CRYSTAL ARTHRITIS

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.

Epidemiology

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.

Clinical features

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)
Drug therapy, e.g. thiazide diuretics, low-dose aspirin
Hypertension
Lead toxicity
Primary hyperparathyroidism
Hypothyroidism
Increased lactic acid production from alcohol, exercise, starvation
Glycogen storage disease type 1 (also increased production of uric acid)

Increased production of uric acid
Increased de novo purine synthesis (rare) due to:
HGPRT deficiency (Lesch–Nyhan syndrome)
PPS overactivity
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
synthetase.

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.

Investigations

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.

Management

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).

Investigations

■ 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.

Management

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.

Ebook Essentials of Kumar and Clark's Clinical Medicine, 5e

1. Ethics and communication

Ethics and communication

2. Infectious diseases

Infectious diseases

3. Gastroenterology and nutrition

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
JAUNDICE
HEPATITIS
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
CIRRHOSIS
COMPLICATIONS AND EFFECTS OF CIRRHOSIS
LIVER TRANSPLANTATION
TYPES OF CHRONIC LIVER DISEASE AND CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
BUDD - CHIARI SYNDROME
LIVER ABSCESS
LIVER DISEASE IN PREGNANCY
LIVER TUMOURS
GALLSTONES
THE PANCREAS
CARCINOMA OF THE PANCREAS
NEUROENDOCRINE TUMOURS OF THE PANCREAS

5. Haematological disease

Haematological disease
ANAEMIA
Assessment and treatment of suspected neutropenic sepsis
HAEMOLYTIC ANAEMIA
INHERITED HAEMOLYTIC ANAEMIAS
ACQUIRED HAEMOLYTIC ANAEMIA
MYELOPROLIFERATIVE DISORDERS
THE SPLEEN
BLOOD TRANSFUSION
THE WHITE CELL
HAEMOSTASIS AND THROMBOSIS
THROMBOSIS
THERAPEUTICS

6. Malignant disease

Malignant disease
MYELOABLATIVE THERAPY AND HAEMOPOIETIC STEM CELL TRANSPLANTATION
THE LYMPHOMAS
THE PARAPROTEINAEMIAS
PALLIATIVE MEDICINE AND SYMPTOM CONTROL

7. Rheumatology

Rheumatology
COMMON INVESTIGATIONS IN MUSCULOSKELETAL DISEASE
COMMON REGIONAL MUSCULOSKELETAL PROBLEMS
BACK PAIN
OSTEOARTHRITIS
INFLAMMATORY ARTHRITIS
THE SERONEGATIVE SPONDYLOARTHROPATHIES
Clinical features, Investigations
INFECTION OF JOINTS AND BONES
AUTOIMMUNE RHEUMATIC DISEASES
SYSTEMIC INFLAMMATORY VASCULITIS
DISEASES OF BONE
THERAPEUTICS

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
THERAPEUTICS

9. Renal disease

Renal disease
INVESTIGATION OF RENAL DISEASE
GLOMERULAR DISEASES
NEPHROTIC SYNDROME
URINARY TRACT INFECTION
TUBULOINTERSTITIAL NEPHRITIS
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
TESTICULAR TUMOUR
URINARY INCONTINENCE

10. Cardiovascular disease

COMMON PRESENTING SYMPTOMS OF HEART DISEASE
INVESTIGATIONS IN CARDIAC DISEASE
CARDIAC ARRHYTHMIAS
HEART FAILURE
ISCHAEMIC HEART DISEASE
RHEUMATIC FEVER
VALVULAR HEART DISEASE
PULMONARY HEART DISEASE
MYOCARDIAL DISEASE
CARDIOMYOPATHY
PERICARDIAL DISEASE
SYSTEMIC HYPERTENSION
ARTERIAL AND VENOUS DISEASE
ELECTRICAL CARDIOVERSION
DRUGS FOR ARRHYTHMIAS
DRUGS FOR HEART FAILURE
DRUGS AFFECTING THE RENIN - ANGIOTENSIN SYSTEM
NITRATES, CALCIUM - CHANNEL BLOCKERS AND POTASSIUM - CHANNEL ACTIVATORS

11. Respiratory disease


Respiratory disease
TUBERCULOSISnd
DIFFUSE DISEASES OF THE LUNG PARENCHYMA
OCCUPATIONAL LUNG DISEASE
CARCINOMA OF THE LUNG
DISEASES OF THE CHEST WALL AND PLEURA
DISORDERS OF THE DIAPHRAGM

12. Intensive care medicine

Intensive care medicine

13. Drug therapy, poisoning, and alcohol misuse

Drug therapy, poisoning, and alcohol misuse

14. Endocrine disease

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
THERAPEUTICS

15. Diabetes mellitus and other disorders of metabolism

DIABETES MELLITUS
DIABETIC METABOLIC EMERGENCIES
COMPLICATIONS OF DIABETES
SPECIAL SITUATIONS
HYPOGLYCAEMIA IN THE NON - DIABETIC
DISORDERS OF LIPID METABOLISM
THE PORPHYRIAS

16. The special senses

THE EAR
THE NOSE AND NASAL CAVITY
THE THROAT
THE EYE

17. Neurology

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
HYDROCEPHALUS
HEADACHE, MIGRAINE AND FACIAL PAIN
SPINAL CORD DISEASE
DEGENERATIVE NEURONAL DISEASES
DISEASES OF THE PERIPHERAL NERVES
MUSCLE DISEASES
MYOTONIAS
DELIRIUM
THERAPEUTICS

18. Dermatology

Dermatology

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