Category Archives: Rheumatology and bone disease

Neck pain

Pain in the neck may be caused by RA, ankylosing spondylitis, soft-tissue rheumatism or fibromyalgia. In addition, disc disease, both acute and chronic, the latter in association with OA, may occur in the neck as well as in the lumbar spine. The three lowest cervical discs are most often affected and there is pain and stiffness of the neck with or without root pain radiating to the arm. Chronic cervical disc disease is known as cervical spondylosis.
Painful stiff necks are common clinical problems, often attributed, without much evidence, to disc disease. The essence of treatment is to mobilize the neck with physiotherapy techniques such as traction or Maitland mobilization. Pain may be relieved with simple analgesics. While cervical collars may be required in the acute stage of cervical disc prolapse and occasionally in patients with cervical spondylosis, they can also perpetuate the problem of a painful stiff neck when the right treatment is mobilization.

Psychogenic back pain

Diagnostic points include:

• Young adult females predominantly affected
• Continuous unvarying pain, often described in vivid terms; no relief from rest, which usually helps even the most severe organic conditions
• Long history of treatment failures, including with analgesics
• Associated symptoms, e.g. headaches; history of fruitless investigation of symptoms from other systems
• Sometimes depression but more often difficult life situations
• No signs-normal tests

MANAGEMENT

• Reassure and explain
• Explore causes
• Treat depression if appropriate
• Avoid inappropriate diagnoses, e.g. ‘arthritis of the spine’ and repeated referrals
• Avoid confrontation
• Avoid prescribing drugs or predicting cures-the drugs will not work and the cures will not happen.

Non-specific low back pain

This is an appropriate term for those cases that defy diagnosis with current knowledge and techniques. Patients will vary from those with acute pain that will quickly resolve to those with long-standing symptoms and little prospect of recovery. Without the possibility of definitive treatment, one must rely on simple symptomatic measures such as analgesic drugs.

Mechanical problems

There are two mechanical problems in the spine that are of particular importance because they are amenable to surgical treatment: spondylolisthesis and spinal stenosis.

Spondylolisthesis

This condition arises because of a defect in the pars interarticularis of the vertebra, which may be either congenital or acquired. It gives rise to a slipping forward of one vertebra on another, most commonly at L4/L5. The acquired variety is usually the result of a fairly major traumatic episode that the patient will remember. A small spondylolisthesis is sometimes found in patients with degenerative disease of the lumbar spine and may contribute to the symptoms. The patients have mechanical pain that is not present on waking in the morning but develops as the day goes on and is aggravated by activities such as standing or walking. The pain may radiate to one or other leg and there may be signs of root irritation. More often there are no physical signs, though there may be some limitation of back movement. The diagnosis is confirmed by X-ray.
Small spondylolistheses are common, especially in patients with degenerative disease of the lumbar spine, and may be managed conservatively. It is appropriate to use simple analgesics to relieve the pain and there is no particular need for anti-inflammatory agents. A corset may provide support; this is one of the few indications for its use. A large spondylolisthesis causing severe pain,
especially in a younger patient without associated degenerative changes, requires spinal fusion. This is usually a very successful procedure.

Spinal stenosis

This is sometimes called spinal claudication because of the resemblance of the symptoms to those of intermittent claudication due to vascular occlusion. The anatomical change in spinal stenosis is narrowing of the central canal, compressing the cauda equina. This can result from a variety of causes:

• Disc prolapse
• Degenerative osteophyte formation
• Tumour-rare
• Congenital narrowing of the spinal canal
The patient typically presents with pain in one or sometimes both legs. The absence of back pain makes the diagnosis difficult. The pain comes after a period of walking and tends to diminish with the passage of time. The symptoms are relieved by rest and occasionally by leaning forward. Signs of root compression such as limitation of straight-leg raising or absent reflexes may be precipitated by exertion.

If spinal stenosis is suspected, CT or MRI scans will be required to confirm the diagnosis. Treatment is by surgical decompression.

Other mechanical problems

Bad posture is sometimes the cause of back pain. An exercise programme designed to improve posture will also therefore improve the pain. Such postural problems may be precipitated by congenital abnormalities of the spine such as a minor kyphoscoliosis. Obesity and presumably lack of activity sometimes appear to be relevant and weight-loss combined with an exercise programme may help.

