PASSMEDICINE NOTES

RHEUMATOLOGY
CONTENTS
No Topic Page
1 ROTATOR CUFF MUSCLES
2 ELBOW PAIN
3 LATERAL EPICONDYLITIS
4 CARPAL TUNNEL SYNDROME
5 CUBITAL TUNNEL SYNDROME
6 DE QUERVAIN’S TENOSYNOVITIS
7 ADHESIVE CAPSULITIS
8 LOWER BACK PAIN
9 LOWER BACK PAIN: PROLAPSED DISC
10 LUMBAR SPINAL STENOSIS
11 SERONEGATIVE SPONDYLOARTHROPATHIES
12 ANKYLOSING SPONDYLITIS: FEATURES
13 ANKYLOSING SPONDYLITIS: INVESTIGATION AND MANAGEMENT
14 PSORIATIC ARTHROPATHY
15 REACTIVE ARTHRITIS
16 REACTIVE ARTHRITIS: FEATURES
17 ILIOPSOAS ABSCESS
18 HIP PAIN IN ADULTS
19 AVASCULAR NECROSIS OF THE HIP
20 HIP PROBLEMS IN CHILDREN
21 SEPTIC ARTHRITIS
22 MERALGIA PARAESTHETICA
23 ANKLE INJURY: OTTAWA RULES
24 OSTEOARTHRITIS: MANAGEMENT
25 OSTEOGENESIS IMPERFECTA
26 OSTEOMALACIA
27 OSTEOMYELITIS
28 OSTEOPETROSIS
29 OSTEOPOROSIS: CAUSES
30 OSTEOPOROSIS: GLUCOCORTICOID-INDUCED
31 OSTEOPOROSIS: DEXA SCAN
32 OSTEOPOROSIS: MANAGEMENT
33 BISPHOSPHONATES
34 DENOSUMAB
35 VITAMIN D SUPPLEMENTATION
36 PAGET’S DISEASE OF THE BONE
37 BONE TUMOURS
38 BONE DISORDERS: LAB VALUES
39 TUMOUR NECROSIS FACTOR
40 AZATHIOPRINE
41 MYCOPHENOLATE MOFETIL
42 CHRONIC FATIGUE SYNDROME
43 DERMATOMYOSITIS
44 DERMATOMYOSITIS: INVESTIGATIONS AND MANAGEMENT
45 POLYMYOSITIS
46 POLYMYALGIA RHEUMATICA
47 FIBROMYALGIA
48 MYOPATHIES
49 ANCA
50 EXTRACTABLE NUCLEAR ANTIGENS
51 SYSTEMIC LUPUS ERYTHEMATOSUS
52 SYSTEMIC LUPUS ERYTHEMATOSUS: FEATURES
53 SYSTEMIC LUPUS ERYTHEMATOSUS: INVESTIGATIONS
54 SYSTEMIC LUPUS ERYTHEMATOSUS: PREGNANCY
55 SYSTEMIC SCLEROSIS
56 RAYNAUD’S
57 DISCOID LUPUS ERYTHEMATOSUS
58 DRUG-INDUCED LUPUS
59 SJOGREN’S SYNDROME
60 MIXED CONNECTIVE TISSUE DISEASE
61 MARFAN’S SYNDROME
62 EHLER-DANLOS SYNDROME
63 RHEUMATOID ARTHRITIS: EPIDEMIOLOGY
64 RHEUMATOID ARTHRITIS: ANTIBODIES
65 RHEUMATOID ARTHRITIS: PRESENTATION
66 RHEUMATOID ARTHRITIS: DIAGNOSIS
67 RHEUMATOID ARTHRITIS: X-RAY CHANGES
68 RHEUMATOID ARTHRITIS: MANAGEMENT
69 LEFLUNOMIDE
70 HYDROXYCHLOROQUINE
71 METHOTREXATE
72 SULFASALAZINE
73 RHEUMATOID ARTHRITIS: DRUG SIDE EFFECTS
74 RHEUMATOID ARTHRITIS: PROGNOSTIC FEATURES
75 RHEUMATOID ARTHRITIS: PREGNANCY
76 RHEUMATOID ARTHRITIS: COMPLICATIONS
77 TEMPORAL ARTERITIS
78 POLYARTERITIS NODOSA
79 BEHCET’S SYNDROME
80 ANTIPHOSPHOLIPID SYNDROME
81 GOUT: PREDISPOSING FACTORS
82 GOUT: DRUG CAUSES
83 GOUT: FEATURES
84 GOUT: MANAGEMENT
85 PSEUDOGOUT
86 PSEUDOXANTHOMA ELASTICUM
87 RELAPSING POLYCHONDRITIS
88 LANGERHANS CELL HISTIOCYTOSIS
89 FAMILIAL MEDITERRANEAN FEVER
90 MCARDLE’S DISEASE
91 STILL’S DISEASE IN ADULTS
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

ELBOW PAIN
The table below details some of the characteristic features of conditions causing elbow pain:

Condition Notes
Lateral epicondylitis Features
(tennis elbow)

 pain and tenderness localised to the lateral epicondyle

 pain worse on resisted wrist extension with the elbow extended or
supination of the forearm with the elbow extended
 episodes typically last between 6 months and 2 years. Patients tend to
have acute pain for 6-12 weeks

Medial epicondylitis Features

(golfer's elbow)

 pain and tenderness localised to the medial epicondyle

 pain is aggravated by wrist flexion and pronation
 symptoms may be accompanied by numbness / tingling in the 4th and
5th finger due to ulnar nerve involvement

Radial tunnel Most commonly due to compression of the posterior interosseous branch of
syndrome the radial nerve. It is thought to be a result of overuse.
 Condition Notes
Features

 symptoms are similar to lateral epicondylitis making it difficult to

diagnose
 however, the pain tends to be around 4-5 cm distal to the lateral
epicondyle
 symptoms may be worsened by extending the elbow and pronating
the forearm

Cubital tunnel Due to the compression of the ulnar nerve.

syndrome
Features

 initially intermittent tingling in the 4th and 5th finger

 may be worse when the elbow is resting on a firm surface or flexed for
extended periods
 later numbness in the 4th and 5th finger with associated weakness

Olecranon bursitis Swelling over the posterior aspect of the elbow. There may be associated
pain, warmth and erythema. It typically affects middle-aged male patients.

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
 pain and tenderness localised to the lateral epicondyle
 pain worse on wrist extension against resistance with the elbow extended or supination of the
forearm with the elbow extended
 episodes typically last between 6 months and 2 years. Patients tend to have acute pain for 6-12
weeks

Management options
 advice on avoiding muscle overload
 simple analgesia
 steroid injection
 physiotherapy
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)

CUBITAL TUNNEL SYNDROME

Cubital tunnel syndrome occurs due to compression of the ulnar nerve as it passes through the
cubital tunnel.

Clincial features
 Tingling and numbness of the 4th and 5th finger which starts off intermittent and then becomes
constant.
 Over time patients may also develop weakness and muscle wasting
 Pain worse on leaning on the affected elbow
 Often a history of osteoarthritis or prior trauma to the area.
Investigations
 the diagnosis is usually clinical
 however, in selected cases nerve conduction studies may be used

Management
 Avoid aggravating activity
 Physiotherapy
 Steroid injections
 Surgery in resistant cases

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: the examiner pulls the thumb of the patient in ulnar deviation and longitudinal
traction. In a patient with tenosynovitis this action causes pain over the radial styloid process
and along the length of extensor pollisis brevis and abductor pollicis longus

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

The diagnosis is usually clinical although imaging may be required for atypical or persistent
symptoms.

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

LOWER BACK PAIN

Lower back pain (LBP) is one of the most common presentations seen in practice. Whilst the
majority of presentations will be of a non-specific muscular nature it is worth keeping in mind
possible causes which may need specific treatment.

Red flags for lower back pain

 age < 20 years or > 50 years
 history of previous malignancy
 night pain
 history of trauma
 systemically unwell e.g. weight loss, fever

The table below indicates some specific causes of LBP:

May be acute or chronic

Pain worse in the morning and on standing
On examination there may be pain over the facets. The pain is typically worse
Facet joint on extension of the back
Spinal stenosis Usually gradual onset
Unilateral or bilateral leg pain (with or without back pain), numbness, and
weakness which is worse on walking. Resolves when sits down. Pain may be
described as 'aching', 'crawling'.
Relieved by sitting down, leaning forwards and crouching down
Clinical examination is often normal
Requires MRI to confirm diagnosis
Ankylosing Typically a young man who presents with lower back pain and stiffness
spondylitis Stiffness is usually worse in morning and improves with activity
Peripheral arthritis (25%, more common if female)
 May be acute or chronic
Pain worse in the morning and on standing
On examination there may be pain over the facets. The pain is typically worse
Facet joint on extension of the back
Peripheral Pain on walking, relieved by rest
arterial disease Absent or weak foot pulses and other signs of limb ischaemia
Past history may include smoking and other vascular diseases

LOWER BACK PAIN: PROLAPSED DISC

A prolapsed lumbar disc usually produces clear dermatomal leg pain associated with neurological
deficits.

