2. Problem Solving in
Rheumatology
KEVIN PILE MB ChB, MD, FRACP
Conjoint Professor of Medicine, University of Western Sydney,
New South Wales, Australia
LEE KENNEDY BSc, MB ChB, MD, PhD, FRCP, FRCPE, FRACP
Professor of Medicine, School of Medicine, Department of Medicine,
James Cook University, Queensland, Australia
CLINICAL PUBLISHING
OXFORD

4. Contents
Abbreviations vii
SECTION 1 General Rheumatology and Soft Tissue
Rheumatism
1. New Onset Painful Joints 1
2. An Acutely Swollen/Hot Joint 6
3. Painful Shoulders – Rotator Cuff and Frozen Shoulder 11
4. Tennis Elbow and Golfer’s Elbow 18
5. Carpal Tunnel Syndrome and Other Entrapment Neuropathies 21
6. Fibromyalgia Syndrome 27
7. Plantar Fasciitis 33
SECTION 2 Osteoarthritis
8. Causes and Prevention 39
9. Non-Pharmacological Treatment 45
10. Drug Treatment 50
11. NSAIDs – Gastric Side Effects and Protection 54
12. NSAIDs – Cardiac Complications 60
13. Joint Replacement Surgery 65
SECTION 3 Rheumatoid Arthritis
14. Causes 71
15. Laboratory and Imaging Investigations 77
16. Managing Rheumatoid Arthritis at Onset 82
17. Evaluating the Response to Treatment 87
18. Pregnancy and Rheumatic Diseases 92
19. Diet and Arthritis 97
20. Polyarthritis in the Elderly 103
SECTION 4 Systemic Lupus Erythematosus, Sjögren’s
Syndrome and Scleroderma
21. Antinuclear Factor 109
22. SLE – Risk Factors and Diagnosis 116
23. Monitoring and Managing SLE 122

5. vi Contents
24. Sjögren’s Syndrome 129
25. Raynaud’s Phenomenon 134
26. Assessing and Treating Scleroderma 139
27. Immunosuppressive Drugs 147
SECTION 5 Vasculitic Syndromes
28. Vasculitic Disease 153
29. Giant Cell Arteritis and Polymyalgia Rheumatica 159
30. Behçet’s Syndrome 165
SECTION 6 Back and Specific Joint Problems
31. Acute Back Pain 169
32. Chronic Back Pain 175
33. Psoriatic Arthritis 178
34. Asymptomatic Hyperuricaemia 184
35. Gout – Acute Attack and Beyond 189
36. Pseudogout – Investigation and Management 195
37. Joint and Bone Infections 199
38. Viral Arthritis 205
39. Rheumatological Complications of Diabetes 211
SECTION 7 Bone Diseases
40. Osteoporosis – Prevention and Lifestyle Management 217
41. Bisphosphonates for Osteoporosis – Which Agent and When? 222
42. Osteoporosis – Drugs Other Than Bisphosphonates 227
43. Male Osteoporosis 233
44. Glucocorticoid-Induced Osteoporosis 237
45. Paget’s Disease of Bone 241
46. Bone Complications of Renal Disease 246
SECTION 8 Muscle Diseases
47. Steroid myopathy 253
48. Inflammatory Myopathies 260
49. Muscle Complications of Statin Therapy 265
General index 271

6. Abbreviations
ABD adynamic bone disease CIM critical iIlness myopathy
ACE angiotensin-converting enzyme CK creatine kinase
ACR American College of Rheumatology CKD chronic kidney disease
ADAMTS a disintegrin and metalloproteinase CKD-MBD CKD-mineral and bone disorder
with thrombospondin motif CLASS Celecoxib Long-term Arthritis
ADFR Activate, Decrease osteoclast Safety Study
activity, Free of treatment and Clc-l chloride channel
Repeat CMC carpometacarpophalangeal
ADP adenosine diphosphate CNS central nervous system
ADR adverse drug reaction CORE Continuing Outcomes Relevant to
AMP adenosine monophosphate Evista
ANA antinuclear antibody COX cyclooxygenase
ANCA anti-neutrophil cytoplasmic COX-1 cyclooxygenase-1
antibodies COX-2 cyclooxygenase-2
ANF antinuclear factor CPEO Chronic Progressive External
AP alkaline phosphatase Ophthalmoplegia
AP-1 activator protein-1 CPPD calcium pyrophosphate dihydrate
APPROVe Adenomatous Polyp Prevention on CREST Calcinosis; Raynaud’s phenomenon;
Vioxx study Esophageal dysmotility;
APS antiphospholipid syndrome Sclerodactyly, Telangiectasia
AS ankylosing spondylitis CRP C-reactive protein
ASC apoptosis-associated speck-like CSS Churg–Strauss syndrome
protein CT computed tomography
ATP adenosine triphosphate CTG cytosine-thymine-guanine
B19 parvovirus B19 CTGF connective tissue growth factor
BASMI British Ankylosing Spondylitis CTS carpal tunnel syndrome
Metrology Index CTLA4-Ig cytotoxic lymphocyte-associated
BMD bone mineral density antigen linked to immunoglobulin
BMI body mass index CVD cardiovascular disease
BP blood pressure CXR chest X-ray
BPs bisphosphonates D3 1,25-dihydroxy-vitamin D3
C5 fifth cervical segment DC dendritic cell
c-ANCA cytoplasmic anti-neutrophil DD Dupuytren’s disease
cytoplasmic antibody DEXA dual-energy X-ray absorptiometry
CCB calcium channel blocker DHA docosahexaenoic acid
CCTG cytosine-cytosine-thymine-guanine DHEA dehydroepiandrosterone
CCL2 monocyte chemoattractant protein- DIL drug-induced lupus
1 (see also MCP-1) DIP distal interphalangeal
CCP cyclic citrullinated peptide DISH diffuse idiopathic skeletal
CDSN corneodesmin hyperostosis
CEP circulating endothelial precursor DLCO diffusing capacity for carbon
cGMP cyclic guanosine monophosphate monoxide
CHB congenital heart block DM dermatomyositis
CI confidence interval DM1 myotonic dystrophy type 1

7. viii Abbreviations
DM2 myotonic dystrophy type 2 hnRNP heterogeneous nuclear
DMARD disease-modifying antirheumatic ribonucleoprotein
drug HPRT hypoxanthine
DMOAD disease-modifying osteoarthritis phosphoribosyltransferase
drug HRCT high-resolution computed
DMPK myotonic dystrophy protein kinase tomography
dsDNA double-stranded DNA HRT hormone replacement therapy
EBV Epstein–Barr virus HSP Henoch-Schönlein purpura
EDTA ethylenediaminetetraacetic acid HTLV-1 human T-lymphotropic virus type 1
EEG electroencephalogram IBD inflammatory bowel disease
EGF epidermal growth factor IBM inclusion body myositis
eGFR estimated glomerular filtration rate IFN interferon
ELISA enzyme-linked immunosorbent Ig immunoglobulin
assay IGF-1 insulin-like growth factor-1
EMG electromyography Iκβ inhibitor of kappa-beta
ENA extractable nuclear antigen IL interleukin
eNOS endothelial nitric oxide synthase IL-1ra interleukin-1 receptor antagonist
EPA eicosapentaenoic acid IMPDH inosine monophosphate
ESR erythrocyte sedimentation rate dehydrogenase
ET endothelin IMT intima-media thickness
FA fatty acid INR International Normalized Ratio
FBC full blood count IP inflammatory polyarthritis
FDG-PET (18)-F-fluorodeoxyglucose-positron IU International Units
emission tomography JSN joint space narrowing
FGF fibroblast growth factor LBP low back pain
FKBP-12 12 kDa FK506-binding protein LDL low-density lipoprotein
FMS fibromyalgia syndrome LFA-1 lymphocyte function-associated
FVC forced vital capacity antigen-1
FSH follicle-stimulating hormone LFT liver function test
GAIT Glucosamine/chondroitin Arthritis LIFE Losartan Intervention for Endpoint
Intervention Trial reduction
GCA giant cell arteritis LJM limited joint mobility
GDM gestational diabetes LORA late-onset RA
GFR glomerular filtration rate LRP-5 LDL receptor-related protein-5
GI gastrointestinal LUMINA Lupus in minorities: nature versus
GMP guanosine monophosphate nurture
GSD glycogen storage disease LH luteinizing hormone
GTP guanosine triphosphate MCP metacarpophalangeal
GVHD graft-versus-host disease MCP-1 monocyte chemoattractant protein-
H2RA histamine H2 receptor antagonist 1 (see also CCL2)
HBA1C glycosylated haemoglobin MCTD mixed connective tissue disease
HBO2 hyperbaric oxygen MELAS Myopathy, Encephalopathy, Lactic
HDL high-density lipoprotein Acidosis and Stroke
HELLP Haemolytic anaemia, Elevated Liver MERRF Myoclonic Epilepsy with Ragged
enzymes, Low Platelets Red Fibres
HIV human immunodeficiency virus MI myocardial infarction
HLA human leukocyte antigen (genetic MMF mycophenolate mofetil
designation for human major MMP matrix metalloproteinase
histocompatibility complex) MORE Multiple Outcome of Raloxifene
HNPP hereditary neuropathy with liability Evaluation
to pressure palsies MPA microscopic polyangiitis