Inflammatory back pain

Ankylosing spondylitis is described  and is the most important cause of inflammatory back pain.

Disc disease

The term ‘disc disease’ is used to describe two common clinical problems which are due to degenerative change in the intervertebral disc, a process in cartilage which is not unlike OA. There is an acute syndrome in which disc prolapse causes conditions that are known to the public as either lumbago or sciatica, depending upon the presence or absence of radiation of the pain to the areas supplied by the sciatic nerve. It is also used to describe a chronic syndrome in which back pain is associated with ‘degenerative changes’ on X-ray. This chronic syndrome is sometimes called spondylosis. Chronic disc disease is often associated with OA of the apophyseal joints of the spine and it is difficult or impossible to separate the role of these two pathologies in the pathogenesis of symptoms. There is a very poor correlation between the presence of radiological changes and symptoms. Severe X-ray changes can be seen in patients without any appropriate symptoms and chronic back pain may also occur in patients with little radiological change.

Acute disc disease

Acute disc disease causes acute back pain (lumbago) with or without sciatic radiation (sciatica). The severity of this syndrome is enormously variable, from a brief and trivial episode to a long and difficult illness that occasionally requires surgical intervention. It is predominantly a disease of younger people with a peale incidence between the ages of 20 and 40 years, since the disc degenerates with age and is no longer capable of prolapse in the elderly. In older patients, sciatica is more likely to be due to compression of the nerve root by osteophytes in the lateral recess of the spinal canal.

Sources of referred pain in the back.

Sources of referred pain in the back.

CLINICAL FEATURES

The back pain is sudden, often severe and often continuous at first. Its onset may be associated with a feeling thatsomething has ‘gone’ in the back. This may occur after some strenuous activity, typically with the back in forward  flexion. The pain is often clearly related to position and at first the back may be fixed in forward flexion. The pain is aggravated by movement and by certain activities. The radiation of the pain and various examination findings are dependent upon the disc affected; these features are summarized. The three lowest discs account for most cases of disc disease; in order of frequency, they are the LS/S1, L4/LS and L3/L4 discs. In a mild case there may be no signs at all, but characteristic findings include loss of lumbar lordosis, sometimes a compensatory scoliosis and limitation of movement in all directions. Severe neurological problems such as foot-drop or bladder or bowel dysfunction are fortunately rare.

INVESTIGATION

Investigations are of very limited value in acute disc disease. X-rays do not visualize the disc itself, although there may be narrowing at the level of the lesion. MRI scanning is usually reserved for patients in whom surgery is beingconsidered and is unnecessary in most cases.

MANAGEMENT

Treatment probably has little effect on the duration of the disease and is therefore aimed at the relief of symptoms and the maintenance of a reasonable way of life forthe duration of the illness.  In the acute stage:
REST for a few days on a firm bed. Longer periods of rest are unnecessary except in the most severe cases. CORSETS may be used in the acute stage. DRUGS: analgesics to relieve pain; anti-inflammatory drugs if required, for example for pain at night or morning stiffness; diazepam for short periods as a muscle relaxant.
EPIDURAL CORTICOSTEROID INJECTION reduces pain and speeds recovery but is unpleasant and requires hospitalization. It is worth considering for acute sciatica  hat is not responding to simpler measures.
SURGERY is required in the acute stage only for severe or increasing neurological impairment, e.g. foot-drop or bladder symptoms. In the recovery stage, which usually begins within a few days of the acute episode:

PHYSIOTHERAPY to relieve pain, correct posture and restore movement. A particularly useful technique is Maitland mobilization, which begins with careful assessment by the therapist to determine levels involved and restriction of movement. Applied movements with local pressure are then used to mobilize individual segments of the lumbar spine. An exercise programme is often useful at this stage. The MacKenzie approach to back care is a self-help system of exercises that emphasize extension, and includes advice about everyday activities that is useful both in treatment and in the prevention of recurrence.
URGERYwill be required for a small proportion of patients «1%) who fail to recover after an adequate period of conservative therapy.

