Polyarthritis:

Differential diagnosis:
1) rheumatoid arthritis
2) SLE
3) seronegative spondyloarthropathies
4) Henoch-Schonlein purpura
5) sarcoidosis
6) tuberculosis
7) pseudogout
8) viral infection: EBV, HIV, hepatitis, mumps, rubella

Systemic lupus erythematosus

Epidemiology:
much more common in females (F:M = 9:1)
more common in Afro-Caribbeans* and Asian communities
onset is usually 20-40 years
incidence has risen substantially during the past 50 years (3 fold using American College
of Rheumatology criteria)
*It is said the incidence in black Africans is much lower than in black Americans - the reasons for
this are unclear

Pathophysiology:
autoimmune disease
associated with HLA B8, DR2, DR3
thought to be caused by immune system dysregulation leading to immune complex
formation
immune complex deposition can affect any organ including the skin, joints, kidneys and
brain

Features: Systemic lupus erythematosus (SLE) is a multisystem, autoimmune disorder.

General features:
fatigue
fever
mouth ulcers
lymphadenopathy
Skin:
malar (butterfly) rash: spares nasolabial folds
Discoid rash: scaly, erythematous, well demarcated rash in sun-exposed areas. Lesions
may progress to become pigmented and hyperkeratotic before becoming atrophic
photosensitivity
Raynaud's phenomenon
livedo reticularis
non-scarring alopecia

[1]
Musculoskeletal:
arthralgia
non-erosive arthritis
Cardiovascular:
myocarditis
Libmansack endocarditis.
Respiratory:
pleurisy
fibrosing alveolitis
Renal:
proteinuria
glomerulonephritis (diffuse proliferative glomerulonephritis is the most common type)
Neuropsychiatric:
anxiety and depression
psychosis ,seizures

SLE investigations:
Immunology:
1) 99% are ANA positive
2) 20% are rheumatoid factor positive
3) anti-dsDNA: highly specific (> 99%), but less sensitive (70%)
4) Anti-Smith: most specific (> 99%), sensitivity (30%)
5) also: anti-U1 RNP, SS-A (anti-Ro) and SS-B (anti-La)
Monitoring:
1) ESR: during active disease.
The CRP is characteristically normal - a raised CRP may indicate underlying infection
2) complement levels (C3, C4) are low during active disease (formation of complexes leads
to consumption of complement)
3) anti-dsDNA titers can be used for disease monitoring (but not present in all patients)

Discoid lupus erythematosus

Benign disorder generally seen in younger females.
It very rarely progresses to systemic lupus erythematosus (in less than 5% of cases).
characterised by follicular keratin plugs and is thought to be autoimmune in aetiology
Features:
1) erythematous, raised rash, sometimes scaly
2) may be photosensitive
3) more common on face, neck, ears and scalp
4) lesions heal with atrophy, scarring (may cause scarring alopecia),pigmentation
Management:
1) topical steroid cream
2) oral antimalarials may be used second-line e.g. hydroxychloroquine
3) avoid sun exposure

[2]
Drug-induced lupus
In drug-induced lupus not all the typical features of systemic lupus erythematosus are seen,
with renal and nervous system involvement being unusual.
It usually resolves on stopping the drug.

Features:
1) arthralgia
2) myalgia
3) skin (e.g. malar rash) and pulmonary involvement (e.g. pleurisy) are common
4) ANA positive in 100%, dsDNA negative
5) anti-histone antibodies are found in 80-90%
6) anti-Ro, anti-Smith positive in around 5%

A woman with drug-induced lupus

Most common causes
1) procainamide
2) hydralazine
Less common causes
1) isoniazid
2) minocycline
3) phenytoin

SLE in pregnancy:
risk of maternal autoantibodies crossing placenta leads to condition termed neonatal lupus
erythematous
neonatal complications include congenital heart block
strongly associated with anti-Ro (SSA) antibodies

Mixed connective tissue disease:

Features of SLE, systemic sclerosis and polymyositis
Anti-RNP positive

[3]
Antiphospholipid syndrome
Acquired disorder characterised by:
1) a predisposition to both venous and arterial thromboses,
2) recurrent fetal loss and
3) thrombocytopenia
It may occur as a primary disorder or secondary to other conditions, most commonly SLE
A key point for the exam is to appreciate that antiphospholipid syndrome causes a
paradoxical rise in the APTT.
This is due to an ex-vivo reaction of the lupus anticoagulant autoantibodies with
phospholipids involved in the coagulation cascade
Features:
1) venous/arterial thrombosis
2) recurrent fetal loss
3) livedo reticularis
4) thrombocytopenia
5) prolonged APTT
6) other features: pre-eclampsia, pulmonary hypertension

Associations other than SLE

1) other autoimmune disorders
2) lymphoproliferative disorders
3) phenothiazines (rare)

Management - based on BCSH guidelines

1) initial venous thromboembolic events: evidence currently supports use of warfarin with a
target INR of 2-3 for 6 months
2) recurrent venous thromboembolic events: lifelong warfarin; if occurred whilst taking
warfarin then increase target INR to 3-4
3) arterial thrombosis should be treated with lifelong warfarin with target INR 2-3

Extractable nuclear antigens:

Overview:
specific nuclear antigens
usually associated with being ANA positive

Examples:
anti-Ro: Sjogren's syndrome, SLE, congenital heart block
anti-La: Sjogren's syndrome
anti-Jo 1: polymyositis
anti-scl-70: diffuse cutaneous systemic sclerosis
anti-centromere: limited cutaneous systemic sclerosis

[4]
Rheumatoid arthritis
peak onset = 30-50 years, although occurs in all age groups
F:M ratio = 3:1
prevalence = 1%
some ethnic differences e.g. high in Native Americans
associated with HLA-DR4 (especially Felty's syndrome)
Rheumatoid arthritis diagnosis:
NICE have stated that clinical diagnosis is more important than criteria such as those defined by
the American College of Rheumatology.
2010 American College of Rheumatology criteria:
Target population; Patients who
1) Have at least 1 joint with definite clinical synovitis
2) With the synovitis not better explained by another disease

Classification criteria for rheumatoid arthritis (add score of categories A-D; a score of 6/10 is
needed definite rheumatoid arthritis)
RF = rheumatoid factor ACPA = anti-cyclic citrullinated peptide antibody
Factor Scoring

A. Joint involvement 1 large joint 0

2 - 10 large joints 1

1 - 3 small joints (with or without involvement of large 2

joints)

4 - 10 small joints (with or without involvement of large 3

joints)

10 joints (at least 1 small joint) 5

Negative RF and negative ACPA 0

B. Serology (at least 1
test result is needed Low-positive RF or low-positive ACPA 2
for classification)
High-positive RF or high-positive ACPA 3

C. Acute-phase Normal CRP and normal ESR 0

reactants (at least 1
test result is needed Abnormal CRP or abnormal ESR 1
for classification)

D. Duration of < 6 weeks 0

symptoms
> 6 weeks 1

[5]
Rheumatoid arthritis: x-ray changes:
Early x-ray findings
loss of joint space
juxta-articular osteoporosis
soft-tissue swelling
Late x-ray findings:
periarticular erosions
subluxation

Rheumatoid factor
Rheumatoid factor (RF) is a circulating antibody (usually IgM) which reacts with the Fc
portion of the patients own IgG
RF can be detected by either:
1) Rose-Waaler test: sheep red cell agglutination
2) Latex agglutination test (less specific)
RF is positive in 70-80% of patients with rheumatoid arthritis,
high titre levels are associated with severe progressive disease (but NOT a marker of
disease activity)

Other conditions associated with a positive RF include:

1) Sjogren's syndrome (around 100%)
2) Felty's syndrome (around 100%)
3) Infective endocarditis (= 50%)
4) SLE (= 20-30%)
5) Systemic sclerosis (= 30%)
6) General population (= 5%)
7) rarely: TB, HBV, EBV, leprosy

