Polyarthritis: Differential diagnosis:

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

The picture shows joint subluxations and swan neck deformities, caused by recurrent episodes
of synovitis that damage tendon sheaths and slings resulting in joint deformity but, in this case,
there is no bone deformity.

Jaccoud's arthropathy is seen in:

1) SLE
2) Rheumatic fever
3) Parkinson's disease, and
4) Hypocomplementaemic urticarial vasculitis.

[1]
 Systemic lupus erythematosus
Epidemiology:
 much more common in females (F:M = 9:1)
 more common in Afro-Caribbean’s* and Asian communities
 onset is usually 20-40 years
 incidence has risen substantially during the past 50 years (3 fold using ACR criteria)
*It is said the incidence in black Africans is much lower than in black Americans -reason unclear
Pathophysiology:
 autoimmune disease, associated with HLA B8, DR2, DR3
 caused by immune system dysregulation leading to immune complex formation
 immune complex deposition can affect any organ including skin, joints, kidney & brain
 HAO hereditary angioneurotic oedema (deficiency of C1 esterase inhibitor): This leads
to persistent activation of classical complement pathway and C4 levels are frequently low,
If treatment fails to normalise C4 level, it is a high risk of developing SLE.
Features: SLE is a multisystem, autoimmune disorder.
General features:
1) fatigue
2) fever
3) mouth ulcers
4) lymphadenopathy
Skin:
1) malar (butterfly) rash: spares nasolabial folds
2) Discoid rash: scaly, erythematous, well demarcated rash in sun-exposed areas. Lesions
may progress to become pigmented and hyperkeratotic before becoming atrophic
3) photosensitivity
4) Raynaud's phenomenon
5) livedo reticularis
6) non-scarring alopecia
Musculoskeletal:
1) arthralgia
2) non-erosive arthritis
Cardiovascular:
1) myocarditis
2) Libmansack endocarditis.
Respiratory:
1) pleurisy
2) fibrosing alveolitis
Renal:
1) proteinuria
2) glomerulonephritis (diffuse proliferative glomerulonephritis is the most common type)
Neuropsychiatric:
1) anxiety, depression, psychosis ,seizures,

[2]
 2) subacute myelopathy with oligoclonal bands in serum and CSF (paraplegia)

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

Discoid lupus erythematosus

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

SACLE is ANA positive in 60% patients. However, only 10-15% progress to SLE with

moderate disease activity. 80% patients are anti-Ro antibody positive.Skin disease may
occur as part of SLE, or be present as CLE (frequently without any systemic disease), and
with variable chance of progression to SLE.
 Discoid lupus erythematosus (DLE)
 Subacute cutaneous lupus erythematosus (SACLE)
 Acute cutaneous lupus erythematosus (ACLE)
are examples of CLE which may or may not progress to SLE. However, ACLE often
accompanies flare of systemic disease & presents as diffuse erythema, maculopapular rash,
photosensitivity & oral ulcers, while DLE presents as well defined scaly plaques heal with
central scarring.‫( انظر الجلدية مكتوبة احسن‬p28)

[3]
Lupus nephritis
Histologically, a number of different types of renal disease are recognised in SLE, with immune-
complex mediated glomerular disease being the most common. The up to date International Society
of Nephrology/Renal Pathology Society 2003 classification divides these into six different patterns:
 I - minimal mesangial
 II - mesangial proliferative
 III - focal
 IV - diffuse
 V - membranous
 VI - advanced sclerosis
Glomeruli appear normal by light microscopy in minimal mesangial lupus nephritis, but
immunofluorescence demonstrates mesangial immune deposits.
Mesangial proliferative nephritis presents clinically as microscopic haematuria and/or proteinuria.
Hypertension is incommon and nephrotic syndrome and renal impairment are very rarely seen.
Biopsy demonstrates segmental areas of increased mesangial matrix and cellularity, with mesangial
immune deposits. A few isolated subepithelial or subendothelial deposits may be visible by
immunofluorescence.The prognosis is good and specific treatment is only indicated if the disease
progresses.
Focal disease is more advanced, but still affects less than 50% of glomeruli. Haematuria and
proteinuria is almost always seen, and nephrotic syndrome, hypertension and elevated creatinine
may be present. Biopsy demonstrates active or inactive focal, segmental or global endo- or
extracapillary glomerulonephritis involving less than 50% of glomeruli, typically with focal
subendothelial immune deposits, with or without mesangial alterations. It is further subdivided:
 A: Active lesions: focal proliferative lupus nephritis
 A/C: Active and chronic lesions: focal proliferative and sclerosing lupus nephritis
 C: Chronic inactive lesions with glomerular scars: focal sclerosing lupus nephritis
Prognosis is variable.
Diffuse glomerulonephritis is the most common and severe form of lupus nephritis. Haematuria and
proteinuria are almost always present, and nephrotic syndrome, hypertension and renal impairment
common. Biopsies demonstrate active or inactive diffuse, segmental or global endo- or extracapillary
glomerulonephritis involving more than 50% of all glomeruli, typically with diffuse subendothelial
immune deposits, with or without mesangial alterations. This class is divided into diffuse segmental
(IV-S) when more than 50% of the involved glomeruli have segmental lesions, and diffuse global (IV-
G) when more than 50% of involved glomeruli have global lesions. Segmental is defined as a
glomerular lesions that involves less than half of the glomerular tuft.
 IV-S (A): Active lesions, diffuse segmental proliferative lupus nephritis
 IV-G (A): Active lesions, diffuse global proliferative
 IV-S (A/C): Active and chronic lesions, diffuse segmental proliferative and sclerosing lupus
nephritis
 IV-S (C): Chronic inactive lesions with scars, diffuse segmental sclerosing lupus nephritis
 IV-G (C): Chronic inactive lesions with scars: diffuse global sclerosing lupus nephritis 

[4]
Immunosuppressive therapy is required in these cases to prevent progressive to end-stage renal
failure.
Patients with membranous lupus nephritis tend to present with nephrotic syndrome. Microscopic
haematuria and hypertension may also be seen. Biopsies show global or segmental subepithelial
immune deposits or their morphologic sequelae, with or without mesangial alterations. It may occur
in combination with class III or IV, in which case both are diagnosed. Progression is variable, and
immunosuppression is not always needed.
In advanced sclerosis, more than 90% of glomeruli are globally sclerosed without residual activity.
With regard to the management of lupus nephritis a biopsy is indicated in those patients with
abnormal urinalysis and/or reduced renal function. This can provide a histological classification as
well as information regarding activity, chronicity and prognosis.
Cyclophosphamide, mycophenolate mofetil and azathioprine reduce mortality in proliferative forms of
lupus glomerulonephritis.
IgA nephropathy is a form of glomerulonephritis characterised by the deposition of IgA in the
glomeruli. It is a very rare lesion in SLE.

