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Palliative Medicine and Symptom Control 263
• An increase in bone marrow plasma cells on bone marrow aspirate or
trephine biopsy.
Other essential investigations are as follows:
• Blood count, which may show anaemia, thrombocytopenia and
leucopenia. The ESR is almost always high.
• Serum biochemistry may show evidence of renal failure and
hypercalcaemia. The alkaline phosphatase is usually normal.
• Serum β2-microglobulin and LDH are used in prognosis.
Management
With good supportive care and chemotherapy with autologous stem cell
transplantation, median survival is now 5 years, with some patients surviving
to 10 years. Young patients receiving more intensive therapy may live longer.
However, myeloma remains incurable.
Supportive therapy includes correction of anaemia with blood transfusion
or erythropoietin, prompt treatment of infections and treatment of bone
pain with radiotherapy or high-dose dexamethasone. Acute kidney injury
(p. 375) and hypercalcaemia (p. 634) may be corrected by adequate
hydration alone. Progression of bone disease is reduced by bisphosphonates,
e.g. zoledronate, which inhibit osteoclastic activity. Hyperviscosity is treated
by plasmapheresis together with systemic therapy.
Initial treatment typically consists of an alkylator (cyclophosphamide
or melphalan), steroid (prednisolone or dexamethasone) and novel agent
(bortezomib or thalidomide). Lenalidomide is a thalidomide analogue that is
also used for relapsed myeloma. It has greater potency than thalidomide with
less toxicity. Younger patients (<65–70 years) are treated with high-dose
melphalan with peripheral blood stem cell rescue.
Monoclonal gammopathy of undetermined significance
This is usually seen in older patients, where a raised level of paraprotein (usually IgA) is found in the blood, but without other features of myeloma. Patients
are often asymptomatic and no treatment is required. Follow-up is necessary
as 20%–30% go on to develop multiple myeloma over a 25-year period.
PALLIATIVE MEDICINE AND SYMPTOM CONTROL
Palliative care describes the multidisciplinary approach to patients with
advanced end-stage disease. Patients with advanced cancer and chronic
non-malignant disease, e.g. organ failure (heart, lung and kidney), neurological disease and HIV infection, all benefit from this approach, which aims to
achieve the best possible quality of life. It includes management of symptoms, access to support services, involving patients and family in their care
and helping them to make decisions about end-of-life care.
264 Malignant disease
paracetamol
e.g. morphine,
oxycodone, fentanyl
Opioid for moderate
to severe pain
±
Non-opioid
Pain persisting or increasing
±
±
Non-opioid
±
Non-opioid
±
Adjuvant
Pain
Adjuvant
Adjuvant
Opioid for mild to moderate pain
Pain persisting or increasing
±
Fig. 6.1 The World Health Organization (WHO) three-step analgesic ladder is a
framework for the prescription of analgesic drugs. The ladder attempts to meet
the ceiling effect of analgesic drugs to the degree of pain present. If pain is
severe or analgesia ineffective, then an ascent of the ladder is recommended.
NSAID, non-steroidal anti-inflammatory drug.
3
2
e.g. codeine
e.g. aspirin,
or a NSAID
1
Management of pain
The approach to successful management of pain includes an assessment
of patient characteristics (mood, previous problems with analgesia, fear of
opioids) and the likely aetiology of the pain. Pain can be controlled in most
patients using a simple step-wise approach (the World Health Organization
[WHO] analgesic ladder) that guides the choice of analgesia according to pain
severity (Fig. 6.1). Morphine is the most commonly used strong opioid and
where possible it should be given regularly by mouth.
• Dose titration of morphine is with a normal release formulation with
a rapid onset and duration of action, e.g. 5–10 mg morphine elixir or
tablets every 4 hours (depending on body weight, renal function and use
of other weak opioids) with extra doses allowed for ‘breakthrough pain’
as often as necessary. The daily requirements can be assessed after
24 hours and the regular dose adjusted as necessary.
• Maintenance of pain relief is with a controlled-release morphine
preparation. When the stable dose requirement is established by titration
Palliative Medicine and Symptom Control 265
the morphine can be changed to a controlled-release preparation, e.g.
20 mg morphine elixir 4-hourly = 60 mg of a twice-daily preparation.
