disease usually settle within 10 days but may last for weeks or months.

• Systemic symptoms including fevers, and chills, and constitutional symptoms may occur.

Chronic CPP crystal arthritis:

• Most affected patients have a polyarticular form of arthritis that resembles osteoarthritis, but with flares of inflammatory signs and symptoms and by unusually severe articular damage. Involvement of joints such as the glenohumeral joint, wrist, and metacarpophalangeal joints, which are not often affected by typical osteoarthritis, should lead one to suspect CPPD disease.

• A rarer form of polyarticular CPPD disease resembles rheumatoid arthritis, with persistent inflammatory arthritis that affects large and small joints. Flares often involve joints sequentially, and involvement is less symmetric than that seen with rheumatoid arthritis.

Differential diagnosis

• Acute gout.

• Septic arthritis.

• OA.

• Rheumatoid arthritis.

Investigations³⁸

• Plain x-ray, ultrasound, CT scan and DECT scans can all be used in the diagnosis of CPPD.

• Crystals can be identified on aspiration of the joint fluid.

Calcium pyrophosphate deposition treatment and management^{8910 11}

Unlike gout, there are no specific disease-modifying treatments for the elimination of CPP crystals from the body. Treatment is therefore largely symptomatic, as well as ensuring good management of any underlying metabolic conditions. Care should be tailored to individual patients and should take account of any comorbidities and existing medication regimes.

The European guidelines advice the use of non-steroidal anti-inflammatory drugs (NSAIDs), colchicine and corticosteroids (intra-articular or systemic). The drug of choice will depend on the patient's age and comorbidities.

In 2023, a large study supported the use of prednisolone 30 mg a day as the first line treatment for CPPD. If colchicine is used, initiation in the first 12 hours of symptoms is important.

For chronic CPP crystal arthritis:

• Daily colchicine is the preferred first-line treatment, whereas methotrexate and tocilizumab are considered second-line options.⁴⁷

• For patients with monoarticular or oligoarticular large-joint involvement, repeated intra-articular injections of glucocorticoids may control symptoms.

Prognosis⁴

• Acute attacks often resolve within ten days.

• However some acute attacks may last for weeks or months.

• Some patients develop progressive joint damage with functional limitation.

• Chronic CPPD is characterised by recurrent flare-ups, with symptoms that frequently overlap those of rheumatoid arthritis.

• Prognosis will also be dependent on any underlying cause.