Useful blood screening tests

Serum autoantibody studies

Table 11.2 Conditions in which rheumatoid factor is found in the serum

Table 11.3 Conditions in which serum antinuclear antibodies are found

Joint aspiration

Examination of joint (or bursa) fluid is used mainly to diagnose septic, reactive or crystal arthritis. The appearance of the fluid is an indicator of the level of inflammation. The procedure is often undertaken in combination with injection of a corticosteroid. Aspiration alone is therapeutic in crystal arthritis (see Practical Box 11.2, p. 508).

Examination of synovial fluid

Aspiration and analysis of synovial fluid are always indicated when an infected or crystal induced arthritis is suspected, particularly a monoarthritis. Normal fluid is clear and straw coloured and contains <3000 WBC/mm³. Inflammatory fluid is cloudy and contains >3000 WBC/mm³. Septic fluid is opaque and less viscous and contains up to 75 000 WCC/mm³. There is much overlap.

Polarized light microscopy is performed for crystals.

Gram staining is essential if septic arthritis is suspected and may identify the organism immediately. Joint fluid should be cultured and antibiotic sensitivities requested.

Diagnostic imaging and visualization

Mechanical or muscular neck pain (shoulder girdle pain)

Unilateral or bilateral muscular-pattern neck pain is common and usually self-limiting. It can follow injury, falling asleep in an awkward position, or prolonged keyboard working. Chronic burning neck pain occurs because of muscle tension from anxiety and stress.

Table 11.4 Pain in the neck and shoulder

Figure 11.2 Common regional musculoskeletal problems.

Spondylosis seen on X-ray increases after the age of 40 years, but it is not always causal. Spondylosis can, however, cause stiffness and increases the risk of mechanical or muscular neck pain. Muscle spasm is palpable and tender and may lead to abnormal neck posture (e.g. acute torticollis). Muscular-pattern neck pain is not localized but affects the trapezius muscle, the C7 spinous process and the paracervical musculature (shoulder girdle pain). Pain often radiates upwards to the occiput and is commonly associated with tension headaches. These features are also seen in chronic widespread pain (see p. 509).

Nerve root entrapment

This is caused by an acute cervical disc prolapse or pressure on the root from spondylotic osteophytes narrowing the root canal.

Acute cervical disc prolapse presents with unilateral pain in the neck, radiating to the interscapular and shoulder regions. This diffuse, aching dural pain is followed by sharp, electric shock-like pain down the arm, in a nerve root distribution, often with pins and needles, numbness, weakness and loss of reflexes (Table 11.5).

Cervical spondylosis occurs in the older patient with posterolateral osteophytes compressing the nerve root and causing root pain (see Fig. 22.58, p. 1148), commonly at C5/C6 or C6/C7; it is seen on oblique radiographs of the neck. An MRI scan clearly distinguishes facet joint OA, root canal narrowing and disc prolapse.

Treatment

A support collar, rest, analgesia and sedation are used initially as necessary. Patients should be advised not to carry heavy items. It usually recovers in 6–12 weeks. MRI is the investigation of choice if surgery is being considered or the diagnosis is uncertain (Fig. 11.3). A cervical root block administered under direct vision by an experienced pain specialist may relieve pain while the disc recovers. Neurosurgical referral is essential if the pain persists or if the neurological signs of weakness or numbness are severe or bilateral. Bilateral root pain with or without long track symptoms or signs is a neurosurgical emergency because a central disc prolapse may compress the cervical spinal cord. Posterior osteophytes may cause spinal claudication and cervical myelopathy.

Figure 11.3 MRI of cervical spine, showing a large central disc prolapse impinging on the spinal cord (arrow) at the C6/7 level.

Whiplash injury

Whiplash injury results from acceleration–deceleration forces applied to the neck, usually in a road traffic accident when the car of a person wearing a seat belt is struck from behind. A simple decision plan based on clinical criteria helps to distinguish those most at risk and who warrant radiography. There is a low probability of serious bony injury if there is:

CT scans are reserved for those with bony injury. MRI scans occasionally show severe soft tissue injury. Whiplash injuries commonly lead to litigation.

Whiplash injury is a common cause of chronic neck pain, although most people recover within a few weeks or months. Delayed recovery depends in part upon the severity of the initial injury. The pattern of chronic neck pain is often complex, involving pain in the neck, shoulder and arm. Subjective symptoms such as headache, dizziness, and poor concentration sometimes accompany this. The subjective nature of these symptoms has led to controversy about their cause. The problem is more commonly seen in industrialized countries where the conflictive nature of the compensation process may actually delay recovery. Non-conflictive means of compensation may lead to a better prognosis.

Treatment is with reassurance (the patient is often distressed and anxious), analgesia, a short-term support collar and physiotherapy. Pain may take a few weeks or months to settle and the patient should be warned of this.

Rotator cuff (supraspinatus) tendonosis

This is a common cause of shoulder pain at all ages. It follows trauma in 30% of cases and is bilateral in under 5%. The pain radiates to the upper arm and is made worse by arm abduction and elevation, which are often limited. The pain is often worse during the middle of the range of abduction, reducing as the arm is raised fully; a so-called ‘painful arc syndrome’. When examined from behind, the scapula rotates earlier than usual during elevation. Passive elevation reduces impingement and is less painful. Severe pain virtually immobilizes the joint, although some rotation is retained (cf. adhesive capsulitis, see below). There is also painful spasm of the trapezius. There may be an associated subacromial bursitis. Isolated subacromial bursitis occurs after direct trauma, falling on to the outstretched arm or elbow. Acromioclavicular osteophytes increase the risk of impingement and may need to be removed surgically.