[5]
 Drug-induced lupus
 In drug-induced lupus not all the typical features of SLE are seen, with renal and nervous
system involvement being unusual.
 It usually resolves on stopping the drug.
Features:
1) Arthralgia, fever, serositis
2) Myalgia, skin (e.g. malar rash) , papular purpuric erythematous
3) and pulmonary involvement (e.g. pleurisy) are common
4) ANA positive in 100%, dsDNA negative
5) anti-histone antibodies are found in 80-90%
6) anti-Ro, anti-Smith positive in around 5%

A woman with drug-induced lupus

Most common causes
1) procainamide
2) hydralazine
Less common causes
1) isoniazid, prazinamide
2) minocycline, statin, anti TNF alpha, INFs, sulfasalzine
3) phenytoin
SLE in pregnancy:
 risk of maternal autoantibodies crossing placenta leads to condition termed neonatal
lupus erythematous
 neonatal complications include congenital heart block (permanent & need PPM)
 strongly associated with anti-Ro (SSA) antibodies

Mixed connective tissue disease:

 Features of SLE, systemic sclerosis and polymyositis

[6]
 Anti-RNP positive

Antiphospholipid syndrome
 Acquired disorder characterised by:
1) a predisposition to both venous and arterial thromboses,
2) recurrent fetal loss and
3) thrombocytopenia
 A key point is that antiphospholipid syndrome causes a paradoxical rise in the APTT.
 This is due to an ex-vivo reaction of the lupus anticoagulant autoantibodies with
phospholipids involved in the coagulation cascade
Features:
1) venous/arterial thrombosis
2) recurrent fetal loss
3) thrombocytopenia, prolonged APTT (not corrected with addition of normal plasma)
4) livedo reticularis
5) other features: pre-eclampsia, pulmonary hypertension
6) It may occur as a primary disorder or secondary to other conditions, most commonly SLE
Associations other than SLE
1) other autoimmune disorders
2) lymphoproliferative disorders
3) phenothiazines (rare)
Management - based on BCSH guidelines
1) initial venous thromboembolic events: warfarin with a target INR of 2-3 for 6 months
2) recurrent venous thromboembolic events: lifelong warfarin; if occurred whilst taking
warfarin then increase target INR to 3-4
3) arterial thrombosis should be treated with lifelong warfarin with target INR 2-3
In pregnancy the following complications may occur:
1) recurrent miscarriage
2) IUGR
3) pre-eclampsia
4) placental abruption
5) pre-term delivery
6) venous thromboembolism
Management:
 low-dose aspirin should be commenced once the pregnancy is confirmed on urine testing
 LMWH: Started once a fetal heart is seen on ultrasound.
 discontinued at 34 weeks gestation
These interventions increase the live birth rate 7-fold
Extractable nuclear antigens:
 specific nuclear antigens, usually associated with being ANA positive
Examples:
[7]
 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
Rheumatoid arthritis
 peak onset = 30-50 years, although occurs in all age groups
 F:M ratio = 3:1
 prevalence = 1%
 some ethnic differences e.g. high in Native Americans
 associated with HLA-DR4 (especially Felty's syndrome)
Rheumatoid arthritis diagnosis:
NICE have stated that clinical diagnosis is more important than criteria such as those defined by
the American College of Rheumatology.
2010 American College of Rheumatology criteria:
Target population; Patients who
1) Have at least 1 joint with definite clinical synovitis
2) With the synovitis not better explained by another disease

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

Factor Scoring

A. Joint involvement 1 large joint 0

2 - 10 large joints 1

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

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

joints)

10 joints (at least 1 small joint) 5

Negative RF and negative ACPA 0

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

C. Acute-phase Normal CRP and normal ESR 0

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

[8]
Factor Scoring

D. Duration of < 6 weeks 0

symptoms
> 6 weeks 1
Rheumatoid arthritis: x-ray changes:
Early x-ray findings
 soft-tissue swelling
 loss of joint space
 juxta-articular osteopenia
Late x-ray findings:
 periarticular erosions
 subluxation

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

Other conditions associated with a positive RF include:

1) Sjogren's syndrome (around 100%)
2) Felty's syndrome (around 100%)
3) Cryoglobulinemia II & III 40-100%
4) Infective endocarditis (= 50%)
5) SLE (= 20-30%)
6) Systemic sclerosis (= 30%)
7) General population (= 5%)
8) rarely: TB, HBV, EBV, leprosy

Rheumatoid arthritis prognostic features:

Poor prognostic features:
1) rheumatoid factor positive
2) anti-CCP antibodies
3) HLA DR4
4) poor functional status at presentation
5) X-ray: early erosions (e.g. after < 2 years)
6) extra articular features e.g. nodules
7) insidious onset

[9]
 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 complications:

A wide variety of extra-articular complications occur in patients with rheumatoid arthritis (RA):
A) respiratory:
1) pulmonary fibrosis,
2) pulmonary nodules
3) Caplan's syndrome: massive fibrotic nodules with occupational coal dust exposure
4) pleurisy
5) pleural effusion,
6) bronchiectasis (especially non smokers) ,
7) bronchiolitis obliterans,
8) complications of drug therapy e.g. methotrexate pneumonitis, sulfasalzine, gold,
9) infection (possibly atypical) secondary to immunosuppression
B) ocular:
1) keratoconjunctivitis sicca (most common)
2) episcleritis (erythema)

3) scleritis (erythema and pain)

4) keratitis
5) corneal ulceration,
6) steroid-induced cataracts,
7) chloroquine retinopathy
C) osteoporosis
D) IHD: RA carries a similar risk to type 2 DM
E) increased risk of infections
F) depression

Less common complications:

1) Felty's syndrome (RA + splenomegaly + low white cell count+ leg ulcer) in chronic
seropositive RA
2) Amyloidosis (AA)

[10]
Management of Rheumatoid arthritis:
 The management of rheumatoid arthritis (RA) has been revolutionized by the introduction of
disease-modifying therapies in the past decade.
 NICE has issued and released general guidelines in 2009.
 Pts with joint inflammation should start a combination of DMARD ASAP.
 Other important treatment options include analgesia, physiotherapy and surgery.
Initial therapy:
In the 2009 NICE guidelines it recommends that patients with newly diagnosed active RA start a
combination of DMARDs (including methotrexate and at least one other DMARD, plus
short-term glucocorticoids)
1) DMARDs:
1) 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
2) sulfasalazine
3) leflunomide
4) hydroxychloroquine
2) TNF-inhibitors: (can cause Drug induced lupus)
 the current indication for TNF-inhibitor is an inadequate response to at least 2
DMARDs including methotrexate,
A) Etanercept:
 recombinant human protein,
 acts as a decoy receptor for TNF-α,
 SC,
 can cause demyelination,
 risks include reactivation of TB (less than Infliximab & Adalimumab, in first 3 months)
B) Infliximab:
 monoclonal antibody,
 binds to TNF-α and prevents it from binding with TNF receptors,
 IV,