Features
 leg pain usually worse than back
 pain often worse when sitting

The table below demonstrates the expected features according to the level of compression:

Site of compression Features

L3 nerve root Sensory loss over anterior thigh
compression Weak quadriceps
Reduced knee reflex
Positive femoral stretch test
L4 nerve root Sensory loss anterior aspect of knee
compression Weak quadriceps
Reduced knee reflex
Positive femoral stretch test
L5 nerve root Sensory loss dorsum of foot
compression Weakness in foot and big toe dorsiflexion
Reflexes intact
Positive sciatic nerve stretch test
S1 nerve root Sensory loss posterolateral aspect of leg and lateral aspect of foot
compression Weakness in plantar flexion of foot
Reduced ankle reflex
Positive sciatic nerve stretch test

Management
 similar to that of other musculoskeletal lower back pain: analgesia, physiotherapy, exercises
 if symptoms persist 9e.g. after 4-6 weeks) then referral for consideration of MRI is appropriate
LUMBAR SPINAL STENOSIS
Lumbar spinal stenosis is a condition in which the central canal is narrowed by tumour, disk prolapse
or other similar degenerative changes.

Patients may present with a combination of back pain, neuropathic pain and symptoms mimicking
claudication. One of the main features that may help to differentiate it from true claudication in the
history is the positional element to the pain. Sitting is better than standing and patients may find it
easier to walk uphill rather than downhill. The neurogenic claudication type history makes lumbar
spinal stenosis a likely underlying diagnosis, the absence of such symptoms makes it far less likely.

Pathology
Degenerative disease is the commonest underlying cause. Degeneration is believed to begin in the
intervertebral disk where biochemical changes such as cell death and loss of proteoglycan and water
content lead to progressive disk bulging and collapse. This process leads to an increased stress
transfer to the posterior facet joints, which accelerates cartilaginous degeneration, hypertrophy,
and osteophyte formation; this is associated with thickening and distortion of the ligamentum
flavum. The combination of the ventral disk bulging, osteophyte formation at the dorsal facet, and
ligamentum flavum hyptertrophy combine to circumferentially narrow the spinal canal and the
space available for the neural elements. The compression of the nerve roots of the cauda equina
leads to the characteristic clinical signs and symptoms of lumbar spinal stenosis.

Diagnosis
MRI scanning is the best modality for demonstrating the canal narrowing. Historically a bicycle test
was used as true vascular claudicants could not complete the test.

Treatment
Laminectomy
SERONEGATIVE SPONDYLOARTHROPATHIES
Common features
 associated with HLA-B27
 rheumatoid factor negative - hence 'seronegative'
 peripheral arthritis, usually asymmetrical
 sacroiliitis
 enthesopathy: e.g. Achilles tendonitis, plantar fasciitis
 extra-articular manifestations: uveitis, pulmonary fibrosis (upper zone), amyloidosis, aortic
regurgitation

Spondyloarthropathies
 ankylosing spondylitis
 psoriatic arthritis
 Reiter's syndrome (including reactive arthritis)
 enteropathic arthritis (associated with IBD)

ANKYLOSING SPONDYLITIS: FEATURES

Ankylosing spondylitis is a HLA-B27 associated spondyloarthropathy. It typically presents in males
(sex ratio 3:1) aged 20-30 years old.

Features
 typically a young man who presents with lower back pain and stiffness of insidious onset
 stiffness is usually worse in the morning and improves with exercise
 the patient may experience pain at night which improves on getting up

Clinical examination
 reduced lateral flexion
 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
 reduced chest expansion

Other features - the 'A's

 Apical fibrosis
 Anterior uveitis
 Aortic regurgitation
 Achilles tendonitis
 AV node block
 Amyloidosis
 and cauda equina syndrome
 peripheral arthritis (25%, more common if female)

ANKYLOSING SPONDYLITIS: INVESTIGATION AND MANAGEMENT

Ankylosing spondylitis is a HLA-B27 associated spondyloarthropathy. It typically presents in males
(sex ratio 3:1) aged 20-30 years old.

Investigation
Inflammatory markers (ESR, CRP) are typically raised although normal levels do not exclude
ankylosing spondylitis.

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

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:
 sacroiliitis: subchondral erosions, sclerosis
 squaring of lumbar vertebrae
 'bamboo spine' (late & uncommon)
 syndesmophytes: due to ossification of outer fibers of annulus fibrosus
 chest x-ray: apical fibrosis

If the x-ray is negative for sacroiliac joint involvement in ankylosing spondylitis but suspicion for AS
remains high, the next step in the evaluation should be obtaining an MRI. Signs of early
inflammation involving sacroiliac joints (bone marrow oedema) confirm the diagnosis of AS and
prompt further treatment.

Spirometry may show a restrictive defect due to a combination of pulmonary fibrosis, kyphosis and
ankylosis of the costovertebral joints.

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

40-year-old male. There is typical appearance of bamboo spine with a single central radiodense line related to
ossification of supraspinous and interspinous ligaments which is called dagger sign. Ankylosing is detectable in both
sacroiliac joints

Ankylosing spondylitis with well formed syndesmophytes

Lateral cervical spine. Complete fusion of anterior and posterior elements in ankylosing spondylitis, so called bamboo
spine

Fusion of bilateral sacroiliac joints. Sacroiliitis may present as sclerosis of joint margins which can be asymmetrical at
early stage of disease, but is bilateral and symmetrical in late disease
Syndesmophytes and squaring of vertebral bodies. Squaring of anterior vertebral margins is due to osteitis of anterior
corners. Syndesmophytes are due to ossification of outer fibers of annulus fibrosus

PSORIATIC ARTHROPATHY
Psoriatic arthropathy correlates poorly with cutaneous psoriasis and often precedes the
development of skin lesions. Around 10-20% percent of patients with skin lesions develop an
arthropathy with males and females being equally affected

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

Management
 should be managed by a rheumatologist
 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.

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

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.

'Can't see, pee or climb a tree'

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
 symptomatic: analgesia, NSAIDS, intra-articular steroids
 sulfasalazine and methotrexate are sometimes used for persistent disease
 symptoms rarely last more than 12 months

REACTIVE ARTHRITIS: FEATURES

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
 typically develops within 4 weeks of initial infection - symptoms generally last around 4-6
months
 arthritis is typically an asymmetrical oligoarthritis of lower limbs
 dactylitis
 symptoms of urethritis
 eye: conjunctivitis (seen in 10-30%), anterior uveitis
 skin: circinate balanitis (painless vesicles on the coronal margin of the prepuce), keratoderma
blenorrhagica (waxy yellow/brown papules on palms and soles)

Around 25% of patients have recurrent episodes whilst 10% of patients develop chronic disease

'Can't see, pee or climb a tree'

Keratoderma blenorrhagica
ILIOPSOAS ABSCESS
An iliopsoas abscess describes a collection of pus in iliopsoas compartment (iliopsoas and iliacus).

Primary
 Haematogenous spread of bacteria
 Staphylococcus aureus: most common

Secondary
 Crohn's (commonest cause in this category)
 Diverticulitis, colorectal cancer
 UTI, GU cancers
 Vertebral osteomyelitis
 Femoral catheter, lithotripsy
 Endocarditis

Note the mortality rate can be up to 19-20% in secondary iliopsoas abscesses compared with 2.4%
in primary abscesses.

Clinical features
 Fever
 Back/flank pain
 Limp
 Weight loss

Clinical examination
 Patient in the supine position with the knee flexed and the hip mildly externally rotated
 Specific tests to diagnose iliopsoas inflammation:
o Place hand proximal to the patient's ipsilateral knee and ask patient to lift thigh against your
hand. This will cause pain due to contraction of the psoas muscle.
o Lie the patient on the normal side and hyperextend the affected hip. This should elicit pain as
the psoas muscle is stretched.

Investigation
 CT is the gold standard

Management
 Antibiotics
 Percutaneous drainage is the initial approach and successful in around 90% of cases
 Surgery is indicated if:
1. Failure of percutaneous drainage
2. Presence of an another intra-abdominal pathology which requires surgery
HIP PAIN IN ADULTS
The table below provides a brief summary of the potential causes of hip pain in adults

Condition Features
Osteoarthritis Pain exacerbated by exercise and relieved by rest
Reduction in internal rotation is often the first sign
Age, obesity and previous joint problems are risk factors
Inflammatory arthritis Pain in the morning
Systemic features
Raised inflammatory markers
Referred lumbar spine Femoral nerve compression may cause referred pain in the hip
pain 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 bursitis) Most common in women aged 50-70 years
Meralgia paraesthetica Caused by compression of lateral cutaneous nerve of thigh
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

AVASCULAR NECROSIS OF THE HIP

Avascular necrosis (AVN) may be defined as death of bone tissue secondary to loss of the blood
supply. This leads to bone destruction and loss of joint function. It most commonly affects the
epiphysis of long bones such as the femur.

