Extractable nuclear antigens

 specific nuclear antigens

 usually associated with being ANA positive
Examples
1. Anti-Ro  Sjogren's syndrome/ SLE/ Congenital heart block
2. Anti-La  Sjogren's syndrome
3. Anti-Jo1  Polymyositis
4. Anti-Scl-70  Diffuse cutaneous systemic sclerosis
5. Anti-Centromere  limited Cutaneous systemic sclerosis

Seronegative spondyloarthropathies
1. Associated with HLA-B27
2. Rh. Factor negative 'Seronegative'
3. Peripheral arthritis  usually asymmetrical
4. Sacroiliitis
5. Enthesopathy  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)
There is an indirect association between HLA-B27 and Crohn's as some patients may develop Enteropathic arthritis, but this is the least common association of the above
Rheumatoid arthritis
 The most important Cytokines in the pathophysiology TNF (pro-inflammatory cytokine.
 mainly by macrophages and acting mainly in a paracrine fashion:
 (++) 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 (Phospholipase Activation)

 TNF-alpha  binds to both the P55 & P75 receptor. (++ Apoptosis & ++ NFkB)
 Endothelial effects  ↑↑ (expression of selectins, platelet activating factor, IL-1 and prostaglandins)
 (+ +) Proliferation of fibroblasts, protease and Collagenase (fragments of receptors act as binding points in serum)
 Systemic effects  pyrexia,↑↑ acute phase proteins and disordered metabolism leading to cachexia
 Important in the pathogenesis of RA  TNF blockers (Infliximab, Etanercept) are now licensed for treatment of severe rheumatoid

Epidemiology Peak onset = 30-50 years, although occurs in all age groups
 F:M ratio = 3:1
 prevalence = 1%
 ↑↑ Native Americans
 associated with HLA-DR4 (especially Felty's syndrome)

Ocular manifestations of rheumatoid arthritis are common, with 25% of patients having eye problems
1. keratoconjunctivitis sicca (most common)
2. Episcleritis (erythema)
3. Scleritis (erythema and pain)
4. Corneal ulceration
5. Keratitis
Iatrogenic
1. steroid-induced cataracts
 2. Chloroquine retinopathy

Complications
 A wide variety of extra-articular complications occur in patients with rheumatoid arthritis (RA):
1. Respiratory
 Pulmonary fibrosis
 Pleural effusion
 Pulmonary nodules
 Bronchiolitis obliterans
 Methotrexate Pneumonitis
 Pleurisy
2. Eye  keratoconjunctivitis sicca (most common), episcleritis, scleritis, corneal ulceration, keratitis, steroid-induced cataracts,
Chloroquine retinopathy
3. Osteoporosis
4. CVS  RA carries a similar risk to type 2 D.M
5. ↑↑ risk of infections
6. CNS  Depression

 Less common
1. Felty's syndrome (RA + Splenomegaly + ↓↓ WBCs)
2. Amyloidosis
Investigtion (Anti-bodies)
1. Rheumatoid factor
 Circulating antibody (usually IgM) reacts with the Fc portion of the patients own IgG. detected by either
 Rose-Waaler test  Sheep Red cell agglutination
 Latex agglutination test (less specific)
 +Ve  70-80% (↑↑ levels are associated with severe progressive D)  but NOT a marker of disease activity
 Other conditions associated with a positive RF include:
 1. Sjogren's syndrome (100%)
2. Felty's syndrome (100%)
3. Infective endocarditis (50%)
4. SLE (20-30%)
5. Systemic sclerosis (30%)
6. general population (5%)
7. rarely: TB, HBV, EBV, leprosy

2. Anti - Cyclic Citrullinated peptide antibody(CCP)

 Detectable up to 10 years before the development RA.  allowing early detection of patients suitable for aggressive anti-TNF therapy.
 Similar sensitivity to rheumatoid factor (around 70%) + ↑↑ specificity of 90-95%.
 For suspected RA W (–Ve Rheumatoid factor).

3. X-Ray Changes
Early x-ray findings Late x-ray findings
 loss of joint space  Periarticular erosions
 juxta \Peri - Articular Osteoporosis/Osteopenia)  Characterize RA  subluxation
 soft-tissue swelling