8.23 Symptoms and signs of common root compression syndromes produced by lumbar disc prolapse.

8.23 Symptoms and signs of common root compression syndromes produced by lumbar disc prolapse.

Acute lumbar disc prolapse and sciatica,

Acute lumbar disc prolapse and sciatica,

COURSE AND PROGNOSIS

Most cases of acute lumbar disc prolapse recover completely,though the process may take as long as 1 year. A  small proportion of patients fail to recover and mayrequire surgery. An MRI scan is required to pin-point the lesion as closely as possible, thus improving the prospects  of surgery. The simplest operation is removal of the prolapsed disc (microdiscectomy).

Chronic disc disease and osteoarthritis

This very common syndrome is characterized by the presence of chronic low back pain associated with ‘degenerative’changes in the lower lumbar discs and apophyseal joints. Pain in these cases is of the mechanical type and is typically aggravated by exercise, although there may be an inflammatory component, reflected in a brief period of morning stiffness. Sciatic radiation of the pain may occur and there may be a past history of acute disc prolapse. In many cases, the pain is long-standing and the prospects for cure are very limited. Nevertheless, there are measures that will alleviate a difficult situation; DRUGS. Analgesic or anti-inflammatory drugs to relieve pain. PHYSIOTHERAPY. The same techniques are used as in acute disc prolapse, described above, and with the same aims. Maitland mobilization is useful when there is restriction of movement. An exercise programme, such as the MacKenzie approach, is usually required and it may be necessary to try different types of programme to achieve the desired result. BACK CARE. Advice about way of life, lifting, firm beds and other aspects of daily living is essential to identify and remove aetiological factors as well as preventing recurrence. Many physiotherapy departments have  ‘back’ schools for this purpose.
CORSETS should be avoided. They may be useful for patients with mechanical abnormalities, such as instability, or a spondylolisthesis, but are grossly overprescribed. Fortunately, many patients have the good sense not to wear them!

SURGERY should be considered especially for a patient with severe pain of mechanical origin, arising from a single identifiable level, that has failed to respond to conservative measures. Fusion at this level would be appropriate together with decompression of affected nerve roots. The results of surgery for chronic disc disease are not particularly good-about 50% of patients recovering completely-and a failed operation is a demoralizing event in the course of a chronic illness.
WEIGHT REDUCTION may help obese patients.
PAIN RELIEF can be achieved in many other waysincluding acupuncture, transcutaneous nerve stimulation, massage, hypnosis and faith healing.

Back pain

Back pain is extremely common. It can be mild and transient, or chronic and disabling. In many cases, the exact cause is not established. In Britain 375000 people lose some time from work each year because of back pain, an annual loss of 11.5 million working days, and back pain accounts for 6% of general-practice consultations. Back pain is not usually serious and mostly resolves; in one survey 44% of cases resolved within a week and 12% within 2 months.

Most back pain can be readily diagnosed from a simple clinical history and physical examination. A diagnostic approach to back pain. In many patients (30%) no cause will be found. It is foolish to label such patients as having ‘spondylosis’ or arthritis of the spine, terms that merely cause anxiety. It is better to use a term such as non-specific low back pain and explain to the patient what this means. The back is a common site of psychogenic pain. If possible a positive diagnosis of psychogenic back pain, rather than a diagnosis by exclusion, should be made. Supportive treatment can then be given.

A diagnostic approach to back pain.

A diagnostic approach to back pain.

HISTORY

The following factors should be considered.

Site

LUMBAR PAIN. This is usually due to degenerative disease, disc prolapse and OA, which are almost never seen in the thoracic spine.
THORACIC PAIN. This is a characteristic site of osteoporotic crush fractures.

Radiation

Sciatic radiation of pain suggests root compression; however, sacroiliac pain can also radiate down the back of the thigh to the knee.

Onset

• Sudden, e.g. disc prolapse or mechanical injury
• Gradual, e.g. ankylosing spondylitis

Aggravating factors

Pain in the back and leg on walking and relieved by stopping, suggestive of intermittent claudication, can be due to spinal stenosis.

Examination of patients with back pain.

Examination of patients with back pain.

Time pattern

• Disc disease is recurrent.
• Ankylosing spondylosis is chronic.

Inflammatory vs. mechanical

The differences in the history given in inflammatory and in mechanical back pain are shown.

EXAMINATION

Examination of the patient is summarized.