Causes
 long-term steroid use
 chemotherapy
 alcohol excess
 trauma

Features
 initially asymptomatic
 pain in the affected joint

Investigation
 plain x-ray findings may be normal initially. Osteopenia and microfractures may be seen early on.
Collapse of the articular surface may result in the crescent sign
 MRI is the investigation of choice. It is more sensitive than radionuclide bone scanning

Management
 joint replacement may be necessary
HIP PROBLEMS IN CHILDREN
The table below provides a brief summary of the potential causes of hip problems in children

Condition Notes
Development Often picked up on newborn examination
dysplasia of the Barlow's test, Ortolani's test are positive
hip Unequal skin folds/leg length

Transient Typical age group = 2-10 years

synovitis Acute hip pain associated with viral infection
(irritable hip) Commonest cause of hip pain in children
Perthes disease Perthes disease is a degenerative condition affecting the hip joints of children,
typically between the ages of 4-8 years. It is due to avascular necrosis of the
femoral head

Perthes disease is 5 times more common in boys. Around 10% of cases are
bilateral

Features

 hip pain: develops progressively over a few weeks

 limp
 stiffness and reduced range of hip movement
 x-ray: early changes include widening of joint space, later changes
include decreased femoral head size/flattening

Slipped upper Typical age group = 10-15 years

femoral More common in obese children and boys
epiphysis Displacement of the femoral head epiphysis postero-inferiorly
Bilateral slip in 20% of cases
May present acutely following trauma or more commonly with chronic,
persistent symptoms

Features

 knee or distal thigh pain is common

 loss of internal rotation of the leg in flexion
 Condition Notes
Juvenile Preferred to the older term juvenile chronic arthritis, describes arthritis occurring
idiopathic in someone who is less than 16 years old that lasts for more than three months.
arthritis (JIA) Pauciarticular JIA refers to cases where 4 or less joints are affected. It accounts
for around 60% of cases of JIA

Features of pauciarticular JIA

 joint pain and swelling: usually medium sized joints e.g. knees, ankles,
elbows
 limp
 ANA may be positive in JIA - associated with anterior uveitis

Septic arthritis Acute hip pain associated with systemic upset e.g. pyrexia. Inability/severe
limitation of affected joint

Image gallery

Perthes disease - both femoral epiphyses show extensive destruction, the acetabula are deformed

Perthes disease - bilateral disease

Slipped upper femoral epiphysis - left side

Slipped upper femoral epiphysis - left side

SEPTIC ARTHRITIS
Overview
 most common organism overall is Staphylococcus aureus
 in young adults who are sexually active Neisseria gonorrhoeae should also be considered
 in adults, the most common location is the knee

The Kocher criteria for the diagnosis of septic arthritis:

 fever >38.5 degrees C
 non-weight bearing
 raised ESR
 raised WCC

Management
 synovial fluid should be obtained before starting treatment
 intravenous antibiotics which cover Gram-positive cocci are indicated. The BNF currently
recommends flucloxacillin or clindamycin if penicillin allergic
 antibiotic treatment is normally be given for several weeks (BNF states 6-12 weeks)
 needle aspiration should be used to decompress the joint
 arthroscopic lavage may be required

MERALGIA PARAESTHETICA
Meralgia paraesthetica comes from the Greek words meros for thigh and algos for pain and is often
described as a syndrome of paraesthesia or anaesthesia in the distribution of the lateral femoral
cutaneous nerve (LFCN). It is an entrapment mononeuropathy of the LFCN, but can also be
iatrogenic after a surgical procedure, or result from a neuroma. Although uncommon, meralgia
paraesthetica is not rare and is hence probably underdiagnosed.

Anatomy
 The LFCN is primarily a sensory nerve, carrying no motor fibres.
 It most commonly originates from the L2/3 segments.
 After passing behind the psoas muscle, it runs beneath the iliac fascia as it crosses the surface of
the iliac muscle and eventually exits through or under the lateral aspect of the inguinal ligament.
 As the nerve curves medially and inferiorly around the anterior superior iliac spine (ASIS), it may
be subject to repetitive trauma or pressure.
 Compression of this nerve anywhere along its course can lead to the development of meralgia
paraesthetica.

Epidemiology
 The majority of cases occur in people aged between 30 and 40.
 In some, both legs may be affected.
 It is more common in men than women.
 Occurs more commonly in those with diabetes than in the general population.

Risk factors 3
 Obesity
 Pregnancy
 Tense ascites
 Trauma
 Iatrogenic, such as pelvic osteotomy, spinal surgeries, laparoscopic hernia repair and bariatric
surgery. In some cases, may result from abduction splints used in the management of Perthe's
disease.
 Various sports have been implicated, including gymnastics, football, bodybuilding and strenuous
exercise.
 Some cases are idiopathic.

Patients typically present with the following symptoms in the upper lateral aspect of the thigh:
 Burning, tingling, coldness, or shooting pain
 Numbness
 Deep muscle ache
 Symptoms are usually aggravated by standing, and relieved by sitting
 They can be mild and resolve spontaneously or may severely restrict the patient for many years.

Signs:
 Symptoms may be reproduced by deep palpation just below the ASIS (pelvic compression) and
also by extension of the hip.
 There is altered sensation over the upper lateral aspect of the thigh.
 There is no motor weakness.

Investigations:
 The pelvic compression test is highly sensitive, and often, meralgia paraesthetica can be
diagnosed based on this test alone
 Injection of the nerve with local anaesthetic will abolish the pain. Using ultrasound is effective
both for diagnosis and guiding injection therapy in meralgia paraesthetica
 Nerve conduction studies may be useful.

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:
 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)
 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)
 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
OSTEOARTHRITIS: MANAGEMENT
NICE published guidelines on the management of osteoarthritis (OA) in 2014
 all patients should be offered help with weight loss, given advice about local muscle
strengthening exercises and general aerobic fitness
 paracetamol and topical NSAIDs are first-line analgesics. Topical NSAIDs are indicated only for
OA of the knee or hand
 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
 non-pharmacological treatment options include supports and braces, TENS and shock absorbing
insoles or shoes
 if conservative methods fail then refer for consideration of joint replacement

What is the role of glucosamine?

 normal constituent of glycosaminoglycans in cartilage and synovial fluid
 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
 more recent studies have however been mixed
 the 2008 NICE guidelines suggest it is not recommended
 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

OSTEOGENESIS IMPERFECTA
Osteogenesis imperfecta (more commonly known as brittle bone disease) is a group of disorders of
collagen metabolism resulting in bone fragility and fractures. The most common, and milder, form
of osteogenesis imperfecta is type 1

Overview
 autosomal dominant
 abnormality in type 1 collagen due to decreased synthesis of pro-alpha 1 or pro-alpha 2 collagen
polypeptides

Features
 presents in childhood
 fractures following minor trauma
 blue sclera
 deafness secondary to otosclerosis
 dental imperfections are common
Investigations
 adjusted calcium, phosphate, parathyroid hormone and ALP results are usually normal in
osteogenesis imperfecta

OSTEOMALACIA
Basics
 normal bony tissue but decreased mineral content
 rickets if when growing
 osteomalacia if after epiphysis fusion

Types
 vitamin D deficiency e.g. malabsorption, lack of sunlight, diet
 renal failure
 drug induced e.g. anticonvulsants
 vitamin D resistant; inherited
 liver disease, e.g. cirrhosis

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

Investigation
 low 25(OH) vitamin D (in 100% of patients, by definition)
 raised alkaline phosphatase (in 95-100% of patients)
 low calcium, phosphate (in around 30%)
 x-ray: children - cupped, ragged metaphyseal surfaces; adults - translucent bands (Looser's zones
or pseudofractures)

Treatment
 calcium with vitamin D tablets

OSTEOMYELITIS
Osteomyelitis describes an infection of the bone.

Staph. aureus is the most common cause except in patients with sickle-cell anaemia where
Salmonella species predominate.
Predisposing conditions
 diabetes mellitus
 sickle cell anaemia
 intravenous drug user
 immunosuppression due to either medication or HIV
 alcohol excess

Investigations
 MRI is the imaging modality of choice, with a sensitivity of 90-100%

Management
 flucloxacillin for 6 weeks
 clindamycin if penicillin-allergic

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.
 calcium, phosphate and ALP are normal
 stem cell transplant and interferon-gamma have been used for treatment
OSTEOPOROSIS: CAUSES
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:
 history of glucocorticoid use
 rheumatoid arthritis
 alcohol excess
 history of parental hip fracture
 low body mass index
 current smoking

Other risk factors

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

Medications that may worsen osteoporosis (other than glucocorticoids):

 SSRIs
 antiepileptics
 proton pump inhibitors
 glitazones
 long term heparin therapy
 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:
 exclude diseases that mimic osteoporosis (e.g. osteomalacia, myeloma);
 identify the cause of osteoporosis and contributory factors;
 assess the risk of subsequent fractures;
 select the most appropriate form of treatment
The following investigations are recommended by NOGG:
 History and physical examination
 Blood cell count, sedimentation rate or C-reactive protein, serum calcium, albumin, creatinine,
phosphate, alkaline phosphatase and liver transaminases
 Thyroid function tests
 Bone densitometry ( DXA)

Other procedures, if indicated

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

So from the first list we should order the following bloods as a minimum for all patients:
 full blood count
 urea and electrolytes
 liver function tests
 bone profile
 CRP
 thyroid function tests

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'.

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.

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

OSTEOPOROSIS: MANAGEMENT
NICE guidelines were updated in 2008 on the secondary prevention of osteoporotic fractures in
postmenopausal women.