Side effects of morphine include nausea and vomiting (see p. 264),
constipation (lactulose and senna should be co-prescribed), confusion,
drowsiness and nightmares. If there is renal dysfunction, caution is
required when prescribing morphine and low doses should be used;
modified-release preparations should be avoided. In mild to moderate
renal impairment oxycodone should be considered as an alternative as
it undergoes hepatic metabolism. If the renal dysfunction is significant
(estimated glomerular filtration rate <30 mL/min), an alternative
opioid, such as alfentanil, should be considered because of the risk
of metabolite accumulation. If there is concurrent significant hepatic
dysfunction, oxycodone should be avoided.
As pain may be due to different physical aetiologies, an appropriate
adjuvant analgesic may be needed in addition to, or instead of, traditional
drug treatments:
• Adjuvant analgesics include non-steroidal anti-inflammatory drugs
(NSAIDs) (p. 315) and bisphosphonates (p. 37) used in addition to opioids,
for bone pain
• Tricyclic antidepressants (e.g. amitriptyline 10–75 mg daily) and
antiepileptics (e.g. gabapentin 600–2400 mg daily or pregabalin 150 mg
increasing to 600 mg daily) for neuropathic pain
• Steroids, e.g. dexamethasone (p. 643) for the headache of raised
intracranial pressure or liver capsule pain.
Palliation of nausea and vomiting
Careful choice of an antiemetic targeted towards the underlying cause
of the nausea and/or vomiting is essential. Nausea and vomiting are
associated with:
• Chemotherapy. Certain agents, e.g. cisplatin, confer a high risk of
nausea and vomiting. A 5-hydroxytryptamine3 (5-HT3) antagonist, such
as ondansetron 8 mg three times daily, may help. Aprepitant, a
neurokinin-1 (NK-1) antagonist, is increasingly being used as an adjunct
in chemotherapy-induced nausea and vomiting.
• Chemical causes, e.g. hypercalcaemia, hepatic failure, uraemia or drugs.
Haloperidol 0.5–1.5 mg as required every 4 hours, up to a maximum of
5mg daily, is the first choice.
• Gastric stasis and distension. Metoclopramide 10 mg three times daily
is a prokinetic and promotes gastric emptying. The prokinetic effects can
also ameliorate constipation.
• Raised intracranial pressure, e.g. brain tumour. Cyclizine 50 mg three
times daily is most useful.
• Any cause of vomiting. It may be necessary to start antiemetic therapy
parenterally by continuous subcutaneous infusion. If the patient has
gastrointestinal obstruction or poor oral/gastrointestinal absorption, this
266 Malignant disease
route may need to be continued. Levomepromazine is a second-line
antiemetic if initial therapy is not successful; 6.25 mg as required, up to
a maximum of 25 mg per day, is recommended. Other medications to
aid nausea and vomiting include corticosteroids, particularly in the case
of bowel obstruction, where reducing tumour oedema may alleviate the
obstruction and improve symptoms.
Care of the dying patient
The dying patient requires appropriate care in their last hours or days of
life. Most people express a wish to die in their own homes, provided their
symptoms are controlled and their carers are supported. However, patients
may die in any setting so all healthcare professionals should be proficient
in end-of-life care, including the management of symptoms such as pain,
agitation, vomiting, breathlessness and respiratory secretions. Reports of
inadequate hospital care have led to the development of integrated pathways
of care for the dying. Pathways act as prompts of care, including psychological, social, spiritual and carer concerns in those who are diagnosed as dying.
The decision that a patient is dying is reached by a multiprofessional team
through careful assessment of the patient and exclusion of reversible causes
of deterioration.
7
Musculoskeletal problems are common and usually short-lived and selflimiting. They account for about one in five consultations in primary care.
Recognition and early treatment of rheumatic conditions can reduce the
incidence of chronic pain disorders in non-inflammatory conditions whereas
early specialist referral in inflammatory arthritis leads to better symptom
control and prevention of long-term joint damage. Pain, stiffness and swelling are the most common presenting symptoms of joint disease and may be
localized to a single joint or affect many joints.
Rheumatology
THE NORMAL JOINT
There are three types of joints: fibrous, fibrocartilaginous and synovial.