8. Abbreviations ix
MRI magnetic resonance imaging PPI proton pump inhibitor
MRSA methicillin-resistant Staphylococcus PPRP 5¢phosphoribosyl 1-pyrophosphate
aureus PRIMO Prediction of Muscular Risk in
MSA myositis-specific antibodies Observational conditions
MTOR mammalian target of rapamycin PsA psoriatic arthritis
MTP metatarsophalangeal PTH parathyroid hormone
MUA manipulation under anaesthesia PTNP22 protein tyrosine phosphate non-
NALP pyrin domain-containing proteins receptor type 22
sharing structural homology with PUFAs polyunsaturated fatty acids
NODs QALY quality-adjusted life year
NCS nerve conduction studies RA rheumatoid arthritis
NFAT nuclear factor of activated T RANK receptor activator of NF-κB
lymphocytes RANKL receptor activator of NF-κB ligand
NF-κB nuclear factor-κ-beta RCT randomized controlled trial
NHANES National Health and Nutrition REM rapid eye movement
Examination Survey RF rheumatoid factor
NIH National Institutes of Health RISC RNA-induced silencing complex
NO nitric oxide RNA ribonucleic acid
NOD nucleotide-binding and RNP ribonucleoprotein
oligomerization domain proteins ROD renal osteodystrophy
NOS nitric oxide synthase ROS reactive oxygen species
NOS-2 inducible nitric oxide synthase RR relative risk
NOS-3 endothelial nitric oxide synthase RS3PE remitting seronegative symmetric
(eNOS) synovitis with pitting oedema
NSAID non-steroidal anti-inflammatory RUTH Raloxifene Use for The Heart
drug SAPHO Synovitis, Acne, Pustulosis,
OA osteoarthritis Hyperostosis and Osteitis
OCP oral contraceptive pill SE shared epitope
25(OH)D 25-hydroxy-vitamin D SELENA Safety of Estrogens in Lupus
OPG osteoprotegerin Erythematosus National Assessment
OR odds ratio SERM selective oestrogen receptor
PADAM partial androgen deficiency in aging modulator
men SHBG sex hormone binding globulin
PADI peptidylarginine deaminase SI sacroiliac
PAH pulmonary artery hypertension sIL-6R soluble receptor for IL-6
PAN polyarteritis nodosa SJC swollen joint count
p-ANCA perinuclear anti-neutrophil SLC22A4 solute carrier family 22 A4
cytoplasmic antibody SLE systemic lupus erythematosus
PCR polymerase chain reaction Sm Smith antigen
PCT plasma procalcitonin SOBOE shortness of breath on exertion
PDGF platelet-derived growth factor SOTI Spinal Osteoporosis Therapeutic
PET positron emission tomography Intervention
PG prostaglandin SPARC secreted protein acidic and rich in
PGI2 prostacyclin cysteine
PIP proximal interphalangeal SPECT single photon emission computed
PM polymyositis tomography
PM/DM polymyositis/dermatomyositis SRP signal recognition particle
PMR polymyalgia rheumatica SRRR sibling recurrence risk ratio
PP pyrophosphate SS Sjögren’s syndrome
PPAR peroxisomal proliferator-activated SSc systemic sclerosis
receptor ssDNA single-stranded DNA

9. x Abbreviations
STAT1 signal transducer and activator of TROPOS Treatment Of Peripheral
transcription-1 Osteoporosis Study
sTNFR soluble receptor for TNF TSH thyroid-stimulating hormone
SSRI selective serotonin reuptake TxA2 thromboxane A2
inhibitor U1RNP uracil-rich 1 ribonucleoprotein
TB tuberculosis UA uric acid
TBF thermal biofeedback U/E urea and electrolytes
TGF-β transforming growth factor-β UDP uridine diphosphate
Th1 T helper 1 cells UK United Kingdom
Th2 T helper 2 cells US United States
TIMP tissue inhibitor of UV ultraviolet light
metalloproteinase VDR vitamin D receptor
TJC tender joint count VEGF vascular endothelial growth factor
TLR Toll-like receptor VIGOR Vioxx Gastrointestinal Outcomes
TKA total knee arthroplasty Research study
TMV turnover, mineralization and WBC white blood cell
volume WHO World Health Organization
TNF tumour necrosis factor WOMAC Western Ontario and McMaster
TNFR2 TNF-α receptor type 2 Universities
TRAP tartrate-resistant acid phosphatase XO xanthine oxidase

10. S E C T I O N O N E 01
General Rheumatology and Soft
Tissue Rheumatism
01 New onset painful joints
02 An acutely swollen/hot joint
03 Painful shoulders – rotator cuff and frozen shoulder
04 Tennis elbow and golfer’s elbow
05 Carpal tunnel syndrome and other entrapment neuropathies
06 Fibromyalgia syndrome
07 Plantar fasciitis
P R O B L E M
01 New Onset Painful Joints
Case History
June is a 32-year-old tour guide with an eight-week history of painful stiff hands and
difficulty walking in the mornings. The symptoms usually last for 90 minutes. For the last
six weeks she has been using diclofenac 50 mg bd with moderate benefit. Her mother has
rheumatoid arthritis treated with methotrexate.
What additional history will help to determine a diagnosis?
What is the relevance of her family history?
What aspects of the examination will be particularly relevant?
Which investigations should be performed?
© Atlas Medical Publishing Ltd

11. 2 §01 General Rheumatology and Soft Tissue Rheumatism
Background
History
Obtaining a clear history of June’s symptoms will assist greatly in narrowing your initial
differential diagnosis as a prelude to examination and investigations. Open questions
that encourage the person to start with their initial symptoms provide chronology and
the pattern of progression. Gentle prompting can, towards the end of consultation, be
supplemented with specific questions. As you listen to the story, you will be assessing the
impact of the symptoms on the individual’s life and its components of family, work and
leisure. Specifically:
b Are symptoms related to a musculoskeletal problem?
b Was there an identified trigger or precipitant?
b What has been the pattern or progression of symptoms?
b Are there features of systemic illness or inflammatory disease?
b Has anything helped the problem?
Pain and loss of function are primary presenting symptoms, but do not always coexist.
Individuals differ in their descriptors of pain, its intensity and its impact. You will be told
when the problem began and where. Is the pain in a joint; in a related joint structure such
as tendon, ligament or bursa; or in a bone? What is the nature of the pain; when does it
occur; and what is the effect of movement? Malignant pain is usually a dull, deep ache
within a bone, occurring at night or when resting. Similar symptoms may occur with
Paget’s disease or with a fracture. Differentiators of inflammatory from non-inflamma-
tory/mechanical joint pain are summarized in Table 1.1.
Table 1.1 Differentiators of joint pain
Inflammatory pain Non-inflammatory/mechanical pain
• Pain and stiffness predominant in morning and at end of day • Short-lived joint stiffness
• Stiffness greater than 30 minutes • Pain worsens with activity
• Symptoms lessen with activity • Pain improves with rest
• Pain does not improve with rest
• Localized erythema, swelling, tenderness
• Systemic features – fatigue, weight loss
Localization of pain requires clarification as to whether symptoms are recreated by
contact or movement in the area, or whether the pain is referred from another site.
Referred pain occurs when sensory perception externalizes nociceptive input from the
sclerotome or myotome of an affected structure to the relevant dermatome. Table 1.2
shows common referred pain patterns.
Onset of symptoms following trauma supports mechanical disruption of a joint, dis-
ruption of a joint’s surrounding capsule and ligaments, or fracture. Less obvious triggers
to explore are infections (Table 1.3), vaccinations (Rubella) and recent travel. A tactful
approach is required when soliciting information on genitourinary symptoms or a

12. 01 New onset painful joints 3
Table 1.2 Common presentations of referred pain
Area pain experienced Origin of pain
Shoulder Cervical spine
Biceps and lateral upper arm Shoulder and rotator cuff
Groin, inner knee Hip
Lateral thigh, buttock Trochanteric bursa
Table 1.3 Common infections associated with arthritis
Viral Gastrointestinal Genitourinary
Hepatitis B, C Salmonella typhimurium Chlamydia trachomatis
Rubella Shigella flexneri
Parvovirus Yersinia enterocolitica
Arbovirus * Campylobacter jejuni
* Serology should be tested according to exposure.
history of a new sexual partner, as it is not obvious to a patient with arthritis as to why
you would be asking such questions.
A comprehensive family history is a key part of every clinical history. A familial pat-
tern of a specific diagnosis such as rheumatoid arthritis (RA), ankylosing spondylitis or
systemic lupus erythematosus (SLE) highlights that diagnosis, and may also raise related
diagnoses that are particularly relevant for seronegative spondyloarthritides such as pso-
riasis or inflammatory bowel disease.
Examination
Examination identifies the pattern and number of joints involved and extra-articular fea-
tures (Table 1.4). Features of inflammation are sought: temperature, pulse and blood
pressure are measured, and an assessment is made of localized erythema and warmth,
tenderness, inflammation obscuring the joint margins, and reduced function. You
should distinguish monoarthritis from oligoarthritis (≤4 joints) and polyarthritis (>4
joints), whether these joints are large or small, and whether there is spinal (particularly
sacroiliac) involvement. Distal to the wrist and ankle there are at least 56 joints, so that as
the number of joints increases, the greater the probability is of involvement of both
hands and feet and of the pattern becoming increasingly ‘symmetrical’. Fingernails are
assessed for pitting or onycholysis suggestive of psoriasis. The scalp, umbilicus, natal cleft
and extensor surfaces of knee and elbow should be inspected. The presence of a malar
rash or photosensitive rash in a young woman suggests SLE.
Investigations
Investigations serve to:
b Confirm or refute a diagnostic possibility