Key points include

 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). 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'
 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
 alendronate is first-line
 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)
 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, theire T-score and the number of risk factors they have from
the following list:
 parental history of hip fracture
 alcohol intake of 4 or more units per day
 rheumatoid arthritis

It is very unlikely that examiners would expect you to have memorised these risk tables so we've not
included them in the revision notes but they may be found by following the NICE link. The most
important thing to remember is:
 the T-score criteria for risedronate or etidronate are less than the others implying that these are
the second line drugs
 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)
 the strictest criteria are for denosumab

Supplementary notes on treatment

Bisphosphonates
 alendronate, risedronate and etidronate are all licensed for the prevention and treatment of
post-menopausal and glucocorticoid-induced osteoporosis
 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
 ibandronate is a once-monthly oral bisphosphonate

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
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

Strontium ranelate
 'dual action bone agent' - increases deposition of new bone by osteoblasts (promotes
differentiation of pre-osteoblast to osteoblast) and 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
 increased risk of cardiovascular events: any history of cardiovascular disease or significant risk of
cardiovascular disease is a contraindication
 increased risk of thromboembolic events: a Drug Safety Update in 2012 recommended it is not
used in patients with a history of venous thromboembolism
 may cause serious skin reactions such as Stevens Johnson syndrome

Denosumab
 human monoclonal antibody that 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

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

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

Hip protectors
 evidence to suggest significantly reduce hip fractures in nursing home patients
 compliance is a problem
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

MRI showing osteoporotic fractures of the 8th and 10th thoracic vertebrae.

BISPHOSPHONATES
Bisphosphonates are analogues of pyrophosphate, a molecule which decreases demineralisation in
bone. They inhibit osteoclasts by reducing recruitment and promoting apoptosis.

Clinical uses
 prevention and treatment of osteoporosis
 hypercalcaemia
 Paget's disease
 pain from bone metatases

Adverse effects
 oesophageal reactions: oesophagitis, oesophageal ulcers (especially alendronate)
 osteonecrosis of the jaw
 increased risk of atypical stress fractures of the proximal femoral shaft in patients taking
alendronate
 acute phase response: fever, myalgia and arthralgia may occur following administration
 hypocalcaemia: due to reduced calcium efflux from bone. Usually clinically unimportant
The BNF suggests the following counselling for patients taking oral bisphosphonates
'Tablets should be swallowed whole with plenty of water while sitting or standing; to be given on an
empty stomach at least 30 minutes before breakfast (or another oral medication); patient should
stand or sit upright for at least 30 minutes after taking tablet'

Hypocalcemia/vitamin D deficiency should be corrected before giving bisphosphonates. However,

when starting bisphosphonate treatment for osteoporosis, calcium should only be prescribed if
dietary intake is inadequate. Vitamin D supplements are normally given.

The duration of bisphosphonate treatment varies according to the level of risk. Some authorities
recommend stopping bisphosphonates at 5 years if the following apply:
 patient is < 75-years-old
 femoral neck T-score of > -2.5
 low risk according to FRAX/NOGG

DENOSUMAB
Denosumab is a relatively new treatment for osteoporosis. It is a human monoclonal antibody that
prevents the development of osteoclasts by inhibiting RANKL. Remember that osteoblasts build
bone, osteoclasts eat bone. It is given as a subcutaneous injection, at a dose of 60mg, every 6
months.

A larger dose of denosumab (120mg) may also be given every 4 weeks for the prevention of
skeletal-related events (i.e. pathological fractures) in adults with bone metastases from solid
tumours. For example, you may have noticed some of your breast cancer patients have been
prescribed denosumab.

Where does it fit in the management of osteoporosis?

Oral bisphosphonates are still given first-line, with oral alendronate being the first-line treatment. If
alendronate is not tolerated then NICE recommend using an alternative bisphosphonate - either
risedronate or etidronate. Following this the advice becomes more complicated with the next-line
medications only being started if certain T score and other risk factor criteria being met. Raloxifene
and strontium ranelate were recommended as next-line drugs in the NICE criteria but following
recent safety concerns regarding strontium ranelate it is likely there will be an increasing role for
denosumab.

NICE published a technology appraisal looking at the role of denosumab in 2010. A link is provided.

What are the known side-effects of denosumab?

Denosumab is generally well tolerated. Dyspnoea and diarrhoea are generally considered the two
most common side effects, occurring in around 1 in 10 patients. Other less common side effects
include hypocalcemia and upper respiratory tract infections.
What does the Drug Safety Update add?
Cases of atypical femoral fractures have been noted in patients taking denosumab. Doctors are
advised to look out for patients complaining of unusual thigh, hip or groin pain.

VITAMIN D SUPPLEMENTATION
Vitamin D supplementation has been a hot topic for a number of years now. The muddied waters
are now slightly clearer following the release of the following:
 2012: letter by the Chief Medical Officer regarding vitamin D supplementation
 2013: National Osteoporosis Society (NOS) release UK Vitamin D guideline

The following groups should be advised to take vitamin D supplementation:

 all pregnant and breastfeeding women should take a daily supplement containing 10µg of
vitamin D
 all children aged 6 months - 5 years. Babies fed with formula milk do not need to take a
supplement if they are taking more than 500ml of milk a day, as formula milk is fortified with
vitamin D
 adults > 65 years
 'people who are not exposed to much sun should also take a daily supplement' e.g. housebound
patients

Testing for vitamin D deficiency

The key message is that not many people warrant a vitamin D test. The NOS guidelines specify that
testing may be appropriate in the following situations:
 patients with bone diseases that may be improved with vitamin D treatment e.g. known
osteomalacia or Paget's disease
 patients with bone diseases, prior to specific treatment where correcting vitamin deficiency is
appropriate e,g, prior to intravenous zolendronate or denosumab
 patients with musculoskeletal symptoms that could be attributed to vitamin D deficiency e.g.
bone pain ?osteomalacia

Patients with osteoporosis should always be given calcium/vitamin D supplements so testing is not
considered necessary. People who are at higher risk of vitamin D deficiency (see above) should be
treated anyway so again testing is not necessary.
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. The skull, spine/pelvis, and long bones of the lower extremities are most commonly
affected.

Predisposing factors
 increasing age
 male sex
 northern latitude
 family history

Clinical features - only 5% of patients are symptomatic

 the stereotypical presentation is an older male with bone pain and an isolated raised ALP
 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
 other markers of bone turnover include: procollagen type I N-terminal propeptide (PINP), serum
C-telopeptide (CTx), urinary N-telopeptide (NTx), and urinary hydroxyproline
 skull x-ray: thickened vault, osteoporosis circumscripta

 Indications for treatment include bone pain, skull or long bone deformity, fracture, periarticular
Paget's
 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
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.

*usually normal in this condition but hypercalcaemia may occur with prolonged immobilisation
BONE TUMOURS
Benign tumours

Tumour Notes
Osteoma  benign 'overgrowth' of bone, most typically occuring on the skull
 associated with Gardner's syndrome (a variant of familial
adenomatous polyposis, FAP)

Osteochondroma  most common benign bone tumour

(exotosis)  more in males, usually diagnosed in patients aged < 20 years
 cartilage-capped bony projection on the external surface of a bone

Giant cell tumour  tumour of multinucleated giant cells within a fibrous stroma
 peak incidence: 20-40 years
 occurs most frequently in the epiphyses of long bones
 X-ray shows a 'double bubble' or 'soap bubble' appearance

Malignant tumours

Tumour Notes
Osteosarcoma  most common primary malignant bone tumour
 seen mainly in children and adolescents
 occurs most frequently in the metaphyseal region of long bones prior to
epiphyseal closure, with 40% occuring in the femur, 20% in the tibia, and
10% in the humerus
 x-ray shows Codman triangle (from periosteal elevation) and 'sunburst'
pattern
 mutation of the Rb gene significantly increases risk of osteosarcoma (hence
association with retinoblastoma)
 other predisposing factors include Paget's disease of the bone and
radiotherapy

Ewing's sarcoma  small round blue cell tumour

 seen mainly in children and adolescents
 occurs most frequently in the pelvis and long bones. Tends to cause severe
pain
 associated with t(11;22) translocation which results in an EWS-FLI1 gene
product
 x-ray shows 'onion skin' appearance

Chondrosarcoma  malignant tumour of cartilage

 Tumour Notes
 most commonly affects the axial skeleton
 more common in middle-age

BONE DISORDERS: LAB VALUES

Disorder Calcium Phosphate ALP PTH
Osteoporosis Normal Normal Normal Normal
Osteomalacia Decreased Decreased Increased Increased
Primary hyperparathyroidism (→ osteitis fibrosa cystica) Increased Decreased Increased Increased
Chronic kidney disease (→ secondary hyperparathyroidism) Decreased Increased Increased Increased
Paget's disease Normal Normal Increased Normal
Osteopetrosis Normal Normal Normal Normal
TUMOUR NECROSIS FACTOR
Tumour necrosis factor (TNF) is a pro-inflammatory cytokine with multiple roles in the immune
system

TNF is secreted mainly by macrophages and has a number of effects on the immune system, acting
mainly in a paracrine fashion:
 activates macrophages and neutrophils
 acts as costimulator for T cell activation
 key mediator of bodies response to Gram negative septicaemia
 similar properties to IL-1
 anti-tumour effect (e.g. phospholipase activation)

TNF-alpha binds to both the p55 and p75 receptor. These receptors can induce apoptosis. It also
cause activation of NFkB

Endothelial effects include increase expression of selectins and increased production of platelet
activating factor, IL-1 and prostaglandins

TNF promotes the proliferation of fibroblasts and their production of protease and collagenase. It is
thought fragments of receptors act as binding points in serum

Systemic effects include pyrexia, increased acute phase proteins and disordered metabolism leading
to cachexia

TNF is important in the pathogenesis of rheumatoid arthritis - TNF blockers (e.g. infliximab,
etanercept) are now licensed for treatment of severe rheumatoid

TNF blockers
 infliximab: monoclonal antibody, IV administration
 etanercept: fusion protein that mimics the inhibitory effects of naturally occurring soluble TNF
receptors, subcutaneous administration
 adalimumab: monoclonal antibody, subcutaneous administration
 adverse effects of TNF blockers include reactivation of latent tuberculosis and demyelination

Infliximab is also used in active Crohn's disease unresponsive to steroids

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 include
 bone marrow depression
 nausea/vomiting
 pancreatitis
 increased risk of non-melanoma skin cancer

A significant interaction may occur with allopurinol and hence lower doses of azathioprine should be
used.

