Rheumatology and bone disease

Chapter 11 Rheumatology and bone disease

Rheumatological and musculoskeletal disorders

Many common locomotor problems are short-lived and self-limiting or settle with a course of simple analgesia and/or physical treatment; e.g. physiotherapy or osteopathy. However, they represent 20–30% of the workload of the primary care physician, where non-inflammatory problems predominate. Recognition and appropriate early treatment of many painful rheumatic conditions may help reduce the incidence of chronic pain disorders. Early recognition and subsequent treatment of inflammatory arthritis by specialist multidisciplinary teams leads to better symptom control and prevents long-term joint damage and disability. The patient should always be included when decisions about treatment are being discussed. Pamphlets and websites offer helpful advice for patients, and their use should be encouraged.

The normal joint

There are three types of joints: fibrous, fibrocartilaginous and synovial.

Juxta-articular bone

The bone which abuts a joint (epiphyseal bone) differs structurally from the shaft (metaphysis) (see Fig. 11.32). It is highly vascular and comprises a light framework of mineralized collagen enclosed in a thin coating of tougher, cortical bone. The ability of this structure to withstand pressure is low and it collapses and fractures when the normal intra-articular covering of hyaline cartilage is worn away as in osteoarthritis (OA; see p. 512). Loss of surface cartilage also leads to the abnormalities of bone growth and remodelling typical of OA (see p. 512).

Ligaments and tendons

These structures stabilize joints. Ligaments are variably elastic and this contributes to the stiffness or laxity of joints (see p. 559). Tendons are inelastic and transmit muscle power to bones. The joint capsule is formed by intermeshing tendons and ligaments. The point where a tendon or ligament joins a bone is called an enthesis and may be the site of inflammation.

Components of extracellular matrix

All connective tissues contain an extracellular matrix of macromolecules: collagens, elastins, non-collagenous glycoproteins and proteoglycans, in addition to cells, e.g. synoviocytes. There are several different types of cell surface receptors that bind extracellular matrix proteins including the integrins, CD44 and the proteoglycan family of receptors, e.g. syndecans.

Collagens. Collagens consist of three polypeptide (α) chains wound into a triple helix. These alpha chains contain repeating sequences of Gly-x-y triplets, where x and y are often prolyl and hydroxypropyl residues. Collagen fibres show genetic heterogeneity, with genes on at least 12 chromosomes. Hyaline cartilage is 90% type II (COL2A1). There are several classes of collagen genes, based on their protein structures, and abnormalities of these may lead to specific diseases (see p. 560).

Elastin, secreted as tropoelastin, is an insoluble protein polymer and is the main component of elastic fibres.

Glycoproteins. Fibronectin is the major non-collagenous glycoprotein in the extracellular matrix. Its molecule contains a number of functional domains, or cell recognition sites that bind ligands and are involved in cellular adhesion. Fibronectin plays a major role in tissue remodelling. Its production is stimulated by interferon-gamma (IFN-γ) and by transforming growth factor-beta and inhibited by tumour necrosis factor and interleukin-1.

Proteoglycans. These proteins contain glycosaminoglycan (GAG) side-chains and are of variable form and size. Many different molecules have been identified at different sites in connective tissue. Their function is to bind extracellular matrix together, retain soluble molecules in the matrix and assist with cell binding. Abnormalities of any of these structures may lead to periarticular or articular symptoms and/or predispose to the development of arthritis.

Skeletal muscle

This consists of bundles of myocytes containing actin and myosin molecules. These molecules interdigitate and form myofibrils which cause muscle contraction in a similar way to myocardial muscle (p. 671). Bundles of myofibrils (fasciculi) are covered by connective tissue, the perimysium, which merges with the epimysium (covering the muscle) and forms the tendon which attaches to the bone surface (enthesis).

Clinical approach to the patient

Taking a musculoskeletal history

The following questions are helpful in assessing the problem and making a diagnosis. A history can often lead to a diagnosis as pattern recognition is the key to diagnosis in rheumatic diseases.