[11]
  risks include reactivation of TB
C) Adalimumab:
 monoclonal antibody,
 SC
3) Rituximab:
 anti-CD20 monoclonal antibody,
 results in B-cell depletion
 two 1g intravenous infusions are given 2 weeks apart
 infusion reactions are common
4) Abatacept:
 fusion protein that modulates a key signal required for activation of T lymphocytes
 leads to decreased T-cell proliferation and cytokine production
 given as an infusion
 not currently recommend by NICE
Methotrexate:
 Methotrexate is an antimetabolite which inhibits DHFR dihydrofolate reductase, an enzyme
essential for the synthesis of purines and pyrimidines
Indications:
1) rheumatoid arthritis
2) psoriasis
3) acute lymphoblastic leukaemia ALL
Adverse effects:
1) mucositis
2) myelosuppression
3) methotrexate pneumonitis (first few months of starting, should be stopped & never given )
4) pulmonary fibrosis
5) liver cirrhosis
Pregnancy:
 women should avoid pregnancy for at least 3 months after treatment has stopped
 BNF also advises that men using methotrexate need to use effective contraception for at
least 3 months after treatment
Prescribing methotrexate:
 Methotrexate is a drug with a high potential for patient harm. It is therefore important that you
are familiar with guidelines relating to its use;
1) methotrexate is taken weekly, rather than daily
2) 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'
3) folic acid 5mg once weekly should be co-prescribed, taken more than 24 hours after
methotrexate dose
4) the starting dose of methotrexate is 7.5 mg weekly (source: BNF)
5) only one strength of methotrexate tablet should be prescribed (usually 2.5 mg)
6) avoid prescribing trimethoprim or cotrimoxazole concurrently - increases risk of
marrow aplasia
[12]
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 (11% have low TPMT).

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

Rheumatoid arthritis in pregnancy:

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

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

Still's disease in adults:

 typically affects 16-35 year old
 typically RF negative
[13]
Features:
1) arthralgia, pyrexia
2) elevated serum ferritin
3) rash: salmon-pink, maculopapular
4) lymphadenopathy
5) rheumatoid factor (RF) and anti-nuclear antibody (ANA) negative

Felty's syndrome
1) (RA + splenomegaly + low white cell count+ leg ulcer) in longstanding RA
2) RF +ve 100%

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

Factors suggesting underlying connective tissue disease:

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

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

Management:
1) first-line: calcium channel blockers e.g. nifedipine
[14]
2) IV prostacyclin infusions: effects may last several weeks/months

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

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

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

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

Infiltrative lymphocytic syndrome (DILS) can present like Sjogren's syndrome:

 Parotid gland enlargement and sicca symptoms, 
[15]
 Extraglandular manifestations are common
 Mostly negative autoantibodies (Unlike Sjogren's)
 Peripheral motor neuropathy, cranial nerve palsies and Aseptic meningitis can also
occur.
 Lymphocytic interstitial pneumonitis is the most serious complication of DILS.

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

Spondyloarthropathies:
1) ankylosing spondylitis
2) psoriatic arthritis
3) Reiter's syndrome (including reactive arthritis)
4) enteropathic arthritis (associated with IBD, pauciarticular, asymmetric related to disease activity )

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

Clinical examination:
1) reduced lateral flexion

[16]
 2) Reduced forward flexion - Schober's test - a line is drawn 10 cm above and 5 cm below
the back dimples (dimples of Venus). The distance between the two lines should increase
by more than 5 cm when the patient bends as far forward as possible
3) reduced chest expansion

Other features - the 'A's:

1) Anterior uveitis
2) Apical fibrosis
3) AV node block
4) Aortic regurgitation
5) Achilles tendonitis
6) Amyloidosis
7) and cauda equina syndrome
8) peripheral arthritis (25%, more common if female)
Ankylosing spondylitis investigation:
1) Inflammatory markers (ESR, CRP) are typically raised although normal levels do not exclude
ankylosing spondylitis.
2) HLA-B27 is of little use in making the diagnosis as it is positive in:
 90% of patients with ankylosing spondylitis
 10% of normal patients
3) Spirometry may show a restrictive defect due to a combination of pulmonary fibrosis,
kyphosis and ankylosis of the costovertebral joints.
4) Plain x-ray of the sacroiliac joints is the most useful investigation in establishing the
diagnosis. Radiographs may be normal early in disease, later changes include:

1. sacroilitis: subchondral erosions, sclerosis, fusion of sacroiliac joints

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

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

There is typical spondylitis with spine. Complete bilateral and squaring of
appearance of well formed fusion of anterior sacroiliac vertebral bodies.
bamboo spine syndesmophytes and posterior joints. Squaring of
with a single elements in Sacroiliitis may anterior vertebral
central radiodense ankylosing present as margins is due to
[17]
line related to spondylitis, so sclerosis of osteitis of anterior
ossification of called bamboo joint margins corners.
supraspinous and spine which can be Syndesmophytes
interspinous asymmetrical are due to
ligaments which is at early stage ossification of
called dagger of disease, but outer fibers of
sign. Ankylosing is bilateral and annulus fibrosus
is detectable in symmetrical in
both sacroiliac late disease
joints

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

[18]
 Reactive arthritis
 Is one of the HLA-B27 (75%) 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 referred to as sexually acquired reactive arthritis, SARA).
 Reactive arthritis is defined as an arthritis that develops following an infection where the
organism cannot be recovered from the joint.
Features:
1) typically develops within 4 weeks of initial infection
2) symptoms generally last around 4-6 months
3) arthritis is typically an asymmetrical oligoarthritis of lower limbs
4) dactylitis
5) Around 25% of patients have recurrent episodes
6) 10% of patients develop chronic disease
7) symptoms of urethritis
8) eye:
 Conjunctivitis (seen in 50%),
 anterior uveitis
9) skin:
 circinate balanitis (painless vesicles on the coronal margin of the prepuce),
 keratoderma blenorrhagica (waxy yellow/brown papules on palms and soles)

Keratoderma blenorrhagica
Epidemiology:

[19]
 1)post-STI form much more common in men (e.g. 10:1)
2) post-dysenteric form equal sex incidence
The table below shows the organisms that are most commonly asso ciated with reactive arthritis:

Post-dysenteric form Post-STI form

Shigella flexneri Chlamydia trachomatis
Salmonella typhimurium,
Salmonella enteritidis
Yersinia enterocolitica
Campylobacter

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

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

Management:
 treat as rheumatoid arthritis
 but better prognosis

[20]
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.

[21]
*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

Osteoarthritis
 The first carpometacarpal joint is a frequent site of osteoarthritis in postmenopausal women,
 tenderness, stiffness, crepitus, swelling and pain on abduction of the thumb.
 Squaring of the hand, caused by swelling, radial subluxation of the metacarpal and atrophy of
the thenar muscles is a characteristic clinical sign.
X-ray changes:
1) decrease of joint space
2) subchondral sclerosis & cysts
3) osteophytes forming at joint margins
Management:
NICE published guidelines on the management of osteoarthritis (OA) in 2014

1) all patients should be offered help with weight loss, given advice about local muscle
strengthening exercises and general aerobic fitness
2) Paracetamol and topical NSAIDs are first-line analgesics.
 Topical NSAIDs are indicated only for OA of the knee or hand
3) Second-line treatment is:
 oral NSAIDs/COX-2 inhibitors (short term),
 opioids,
 capsaicin cream and
 intra-articular corticosteroids
 A proton pump inhibitor should be co-prescribed with NSAIDs and COX-2 inhibitors.
[22]
  These drugs should be avoided if the patient takes aspirin
4) non-pharmacological treatment options include supports and braces, TENS and shock
absorbing insoles or shoes
5) if conservative methods fail then refer for consideration of joint replacement
(TENS Transcutaneous electrical nerve stimulation)

What is the role of glucosamine?