Rheumatoid arthritis prognostic features:

A number of features have been shown to predict a poor prognosis in patients with
rheumatoid arthritis, as listed below
Poor prognostic features:
1) rheumatoid factor positive
2) poor functional status at presentation
3) HLA DR4
4) X-ray: early erosions (e.g. after < 2 years)
5) extra articular features e.g. nodules
6) insidious onset
7) anti-CCP antibodies

In terms of gender there seems to be a split in what the established sources state is
associated with a poor prognosis. However both the American College of Rheumatology and
the recent NICE guidelines (which looked at a huge number of prognosis studies) seem to
conclude that female gender is associated with a poor prognosis.
[6]
Rheumatoid arthritis complications:
A wide variety of extra-articular complications occur in patients with rheumatoid arthritis (RA):
A) respiratory:
1) pulmonary fibrosis,
2) pleurisy
3) pleural effusion,
4) pulmonary nodules,
5) bronchiolitis obliterans,
6) methotrexate pneumonitis,
B) ocular:
1) keratoconjunctivitis sicca (most common)
2) episcleritis (erythema)
3) scleritis (erythema and pain)
4) corneal ulceration,
5) keratitis,
6) steroid-induced cataracts,
7) chloroquine retinopathy
C) osteoporosis
D) ischaemic heart disease: RA carries a similar risk to type 2 diabetes mellitus
E) increased risk of infections
F) depression

Less common complications:

Felty's syndrome (RA + splenomegaly + low white cell count)
amyloidosis

[7]
Rheumatoid arthritis: management
The management of rheumatoid arthritis (RA) has been revolutionized by the introduction of
disease-modifying therapies in the past decade.
NICE has issued and released general guidelines in 2009.
Pts with joint inflammation should start a combination of DMARD as soon as possible.
Other important treatment options include analgesia, physiotherapy and surgery.
Initial therapy:
In the 2009 NICE guidelines it is recommend that patients with newly diagnosed active RA start
a combination of DMARDs (including methotrexate and at least one other DMARD, plus
short-term glucocorticoids)
1) DMARDs:
Methotrexate is the most widely used DMARD.
Monitoring of FBC & LFTs is essential due to the risk of myelosuppression and liver
cirrhosis. Other important side-effects include pneumonitis
sulfasalazine
leflunomide
hydroxychloroquine
2) TNF-inhibitors:
the current indication for a TNF-inhibitor is an inadequate response to at least two
DMARDs including methotrexate
A) Etanercept:
recombinant human protein,
acts as a decoy receptor for TNF-,
subcutaneous administration,
can cause demyelination,
risks include reactivation of tuberculosis
B) Infliximab:
monoclonal antibody,
binds to TNF- and prevents it from binding with TNF receptors,
intravenous administration,
risks include reactivation of tuberculosis
C) Adalimumab:
monoclonal antibody,
subcutaneous administration
3) Rituximab:
anti-CD20 monoclonal antibody,
results in B-cell depletion
two 1g intravenous infusions are given two weeks apart
infusion reactions are common
4) Abatacept:
fusion protein that modulates a key signal required for activation of T lymphocytes
leads to decreased T-cell proliferation and cytokine production
given as an infusion
not currently recommend by NICE

[8]
Methotrexate:
Methotrexate is an antimetabolite which inhibits dihydrofolate reductase, an enzyme essential
for the synthesis of purines and pyrimidines
Indications:
1) rheumatoid arthritis
2) psoriasis
3) acute lymphoblastic leukaemia
Adverse effects:
1) mucositis
2) myelosuppression
3) pneumonitis
4) pulmonary fibrosis
5) liver cirrhosis
Pregnancy:
women should avoid pregnancy for at least 3 months after treatment has stopped
the BNF also advises that men using methotrexate need to use effective contraception for
at least 3 months after treatment
Prescribing methotrexate:
Methotrexate is a drug with a high potential for patient harm. It is therefore important that you
are familiar with guidelines relating to its use
methotrexate is taken weekly, rather than daily
FBC, U&E and LFTs need to be regularly monitored. The Committee on Safety of Medicines
recommend 'FBC and renal and LFTs before starting treatment and repeated weekly until
therapy stabilised, thereafter patients should be monitored every 2-3 months'
folic acid 5mg once weekly should be co-prescribed, taken more than 24 hours after
methotrexate dose
the starting dose of methotrexate is 7.5 mg weekly (source: BNF)
only one strength of methotrexate tablet should be prescribed (usually 2.5 mg)
avoid prescribing trimethoprim or cotrimoxazole concurrently - increases risk of marrow
aplasia

Azathioprine:
Azathioprine is metabolised to the active compound mercaptopurine, a purine analogue that
inhibits purine synthesis.
A thiopurine methyltransferase (TPMT) test may be needed to look for individuals prone to
azathioprine toxicity.

Adverse effects:
1) bone marrow depression
2) nausea/vomiting
3) pancreatitis
4) A significant interaction may occur with allopurinol and hence lower doses of azathioprine
should be used.

[9]
Rheumatoid arthritis in pregnancy:
Rheumatoid arthritis (RA) typically develops in women of a reproductive age.
Issues surrounding conception are therefore commonly encountered.
There are no current published guidelines regarding how patients considering conception
should be managed although expert reviews are largely in agreement.

Key points:
1) patients with early or poorly controlled RA should be advised to defer conception until their
disease is more stable
2) RA symptoms tend to improve in pregnancy but only resolve in a small minority.
3) Patients tend to have a flare following delivery
4) methotrexate is not safe in pregnancy and needs to be stopped at least 3 months before
conception
5) leflunomide is not safe in pregnancy
6) sulfasalazine and hydroxychloroquine are considered safe in pregnancy
7) interestingly studies looking at pregnancy outcomes in patients treated with TNF-
blockers do not show any significant increase in adverse outcomes. It should be noted
however that many of the patients included in the study stopped taking TNF- blockers
when they found out they were pregnant
8) low-dose corticosteroids may be used in pregnancy to control symptoms
9) NSAIDs may be used until 32 weeks but after this time should be withdrawn due to the
risk of early close of the ductus arteriosus
10) patients should be referred to an obstetric anaesthetist due to the risk of atlanto-axial
subluxation

Still's disease in adults:

typically affects 16-35 year old
typically rheumatoid factor negative

Features:
1) arthralgia
2) elevated serum ferritin
3) rash: salmon-pink, maculopapular
4) pyrexia
5) lymphadenopathy
6) rheumatoid factor (RF) and anti-nuclear antibody (ANA) negative

Felty's syndrome (RA + splenomegaly + low white cell count) RF +ve 100%

[10]
Raynaud's:
Raynaud's phenomena may be primary (Raynaud's disease) or secondary (Raynaud's
phenomenon)
Raynaud's disease typically presents in young women (e.g. 30 years old) with symmetrical
attacks

Factors suggesting underlying connective tissue disease:

1) onset after 40 years
2) unilateral symptoms
3) rashes
4) presence of autoantibodies
5) features which may suggest rheumatoid arthritis or SLE, for example arthritis or recurrent
miscarriages
6) digital ulcers, calcinosis
7) very rarely: chilblains

Secondary causes:
1) connective tissue disorders: scleroderma (most common), rheumatoid arthritis, SLE
2) leukaemia
3) type I cryoglobulinaemia, cold agglutinins
4) use of vibrating tools
5) drugs: oral contraceptive pill, ergot
6) cervical rib

Management:
1) first-line: calcium channel blockers e.g. nifedipine
2) IV prostacyclin infusions: effects may last several weeks/months