Gout (see p. 530), reactive arthritis (p. 529) and ankylosing spondylitis (p. 527) are more common in men. Rheumatoid arthritis and other autoimmune rheumatic diseases are more common in women.


image Is the person young, middle-aged or older?

image How old was the patient when the problem first started? Osteoarthritis (see p. 512) and polymyalgia rheumatica (p. 542) rarely affect the under-50s. Rheumatoid arthritis starts most commonly in women aged 30–50 years.

Examination of the joints

Always observe a patient, looking for disabilities, as he or she walks into the room and sits down. General and neurological examinations are often necessary. Guidelines for rapid examinations of the limbs and spine are shown in Practical Box 11.1.

image Practical Box 11.1

Rapid examinations of the limb and spine

Examining an individual joint involves three stages: looking, feeling and moving (Table 11.1). A screening examination of the locomotor system, known by the acronym GALS (Global Assessment of the Locomotor System) has been devised. X-ray or ultrasound of the joint often forms an integral part of the examination.

Table 11.1 Examination of the joint

LOOK at the appearance of the joint

Swelling – could be bony, fluid or synovial

Deformity – valgus, where the distal bone is deviated laterally (e.g. knock-knees or genu valgum)

 Varus where the distal bone is deviated medially (bow-legs or genu varum)

 Fixed flexion or hyperextension

Rash – especially psoriasis

Muscle wasting – easier to see in large muscles like the quadriceps

Scars – from surgery or trauma

Signs of inflammationSymmetry – are the right and left joints (e.g. hips, knees, any other paired joint) the same? If not which do you think is abnormal?


Swelling – fluid swelling (effusion) usually represents increased synovial fluid in inflammatory arthritis, but can be due to blood or pus

 Synovial swelling is rubbery or boggy and usually occurs in inflammatory arthritis

 Bony swelling, such as Heberden’s nodes in the fingers is usually seen in osteoarthritis

Warmth – a warm joint may be inflamed or infected

Tenderness – may represent joint inflammation, but many people have chronic tenderness all over the body (e.g. in fibromyalgia)


Active movement – is the range full and pain-free? Is the movement fluid? In the hands – can the patient perform fine movements? In the legs – can the patient walk properly?

Compare movements on the right and left side – are they symmetrical?

Is there crepitus when the joint is moved?

 If active movement is limited try passive movement. In a joint problem both will usually be affected. If it is a muscle or nerve problem passive movement may remain full.


Investigations are unnecessary in many of the common musculoskeletal problems; the diagnosis is clear from the history and examination findings. Tests help to exclude another condition and to reassure the patient or their primary care physician.

Serum autoantibody studies

image Rheumatoid factors (RFs) (see also p. 518). Rheumatoid factors are detected by enzyme linked immunoabsorbent assay (ELISA). RFs are antibodies (usually IgM, but also IgG or IgA) against the Fc portion of IgG. They are detected in 70% of people with rheumatoid arthritis (RA), but are not diagnostic. RFs are detected in many autoimmune rheumatic disorders (e.g. SLE), in chronic infections, and in asymptomatic older people (Table 11.2).

image Anti-citrullinated peptide antibodies (ACPA). These antibodies are directed against citrullinated antigens, vimentin, fibrinogen, alpha enolase and type II collagen. They are measured by an ELISA technique and are present in up to 80% of people with RA. They have a high specificity for RA (90% with a sensitivity of 60%). They are helpful in early disease when the RF is negative to distinguish it from acute transient synovitis (see Box 11.6, p. 519). Positivity for RF and/or ACPA is associated with a worse prognosis and an increase in the likelihood of bony erosions in people with RA.

image Antinuclear antibodies (ANAs). These are detected by indirect immunofluorescent staining of fresh-frozen sections of rat liver or kidney or Hep-2 cell lines. Different patterns reflect a variety of antigenic specificities that occur with different clinical pictures (see Box 11.16, p. 537). ANA is used as a screening test for systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) – a negative ANA makes either condition highly unlikely – but low titres occur in RA and chronic infections and in normal individuals, especially the elderly (Table 11.3).

