Medicine – Pyrophosphate Arthropathy (Pseudogout)

Pyrophosphate arthropathy, commonly called pseudogout or calcium pyrophosphate deposition disease (CPPD), is an inflammatory joint disorder caused by the deposition of calcium pyrophosphate dihydrate crystals within articular cartilage and surrounding joint structures. These crystals can trigger acute episodes of intense joint inflammation that may resemble gout, although the crystal type and typical pattern of joint involvement are different.

1. Calcium Pyrophosphate Crystals

The underlying abnormality is the accumulation of calcium pyrophosphate crystals within the joint. These crystals may remain asymptomatic for long periods or provoke sudden inflammatory attacks when they are released into the joint space.

On polarised light microscopy, calcium pyrophosphate crystals are classically weakly positively birefringent. This helps distinguish them from monosodium urate crystals seen in gout, which are negatively birefringent.

2. Typical Joint Involvement

Pseudogout most commonly affects large joints, particularly the knee, although the wrist, shoulder, elbow, ankle, and other joints may also be involved. Acute attacks usually present with sudden onset of joint pain, swelling, warmth, and restricted movement, closely resembling septic arthritis or gout.

3. Chondrocalcinosis on Radiography

A characteristic radiographic finding is chondrocalcinosis, which refers to visible calcium deposition within articular cartilage or fibrocartilage. This appears as linear or punctate calcification on plain radiographs and is particularly common in structures such as the knee menisci or wrist cartilage.

Chondrocalcinosis supports a diagnosis of CPPD, although its absence does not completely exclude the condition.

Causes and Associations

1. Increasing Age

CPPD becomes much more common with advancing age. In older adults, it may occur without any specific underlying metabolic disorder.

2. Osteoarthritis

There is a strong association between CPPD and osteoarthritis. Calcium pyrophosphate deposition may coexist with degenerative joint disease and can alter the usual distribution or severity of osteoarthritic changes.

3. Familial Predisposition

Some patients have a familial form of CPPD, particularly when disease develops at a younger age. In such cases, inherited abnormalities in cartilage metabolism may promote early crystal deposition.

4. Diabetes Mellitus

Diabetes mellitus has historically been listed among disorders associated with CPPD, although the association is less strong than with some other metabolic conditions.

5. Acromegaly

Acromegaly may predispose to abnormal cartilage and joint changes and has been associated with calcium pyrophosphate crystal deposition.

6. Haemochromatosis

Haemochromatosis is one of the most important metabolic associations. Iron deposition within tissues can alter cartilage metabolism and promote CPPD. Pseudogout occurring in a younger patient should therefore raise consideration of haemochromatosis.

7. Hypothyroidism

Hypothyroidism has also been reported in association with CPPD, although the relationship is weaker and less consistent than with haemochromatosis or hyperparathyroidism.

8. Hyperparathyroidism

Hyperparathyroidism is a recognised metabolic cause of CPPD. Abnormal calcium and phosphate metabolism can promote crystal deposition within cartilage and increase the likelihood of pseudogout attacks.

Treatment

Treatment is primarily symptomatic, with the goal of reducing pain and inflammation during acute attacks. Management may include NSAIDs, provided there are no contraindications, as well as colchicine in selected patients. If a single large joint is involved, aspiration of the joint followed by intra-articular corticosteroid injection can be effective after infection has been excluded.

For patients who cannot receive local therapy or who have multiple inflamed joints, a short course of systemic corticosteroids may be considered. When recurrent CPPD occurs, any associated metabolic disorder such as hyperparathyroidism or haemochromatosis should also be identified and managed appropriately.

Key Clinical Pattern

Pseudogout is best remembered as an acute large-joint inflammatory arthritis caused by calcium pyrophosphate crystals, typically involving the knee, with weakly positive birefringence on crystal analysis and chondrocalcinosis on radiographs. Important associations include advanced age, osteoarthritis, haemochromatosis, hyperparathyroidism, acromegaly, and familial disease.