X-rays or ultrasound are necessary only when rotator cuff tendonosis is persistent or the diagnosis is uncertain.

Torn rotator cuff

This is caused by trauma but also occurs spontaneously in the elderly and in rheumatoid arthritis (RA). It prevents active abduction of the arm, but patients learn to initiate elevation using the unaffected arm. Once elevated, the arm can be held in place by the deltoid muscle. In younger people, the tear is repaired surgically but this is rarely possible in the elderly or in RA. Some patients require arthroscopic surgery.

Calcific tendonosis and bursitis

Calcium pyrophosphate deposits in the tendon are visible on X-ray, but they are not always symptomatic. The pathogenesis is unclear, although ischaemia may play a part. The deposit is usually just proximal to the greater tuberosity. It may lead to acute or chronic recurrent shoulder pain and restriction of movement. A local corticosteroid injection may relieve the pain. The calcification may persist or resolve. Aspiration or breaking up of the deposit under ultrasound control may be required for persistent pain. Rarely, arthroscopic removal is necessary.

Shedding of crystals into the subacromial bursa causes a bursitis with severe pain and shoulder restriction. The shoulder feels hot and is swollen, and an X-ray shows a diffuse opacity in the bursa. The differential diagnosis of calcific bursitis is gout, pseudogout or septic arthritis. Aspiration and injection with corticosteroid can help.

Adhesive capsulitis (true ‘frozen’ shoulder)

This is uncommon but can develop with rotator cuff lesions, or following hemiplegia, chest or breast surgery or myocardial infarction. It causes severe shoulder pain and complete loss of all shoulder movements, including rotation. High doses of NSAIDs and intra-articular injections of local anaesthetic and corticosteroids are helpful. Once the pain settles, arthroscopic release speeds functional recovery.

Epicondylitis

Two common sites where the insertions of tendons into bone become inflamed (enthesitis) are the insertions of the wrist extensor tendon into the lateral epicondyle (‘tennis elbow’) and the wrist flexor tendon into the medial epicondyle (‘golfer’s elbow’). Both are usually unrelated to either sporting activity.

There is local tenderness. Pain radiates into the forearm on using the affected muscles – typically, gripping or holding a heavy bag in tennis elbow or carrying a tray in golfer’s elbow. Pain at rest also occurs.

Treatment

Advise rest and arrange review by a physiotherapist. A local injection of corticosteroid at the point of maximum tenderness is helpful when the pain is severe but needs physiotherapy follow-up to prevent recurrences (Fig. 11.5). Avoid the ulnar nerve when injecting golfer’s elbow. Both conditions settle spontaneously eventually, but occasionally persist and require surgical release.

Figure 11.5 Injection for tennis elbow.

Tenosynovitis

The finger flexor tendons run through synovial sheaths and under loops which hold them in place. Inflammation occurs with repeated or unaccustomed use, or in inflammatory arthritis. The thickened sheaths are often palpable.

Flexor tenosynovitis causes finger pain when gripping and stiffness of the fingers in the morning. Occasionally a tendon causes a trigger finger, when the finger remains flexed in the morning or after gripping and has to be pulled straight. A tender tendon nodule is palpable, usually in the distal palm. Trigger finger or thumb is commoner in diabetic patients.

Dorsal tenosynovitis is less common except in rheumatoid arthritis. The hourglass swelling extends from the back of the hand and under the extensor retinaculum.

De Quervain’s tenosynovitis causes pain and swelling around the radial styloid where the abductor pollicis longus tendon is held in place by a retaining band. There is local tenderness, and the pain at the styloid is worsened by flexing the thumb into the palm.

Carpal tunnel syndrome

This is due to median nerve compression in the limited space of the carpal tunnel. Thickened ligaments, tendon sheaths or bone enlargement can cause it, but it is usually idiopathic. (Causes are discussed on p. 1144.) The history is usually typical and diagnostic with the patient waking with numbness, tingling and pain in a median nerve distribution. The pain radiates to the forearm. The fingers feel swollen but usually are not. Wasting of the abductor pollicis brevis develops with sensory loss in the radial three and a half fingers. The pain may be produced by tapping the nerve in the carpal tunnel (Tinel’s sign) or by holding the wrist in flexion (Phalen’s test).

Treatment is with a splint to hold the wrist in dorsiflexion overnight. This relieves the symptoms and is diagnostic; used nightly for several weeks it may produce full recovery. If it does not, a corticosteroid injection into the carpal tunnel (avoid the nerve!) helps in about 70% of cases, although it may recur. Persistent symptoms or nerve damage produce prolonged latency across the carpal tunnel on nerve conduction studies and require surgical decompression.

Other conditions causing pain

Inflammatory arthritis. This may present with pain, swelling and stiffness of the hands. In RA the wrists, proximal interphalangeal (PIP) joints and metacarpophalangeal (MCP) joints are affected symmetrically. In psoriatic arthritis and reactive arthritis a finger may be swollen (dactylitis) or the distal interphalangeal (DIP) joints and nails are affected asymmetrically.

Nodal osteoarthritis. This affects the DIP and less commonly PIP joints, which are initially swollen and red. The inflammation and pain settle but bony swellings remain (p. 514).

First carpometacarpal osteoarthritis. This causes pain at the base of the thumb when gripping, or painless stiffness at the base of the thumb, often in persons with nodal osteoarthritis.