Azathioprine is generally considered safe to use in pregnancy.

MYCOPHENOLATE MOFETIL
Mode of action
 inhibits inosine monophosphate dehydrogenase, which is needed for purine synthesis
 as T and B cells are particularly dependent on this pathway it can reduce proliferation of immune
cells
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

 sleep problems, such as insomnia, hypersomnia, unrefreshing sleep, a disturbed sleep-wake
cycle
 muscle and/or joint pains
 headaches
 painful lymph nodes without enlargement
 sore throat
 cognitive dysfunction, such as difficulty thinking, inability to concentrate, impairment of short-
term memory, and difficulties with word-finding
 physical or mental exertion makes symptoms worse
 general malaise or 'flu-like' symptoms
 dizziness
 nausea
 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

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

Better prognosis in children

*children and young people only

DERMATOMYOSITIS
Overview
 an inflammatory disorder causing symmetrical, proximal muscle weakness and characteristic skin
lesions
 may be idiopathic or associated with connective tissue disorders or underlying malignancy
(typically ovarian, breast and lung cancer, found in 20-25% - more if patient older). Screening for
an underlying malignancy is usually performed following a diagnosis of dermatomyositis
 polymyositis is a variant of the disease where skin manifestations are not prominent

Skin features
 photosensitive
 macular rash over back and shoulder
 heliotrope rash in the periorbital region
 Gottron's papules - roughened red papules over extensor surfaces of fingers
 'mechanic's hands': extremely dry and scaly hands with linear 'cracks' on the palmar and lateral
aspects of the fingers
 nail fold capillary dilatation

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

Investigations
 the majority of patients (around 80%) are ANA positive
 around 30% of patients have antibodies to aminoacyl-tRNA synthetases (anti-synthetase
antibodies), including:
o antibodies against histidine-tRNA ligase (also called Jo-1)
o antibodies to signal recognition particle (SRP)
o anti-Mi-2 antibodies

DERMATOMYOSITIS: INVESTIGATIONS AND MANAGEMENT

Investigations
 elevated creatine kinase
 EMG
 muscle biopsy
 ANA positive in 60%
 anti-Mi-2 antibodies are highly specific for dermatomyositis, but are only seen in around 25% of
patients
 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

POLYMYOSITIS
Overview
 inflammatory disorder causing symmetrical, proximal muscle weakness
 thought to be a T-cell mediated cytotoxic process directed against muscle fibres
 may be idiopathic or associated with connective tissue disorders
 associated with malignancy
 dermatomyositis is a variant of the disease where skin manifestations are prominent, for
example a purple (heliotrope) rash on the cheeks and eyelids
 typically affects middle-aged, female:male 3:1

Features
 proximal muscle weakness +/- tenderness
 Raynaud's
 respiratory muscle weakness
 interstitial lung disease: e.g. fibrosing alveolitis or organising pneumonia
 dysphagia, dysphonia

Investigations
 elevated creatine kinase
 other muscle enzymes (lactate dehydrogenase (LD), aldolase, AST and ALT) are also elevated in
85-95% of patients
 EMG
 muscle biopsy
 anti-synthetase antibodies
o anti-Jo-1 antibodies are seen in pattern of disease associated with lung involvement,
Raynaud's and fever
POLYMYALGIA RHEUMATICA
Polymyalgia rheumatica (PMR) is a relatively common condition seen in older people characterised
by muscle stiffness and raised inflammatory markers. Whilst it appears to be closely related to
temporal arteritis the underlying cause is not fully understood and it does not appear to be a
vasculitic process.

Features
 typically patient > 60 years old
 usually rapid onset (e.g. < 1 month)
 aching, morning stiffness in proximal limb muscles
 weakness is not considered a symptom of polymyalgia rheumatica
 also mild polyarthralgia, lethargy, depression, low-grade fever, anorexia, night sweats

Investigations
 raised inflammatory markers e.g. ESR > 40 mm/hr
 note creatine kinase and EMG normal

Treatment
 prednisolone e.g. 15mg/od
o patients typically respond dramatically to steroids, failure to do so should prompt
consideration of an alternative diagnosis

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 around 5 times more likely to be affected
 typically presents between 30-50 years old

Features
 chronic pain: at multiple site, sometimes 'pain all over'
 lethargy
 cognitive impairment: 'fibro fog'
 sleep disturbance, headaches, dizziness are common

Diagnosis is clinical and sometimes refers to the American College of Rheumatology

classification criteria which lists 9 pairs of tender points on the body. If a patient is tender in at least
11 of these 18 points it makes a diagnosis of fibromyalgia more likely
The management of fibromyalgia is often difficult and needs to be tailored to the individual patient.
A psychosocial and multidisciplinary approach is helpful. Unfortunately there is currently a paucity
of evidence and guidelines to guide practice. 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.
 explanation
 aerobic exercise: has the strongest evidence base
 cognitive behavioural therapy
 medication: pregabalin, duloxetine, amitriptyline

MYOPATHIES
Features
 symmetrical muscle weakness (proximal > distal)
 common problems are rising from chair or getting out of bath
 sensation normal, reflexes normal, no fasciculation

Causes
 inflammatory: polymyositis
 inherited: Duchenne/Becker muscular dystrophy, myotonic dystrophy
 endocrine: Cushing's, thyrotoxicosis
 alcohol
ANCA
There are two main types of anti-neutrophil cytoplasmic antibodies (ANCA) - cytoplasmic (cANCA)
and perinuclear (pANCA)

For the exam, remember:

 cANCA - granulomatosis with polyangiitis (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
 granulomatosis with polyangiitis, 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%
 granulomatosis with polyangiitis, 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

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
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)

Pathophysiology
 autoimmune disease: SLE a type 3 hypersensitivity reaction
 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

*It is said the incidence in black Africans is much lower than in black Americans - the reasons for this
are unclear

SYSTEMIC LUPUS ERYTHEMATOSUS: FEATURES

Systemic lupus erythematosus (SLE) is a multisystem, autoimmune disorder. It typically presents in
early adulthood and is more common in women and people of Afro-Caribbean origin.

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

Musculoskeletal
 arthralgia
 non-erosive arthritis
Cardiovascular
 pericarditis: the most common cardiac manifestation
 myocarditis

Respiratory
 pleurisy
 fibrosing alveolitis

Renal
 proteinuria
 glomerulonephritis (diffuse proliferative glomerulonephritis is the most common type)

Neuropsychiatric
 anxiety and depression
 psychosis
 seizures

SYSTEMIC LUPUS ERYTHEMATOSUS: INVESTIGATIONS

Antibodies
 99% are ANA positive
o this high sensitivity makes it a useful rule out test, but it has low specificity
 20% are rheumatoid factor positive
 anti-dsDNA: highly specific (> 99%), but less sensitive (70%)
 anti-Smith: highly specific (> 99%), sensitivity (30%)
 also: anti-U1 RNP, SS-A (anti-Ro) and SS-B (anti-La)

Monitoring
 inflammatory markers
o ESR is generally used
o during active disease the CRP is characteristically normal - a raised CRP may indicate
underlying infection
 complement levels (C3, C4) are low during active disease (formation of complexes leads to
consumption of complement)
 anti-dsDNA titres can be used for disease monitoring (but note not present in all patients)
SYSTEMIC LUPUS ERYTHEMATOSUS: PREGNANCY

Overview
 risk of maternal autoantibodies crossing the placenta
 leads to a condition termed neonatal lupus erythematosus
 neonatal complications include congenital heart block
 strongly associated withanti-Ro (SSA) antibodies

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:

Limited cutaneous systemic sclerosis

 Raynaud's may be first sign
 scleroderma affects face and distal limbs predominately
 associated with anti-centromere antibodies
 a subtype of limited systemic sclerosis is CREST syndrome: Calcinosis, Raynaud's phenomenon,
oEsophageal dysmotility, Sclerodactyly, Telangiectasia

Diffuse cutaneous systemic sclerosis

 scleroderma affects trunk and proximal limbs predominately
 associated with scl-70 antibodies
 the most common cause of death is now respiratory involvement, which is seen in around 80%:
interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH)
 other complications include renal disease and hypertension
 poor prognosis

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

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 bilateral symptoms.

