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Crystal-related arthropathies 

Crystal-related arthropathies

Chapter:
Crystal-related arthropathies
Author(s):

Edward Roddy

and Michael Doherty

DOI:
10.1093/med/9780199204854.003.1910

August 28, 2014: This chapter has been re-evaluated and remains up-to-date. No changes have been necessary.

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date: 28 March 2017

Many crystals have been associated with arthropathies or periarticular syndromes: only monosodium urate monohydrate (gout), calcium pyrophosphate dehydrate (pseudogout, chondrocalcinosis), and basic calcium phosphates (mainly hydroxyapatite) are common.

Crystals implicated in joint disease are stable, hard particles that exert biological effects via surface-active (activation of humoral and cell-derived mediators, interaction with cell membranes) and mechanical properties. In general, smaller particle size, marked surface irregularity, and high negative surface charge correlate with inflammatory potential.

Gout

Aetiology and pathogenesis—gout is caused by the formation of monosodium urate crystals, and the primary risk factor for its development is hyperuricaemia. It is common (prevalence 0.5–1.4%, rising with age). Risk factors for primary gout include being male, hypertension, obesity, insulin resistance, metabolic syndrome, excess alcohol consumption (especially beer), and a diet rich in purines. These act primarily by reducing efficient elimination of uric acid via the kidney. Important risk factors for secondary gout are diuretic therapy, chronic renal impairment, and osteoarthritis.

Clinical features—four clinical phases are recognized. (1) Asymptomatic hyperuricaemia—the risk of developing gout increases with the degree of hyperuricaemia, but around 95% of hyperuricaemic patients remain asymptomatic throughout life. (2) Acute gout—in almost all initial episodes a single peripheral joint is involved, with the first metatarsophalangeal joint (podagra) the site of the first attack in 50% of patients. Other common sites are the midtarsal joints, ankle, knee, small hand joints, wrist, and elbow. The pain is often described as ‘the worst ever experienced’. The joint and surrounding tissues are swollen, hot, red, shiny, and extremely tender. (3) Intercritical gout—after resolution of the first attack there is a variable time period before the second, but this usually occurs within 1 year and chronic symptoms usually develop within 10 years. (4) Chronic tophaceous gout—large crystal deposits (tophi) produce irregular firm nodules and chronic joint damage. Gout is associated with renal disease—uric acid stones (10–25% of patients) and chronic urate nephropathy (endstage renal failure occurs in up to 25% of cases of untreated chronic tophaceous gout).

Diagnosis—proof of gout requires the identification of monosodium urate crystals on polarized light microscopy of aspirates from synovial fluid or tophus (strongly birefringent, negative sign). Although gout is strongly associated with hyperuricaemia, serum urate is frequently normal during an acute attack, and hyperuricaemia per se is not a diagnostic test for gout.

Management—treatment of an acute attack aims to reduce inflammation: options include nonsteroidal anti-inflammatory drugs, low-dose colchicine, joint aspiration, intra-articular (occasionally systemic) steroids, and ice packs. Alteration of uric acid levels is avoided until the attack has resolved. Long-term management involves lifestyle modification advice and urate-lowering therapy. Encouragement concerning weight loss and restriction of the consumption of alcohol (especially beer) and purine-rich foods should be offered to all appropriate patients with primary gout. Urate-lowering therapy should be titrated with the aim of lowering the serum urate well below 360 µmol/litre (6 mg/dl)—the physiological saturation point for urate crystal formation. Allopurinol, a xanthine oxidase inhibitor, is the usual drug of choice. The uricosurics probenecid and sulfinpyrazone are rarely used, but benzbromarone, a potent uricosuric, is now increasingly used in parts of Europe.

Pyrophosphate arthropathy

Deposition of calcium pyrophosphate dihydrate crystals in articular cartilage can be seen on radiographs in 4.5% of adults over the age of 40. It is almost always of unknown cause (sporadic/idiopathic, associated with osteoarthritis), but can be associated with metabolic disease (hyperparathyroidism, haemochromatosis, hypophosphatasia, hypomagnesaemia) or be hereditary.

Clinical features, diagnosis and management—the following are common presentations. (1) Acute synovitis (pseudogout)—one of the commonest causes of acute monoarthritis in older people. A typical attack develops rapidly (6–24 h)—usually in the knee—with severe pain, stiffness and swelling, and a florid synovitis on examination. Fluid aspirated from the joint is often turbid or bloodstained with an elevated cell count, and polarized light microscopy reveals calcium pyrophosphate crystals (weakly birefringent, positive sign). Local therapy is preferred with ice packs and aspiration (combined with intra-articular steroid in florid cases). (2) Chronic pyrophosphate arthropathy—a common condition that affects mainly elderly women and targets the same large and medium-sized joints as pseudogout. Presentation is with chronic pain, stiffness, and functional impairment, with or without superimposed acute attacks. Affected joints show signs of osteoarthritis with varying degrees of synovitis. There is no specific therapy and treatment of any underlying metabolic disease does not influence outcome, which is generally good. (3) Asymptomatic incidental radiographic finding.

Apatite-associated syndromes

Apatites, or basic calcium phosphates, are the usual minerals deposited in extraskeletal tissues, e.g. in arterial walls or tuberculous lesions. Apatite deposition in the supraspinatus tendon is a not uncommon incidental finding, occasionally resulting in severe acute inflammation (acute calcific periarthritis).

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