INVESTIGATION

In back pain, investigations are less important than the history and examination. They can also be misleading; for example, degenerative changes on X-ray are virtually always present in older people and may not be the cause of the pain.
X-rays are particularly useful for excluding serious bone disease. Normal X-rays usually exclude metastases but not invariably. They are of little value in acute disc disease, although a narrowed disc space may suggest a prolapse.
Bone scans are useful to detect metastases; a slightly increased uptake in areas of degenerative disease is usually easily distinguished. MRI scans are now the investigation of choice in disc disease. Abnormal discs are distinguished on MRI scans because of changes in their water content. Impingement of disc material on the nerve roots is usually well seen and it is seldom neccesary to undertake the old-fashioned and invasive radiculogram.

Blood tests

ESR 0R C RP is a particularly useful investigation. A normal ESR or CRP makes serious disease unlikely. A very high ESR suggests myeloma.
CALCIUM, PHOSPHATE AND ALKALINE PHOSPHATASE LEVELS are measured to look for metabolic bone
disease such as osteomalacia.

ACID PHOSPHATASE AND PROSTATE-SPECIFIC ANTIGEN are measured to look for metastases from prostatic carcinoma.
PROTEIN ELECTROPHORESIS, IMMUNOGLOBULINS
(AND BONE MARROW ASPIRATION) are performed to look for myeloma.

Investigations to consider in a patient with back pain.

Investigations to consider in a patient with back
pain.

Less-common arthropathies

Amyloidosis

Primary amyloidosis causes a polyarthritis that resembles RA in distribution and it is also often associated with carpal tunnel syndrome and subcutaneous nodules. Ankylosing vertebral hyperostosis (Forrestier’s disease)
This is a condition of elderly people in which exuberant osteophytes are found in the spine, particularly the dorsal region. It is often asymptomatic, but it may be confused with ankylosing spondylitis. Sometimes there is stiffness and occasionally some discomfort. It may be accompanied by peripheral soft-tissue problems associated with calcification, ossification and spur formation, when it is called diffuse idiopathic skeletal hyperostosis (DISH).

Avascular necrosis

In this condition, bone infarction disrupts the surface of the joint and often leads to changes resembling OA. The hip is particularly affected, for example following fractures of the neck of the femur, perhaps because of its precarious blood supply. It also occurs in various systemic conditions, including sickle cell disease, prolonged steroid therapy, SLE, alcohol abuse and Gaucher’s disease. It occurs in deep-sea divers (caisson disease). It may occur for no obvious reason, particularly in middle-aged men. Avascular necrosis presents with a single painful joint. X-rays are usually diagnostic in the latter phases, showing rarefaction and dense bone in the subcortical areas with distortion of the epiphysis. In the early stages, a bone scan will show increased uptake and an MRI scan will confirm the diagnosis.

Behcet’s syndrome

This is a rare condition characterized by oral and genital ulceration, iritis, and a polyarthritis of variable distribution that may be either chronic or episodic. There are many less-common features of the disease, including erythema nodosum, pustular skin lesions, and neurological and gastrointestinal manifestations. Treatment is with oral steroids but response is variable.

Drugs

Drugs may cause arthritis. SLE may be induced by procainamide, hydralazine and other drugs. Certain drugs may also precipitate or aggravate gout.

Familial Mediterranean fever

This condition occurs in certain ethnic groups, particularly Jews and Arabs. The aetiology is unknown. It is characterized by recurrent attacks of fever, arthritis and abdominal or chest pain due to pleurisy. The arthritis is usually monoarticular and attacks last up to 1 week. The condition may be mistaken for palindromic rheumatism, but such attacks are not usually accompanied by fever. In familial Mediterranean fever, attacks can usually be prerented by regular treatment with colchicine 1.0-1.5 mg daily. In general the disorder is benign but in some cases amyloidosis develops.
Hypermobility syndrome Hypermobility syndrome occurs in children or young adults with lax joints. The musculoskeletal manifestations f this syndrome include recurrent attacks of joint pain and effusion, dislocation, ligamentous injuries, low back oain and premature OA. Hypermobility is also associated ith some rare congenital disorders such as the EhlersDanlos syndrome. Joints become stiffer with increasing age. Treatment should be directed at improving muscle power.

Osteochondritis dissecans

This is a rare condition of adolescent sportsmen in which there is separation of an avascular osteochondral fragment in the knee joint. It results in disruption of the joint surface and the formation of loose bodies within the joint. OA may develop.