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

Systemic sclerosis
 Systemic sclerosis is a condition of unknown aetiology characterised by hardened, sclerotic skin and other
connective tissues.
 It is 4 times more common in females
 Lung involvement is a frequent complication of systemic sclerosis, and can be split into two main
syndromes:
1) A pulmonary vascular disorder evolving over time into relatively isolated pulmonary hypertension
2) Interstitial lung disease.
 Raynaud's phenomenon is seen in 90-95% of patients with systemic sclerosis. It is the most common sign
of vascular involvement and is often one of the earliest clinical manifestations.

A) Limited cutaneous systemic sclerosis: (CREST syndrome)

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

B) Diffuse cutaneous systemic sclerosis:

 scleroderma affects trunk and proximal limbs predominately
 associated with scl-70 antibodies, poor prognosis
 HTN, lung fibrosis (decreased TLCO is early marker), pulmonary HTN (isolated or with lung
fibrosis) & renal involvement seen

[23]
  Scleroderma renal crisis (SRC) in up to 10% cases. SRC may present with rapid onset renal
failure, malignant hypertension, retinopathy, MAHA with schistocytes. 
HTN should be treated with an ACE inhibitor and calcium channel blockers can be added. 
C) Scleroderma (without internal organ involvement):
 tightening and fibrosis of skin
 may be manifest as plaques (morphoea) or linear

Antibodies:
 ANA positive in 90%
 RF positive in 30%
 anti-scl-70 antibodies associated with diffuse cutaneous systemic sclerosis
 anti-centromere antibodies associated with limited cutaneous systemic sclerosis
Dermatomyositis
Overview
 inflammatory disorder causing:
1) symmetrical, proximal muscle weakness and
2) charascteristic skin lesions
 may be idiopathic or associated with connective tissue disorders or underlying malignancy
(typically lung cancer, found in 20-25% - more if patient older)
 polymyositis is a variant of the disease where skin manifestations are not prominent
Skin features:
1) photosensitive
2) macular rash over back and shoulder
3) heliotrope rash in the periorbital region
4) Gottron's papules - roughened red papules over extensor surfaces of fingers
5) nail fold capillary dilatation

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

[24]
2) EMG
3) muscle biopsy
4) ANA positive in 60%
5) anti-Mi-2 antibodies are highly specific for dermatomyositis, but are only seen in around
25% of patients
6) anti-Jo-1 antibodies are not commonly seen in dermatomyositis - they are more common in
polymyositis where they are seen in a pattern of disease associated with lung
involvement, Raynaud's and fever

Management: prednisolone

Typical mechanics hands found in a subtype of polymyositis called antisynthetase syndrome or Jo-1
syndrome Raynaud's phenomenon, Myositis, Fibrosing alveolitis, and typical mechanic's hands (thickened,
cracking, and peeling skin).

Inclusion body myositis (IBM)

 An inflammatory condition that affects the over 50s men > women.
 Proximal muscles and finger flexors are predominantly involved
 The onset of muscle weakness is generally gradual (over months or years).
 Creatine kinase (CK) may be normal.
 Electromyogram (EMG) shows a similar pattern in polymyositis and IBM
 IBM not associated with malignancy.
 Biopsy in IBM shows intranuclear or cytoplasmic tubofilaments on electron microscopy.
 Polymyositis and dermatomyositis show a much better response to steroids than IBM.

Behcet's syndrome
 A complex multisystem disorder associated with presumed autoimmune mediated
inflammation of the arteries and veins.
 The precise aetiology has yet to be elucidated however. exacerbations and remissions
 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)
[25]
 Associated with HLA B5* and MICA6 allele. HLA B5 is associated with ocular disease; HLA
B12 is associated with recurrent oral ulcers.
 around 30% of patients have a positive FH
*more specifically HLA B51, a split antigen of HLA B5
Features:
1) classically: 1) oral ulcers 2) genital ulcers 3) anterior uveitis
2) thrombophlebitis, DVT (no risk of embolism)
3) arthritis, fever
4) neurological involvement (e.g. aseptic meningitis, headache)
5) GI: abdo pain, diarrhoea, colitis
6) erythema nodosum,
Diagnosis:
1) no definitive test
2) diagnosis based on clinical findings
3) positive pathergy test is suggestive (puncture site following needle prick becomes inflamed
with small pustule forming)
TTT: Corticosteroids in conjunction with immunosuppressants like azathioprine, cyclosporine,
and cyclophosphamide may be used in those with venous or arterial involvement (as the cause
of clot is inflammation of the vessel wall).
Anticoagulants, antiplatelet are not recommended (risk of pulmonary aneurysm rupture)
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 not a risk factor
 Fatigue is the central feature,
 other recognised features include
1) sleep problems, such as insomnia, hypersomnia, unrefreshing sleep, a disturbed
sleep-wake cycle
2) muscle and/or joint pains
3) headaches
4) painful lymph nodes without enlargement
5) sore throat
6) cognitive dysfunction, such as difficulty thinking, inability to concentrate, impairment
of short-term memory, and difficulties with word-finding
7) physical or mental exertion makes symptoms worse
8) general malaise or 'flu-like' symptoms
9) dizziness
10) nausea
11) palpitations

[26]
Investigation:
 NICE guidelines suggest carrying out a large number of screening blood tests to exclude
other pathology e.g. FBC, U&E, LFT, glucose, TFT, ESR, CRP, calcium, CK, ferritin*,
coeliac screening and also urinalysis

*children and young people only

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

Fibromyalgia
 Fibromyalgia is a syndrome characterised by widespread pain throughout the body with
tender points at specific anatomical sites.
 The cause of fibromyalgia is unknown.
Epidemiology:
 women are 10 times more likely to be affected, typically presents between 30-50 years old
Features:
1) chronic pain: at multiple site, sometimes 'pain all over'
2) lethargy
3) sleep disturbance, headaches, dizziness are common
Diagnosis:
1) Diagnosis is clinical
2) Sometimes refers to the American College of Rheumatology classification criteria which
list 9 pairs of tender points on the body.
3) If a patient is tender in at least 11 of these 18 points it makes the diagnosis more likely
Manaegement:
1) The management is often difficult and needs to be tailored to the individual patient.
2) A psychosocial and multidisciplinary approach is helpful.
3) Unfortunately there is currently a paucity of evidence and guidelines to guide practice.
4) The following is partly based on consensus guidelines from the European League against
Rheumatism (EULAR) published in 2007 and also a BMJ review in 2014.
1) explanation
2) aerobic exercise: has the strongest evidence base
3) cognitive behavioural therapy
[27]
 4) medication: pregabalin, duloxetine, amitriptyline

Polymyalgia rheumatic (PMR)

Pathophysiology:
 overlaps with temporal arteritis
 histology shows vasculitis with giant cells, characteristically 'skips' certain sections of
affected artery whilst damaging others
 muscle bed arteries affected most in polymyalgia rheumatica
Features: Polymyalgia rheumatica/temporal arteritis may be associated  with:
 Predominantly polymyalgia symptoms, for example, proximal muscle pain, stiffness(no
weakness)
or
 Arteritis symptoms, for example, headaches, scalp tenderness and jaw claudication.
1) typically patient > 60 years old
2) usually rapid onset (e.g. < 1 month)
3) aching, morning stiffness in proximal limb muscles (not weakness)
4) mild polyarthralgia, lethargy, depression, low-grade fever, anorexia, night sweats, Wt loss
Investigations:
 ESR > 40 mm/hr
 note CK and EMG normal(‫ عكس ال‬myositis and polymyositis)
 reduced CD8+ T cells
Treatment: prednisolone e.g. 15mg/od - dramatic response

 Corticosteroids remain the mainstay of treatment for polymyalgia rheumatica (PMR).