[11]
Sjogren's syndrome:
Autoimmune disorder affecting exocrine glands resulting in dry mucosal surfaces.
It may be primary (PSS) or secondary to rheumatoid arthritis or other connective tissue
disorders, where it usually develops around 10 years after the initial onset.
Sjogren's syndrome is much more common in females (ratio 9:1).
There is a marked increased risk of lymphoid malignancy (40-60 fold)

Features:
1) dry eyes: keratoconjunctivitis sicca
2) dry mouth
3) vaginal dryness
4) arthralgia
5) Raynaud's, myalgia
6) sensory polyneuropathy
7) renal tubular acidosis (usually subclinical)

Investigation:
1) rheumatoid factor (RF) positive in nearly 100% of patients
2) ANA positive in 70%
3) anti-Ro (SSA) antibodies in 70% of patients with PSS
4) anti-La (SSB) antibodies in 30% of patients with PSS
5) Schirmer's test: filter paper near conjunctival sac to measure tear formation
6) histology: focal lymphocytic infiltration
7) also: hypergammaglobulinaemia, low C4

Management:
1) artificial saliva and tears
2) pilocarpine may stimulate saliva production

[12]
Seronegative spondyloarthropathies
Common features:
1) associated with HLA-B27
2) rheumatoid factor negative - hence 'seronegative'
3) peripheral arthritis, usually asymmetrical
4) sacroiliitis
5) enthesopathy: e.g. Achilles tendonitis, plantar fasciitis
6) extra-articular manifestations: uveitis, pulmonary fibrosis (upper zone), amyloidosis, aortic
regurgitation

Spondyloarthropathies:
1) ankylosing spondylitis
2) psoriatic arthritis
3) Reiter's syndrome (including reactive arthritis)
4) enteropathic arthritis (associated with IBD)

Ankylosing spondylitis:
Features:
1) Ankylosing spondylitis is a HLA-B27 associated spondyloarthropathy.
2) It typically presents in males (sex ratio 5:1) aged 20-30 years old.
3) typically a young man who presents with lower back pain and stiffness of insidious onset
4) stiffness is usually worse in the morning and improves with exercise
5) the patient may experience pain at night which improves on getting up

Clinical examination:
1) reduced lateral flexion
2) Reduced forward flexion - Schober's test - a line is drawn 10 cm above and 5 cm below
the back dimples (dimples of Venus). The distance between the two lines should increase
by more than 5 cm when the patient bends as far forward as possible
3) reduced chest expansion

Other features - the 'A's:

1) Apical fibrosis
2) Anterior uveitis
3) Aortic regurgitation
4) Achilles tendonitis
5) AV node block
6) Amyloidosis
7) and cauda equina syndrome
8) peripheral arthritis (25%, more common if female)

[13]
Ankylosing spondylitis investigation:
1) Inflammatory markers (ESR, CRP) are typically raised although normal levels do not exclude
ankylosing spondylitis.
2) HLA-B27 is of little use in making the diagnosis as it is positive in:
90% of patients with ankylosing spondylitis
10% of normal patients
3) Spirometry may show a restrictive defect due to a combination of pulmonary fibrosis,
kyphosis and ankylosis of the costovertebral joints.
4) Plain x-ray of the sacroiliac joints is the most useful investigation in establishing the
diagnosis. Radiographs may be normal early in disease, later changes include:

1. sacroilitis: subchondral erosions, sclerosis

2. squaring of lumbar vertebrae
3. bamboo spine (late & uncommon)
4. syndesmophytes: due to ossification of outer fibers of annulus fibrosus
5. chest x-ray: apical fibrosis

40-year-old male. Ankylosing Lateral cervical Fusion of Syndesmophytes

There is typical spondylitis with spine. Complete bilateral and squaring of
appearance of well formed fusion of anterior sacroiliac vertebral bodies.
bamboo spine syndesmophytes and posterior joints. Squaring of
with a single elements in Sacroiliitis may anterior vertebral
central radiodense ankylosing present as margins is due to
line related to spondylitis, so sclerosis of osteitis of
ossification of called bamboo joint margins anterior corners.
supraspinous and spine which can be Syndesmophytes
interspinous asymmetrical are due to
ligaments which is at early stage ossification of
called dagger of disease, but outer fibers of
sign. Ankylosing is is bilateral and annulus fibrosus
detectable in both symmetrical in
sacroiliac joints late disease

[14]
Management:
The following is partly based on the 2010 EULAR guidelines (please see the link for more
details):
1) encourage regular exercise such as swimming
2) physiotherapy
3) NSAIDs are the first-line treatment
4) the disease-modifying drugs which are used to treat rheumatoid arthritis (such as
sulphasalazine) are only really useful if there is peripheral joint involvement
5) the 2010 EULAR guidelines suggest: 'Anti-TNF therapy should be given to patients with
persistently high disease activity despite conventional treatments'
6) research is ongoing to see whether anti-TNF therapies such as etanercept and adalimumab
should be used earlier in the course of the disease

[15]
Reactive arthritis:
Reactive arthritis is one of the HLA-B27 associated seronegative spondyloarthropathies.
It encompasses Reiter's syndrome, a term which described a classic triad of urethritis,
conjunctivitis and arthritis following a dysenteric illness during the Second World War.
Later studies identified patients who developed symptoms following a sexually transmitted
infection (post-STI, now sometimes referred to as sexually acquired reactive arthritis, SARA).
Reactive arthritis is defined as an arthritis that develops following an infection where the
organism cannot be recovered from the joint.
Features:
1) typically develops within 4 weeks of initial infection
2) symptoms generally last around 4-6 months
3) arthritis is typically an asymmetrical oligoarthritis of lower limbs
4) Around 25% of patients have recurrent episodes
5) 10% of patients develop chronic disease
6) dactylitis
7) symptoms of urethritis
8) eye:
Conjunctivitis (seen in 50%),
anterior uveitis
9) skin:
circinate balanitis (painless vesicles on the coronal margin of the prepuce),
keratoderma blenorrhagica (waxy yellow/brown papules on palms and soles)

Keratoderma blenorrhagica
Epidemiology:
post-STI form much more common in men (e.g. 10:1)
post-dysenteric form equal sex incidence
The table below shows the organisms that are most commonly associated with reactive arthritis:

Post-dysenteric form Post-STI form

Shigella flexneri Chlamydia trachomatis

Salmonella typhimurium,
Salmonella enteritidis
Yersinia enterocolitica
Campylobacter

Management:
1) symptomatic: analgesia, NSAIDS, intra-articular steroids
2) sulfasalazine and methotrexate are sometimes used for persistent disease
3) symptoms rarely last more than 12 months
[16]
Psoriatic Arthropathy:
Psoriatic arthropathy correlates poorly with cutaneous psoriasis
often precedes the development of skin lesions
Around 10% percent of patients with skin lesions develop an arthropathy
males and females being equally affected

Types*:
1) rheumatoid-like polyarthritis: (30-40%, most common type)
2) Asymmetrical oligoarthritis: typically affects hands and feet (20-30%)
3) sacroilitis
4) DIP joint disease (10%)
5) arthritis mutilans (severe deformity fingers/hand, 'telescoping fingers')

Management:
treat as rheumatoid arthritis
but better prognosis

Notice the nail changes on this image as

well

X-ray showing some of changes in seen in psoriatic

arthropathy. Note that the DIPs are predominately
affected, rather than the MCPs and PIPs as would be
seen with rheumatoid. Extensive juxta-articular
periostitis is seen in the DIPs but the changes have
not yet progressed to the classic 'pencil-in-cup'
changes that are often seen.

[17]
This x-ray shows changes
affecting both the PIPs and
DIPs. The close-up images
show extensive changes
including large eccentric
erosions, tuft resorption and
progresion towards a 'pencil-in-
cup' changes.

