Two main types of crystal account for the majority of crystal-induced arthritis: sodium urate and calcium pyrophosphate. Neutrophils ingest the crystals and initiate a pro-inflammatory reaction.
Gout and hyperuricaemia
Gout is an inflammatory arthritis caused by hyperuricaemia and intra-articular sodium urate crystals. Hyperuricaemia and sodium urate deposition is also often asymptomatic.
Gout is common. The disease is 10 times more common in men, occurs rarely before young adulthood (when it suggests a specific enzyme defect), and seldom in premenopausal females. There is often a family history of gout.
Hyperuricaemia results from overproduction of uric acid or renal under-excretion (Table 7.8). Urate is derived from the breakdown of purines (adenine and guanine in DNA and RNA), which are mainly synthesized in the body. Idiopathic (primary) gout is the most common form and most have impaired renal excretion of uric acid.
Hyperuricaemia and deposition of sodium urate crystals result in four clinical syndromes:
■ Acute sodium urate synovitis - acute gout
■ Chronic polyarticular gout
■ Chronic tophaceous gout
■ Urate renal stone formation (p. 378).
Acute gout presents typically in a middle-aged male with sudden onset of severe pain, swelling and redness of the metatarsophalangeal joint of the big toe. The signs of inflammation may extend beyond the joint giving the impres-sion of cellulitis. The attack may be precipitated by dietary or alcoholic excess, by dehydration or by starting a diuretic. In 25% a joint other than in the big toe is affected. Acute attacks must be differentiated from other causes
|Table 7.8 Causes of hyperuricaemia|
|Impaired excretion of uric acid|
Chronic kidney disease (clinical gout unusual)
|Increased production of uric acid|
|Increased de novo purine synthesis (rare) due to:
HGPRT deficiency (Lesch–Nyhan syndrome)
Increased turnover of purines
Myeloproliferative disorders, e.g. polycythaemia vera
Lymphoproliferative disorders, e.g. leukaemia
Others, e.g. carcinoma, severe psoriasis
|HGPRT, hypoxanthine-guanine phosphoribosyltransferase; PPS, hosphoribosylpyrophosphate
of monoarthritis, particularly septic arthritis. Presentation can also be with a polyarticular inflammatory arthritis particularly in elderly women on long-term diuretics.
Chronic tophaceous gout presents with large, smooth, white deposits (tophi) in the skin and around the joints particularly on the ear, the fingers and on the Achilles tendon.
The clinical picture is often diagnostic, as is the rapid response to NSAIDs or colchicine.
■ Joint fluid microscopy is the most specific and diagnostic test, revealing long, needle-shaped crystals which are negatively birefringent under polarized light. This is not usually necessary in clinical practice.
■ Serum uric acid is usually raised, but may be normal during an acute attack - the levels subsequently increase and should be rechecked several weeks after. However, the diagnosis is excluded if the serum uric acid is in the lower half of the normal range.
■ Serum urea and creatinine for signs of renal impairment.
Acute attacks are treated with anti-inflammatory drugs:
■ NSAIDs (p. 317) e.g. diclofenac (75-100 mg immediately, then 50 mg every 6-8 hours), or coxibs, e.g. lumiracoxib 100 mg once daily. After 24-48 hours reduced doses are given for a further week.
■ Colchicine (1000 μg immediately, then 500 μg every 6-12 hours) but only if NSAIDs are not tolerated or ineffective. It has a narrow therapeutic window and is extremely toxic in overdose (diarrhoea, abdominal pain, multi-organ failure).
■ Corticosteroids: intramuscular or intra-articular depot methylprednis-olone.
Further attacks are prevented by reducing serum uric acid levels. Obese patients should lose weight, alcohol consumption should be reduced, and drugs such as thiazides and salicylates should be withdrawn. A diet which reduces total calorie and cholesterol intake and avoids purine-rich foods (offal, some fish and shellfish and spinach) is advised. Patients with frequent attacks (>2 per year) despite dietary changes or with gouty tophi or renal impairment are treated with allopurinol. Treatment is not started within 1 month after an acute attack and NSAIDs or colchicine are given for 4 weeks before and after starting allopurinol, as it may induce an acute attack. Allopu-rinol inhibits xanthine oxidase (an enzyme in the purine breakdown pathway) and reduces serum urate levels rapidly. Febuxostat is a new non-purine analogue inhibitor of xanthine oxidase and available in some countries but long-term studies are needed.
Asymptomatic hyperuricaemia is not usually treated unless plasma levels are very high or in patients with cancer to prevent the tumour lysis syndrome (p. 255).
Pseudogout (pyrophosphate arthropathy)
Deposition of calcium pyrophosphate dihydrate in articular cartilage and periarticular tissue produces the radiological appearance of chondrocalcino-sis (linear calcification parallel to the articular surfaces). Shedding of crystals into a joint produces acute synovitis that resembles acute gout, except that it is more common in elderly women and usually affects the knee or wrist. In young people it may be associated with haemochromatosis, hyperpara-thyroidism, Wilson's disease or alkaptonuria (excess homogentisic acid polymerizes to produce a black/brown product deposited in cartilage and other tissues).