image Anti-double-stranded DNA (dsDNA) antibodies. These are usually detected by a precipitation test (Farr assay), by ELISA, or by an immunofluorescent test using Crithidia luciliae (which contains double-stranded DNA). Raised anti-dsDNA is highly specific for SLE and the levels usually rise and fall in parallel with disease activity so can be used to monitor the level of treatment required.

image Anti-extractable nuclear antigen (ENA) antibodies (see Box 11.16, p. 537). These produce a speckled ANA fluorescent pattern, and can be identified by ELISA. The most commonly measured ENAs are:

image Anti-neutrophil cytoplasmic antibodies (ANCAs) (see p. 544). These are predominantly IgG autoantibodies directed against the primary granules of neutrophil and macrophage lysosomes. They are strongly associated with small-vessel vasculitis. Two major clinically relevant ANCA patterns are recognized on immunofluorescence:

image Antiphospholipid antibodies (see p. 538). These are detected in the antiphospholipid syndrome (see p. 538).

image Immune complexes. Immune complexes are infrequently measured, largely because of variability between assays and difficulty in interpreting their meaning. Assays based on the polyethylene glycol precipitation method (PEG) or C1q binding are available commercially.

image Complement. Low complement levels indicate consumption and suggest an active disease process in SLE.

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

Autoimmune rheumatic diseases

RF (IgM) %

 Rheumatoid arthritis


 Systemic lupus erythematosus


 Sjögren’s syndrome


 Systemic sclerosis




 Juvenile idiopathic arthritis


Viral infections



 Chronic liver disease

 Infectious mononucleosis




Chronic infections

Normal population



 Infective endocarditis

 Relatives of people with RA



Table 11.3 Conditions in which serum antinuclear antibodies are found


Systemic lupus erythematosus


Systemic sclerosis


Sjögren’s syndrome


Polymyositis and dermatomyositis


Rheumatoid arthritis


Juvenile idiopathic arthritis


Other diseases


 Autoimmune hepatitis


 Drug-induced lupus


 Myasthenia gravis


 Idiopathic pulmonary fibrosis


 Diabetes mellitus


 Infectious mononucleosis


Normal population


Diagnostic imaging and visualization

image X-rays can be diagnostic in certain conditions (e.g. established rheumatoid arthritis) and are the first investigation in many cases of trauma. X-rays can detect joint space narrowing, erosions in rheumatoid arthritis, calcification in soft tissue, new bone formation, e.g. osteophytes and decreased bone density (osteopenia) or increased bone density (osteosclerosis):

1. In acute low back pain (see p. 503), X-rays are indicated only if the pain is persistent, recurrent, associated with neurological symptoms or signs, or worse at night or associated with symptoms such as fever or weight loss.

image Ultrasound (US) is particularly useful for periarticular structures, soft tissue swellings and tendons and for detecting active synovitis in inflammatory arthritis. It is increasingly used to examine the shoulder and other structures during movement, e.g. shoulder impingement syndrome (see p. 500). Doppler US measures blood flow and hence inflammation. US is used to guide local injections.

image Magnetic resonance imaging (MRI) shows bone changes and intra-articular structures in striking detail. Visualization of particular structures can be enhanced with different resonance sequences. T1-weighted is used for anatomical detail, T2-weighted for fluid detection and short tau inversion recovery (STIR) for the presence of bone marrow oedema. It is more sensitive than X-rays in the early detection of articular and periarticular disease. It is the investigation of choice for most spinal disorders but is inappropriate in uncomplicated mechanical low back pain. Gadolinium injection enhances inflamed tissue. MRI can also detect muscle changes, e.g. myositis.

image Computerized axial tomography (CT) is useful for detecting changes in calcified structures but dose of irradiation is high.