Factors suggesting underlying connective tissue disease

 onset after 40 years
 unilateral symptoms
 rashes
 presence of autoantibodies
 features which may suggest rheumatoid arthritis or SLE, for example arthritis or recurrent
miscarriages
 digital ulcers, calcinosis
 very rarely: chilblains

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

Management
 all patients with suspected secondary Raynaud's phenomenon should be referred to secondary
care
 first-line: calcium channel blockers e.g. nifedipine
 IV prostacyclin (epoprostenol) infusions: effects may last several weeks/months

DISCOID LUPUS ERYTHEMATOUS

Discoid lupus erythematosus is a benign disorder generally seen in younger females. It very rarely
progresses to systemic lupus erythematosus (in less than 5% of cases). Discoid lupus erythematosus
is characterised by follicular keratin plugs and is thought to be autoimmune in aetiology
Features
 erythematous, raised rash, sometimes scaly
 may be photosensitive
 more common on face, neck, ears and scalp
 lesions heal with atrophy, scarring (may cause scarring alopecia), and pigmentation

Management
 topical steroid cream
 oral antimalarials may be used second-line e.g. hydroxychloroquine
 avoid sun exposure

Discoid lupus erythematous affecting the scalp

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
 arthralgia
 myalgia
 skin (e.g. malar rash) and pulmonary involvement (e.g. pleurisy) are common
 ANA positive in 100%, dsDNA negative
 anti-histone antibodies are found in 80-90%
 anti-Ro, anti-Smith positive in around 5%
A woman with drug-induced lupus

Most common causes

 procainamide
 hydralazine

Less common causes

 isoniazid
 minocycline
 phenytoin

SJOGREN'S SYNDROME
Sjogren's syndrome is an 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
 dry eyes: keratoconjunctivitis sicca
 dry mouth
 vaginal dryness
 arthralgia
 Raynaud's, myalgia
 sensory polyneuropathy
 recurrent episodes of parotitis
 renal tubular acidosis (usually subclinical)
Investigation
 rheumatoid factor (RF) positive in nearly 100% of patients
 ANA positive in 70%
 anti-Ro (SSA) antibodies in 70% of patients with PSS
 anti-La (SSB) antibodies in 30% of patients with PSS
 Schirmer's test: filter paper near conjunctival sac to measure tear formation
 histology: focal lymphocytic infiltration
 also: hypergammaglobulinaemia, low C4

Management
 artificial saliva and tears
 pilocarpine may stimulate saliva production

MIXED CONNECTIVE TISSUE DISEASE

Mixed connective tissue disease (MCTD, Sharp's syndrome) is a rare, heterogeneous, multi-system
autoimmune disorder. It is a distinct clinical entity, but features of systemic lupus erythematosus
(SLE), systemic sclerosis (SSc) and myositis may all be present. It is associated with anti-U1
ribonucleoprotein (RNP) antibodies.* It is not to be confused with 'undifferentiated connective
tissue disease'.**

Epidemiology
 Male:female ratio 1:3
 Average age of presentation 30-40, may present in children
 Rare - incidence in adult population is estimated to be 2.1/million/year in one Norwegian study

Presentation:
 Raynaud's phenomenon often precedes other symptoms and occurs in 90% of cases
 Polyarthralgia/arthritis
 Myalgia
 'Sausage fingers'(dactylitis)

Other clinically important features:

 Dermatological: photosensitive rash, scleroderma-like changes, alopecia
 Oesophageal dysfunction
 Respiratory: pleuritis, pulmonary hypertension, interstitial lung disease
 Haematological: anaemia, lymphadenopathy, splenomegaly, rarely TTP
 Cardiac: pericarditis, pericardial effusion, accelerated coronary artery disease
 Renal: glomerulonephritis (tends to be milder than SLE)
 Neuropsychiatric: seizures, mood disturbance
Investigations:
 Exclude other connective tissue disease/vasculitis
 Bloods FBC: anaemia, leucopenia, thrombocytopenia, U+E: renal impairment, CRP/ESR raised
 ANA (usually) positive, anti Ds-DNA and scleroderma-specific antibodies (e.g. Anti-Scl70) are
negative
 Anti-U1 RNP (an extractable nuclear antigen, ENA), must be positive*.
 Organ-specific investigations, e.g. ECG, echo, CT chest, MRI brain

Management:
 No large-scale trials - patients have been included in trials for SLE/SSc and show similar levels of
response to immunosuppression/DMARDs
 Calcium channel blockers may be used for the treatment of Raynaud's
 Proton pump inhibitors for reflux disease
 Endothelin receptor antagonists/prostacyclin analogues in pulmonary hypertension
 Smoking cessation, moderate exercise

Prognosis:
 1/3 long-term remission, 1/3 have chronic symptoms, 1/3 develop severe systemic involvement
and premature death.

*Note that anti-U1 RNP antibodies are not completely specific and may also be seen in definite SSc
and SLE
**Undifferentiated connective tissue disease refers to syndromes in which features of one or more
'classical' connective tissue disease may be present, but do not meet diagnostic criteria. Anti-U1
RNP is absent.

MARFAN'S SYNDROME
Marfan's syndrome is an autosomal dominant connective tissue disorder. It is caused by a defect in
the FBN1 gene on chromosome 15 that codes for the protein fibrillin-1. It affects around 1 in 3,000
people.

Features
 tall stature with arm span to height ratio > 1.05
 high-arched palate
 arachnodactyly
 pectus excavatum
 pes planus
 scoliosis of > 20 degrees
 heart: dilation of the aortic sinuses (seen in 90%) which may lead to aortic aneurysm, aortic
dissection, aortic regurgitation, mitral valve prolapse (75%),
 lungs: repeated pneumothoraces
 eyes: upwards lens dislocation (superotemporal ectopia lentis), blue sclera, myopia
 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.

EHLER-DANLOS SYNDROME
Ehler-Danlos syndrome is an autosomal dominant connective tissue disorder that mostly affects
type III collagen. This results in the tissue being more elastic than normal leading to joint
hypermobility and increased elasticity of the skin.

Features and complications

 elastic, fragile skin
 joint hypermobility: recurrent joint dislocation
 easy bruising
 aortic regurgitation, mitral valve prolapse and aortic dissection
 subarachnoid haemorrhage
 angioid retinal streaks
RHEUMATOID ARTHRITIS: EPIDEMIOLOGY
Epidemiology
 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: ANTIBODIES

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

 Rose-Waaler test: sheep red cell agglutination
 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:

 Sjogren's syndrome (around 100%)
 Felty's syndrome (around 100%)
 infective endocarditis (= 50%)
 SLE (= 20-30%)
 systemic sclerosis (= 30%)
 general population (= 5%)
 rarely: TB, HBV, EBV, leprosy

Anti-cyclic citrullinated peptide antibody

Anti-cyclic citrullinated peptide antibody may be detectable up to 10 years before the development
of rheumatoid arthritis. It may therefore play a key role in the future of rheumatoid arthritis,
allowing early detection of patients suitable for aggressive anti-TNF therapy. It has a sensitivity
similar to rheumatoid factor (around 70%) with a much higher specificity of 90-95%.

NICE recommends that patients with suspected rheumatoid arthritis who are rheumatoid factor
negative should be test for anti-CCP antibodies.
RHEUMATOID ARTHRITIS: PRESENTATION
Typical features
 swollen, painful joints in hands and feet
 stiffness worse in the morning
 gradually gets worse with larger joints becoming involved
 presentation usually insidiously develops over a few months
 positive 'squeeze test' - discomfort on squeezing across the metacarpal or metatarsal joints

Swan neck and boutonnière deformities are late features of rheumatoid arthritis and unlikely to be
present in a recently diagnosed patient.

Other presentations:
 acute onset with marked systemic disturbance
 relapsing/remitting monoarthritis of different large joints (palindromic rheumatism)

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)

Key
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 2
large joints)
 Factor Scoring
4 - 10 small joints (with or without involvement 3
of large joints)
10 joints (at least 1 small joint) 5
B. Serology (at least 1 test result is needed
for classification)
Negative RF and negative ACPA 0
Low-positive RF or low-positive ACPA 2
High-positive RF or high-positive ACPA 3
C. Acute-phase reactants (at least 1 test
result is needed for classification)
Normal CRP and normal ESR 0
Abnormal CRP or abnormal ESR 1
D. Duration of symptoms
< 6 weeks 0
> 6 weeks 1

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 ARTHRITIS: MANAGEMENT

The management of rheumatoid arthritis (RA) has been revolutionised by the introduction of
disease-modifying therapies in the past decade.

Patients with evidence of joint inflammation should start a combination of disease-modifying drugs
(DMARD) as soon as possible. Other important treatment options include analgesia, physiotherapy
and surgery.