Osteochondromatosis

In this condition, foci of cartilage form within the synovial membrane. These foci become calcified and then ossified (osteochondromas). They may give rise to loose bodies within the joint. The condition occurs in a single joint of a young adult and X-rays are usually diagnostic. Treatment involves removal of loose bodies and synovectomy.

Palindromic rheumatism

This condition is a variant of RA, characterized by recurrent attacks of arthritis. They occur at irregular intervals, sometimes with long periods of freedom between them, begin suddenly, reach a peak after a few hours and fade over the course of the next 2 days. A single joint is affected in each attack and during the attack it is red, warm, swollen and very painful. Between attacks the joints are normal. Tests for rheumatoid factor are positive in 50% and one-third of cases go on to develop chronic RA. Pigmented villonodular synovitis This is characterized by exuberant synovial proliferation that occurs either in joints or in tendon sheaths. The main manifestation in joints is recurrent haemarthrosis. Treatment is synovectomy. In tendons, the condition gives rise to a nodular mass that requires excision.

Relapsing polychondritis

Relapsing polychondritis is a rare condition of cartilage. It gives rise to a polyarthritis accompanied by chest disease due to tracheal or bronchial involvement. The diagnosis is often made on the basis of recurrent attacks of pain and swelling of the nose or external ear.

Temporomandibular

pain/dysfunction syndrome

This is a functional disorder of the temporomandibular joint associated with abnormalities of bite. It particularly occurs in anxious people who grind their teeth at night.It gives rise to pain and clicking in one or both temporomandibular  joints. Treatment is dental-correction of the bite.

Sarcoidosis

The commonest type of arthritis is that associated with erythema nodosum, which occurs in 20% of cases of sarcoidosis at or soon after the onset of the disease. The most useful diagnostic test is a chest X-ray, which shows hilar lymphadenopathy in 80% of cases. Other patterns of arthritis including a transient rheumatoid- like polyarthritis and an acute monoarthritis that can be mistaken for gout occur later in the course of the disease. If NSAIDs fail to control the symptoms, corticosteroids are usually very effective.

Arthritis associated with other diseases

Gastrointestinal and liver disease

Enteropathic synovitis

This is associated with HLA B27 and IS described. Autoimmune chronic active hepatitis  This may be accompanied by an arthralgia that is like that seen in SLE. Joint pain occurs in a bilateral, symmetrical distribution, with the small joints of the hands being prominently affected. Joints usually look normal but sometimes there is a slight soft-tissue swelling. These patients often have positive tests for antinuclear antibodies.

Primary biliary cirrhosis

Patients occasionally have a similar symmetrical arthropathy to the above.

Haemochromatosis

This is associated with osteoarthritis in 50% of cases; it is often the first sign of the disease and chondrocalcinosis is common. The metacarpophalangeal joints of the hands are particularly affected and the disease tends to be polyarticular, severe and progressive. Iron depletion does not solve the problem of the arthritis.

Whipple’s disease

This is accompanied by fever and arthralgia.

Malignant dissease

Hypertrophic pulmonary osteoarthropathy Hypertrophic osteoarthropathy is most often associated with carcinoma of the bronchus. It is a non-metastatic complication and may be the presenting feature of the disease. It occurs only rarely with other conditions that cause clubbing. It is seen most often in middle-aged men, who present with pain and swelling of the wrists and ankles. Other joints are occasionally involved. The diagnosis is made on the presence of clubbing of the fingers, which is usually gross, and periosteal new bone formation along the shafts of the distal ends of the radius, ulna, tibia and fibula seen on X-ray. A chest Xray usually shows the malignancy. Treatment should be directed at the underlying carcinoma; if this can be removed, the arthropathy disappears. NSAIDs may help to relieve the symptoms.

Other disorders

Secondary gout occurs in conditions such as chronic myeloid leukaemia. Pain in the shoulder or back may be referred from malignant disease of the chest or abdomen. Secondaries around the joints may present with pain, but primary joint turn ours are very rare. A synovioma presents as a painless soft-tissue swelling adjacent to joints. It is highly malignant but extremely rare.

Skin disease

Psoriatic arthritis

This is a seronegative arthritis occurring in patients with psoriasis.