Scaphoid fractures. These cause pain in the anatomical snuffbox. They are not seen immediately on X-ray. A cast is necessary. Untreated scaphoid fractures can eventually cause pain because of failed union.

Ganglion. A ganglion is a jelly-filled, often painless swelling caused by a partial tear of the joint capsule or tendon sheath. The wrist is a common site. Treatment is not essential as many resolve or cause little trouble, otherwise surgical excision is the best option.

Dupuytren’s contracture

This is a painless, palpable fibrosis of the palmar aponeurosis, with fibroblasts invading the dermis due to abnormal signalling in the Wnt pathway. It causes puckering of the skin and gradual flexion, usually of the ring and little fingers. It is more common in males, Caucasians, in diabetes mellitus and in those who overuse alcohol. A similar fibrosis occurs in the feet and is often more aggressive. It is also associated with Peyronie’s disease of the penis – a painful inflammatory disorder of the corpora cavernosa, leading eventually to painless fibrosis and angulation of the penis during erection. Intralesional steroid injections may help in early disease and some advocate transcutaneous needle aponeurotomy. Collagenase injection into the collagen contracted cord improved the amount of movement in one randomized study. Plastic surgical release of the contracture is restricted to those with severe deformity of the fingers.

Mechanical low back pain

Mechanical low back pain starts suddenly, may be recurrent and is helped by rest. It is often precipitated by an injury and may be unilateral or bilateral. It is usually short-lived.

Examination and management

The back is stiff and a scoliosis may be present when the patient is standing. Muscular spasm is visible and palpable and causes local pain and tenderness. It lessens when sitting or lying. Pain relief and physiotherapy are helpful. Acupuncture helps some. Excessive rest should be avoided. Re-education in lifting and exercises help to prevent recurrent attacks of pain. Once a patient develops low back pain, although the episode itself is usually self-limiting, there is a significantly increased risk of further back pain episodes. Risk factors for recurrent back pain include:

female sex

increasing age

pre-existing chronic widespread pain (fibromyalgia)

psychosocial factors such as high levels of psychological distress, poor self-rated health and dissatisfaction with employment.

Chronic low back pain is a major cause of disability and time off work and is reduced by appropriate early management.

Spinal movement occurs at the disc and the posterior facet joints, and stability is normally achieved by a complex mechanism of spinal ligaments and muscles. Any of these structures may be a source of pain. An exact anatomical diagnosis is difficult, but some typical syndromes are recognized (see below). They are often associated with but not necessarily caused by radiological spondylosis (see p.1148).

Postural back pain develops in individuals who sit in poorly designed, unsupportive chairs.

Lumbar spondylosis. The fundamental lesion in spondylosis occurs in an intervertebral disc, a fibrous joint whose tough capsule inserts into the rim of the adjacent vertebrae. This capsule encloses a fibrous outer zone and a gel-like inner zone. The disc allows rotation and bending.

Changes in the discs occasionally start in teenage years or early 20s and often increase with age. The gel changes chemically, breaks up, shrinks and loses its compliance. The surrounding fibrous zones develop circumferential or radial fissures. In the majority this is initially asymptomatic but visible on MRI as decreased hydration. Later the discs become thinner and less compliant. These changes cause circumferential bulging of the intervertebral ligaments.

Reactive changes develop in adjacent vertebrae; the bone becomes sclerotic and osteophytes form around the rim of the vertebra (Fig. 11.6). The most common sites of lumbar spondylosis are L5/S1 and L4/L5.

Figure 11.6 MRI of lumbar spine, showing a central disc prolapse at the L4/L5 level (arrow). The signal from the L4/L5 and L5/S1 discs indicates dehydration, while the L3/L4 signal appearance is normal.

In young people, disc prolapse through an adjacent vertebral endplate produces a Schmorl’s node on X-ray. This is painless but may accelerate disc degeneration.

Spondylosis may be symptomless, but it can cause:

Episodic mechanical spinal pain

Progressive spinal stiffening

Facet joint pain

Acute disc prolapse, with or without nerve root irritation

Spinal stenosis

Spondylolisthesis.

Facet joint syndrome. Lumbar spondylosis also causes secondary osteoarthritis of the misaligned facet joints. Pain is typically worse on bending backwards and when straightening from flexion. It is lumbar in site, unilateral or bilateral and radiates to the buttock. The facet joints are well seen on MRI and may show osteoarthritis, an effusion or a ganglion cyst. Direct corticosteroid injections into the joints under imaging may help but their long-term value is unclear. Physiotherapy to reduce hyperlordosis and reducing weight are helpful.

Fibrositic nodulosis. This causes unilateral or bilateral low back and buttock pain. There are tender nodules in the upper buttock and along the iliac crest. Such nodules are relevant only if they are tender. They are probably traumatic. Local, intralesional corticosteroid injections help.

Postural back pain and sway back of pregnancy. Low back pain is common in pregnancy and reflects altered spinal posture and increased ligamentous laxity. There is usually a hyperlordosis on examining the patient standing. Weight control and pre- and postnatal exercises are helpful, and the pain usually settles after delivery. Analgesics and NSAIDs are best avoided during pregnancy and breast-feeding. Epidurals during delivery are not associated with an increased incidence of subsequent back pain. Poor posture causes a similar syndrome in the non-pregnant, owing to obesity or muscular weakness. Poor sitting posture at work is a frequent cause of chronic low back pain.

FURTHER READING

Balagué F, Mannion A, Pellise F, Cedraschi C. Non-specific low back pain. Lancet 2012; 379:482–491.

FURTHER READING

Lamb SE et al. group cognitive behavioural therapy for low back pain in primary care. Lancet 2010; 375:916–923.