 The starting dose depends on patient's weight and severity of symptoms.
 The optimum duration of treatment is uncertain and is largely guided by response to therapy.

[28]
 Calcium and vitamin D supplementation should be initiated for all patients with PMR who are
starting corticosteroid therapy.
 Bisphosphonates should be added for long term steroid therapy.
 The usual starting dose is 15 mg prednisolone per day. Patients should expect relief of symptoms
within 24-72 hours.
 The dose should be increased if symptoms are not well controlled within one week.
 The effective starting dose should be maintained for two to four weeks after the patient becomes
asymptomatic.
 Generally, the daily dose can be lowered by 1.0-2.5 mg every two to four weeks to find the
minimum dose needed to maintain symptom suppression.
 Once the patient is reduced to 10 mg per day, the daily dose can be tapered by 1 mg every four
weeks.
 Tapering should be guided by clinical response.
 Normalisation of inflammatory markers (especially erythrocyte sedimentation rate [ESR]) are
helpful but should not set the guidelines for decreasing or stopping the treatment.
 An isolated increase of ESR without symptoms during the course of treatment is not a valid
reason to increase corticosteroid dose; however, a temporary delay in dosage reduction may be
necessary.
 Approximately 50-75% of patients can discontinue corticosteroid therapy after two years of
treatment.
 Relapses are more likely to occur during the initial 18 months of therapy and within one year of
corticosteroid withdrawal.
 Patients should be closely monitored for recurrence of symptoms throughout the period of
corticosteroid tapering and until 12 months after therapy stops.
 Methotrexate and azathioprine have been used in patients with corticosteroid intolerance or as
corticosteroid-sparing agents.
 These are generally reserved for patients in whom it has been difficult to reduce the prednisolone
after prolonged high dosages (for example, 10 mg or more per day for more than a year).
 These agents should be added to the prednisolone initially, but with a view to slowly reduce and
withdraw prednisolone.
 As with steroid therapy, azathioprine or methotrexate can be discontinued if there has been
sufficient response.

[29]
 Vasculitides
Marked constitutional (systemic) features: fever, malaise and weight loss. R‫هام‬..... ‫تذكر‬
ANCA should always be done in suspected systemic vasculitis.
Large vessel: TT
 Temporal arteritis
 Takayasu's arteritis
Medium vessel:
 polyarteritis nodosa
 Kawasaki disease
Small vessel:
1) ANCA-associated vasculitides (Wegener's*, Churg-Strauss*, microscopic polyangiitis)
2) Henoch-Schonlein purpura
3) cryoglobulinaemic vasculitis
*may also affect medium-sized vessels

Large Vessel Vasculitides

Temporal arteritis
 Temporal arteritis is large vessel vasculitis which overlaps with polymyalgia rheumatica.
 Histology shows changes which characteristically 'skips' certain sections of affected artery
whilst damaging others.
Features:
1) typically patient > 60 years old
2) usually rapid onset (e.g. < 1 month)
3) Headache (found in 85%)
[30]
 4) Jaw claudication (65%)
5) visual disturbances secondary to anterior ischemic optic neuropathy
6) tender, palpable temporal artery
7) features of PMR: aching, morning stiffness in proximal limb muscles (not weakness)
8) also lethargy, depression, low-grade fever, anorexia, night sweats

Investigations:
1) raised inflammatory markers:
 ESR > 50 mm/hr (note ESR < 30 in 10% of patients).
 CRP may also be elevated
2) temporal artery biopsy: skip lesions may be present
3) note CK and EMG normal
Treatment:
1) high-dose prednisolone - there should be a dramatic response, if not the diagnosis should
be reconsidered
2) Urgent ophthalmology review. Patients with visual symptoms should be seen the same-day
by an ophthalmologist.
3) Visual damage is often irreversible
Large Vessel Vasculitides
Takayasu's arteritis
 Takayasu's arteritis is a large vessel vasculitis.
 It typically causes occlusion of the aorta and questions commonly refer to an absent limb
pulse.
 It is more common in females and Asian people

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

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

Associations
[31]
  renal artery stenosis

Management:
 steroids

Medium Vessel Vasculitides

 polyarteritis nodosa
 Kawasaki disease

Polyarteritis nodosa (PAN)

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

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

[32]
Livedo reticularis

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

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

For the exam, remember:

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

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

pANCA:
 most common target is myeloperoxidase (MPO)

[33]
  cannot use level of pANCA to monitor disease activity
 associated with immune crescentic glomerulonephritis (positive in c. 80% of patients)
 microscopic polyangiitis, positive in 50-75%
 Churg-Strauss syndrome, positive in 60%
 primary sclerosing cholangitis, positive in 60-80%
 Wegener's granulomatosis, positive in 25%

Other causes of positive ANCA (usually pANCA)

 inflammatory bowel disease (UC > Crohn's) & autoimmune hepatitis

 connective tissue disorders: RA, SLE, Sjogren's

Non-vasculitic causes of positive ANCA have negative anti-myeloperoxidase antibodies (MPO)

Granulomatosis with polyangiitis

(Wegener's granulomatosis)
 Granulomatosis with polyangiitis is now the preferred term for Wegener's granulomatosis.
 It is an autoimmune condition associated with a necrotizing granulomatous vasculitis,
affecting both the upper and lower respiratory tract as well as the kidneys.
Features:
1) upper respiratory tract: epistaxis, sinusitis, nasal crusting
2) lower respiratory tract: dyspnoea, haemoptysis, cavitating lesions
3) rapidly progressive glomerulonephritis ('pauci-immune', 80% of patients)
4) saddle-shape nose deformity
5) also: vasculitic rash, eye involvement (e.g. proptosis), cranial nerve lesions

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

Management:
1) steroids
2) cyclophosphamide (90% response)

[34]
3) plasma exchange
4) median survival = 8-9 years

Chest x-ray from a young male patient

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

CT of the same patient showing the

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

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

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

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

[35]
Type I
 monoclonal - IgG or IgM
 associations: multiple myeloma, Waldenström macroglobulinaemia
Type II
 mixed monoclonal and polyclonal: usually with RF
 associations: hepatitis C, RA, Sjogren's, lymphoma
Type III
 polyclonal: usually with RF
 associations: RA, Sjogren's

Symptoms (if present in high concentrations)