13. 4 §01 General Rheumatology and Soft Tissue Rheumatism
Table 1.4 Patterns of arthritis
Pattern Monoarthritis Inflammatory Asymmetrical Symmetrical small DIP hands
spinal disease large joint joint arthritis
Sacroiliitis arthritis (MCP, PIP, MTP)
Differential Trauma Ankylosing Psoriatic arthritis RA Inflammatory OA
diagnosis spondylitis (if involves PIP and
1st CMC)
Haemophilia Psoriatic arthritis Reactive arthritis SLE Psoriatic arthritis
Septic IBD IBD Psoriatic arthritis
Gout
Pseudogout
Further X-ray Review personal Review personal Examine X-ray hands
investigations and family history and family history rheumatoid nodules
Aspirate for HLA-B27 Examine for Skin rashes,
crystals and conjunctivitis and serositis or
culture urethritis, and scalp mucositis
and buttocks for
psoriasis
X-ray lumbar Infection screen Urinalysis
spine and SI joints RF, CCP antibodies,
ANA
X-ray hands
and feet
ANA, antinuclear antibodies; CCP, cyclic citrullinated peptides; CMC, carpometacarpophalangeal; DIP, distal interphalangeal; IBD, inflammatory bowel
disease; MCP, metacarpophalangeal; MTP, metatarsophalangeal; OA, osteoarthritis; PIP, proximal interphalangeal; RA, rheumatoid arthritis; RF,
rheumatoid factor; SI, sacroiliac; SLE, systemic lupus erythematosus.
b Monitor for known complications of the disease process or proposed treatment
b Document a parameter that changes with disease activity or treatment
The latter includes the inflammatory markers erythrocyte sedimentation rate (ESR)
and C-reactive protein (CRP), which are non-specific markers. Whenever the possibility
of a septic joint is considered, obtaining aspirate and culture from the joint is mandatory.
Aspirated fluid is collected into a sterile container and an ethylenediaminetetraacetic acid
(EDTA)-containing tube to enable a cell count, and is sent with a request for Gram stain-
ing, polarized light microscopy, culture and sensitivity, and cell count and differential
cell count. If there will be a significant delay in the sample reaching the laboratory, fluid
can be inoculated into a blood culture system.
The early signs and symptoms of RA are not always typical. RA is characterized as
autoimmune partly on the basis of the presence of rheumatoid factor (RF), an autoanti-
body (usually immunoglobulin M [IgM]) targeting the Fc portion of IgG. Its sensitivity is
low, ranging from 60%–80%, and specificity is lower, the antibody being frequently pre-
sent in other connective tissue diseases, which limits the diagnostic utility.
Recent Developments
1 RF is present in 70% of RA cases but is not specific, occurring in 5% of healthy
individuals, and globally is more associated with chronic infection than rheumatic
diseases. Non-RF antibodies were first described in the 1960s, with the target

14. 01 New onset painful joints 5
epitopes now identified as citrulline residues, which are arginine residues
modified by peptidylarginine deaminase (PADI). Assays are now available for the
detection of antibodies to cyclic citrullinated peptides (anti-CCP antibodies),
which are highly sensitive and specific for RA and are a poor prognostic marker
of joint erosion, vasculitis and rheumatoid nodules.1 The specificity of anti-CCP
in RA is >90% with sensitivity of 33%–87%. When combined with IgM-RF, anti-
CCP has positive predictive value of >90% for RA.2 A study of undifferentiated
polyarthritis found that 93% of subjects positive for anti-CCP at first clinic visit
progressed to RA compared to 25% who were anti-CCP negative.3
2 Smoking increases the risk of RA 2–4 fold and also influences the manifestations
of the disease – with increased RF positivity and erosive disease, nodularity and
vasculitis – similar to the findings noted with anti-CCP antibodies. Smoking may
break immune tolerance by creating neo-epitopes on IgG and thus leading to RF
development. Recent work has shown that smoking is associated with increased
citrullination. The subsequent citrullinated antigens bind with more affinity to
the HLA-DR4 shared epitope subtypes, leading to increased risk of RA.4
Conclusion
Persistent arthropathy in a younger patient necessitates both accurate diagnosis and
effective management. A working knowledge of local infectious triggers is required, with
supplemental knowledge of the likely pathologies based on age and gender. History and
examination need to include potential exposure to infectious triggers, along with per-
sonal and family history. Examination will confirm or exclude significant joint inflam-
mation, and provide information on its pattern and severity (number of joints and
functional impact). Targeted investigations will narrow the diagnosis, with the urgent
investigation being exclusion of septic arthritis if there is clinical suspicion.
Further Reading
1 Mimori T. Clinical significance of anti-CCP antibodies in rheumatoid arthritis. Intern Med
2005; 44: 1122–6.
2 Schellekens GA, Visser H, De Jong BAW et al. The diagnostic properties of rheumatoid arthri-
tis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum 2000; 43: 155–63.
3 van Gaalen FA, Linn-Rasker SP, van Venrooij WJ et al. Autoantibodies to cyclic citrullinated
peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis:
a prospective cohort study. Arthritis Rheum 2004; 50: 709–15.
4 Gorman JD. Smoking and rheumatoid arthritis: another reason just to say no. Arthritis Rheum
2006; 54: 10–13.

15. 6 §01 General Rheumatology and Soft Tissue Rheumatism
P R O B L E M
02 An Acutely Swollen/Hot Joint
Case History
You have been asked to see a 28-year-old man who presents with a 36-hour history of a
red and very swollen right knee, upon which he is unable to weight bear. He has been
previously well and has no relevant family history. The clinic nurse has recorded his
temperature as 37.9°C and a random blood glucose is 7.3 mmol/l.
What is your preliminary differential diagnosis?
What additional history and examination is relevant?
What are the key investigations?
How should he be managed?
Background
Differential diagnosis
The knee is one of the most common joints affected by monoarthritis, which is fortunate
since it is so easy to aspirate. The differential diagnosis of monoarthritis is listed in Table
2.1.
Table 2.1 Differential diagnosis of monoarthritis
Trauma – Meniscal or ligamentous tears ± haemarthrosis
Sepsis – Gonococcal arthritis, Staphylococcus aureus, penetrating injury, foreign body
Reactive arthritis – Following gastrointestinal or genitourinary infection
Haemophilia
Crystal arthritis – Gout, pseudogout
Inflammatory – e.g. Rheumatoid, psoriatic
Trauma conjures images of motor vehicle accidents or dramatic tackles in rugby; how-
ever, much more mundane twisting injuries or valgus/varus strains when under load are
common. A rapidly developing joint swelling within minutes of the injury is suspicious
of an anterior cruciate ligament tear with involvement of the blood vessel running along
its surface. If internal mechanical derangement is considered possible, then imaging or
© Atlas Medical Publishing Ltd

16. 02 An acutely swollen/hot joint 7
Table 2.2 Common errors in diagnosing acute monarthritis
Error Reality
The problem is the joint because the patient Surrounding soft tissues, including bursitis, may be the
has ‘joint pain’ source of pain
The presence of intra-articular crystals excludes Crystals can be present in a septic joint
infection
Fever distinguishes infectious causes from Fever may be absent in septic monoarthritis, and in the
other causes immunocompromised patient. Acute crystal arthritis may cause
fever
A normal serum urate makes gout unlikely, and a Serum urate is normal for 30% of acute gout attacks, and only
high level confirms gout 5% of those with hyperuricaemia develop gout each year
Gram staining and culture of synovial fluid are Fastidious, slow-growing organisms, or fragile organisms, may
sufficient to exclude infection not be identified in early infection. Liaison with the laboratory is
required for specialist media and prolonged incubation
orthopaedic review is warranted. Table 2.2 highlights some common errors in diagnosing
acute monoarthritis.
The presence of fever suggests infection, and the patient should be questioned and
examined to determine the likely source. Septic arthritis is usually exquisitely tender with
resistance to joint movement. Staphylococci are the most common cause of muscu-
loskeletal sepsis, with the prevalence of both streptococcal and mycobacterial infection
increasing. For infections with staphylococci, streptococci, Gram-negative bacteria and
anaerobes, only one joint is usually involved. Polyarticular involvement is more likely in
the elderly or immunosuppressed, with infection by Haemophilus influenza, meningo-
cocci and Neisseria gonorrhoeae. Lyme disease can present with knee involvement,
although the diagnosis can be quickly excluded if there has been no exposure to the tick
vector of Borrelia burgdorferi.
In young patients, gonococcal arthritis is the most common non-traumatic acute
monoarthritis, and questioning regarding sexual partners and genitourinary symptoms
is necessary. In addition to arthritis (often polyarticular), tenosynovitis and a pustular
rash of the extremities should be sought. Gonococcal arthritis is 3–4 times more com-
mon in women, who often develop arthritis in the perimenstrual period. Men often
experience a urethritis as dysuria, and may notice a morning discharge, whereas women
may be asymptomatic.
Reactive arthritis is a sterile arthritis, occurring distant in both time and place from an
inciting infection (usually gastrointestinal or genitourinary). Lower limb asymmetric
oligoarthritis is most common, with associated enthesitis such as Achilles tendinitis, and
mucocutaneous features of conjunctivitis, pustular rash on the hands and feet and sterile
urethritis. Common triggers are genitourinary infection with Chlamydia trachomatis and
gastrointestinal infection with Salmonella typhimurium, Shigella flexneri, Campylobacter
jejuni and Yersinia enterocolitica. Stool culture and collection of early morning urine for
detection of chlamydia DNA by polymerase chain reaction (PCR) should be considered.
Crystal arthritis is both dramatic and rapid in onset, with the most commonly impli-
cated crystals being uric acid, calcium pyrophosphate and hydroxyapatite. Gout is

17. 8 §01 General Rheumatology and Soft Tissue Rheumatism
unusual in the young and is usually preceded by more distal joint involvement, classically
the first metatarsophalangeal joint (podagra). Pseudogout or calcium pyrophosphate
dihydrate (CPPD) deposition disease is uncommon below the age of 50 years and
the knee is most often involved, followed by wrist and shoulder. Basic calcium phosphate
(hydroxyapatite) results in a calcific periarthritis, which most commonly affects the
shoulder.
Aspirating a knee joint
Every medical graduate should feel confident to undertake knee aspiration (Figure 2.1).
The knee is exposed with the patient lying so that you can obtain access to either the
medial or lateral aspect. The knee is generously cleaned with antiseptic and allowed to dry
whilst you are preparing the aspiration syringes. The patella is pinched between thumb
and index finger at its midpoint, which allows you to detect tension in the quadriceps
muscles and also allows you to distract the patella upwards to increase the infrapatellar
space. Local anaesthetic (5–10 ml) is infiltrated via a 21G or 23G needle at a point proxi-
mal and inferior to where you are holding the patella, noting that the pain-sensitive
structures are the dermis and the thickened synovium as you enter the joint. When the
anaesthetic has been given time to work, the joint is aspirated along the same needle track
with a fresh 10–20 ml syringe and 18G needle. Afterwards, a dressing is applied firmly for
several minutes to ensure haemostasis and to prevent synovial fluid leakage.
Figure 2.1 Arthrocentesis of the left knee – medial approach.
Only 1–2 ml of fluid is sufficient to complete all investigations; however, the joint
should be aspirated of as much fluid as possible without increasing the trauma of the pro-
cedure. Substantial pain relief is achieved by aspirating a tense effusion, and while reac-
cumulation will occur, it buys some time while the preliminary investigation results are
received. As the aspirate is removed, you should note its colour, viscosity and turbidity.
Normal synovial fluid is similar to egg white (syn = resembling, ovium = egg) and is both
viscous and acellular. As the degree of inflammation increases – from the negligible
amount found in osteoarthritis to the mid-range of rheumatoid arthritis and the extreme
of septic arthritis – the viscosity decreases and the cellularity and turbidity increase.