Acute lumbar disc prolapse

The central disc gel may extrude into a fissure in the surrounding fibrous zone and cause acute pain and muscle spasm. These events are often self-limiting. A disc prolapse occurs when the extrusion extends beyond the limits of the fibrous zone (Fig. 11.6). The weakest point is posterolateral, where the disc may impinge on emerging spinal nerve roots in the root canal.

The episode often starts dramatically during lifting, twisting or bending and produces a typical combination of low back pain and muscle spasm, and severe, lancinating pains, paraesthesia, numbness and neurological signs in one leg (rarely both). The back pain is diffuse, usually unilateral and radiates into the buttock. The muscle spasm leads to a scoliosis that reduces when lying down. The nerve root pain develops with, or soon after, the onset. The site of the pain and other symptoms is determined by the root affected (Table 11.8). A central high lumbar disc prolapse may cause spinal cord compression and long tract signs (i.e. upper motor neurone). Below L2/L3 it produces lower motor neurone lesions.

On examination, the back often shows a marked scoliosis and muscle spasm. The straight-leg-raising test, whilst lying, is positive in a lower lumbar disc prolapse – raising the straight leg beyond 30° produces pain in the leg. Slight limitation or pain in the back limiting this movement is seen with mechanical back pain. Pain in the affected leg produced by a straight raise of the other leg suggests a large or central disc prolapse. Look for perianal sensory loss and urinary retention, which indicate a cauda equina lesion – a neurosurgical emergency (see p. 1135). An upper lumbar disc prolapse produces a positive femoral stretch test; pain in the anterior thigh when the knee is flexed in the prone position.

Spinal and root canal stenosis

Progressive loss of disc height, OA of the facet joints, posterolateral osteophytes and buckling of the ligamentum flavum all contribute to root canal stenosis. This causes nerve root pain or spinal root claudication – pain and paraesthesiae in a root distribution brought on by walking and relieved slowly by rest. The associated sensory symptoms, slower recovery when the patient rests, and presence of normal foot pulses distinguish this from peripheral arterial claudication. Severe cervical spondylosis may also produce spinal claudication, often with arm symptoms and signs.

Spinal canal stenosis at more than one level is often associated with severe spondylosis and/or a congenitally narrow spinal canal. It causes buttock and bilateral leg pain, ‘heaviness’, paraesthesiae and numbness when walking. Rest helps, as does bending forwards, a manoeuvre that opens the spinal canal. Specialist surgical advice is necessary.

Spondylolisthesis

This occurs in adolescents and young adults when bilateral congenital pars interarticularis defects cause instability and permit a vertebra to slip, with or without preceding injury. Rarely, a cauda equina syndrome with loss of bladder and anal sphincter control and saddle-distribution anaesthesia develops. It is diagnosed radiologically. Low back pain in adolescents warrants investigation, and spondylolisthesis requires orthopaedic assessment. It needs careful monitoring during the growth spurt.

A degenerative spondylolisthesis may also develop in older people with lumbar spondylosis and osteoarthritis of the facet joints.

Diffuse idiopathic skeletal hyperostosis (DISH)

DISH (Forestier’s disease) affects the spine and extraspinal locations. It causes bony overgrowths and ligamentous ossification and is characterized by flowing calcification over the anterolateral aspects of the vertebrae. The spine is stiff but not always painful, despite the dramatic X-ray changes. Ossification at muscle insertions around the pelvis produces radiological ‘whiskering’. Similar changes occur at the patella and in the feet. It is commoner in people with metabolic syndrome (high BMI, diabetes mellitus, hypertension and dyslipidaemia; see p. 1006).

Treatment is with analgesics or NSAIDs for pain, and exercise to retain movement and muscle strength.

Osteoporotic crush fracture of the spine

Osteoporosis is asymptomatic but leads to an increased risk of fracture of peripheral bones, particularly neck of femur and wrist, and thoracic or lumbar vertebral crush fractures. Such vertebral fractures develop without trauma, after minimal trauma, or as part of a major accident. They may develop painlessly or cause agonizing localized pain that radiates around the ribs and abdomen. Multiple fractures lead to an increased thoracic kyphosis (‘widow’s stoop’). They cause disability and reduced QoL. The diagnosis is confirmed by X-rays, showing loss of anterior vertebral body height and wedging, with sparing of the vertebral endplates and pedicles. Bone oedema on MRI indicates that a fracture is recent. An underlying tumour and pathological fracture need to be excluded.

Osteoarthritis (OA)

OA (see p. 512) is the most common cause of hip joint pain in a person over the age of 50 years. It causes pain in the buttock and groin on standing and walking. Stiff hip movements cause difficulty in putting on a sock and may produce a limp. Sudden onset pain may be associated with an effusion on MRI and can be treated by an ultrasound guided steroid injection.

Lateral hip pain syndrome: trochanteric bursitis and gluteus medius tendonopathy

This may be due to trochanteric bursitis and caused by trauma or unaccustomed exercise. It also occurs in inflammatory arthritis. The pain over the trochanter is worse going up stairs, and the trochanter is tender to lie on. Its best management is unclear but exercises help, as may a local corticosteroid injection, although the evidence base for treatment is poor. Surgery is occasionally necessary. Lateral hip pain may be referred from the upper lumbar spine. A tear of the gluteus medius tendon at its insertion into the trochanter causes a similar syndrome but does not respond to injection. MRI scans have demonstrated this new syndrome.