Initial therapy
 In 2018 NICE updated their rheumatoid arthritis guidelines. They now recommend DMARD
monotherapy +/- a short-course of bridging prednisolone. In the past dual DMARD therapy was
advocated as the initial step.
Monitoring response to treatment
 NICE recommends using a combination of CRP and disease activity (using a composite score such
as DAS28) to assess response to treatment

Flares
 flares of RA are often managed with corticosteroids - oral or intramuscular

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

TNF-inhibitors
 the current indication for a TNF-inhibitor is an inadequate response to at least two DMARDs
including methotrexate
 etanercept: recombinant human protein, acts as a decoy receptor for TNF-α, subcutaneous
administration, can cause demyelination, risks include reactivation of tuberculosis
 infliximab: monoclonal antibody, binds to TNF-α and prevents it from binding with TNF
receptors, intravenous administration, risks include reactivation of tuberculosis
 adalimumab: monoclonal antibody, subcutaneous administration

Rituximab
 anti-CD20 monoclonal antibody, results in B-cell depletion
 two 1g intravenous infusions are given two weeks apart
 infusion reactions are common

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

LEFLUNOMIDE
Leflunomide is a disease modifying anti-rheumatic drug (DMARD) mainly used in the management
of rheumatoid arthritis. It has a very long half-life which should be remembered considering it's
teratogenic potential.
Contraindications
 pregnancy - the BNF advises: 'Effective contraception essential during treatment and for at least
2 years after treatment in women and at least 3 months after treatment in men (plasma
concentration monitoring required'
 caution should also be exercised with pre-existing lung and liver disease

Adverse effects
 gastrointestinal, especially diarrhoea
 hypertension
 weight loss/anorexia
 peripheral neuropathy
 myelosuppression
 pneumonitis

Monitoring
 FBC/LFT and blood pressure

Stopping
 leflunomide has a very long wash-out period of up to a year which requires co-administration of
cholestyramine

HYDROXYCHLOROQUINE
Hydroxychloroquine is used in the management of rheumatoid arthritis and systemic/discoid lupus
erythematosus. It is pharmacologically very similar to chloroquine which is used to treat certain
types of malaria.

Adverse effects
 bull's eye retinopathy - may result in severe and permanent visual loss
o recent data suggest that retinopathy caused by hydroxychloroquine is more common than
previously thought and the most recent RCOphth guidelines (March 2018) suggest colour
retinal photography and spectral domain optical coherence tomography scanning of the
macula
o baseline ophthalmological examination and annual screening is generally recommened

A contrast to many drugs used in rheumatology, hydroxychloroquine may be used if needed in

pregnant women.

Monitoring
 the BNF advises: 'Ask patient about visual symptoms and monitor visual acuity annually using the
standard reading chart'
METHOTREXATE
Methotrexate is an antimetabolite that inhibits dihydrofolate reductase, an enzyme essential for the
synthesis of purines and pyrimidines. It is considered an 'important' drug as whilst it can be very
effective in controlling disease the side-effects may be potentially life-threatening - careful
prescribing and close monitoring is essential.

Indications
 inflammatory arthritis, especially rheumatoid arthritis
 psoriasis
 some chemotherapy acute lymphoblastic leukaemia

Adverse effects
 mucositis
 myelosuppression
 pneumonitis
 pulmonary fibrosis
 liver fibrosis
 mucositis

Pregnancy
 women should avoid pregnancy for at least 6 months after treatment has stopped
 the BNF also advises that men using methotrexate need to use effective contraception for at
least 6 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)

Interactions
 avoid prescribing trimethoprim or co-trimoxazole concurrently - increases risk of marrow aplasia
 high-dose aspirin increases the risk of methotrexate toxicity secondary to reduced excretion

Methotrexate toxicity
 the treatment of choice is folinic acid
SULFASALAZINE
Sulfasalazine is a disease modifying anti-rheumatic drug (DMARDs) used in the management of
inflammatory arthritis, especially rheumatoid arthritis. It is also used in the management of
inflammatory bowel disease.

Sulfasalazine is a prodrug for 5-ASA which works through decreasing neutrophil chemotaxis
alongside suppressing proliferation of lymphocytes and pro-inflammatory cytokines.

Cautions
 G6PD deficiency
 allergy to aspirin or sulphonamides (cross-sensitivity)

Adverse effects
 oligospermia
 Stevens-Johnson syndrome
 pneumonitis / lung fibrosis
 myelosuppression, Heinz body anaemia, megaloblastic anaemia
 may colour tears → stained contact lenses

In contrast to other DMARDs, sulfasalazine is considered safe to use in both pregnancy and
breastfeeding.

RHEUMATOID ARTHRITIS: DRUG SIDE-EFFECTS

The table below lists some of the characteristic (if not common) side-effects of drugs used to treat
rheumatoid arthritis:

Drug Side-effects
Methotrexate Myelosuppression
Liver cirrhosis
Pneumonitis
Sulfasalazine Rashes
Oligospermia
Heinz body anaemia
Interstitial lung disease
Leflunomide Liver impairment
Interstitial lung disease
Hypertension
Hydroxychloroquine Retinopathy
Corneal deposits
 Drug Side-effects
Prednisolone Cushingoid features
Osteoporosis
Impaired glucose tolerance
Hypertension
Cataracts
Gold Proteinuria
Penicillamine Proteinuria
Exacerbation of myasthenia gravis
Etanercept Demyelination
Reactivation of tuberculosis
Infliximab Reactivation of tuberculosis
Adalimumab Reactivation of tuberculosis
Rituximab Infusion reactions are common
NSAIDs (e.g. naproxen, ibuprofen) Bronchospasm in asthmatics
Dyspepsia/peptic ulceration

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

 rheumatoid factor positive
 poor functional status at presentation
 HLA DR4
 X-ray: early erosions (e.g. after < 2 years)
 extra articular features e.g. nodules
 insidious onset
 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.

RHEUMATOID ARTHRITIS: 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
 patients with early or poorly controlled RA should be advised to defer conception until their
disease is more stable
 RA symptoms tend to improve in pregnancy but only resolve in a small minority. Patients tend to
have a flare following delivery
 methotrexate is not safe in pregnancy and needs to be stopped at least 6 months before
conception
 leflunomide is not safe in pregnancy
 sulfasalazine and hydroxychloroquine are considered safe in pregnancy
 interestingly studies looking at pregnancy outcomes in patients treated with TNF-α 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-α blockers when they found out they were
pregnant
 low-dose corticosteroids may be used in pregnancy to control symptoms
 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
 patients should be referred to an obstetric anaesthetist due to the risk of atlanto-axial
subluxation

RHEUMATOID ARTHRITIS: COMPLICATIONS

A wide variety of extra-articular complications occur in patients with rheumatoid arthritis (RA):
 respiratory: pulmonary fibrosis, pleural effusion, pulmonary nodules, bronchiolitis obliterans,
methotrexate pneumonitis, pleurisy
 ocular: keratoconjunctivitis sicca (most common), episcleritis, scleritis, corneal ulceration,
keratitis, steroid-induced cataracts, chloroquine retinopathy
 osteoporosis
 ischaemic heart disease: RA carries a similar risk to type 2 diabetes mellitus
 increased risk of infections
 depression

Less common
 Felty's syndrome (RA + splenomegaly + low white cell count)
 amyloidosis
TEMPORAL ARTERITIS
Temporal arteritis is large vessel vasculitis which overlaps with polymyalgia rheumatica (PMR).
Histology shows changes which characteristically 'skips' certain sections of affected artery whilst
damaging others.

Features
 typically patient > 60 years old
 usually rapid onset (e.g. < 1 month)
 headache (found in 85%)
 jaw claudication (65%)
 visual disturbances secondary to anterior ischemic optic neuropathy
 tender, palpable temporal artery
 around 50% have features of PMR: aching, morning stiffness in proximal limb muscles (not
weakness)
 also lethargy, depression, low-grade fever, anorexia, night sweats

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

Treatment
 high-dose prednisolone - there should be a dramatic response, if not the diagnosis should be
reconsidered
 urgent ophthalmology review. Patients with visual symptoms should be seen the same-day by an
ophthalmologist. Visual damage is often irreversible

POLYARTERITIS NODOSA
Polyarteritis nodosa (PAN) is 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
 fever, malaise, arthralgia
 weight loss
 hypertension
 mononeuritis multiplex, sensorimotor polyneuropathy
 testicular pain
 livedo reticularis
 haematuria, renal failure
 perinuclear-antineutrophil cytoplasmic antibodies (ANCA) are found in around 20% of patients
with 'classic' PAN
 hepatitis B serology positive in 30% of patients

Livedo reticularis
Angiogram from a patient with polyarteritis nodosa. Both kidneys demonstrate beading and numerous microaneurysms
affecting the intrarenal vessels. Similar changes are seen affecting the intrahepatic vessels with a few small
microaneurysms noted. The proximal branches of the SMA appears normal; however there are no normal straight
arteries from the jejunal arteries and lack of normal anastomotic arcades and loops. This is associated with multiple
microaneurysms.
BEHCET'S SYNDROME
Behcet's syndrome is 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 B51
 around 30% of patients have a positive family history

Features
 classically: 1) oral ulcers 2) genital ulcers 3) anterior uveitis
 thrombophlebitis and deep vein thrombosis
 arthritis
 neurological involvement (e.g. aseptic meningitis)
 GI: abdo pain, diarrhoea, colitis
 erythema nodosum

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

*more specifically HLA B51, a split antigen of HLA B5

ANTIPHOSPHOLIPID SYNDROME
Antiphospholipid syndrome is an acquired disorder characterised by a predisposition to both venous
and arterial thromboses, recurrent fetal loss and thrombocytopenia. It may occur as a primary
disorder or secondary to other conditions, most commonly systemic lupus erythematosus (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
 venous/arterial thrombosis
 recurrent fetal loss
 livedo reticularis
 thrombocytopenia
 prolonged APTT
 other features: pre-eclampsia, pulmonary hypertension

Associations other than SLE

 other autoimmune disorders
 lymphoproliferative disorders
 phenothiazines (rare)

Management - based on BCSH guidelines

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

Decreased excretion of uric acid

 drugs*: diuretics
 chronic kidney disease
 lead toxicity

Increased production of uric acid

 myeloproliferative/lymphoproliferative disorder
 cytotoxic drugs
 severe psoriasis

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

*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

GOUT: DRUG CAUSES

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).