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

Treatment:
1) immunosuppression
2) plasmapheresis
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)
 Acute Gout: 50% of all attacks and 70% of first attacks affect first metatarsophalangeal joint.
A) Decreased excretion of uric acid:
1) drugs*: diuretics
2) chronic kidney disease
3) lead toxicity

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

B) Increased production of uric acid:

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

Gout: drug causes

[36]
 1) thiazides, furosemide
2) alcohol
3) cytotoxic agents
4) pyrazinamide

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

Gout management:
A) Acute management:
1) NSAIDs
2) intra-articular steroid injection
3) Colchicine:
 has a slower onset of action.
 The main side-effect is diarrhoea
 It inhibits microtubule polymerization by binding to tubulin, interfering with mitosis. Also
inhibits neutrophil motility and activity
4) Oral steroids:
 May be considered if NSAIDs and colchicine are contraindicated.
 A dose of prednisolone 15mg/day is usually used
5) if the patient is already taking allopurinol it should be continued
B) Allopurinol prophylaxis:
1) allopurinol should not be started until 2 weeks after an acute attack has settled as it may
precipitate a further attack if started too early
2) initial dose of 100 mg od, with the dose titrated every few weeks to aim for a serum uric
acid of < 300 µmol/l
3) NSAID or colchicine cover should be used when starting allopurinol
Indications for allopurinol
1) recurrent attacks:
 the British Society for Rheumatology recommend In uncomplicated gout uric acid lowering
drug therapy should be started if a second attack, or further attacks occur within 1 year
2) tophi
3) renal disease
4) uric acid renal stones
5) prophylaxis if on cytotoxics or diuretics
6) patients with Lesch-Nyhan syndrome often take allopurinol for life
Lifestyle modifications:
1) reduce alcohol intake and avoid during an acute attack
2) lose weight if obese
3) avoid food high in purines e.g. Liver, kidneys, seafood, oily fish (mackerel, sardines) and
yeast products
Other points
[37]
1) increased vitamin C intake (either supplements or through normal diet) may also decrease
serum uric acid levels
2) Losartan has a specific uricosuric action and may be particularly suitable for the many
patients who have coexistent hypertension
3) calcium channel blockers also increase uric acid levels, possibly by a renal vasodilatory effect

Well defined punched-out juxta-articular erosions related to both sides of the first
metatarsal bone. This is a classical site for gout. Rat Bite

Pseudogout
 Pseudogout is a form of microcrystal synovitis
 caused by the deposition of calcium pyrophosphate dihydrate in the synovium
Risk factors:
1) hyperparathyroidism
2) hypothyroidism
3) acromegaly
4) low magnesium, low phosphate
5) haemochromatosis
6) Wilson's disease
Features:
1) knee, wrist and shoulders most commonly affected
2) joint aspiration: weakly-positively birefringent rhomboid shaped crystals
3) x-ray: chondrocalcinosis
Management:
1) aspiration of joint fluid, to exclude septic arthritis
2) NSAIDs or intra-articular, intra-muscular or oral steroids as for gout

[38]
 Familial Mediterranean Fever
 Familial Mediterranean Fever (FMF, also known as recurrent polyserositis)
 An autosomal recessive disorder
 typically presents by the second decade
 It is more common in people of Turkish, Armenian and Arabic descent

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

Management:
 colchicine may help

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

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

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

Investigation:
1) low calcium, phosphate, 25(OH) vitamin D
[39]
 2) raised alkaline phosphatase
3) x-ray:
Children - cupped, ragged metaphyseal surfaces;
Adults - translucent bands (Looser's zones or pseudofractures)

Treatment:
 calcium with vitamin D tablets

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

Investigation:
Calcium, phosphate and ALP are normal

Management:
Stem cell transplant and
Interferon-gamma have been used for treatment

Osteoporosis
Causes:
Risk Factors:
 Advancing age and female sex are significant risk factors for osteoporosis.
 Prevalence of osteoporosis increases from 2% at 50 years to more than 25% at 80 years in
women.

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

Other risk factors:

1) sedentary lifestyle
2) premature menopause
3) Caucasians and Asians
[40]
 4) endocrine disorders:
 hyperthyroidism, hyperparathyroidism ,
 hypogonadism (e.g. Turner's, testosterone deficiency),
 growth hormone deficiency, diabetes mellitus
5) multiple myeloma, lymphoma
6) gastrointestinal disorders: inflammatory bowel disease, malabsorption (e.g. Coeliac's),
gastrectomy, liver disease
7) chronic kidney disease
8) osteogenesis imperfecta, homocystinuria

Medications that may worsen osteoporosis (other than glucocorticoids):

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

Investigations for secondary causes:

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

Other procedures, if indicated

1) Lateral radiographs of lumbar and thoracic spine/DXA-based vertebral imaging
2) Protein immunoelectrophoresis and urinary Bence-Jones proteins
3) 25OH vitD
4) PTH
5) Serum testosterone, SHBG, FSH, LH (in men),
6) Serum prolactin
7) 24 hour urinary cortisol/dexamethasone suppression test
8) Endomysial and/or tissue transglutaminase antibodies (coeliac disease)
9) Isotope bone scan
10) Markers of bone turnover, when available
11) Urinary calcium excretion
[41]
So from the first list we should order the following bloods as a minimum for all patients:
1) full blood count
2) urea and electrolytes
3) liver function tests
4) bone profile
5) CRP
6) thyroid function tests

Osteoporosis: DEXA scan:

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

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

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

Treatment criteria for patients not taking alendronate:

[42]
 Unfortunately, a number of complicated treatment cut-off tables have been produced in the
latest guidelines for patients who do not tolerate alendronate
 These take into account a patients age, their T-score and the number of risk factors they
have from the following list:
1) parental history of hip fracture
2) alcohol intake of 4 or more units per day
3) rheumatoid arthritis
 The most important thing to remember is:
1) the T-score criteria for risedronate or etidronate are less than the others implying that
these are the second line drugs
2) if alendronate, risedronate or etidronate cannot be taken then strontium ranelate or
raloxifene may be given based on quite strict T-scores (e.g. a 60-year-old woman
would need a T-score < -3.5)
3) the strictest criteria are for denosumab
A) Bisphosphonates:
1) alendronate, risedronate and etidronate are all licensed for the prevention and
treatment of post-menopausal and glucocorticoid-induced osteoporosis
2) all three have been shown to reduce the risk of both vertebral and non-vertebral
fractures although alendronate, risedronate may be superior to etidronate in preventing
hip fractures
3) ibandronate is a once-monthly oral bisphosphonate

B) Vitamin D and calcium:

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

D) Strontium ranelate:
 dual action bone agent:
1) increases deposition of new bone by osteoblasts (promotes differentiation of pre-
osteoblast to osteoblast) and
2) reduces the resorption of bone by inhibiting osteoclasts
 Concerns regarding the safety profile of strontium have been raised recently.
 It should only be prescribed by a specialist in secondary care

[43]
  due to these concerns the European Medicines Agency in 2014 said it should only be
used by people for whom there are no other treatments for osteoporosis

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

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

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

G)Hormone replacement therapy:

 has been shown to reduce the incidence of vertebral fracture and non-vertebral
fractures
 due to concerns about increased rates of cardiovascular disease and breast cancer it
is no longer recommended for primary or secondary prevention of osteoporosis unless the
woman is suffering from vasomotor symptoms
H) Hip protectors:
 evidence to suggest significantly reduce hip fractures in nursing home patients
 compliance is a problem
I) Falls risk assessment:
 no evidence to suggest reduced fracture rates
 however, do reduce rate of falls and should be considered in management of high risk
patients
 Strontium ranelate: ------> Stevens Johnson syndrome----> TNE

 ‫تذكر الى كانوا بيعملوها‬

 penicillin, sulpha, phenytoin, cabamazebin, NSAID, allopurinol, Nevirapine

Glucocorticoid-induced Osteoporosis:
 We know that one of the most important risk factors for osteoporosis is the use of
corticosteroids.
[44]
 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:
 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.