Meralgia paraesthetica

This causes numbness and burning dysaesthesia (increased sensitivity to light touch) over the anterolateral thigh and may be precipitated by a sudden increase in weight, an injury or during pelvic surgery. It is usually self-limiting but can be helped by amitriptyline or gabapentin at night.

Fracture of the femoral neck

This usually occurs after a fall, occasionally spontaneously. There is pain in the groin and thigh, weight-bearing is painful or impossible, and the leg is shortened and externally rotated. Occasionally, a fracture is not displaced and remains undetected. X-rays are diagnostic. Anyone with a hip fracture, especially after minimal trauma, should be reviewed for osteoporosis (see p. 553).

Avascular necrosis (osteonecrosis) of the femoral head

This is uncommon but occurs at any age. (Risk factors are discussed on p. 556.) There is severe hip pain. X-rays are diagnostic after a few weeks, when a well-demarcated area of increased bone density is visible at the upper pole of the femoral head. The affected bone may collapse. Early, the X-ray is normal but bone scintigraphy or MRI demonstrates the lesion and shows bone marrow oedema.

Inflammatory arthritis of the hip

This produces pain in the groin and stiffness, which are worse in the morning. Rheumatoid arthritis (RA) rarely presents with hip pain, although the hip is involved eventually in severe RA. Ankylosing spondylitis and other seronegative spondyloarthropathies cause inflammatory hip arthritis in younger people.

Polymyalgia rheumatica

Bilateral hip, buttock and thigh pain and stiffness that are worse in the morning in an elderly patient may be attributable to polymyalgia rheumatica (see p. 542). Neck and shoulder pain and stiffness are usually also present.

Treatment (see p. 1163)

A sympathetic, psychosocial, multidisciplinary approach is appropriate. A graded, supervised aerobic exercise regimen over 3 months is safe and effective. When depression is present, it should be treated. Cognitive behavioural therapy can help the person to pace their life more effectively and to cope better, although patients often resist referral for psychological help.

Treatment

If possible, there should be a brief period off work and a gradual return to activity as the pain settles. Use of analgesia and NSAIDs, with physiotherapy, is helpful during the initial phase to prevent a vicious circle developing. Amitriptyline or pregabalin is helpful for some patients.

A review of working practices and the positioning of screen, keyboard and chair are essential, as is support of the patient by their manager. Musicians are helped by expert advice on playing technique and should reduce playing times temporarily, but not stop completely.

Treatment

Management is difficult and the problem often very disabling. The evidence base for treatment is poor. Early diagnosis, effective pain relief and general care of the patient are essential. NSAIDs, corticosteroids and pregabalin or gabapentin are used in the early phase, together with active exercise of the limb encouraged by a physiotherapist. Intravenous disodium pamidronate can be used at this stage. Referral to a specialist pain clinic is essential. A stellate ganglion block may help upper limb involvement and a sympathetic chain block for the lower limb. Guanethidine (an alpha-blocking agent) or lidocaine administered to the limb under tourniquet are also used.

Epidemiology

The prevalence of OA increases with age; it is uncommon below the age of 50 years and most people over 60 years will have some radiological evidence of it, although only a quarter of these will be symptomatic. It occurs worldwide, but with a variable distribution, e.g. in Asians, hip OA is less common and knee OA is more common than in Europeans. Women over 55 years are affected more commonly than men of a similar age. There is a familial pattern of inheritance in nodal OA and in primary generalized OA. OA has a variable distribution (Fig. 11.10). The resulting disabilities have major socioeconomic resource implications, particularly in the developed world. OA is the most common cause of disability in the Western world in older adults.

Figure 11.10 Typical distribution of affected joints in (a) primary generalized OA and (b) pyrophosphate arthropathy; dark blobs, more commonly affected; pale blobs, less commonly affected.

Aetiology (Box 11.4)

The gene that encodes collagen type II (COL2A1) is a candidate gene for familial OA but there is no single gene that associates with all patterns of OA. Abnormal local mechanical factors which affect loading and wear, such as prior injury, instability, hypermobility and joint dysplasia, play a role in most types of OA. Inflammation starting at periarticular entheses is seen during the inflammatory phase on MRI in nodal OA. Osteoarthritis is the result of active, sometimes inflammatory but potentially reparative processes rather than the inevitable result of trauma and ageing. Focal destruction of the articular cartilage is the common pathological feature. The spectrum of OA ranges from atrophic disease in which cartilage destruction occurs without any subchondral bone response, to hypertrophic disease in which there is massive new bone formation at the joint margins.

Cartilage is a matrix of collagen fibres, which enclose a mixture of proteoglycans and water (see p. 494). The gene for human aggrecan has been cloned, and polymorphisms of the gene have been correlated with OA of the hand in older men.

Cartilage is smooth-surfaced and shock-absorbing. Under normal circumstances, there is a dynamic balance between cartilage degradation by wear and its production by chondrocytes. Early in the development of OA, this balance is lost and, despite increased synthesis of extracellular matrix, the cartilage becomes oedematous. Focal erosion of cartilage develops. Chondrocytes die and, although repair is attempted from adjacent cartilage, the process is disordered. Eventually the synthesis of extracellular matrix fails and the surface becomes fibrillated and fissured. Cartilage ulceration exposes underlying bone to increased stress, producing microfractures and cysts. The bone attempts repair but produces abnormal sclerotic subchondral bone and overgrowths at the joint margins, called osteophytes (Fig. 11.11). There is some secondary inflammation.

Figure 11.11 Early osteoarthritis of a knee (diagram and X-ray). There is a medial compartment narrowing owing to cartilage thinning with subarticular sclerosis and marginal osteophyte formation (arrows).