Drug causes
 diuretics: thiazides, furosemide
 ciclosporin
 alcohol
 cytotoxic agents
 pyrazinamide
 aspirin: it was previously thought that only high-dose aspirin could precipitate gout. However, a
systematic review (see link) showed that low-dose (e.g. 75mg) also increases the risk of gout
attacks. This obviously needs to be balanced against the cardiovascular benefits of aspirin and
the study showed patients coprescribed allopurinol were not at an increased risk
GOUT: FEATURES
Gout is a form of inflammatory arthritis. Patients typically have episodes lasting several days when
their gout flares and are often symptom-free between episodes. The acute episodes typically
develop maximal intensity with 12 hours/ The main features it presents with are:
 pain: this is often very significant
 swelling
 erythema

Around 70% of first presentations affect the 1st metatarsophalangeal (MTP) joint. Attacks of gout
affecting this area were historically called podagra. Other commonly affected joints include:
 ankle
 wrist
 knee

If untreated repeated acute episodes of gout can damage the joints resulting in a more chronic joint
problem.

Radiological features of gout include:

 joint effusion is an early sign
 well-defined 'punched-out' erosions with sclerotic margins ina juxta-articular distribution, often
with overhanging edges
 relative preservation of joint space until late disease
 eccentric erosions
 no periarticular osteopenia (in contrast to rheumatoid arthritis)
 soft tissue tophi may be seen

X ray of a patient with gout affecting his feet. It demonstrates juxta-articular erosive changes around the 1st MTP joint
with overhanging edges and associated with a moderate soft tissue swelling. The joint space is maintained.
X-ray of a patient with gout affecting his hands. There are multiple periarticular erosions bilaterally with adjacent large
soft tissue masses and relatively preserved joint spaces. In the right hand, these findings are most prominent at the 1st
interphalangeal, 2nd-4th proximal interphalangeal, 1st-3rd metacarpophalangeal and carpometacarpal joints. In the left
hand, the findings are most prominent at the ulnar styloid, scapholunate joint, first and fifth carpometacarpal joints,
second and fifth metacarpophalangeal joints and 1st interphalangeal joint.

GOUT: MANAGEMENT
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 > 450 µmol/l)

Acute management
 NSAIDs or colchicine are first-line
 the maximum dose of NSAID should be prescribed until 1-2 days after the symptoms have
settled. Gastroprotection (e.g. a proton pump inhibitor) may also be indicated
 colchicine* has a slower onset of action. The main side-effect is diarrhoea
 oral steroids may be considered if NSAIDs and colchicine are contraindicated. A dose of
prednisolone 15mg/day is usually used
 another option is intra-articular steroid injection
 if the patient is already taking allopurinol it should be continued
Indications for urate-lowering therapy (ULT)
 the British Society of Rheumatology Guidelines now advocate offering urate-lowering therapy to
all patients after their first attack of gout
 ULT is particularly recommended if:
 → >= 2 attacks in 12 months
 → tophi
 → renal disease
 → uric acid renal stones
 → prophylaxis if on cytotoxics or diuretics

Urate-lowering therapy
 allopurinol is first-line
 it has traditionally been taught that urate-lowering therapy should not be started until 2 weeks
after an acute attack, as starting too early may precipitate a further attack. The evidence base to
support this however looks weak
 in 2017 the BSR updated their guidelines. They still support a delay in starting urate-lowering
therapy because it is better for a patient to make long-term drug decisions whilst not in pain
 initial dose of 100 mg od, with the dose titrated every few weeks to aim for a serum uric acid of
< 300 µmol/l. Lower initial doses should be given if the patient has a reduced eGFR
 colchicine cover should be considered when starting allopurinol. NSAIDs can be used if colchicine
cannot be tolerated. The BSR guidelines suggest this may need to be continued for 6 months
 the second-line agent when allopurinol is not tolerated or ineffective is febuxostat (also a
xanthine oxidase inhibitor)
 in refractory cases other agents may be tried:
o uricase (urate oxidase) is an enzyme that catalyzes the conversion of urate to the degradation
product allantoin. It is present in certain mammals but not humans
o in patients who have persistent symptomatic and severe gout despite the adequate use of
urate-lowering therapy, pegloticase (polyethylene glycol modified mammalian uricase) can
achieve rapid control of hyperuricemia. It is given as an infusion once every two weeks

Lifestyle modifications
 reduce alcohol intake and avoid during an acute attack
 lose weight if obese
 avoid food high in purines e.g. Liver, kidneys, seafood, oily fish (mackerel, sardines) and yeast
products

Other points
 consideration should be given to stopping precipitating drugs (such as thiazides)
 losartan has a specific uricosuric action and may be particularly suitable for the many patients
who have coexistent hypertension
 increased vitamin C intake (either supplements or through normal diet) may also decrease serum
uric acid levels
*inhibits microtubule polymerization by binding to tubulin, interfering with mitosis. Also inhibits
neutrophil motility and activity

PSEUDOGOUT
Pseudogout is a form of microcrystal synovitis caused by the deposition of calcium pyrophosphate
dihydrate crystals in the synovium.

Risk factors
 haemochromatosis
 hyperparathyroidism
 acromegaly
 low magnesium, low phosphate
 Wilson's disease

Features
 knee, wrist and shoulders most commonly affected
 joint aspiration: weakly-positively birefringent rhomboid-shaped crystals
 x-ray: chondrocalcinosis
 in the knee this can be seen as linear calcifications of the meniscus and articular cartilage

Management
 aspiration of joint fluid, to exclude septic arthritis
 NSAIDs or intra-articular, intra-muscular or oral steroids as for gout
PSEUDOXANTHOMA ELASTICUM
Pseudoxanthoma elasticum is an inherited condition (usually autosomal recessive*) characterised
by an abnormality in elastic fibres

Features
 retinal angioid streaks
 'plucked chicken skin' appearance - small yellow papules on the neck, antecubital fossa and
axillae
 cardiac: mitral valve prolapse, increased risk of ischaemic heart disease
 gastrointestinal haemorrhage

*there are reports of autosomal dominant inheritance in a minority of cases

RELAPSING POLYCHONDRITIS
Relapsing polychondritis is a multi-systemic condition characterised by repeated episodes of
inflammation and deterioration of cartilage. This most commonly affects the ears, however, can
affect other parts of the body such as the nose and joints.

Key features:
 Ears: auricular chondritis, hearing loss, vertigo
 Nasal: nasal chondritis → saddle-nose deformity
 Respiratory tract: e.g. hoarseness, aphonia, wheezing, inspiratory stridor
 Ocular: episcleritis, scleritis, iritis, and keratoconjunctivitis sicca
 Joints: arthralgia
 Less commonly: cardiac valcular regurgitation, cranial nerve palsies, peripheral neuropathies,
renal dysfunction

Diagnosis:
 Various scoring systems based on clinical, pathological, and radiological criteria

Treatment
 Induce remission: steroids
 Maintenance: azathioprine, methotrexate, cyclosporin, cyclophosphamide

LANGERHANS CELL HISTIOCYTOSIS

Langerhans cell histiocytosis is a rare condition associated with the abnormal proliferation of
histiocytes. It typically presents in childhood with bony lesions.
Features
 bone pain, typically in the skull or proximal femur
 cutaneous nodules
 recurrent otitis media/mastoiditis
 tennis racket-shaped Birbeck granules on electromicroscopy

FAMILIAL MEDITERRANEAN FEVER

Familial Mediterranean Fever (FMF, also known as recurrent polyserositis) is an autosomal recessive
disorder which typically presents by the second decade. It is more common in people of Turkish,
Armenian and Arabic descent

Features - attacks typically last 1-3 days

 pyrexia
 abdominal pain (due to peritonitis)
 pleurisy
 pericarditis
 arthritis
 erysipeloid rash on lower limbs

Management
colchicine may help

MCARDLE'S DISEASE
Overview
 autosomal recessive type V glycogen storage disease
 caused by myophosphorylase deficiency
 this causes decreased muscle glycogenolysis

Features
 muscle pain and stiffness following exercise
 muscle cramps
 myoglobinuria
 low lactate levels during exercise
STILL'S DISEASE IN ADULTS
Epidemiology
 has a bimodal age distribution - 15-25 yrs and 35-46 yrs

Features
 arthralgia
 elevated serum ferritin
 rash: salmon-pink, maculopapular
 pyrexia
o typically rises in the late afternoon/early evening in a daily pattern and accompanies a
worsening of joint symptoms and rash
 lymphadenopathy
 rheumatoid factor (RF) and anti-nuclear antibody (ANA) negative

The diagnosis of Still's disease in adults can be challenging. The Yamaguchi criteria is the most
widely used criteria and has a sensitivity of 93.5%.

Management
 NSAIDs
o should be used first-line to manage fever, joint pain and serositis
o they should be trialled for at least a week before steroids are added.
 steroids
o may control symptoms but won't improve prognosis
 if symptoms persist, the use of methotrexate, IL-1 or anti-TNF therapy can be considered