18. 02 An acutely swollen/hot joint 9
Table 2.3 Synovial fluid characteristics
Normal Non-inflammatory Inflammatory Septic
Colour Clear Straw yellow Yellow Variable
Clarity Transparent Transparent Hazy opaque Opaque
Viscosity High High Low Low–Thick
WBC (¥ 106/l) 0–200 200–2000 2000–75 000 >75 000
Neutrophils <25% <25% 25%–50% >75%
WBC, white blood cell.
Blood-coloured effusions suggest either trauma or CPPD deposition disease. Synovial
fluid characteristics are shown in Table 2.3.
It is suggested that approximately 2 ml of fluid is collected into a container plus anti-
coagulant, and the remaining fluid collected in a large-volume sterile container. Tests
requested should include an urgent Gram stain, cell count and differential count, crystal
examination using polarized light microscopy and culture. If gonococcal or fungal infec-
tions are suspected, this needs to be highlighted as it influences the culture medium and
length of culture required.
Analgesics, antipyretics and rest should be employed in the first instance, with the
aspiration itself often affording a considerable pain relief. If septic arthritis is suspected,
then intravenous antibiotics covering Staphylococcus aureus and N. gonorrhoeae should
be commenced after the synovial fluid aspiration. The presence of bacteria on Gram
staining or subsequent bacterial growth requires specialist medical and orthopaedic
review to combine antibiotic therapy with joint lavage.
Gout is confirmed by the presence of intracellular, negatively birefringent urate crys-
tals, with intracellular pyrophosphate crystals confirming pseudogout. Both of these con-
ditions are self-limited and spontaneously improve over a few days. Adequate hydration
combined with analgesia and the introduction of a non-steroidal anti-inflammatory
drug will generally suffice. Colchicine at a dose sufficient to impact on acute gout invari-
ably causes diarrhoea. If you have confirmed the joint is sterile, then intra-articular corti-
costeroid injection provides excellent resolution.
Recent Developments
1 A prospective study of children presenting for investigation of possible septic
arthritis of the hip concluded that oral temperature >38.5°C was the best
predictor, followed by an elevated serum C-reactive protein (CRP), an elevated
erythrocyte sedimentation rate, refusal to weight bear and an elevated white cell
count.2 CRP >20 mg/l was a strong independent risk factor and a valuable tool
for assessing and diagnosing septic arthritis of the hip. As the number of risk
factors increases so does the predicted probability of septic arthritis, such that
three to five factors present is associated with 83%–98% predictive probability.

19. 10 §01 General Rheumatology and Soft Tissue Rheumatism
2 Increased plasma procalcitonin (PCT) may be a useful marker for osteomyelitis
but not septic arthritis. Procalcitonin is cleaved in neuroendocrine tissues – such
as thyroid C cells, lung and pancreatic tissue – to calcitonin. During infection,
large amounts of PCT are released. The source is probably monocytes stimulated
by endotoxin, and hepatocytes stimulated by tumour necrosis factor or
interleukin-6. The role of PCT measurement with a rapid immunoassay was
investigated in children admitted with suspected osteomyelitis or septic arthritis.3
The authors reported specificity of 100% and sensitivity of 58% for osteomyelitis
and the same specificity, but lower 27% sensitivity, in septic arthritis.
3 High-resolution magnetic resonance imaging (MRI) of soft tissues and joints is
increasingly used prior to interventions such as arthroscopy. In a cohort of
children, Luhmann and colleagues4 compared radiological interpretation of knee
MRI with that of the surgeon who integrated the history, clinical examination,
plain radiographs, MRI scans and radiologist report. The pre-operative diagnosis
by the surgeon was better (P <0.05) than the formal radiology interpretation with
respect to anterior cruciate ligament tear, lateral meniscal tear, osteochondritis
dissecans and discoid lateral meniscus.
Conclusion
An acutely hot, swollen joint is an urgent presentation. Exclusion of sepsis is mandatory,
particularly in children and immunocompromised patients. Joint aspiration remains the
investigation of choice. Subsequently, treatment will often include antibiotics, pending
laboratory results, combined with judicious use of analgesia and anti-inflammatory
medications. Analysis of synovial fluid is valuable in establishing the diagnosis of gout,
particularly in joints other than the classical podagra of the great toe. Patients often inter-
pret the doctor’s ‘it could be gout’ comment about their sore joint as either a definitive
diagnosis or as a slur on an indulgent lifestyle, when neither may be intended.
Further Reading
1 Siva C, Velazquez C, Mody A, Brasington R. Diagnosing acute monoarthritis in adults: a
practical approach for the family physician. Am Fam Physician 2003; 68: 83–90.
2 Caird MS, Flynn JM, Leung YL, Millman JE, D’Italia JG, Dormans JP. Factors distinguishing
septic arthritis from transient synovitis of the hip in children. A prospective study. J Bone Joint
Surg Am 2006; 88: 1251–7.
3 Butbul-Aviel Y, Koren A, Halevy R, Sakran W. Procalcitonin as a diagnostic aid in
osteomyelitis and septic arthritis. Pediatr Emerg Care 2005; 21: 828–32.
4 Luhmann SJ, Schootman M, Gordon JE, Wright RW. Magnetic resonance imaging of the knee
in children and adolescents. Its role in clinical decision-making. J Bone Joint Surg Am 2005; 87:
497–502.

20. 03 Painful shoulders – rotator cuff and frozen shoulder 11
P R O B L E M
03 Painful Shoulders – Rotator Cuff and
Frozen Shoulder
Case History
Mr Lawrence, a 76-year-old retired driver, is having difficulty living independently after
returning home following a recent myocardial infarction. On the day of discharge he fell
heavily, landing on his left upper arm. His concern is a very painful left shoulder,
especially at night and when he tries to move his left arm during the day.
How would you determine whether he has adhesive capsulitis (frozen shoulder)?
Is there a role for medical imaging, and if so, what modality?
What treatment should be initiated?
Background
Shoulder pain is an almost unavoidable life experience; in one study, 7% of an adult pop-
ulation aged 25–75 years reported at least one month’s shoulder pain in the previous
year. The peak annual incidence of shoulder disorders is in the fourth and fifth decades,
at a rate of 0.25%. A Dutch study found that 25% of all 85-year-olds in Leiden suffered
from chronic shoulder pain and restriction. Community-based surveys concur with this
high incidence of soft tissue lesions about the shoulder, with roughly equal sex incidence.
Up to 20% of patients with chronic symptoms and 65% of all diagnoses relate to lesions
of the rotator cuff. Rotator cuff disease is the most common cause of shoulder pain found
in these studies. An ultrasound study found rotator cuff tears in 13% of 50–59-year-olds,
20% of 60–69-year-olds, 31% of 70–79-year-olds and 51% of subjects aged over 80 years,
even when they were asymptomatic.
Table 3.1 summarizes causes of shoulder pain. The pain-sensitive structures of the
shoulder are mainly innervated by the fifth cervical segment (C5), so that pain from these
structures is referred to the C5 dermatome creating the sensation of pain over the anter-
ior arm, especially the deltoid insertion. The acromioclavicular joint is innervated by the
C4 segment – pain arising here is felt at the joint itself and radiates over the top of the
shoulder into the trapezius muscle and to the side of the neck.
Clinical assessment
A history of trauma, marked night pain and weakness on resisted abduction strongly sug-
gests a rotator cuff tear. The sleeping position that induces night pain is an important clue:
© Atlas Medical Publishing Ltd