Pathogenesis

Several mechanisms have been suggested:

The term primary OA is sometimes used when there is no obvious known predisposing factor.

Box 11.4 shows some of the predisposing factors for the development of OA, and Table 11.12 shows other conditions that sometimes cause secondary arthritis.

Table 11.12 Causes of osteoarthritis

Clinical features

Osteoarthritis affects many joints, with diverse clinical patterns. Hip and knee OA are major causes of disability. Early OA is rarely symptomatic unless accompanied by a joint effusion, whilst advanced radiological and pathological OA is not always symptomatic.

Some flare-ups are due to inflammation and there may be a slight rise in ESR or CRP. Focal synovitis is caused by fragments of shed bone or cartilage. Radiological OA is usually, but not inevitably, progressive. This progression may be stepwise or continual. Radiological improvement is uncommon but has been observed, suggesting that repair is possible.

Clinical subsets

Localized OA

Nodal OA (Table 11.13)

Joints of the hand are usually affected one at a time over several years, with the distal interphalangeal joints (DIPs) being more often involved than the proximal interphalangeal joints (PIPs). Nodal OA often starts around the female menopause. The onset may be painful and associated with tenderness, swelling and inflammation and impairment of hand function. At this stage, enthesitis can be seen on MRI. An intra-articular corticosteroid injection can be used at this stage, if deemed necessary. The inflammatory phase settles after some months or years, leaving painless bony swellings posterolaterally: Heberden’s nodes (DIPs) and Bouchard’s nodes (PIPs), along with stiffness and deformity (Fig. 11.12). Functional impairment is slight for most, although PIP osteoarthritis restricts gripping more than DIP involvement. On X-ray, the nodes are marginal osteophytes and there is joint space loss.

Table 11.13 Features of nodal OA

Familial Has a higher incidence in women Typical pattern of polyarticular involvement of the hand joints Develops in late middle age and around female menopause Has a generally good long-term functional outcome Associated with OA of the knee, hip and spine (NGOA)

Figure 11.12 Severe nodal osteoarthritis. The DIP joints demonstrate Heberden’s nodes (arrows). The middle finger DIP joint is deformed and unstable. The thumb is adducted and the bony swelling of the first carpometacarpal joint is clearly shown – ‘the squared hand of nodal OA’.

Thumb base OA co-exists with nodal OA and causes pain and disability, which decrease as the joint stiffens. The ‘squared’ hand in OA (Fig. 11.12) is caused by bony swelling of the carpometacarpal joint and fixed adduction of the thumb. Function is rarely severely compromised.

Polyarticular hand OA is associated with a slightly increased frequency of OA at other sites.

Hip OA

Hip OA (see p. 494) affects 7–25% of adult Caucasians but is significantly less common in black African and Asian populations. There are two major subgroups defined by the radiological appearance. The most common is superior-pole hip OA, where joint space narrowing and sclerosis predominantly affect the weight-bearing upper surface of the femoral head and adjacent acetabulum. This is most common in men and unilateral at presentation, although both hips may become involved because the disease is progressive. Early onset of hip OA is associated with acetabular dysplasia or labral tears. Less commonly, medial cartilage loss occurs. This is most common in women and associated with hand involvement (nodal generalized OA – NGOA), and is usually bilateral. It is more rapidly disabling.

Knee OA

The prevalence of symptomatic knee OA is 40% in individuals aged over 75 years. It is commoner in women than in men. There is a strong relationship with obesity. The disease is generally bilateral and strongly associated with nodal OA of the hand in elderly women, or as part of generalized OA. The medial compartment is most commonly affected and leads to a varus (bow-legged) deformity. There is often also retropatellar OA. Previous trauma, meniscal and cruciate ligament tears are risk factors for developing knee OA. Bone marrow lesions seen on MRI predict disease progression and eventual joint replacement.

Primary generalized OA

This is rare but is usually seen in combination with nodal OA – NGOA. The other joints affected are the knees, first MTP, hip, and intervertebral (spondylosis). Its onset is often sudden and severe. There is a female preponderance and a strong familial tendency. Periarticular ligamentous pathology may have an important role in the phenotypic expression of NGOA.

Erosive OA

This is rare. The DIPs and PIPs are inflamed and equally affected and the functional outcome is poor. Radiologically, there is marked osteolysis. Destructive phases are followed by phases of remodelling.

Crystal-associated OA

This is most commonly seen with calcium pyrophosphate deposition in the cartilage (chondrocalcinosis). Chondrocalcinosis increases in frequency with age and is seen on over 40% of knee X-rays in the over-80s, but is usually asymptomatic. The joints most commonly affected are the knees (hyaline cartilage and fibrocartilage) and wrists (triangular fibrocartilage, see Fig. 11.10). There is patchy linear calcification on X-ray (Fig. 11.13).

Figure 11.13 Chondrocalcinosis of the knee. Note the linear calcification in the hyaline cartilage and calcification of the lateral meniscus (plus mild secondary OA).

A chronic arthropathy (pseudo-OA) occurs, predominantly in elderly women with severe chondrocalcinosis. There is a florid inflammatory component and marked osteophyte and cyst formation visible on X-rays. The joints affected differ from NGOA, being predominantly the knees, then wrists and shoulders. Chondrocalcinosis is associated with pseudogout, an acute crystal-induced arthritis (see p. 532).

A rare, rapidly destructive arthritis in elderly women, affecting shoulders, hips and knees, is associated with finding crystals of calcium apatite in a bloody joint effusion. The outlook is poor and joints require early surgical replacement.