*Until recently it was thought asymmetrical oligoarthritis was the most common type, based on
data from the original 1973 Moll and Wright paper. Please see the link for a comparison of more
recent studies

[18]
Osteoarthritis:
X-ray changes:
1) decrease of joint space
2) subchondral sclerosis
3) subchondral cysts
4) osteophytes forming at joint margins

Management:
NICE published guidelines on the management of osteoarthritis (OA) in 2014

1) all patients should be offered help with weight loss, given advice about local muscle
strengthening exercises and general aerobic fitness
2) Paracetamol and topical NSAIDs are first-line analgesics.
3) Topical NSAIDs are indicated only for OA of the knee or hand
4) Second-line treatment is:
oral NSAIDs/COX-2 inhibitors,
opioids,
capsaicin cream and
intra-articular corticosteroids
A proton pump inhibitor should be co-prescribed with NSAIDs and COX-2 inhibitors.
These drugs should be avoided if the patient takes aspirin
5) non-pharmacological treatment options include supports and braces, TENS and shock
absorbing insoles or shoes
6) if conservative methods fail then refer for consideration of joint replacement

What is the role of glucosamine?

1) normal constituent of glycosaminoglycans in cartilage and synovial fluid

2) a systematic review of several double blind RCTs of glucosamine in knee osteoarthritis
reported significant short-term symptomatic benefits including significantly reduced joint
space narrowing and improved pain scores
3) more recent studies have however been mixed
4) the 2008 NICE guidelines suggest it is not recommended
5) a 2008 Drug and Therapeutics Bulletin review advised that whilst glucosamine provides
modest pain relief in knee osteoarthritis it should not be prescribed on the NHS due to limited
evidence of cost-effectiveness

[19]
Systemic sclerosis
Systemic sclerosis is a condition of unknown aetiology characterised by hardened, sclerotic
skin and other connective tissues.
It is four times more common in females
There are three patterns of disease:

A) Limited cutaneous systemic sclerosis:

Raynaud's may be first sign
scleroderma affects face and distal limbs predominately
associated with anti-centromere antibodies (are the most specific test for limited
cutaneous systemic sclerosis)
a subtype of limited systemic sclerosis is CREST syndrome
CREST syndrome: Calcinosis, Raynaud's phenomenon, oEsophageal dysmotility,
Sclerodactyly, Telangiectasia

B) Diffuse cutaneous systemic sclerosis:

scleroderma affects trunk and proximal limbs predominately
associated with scl-70 antibodies
hypertension, lung fibrosis and renal involvement seen
poor prognosis

C) Scleroderma (without internal organ involvement):

tightening and fibrosis of skin
may be manifest as plaques (morphoea) or linear

Antibodies:
ANA positive in 90%
RF positive in 30%
anti-scl-70 antibodies associated with diffuse cutaneous systemic sclerosis
anti-centromere antibodies associated with limited cutaneous systemic sclerosis

[20]
Dermatomyositis
Overview
inflammatory disorder causing:
1) symmetrical, proximal muscle weakness and
2) characteristic skin lesions
may be idiopathic or associated with connective tissue disorders or underlying malignancy
(typically lung cancer, found in 20-25% - more if patient older)
polymyositis is a variant of the disease where skin manifestations are not prominent

Skin features:
1) photosensitive
2) macular rash over back and shoulder
3) heliotrope rash in the periorbital region
4) Gottron's papules - roughened red papules over extensor surfaces of fingers
5) nail fold capillary dilatation

Other features:
1) proximal muscle weakness +/- tenderness
2) Raynaud's
3) respiratory muscle weakness
4) interstitial lung disease: e.g. Fibrosing alveolitis or organising pneumonia
5) dysphagia, dysphonia

Investigations:
1) elevated creatine kinase
2) EMG
3) muscle biopsy
4) ANA positive in 60%
5) anti-Mi-2 antibodies are highly specific for dermatomyositis, but are only seen in around
25% of patients
6) anti-Jo-1 antibodies are not commonly seen in dermatomyositis - they are more common in
polymyositis where they are seen in a pattern of disease associated with lung involvement,
Raynaud's and fever

Management:
prednisolone

[21]
Behcet's syndrome
A complex multisystem disorder associated with presumed autoimmune mediated
inflammation of the arteries and veins.
The precise aetiology has yet to be elucidated however.
The classic triad of symptoms are:
oral ulcers,
genital ulcers and
anterior uveitis

Epidemiology:
more common in the eastern Mediterranean (e.g. Turkey)
More common in men (complicated gender distribution which varies according to country.
Overall, Behcet's is considered to be more common and more severe in men)
tends to affect young adults (e.g. 20 - 40 years old)
associated with HLA B5* and MICA6 allele
around 30% of patients have a positive family history
*more specifically HLA B51, a split antigen of HLA B5

Features:
1) classically: 1) oral ulcers 2) genital ulcers 3) anterior uveitis
2) thrombophlebitis
3) arthritis
4) neurological involvement (e.g. aseptic meningitis)
5) GI: abdo pain, diarrhoea, colitis
6) erythema nodosum, DVT

Diagnosis:
1) no definitive test
2) diagnosis based on clinical findings
3) positive pathergy test is suggestive (puncture site following needle prick becomes inflamed
with small pustule forming)

[22]
Chronic fatigue syndrome
Diagnosed after at least 4 months of disabling fatigue affecting mental and physical
function more than 50% of the time in the absence of other disease which may explain
symptoms

Epidemiology:
more common in females
past psychiatric history has not been shown to be a risk factor
Fatigue is the central feature, other recognised features include
1) sleep problems, such as insomnia, hypersomnia, unrefreshing sleep, a disturbed
sleep-wake cycle
2) muscle and/or joint pains
3) headaches
4) painful lymph nodes without enlargement
5) sore throat
6) cognitive dysfunction, such as difficulty thinking, inability to concentrate, impairment of
short-term memory, and difficulties with word-finding
7) physical or mental exertion makes symptoms worse
8) general malaise or 'flu-like' symptoms
9) dizziness
10) nausea
11) palpitations

Investigation:
NICE guidelines suggest carrying out a large number of screening blood tests to exclude
other pathology e.g. FBC, U&E, LFT, glucose, TFT, ESR, CRP, calcium, CK, ferritin*,
coeliac screening and also urinalysis

*children and young people only

Management:
1) cognitive behaviour therapy - very effective, number needed to treat = 2
2) graded exercise therapy - a formal supervised program, not advice to go to the gym
3) 'pacing' - organising activities to avoid tiring
4) low-dose amitriptyline may be useful for poor sleep
5) referral to a pain management clinic if pain is a predominant feature
6) Better prognosis in children

[23]
Fibromyalgia
Fibromyalgia is a syndrome characterised by widespread pain throughout the body with
tender points at specific anatomical sites. The cause of fibromyalgia is unknown.
Epidemiology:
women are 10 times more likely to be affected
typically presents between 30-50 years old
Features:
1) chronic pain: at multiple site, sometimes 'pain all over'
2) lethargy
3) sleep disturbance, headaches, dizziness are common
Diagnosis:
1) Diagnosis is clinical
2) Sometimes refers to the American College of Rheumatology classification criteria which
lists 9 pairs of tender points on the body.
3) If a patient is tender in at least 11 of these 18 points it makes the diagnosis more likely
Manaegement:
1) The management is often difficult and needs to be tailored to the individual patient.
2) A psychosocial and multidisciplinary approach is helpful.
3) Unfortunately there is currently a paucity of evidence and guidelines to guide practice.
4) The following is partly based on consensus guidelines from the European League against
Rheumatism (EULAR) published in 2007 and also a BMJ review in 2014.
1) explanation
2) aerobic exercise: has the strongest evidence base
3) cognitive behavioural therapy
4) medication: pregabalin, duloxetine, amitriptyline

Polymyalgia rheumatic (PMR)

Pathophysiology:
overlaps with temporal arteritis
histology shows vasculitis with giant cells, characteristically 'skips' certain sections of affected
artery whilst damaging others
muscle bed arteries affected most in polymyalgia rheumatica
Features:
1) typically patient > 60 years old
2) usually rapid onset (e.g. < 1 month)
3) aching, morning stiffness in proximal limb muscles (not weakness)
4) also mild polyarthralgia, lethargy, depression, low-grade fever, anorexia, night sweats
Investigations:
ESR > 40 mm/hr
note CK and EMG normal
reduced CD8+ T cells
Treatment:
prednisolone e.g. 15mg/od - dramatic response

[24]
Vasculitides
Large vessel:
Temporal arteritis
Takayasu's arteritis

Medium vessel:
polyarteritis nodosa
Kawasaki disease

Small vessel:
1) ANCA-associated vasculitides (Wegener's*, Churg-Strauss*, microscopic polyangiitis)
2) Henoch-Schonlein purpura
3) cryoglobulinaemic vasculitis
*may also affect medium-sized vessels

Large Vessel Vasculitides

Temporal arteritis
Temporal arteritis is large vessel vasculitis which overlaps with polymyalgia rheumatica.
Histology shows changes which characteristically 'skips' certain sections of affected artery
whilst damaging others.