21. 12 §01 General Rheumatology and Soft Tissue Rheumatism
Table 3.1 Causes and clinical characteristics of shoulder pain
Category Cause Clinical features
Extracapsular Rotator cuff and subacromial bursa (e.g. impingement Painful arc of abduction
lesions syndromes, calcific tendinitis, cuff tears, bursitis) Pain on resisted cuff muscle movements, with intact
passive movement (allowing for pain and guarding)
Pain on impingement manoeuvres as the inflamed
rotator cuff tendons impinge on the inferior surface of
the acromion and coracoacromial arch
Intracapsular Glenohumeral joint (inflammatory arthritis – RA, Loss of both active and passive movement
lesions spondyloarthritis, pseudogout) Reduced glenohumeral range
Joint capsule (adhesive capsulitis) Night pain
Bone disease (Paget’s disease, metastases) Muscle strength, allowing for pain, is intact
Referred pain Cervical spine (facet joint root impingement, discitis) Arm and hand pain with paraesthesia
Brachial plexus (brachial amyotrophy) Marked muscle weakness and wasting
Thorax (Pancoast’s tumour) Neck pain and stiffness
Thoracic outlet syndrome Herpes zoster rash
Suprascapular nerve entrapment Systemic features with weight loss
Subdiaphragmatic (abscess, blood, hepatic lesions)
shoulder pain that results in awakening when not lying on that shoulder is found in adhe-
sive capsulitis and inflammatory arthritis; pain when lying on the affected shoulder is seen
in acromioclavicular joint disease and rotator cuff disease. Prior shoulder problems sug-
gest rotator cuff disease with chronic impingement, or calcific tendinitis. A history of
marked shoulder joint swelling suggests inflammatory arthropathy with the presence of
an anterior bulge in the shoulder usually secondary to a subacromial bursa effusion.
Glenohumeral osteoarthritis (OA) is characterized by morning stiffness, pain with use and
chronicity of symptoms. OA, however, is less common than rotator cuff dysfunction.
Examination of the shoulder is best undertaken with the patient wearing the mini-
mum of upper body clothing. The contours of the shoulder are examined for wasting,
asymmetry and muscle fasciculation. Palpation should proceed from the sternoclavicular
joint along the clavicle to the acromioclavicular joint, to the tip of the acromion and the
humeral head beneath the acromion. The shoulder range of movement should be exam-
ined both actively and passively, with muscle strength and pain on resistance assessed.
There are essentially three movements to test in the shoulder: abduction due to
supraspinatus contraction; external rotation as a result of infraspinatus and teres minor
movement; and internal rotation due to subscapularis movement (Box 3.1).
Box 3.1 Practice Point
Three positive clinical tests (supraspinatus weakness, weakness of external rotation and
impingement) or two positive results for a patient older than 60 years are highly pre-
dictive of a rotator cuff tear.1
Complete rotator cuff tears will show no active abduction but near full-range movement
when passively moved. During examination ask about a painful arc during abduction
(Figure 3.1). When examining active and passive abduction you should stand behind the
patient and place one hand over the shoulder and scapula. The scapula should not begin to

22. 03 Painful shoulders – rotator cuff and frozen shoulder 13
Painful arc of abduction
acromioclavicular joint
180°
Painful arc of
abduction in
rotator cuff
120°
70°
Figure 3.1 Painful arc: the patient slowly abducts the arm as high as possible, describing symptoms as the
arm rises.
elevate or rotate until at least 90 degrees of abduction has been reached. Early scapulotho-
racic movement localizes the abnormality to the glenohumeral joint or capsule, as seen in
frozen shoulder. You should examine external rotation at 0 degrees abduction, with the
elbow beside the chest, and if external rotation is absent then a frozen shoulder is likely.
Next re-examine both internal and external rotation at 90 degrees abduction; if both are
restricted, a frozen shoulder is again likely. Bicipital tendinitis is examined by testing
resisted flexion at 30 degrees external rotation, and feeling for tenderness in the bicipital
groove. Shoulder impingement can be reproduced by internally rotating the arm held
flexed at 90 degrees and bringing the inflamed rotator cuff against the anterior acromion.
The ‘empty can’ test is suggestive of a rotator cuff tear: it shows pain on resisted elevation of
the inverted arm held extended at 90 degrees, as if emptying a can of drink.
Rotator cuff disease
The glenohumeral joint is, by virtue of its anatomical shape, inherently unstable, relying
on the joint capsule as well as the rotator cuff muscles (supraspinatus, infraspinatus and
subscapularis) for additional stability. Impingement of the rotator cuff between the prox-
imal humerus and the acromioclavicular arch may occur from anomalies of the arch
(structural impingement) and from instability due to joint hyperlaxity or weak rotator
cuff muscles (functional impingement). Coracoacromial arch anomalies may be congen-
ital, dependent on acromial shape. Three shapes have been described – flat, curved and

23. 14 §01 General Rheumatology and Soft Tissue Rheumatism
hooked – although there is poor inter-observer agreement on identifying the shape.
Acquired impingement occurs secondary to osteophytes growing from the acromioclav-
icular joint or calcification of the acromioclavicular ligament. Impingement occurs when
the cuff becomes compressed in the subacromial space as the arm is elevated. As the
humeral head rotates, the rotator cuff tendons are compressed between the greater
tuberosity of the humerus and the anterior edge of the acromion, the coracoacromial lig-
ament, the under-surface of the acromioclavicular joint and with the reactive inflamma-
tory subacromial bursa.
In addition to the impingement theory, a vascular theory has been proposed. With the
arm at the side, it has been suggested that the supraspinatus tendon has a relative avascu-
lar area 1 cm proximal to its insertion at the greater tuberosity, directly beneath the
impingement zone. This may be affected by the position of the shoulder and increases
with age. However, the infraspinatus tendon has a similar vascular watershed area, sug-
gesting that factors other than vascularity are important. Chronic irritation in the avascu-
lar region produces tendinitis, leading to local inflammation and further compression.
Other causes of tendinitis include trauma, instability and possibly infarction of the cuff in
patients with vascular disease. The vascular and impingement theories are not mutually
exclusive and it is possible that the high incidence of supraspinatus pathology is the result
of impingement in and around a critical zone of vascular supply.
With time, wearing and attrition of the cuff leads to impaired action or rupture of the
short rotators stabilizing the humeral head into the glenoid fossa, so that the deltoid pulls
the humerus against the under-surface of the acromion and a vicious impingement cycle
is established. Impingement-caused tears are usually incomplete in the supraspinatus
and infraspinatus tendons and complete in the long head of biceps. Complications of
impingement include a frozen shoulder, rupture of the rotator cuff tendons or long head
of biceps and, in elderly patients with a long-standing tear, a feared end-stage lesion,
‘recurrent haemorrhagic shoulder of the elderly’.
Treatment depends on the mechanism of impingement. Patients with functional
impingement are treated with a resting sling for 24–36 hours, pendular exercises and full-
dose non-steroidal anti-inflammatory drug (NSAID). Structural impingement is treated
similarly but the surgical options of arthroscopic surgery to remove osteophytes or trim
the acromion are available. Corticosteroid injection to the subacromial space can be
combined with an initial 4–7 days of pendulum exercises and avoidance of abduction
prior to a programme of shoulder-strengthening exercises. Infraspinatus strengthening
may be important to provide stabilization of the humeral head to prevent superior sub-
luxation on abduction.
Studies of eccentric loading exercises have shown promising results, particularly in
lesion of the Achilles tendon. Eccentric loading exercises involve a load being applied to a
muscle in its contracted position and the muscle is lengthened under the load. In the
shoulder, the supraspinatus would be contracted with the arm abducted and under load
the arm would slowly return to the side. Exercise programmes require highly motivated
people and there is concern that exercises can increase symptoms initially.
Frozen shoulder/adhesive capsulitis
Initially described in 1872, this condition remains as ‘difficult to treat and difficult to
explain from the point of pathology’ as Codman observed in 1934. This common disor-

24. 03 Painful shoulders – rotator cuff and frozen shoulder 15
der (2% cumulative risk in an at-risk population annually) is frequently misdiagnosed
and is characterized by painful restriction of all shoulder movements, both active and
passive, with characteristic restriction in the glenohumeral range. There is marked reduc-
tion or absence of shoulder external rotation at 0 degrees abduction, reduction of both
internal and external rotation at 90 degrees abduction, as well as prominent restriction of
placing the hand behind the back on internal rotation. Frozen shoulder is characterized
pathologically by fibrosis and retraction affecting predominantly the anterior and infer-
ior structures of the glenohumeral joint capsule. Patients usually present in the sixth
decade and onset before the age of 40 years is uncommon. Table 3.2 lists the diseases
associated with frozen shoulder, diabetes being the most significant. Diabetes, particu-
larly long-standing insulin-dependent diabetes, is associated with glycosylation of subcu-
taneous collagen and the development of soft tissue contraction – so called diabetic
cheiroarthropathy.
Table 3.2 Common disorders associated with frozen shoulder
• Acute shoulder trauma and shoulder immobilization
• Diabetes mellitus
• Thyroid disease (both hyper- and hypothyroidism)
• Cardiac disease, particularly after cardiac surgery
• Neurological disease with loss of consciousness or hemiplegia
• Pulmonary disease – tuberculosis and carcinoma
• Rotator cuff disease, especially cuff tear
• Acute glenohumeral joint inflammation
Three phases of frozen shoulder are recognized:
1 Painful inflammatory phase. Beginning insidiously, with often only a minor injury
being recalled, nocturnal awakening pain develops. The pain may be constant and
prevents the patient lying on the shoulder. Physiotherapy often aggravates symptoms
at this stage and corticosteroid injections are of limited benefit. This phase lasts
2–9 months.
2 Frozen shoulder. With time, the night and rest pain eases, but the shoulder remains
‘frozen’. Mean duration is 4–12 months.
3 Recovery phase. After a mean delay of 5–26 months, shoulder limitation slowly
recovers in the majority of patients towards normal range (usually a 10%–30% loss
of motion, which is often undetected by the patient). The total duration of
symptoms lasts 12–42 months, with mean disease duration of 30 months.
In 10%–20% of patients a contralateral frozen shoulder develops, usually milder than
the first, while the original shoulder is ‘thawing’. It is important to educate patients that
the condition will spontaneously resolve and the stiffness will greatly reduce. NSAIDs
and analgesics are used but there are no randomized controlled trials studying efficacy. A
prospective study in frozen shoulder compared exercise within the limits of pain with
intensive physiotherapy. Those who performed exercises within the limits of pain had
better results, recorded as near-normal painless shoulder movement (64% of patients at
12 months, 89% at 24 months), compared to intensive physiotherapy (63% of patients at