image Bone scintigraphy utilizes radionuclides, usually 99mTc, and detects abnormal bone turnover and blood circulation and, although nonspecific, helps in detecting areas of inflammation, infection or malignancy. It is best used in combination with other anatomical imaging techniques.

image DXA scanning uses very low doses of X-irradiation to measure bone density and is used in the screening and monitoring of osteoporosis.

image Positron emission tomography (PET) scanning uses radionuclides, which decay by emission of positrons. 18F-Fluorodeoxyglucose uptake indicates areas of increased glucose metabolism. It is used to locate tumours and demonstrate large vessel vasculitis, e.g. Takayasu’s arteritis (see p. 789). PET scans are combined with CT to improve anatomical details.

image Arthroscopy is a direct means of visualizing a joint, particularly the knee or shoulder. Biopsies can be taken, surgery performed in certain conditions (e.g. repair or trimming of meniscal tears), and loose bodies removed.

Common regional musculoskeletal problems (fig. 11.2)

Pain in the neck and shoulder (Table 11.4)

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

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.


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.

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.

Pain in the shoulder

The shoulder is a shallow joint with a large range of movement. The humeral head is held in place by the rotator cuff (Fig. 11.4) which is part of the joint capsule. It comprises the tendons of infraspinatus and teres minor posteriorly, supraspinatus superiorly and teres major and subscapularis anteriorly. The rotator cuff (particularly supraspinatus) prevents the humeral head blocking against the acromion during abduction; the deltoid pulls up and the supraspinatus pulls in to produce a turning movement and the greater tuberosity glides under the acromion without impingement. Shoulder pathology restricts or is made worse by shoulder movement. Specific diagnoses are difficult to make clinically but this may not matter for pain management.

Pain in the shoulder can sometimes be due to problems in the neck. The differential diagnosis of this is shown in Box 11.1. Adhesive capsulitis (true frozen shoulder) is uncommon (see below). Early inflammatory arthritis and polymyalgia rheumatica in the elderly may present with shoulder pain. Shoulder pain is more common in diabetic patients than in the general population.

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.


Analgesics, NSAIDs and/or physiotherapy may suffice, but severe pain responds to an injection of corticosteroid into the subacromial bursa (Fig. 11.4). Patients should be warned that 10% will develop worse pain for 24–48 hours after injection. Some 70% improve over 5–20 days and mobilize the joint themselves. Physiotherapy helps persistent stiffness. Further ultrasound-guided corticosteroid injections may be needed but the long-term benefit is unclear.

Pain in the hand and wrist (table 11.6)

Hand pain is commonly caused by injury or repetitive work-related activities. When associated with pins and needles or numbness it suggests a neurological cause arising at the wrist, elbow or neck. Pain and stiffness that are worse in the morning are due to tenosynovitis or inflammatory arthritis. The distribution of hand pain often indicates the diagnosis.

Table 11.6 Pain in the hand and wrist: causes

All ages Older patients


Nodal OA:


 DIPs (Heberden’s nodes)

 Flexor with/without triggering

 PIPs (Bouchard’s nodes)
 First carpometacarpal joint


 De Quervain’s
Carpal tunnel syndromeGanglionInflammatory arthritisRaynaud’s syndrome (p. 510)Chronic regional pain syndrome type I (in this chapter)

Trauma – scaphoid fracture






DIPs, PIPs, distal and proximal interphalangeal joints.

Pain in the lower back

Low back pain is a common symptom. It is often traumatic and work-related, although lifting apparatus and other mechanical devices and improved office seating help to avoid it. Episodes are generally short-lived and self-limiting, and patients attend a physiotherapist or osteopath more often than a doctor. Chronic back pain is the cause of 14% of long-term disability in the UK. The causes are listed in Table 11.7, and the management of back pain is summarized in Box 11.2.

Table 11.7 Pain in the back (lumbar region): causes




Neoplastic (see p. 589)

Referred pain

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:

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.

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Apr 1, 2017 | Posted by in GENERAL & FAMILY MEDICINE | Comments Off on Rheumatology and bone disease

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