Three types of crystal are deposited in joints; each is associated with a characteristic clinical syndrome:
1 Monosodium urate deposition is associated with acute gout, typically affecting the big toe.
2 Calcium pyrophosphate deposition causes many different syndromes including pseudo gout, which most often affects the knee.
3 Hydroxyapatite deposition causes acute calcific periarthritis and most often affects the shoulder.
In addition, calcium pyrophosphate and hydroxyapatite crystals are found in the joints of patients with OA and may contribute to the inflammation.
Gout is an abnormality of uric acid metabolism that results in the deposition of sodium urate crystals in: Io ne-r s=-causing acute gouty arthritis SOFT r rssu a= causing tophi and tenosynovitis URINARY TRACT-causing urate stones.
The prevalence varies from approximately 0.2% in Europe and the USA to 10% in the adult male Maori of New Zealand. Filipinos have high prevalences in the USA but not in the Philippines, suggesting an environmental factor. Gout is commoner in the upper social classes and one-third of patients give a family history. At least 50% are regular alcohol drinkers.
The biochemical abnormality is hyperuricaemia resulting from overproduction or under-excretion of uric acid. A high dietary intalce of purines can be an additional factor, but does not in itself produce hyperuricaemia.
Uric acid production
Uric acid is the last step in the brealcdown pathway of nucleoprotein and purines. The last two steps-the conversion of hypoxanthine to xanthine and of xanthine to uric acid-are catalysed by the enzyme xanthine oxidase.
Uric acid excretion
Uric acid is completely filtered by the glomerulus; 100% is then reabsorbed in the proximal tubule and 75% is secreted by the distal tubule. Some postsecretory reabsorption also talces place.
Causes of hyperuricaemia
In most patients with idiopathic (primary) gout the major cause of the hyperuricaemia is increased urate production,but there is also impaired renal excretion. Conditions in which hyperuricaemia occur are shown.
Gout is predominantly a disease of men. Hippocrates wasthe first to note that it does not occur in men before puberty or in women until after the menopause. It is a disease that mostly begins in middle life. Asymptomatic hyperuricaemia is 10 times more common than gout.
There are two stages in the natural history of the disease. First, recurrent acute attacks of arthritis occur. Secondly, the attacks fail to resolve completely and there are persistent symptoms associated with the permanent deposition of urate in and around joints; this stage is known as chronic tophaceous gout.
The typical acute attack begins suddenly in the early hours of the morning with excruciating pain in the big toe. Attacks may be precipitated by events such as:
• A surgical operation (hence postoperative arthritis is usually due to gout)
• Dietary or alcoholic excess
• Drugs, e.g. diuretics, particularly thiazides In 25% of attacks, a joint other than the big toe is the site of the disease. Joints of the lower limb are most often affected, including the toes, ankles and knees. Occasionallyattacks occur in the upper limb, particularly in the distal interphalangeal joints of the fingers. One joint only is affected in 90% of attacks.
The typical gouty joint is red, warm, swollen and exquisitely tender. The presence of tophi in the ear lobes or around joints may provide a clue to the correct diagnosis, but they usually occur in the later stages of the disease, by which time the nature of the problem is obvious.
Patients with gout have a higher than expected incidence of vascular disease, hypertension and renal disease. Renal disease may be due to uric acid stones or very rarely to deposition of uric acid in the kidney itself, a condition known as chronic hyperuricaemic nephropathy. However, most often the renal disease is due to hypertension and vascular disease, which are genetic associations of gout rather than complications of hyperuricaemia.
SYNOVIAL FLUID EXAMINATION. The affected joint is aspirated and the synovial fluid is examined under polarizedlight microscopy. In acute gout, the presence of Long, needle-shaped, negatively birefringent crystals is diagnostic. The test takes just a few minutes and is the best way to make the diagnosis if this is in doubt.
SERUM URIC ACID has a number of limitations as a diagnostic test. It takes time, and a high incidence of false-positive and false-negative results makes interpretation difficult. Acute gout never occurs with a serum uric acid in the lower half of the normal range. However, in the first few attacks, which are the most difficult to diagnose, the serum uric acid is often below the upper limit of normal. The level also falls after an acute attack. Thus, a normal serum uric acid does not exclude the diagnosis of gout. Similarly, a high level alone is not diagnostic. However, the serum uric acid is useful in monitoring treatment.
Acute gout is treated with anti-inflammatory drugs:
INDOMETHACIN, 50 mg three to four times daily, should produce substantial relief within 24-48 hours, when the dose should be reduced to 25 mg three to four times daily. The attack should resolve completelywithin a few weeks. Azapropazone, 600 mg twice daily, is an alternative.
COLCHICINE works slowly and produces diarrhoea; it is rarely used.