25. 16 §01 General Rheumatology and Soft Tissue Rheumatism
24 months).2 An early meta-analysis by Hazleman on the use of intra-articular steroids
reported that the outcome depended on the duration of symptoms and hence possible
stage of disease. Patients who receive the injection earlier in the course of the disease
recover more quickly.3 An extensive meta-analysis by Buchbinder et al. found a benefit
for glenohumeral intra-articular corticosteroid injection for frozen shoulder compared
with placebo.4
For those unable to tolerate the pain and disability of a frozen shoulder, manipulation
under anaesthesia (MUA) is a reliable way to improve the range of movement. It is par-
ticularly indicated when disability persists after six months of non-operative therapy.
More recently, arthroscopic release of the capsule has been advocated as a more con-
trolled release of the capsule than MUA. Arthroscopic release also avoids the complica-
tions of MUA such as fracture of the humerus and iatrogenic intra-articular shoulder
lesions.5
Imaging
Imaging is undertaken primarily when considering referred pain or a malignant process.
In the assessment of rotator cuff disease, no imaging may be required initially, and may
only be undertaken subsequently if the clinical progression is not as expected. A plain X-
ray should then be the initial imaging modality, because if there is marked superior
migration of the humeral head, there must be complete rotator cuff disruption. Either
magnetic resonance imaging or ultrasound can confirm a possible full-thickness rotator
cuff tear, although ultrasound is significantly cheaper and is preferred by patients.
Suspected partial-thickness tears are best verified with an ultrasound scan.1
Recent Developments
1 Oral steroids may be useful in frozen shoulder, particularly during the early
inflammatory phase. Buchbinder et al.6 undertook a randomized controlled trial
on a series of 50 patients and found that oral steroid therapy initially improved
the frozen shoulder but the effect did not last beyond six weeks. Their subsequent
analysis of five small trials, in which all subjects received physiotherapy or an
exercise programme, confirmed that oral prednisolone or cortisone when given
for 3–4 weeks had a modest benefit on pain and disability and ability to move
the shoulder.7
2 Recently, a neural aetiology for tendinopathy has been considered.8 Tendinopathy
was proposed as an appropriate term for a symptomatic primary tendon disorder,
as it made no assumption as to the underlying pathological process. Underlying
the neural theory are four basic observations: tendons are innervated; substance P
has been found in rotator cuff tendinopathy and is a pro-inflammatory mediator;
the neurotransmitter glutamate is also present in tendinopathy; and tendon nerve
cell endings are closely associated with mast cells. It has been tentatively
postulated that neural stimuli secondary to overuse or mechanical irritation lead
to mast cell degranulation and release of mediators that begin an inflammatory
cascade.

26. 03 Painful shoulders – rotator cuff and frozen shoulder 17
Conclusion
Frozen shoulder is a common and painful condition that impacts adversely on an indi-
vidual’s activities of daily living. Despite being self-limited, recovery is protracted and a
high proportion of patients do not regain full function. As a condition, it is largely man-
aged in the community by primary physicians, physiotherapists and occupational thera-
pists. Treatments that aim to mechanically stretch or disrupt the joint capsule (MUA,
arthroscopic release or hydrodilation of the capsule) are reserved for those with severe
symptoms who have failed to progress with conservative therapy.
Further Reading
1 Diehr S, Ison D, Jamieson B, Oh R. Clinical inquiries. What is the best way to diagnose a
suspected rotator cuff tear? J Fam Pract 2006; 55: 621–4.
2 Diercks RL, Stevens M. Gentle thawing of the frozen shoulder: a prospective study of
supervised neglect versus intensive physical therapy in seventy-seven patients with frozen
shoulder syndrome followed up for two years. J Shoulder Elbow Surg 2004; 13: 499–502.
3 Hazleman BD. The painful stiff shoulder. Rheumatol Phys Med 1972: 11: 413–21.
4 Buchbinder R, Green S, Youd JM. Corticosteroid injections for shoulder pain. Cochrane
Database Syst Rev 2003; CD004016.
5 Dias R, Cutts S, Massoud S. Frozen shoulder. BMJ 2005; 331: 1453–6.
6 Buchbinder R, Hoving JL, Green S, Hall S, Forbes A, Nash P. Short course prednisolone
for adhesive capsulitis (frozen shoulder or stiff painful shoulder): a randomised, double
blind, placebo controlled trial. Ann Rheum Dis 2004; 63: 1460–9.
7 Buchbinder R, Green S, Youd JM, Johnston RV. Oral steroids for adhesive capsulitis.
Cochrane Database Syst Rev 2006; CD006189.
8 Rees JD, Wilson AM, Wolman RL. Current concepts in the management of tendon
disorders. Rheumatology 2006; 45: 508–21.

27. 18 §01 General Rheumatology and Soft Tissue Rheumatism
P R O B L E M
04 Tennis Elbow and Golfer’s Elbow
Case History
Simon is a 48-year-old labourer. His work has required a large amount of manual
screwdriver use, and he presents with a three-month history of an increasingly painful
elbow. He now has trouble grasping objects such as a cup.
What is the difference between tennis elbow and golfer’s elbow?
What are the characteristics of each condition, and what treatment is indicated?
Background
Tennis elbow
Tennis elbow or lateral epicondylitis is an overload injury, which occurs after minor or
unrecognized microtrauma to the proximal insertion of the extensor muscles of the fore-
arm – particularly extensor carpi radialis brevis. Tennis elbow is the most frequently
diagnosed elbow condition (Box 4.1); it occurs commonly in middle life (age 35–55
years) and has an incidence in general practice of 4–7 cases per 1000. Despite its common
name, most cases occur in non–tennis players and it is frequently a work-related enthe-
sopathy affecting up to 15% of workers in at-risk industries. Operative specimens reveal
tendon glycosaminoglycan infiltration and microtears, as well as new bone formation at
the attachment site. Both traction injury and ischaemia play a role in its development.
Flexion deformity is unusual, occurs late and is minimal. Loss of 20 degrees of exten-
sion cannot be attributed to tennis elbow and warrants investigation for arthritis,
impingement at the olecranon fossa or a soft tissue mass in the posterior aspect of the
elbow. Tennis elbow is usually self-limiting, having an average duration of six months to
two years, with 90% of subjects recovering within one year. Various conservative inter-
ventions exist including pain-relieving medications, corticosteroid injections, physio-
therapy, elbow supports, acupuncture, surgery and shockwave therapy (Box 4.2).
Box 4.1 Diagnosis of tennis elbow
b Lateral elbow pain with tenderness on palpation just distal to the lateral
epicondyle
b Worsening pain localizing to the lateral epicondyle on resisted wrist dorsiflexion
b X-rays excluding calcific tendinitis, exostoses and osteoarthritis of the radio-ulnar
joint
© Atlas Medical Publishing Ltd

28. 04 Tennis elbow and golfer’s elbow 19
Box 4.2 Treatment of tennis elbow
b Structured physiotherapy consisting of elbow manipulation and exercise, supple-
mented with home exercises and self-manipulation
b Practical advice booklet on self-management and ergonomics
b Recommend avoidance of corticosteroid injections, as short-term benefit is offset
by a poorer longer-term outcome
Most important in treatment is activities modification – both frequency and method
of performance. In tennis players, common errors are inadequate conditioning, incorrect
grip size, faulty backhand style and problems with the racquet and its stringing. In the
work setting, a review by an occupational therapist is recommended, particularly focus-
ing on pronation/supination movements and grip size. A physiotherapy programme that
includes strengthening exercises for the entire upper limb and a graded resistive pro-
gramme for wrist dorsiflexors is recommended.
In the setting of localized tenderness it is tempting to inject the lesion. As noted in Box
4.2, the short-term gain may be offset by a poorer long-term outcome. The injection
technique is a small volume of corticosteroid and local anaesthetic injected into the
tendinous insertion of extensor carpi radialis brevis into the lateral epicondyle. As the
injection is not into a potential space but into an already tender, dense area, the injection
is against resistance and is both uncomfortable and has the risk of steroid tracking super-
ficially to the subcutaneous tissues, leading to depigmentation and atrophy. In contrast
to other painful overuse syndromes in which total tendon ruptures have been reported
(Achilles, biceps, patella), the tendon of the extensor carpi radialis brevis is strongly con-
nected and supported by other extensors of the wrist.
A small number of patients have recalcitrant lateral epicondylitis and are considered
for operative intervention – open, arthroscopic and percutaneous. Operative interven-
tions followed for a minimum of two years demonstrate an improvement compared to
pre-operative status, with no difference in outcome according to procedure technique.1
Golfer’s elbow
Golfer’s elbow or medial epicondylitis is the mirror image of tennis elbow, and is thought
also to relate to repetitive traction stress and microtears at the insertion of the forearm
flexors (flexor carpi radialis) and pronator teres into the medial epicondyle. It occurs in
both professional and amateur sports players, as well as manual workers such as brick-
layers. It is much less common than tennis elbow, with approximately one-twentieth the
incidence. Similar to tennis elbow, the diagnosis is clinical, with localized tenderness that
worsens on resisted wrist flexion and forearm pronation (Box 4.3).
Box 4.3 Golfer‘s elbow
b Elbow pain at the medial epicondyle
b Increasing symptoms on resisted wrist flexion and resisted forearm pronation
b Treatment includes modification of activities, upper limb exercises and analgesics