Paget's disease of the bone

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

Predisposing factors:
 increasing age
 male sex
 northern latitude
 FH
Clinical features:
 only 5% of patients are symptomatic
 bone pain (e.g. pelvis, lumbar spine, femur)
 classical, untreated features: bowing of tibia, bossing of skull
[45]
  raised (ALP) - calcium* and phosphate are typically normal
 skull x-ray: thickened vault, osteoporosis circumscripta
 Angioid retinal streaks** in fundus
*usually normal in this condition but hypercalcaemia may occur with prolonged immobilisation
Indications for treatment:
 bone pain,
 skull or long bone deformity,
 fracture,
 periarticular Paget's
Treatment:
 bisphosphonate (either oral risedronate or IV zoledronate)
 calcitonin is less commonly used now
Complications:
 deafness (cranial nerve entrapment)
 bone sarcoma (1% if affected for > 10 years)
 high-output cardiac failure
 fractures
 skull thickening

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.

[46]
Isotope bone scan from a patient with Paget's disease showing a typical distribution in the
spine, asymmetrical pelvic disease and proximal long bones

Angioid streaks in retina

 **Irregular dark red streaks radiating from the optic nerve head.
 They are caused by degeneration, calcification and breaks in Bruch's membrane.
 Causes SLAPPERS:
 S - Sickle
 L - Lead poisoming
 A - Abetalipoproteinaemia/acromegaly
 P - Pagets/phacomatoses (tuberous sclerosis, neurofibromatosis, Sturge-Weber)
 P - Pseudoxanthoma elasticum
 E - Ehlers-Danlos
 R - Raised calcium or phosphate
 S – Short people (dwarfism).

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

Elbow pain:
[47]
Lateral Features:
epicondylitis 1) pain and tenderness localised to the lateral epicondyle
(tennis 2) pain worse on resisted wrist extension with the elbow extended or supination
elbow) of the forearm with the elbow extended
3) episodes typically last between 6 months and 2 years. Patients tend to have
acute pain for 6-12 weeks
Medial Features:
epicondylitis 1) pain and tenderness localised to the medial epicondyle
(golfer's 2) pain is aggravated by wrist flexion and pronation
elbow) 3) symptoms may be accompanied by numbness / tingling in the 4th and 5th
finger due to ulnar nerve involvement
Radial Most commonly due to compression of the posterior interosseous branch of
tunnel the radial nerve. It is thought to be a result of overuse.
syndrome Features:
1) symptoms are similar to lateral epicondylitis making it difficult to diagnose
2) however, the pain tends to be around 4-5 cm distal to the lateral epicondyle
3) symptoms may be worsened by extending the elbow and pronating the
forearm
Cubital Due to the compression of the ulnar nerve.
tunnel Features:
syndrome 1) initially intermittent tingling in the 4th and 5th finger
2) may be worse when the elbow is resting on a firm surface or flexed for
extended periods
3) later numbness in the 4th and 5th finger with associated weakness

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

bursitis 2) There may be associated pain, warmth and erythema.
3) It typically affects middle-aged male patients.
Lateral epicondylitis:
 Lateral epicondylitis typically follows unaccustomed activity such as house painting or playing
tennis ('tennis elbow').
 It is most common in people aged 45-55 years and typically affects the dominant arm.
Features:
1) pain and tenderness localised to the lateral epicondyle
2) pain worse on wrist extension against resistance with the elbow extended or supination of
the forearm with the elbow extended
3) episodes typically last between 6 months and 2 years. Patients tend to have acute pain
for 6-12 weeks
Management options:
1) advice on avoiding muscle overload
2) simple analgesia
3) steroid injection
[48]
4) 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)
Dactylitis:
Dactylitis describes the inflammation of a digit (finger or toe).
Causes include:
 spondyloarthritis: e.g. Psoriatic and reactive arthritis
 sickle-cell disease
 other rare causes include tuberculosis, sarcoidosis and syphilis

De Quervain's tenosynovitis:
 De Quervain's tenosynovitis is a common condition in which the sheath containing the
extensor pollicis brevis and abductor pollicis longus tendons is inflamed.
 It typically affects females 30 - 50 years old
Features:
 pain on the radial side of wrist
 tenderness over the radial styloid process

[49]
 abduction of the thumb against resistance is painful
 Finkelstein's test: with the thumb is flexed across the palm of the hand, pain is
reproduced by movement of the wrist into flexion and ulnar deviation
Management:
 analgesia
 steroid injection
 immobilisation with a thumb splint (spica) may be effective
 surgical treatment is sometimes required

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

Associations:
 DM: up to 20% of diabetics may have an episode of frozen shoulder

Features:
 typically develop over days bilateral in up to 20% of patients
 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
 the episode typically lasts between 6 months and 2 years

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

Charcot neuroarthropathy
 In patients with long-standing diabetes and peripheral neuropathy, a red hot swollen foot should
raise suspicion of Charcot neuroarthropathy.
 Charcot neuropathy presents as a warm, swollen, erythematous foot and ankle, and infection is
important to exclude.
 The majority of patients are in their 50-60s, and they often present in the latter stages of the
disease.
 It can occur in association with a variety of conditions, including leprosy, poliomyelitis, rheumatoid
arthritis, although today the most common cause is diabetes mellitus.
 The pathophysiology of Charcot neuroarthropathy is not completely understood, but is thought to
start with peripheral neuropathy.
 The lack of pain sensation may mean that patients subject the foot joints (commonly the mid foot)
to stress injuries that lead to the Charcot process.
 It is important to note however that about half of patients present with pain.

[50]
Four stages of Charcot neuropathy are recognised:
Stage 0 (inflammation)
 characterised by erythema and oedema, but no structural changes.
Stage 1 (development)
 bone resorption, fragmentation and joint dislocation.
 Swelling, warmth and erythema persist but there are also radiographic changes such as
debris formation at the articular margins, osseous fragmentation and joint disruption.
Stage 2 (coalescence)
 bony consolidation, osteosclerosis and fusion are all seen on plain radiographs.
Stage 3 (reconstruction)
 osteogenesis,
 decreased osteosclerosis, progressive fusion.
 Healing and new bone formation occur, and the deformity becomes permanent.