Features:
1) typically patient > 60 years old
2) usually rapid onset (e.g. < 1 month)
3) headache (found in 85%)
4) jaw claudication (65%)
5) visual disturbances secondary to anterior ischemic optic neuropathy
6) tender, palpable temporal artery
7) features of PMR: aching, morning stiffness in proximal limb muscles (not weakness)
8) also lethargy, depression, low-grade fever, anorexia, night sweats

Investigations:
1) raised inflammatory markers:
ESR > 50 mm/hr (note ESR < 30 in 10% of patients).
CRP may also be elevated
2) temporal artery biopsy: skip lesions may be present
3) note creatine kinase and EMG normal

Treatment:
1) high-dose prednisolone - there should be a dramatic response, if not the diagnosis should
be reconsidered
2) Urgent ophthalmology review. Patients with visual symptoms should be seen the same-day
by an ophthalmologist.
3) Visual damage is often irreversible
[25]
Takayasu's arteritis
Takayasu's arteritis is a large vessel vasculitis.
It typically causes occlusion of the aorta and questions commonly refer to an absent limb
pulse.
It is more common in females and Asian people

Features:
1) systemic features of a vasculitis e.g. malaise, headache
2) unequal blood pressure in the upper limbs
3) carotid bruit
4) intermittent claudication
5) Aortic regurgitation (around 20%)

Angiography showing multiple stenoses in the branches of the aorta secondary to Takayasu's
arteritis

Associations
renal artery stenosis

Management:
steroids

[26]
Medium Vessel Vasculitides:
polyarteritis nodosa
Kawasaki disease

Polyarteritis nodosa: (PAN)

A vasculitis affecting medium-sized arteries with necrotizing inflammation leading to
aneurysm formation.
PAN is more common in middle-aged men and is associated with hepatitis B infection

Features:
1) fever, malaise, arthralgia
2) weight loss
3) hypertension
4) mononeuritis multiplex, sensorimotor polyneuropathy
5) testicular pain
6) livedo reticularis
7) haematuria, renal failure
8) perinuclear-antineutrophil cytoplasmic antibodies (ANCA) are found in around 20% of
patients with 'classic' PAN
9) hepatitis B serology positive in 30% of patients

Livedo reticularis

[27]
Small vessel
1) ANCA-associated vasculitides (Wegener's*, Churg-Strauss*, microscopic polyangiitis)
2) Henoch-Schonlein purpura
3) cryoglobulinaemic vasculitis

ANCA
There are two main types of anti-neutrophil cytoplasmic antibodies (ANCA) - cytoplasmic
(cANCA) and perinuclear (pANCA)

For the exam, remember:

cANCA - Wegener's granulomatosis
pANCA - Churg-Strauss syndrome + others (see below)

cANCA:
most common target serine proteinase 3 (PR3)
some correlation between cANCA levels and disease activity
Wegener's granulomatosis, positive in > 90%
microscopic polyangiitis, positive in 40%

pANCA:
most common target is myeloperoxidase (MPO)
cannot use level of pANCA to monitor disease activity
associated with immune crescentic glomerulonephritis (positive in c. 80% of patients)
microscopic polyangiitis, positive in 50-75%
Churg-Strauss syndrome, positive in 60%
primary sclerosing cholangitis, positive in 60-80%
Wegener's granulomatosis, positive in 25%

Other causes of positive ANCA (usually pANCA)

inflammatory bowel disease (UC > Crohn's)

connective tissue disorders: RA, SLE, Sjogren's
autoimmune hepatitis

[28]
Granulomatosis with polyangiitis (Wegener's granulomatosis)
Granulomatosis with polyangiitis is now the preferred term for Wegener's granulomatosis.
It is an autoimmune condition associated with a necrotizing granulomatous vasculitis,
affecting both the upper and lower respiratory tract as well as the kidneys.

Features:
1) upper respiratory tract: epistaxis, sinusitis, nasal crusting
2) lower respiratory tract: dyspnoea, haemoptysis, cavitating lesions
3) rapidly progressive glomerulonephritis ('pauci-immune', 80% of patients)
4) saddle-shape nose deformity
5) also: vasculitic rash, eye involvement (e.g. proptosis), cranial nerve lesions

Investigations:
1) cANCA positive in > 90%, pANCA positive in 25%
2) chest x-ray: wide variety of presentations, including cavitating lesions
3) renal biopsy: epithelial crescents in Bowman's capsule

Management:
1) steroids
2) cyclophosphamide (90% response)
3) plasma exchange
4) median survival = 8-9 years

Chest x-ray from a young male patient

with granulomatosis with polyangiitis.
Whilst the changes are subtle it
demonstrates a number of ill-defined
nodules the largest of which projects over
the dome of the right hemidiaphragm.
This nodule appears to have a central
lucency suggesting cavitation

CT of the same patient showing the

changes in a much more obvious way,
confirming the presence of at least 2
nodules, the larger of the two having a
large central cavity and and air-fluid level

[29]
Churg-Strauss syndrome
Churg-Strauss syndrome is an ANCA associated small-medium vessel vasculitis.

Features:
1) asthma
2) blood eosinophilia (e.g. > 10%)
3) paranasal sinusitis
4) mononeuritis multiplex
5) pANCA positive in 60%
6) Leukotriene receptor antagonists may precipitate the disease

Cryoglobulinaemia
Immunoglobulins which undergo reversible precipitation at 4 deg C, dissolve when warmed to
37 deg C.
One third of cases are idiopathic
Three types
type I (25%): monoclonal
type II (25%): mixed monoclonal and polyclonal: usually with RF
type III (50%): polyclonal: usually with RF

Type I
monoclonal - IgG or IgM
associations: multiple myeloma, Waldenstrm macroglobulinaemia
Type II
mixed monoclonal and polyclonal: usually with RF
associations: hepatitis C, RA, Sjogren's, lymphoma
Type III
polyclonal: usually with RF
associations: RA, Sjogren's

Symptoms (if present in high concentrations)

1) Raynaud's only seen in type I
2) cutaneous: vascular purpura, distal ulceration, ulceration
3) arthralgia
4) renal involvement (diffuse glomerulonephritis)
Tests:
low complement (esp. C4)
high ESR

Treatment:
1) immunosuppression
2) plasmapheresis

[30]
Gout
Predisposing factors:
Gout is a form of microcrystal synovitis caused by the deposition of monosodium urate
monohydrate in the synovium.
It is caused by chronic hyperuricaemia (uric acid > 0.45 mmol/l)

A) Decreased excretion of uric acid:

1) drugs*: diuretics
2) chronic kidney disease
3) lead toxicity

*aspirin in a dose of 75-150mg is not thought to have a significant effect on plasma urate
levels - the British Society for Rheumatology recommend it should be continued if required for
cardiovascular prophylaxis