INTRAMUSCULAR ADRENOCORTICOTROPHIN (ACT H) is very effective in difficult cases.
EFFUSIONS IN LARGE JOINTS should be aspirated and a corticosteroid injected to reduce inflammation. Long-term therapy Long-term therapy should be considered when the acute attack has settled. Simple measures to reduce uric acid levels include:
• Weight reduction
• Reduction in alcohol intake
• Avoidance of foods and drinks containing high levels of purine, e.g. game and lager
• Good fluid intake
• Withdrawal of drugs such as salicylates and thiazides DR UGs. Allopurinol (a xanthine oxidase inhibitor) is the drug of choice. Indications include:
• Frequent acute attacks
• Tophi or chronic gouty arthritis
• Renal stones
• Very high serum uric acid levels (0.55 mmollitre-1 or >9 mg dl’)
• Prophylaxis when treating malignant disease Allopurinol should not be started until 4 weeks after the last acute attack. It may precipitate acute gout and should be given with a prophylactic to prevent attacks. Colchicine in a dose of 0.5 mg twice daily is ideal for this purpose and should be continued for 6 months.
The dosage of allopurinol is 300 mg daily, which should be sufficient to bring the serum urate down to normal levels. In renal disease 100 mg daily is given. Sideeffects are uncommon but include skin rashes. The tophi disappear slowly with the reduction in serum urate. Probenecid, a uricosuric drug, is used as an alternative to allopurinol in allergic patients. Asymptomatic hyperuricaemia, found on screening, does not require treatment. Simple measures outlined above are, however, usually advised.
This condition is associated with the deposition of calcium pyrophosphate dihydrate (CPPD) in articular cartilage and periarticular tissue. The acute attacks of crystal synovitis that occur in about 25% of patients with the disease are known as pseudo gout.
The aetiology of CPPD arthropathy is unknown but there is an association with primary hyperparathyroidism, haemochrornatosis, hypothyroidism, hypophosphatasia and true gout. CPPD crystal deposition often complicates OA, particularly in the knees and hips. Pyrophosphate arthropathy is a disease of older people, with the typical age of onset being 60 years. It is equally ommon in men and women.
Pyrophosphate arthropathy is not dissimilar to primary OA but tends to be polyarticular, sometimes with involvement of unusual joints such as the wrist. The course of OA associated with pyrophosphate deposition may be punctuated by attacks of pseudogout. Acute attacks most commonly affect the knee but they can affect other joints, usually large ones and mainly one at a time. The attacks begin suddenly with pain and swelling. The affected joint is warm and swollen with a large effusion. The attack resolves within weeks or months but recurs at irregular intervals. Patients may have other changes associated with OA, such as Heberden’s nodes. Occasionally, pyrophosphate deposition is entirely asymptomatic. Rarely, it causes a polyarthritis resembling RA, a severe destructive arthritis of weight-bearing joints (resembling a Charcot joint), an acute spinal syndrome or polymyalgia rheumatica.
SERUM CALCIUM is normal.
ESR may be raised during an attack.
ASPIRATION OF SYNOVIAL FLUID and identification of crystals by polarized light microscopy is diagnostic. Calcium pyrophosphate crystals are smaller than urate crystals. They are brick-shaped and postively birefringent, and are therefore easily distinguished from urate crystals.
X-RAYS 0 F THE K NEE and occasionally the wrist may show linear calcification lying between and parallel to the articular surfaces (chondrocalcinosis articularis). X-rays may also show changes of OA, with joint space narrowing and osteophyte formation.
Pyrophosphate arthropathy is not as easy to treat and control as gout. Rest and aspiration of as much fluid as possible from an affected joint and an injection of corticosteroid are helpful. NSAIDs are less dramatic in their effects than in gout but are, nevertheless, useful.
Acute calcific periarthritis
This syndrome is associated with deposition of hydroxyapatite in the soft tissues around joints. It is the leastcommon of the crystal deposition diseases, but is by no means rare. It typically occurs in adults aged about 40 rears and is equally common in men and women. The shoulder joint is the commonest site, but it can affect the small joints of the hands and feet, the wrists, e knees and other joints. When the big toe is affected, the condition is often confused with gout. There is a sudden onset of pain, which is often very severe. The affected joint is red, warm and swollen, and there is sometimes a small effusion. The attack resolves within days or weeks, but attacks recur at irregular intervals.
X-rays are diagnostic: there is a rounded well-defined radiopaque deposit in the soft tissue adjacent to the joint. Treatment is with NSAIDs such as indomethacin. Potent analgesics such as opiates are sometimes required in the acute stage. It is often useful to inject the affected joint or soft tissues with a combination of local anaesthetic and corticosteroid. It is seldom, if ever, necessary to remove the calcific deposit.