29. 20 §01 General Rheumatology and Soft Tissue Rheumatism
Recent Developments
A randomized controlled trial compared the effectiveness of physiotherapy, cortico-
steroid injections and a ‘wait and see’ approach in 198 patients with tennis elbow who
were randomized to the three treatment arms.2 Physiotherapy was eight sessions of
mobilization with movement and exercises plus home exercises and self-manipulation.
Injection therapy with triaminolone acetonide (10 mg) and 1% lidocaine was the second
study arm. The ‘wait and see’ approach consisted of ergonomic instruction and use of
analgesics, heat, cold and braces if needed. At six weeks the main outcome measures
(global improvement, pain-free grip strength, assessor’s rating of complaints, severity of
elbow pain and elbow disability) were significantly better in the corticosteroid-treated
group than in the other groups. However, all groups were improving and the benefit of
the steroid injection was short-lived, such that a crossover occurred around twelve weeks,
with the one-year results showing physiotherapy superior to corticosteroid injections for
all outcome measures. Importantly, at one year, the injection-treated group was signifi-
cantly worse on all outcomes compared with the physiotherapy group, and on two out of
three measures compared with the ‘wait and see’ group. The corticosteroid injection
group also had the most reported recurrences. A similar study with only seven weeks of
follow-up confirmed the benefits of steroid injections in the short term.3
Conclusion
Tennis elbow is a common problem in general practice and is best treated with the
knowledge that it is a self-limiting condition, with the majority of patients improving in
the medium term. Whilst corticosteroid injections offer short-term benefit, there is the
potential for both short-term adverse effects and the possibility of a worse outcome at
one year. Physiotherapy provides benefit that is slower in onset but is more sustained and
allows patients to become self-reliant in their own management.
Further Reading
1 Szabo SJ, Savoie FH, Field LD, Ramsey JR, Hosemann CD. Tendinosis of the extensor carpi
radialis brevis: an evaluation of three methods of operative treatment. J Shoulder Elbow Surg
2006; 15: 721–7.
2 Bisset L, Beller E, Jull G, Brooks P, Darnell R, Vicenzino B. Mobilisation with movement and
exercise, corticosteroid injection, or wait and see for tennis elbow: randomised trial. BMJ
2007; 333; 939–45.
3 Tonks JH, Pai SK, Murali SR. Steroid injection therapy is the best conservative treatment for
lateral epicondylitis: a prospective randomised controlled trial. Int J Clin Pract 2007; 61:
240–6.

30. 05 Carpal tunnel syndrome and other entrapment neuropathies 21
P R O B L E M
05 Carpal Tunnel Syndrome and Other
Entrapment Neuropathies
Case History
Beatrix is a 33-year-old production-line worker. For the last four weeks she has been
awakening with painful pins and needles in her left hand and a dull pain that radiates
from her wrist to her elbow. Shaking the arm improves the symptoms and she sometimes
sleeps with her arm hanging out of the bed.
What are the clinical features of the carpal tunnel syndrome?
What is the role for imaging and nerve conduction studies?
What investigations are appropriate to determine the cause?
How would you manage this problem?
Background
Entrapment neuropathies are disorders where peripheral nerves are damaged by com-
pression as they pass through a bony or fibrous canal. The disorders may be precipitated
by repetitive motion or strain, and carpal tunnel syndrome (CTS) is by far the common-
est entrapment neuropathy and the most common focal peripheral neuropathy. The
median nerve, along with the flexor tendons, passes through the carpal tunnel, which is
bridged by the transverse carpal ligament (Figure 5.1). CTS affects 3% of the population
although there is an imperfect correlation between reported symptoms and electrophysi-
ological findings. Women are three times more likely than men to be affected with CTS,
and a number of predisposing conditions are recognized (Box 5.1).
CTS causes pain, numbness and tingling in the distribution of the median nerve: i.e.
anteriorly, in the lateral half of the ring finger to the median half of the thumb; and poste-
riorly, in the distal halves of the ring and middle fingers. If severe, the symptoms may
radiate up the arm and they can often occur at night, thus disturbing sleep. In severe cases
there is a loss of small muscle function, which impairs manual dexterity and can lead to
wasting of muscles of the thenar eminence. The symptoms of CTS are common and clin-
ical signs (Box 5.2) are not always present. Accurate diagnosis is one of the major deter-
minants of successful treatment. The diagnosis should be confirmed wherever possible
by nerve conduction studies.
© Atlas Medical Publishing Ltd

31. 22 §01 General Rheumatology and Soft Tissue Rheumatism
Median nerve
Tendon sheath
Carpal ligament
Bundle of tendons
Figure 5.1 Anatomy of the carpal tunnel.
Other common nerve entrapment syndromes
Thoracic outlet syndromes
These are due to compression of the brachial plexus and brachial vessels in the neck.
Costoclavicular syndrome, due to a narrowing of the space between the clavicle and first
rib, may arise from congenital abnormality or because of poor posture. Cervical rib syn-
drome is due either to an extra rib or to a fibrous band between the seventh cervical ver-
tebra and the sternum. Compression of nerves and vessels occurs as they pass over the
additional structures. Adson’s test may be positive: the patient looks to the affected side
and takes a deep breath while the examiner lifts the arm to 90 degrees. If compression is
present, the radial pulse may disappear.
Suprascapular neuritis
The suprascapular nerve (cervical segments C5/C6) supplies sensation to the shoulder joint
and motor supply to the infraspinatus and supraspinatus muscles. It can become com-
pressed as it passes through the suprascapular notch and under the transverse ligament.
Ulnar neuritis
Compression of the ulnar nerve usually occurs in the canal, where it is covered by the arcu-
ate ligament. It may also occur between the two heads of flexor carpi ulnaris just distal to
the elbow joint. The syndrome may occur as a result of direct trauma or fracture, repetitive

32. 05 Carpal tunnel syndrome and other entrapment neuropathies 23
Box 5.1 Causes of CTS
Overuse Repetitive flexion or extension of the wrist, particularly while
gripping objects firmly
Use of walking stick in patients with mobility disorders
Occupational – use of power tools, assembly-line work
Injury Colles fracture
Subluxation of the lunate bone
Arthritis Rheumatoid – tendon sheath inflammation
Osteoarthritis
Gout or pseudogout
Wrist ganglion Outpouching of the wrist joint capsule
Increased canal Pregnancy
volume Obesity
Congestive cardiac failure
Lipoma
Infections Septic arthritis
Lyme disease
Tuberculosis
Metabolic Diabetes
Hypothyroidism
Acromegaly
Amyloidosis
Box 5.2 Clinical signs of CTS
Tinel’s sign Tapping over the median nerve elicits symptoms in the distribution
of the nerve
Phalen’s sign Place both hands together palm to palm, with the wrists extended to
90 degrees, and forearms horizontal and close to the chest. The
affected hand will begin to tingle within 1–2 minutes
Reverse Phalen’s As above, but with the hands placed back to back
movements or rheumatoid arthritis affecting the elbow joint. It causes pain and tingling
down the inside of the forearm to the little finger and medial aspect of the ring finger. The
nerve gives rise to a sensory supply to the skin of the hypothenar eminence and a motor
supply to muscles of the hypothenar eminence and other small muscles in the hand.
Median neuritis
This is a much less common syndrome and is usually due to entrapment of the nerve at
the elbow. Symptoms are similar to those of the carpal tunnel syndrome and may be
exacerbated by pronation of the forearm.
Radial neuritis
Again, this is relatively uncommon. Compression usually occurs at the elbow and causes
sensory symptoms in the forearm bone to the base of the thumb.

33. 24 §01 General Rheumatology and Soft Tissue Rheumatism
Meralgia paraesthetica
The lateral cutaneous nerve of the thigh passes through the femoral canal, where it is
sharply angulated and liable to compression. The syndrome leads to sensory symptoms
in the middle and lower part of the lateral aspect of the thigh. It is caused by obesity,
direct trauma or by repetitive flexion of the thigh.
Anterior compartment syndrome
This part of the lower leg contains the tibialis anterior and extensor digitorum muscles
and the deep peroneal nerve (supplies skin between the first and second toes). The nerve
may be injured by unaccustomed running, as a result of tibial or fibular fractures or
through direct trauma.
Medial compartment syndrome
This is the most common lower-leg nerve entrapment syndrome. The symptoms include
pain and tenderness on the medial aspect of the shin (‘shin splints’). It is often precipi-
tated by unaccustomed running on a hard surface.
Posterior compartment syndrome
This compartment contains the soleus and gastrocnemius muscles, which join together to
form the Achilles tendon and are responsible for plantar flexion. The syndrome is associated
with calf pain precipitated by exercise and with altered sensation on the sole of the foot.
The management of all of these nerve entrapment syndromes is somewhat similar: the
patient should rest wherever possible and avoid movements or actions that exacerbate
the symptoms; local injection with anaesthetic or steroid is indicated in some cases, and a
minority of patients require surgical decompression of the affected nerve.
Management of CTS1,2
b General measures include trying to relax the grip, using grip-adapted implements
such as large pens, taking frequent breaks, keeping the hands warm and considering
posture and position (e.g. if using a keyboard, this should be at elbow height).
Conservative management with ultrasound has been advocated but there are limited
trial data to support this therapy.
b Splinting the wrist in neutral position may alleviate symptoms related to soft tissue
swelling and is most effective when used soon after the onset of symptoms. Night-
time splinting is often sufficient.
b Non-steroidal anti-inflammatory drugs are effective in some cases, although
improvement may be short-lived. Oral corticosteroids are more effective (e.g.
prednisolone 20 mg/day for 2–3 weeks, followed by reducing doses). Diuretics are
widely used but are often disappointing in their effect.
b The use of local injection of anaesthetic and steroid into the proximal carpal tunnel
is supported by trial data. The outcome is probably comparable to that of systemic
steroids, but the patient is not exposed to the risk of side effects associated with high-
dose steroid therapy. The injection may be directly into the carpal tunnel or
proximal to the carpal tunnel. Benefit from local injection may last for up to three
months and is increased by concurrent splinting.
b For patients who have either severe symptoms or do not respond to conservative
measures, surgery is required. This has traditionally been carried out by an open