B) Increased production of uric acid:

1) myeloproliferative/lymphoproliferative disorder
2) cytotoxic drugs
3) severe psoriasis

Lesch-Nyhan syndrome:
hypoxanthine-guanine phosphoribosyl transferase (HGPRTase) deficiency
x-linked recessive
features: gout, renal failure, neurological deficits, learning difficulties, self-mutilation

Gout: drug causes

1) thiazides, furosemide
2) alcohol
3) cytotoxic agents
4) pyrazinamide

Gout management:
A) Acute management:
1) NSAIDs
2) intra-articular steroid injection
3) Colchicine* has a slower onset of action. The main side-effect is diarrhoea
4) Oral steroids:
May be considered if NSAIDs and colchicine are contraindicated.
A dose of prednisolone 15mg/day is usually used
5) if the patient is already taking allopurinol it should be continued

*inhibits microtubule polymerization by binding to tubulin, interfering with mitosis. Also inhibits
neutrophil motility and activity

[31]
B) Allopurinol prophylaxis:
1) allopurinol should not be started until 2 weeks after an acute attack has settled as it may
precipitate a further attack if started too early
2) initial dose of 100 mg od, with the dose titrated every few weeks to aim for a serum uric
acid of < 300 mol/l
3) NSAID or colchicine cover should be used when starting allopurinol
Indications for allopurinol**
1) recurrent attacks: the British Society for Rheumatology recommend In uncomplicated gout uric
acid lowering drug therapy should be started if a second attack, or further attacks occur within 1
year
2) tophi
3) renal disease
4) uric acid renal stones
5) prophylaxis if on cytotoxics or diuretics
Lifestyle modifications:
1) reduce alcohol intake and avoid during an acute attack
2) lose weight if obese
3) avoid food high in purines e.g. Liver, kidneys, seafood, oily fish (mackerel, sardines) and
yeast products
Other points
1) increased vitamin C intake (either supplements or through normal diet) may also decrease
serum uric acid levels
2) Losartan has a specific uricosuric action and may be particularly suitable for the many
patients who have coexistent hypertension
3) calcium channel blockers also increase uric acid levels, possibly by a renal vasodilatory
effect
**patients with Lesch-Nyhan syndrome often take allopurinol for life
Pseudogout:
Pseudogout is a form of microcrystal synovitis
caused by the deposition of calcium pyrophosphate dihydrate in the synovium
Risk factors:
1) hyperparathyroidism
2) hypothyroidism
3) acromegaly
4) low magnesium, low phosphate
5) haemochromatosis
6) Wilson's disease
Features:
1) knee, wrist and shoulders most commonly affected
2) joint aspiration: weakly-positively birefringent rhomboid shaped crystals
3) x-ray: chondrocalcinosis
Management:
1) aspiration of joint fluid, to exclude septic arthritis
2) NSAIDs or intra-articular, intra-muscular or oral steroids as for gout
[32]
Familial Mediterranean Fever
Familial Mediterranean Fever (FMF, also known as recurrent polyserositis)
An autosomal recessive disorder
typically presents by the second decade
It is more common in people of Turkish, Armenian and Arabic descent

Features:
1) attacks typically last 1-3 days
2) pyrexia
3) abdominal pain (due to peritonitis)
4) pleurisy
5) pericarditis
6) arthritis
7) erysipeloid rash on lower limbs

Management:
colchicine may help

[33]
Osteomalacia
Basics:
normal bony tissue but decreased mineral content
rickets if when growing
Osteomalacia if after epiphysis fusion

Types:
1) vitamin D deficiency e.g. malabsorption, lack of sunlight, diet
2) renal failure
3) drug induced e.g. anticonvulsants
4) vitamin D resistant; inherited
5) liver disease, e.g. cirrhosis

Features:
A) rickets: knock-knee, bow leg, features of hypocalcaemia
B) osteomalacia: bone pain, fractures, muscle tenderness, proximal myopathy

Investigation:
low calcium, phosphate, 25(OH) vitamin D
raised alkaline phosphatase
x-ray:
Children - cupped, ragged metaphyseal surfaces;
Adults - translucent bands (Looser's zones or pseudofractures)

Treatment:
calcium with vitamin D tablets

Osteopetrosis
Overview:
also known as marble bone disease
rare disorder of defective osteoclast function resulting in failure of normal bone resorption
results in dense, thick bones that are prone to fracture
bone pains and neuropathies are common.

Investigation:
3) calcium, phosphate and ALP are normal

Management:
4) stem cell transplant and
5) interferon-gamma have been used for treatment

[34]
Osteoporosis
Causes:
Risk Factors:
Advancing age and female sex are significant risk factors for osteoporosis.
Prevalence of osteoporosis increases from 2% at 50 years to more than 25% at 80 years in
women.
There are many other risk factors and secondary causes of osteoporosis. We'll start by
looking at the most 'important' ones - these are

Risk factors that are used by major risk assessment tools such as FRAX:
1) history of glucocorticoid use
2) rheumatoid arthritis
3) alcohol excess
4) history of parental hip fracture
5) low body mass index
6) current smoking

Other risk factors:

1) sedentary lifestyle
2) premature menopause
3) Caucasians and Asians
4) endocrine disorders: hyperthyroidism, hyperparathyroidism ,hypogonadism (e.g. Turner's,
testosterone deficiency), growth hormone deficiency, diabetes mellitus
5) multiple myeloma, lymphoma
6) gastrointestinal disorders: inflammatory bowel disease, malabsorption (e.g. Coeliac's),
gastrectomy, liver disease
7) chronic kidney disease
8) osteogenesis imperfecta, homocystinuria

Medications that may worsen osteoporosis (other than glucocorticoids):

1) long term heparin therapy
2) proton pump inhibitors
3) glitazones
4) aromatase inhibitors e.g. anastrozole

Investigations for secondary causes:

If a patient is diagnosed with osteoporosis or has a fragility fracture further investigations may
be warranted.
NOGG recommend testing for the following reasons:
1) exclude diseases that mimic osteoporosis (e.g. osteomalacia, myeloma);
2) identify the cause of osteoporosis and contributory factors;
3) assess the risk of subsequent fractures;
4) select the most appropriate form of treatment
[35]
The following investigations are recommended by NOGG:
1) History and physical examination
2) Blood cell count, sedimentation rate or C-reactive protein, serum calcium, albumin,
creatinine, phosphate, alkaline phosphatase and liver transaminases
3) Thyroid function tests
4) Bone densitometry ( DXA)

Other procedures, if indicated

1) Lateral radiographs of lumbar and thoracic spine/DXA-based vertebral imaging
2) Protein immunoelectrophoresis and urinary Bence-Jones proteins
3) 25OHD
4) PTH
5) Serum testosterone, SHBG, FSH, LH (in men),
6) Serum prolactin
7) 24 hour urinary cortisol/dexamethasone suppression test
8) Endomysial and/or tissue transglutaminase antibodies (coeliac disease)
9) Isotope bone scan
10) Markers of bone turnover, when available
11) Urinary calcium excretion

So from the first list we should order the following bloods as a minimum for all patients:
1) full blood count
2) urea and electrolytes
3) liver function tests
4) bone profile
5) CRP
6) thyroid function tests

Osteoporosis: DEXA scan:

Basics:
T score: based on bone mass of young reference population
T score of -1.0 means bone mass of one standard deviation below that of young reference
population
Z score is adjusted for age, gender and ethnic factors