 Radiographs are an important part of investigating a patient with possible Charcot arthropathy.
 All radiographs should be taken in the weight-bearing position.
 MRI can demonstrate changes in the earlier stages of the condition, and is therefore important in
allowing treatment to be instigated earlier.
 In stages 0 and 1 the treatment is immediate immobilisation and avoidance of weight-bearing. A
total contact cast is worn until the redness, swelling and heat subside (generally eight to 12
weeks, changed every one to two weeks to minimise skin damage). After this the patient should
use a removable brace for a total of four to six months.

Diabetic cheiro-arthropathy
 A condition of limited joint mobility that occurs in diabetics.
 It is characterised by thickening of the skin resulting in contracture of the fingers.
 Cheiroarthropathy causes such limited motion of the fingers that the affected individual is
unable to extend the fingers to flatten the hand fully. Typically both hands are affected by
Cheiroarthropathy (prayer sign).
 Cheiroarthropathy has been reported in over 50% of patients with IDDM and approximately
75% of those with NIDDM.
 Cheiroarthropathy occurs more frequently in those with a longer history of diabetes.
Treatment:
Pain relief and/or anti-inflammatory drugs, physiotherapy and tight glycaemic control.

Relapsing polychondritis (RP)

[51]
 The picture of his ear shows auricular chondritis, inflammation of the auricle with sparing of the
earlobe. This is a characteristic finding of RP, because only the cartilaginous portion of the ear is
affected, separating it from cellulitis/infection.
 Attacks are recurring and may last from a few days to several weeks.
 Other manifestations include:
1) Nasal chondritis
2) Ocular inflammation, and
3) Arthritis.
 The sternoclavicular, costochondral and sternomanubrial joints are commonly involved.
 Costochondritis can manifest as pleuritic chest pain.
 Involvement of the tracheal cartilage may result in tracheal stenosis and result in life-threatening
stridor.
 Renal disease is rare in RP and in this case there was no evidence of casts/RBCs in the
urinalysis.
 Cartilage can also be destroyed in Wegener's granulomatosis, resulting in saddle nose deformity
and tracheal stenosis. However this is not typically recurring in nature as in RP.

Hip pain in adults:

Condition Features

Osteoarthritis 1) Pain exacerbated by exercise and relieved by rest

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

Inflammatory 1) Pain in the morning,

arthritis 2) Systemic features
3) Raised inflammatory markers

Referred lumbar 1) Femoral nerve compression may cause referred pain in the hip
spine pain 2) Femoral nerve stretch test may be positive:

[52]
Condition Features

 Lie the patient prone. Extend the hip joint with a straight leg then
bend the knee.
 This stretches the femoral nerve and will cause pain if it is trapped

Greater trochanteric  Due to repeated movement of the fibroelastic iliotibial band

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

Meralgia  Caused by compression of lateral cutaneous nerve of thigh

paraesthetica  Typically burning sensation over antero-lateral aspect of thigh

Avascular necrosis  Symptoms may be of gradual or sudden onset

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

Pubic symphysis  Common in pregnancy

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

Transient idiopathic  An uncommon condition sometimes seen in the 3rd 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

Ankle injury: Ottawa rules:

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

1) bony tenderness at the lateral malleolar zone (from the tip of the lateral malleolus to
include the lower 6 cm of posterior border of the fibular)
2) bony tenderness at the medial malleolar zone (from the tip of the medial malleolus to
the lower 6 cm of the posterior border of the tibia)
3) inability to walk 4 weight bearing steps immediately after the injury and in the
emergency department

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

[53]
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

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

Features
1) tall stature with arm span to height ratio > 1.05
2) high-arched palate
3) arachnodactyly
4) pectus excavatum
5) pes planus
6) scoliosis of > 20 degrees
7) dural ectasia (ballooning of the dural sac at the lumbosacral level)

[54]
 8) heart: dilation of the aortic sinuses (seen in 90%) which may lead to aortic aneurysm,
aortic dissection, aortic regurgitation, mitral valve prolapse (75%),
9) lungs: repeated pneumothoraces
10) eyes: upwards lens dislocation (superotemporal ectopia lentis), blue sclera, myopia

 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.

Homocystinuria
 a rare autosomal recessive disease
 Caused by deficiency of cystathionine beta synthase.
 This results in an accumulation of homocysteine which is then oxidized to homocystine.

Features:
 often patients have fine, fair hair
 musculoskeletal: may be similar to Marfan's - arachnodactyly etc
 neurological patients may have learning difficulties, seizures
 ocular: downwards (inferonasal) dislocation of lens
 increased risk of arterial and venous thromboembolism
 also malar flush, livedo reticularis

Diagnosis:
 Is made by the cyanide-nitroprusside test,
 which is also positive in cystinuria

Treatment:
Vitamin B6 (pyridoxine) supplements

Cystinuria
 Cystinuria is an autosomal recessive disorder
 Characterised by the formation of recurrent renal stones.
 It is due to a defect in the membrane transport of cystine, ornithine, lysine, arginine
(mnemonic = COLA)

Genetics:
 chromosome 2: SLC3A1 gene,
 chromosome 19: SLC7A9

Features:
 recurrent renal stones
 are classically yellow and crystalline, appearing semi-opaque on x-ray

[55]
Diagnosis:
 cyanide-nitroprusside test

Management:
 hydration
 urinary alkalinization
 D-penicillamine

A 33-year-old teacher presents with a three week history of dry cough, low grade fever, and
erythematous nodular lesions on the cheek, nose, forehead and chin.

Systemic examination is normal.

A chest x ray showed bilateral hilar adenopathy. The lesions on her face were biopsied and showed
multiple non-caseating granulomata.

What is the most likely diagnosis?

(Please select 1 option)

1) Lymphoma
2) Sarcoidosis
[56]
 3) SlE
4) TB
5) Wegner

Answer 2

This patient has got lupus pernio, a skin manifestation that is specific to sarcoidosis.

Differential diagnosis of bilateral hilar adenopathy includes:

 Sarcoidosis
 Lymphoma

 Tuberculosis
 Pneumoconiosis
 Berylliosis, and
 Fungal diseases like histoplasmosis.

Unlike in sarcoidosis, the granulomata in tuberculosis show caseating necrosis.

[57]
The differential diagnosis of lupus pernio includes:
 Wegener's granulomatosis
 Lymphoma cutis, and

 Cutaneous lupus.

The clinical presentation helps differentiate some lesions, but a biopsy may be required.

Wegener's granulomatosis patients usually present with symptoms of sinusitis, otitis, or nasal
ulceration. The skin lesions include ulcers, nodules, and granuloma formation.

The lesions of lymphoma cutis can occur anywhere on the skin and typically appear as a pink-red to
red-purple papule or plaque.

There are many cutaneous manifestations of systemic lupus erythematosus, but the two most
common are discoid lesions and the butterfly rash:
 Discoid lupus lesions are circular with slightly raised, scaly hyper-pigmented erythematous
rims and depigmented atrophic centres
 The butterfly rash, with its characteristic location over the cheeks and nose, is typically
photosensitive and appears as a slightly raised erythematous lesion.

Frequently, these patients have accompanying arthralgias that suggest the diagnosis.

[58]