Investigations in OA

Management

The guiding principle is to treat the symptoms and disability, not the radiological appearances; depression and poor quadriceps strength are better predictors of pain than is radiological severity in OA of the knee. Education of the individual about the disease and its effects reduces pain, distress and disability and increases compliance with treatment. Psychological or social factors alter the impact of the disease.

Epidemiology

RA has a worldwide distribution and affects 0.5–1% (with a female preponderance of 3:1) of the population. The prevalence is low in black Africans and Chinese people. The incidence is falling. RA remains a significant cause of disability and mortality and carries a high socioeconomic cost. It presents from early childhood (when it is rare) to late old age. The most common age of onset is between 30 and 50 years.

Aetiology and pathogenesis

The cause is multifactorial and genetic and environmental factors play a part.

Pathology

Rheumatoid arthritis is typified by widespread persistent synovitis (inflammation of the synovial lining of joints, tendon sheaths or bursae). The normal synovium is thin and comprises a lining layer a few cells thick containing fibroblast-like synoviocytes and macrophages overlying loose connective tissue. The synoviocytes play a central role in synovial inflammation. In RA the synovium becomes greatly thickened and causes ‘boggy’ swelling around the joints and tendons. There is proliferation of the synovium into folds and fronds, and it is infiltrated by a variety of inflammatory cells, including polymorphs, which transit through the tissue into the joint fluid, and lymphocytes and plasma cells. There are disorganized lymphoid follicles. The normally sparse surface layer of lining cells becomes hyperplastic and thickened (Fig. 11.14). There is marked vascular proliferation. Increased permeability of blood vessels and the synovial lining layer leads to joint effusions that contain lymphocytes and dying polymorphs.

Figure 11.14 Histological appearance of RA synovium. (a) Normal synovium. (b) Synovial appearances in established RA, showing marked hypertrophy of the tissues with infiltration by lymphocytes and plasma cells.

(From Shipley M. Colour Atlas of Rheumatology, 3rd edn. London: Mosby-Wolfe; 1993, with permission.)

The hyperplastic synovium spreads from the joint margins on to the cartilage surface. This ‘pannus’ of inflamed synovium damages the underlying cartilage by blocking its normal route for nutrition and by the direct effects of cytokines on the chondrocytes. The cartilage becomes thinned and the underlying bone exposed. Local cytokine production and joint disuse combine to cause juxta-articular osteoporosis during active synovitis.

Fibroblasts from the proliferating synovium also grow along the course of blood vessels between the synovial margins and the epiphyseal bone cavity and damage the bone. This is shown by MRI to occur in the first 3–6 months following onset of the arthritis, and before the diagnostic, ill-defined juxta-articular bony ‘erosions’ appear on X-ray (Fig. 11.15). This early damage justifies the use of DMARDs (see p. 523) within 3–6 months of onset of the arthritis. Low-dose steroids delay and anti-TNF-α agents halt and occasionally reverse erosion formation. Erosions lead to a variety of deformities and contribute to long-term disability.

Figure 11.15 X-ray of early RA, showing typical erosions at the thumb (black and white arrows) and middle MCP joints (black arrow) and at the ulnar styloid (white arrow).

Typical presentation

The most typical presentation of rheumatoid arthritis (approximately 70% of cases) begins as a slowly progressive, symmetrical, peripheral polyarthritis, evolving over a period of a few weeks or months. The patient is usually between 30 and 50 years of age, but the disease can occur at any age. Less commonly (15%) a rapid onset can occur over a few days (or explosively overnight) with a severe symmetrical polyarticular involvement, especially in the elderly. Factors which indicate a poor prognosis are listed in Box 11.6. The differential diagnosis of early RA is shown in Box 11.7.

Older classification criteria used to distinguish RA from other forms of arthritis (American College of Rheumatology, ACR criteria 1987) are now mainly used to ensure matched groups for research. The newer criteria that have replaced them are more suitable for assessing early arthritis because they do not rely on later changes such as erosions and extra-articular disease (Box 11.8).

In early RA, the combination of at least one swollen joint for more than 6 weeks with no prior injury and no associated history or family history of spondyloarthritis or associated conditions such as psoriasis (see p. 1207) and a positive ACPA test is the best way to select patients for earlier treatment to avoid joint damage. This earlier treatment is evidence based and has been shown to reduce the risk of the development of damage and thus reduce permanent joint deformities.

Symptoms and signs

Other presentations

The presentation and progression of RA is variable. Presentations are shown in Box 11.9. Relapses and remissions occur either spontaneously or on drug therapy. In some patients, the disease remains active, producing progressive joint damage. Rarely, the process may cease (‘burnt-out RA’).

Seronegative RA initially affects the wrists more often than the fingers and has a less symmetrical joint involvement. It has a better long-term prognosis, but some cases progress to severe disability. This form can be confused with psoriatic arthropathy, which has a similar distribution (p. 528).

Palindromic rheumatism is unusual (5%) and consists of short-lived (24–72 hours) episodes of acute monoarthritis. The joint becomes acutely painful, swollen and red, but resolves completely. Further attacks occur in the same or other joints. About 50% go on to develop typical chronic rheumatoid synovitis after a delay of months or years. The rest remit or continue to have acute episodic arthritis. The detection of RF or ACPA predicts conversion to chronic, destructive synovitis.