T score:
> -1.0 = normal
-1.0 to -2.5 = osteopaenia
< -2.5 = osteoporosis

[36]
Osteoporosis management:
NICE guidelines were updated in 2008 on the secondary prevention of osteoporotic fractures
in postmenopausal women.
Key points include:
1) Treatment is indicated following osteoporotic fragility fractures in postmenopausal women
who are confirmed to have osteoporosis (a T-score of - 2.5 SD or below).
2) In women aged 75 years or older, a DEXA scan may not be required 'if the responsible
clinician considers it to be clinically inappropriate or unfeasible'
3) vitamin D and calcium supplementation should be offered to all women unless the clinician
is confident they have adequate calcium intake and are vitamin D replete
4) alendronate is first-line
5) Around 25% of patients cannot tolerate alendronate, usually due to upper gastrointestinal
problems. These patients should be offered risedronate or etidronate (see treatment
criteria below)
6) strontium ranelate and raloxifene are recommended if patients cannot tolerate
bisphosphonates (see treatment criteria below)

Treatment criteria for patients not taking alendronate:

Unfortunately, a number of complicated treatment cut-off tables have been produced in the
latest guidelines for patients who do not tolerate alendronate
These take into account a patients age, their T-score and the number of risk factors they
have from the following list:
1) parental history of hip fracture
2) alcohol intake of 4 or more units per day
3) rheumatoid arthritis
The most important thing to remember is:
1) the T-score criteria for risedronate or etidronate are less than the others implying that
these are the second line drugs
2) if alendronate, risedronate or etidronate cannot be taken then strontium ranelate or
raloxifene may be given based on quite strict T-scores (e.g. a 60-year-old woman
would need a T-score < -3.5)
3) the strictest criteria are for denosumab
A) Bisphosphonates:
1) alendronate, risedronate and etidronate are all licensed for the prevention and
treatment of post-menopausal and glucocorticoid-induced osteoporosis
2) all three have been shown to reduce the risk of both vertebral and non-vertebral
fractures although alendronate, risedronate may be superior to etidronate in preventing
hip fractures
3) ibandronate is a once-monthly oral bisphosphonate

B) Vitamin D and calcium:

poor evidence base to suggest reduced fracture rates in the general population at risk of
osteoporotic fractures - may reduce rates in frail, housebound patients
[37]
C) Raloxifene:
selective oestrogen receptor modulator (SERM)
has been shown to prevent bone loss and to reduce the risk of vertebral fractures, but
has not yet been shown to reduce the risk of non-vertebral fractures
has been shown to increase bone density in the spine and proximal femur
may worsen menopausal symptoms
increased risk of thromboembolic events
may decrease risk of breast cancer

D) Strontium ranelate:
dual action bone agent:
1) increases deposition of new bone by osteoblasts (promotes differentiation of pre-
osteoblast to osteoblast) and
2) reduces the resorption of bone by inhibiting osteoclasts
Concerns regarding the safety profile of strontium have been raised recently.
It should only be prescribed by a specialist in secondary care
due to these concerns the European Medicines Agency in 2014 said it should only be
used by people for whom there are no other treatments for osteoporosis

Adverse Effects:
1) increased risk of cardiovascular events: any history of cardiovascular disease or
significant risk of cardiovascular disease is a contraindication
2) increased risk of thromboembolic events: a Drug Safety Update in 2012 recommended
it is not used in patients with a history of venous thromboembolism
3) may cause serious skin reactions such as Stevens Johnson syndrome

E) Denosumab:
human monoclonal antibody
inhibits RANK ligand, which in turn inhibits the maturation of osteoclasts
given as a single subcutaneous injection every 6 months
initial trial data suggests that it is effective and well tolerated

F) Teriparatide:
recombinant form of parathyroid hormone
very effective at increasing bone mineral density but role in the management of
osteoporosis yet to be clearly defined

G)Hormone replacement therapy:

has been shown to reduce the incidence of vertebral fracture and non-vertebral
fractures
due to concerns about increased rates of cardiovascular disease and breast cancer it
is no longer recommended for primary or secondary prevention of osteoporosis unless the
woman is suffering from vasomotor symptoms
[38]
H) Hip protectors:
evidence to suggest significantly reduce hip fractures in nursing home patients
compliance is a problem

I) Falls risk assessment:

no evidence to suggest reduced fracture rates
however, do reduce rate of falls and should be considered in management of high risk
patients

Osteoporosis: glucocorticoid-induced:
We know that one of the most important risk factors for osteoporosis is the use of
corticosteroids.
As these drugs are so widely used in clinical practice it is important we manage this risk
appropriately.
The most widely followed guidelines are based around the 2002 Royal College of
Physicians (RCP) 'Glucocorticoid-induced osteoporosis: A concise guide to prevention
and treatment', a link to which is provided below.
The risk of osteoporosis is thought to rise significantly once a patient is taking the equivalent
of prednisolone 7.5mg a day for 3 or more months.
It is important to note that we should manage patients in an anticipatory, i.e. if it likely that
the patient will have to take steroids for at least 3 months then we should start bone
protection straight away, rather than waiting until 3 months has elapsed.
A good example is a patient with newly diagnosed polymyalgia rheumatica. As it is very likely
they will be on a significant dose of prednisolone for greater than 3 months bone protection
should be commenced immediately.

Management of patients at risk of corticosteroid-induced osteoporosis:

The RCP guidelines essentially divide patients into two groups.
1) Patients over the age of 65 years or those who've previously had a fragility fracture should be
offered bone protection.
2) Patients under the age of 65 years should be offered a bone density scan, with further
management dependent:
T score Management

Greater than 0 Reassure

Between 0 and -1.5 Repeat bone density scan in 1-3 years

Less than -1.5 Offer bone protection

The first-line treatment is alendronate. Patients should also be calcium and vitamin D
replete.

[39]
Septic arthritis
Overview:
most common organism overall is Staphylococcus aureus
in young adults who are sexually active Neisseria gonorrhoeae should also be considered
Management:
1) synovial fluid should be obtained before starting treatment
2) intravenous antibiotics which cover Gram-positive cocci are indicated. The BNF currently
recommends flucloxacillin or clindamycin if penicillin allergic
3) antibiotic treatment is normally be given for several weeks (BNF states 6-12 weeks)
4) needle aspiration should be used to decompress the joint
5) surgical drainage may be needed if frequent needle aspiration is required

Elbow pain:
The table below details some of the characteristic features of conditions causing elbow pain:
Lateral Features:
epicondylitis 1) pain and tenderness localised to the lateral epicondyle
(tennis 2) pain worse on resisted wrist extension with the elbow extended or supination
elbow) of the forearm with the elbow extended
3) episodes typically last between 6 months and 2 years. Patients tend to have
acute pain for 6-12 weeks

Medial Features:
epicondylitis 1) pain and tenderness localised to the medial epicondyle
(golfer's 2) pain is aggravated by wrist flexion and pronation
elbow) 3) symptoms may be accompanied by numbness / tingling in the 4th and 5th
finger due to ulnar nerve involvement

Radial Most commonly due to compression of the posterior interosseous branch of the
tunnel radial nerve. It is thought to be a result of overuse.
syndrome Features:
1) symptoms are similar to lateral epicondylitis making it difficult to diagnose
2) however, the pain tends to be around 4-5 cm distal to the lateral epicondyle
3) symptoms may be worsened by extending the elbow and pronating the
forearm

Cubital Due to the compression of the ulnar nerve.

tunnel Features:
syndrome 1) initially intermittent tingling in the 4th and 5th finger
2) may be worse when the elbow is resting on a firm surface or flexed for
extended periods
3) later numbness in the 4th and 5th finger with associated weakness

Olecranon 1) Swelling over the posterior aspect of the elbow.

bursitis 2) There may be associated pain, warmth and erythema.
3) It typically affects middle-aged male patients.
[40]
Lateral epicondylitis:
Lateral epicondylitis typically follows unaccustomed activity such as house painting or playing
tennis ('tennis elbow').
It is most common in people aged 45-55 years and typically affects the dominant arm.
Features:
1) pain and tenderness localised to the lateral epicondyle
2) pain worse on wrist extension against resistance with the elbow extended or supination of
the forearm with the elbow extended
3) episodes typically last between 6 months and 2 years. Patients tend to have acute pain for
6-12 weeks
Management options:
1) advice on avoiding muscle overload
2) simple analgesia
3) steroid injection
4) physiotherapy