■ The diagnosis is made on joint fluid microscopy demonstrating small brick-shaped pyrophosphate crystals which are positively birefringent under polarized light (compare uric acid) or deduced from the presence of chondrocalcinosis on X-ray.
■ Blood count may show a raised white cell count.
Joint aspiration with NSAIDs or colchicine forms the mainstay of treatment. Injection of local corticosteroids may also be useful once septic arthritis is excluded on joint fluid examination.
1. Ethics and communication
2. Infectious diseases
3. Gastroenterology and nutrition
4. Liver, biliary tract and pancreatic disease
Liver, biliary tract and pancreatic disease
LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS
SYMPTOMS AND SIGNS OF LIVER DISEASE
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
COMPLICATIONS AND EFFECTS OF CIRRHOSIS
TYPES OF CHRONIC LIVER DISEASE AND CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
BUDD - CHIARI SYNDROME
LIVER DISEASE IN PREGNANCY
CARCINOMA OF THE PANCREAS
NEUROENDOCRINE TUMOURS OF THE PANCREAS
5. Haematological disease
Assessment and treatment of suspected neutropenic sepsis
INHERITED HAEMOLYTIC ANAEMIAS
ACQUIRED HAEMOLYTIC ANAEMIA
THE WHITE CELL
HAEMOSTASIS AND THROMBOSIS
6. Malignant disease
COMMON INVESTIGATIONS IN MUSCULOSKELETAL DISEASE
COMMON REGIONAL MUSCULOSKELETAL PROBLEMS
THE SERONEGATIVE SPONDYLOARTHROPATHIES
Clinical features, Investigations
INFECTION OF JOINTS AND BONES
AUTOIMMUNE RHEUMATIC DISEASES
SYSTEMIC INFLAMMATORY VASCULITIS
DISEASES OF BONE
8. Water, electrolytes and acid–base balance
WATER AND ELECTROLYTE REQUIREMENTS
BODY FLUID COMPARTMENTS
REGULATION OF BODY FLUID HOMEOSTASIS
PLASMA OSMOLALITY AND DISORDERS OF SODIUM REGULATION
DISORDERS OF POTASSIUM REGULATION
DISORDERS OF MAGNESIUM REGULATION
DISORDERS OF ACID - BASE BALANCE
9. Renal disease
INVESTIGATION OF RENAL DISEASE
URINARY TRACT INFECTION
HYPERTENSION AND THE KIDNEY
RENAL CALCULI AND NEPHROCALCINOSIS
URINARY TRACT OBSTRUCTION
ACUTE RENAL FAILURE/ACUTE KIDNEY INJURY
CHRONIC KIDNEY DISEASE
RENAL REPLACEMENT THERAPY
CYSTIC RENAL DISEASE
TUMOURS OF THE KIDNEY AND GENITOURINARY TRACT
DISEASES OF THE PROSTATE GLAND
10. Cardiovascular disease
COMMON PRESENTING SYMPTOMS OF HEART DISEASE
INVESTIGATIONS IN CARDIAC DISEASE
ISCHAEMIC HEART DISEASE
VALVULAR HEART DISEASE
PULMONARY HEART DISEASE
ARTERIAL AND VENOUS DISEASE
DRUGS FOR ARRHYTHMIAS
DRUGS FOR HEART FAILURE
DRUGS AFFECTING THE RENIN - ANGIOTENSIN SYSTEM
NITRATES, CALCIUM - CHANNEL BLOCKERS AND POTASSIUM - CHANNEL ACTIVATORS
11. Respiratory disease
12. Intensive care medicine
13. Drug therapy, poisoning, and alcohol misuse
14. Endocrine disease
PITUITARY HYPERSECRETION SYNDROMES
THE THYROID AXIS
MALE REPRODUCTION AND SEX
FEMALE REPRODUCTION AND SEX
THE GLUCOCORTICOID AXIS
THE THIRST AXIS
DISORDERS OF CALCIUM METABOLISM
DISORDERS OF PHOSPHATE CONCENTRATION
ENDOCRINOLOGY OF BLOOD PRESSURE CONTROL
DISORDERS OF TEMPERATURE REGULATION
15. Diabetes mellitus and other disorders of metabolism
16. The special senses
COMMON NEUROLOGICAL SYMPTOMS
COORDINATION OF MOVEMENT
THE CRANIAL NERVES
COMMON INVESTIGATIONS IN NEUROLOGICAL DISEASE
UNCONSCIOUSNESS AND COMA
STROKE AND CEREBROVASCULAR DISEASE
EPILEPSY AND LOSS OF CONSCIOUSNESS
NERVOUS SYSTEM INFECTION AND INFLAMMATION
HEADACHE, MIGRAINE AND FACIAL PAIN
SPINAL CORD DISEASE
DEGENERATIVE NEURONAL DISEASES
DISEASES OF THE PERIPHERAL NERVES