Erythema nodosum

Erythema nodosum can be due to several conditions, e.g. sarcoidosis, and is accompanied by arthritis in over 50% of cases. The knees and ankles are particularly affected and are swollen, red and tender. The arthritis subsides, along with the skin lesions, within a few months. Treatment is with NSAIDs or occasionally steroids.

Neurological disease

Neuropathic joints (Charcot’s joints) are joints damaged by trauma as a result of the loss of the protective pain sensation. They were first described by Charcot in relation to tabes dorsalis. They are also seen in syringomyelia, diabetes mellitus and leprosy. The site of the neuropathic joint depends upon the localization of the pain loss:
• In tabes dorsalis, the knees and ankles are most often affected.
• In diabetes mellitus, the joints of the tarsus are involved.
• In syringomyelia, the shoulder is involved.
Neuropathic joints are not painful, although there may be painful episodes associated with crystal deposition. Presentation is usually with swelling and instability and eventually grotesque deformities appear. The characteristic finding is a swollen joint with abnormal but painless movement. This is associated with neurological findings that depend upon the underlyingdisease, e.g. dissociated sensory loss in syringomyelia or peripheral neuropathy in diabetes. X-ray changes are characteristic, with gross joint disorganization and bony distortion.
Treatment is symptomatic; surgery may be required in advanced cases.

Blood disease

Arthritis due to haem arthrosis is a common presenting feature of haemophilia. Attacks begin in early childhood in most cases and are recurrent. The knee is the commonest affected joint but the elbows and ankles are sometimes involved. The arthritis can lead to bone destruction and disorganization of joints. Apart from replacement of factor VIII, affected joints require initial immobilization followed by physiotherapy to restore movement and measures to prevent and correct deformities. Sickle cell crises are often accompanied by joint pain that particularly affects the hands and feet in a bilateral, symmetrical distribution. Affected joints usually look normal but are occasionally swollen. This condition may also be complicated by avascular necrosis and by Salmonella osteoarthritis.
Arthritis can also occur in acute leukaemia; it may be the presenting feature in childhood. The knee is particularly affected and is very painful, warm and swollen. Treatment is directed at the underlying leukaemia. Arthritis may also occur in chronic leukaemia, with leukaemic deposits in and around the joints.

Endocrine and metabolic disorders

Hypothyroid patients may complain of pain and stiffness of proximal muscles, resembling polymyalgia rheurnatica. They may also have carpal tunnel syndrome. Less often, there is an arthritis accompanied by joint effusions, particularly in the knees, wrist and small joints of the hands and feet. These problems respond rapidly to thyroxine. In acromegaly an arthritis occurs in about 50% of patients. It resembles OA and particularly affects the small joints of the hands and knees. It may be associated with the carpal tunnel syndrome. Diabetes mellitus-related joint disorders are described.
Familial hypercholesterolaemia is associated with oligoarthritis or polyarthritis usually with tendon xanthomata. Arthritis also occurs in combined hyperlipidaerma,

Crystal deposition diseases

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

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.

EPIDEMIOLOGY

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 typical patterns of joint involvement seen in -j5tal deposition disease.

The typical patterns of joint involvement seen in
-j5tal deposition disease.

PATHOGENESIS

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.

CLINICAL FEATURES

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
• Starvation
• 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.

Causes of hyperuricaemia.

Causes of hyperuricaemia.

Signs

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.

Associated features

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.

INVESTIGATION

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.

MANAGEMENT

Acute attacks

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.

Pyrophosphate arthropathy

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.

CLINICAL FEATURES

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.

INVESTIGATION

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.

MANAGEMENT

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.

Arthritis in children

Joint pain is a common problem in childhood but arthritis is fortunately rare. Benign limb pain in childhood is sometimes called ‘growing pain’ and, though meaningless, this is probably a convenient term that parents readily accept.

JUVENILE CHRONIC ARTHRITIS

Juvenile chronic arthritis is a general term used to cover a group of diseases in which an exact diagnosis is not always possible. There are three main types: Still’s disease, juvenile RA and juvenile ankylosing spondylitis.

The differential diagnosis of arthritis in children.

The differential diagnosis of arthritis in children.

