Calcium pyrophosphate deposition

What is pseudogout?¹

Pseudogout is an inflammation of joints, caused by the deposition of calcium pyrophosphate (CPP) crystals in articular and periarticular tissues. Although the name is still widely used, pseudogout is now referred to as calcium pyrophosphate deposition (CPPD) disease. The name pseudogout originated from an early description of this disease in patients with an acute gout-like arthritis but who did not have gout.

How common is calcium pyrophosphate deposition? (Epidemiology)^{2 3}

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

• One English study reported a prevalence of CPPD of 7-10% in people over the age of 60. This study also reported an equal gender distribution⁴ .

• Most cases of CPPD are non-familial but mutations in the ANK human gene (ANKH) have been demonstrated in some families⁵ .

May be precipitated by:

• Dehydration

• Intercurrent illness

• Hyperparathyroidism

• Long-term use of steroids

• Hypothyroidism

• Any cause of arthritis

• Haemochromatosis

• Wilson's disease

• Acromegaly

• Dialysis

• Surgery or trauma

• Hypomagnesaemia

Calcium pyrophosphate symptoms^{1 2}

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.

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

• Acute attacks of CPPD disease may last for weeks or months.

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

Investigations²

• Joint X-rays: linear opacification of articular cartilage.

• Ultrasound may also be a useful diagnostic tool.

• Dual-energy CT and diffraction-enhanced synchrotron imaging are being evaluated as potential avenues for improved visualisation of CPP deposits⁶ .

• Aspiration of the joint fluid: raised white cell count which is predominantly neutrophils. Glucose levels usually are normal. Intracellular and extracellular weakly positive birefringent crystals (intracellular crystals are pathognomonic for acute pseudogout). The joint fluid often looks purulent and septic arthritis must be excluded.

• Exclusion of other causes of acute arthritis.

• Evaluation of possible underlying cause as listed above.

Calcium pyrophosphate deposition treatment and management⁷

Unlike gout, there are no specific treatments for the elimination of CPP crystals from the body. Apart from therapy for any underlying cause, treatment is therefore symptomatic. Care should be tailored to individual patients and should take account of any comorbidities and existing medication regimes. Non-steroidal anti-inflammatory drugs (NSAIDs), for example, may not be ideal for the group most commonly developing symptomatic calcium pyrophosphate deposition disease - ie the elderly.

The body of evidence supporting the use of various treatments is not as well established in CPPD-related conditions as that for gout. It is acknowledged, therefore, that the management regimes have often been developed as a result of the custom and practice over the years rather than supported by large-scale clinical trials.

The most widely used treatments for acute crystal arthritis are as follows:

• Ice, cool packs, temporary rest.

• Aspiration of the joint.

• NSAIDs.

• Intra-articular steroid injections.

• Systemic steroids.

• Colchicine - an alternative if NSAIDs or steroids are contra-indicated.

Treatment of OA with CPPD should be managed according to the general guidelines for treating OA. See the separate Osteoarthritis article.

Chronic CPP crystal arthritis is much more difficult to manage than acute CPP crystal arthritis¹ :

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

• No current disease-modifying drugs are available for CPPD disease.

• The daily use of oral colchicine at a low dose may be useful in reducing the frequency of acute attacks. Alternatively, NSAIDs may produce similar beneficial effects if that they do not cause side-effects.

• Low-dose systemic glucocorticoids may be necessary to control pain and inflammation if colchicine or NSAIDs are ineffective or associated with unacceptable side-effects.

Prognosis³

• Acute attacks often resolve within ten days⁸ .

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

• Some patients develop progressive joint damage with functional limitation.

• Prognosis will also be dependent on any underlying cause.