Fibrous and fibrocartilaginous joints include the intervertebral discs, the
sacroiliac joints, the pubic symphysis and the costochondral joints. Little
movement occurs at such joints. Synovial joints include the ball-and-socket
joints (e.g. hip) and the hinge joints (e.g. interphalangeal). In synovial joints
the opposed cartilaginous articular surfaces move painlessly over each other,
stability is maintained during use and the load is distributed across the surface of the joint (Fig. 7.1).
MUSCULOSKELETAL SYMPTOMS
Arthralgia describes joint pains when the joint appears normal on examination while arthritis is the term used when there is objective evidence of joint
inflammation (swelling, deformity or an effusion).
In a patient presenting with joint pains, the history and examination must
assess the distribution of the joints affected (e.g. is the pain symmetrical,
axial or peripheral), the presence and duration of morning stiffness (>30
minutes in inflammatory arthropathies), aggravating and relieving factors,
past medical history and family history. Table 7.1 lists the likely causes of
joint pains based on the age and gender of the patient.
Pain in or around a single joint may arise from the joint itself (articular
problem) or from structures surrounding the joint (periarticular problem).
Enthesitis (inflammation at the site of the attachment of ligaments, tendons
and joint capsules), bursitis and tendinitis are all causes of periarticular pain.
Pain arising from the joint may be the result of a mechanical problem (e.g.
torn meniscus) or an inflammatory problem.
268 Rheumatology
– point at which ligaments and tendons (both stabilize joints) insert into bone;
Articular
cartilage
Joint capsule
– connected to
periosteum and
lined by synovium;
Synovial fluid
– viscous fluid
which lubricates
the joint. Secreted by
synovial cells into
synovial cavity;
Articular cartilage
(hyaline cartilage)
– composed of water,
type II collagen and
proteoglycans.
Muscle
Synovial
cavity
Bursa
Joint capsule
and synovial lining
Tendon
Enthesis
Creates a smooth highly compressible structure which acts as a shock absorber and
distributes loads over the joint surface;
Enthesis
Epiphyseal bone abuts the joint and differs structurally from the shaft (metaphysis).
Enthesis
Epiphyseal
bone
Ligament
Enthesis
Fig. 7.1 Anatomy and physiology of a normal synovial joint.
Table 7.1 Differential diagnosis of polyarticular arthritis in
adults in the UK
Age Predominantly
males
Young
Reactive
arthritis
Ankylosing
spondylitis
Psoriatic arthropathy
Enteropathic
arthropathy
Middle age
Elderly
Gout Osteoarthritis
Osteoarthritis
Polymyalgia
rheumatica
Pseudogout
Any age: Lyme disease, endocarditis, acute hepatitis B infection, human
immunodeficiency virus infection, parvovirus.
Uncommon arthropathies: malignancy (hypertrophic pulmonary osteoarthropathy),
rheumatic fever, Henoch–Schönlein purpura, Behçet’s syndrome.
Predominantly
females
Systemic lupus
erythematosus
Rheumatoid arthritis
Sjögren’s syndrome
Rheumatoid arthritis
Common Investigations in Musculoskeletal Disease 269
The causes of a large-joint monoarthritis include osteoarthritis, gout,
pseudogout, trauma and septic arthritis. Disseminated gonococcal infection
is a common cause of acute non-traumatic monoarthritis or oligoarthritis
in young adults. Less common causes are rheumatoid arthritis (RA), the
spondyloarthropathies, tuberculous infection and haemarthrosis (e.g. in
haemophilia, or in an anticoagulated patient). Acute monoarthritis requires
urgent investigation and treatment (p. 296). The key investigation is synovial
fluid aspiration with Gram stain and culture and analysis for crystals in gout
and pseudogout.
If the patient presents with stiffness, it is necessary to establish whether
it is localized or generalized, whether it affects the limb girdles or periphery
and whether it is worse first thing in the morning or following activity. If joint
swelling is present, the distribution of joints affected can be helpful. In certain
rheumatological conditions, the presence of extra-articular features can also
clarify the diagnosis.
COMMON INVESTIGATIONS IN MUSCULOSKELETAL DISEASE
Blood tests
Routine blood tests will usually show evidence of a non-specific acute-
phase response in inflammatory arthritides and autoimmune rheumatic
conditions. Normochromic, normocytic anaemia is common. Hypochromic,
microcytic anaemia may be present and indicates iron deficiency, likely due
to non-steroidal anti-inflammatory drug (NSAID)-induced gastrointestinal
bleeding. Thrombocytopenia may be a feature of systemic lupus erythematosus (SLE). Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
are the most widely used indicators of the acute-phase response and are
frequently used to monitor disease activity. A raised alkaline phosphatase
may indicate bony disease (p. 136).