[41]
Hip pain in adults:

Condition Features

Osteoarthritis 1) Pain exacerbated by exercise and relieved by rest

2) Reduction in internal rotation is often the first sign
3) Age, obesity and previous joint problems are risk factors

Inflammatory 1) Pain in the morning,

arthritis 2) Systemic features
3) Raised inflammatory markers

Referred lumbar 1) Femoral nerve compression may cause referred pain in the hip
spine pain 2) Femoral nerve stretch test may be positive:
Lie the patient prone. Extend the hip joint with a straight leg then
bend the knee.
This stretches the femoral nerve and will cause pain if it is
trapped

Greater trochanteric Due to repeated movement of the fibroelastic iliotibial band

pain syndrome Pain and tenderness over the lateral side of thigh
(Trochanteric Most common in women aged 50-70 years
bursitis)

Meralgia Caused by compression of lateral cutaneous nerve of thigh

paraesthetica Typically burning sensation over antero-lateral aspect of thigh

Avascular necrosis Symptoms may be of gradual or sudden onset

May follow high dose steroid therapy or previous hip fracture of
dislocation

Pubic symphysis Common in pregnancy

dysfunction Ligament laxity increases in response to hormonal changes of
pregnancy
Pain over the pubic symphysis with radiation to the groins and the
medial aspects of the thighs.
A waddling gait may be seen

Transient idiopathic An uncommon condition sometimes seen in the third trimester of

osteoporosis pregnancy
Groin pain associated with a limited range of movement in the hip
Patients may be unable to weight bear
ESR may be elevated

[42]
Dactylitis:
Dactylitis describes the inflammation of a digit (finger or toe).
Causes include:
spondyloarthritis: e.g. Psoriatic and reactive arthritis
sickle-cell disease
other rare causes include tuberculosis, sarcoidosis and syphilis

De Quervain's tenosynovitis:
De Quervain's tenosynovitis is a common condition in which the sheath containing the
extensor pollicis brevis and abductor pollicis longus tendons is inflamed.
It typically affects females aged 30 - 50 years old
Features:
pain on the radial side of the wrist
tenderness over the radial styloid process
abduction of the thumb against resistance is painful
Finkelstein's test: with the thumb is flexed across the palm of the hand, pain is reproduced
by movement of the wrist into flexion and ulnar deviation
Management:
analgesia
steroid injection
immobilisation with a thumb splint (spica) may be effective
surgical treatment is sometimes required

Adhesive capsulitis:
Adhesive capsulitis (frozen shoulder) is a common cause of shoulder pain.
It is most common in middle-aged females.
The aetiology of frozen shoulder is not fully understood.

Associations:
diabetes mellitus: up to 20% of diabetics may have an episode of frozen shoulder

Features:
typically develop over days
external rotation is affected more than internal rotation or abduction
both active and passive movement are affected
patients typically have a painful freezing phase, an adhesive phase and a recovery phase
bilateral in up to 20% of patients
the episode typically lasts between 6 months and 2 years

Management:
no single intervention has been shown to improve outcome in the long-term
treatment options include NSAIDs, physiotherapy, oral corticosteroids and intra-articular
corticosteroids

[43]
Ankle injury: Ottawa rules:
The Ottawa Rules with for ankle x-rays have a sensitivity approaching 100%
An ankle x-ray is required only if there is any pain in the malleolar zone and any one of the
following findings:

1) bony tenderness at the lateral malleolar zone (from the tip of the lateral malleolus to
include the lower 6 cm of posterior border of the fibular)
2) bony tenderness at the medial malleolar zone (from the tip of the medial malleolus to the
lower 6 cm of the posterior border of the tibia)
3) inability to walk four weight bearing steps immediately after the injury and in the
emergency department

There are also Ottawa rules available for both foot and knee injuries

Carpal tunnel syndrome:

Carpal tunnel syndrome is caused by compression of median nerve in the carpal tunnel.

History
pain/pins and needles in thumb, index, middle finger
unusually the symptoms may 'ascend' proximally
patient shakes his hand to obtain relief, classically at night

Examination:
weakness of thumb abduction (abductor pollicis brevis)
wasting of thenar eminence (NOT hypothenar)
Tinel's sign: tapping causes paraesthesia
Phalen's sign: flexion of wrist causes symptoms

Causes:
idiopathic
pregnancy
oedema e.g. heart failure
lunate fracture
rheumatoid arthritis

Electrophysiology
motor + sensory: prolongation of the action potential

Treatment
corticosteroid injection
wrist splints at night
surgical decompression (flexor retinaculum division)

[44]
Rotator cuff muscles:
SItS - small t for teres minor

Supraspinatus
Infraspinatus
teres minor
Subscapularis

Muscle Notes

Supraspinatus aBDucts arm before deltoid

Most commonly injured

Infraspinatus Rotates arm laterally

teres minor aDDucts & rotates arm laterally

Subscapularis aDDuct & rotates arm medially

[45]
Paget's disease of the bone:
Paget's disease is a disease of increased but uncontrolled bone turnover.
It is thought to be primarily a disorder of osteoclasts, with excessive osteoclastic resorption
followed by increased osteoblastic activity.
Paget's disease is common (UK prevalence 5%) but symptomatic in only 1 in 20 patients

Predisposing factors:
increasing age
male sex
northern latitude
family history

Clinical features:
only 5% of patients are symptomatic
bone pain (e.g. pelvis, lumbar spine, femur)
classical, untreated features: bowing of tibia, bossing of skull
raised alkaline phosphatase (ALP) - calcium* and phosphate are typically normal
skull x-ray: thickened vault, osteoporosis circumscripta
*usually normal in this condition but hypercalcaemia may occur with prolonged immobilisation

Indications for treatment:

bone pain,
skull or long bone deformity,
fracture,
periarticular Paget's

Treatment:
bisphosphonate (either oral risedronate or IV zoledronate)
calcitonin is less commonly used now

Complications:
deafness (cranial nerve entrapment)
bone sarcoma (1% if affected for > 10 years)
fractures
skull thickening
high-output cardiac failure

[46]
The radiograph demonstrates marked thickening of the calvarium. There are also ill-defined
sclerotic and lucent areas throughout. These features are consistent with Paget's disease.

Pelvic x-ray from an elderly man with Paget's disease. There is a smooth cortical expansion of
the left hemipelvic bones with diffuse increased bone density and coarsening of trabeculae.

Isotope bone scan from a patient with Paget's disease showing a typical distribution in the spine,
asymmetrical pelvic disease and proximal long bones.

[47]
Marfan's syndrome:
Marfan's syndrome is an autosomal dominant connective tissue disorder.
It is caused by a defect in the fibrillin-1 gene on chromosome 15 and affects around 1 in
3,000 people.

Features
1) tall stature with arm span to height ratio > 1.05
2) high-arched palate
3) arachnodactyly
4) pectus excavatum
5) pes planus
6) scoliosis of > 20 degrees
7) heart: dilation of the aortic sinuses (seen in 90%) which may lead to aortic aneurysm,
aortic dissection, aortic regurgitation, mitral valve prolapse (75%),
8) lungs: repeated pneumothoraces
9) eyes: upwards lens dislocation (superotemporal ectopia lentis), blue sclera, myopia
10) dural ectasia (ballooning of the dural sac at the lumbosacral level)

The life expectancy of patients used to be around 40-50 years. With the advent of regular
echocardiography monitoring and beta-blocker/ACE-inhibitor therapy this has improved
significantly over recent years. Aortic dissection and other cardiovascular problems remain the
leading cause of death however.

[48]

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