Still’s disease

This is the commonest type of juvenile chronic arthritis, accounting for about 70% of cases. It is entirely distinct from RA, being distinguished by a number of clinical features and negative tests for rheumatoid factor. There are two peaks in the age of onset: the first and largest is between the ages of 2 and 5 years, and the second between the ages of 10 and 15 years. Still’s disease occasionally begins after the age of 16 years, and rarely in the twenties. The disease is often episodic, with bouts of fever and arthritis. It can be divided into three subtypes:

1 The systemic type is usually seen in children under the age of 5 years. They present with a high fever, a characteristic rash and various other features, including lymphadenopathy, splenomegaly and pericarditis. The rash is characterized by patches of erythema on the trunk or limbs, often appearing in the evening and brought out by warmth. Arthritis or arthralgia are minor features of the illness and may be absent. Arthritis may, however, develop later in the course of the disease.
2 The pauciarticular or oligoarticular type of Still’s disease affects up to four of the large joints such as the hips, knees or ankles. These patients are particularly liable to chronic iritis, which may lead to blindness without any preceding symptoms. Antinuclear antibodies are often positive and provide a useful warning that iritis may develop. Slit-lamp examination should be performed at regular intervals in these patients. 3 Polyarticular Still’s disease presents with a bilateral symmetrical polyarthritis not unlike that of RA, but with less prominent and less frequent involvement of the small joints of the hands and feet. The characteristic systemic features described above may be associated with arthritis, whether polyarticular or pauciarticular.

DIAGNOSIS

The non-articular features of Still’s disease are often helpful in making a diagnosis. A high swinging fever is also characteristic. This can be misleading to the unwary, as it suggests the possibility of infection. The joints themselves are swollen, but pain and tenderness are much less prominent than in adult RA. The ESR is usually raised and there is frequently an anaemia.

TREATMENT

Treatment is with NSAIDs as in RA. Gold and penicillamine are effective but probably in a smaller proportion of cases than in RA. Corticosteroids should be avoided because of their effect on growth. It is important to protect the joints and prevent deformity during relapses, particularly as spontaneous remissions occur in 85% of patients before the age of 20 years. Long periods of rest and splinting of joints may be necessary. The patient’s education and normal life-style should be continued if possible.

Juvenile rheumatoid arthritis

RA may begin before 16 years of age. The clinical features re identical to those of adults and tests for rheumatoid factor are usually positive. However, the prognosis is much worse than in adults. Juvenile RA accounts for about 15% of cases of juvenile chronic arthritis. Juvenile ankylosing spondylitisThis accounts for  the remaining 15% of cases of juvenile chronic arthritis. It is the most benign of the subtypes and usually presents between the ages of 10 and 15 years. A peripheral arthritis occurs, with the lower limb joints being particularly affected. Joints are swollen and painful in the acute stage, but often respond well to antiinflammatory drugs and usually settle within a few years. These patients may develop iritis and there may be other features of HLA-B27-associated diseases . Back pain is not a prominent feature at this age. A family history of ankylosing spondylitis or related diseases is sometimes helpful in the diagnosis. Tests for rheumatoid factor are negative. Although the arthritis usually resolves, 50% of these patients go on to develop ankylosing spondylitis in adult life.

OTHER CONDITIONS

Other types of arthritis that are seen in childhood are summarized.
Some soft tissue syndromes particularly affect childrenincluding Osgood-Schlatter disease, which is characterized  by localized pain over the tibial tubercle and is usually seen in athletic teenagers. A mysterious condition called transient synovitis of the hip, which causes hip pain, may give rise to concern because of the possibility of tuberculosis or other serious conditions. It presents as painful limitation of movement of one hip, and usually resolves within a few weeks or months.

Differential diagnosis of arthritis in the elderly

Common conditions are summarized . OA is common from the age of 50 years onwards but is easily distinguished from polymyalgia rheumatica by its less dramatic onset, peripheral distribution and normal ESR; if there is any doubt, a 1 week trial of prednisolone should be given. RA can begin in elderly patients. It is often sudden in onset, with very dramatic joint inflammation (‘explosive’ RA). Unlike the disease in young patients, it often responds very well to small doses of steroids (prednisolone 10-15 mg daily) and has a good prognosis. Pyrophosphate deposition is common in elderly patients, typically presenting as a painful swollen knee. Gout and septic arthritis are other causes of acute problems in the elderly.