Autoantibodies (see rheumatoid factor (p. 282) and Table 7.2) may be
non-specific and found in normal individuals. At high titre (>1:160) their disease specificity increases and they help to establish a diagnosis in patients
with clinical features suggestive of an autoimmune disease. They can
sometimes be used to monitor disease activity and provide prognostic data,
e.g. seropositive RA (i.e. cyclic citrullinated peptide antibodies (anti-CCP) or
rheumatoid factor are present) is associated with more erosive joint disease
and extra-articular manifestations than seronegative RA.
Imaging
Plain X-rays may show fractures, deformity, soft tissue swelling, decreased
bone density, osteolytic and osteosclerotic areas suggestive of metastases,
joint erosions, joint space narrowing and new bone formation. X-rays may
270 Rheumatology
Table 7.2 Autoantibodies and disease associations
Antibody Disease
Anti-citrullinated peptide
antibodies (ACPA); rheumatoid
factor
Antinuclear antibodies Non-specific – autoimmune disease,
Anti-dsDNA SLE
Anti-histone Drug-induced lupus
Anti-topoisomerase I (Scl-70) Diffuse cutaneous SSc
Anti-centromeric Limited SS
Anti-Ro (SS-A) Primary SS, SLE
Anti-La (SS-B) Primary SS, SLE
Anti-Smith (Sm) SLE
Anti-UI-RNP SLE, overlap syndrome
Anti-Jo-1 Polymyositis, dermatomyositis
Cytoplasmic ANCA Granulomatosis with polyangiitis (formerly
Perinuclear ANCA Microscopic polyarteritis, eosinophilic
Antiphospholipid Antiphospholipid syndrome, SLE
ds, double-stranded; SLE, systemic lupus erythematosus; SS, Sjögren’s syndrome; RNP,
ribonucleoprotein; SSc, systemic scleroderma; ANCA, antineutrophil cytoplasmic antibody.
High specificity for rheumatoid arthritis
infections, normal individuals
known as Wegener’s granulomatosis)
granulomatosis with polyangiitis (formerly
known as Churg–Strauss syndrome)
be normal in early inflammatory arthritis but are used as a baseline for later
comparison.
Bone scintigraphy (isotope bone scan) uses a tracer (99Tc-
bisphosphonate) administered intravenously which localizes to sites of
increased bone turnover and blood circulation. ‘Hot spots’ are non-specific
and occur in osteomyelitis, septic arthritis, malignancy, Paget’s disease
and following surgery or trauma. It is best used in combination with other
anatomical imaging techniques.
Ultrasound is useful for assessment of soft tissue and periarticular
changes, such as hip joint effusion, Baker’s cyst and inflamed/damaged
tendons. It is sometimes used to assess bone density (at the heel), as a
screening procedure prior to dual-energy X-ray absorptiometry (DXA) and is
increasingly being used to examine the shoulder and other structures during
movement.
Common Regional Musculoskeletal Problems 271
Magnetic resonance imaging (MRI) is particularly useful in the investi-
gation of articular disease and spinal disorders. It is not indicated in patients
with uncomplicated mechanical low back pain. Visualization of particular
structures can be enhanced with different resonance sequences. T1-weighted
MRI is used for anatomical detail, T2-weighted for fluid detection and short
tau inversion recovery (STIR) for the presence of bone marrow oedema. MRI
is more sensitive than X-rays in the early detection of articular and periarticular disease. Gadolinium injection enhances inflamed tissue.
Computed tomography (CT) is useful for detecting changes in calcified
structures but the dose of irradiation is high.
Positron emission tomography (PET) scanning uses radionuclides,
which decay by emission of positrons. 18F-Fluorodeoxyglucose uptake indicates areas of increased glucose metabolism. PET is used to locate tumours
and demonstrate large-vessel vasculitis (e.g. Takayasu’s arteritis). PET scans
are combined with CT to improve anatomical details.
DXA measures bone mineral density (BMD) in the diagnosis and monitor-
ing of osteoporosis (p. 309).