Complications (Table 11.15)

Non-steroidal anti-inflammatory drugs (NSAIDs) and coxibs

Most people with RA are unable to cope without an NSAID to relieve night pain and morning stiffness. NSAIDs do not reduce the underlying inflammatory process. They all act on the cyclo-oxygenase (COX) pathway (see Fig. 15.30). The individual response to NSAIDs varies greatly. It is desirable therefore to try several different drugs for a particular patient in order to find the best (Box 11.13). Each compound should be given for at least a week. Start with an inexpensive NSAID with few side-effects and with which you are familiar. Regular doses are needed to be effective. The major side-effects of NSAIDs and the use of coxibs are discussed on page 511. If gastrointestinal side-effects are prominent, or the patient is over 65 years of age, add a proton pump inhibitor. Slow-release preparations (e.g. slow-release diclofenac, 75 mg, taken after supper), or a suppository at bedtime, usually work well. For additional relief, a simple analgesic is taken as required (e.g. paracetamol or a combination of codeine or dihydrocodeine and paracetamol). Many patients need night sedation.

Corticosteroids

There is evidence to suggest that the early use of corticosteroids slows down the course of the disease but intensive short courses in very early arthritis do not appear to stop progressive disease. Corticosteroids are the commonest cause of secondary osteoporosis. Treatment for more than 3 months or with repeated courses is a risk, and concomitant calcium with vitamin D and bisphosphonates is necessary.

Intra-articular injections with semicrystalline steroid preparations have a powerful but sometimes only short-lived effect.

Intramuscular depot injections (40–120 mg depot methylprednisolone) help whilst waiting for DMARDs to work and to control severe disease flares, or they can be used before a holiday or other life event. They should be used infrequently.

Oral corticosteroids have a number of problems (Boxes 11.11 and 19.11). They are powerful disease-controlling drugs, but are avoided in the long term because side-effects are inevitable. Early intensive short-term regimens are often used. Doses of 5–7.5 mg daily as maintenance therapy are used in some centres. Corticosteroids are invaluable to people with severe disease with extra-articular manifestations such as vasculitis.

Disease-modifying anti-rheumatic drugs (DMARDs)

DMARDs, prescribed by a rheumatologist, are listed in Table 11.16 (see also Fig. 11.19).

Figure 11.19 American College of Radiology ACR50 responses in trials of DMARDs and biological agents (50% improvement in five of seven measures in the ACR 1987 criteria).^a,b (a) ACR50 response in trials of DMARDs and biological agents. (b) Impact of treatment duration, disease stage and prior treatment on ARC50 response. The difference between patients treated with active drug and placebo is greatest in people with late rheumatoid arthritis who have failed biological treatment and whose disease is managed for short periods. The difference is smallest in individuals with early arthritis who have not previously received DMARDs and are treated for a long time. American College of Rheumatology 1987 criteria for diagnosis of RA (revised 1988) have been superseded (see Box 11.8) but are used in trials, with ≥4 criteria necessary for diagnosis: morning stiffness >1 hours for ≥6 weeks; arthritis of ≥3 joints for ≥6 weeks; arthritis of hand joints and wrists for ≥6 weeks; symmetrical arthritis, subcutaneous nodules; positive serum rheumatoid factor; typical radiological changes (erosions and/or periarticular osteopenia). Error bars 95% CIs.

(From Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet 2010; 376:1094–1108, with permission.)

DMARDs are used as early as possible once RA has been diagnosed. Studies suggest that early intervention with DMARDs at 6 weeks to 6 months improves the outcome. Combinations of three or four drugs (steroids, sulfasalazine, methotrexate and hydroxychloroquine) in early RA are increasingly common, reducing the number of agents once remission has been achieved. Most DMARDs are contraindicated in pregnancy (Box 11.13). Effective treatment with DMARDs reduces the increased cardiovascular risk seen in people with RA.

Drugs used less commonly

Gold (sodium aurothiomalate) is given by deep intramuscular injection. A response (occasionally remission) is seen in about 3 months. Side-effects or lack of effect mean that few patients remain on it beyond 2 years. Blood and urine testing are mandatory.

D-Penicillamine is given before food for at least 3 months before improvement occurs. If proteinuria exceeds 2 g/24 hours the drug must be stopped. Loss of taste is reversible. Other rare side-effects include a lupus erythematosus-like syndrome and a myasthenia gravis-like syndrome.

Azathioprine at a maximum dose of 2.5 mg/kg and cyclophosphamide 1–2 mg/kg have been used, usually when other DMARDs have been ineffective. They are often used when extra-articular features are severe, particularly with vasculitis. There is a high risk of neutropenia and possibly liver toxicity from azathioprine in patients who have low levels of the enzyme thiopurine methyltransferase (TPMT) which metabolizes azathioprine into its active metabolites. Pretesting is a wise precaution.

Ciclosporin 2.5–4 mg/kg is used for active rheumatoid arthritis when conventional therapy has been ineffective. Side-effects include a rise in creatinine level and hypertension.

Surgery

Surgery has a useful role in the long-term approach to patient management but is less frequently needed as therapeutic disease control becomes more effective. Its main objectives are prophylactic, to prevent joint destruction and deformity, and reconstructive, to restore function.

Single-joint disease can be treated by surgical synovectomy to reduce the bulk of inflamed tissue and prevent damage. Excision arthroplasty of the ulnar styloid reduces pain and the risk of extensor tendon damage. Excision arthroplasties of the metatarsal heads reduce metatarsal pain and relieve pressure points. The major surgical advance has been the development of total replacement arthroplasty of the hip, knee, finger joints, elbow and shoulder. Such procedures need careful planning and preparation, and the expected outcomes and risks should be explained to the patient.