34. 05 Carpal tunnel syndrome and other entrapment neuropathies 25
Confirm symptoms are in median nerve distribution
History and examination to search for underlying causes
Enquire about occupation and repetitive strain
Mild symptoms Moderate symptoms with signs Severe symptoms
Rest
Remove precipitating cause NCS ± imaging
Trial of splinting
No further action Confirmed diagnosis
Conservative measures
Local injection
Systemic steroids
Repeat treatment Consider surgery
at 3 months • Open
• Endoscopic
Figure 5.2 Investigation and management of CTS. Imaging is with high-resolution ultrasound or with
MRI. NCS, nerve conduction studies.
procedure, which can be performed without admission to hospital. More recently,
endoscopic carpal tunnel release through two small incisions has been used by many
surgeons. This has the advantage of causing less scarring.
Recent Developments
1 Not all patients have ready access to nerve conduction studies. Several studies have
shown that high-resolution ultrasound and magnetic resonance imaging (MRI) may
be very accurate in diagnosing CTS.3,4 These methods can demonstrate altered

35. 26 §01 General Rheumatology and Soft Tissue Rheumatism
anatomy and decreased volume of the carpal tunnel, and in patients with CTS show
the median nerve is swollen distal to the compression.
2 Some familial cases of nerve entrapment are due to inherited anatomical
abnormalities. Recently, the condition of hereditary neuropathy with liability to the
pressure palsies (HNPP) has been described.5,6 This condition is inherited in an auto-
somal dominant manner and is due to a deletion at locus 17p11.2. HNPP is a slowly
progressive condition, punctuated by episodes of acute peripheral neuropathy at sites
that are liable to nerve entrapment.
3 Endoscopic surgery has revolutionized treatment of CTS. The two-portal endoscopic
approach to managing CTS has been adopted in many centres. Although this
approach is attractive, recent trials7,8 suggest that it has very little to offer over tradi-
tional open surgery. In general, surgical treatment is more successful than medical or
conservative treatment in patients with proven CTS.9
Conclusion
CTS is the most common form of entrapment neuropathy. Definitive diagnosis is by
nerve conduction studies, but ultrasound and MRI are increasingly being used to confirm
the diagnosis. It is worth routinely excluding hypothyroidism and diabetes as predispos-
ing causes but there is not usually a treatable or identifiable underlying cause. A limited
trial of conservative or medical measures is justified in mild cases but surgery is generally
required for severe, progressive or unresponsive cases.
Further Reading
1 Viera AJ. Management of carpal tunnel syndrome. Am Family Physician 2003; 68: 265–72.
2 Ashworth N. Carpal tunnel syndrome. Clin Evid 2006; 15: 1–18.
3 Wiesler ER, Chloros GD, Cartwright MS, Smith BP, Rushing J, Walker FO. Use of diagnostic
ultrasound in carpal tunnel syndrome. J Hand Surg 2006; 31: 726–32.
4 de Noordhout AM. Diagnosing entrapment neuropathies: probes and magnets instead of
electrodes and needles? Clin Neurophysiol 2006; 117: 484–5.
5 Sander MD, Abbasi D, Ferguson AL, Steyers CM, Wang K, Morcuende JA. The prevalence of
hereditary neuropathy with liability to pressure palsies in patients with multiple surgically
treated entrapment neuropathies. J Hand Surg 2005; 30: 1236–41.
6 Koc F, Guzel R, Benlidayi IC, Yerdelen D, Guzel I, Sarca Y. A rare genetic disorder in the
differential diagnosis of the entrapment neuropathies: hereditary neuropathy with liability to
pressure palsies. J Clin Rheumatol 2006; 12: 78–82.
7 Rab M, Grunbeck M, Beck H et al. Intra-individual comparison between open and 2-portal
endoscopic release in clinically matched bilateral carpal tunnel syndrome. J Plast Reconstr
Aesthet Surg 2006; 59: 730–6.
8 Atroshi I, Larsson G-U, Ornstein E, Hofer M, Johnsson R, Ranstam J. Outcomes of endoscopic
surgery compared with open surgery for carpal tunnel syndrome among employed patients:
randomised controlled trial. BMJ 2006; 332: 1473–6.
9 Hui ACF, Wong S, Leung CH et al. A randomized controlled trial of surgery vs steroid
injection for carpal tunnel syndrome. Neurology 2005; 64: 2074–8.

36. 06 Fibromyalgia syndrome 27
P R O B L E M
06 Fibromyalgia Syndrome
Case History
Sandra is in her early 40s and is seeing you because she hurts from her scalp to her toes.
This has been present for at least eight years and is ruining her life. She tires easily and
aches with any activity. Her sleeping is restless, she awakes tired and she has an irritable
bowel. There are no abnormalities on physical examination.
What is fibromyalgia and how would you support this diagnosis?
Are there any investigations that might help?
What treatment, if any, would you suggest to Sandra?
Background
Fibromyalgia syndrome (FMS) is a soft tissue musculoskeletal condition with many
features in common with chronic fatigue syndrome, the major difference being the pre-
dominance of musculoskeletal features in FMS. Diagnosis of FMS is based on the
American College of Rheumatology (ACR) criteria (1990):
b Pain on both sides of the body
b Pain above and below the waist
b Pain in an axial distribution
b Local tenderness in at least 11 out of 18 defined trigger points (Figure 6.1)
The pain is often defined as ‘aching’ or ‘burning’ and varies in intensity and location
from day to day. Other features of FMS are shown in Table 6.1.
Table 6.1 Frequency of FMS symptoms
Symptom % Symptom %
Muscular pain 100 Paraesthesiae 52
Fatigue 96 Memory impairment 46
Insomnia 86 Leg cramps 42
Joint pains 72 Poor concentration 41
Headaches 60 Anxiety 32
Restless legs 56 Major depression 20
© Atlas Medical Publishing Ltd

37. 28 §01 General Rheumatology and Soft Tissue Rheumatism
Figure 6.1 Trigger points for the diagnosis of FMS. There are 18 points in total (nine identical locations on
each side). Anterior: anterior aspects of C5, C6 and C7; second rib; lateral epicondyle; knee (medial fat pad).
Posterior: suboccipital muscle insertions; supraspinatus muscle origin; trapezius (midpoint upper border);
gluteal (upper outer quadrants); greater trochanter. Adapted with permission from Borg-Stein 2006.1
Musculoskeletal pain is the most consistent feature of FMS. Fatigue can be almost as
debilitating. Disordered sleep is also a very frequent feature and contributes to fatigue
and to the mood disturbances. Sleep abnormalities are strongly correlated with the
alpha-electroencephalogram (EEG) abnormality and movement disorders including the
periodic jerking of arms and legs, teeth grinding (bruxism) and restless legs. Gastro-
oesophageal reflux disease occurs with high frequency, as does irritable bowel syndrome.
Headaches may be of the migraine or tension type. Facial pain is also relatively common,
including discomfort related to temporomandibular joint dysfunction. Psychological
and psychiatric morbidity are increased. There is high prevalence of anxiety disorders
including obsessive-compulsive disorder and post-traumatic stress disorder.2

38. 06 Fibromyalgia syndrome 29
Epidemiology and aetiology
A number of recent studies2–4 have examined incidence and prevalence of FMS. The esti-
mated prevalence is between 1% and 4%. FMS is between two and six times more likely
to occur in women. Incidence in the female population has been estimated at 11.3 per
1000 person-years. It can occur at any age but becomes more common with advancing
years. FMS has been associated with other rheumatic disorders including rheumatoid
arthritis (RA) and systemic lupus erythematosus (SLE).
There is clearly strong interplay between physical and psychological factors in FMS.
The onset of illness may be triggered by physical illness (including viral diseases) or by
trauma (including surgery). There is some suggestion that heredity may play a part, with
components of the serotonergic and dopaminergic systems being potential candidates
for involvement. Some of the symptomatology around the trigger points may be due to
increased acetylcholine at the motor endplate causing contraction and shortening of the
sarcomere. This may lead to increased energy consumption and increased local blood
supply, with resulting local tenderness. A number of local and systemic mediators have
been implicated. These include bradykinin, calcitonin gene-related peptide, substance P,
tumour necrosis factor-a, interleukin-1, noradrenaline and serotonin.
Investigations
Routine investigations – including full blood count and biochemistry, plus erythrocyte
sedimentation rate (ESR), C-reactive protein (CRP) and other inflammatory markers –
are within the normal range. Because thyroid disease is common, it is useful to include
thyroid function tests. There are no specific endocrine abnormalities. X-ray, computed
tomography (CT) and magnetic resonance imaging (MRI) scans are generally normal.
There are no specific abnormalities on muscle biopsy, electromyography or nerve con-
duction studies. EEG or more formal sleep studies may be requested in patients who have
marked sleep disturbance. This may reveal abnormalities including periodic limb move-
ment disorder, rapid eye movement (REM) sleep disorder or sleep apnoea. The diagnosis
of FMS is one of exclusion and is made clinically.
Prognosis, differential diagnosis and treatment
The outlook for FMS is variable and the condition tends to become chronic. However,
more widespread understanding and clearer definition, along with a more highly devel-
oped treatment flow, are beginning to streamline management and improve the outlook.
There is a danger that over-enthusiastic investigation might contribute to making the
condition more chronic. However, this should not deter the clinician from making a full
investigation and the clinical picture warrants it. The major differential diagnosis is other
connective tissue disorders, including rheumatoid disease, SLE and scleroderma. Major
differential diagnoses of FMS and investigation of the condition are summarized in
Figure 6.2.
There is no specific treatment for FMS. Therapeutic measures include the following:
b General: investigation and clear diagnosis; educating the patient as to the nature of
the diagnosis and reassuring them; attention to psychological and social factors, and
encouraging the patient to have a normal sleep pattern as well as to engage in
physical activity consistent with their state of health and preferences.