Arthroscopy is a direct means of visualizing the inside of 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.
Synovial fluid analysis
A needle may be inserted into a joint in order to aspirate synovial fluid for
diagnosis or to relieve pressure. Corticosteroids or local anaesthetics may
also be administered intra-articularly. The most common indications for joint
aspiration are evaluation for sepsis in a single inflamed joint (p. 296) and
confirmation of gout and pseudogout by polarized light. Synovial fluid should
be analysed for colour, viscosity, cell count, culture, glucose and protein.
COMMON REGIONAL MUSCULOSKELETAL PROBLEMS
Inflammatory arthritis or osteoarthritis causes pain in one or more joints.
This section describes specific regional problems. The diagnosis of most of
these conditions is usually clinical and initial treatment is with analgesia, e.g.
paracetamol and NSAIDs. Physiotherapy and local steroid injections are used
in some cases.
Pain in the neck and shoulder is often due to muscular spasm. There
is unilateral or bilateral pain which may radiate upwards to the occiput
and is often associated with tension headaches. Nerve root compression
by cervical disc prolapse or spondylotic osteophytes causes unilateral
neck pain radiating to interscapular and shoulder regions (see below). It is
associated with paraesthesia and neurological signs in the arms. Pain in
272 Rheumatology
the neck may also be caused by RA, ankylosing spondylitis or fibromyalgia
(chronic widespread muscle pain often in young women with no underlying
cause; large psychological overlay in some patients). Polymyalgia rheumatica
(p. 305) causes pain and stiffness in the shoulder girdle.
Rotator cuff injury and inflammation is one of the most common causes
of shoulder pain. The rotator cuff muscles (supraspinatus, infraspinatus,
subscapularis, teres minor) are positioned around the shoulder joint. They
stabilize the joint and help with movement. The muscular tendons join to form
the rotator cuff tendon, which inserts into the humerus. Rotator cuff tendinitis,
impingement and tears cause shoulder pain with a painful arc (between
70 and 120°) on shoulder abduction in the former two and prevention of
active abduction (in the first 90°) in the latter. Adhesive capsulitis (‘frozen
shoulder’) causes severe shoulder pain with all movements, leading to the
‘frozen phase’ where there is loss of all shoulder movements but little pain.
Ultrasound examination is the best investigation to differentiate between
these causes.
Elbow pain occurs due to inflammation of the insertion site of the wrist
extensor tendon into the lateral epicondyle (tennis elbow) or the wrist flexor
tendon into the medial epicondyle (golfer’s elbow). There is local tenderness,
and pain radiates into the forearm on using the affected muscles.
Hip problems Pain arising from the hip joint itself is felt in the groin,
lower buttock and anterior thigh, and may radiate to the knee. Occasionally
and inexplicably, hip arthritis causes pain only in the knee. Fracture of the
femoral neck (pain in the hip, usually after a fall, leg shortened and externally
rotated) or avascular necrosis of the femoral head (severe hip pain in a
patient with risk factors, p. 313) will often be suspected from the history
and examination. Pain over the trochanter which is worse going up stairs
and when abducting the hip can be due to trochanteric bursitis or a tear
of the gluteus medius tendon at its insertion into the trochanter. MRI will
differentiate the two. Meralgia paraesthetica (lateral cutaneous nerve of thigh
compression) causes numbness and increased sensitivity to light touch over
the anterolateral thigh. It is usually self-limiting.
The knee is a frequent site of sports injuries that lead to torn menisci
and cruciate ligaments. These injuries may be associated with bleeding
into the joint (haemarthrosis). The knee is also frequently involved in
inflammatory arthritides, osteoarthritis and pseudogout. An associated
effusion causes swelling, stiffness and pain, with the ‘bulge sign’ and
‘patellar tap’ on examination. In a few patients with an effusion there is a
connection to a bursa, forming a cyst (Baker’s cyst) in the popliteal fossa.
This may rupture (ruptured popliteal or Baker’s cyst) and the escape of fluid
into the soft tissue of the popliteal fossa and upper calf causes sudden
and severe pain, swelling and tenderness. It may be confused with a deep
venous thrombosis (DVT) and is diagnosed on ultrasonography. Treatment
is with analgesics, rest with the leg elevated, aspiration and injection of
corticosteroids into the knee joint.