Management
 Evidence of joint inflammation  Start a combination of disease-modifying drugs (DMARD) ASAP.-/+ analgesia, physiotherapy and surgery.
 Initial Therapy
 DMARD monotherapy +/- a short-course of bridging Prednisolone.
 Monitoring response  Combination (CRP + Disease Activity (using a composite score "DAS28").
 Flares  Corticosteroids (Oral or IM)
 DMARDs
1. Methotrexate is the most widely used
  Monitoring of FBC & LFTs ( Risk of myelosuppression and liver cirrhosis).
 Other S/E include Pneumonitis
2. Sulfasalazine
 Management of inflammatory arthritis(RA) and IBD
 Prodrug for 5-ASA  ↓↓Neutrophils Chemotaxis + (--) proliferation of lymphocytes and pro-inflammatory cytokines.
 Cautions  G6PD deficiency & allergy to aspirin or sulphonamides (cross-sensitivity)
 safe to use in both pregnancy and breastfeeding.
 Adverse effects
Oligospermia
Stevens-Johnson syndrome
Pneumonitis / lung fibrosis
Myelosuppression, Heinz body anaemia, megaloblastic anaemia
Colour tears → stained contact lenses
3. Leflunomide
4. Hydroxychloroquine
Azathioprine
 Metabolized to the active compound mercaptopurine (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
1. bone marrow depression
2. nausea/vomiting
3. pancreatitis
4. ↑↑risk of non-melanoma skin cancer
 Drug interaction  significant with allopurinol  lower doses of azathioprine should be used.
 Azathioprine is generally considered safe to use in pregnancy

Hydroxychloroquine
Management of rheumatoid arthritis and systemic/discoid lupus erythematosus.  very similar to chloroquine
Adverse effects
  bull's eye retinopathy - may result in severe and permanent visual loss
 More common recently  Colour retinal photography + Spectral domain optical coherence tomography scanning of the macula
 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  Ask patient about visual symptoms and monitor visual acuity annually using the standard reading chart'

Leflunomide
 Disease modifying anti-rheumatic drug (DMARD)  a very long half-life and teratogenic potential.
 Contraindications
1. Pregnancy  Effective contraception (plasma concentration monitoring required' during treatment and
 for at least 2 years after treatment in women
 at least 3 months after treatment in men
2. Caution W Pre-existing lung and liver disease
 Adverse effects
1. GIT  Diarrhoea, Liver ↓↓
2. Hypertension
3. Myelosuppression
4. Pneumonitis
5. weight loss/anorexia
6. peripheral neuropathy

Monitoring
1. FBC
2. LFT
3. blood pressure

Stopping
leflunomide has a very long wash-out period of up to a year which requires co-administration of Cholestyramine
TNF-inhibitors
 Indication  inadequate response to at least two DMARDs including Methotrexate
1. Etanercept
 Recombinant human fusion protein (decoy receptor for TNF-α)  S.C administration
 S/E demyelination, risks include reactivation of T.B
2. Infliximab
 Monoclonal antibody (binds to TNF-α and prevents it from binding with TNF receptors)  I.V administration
 S/E  reactivation of T.B
3. Idalimumab
 Monoclonal antibody, S.C administration

4. Rituximab(
 Anti-CD20 (Twenty) monoclonal antibody  B-cell depletion
 two 1g IV infusions 2weeks apart
 infusion reactions are common

5. Abatacept
 Fusion protein  modulates a key signal required for activation of T lymphocytes ↓↓ T-cell proliferation and cytokine
 given as an infusion
 not currently recommend by NICE
Poor prognostic features
1. Rh. factor +Ve
2. Anti-CCP +Ve
3. HLA DR4
4. Insidious onset
5. Poor functional status at presentation
6. X-ray  early erosions (after < 2 years)
7. Extra articular features  nodules
 8. Female gender (debatable)

Rheumatoid arthritis: pregnancy

 RA typically develops in women of a reproductive age.
 patients with early or poorly controlled RA  defer conception until their disease is more stable
 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  Safe in pregnancy
 Anti-TNF agents
 infliximab and adalimumab
 not known to cause harm but (insufficient data)  Cross the placenta in high doses in the third trimester
 Low-dose corticosteroids  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
 Obstetric anaesthetist  due to the risk of atlanto-axial subluxation

Psoriatic arthropathy
Psoriatic arthropathy correlates poorly with cutaneous psoriasis "skin lesions".
 10-20% with skin lesions  develop an Arthropathy, males = females
 Types
Rheumatoid-like polyarthritis
1. Asymmetrical Oligoarthritis 2. Sacroilitis
3. DIP joint disease (10%) Arthritis Mutilans

30-40%, most common  Hands and feet (20-30%) more in line with   DIP and Dactylitis Severe deformity
type)  PA, uveitis and achilles tendonitis, synovitis,  (Whole digit is swollen along its length )↑↑common fingers/hand,
sacroiliitis, Dactylitis, enthesitis, Nail disease in psoriatic arthritis (DD. RA) 'Telescoping
 (Yellow& pitted X-ray (large eccentric erosions, tuft resorption and Fingers')
progresion towards 'pencil-in-cup' changes.

Management
1. should be managed by a rheumatologist
2. Treat as rheumatoid arthritis but better prognosis

Systemic Lupus Erythematosus:

 A multisystem, autoimmune Type 3 hypersensitivity (immune complex formation) W HLA B8, DR2, DR3
 immune complex deposition ( skin, joints, kidneys and brain
 20-40 and is ↑↑women (9:1) and people of Afro-Caribbean (African < American) & Asian origin.
Features
Photosensitive Rash + Reynaud's Syndrome + Small joint arthritis  likely diagnosis of systemic lupus erythematosus (SLE).
1. General
 Fatigue
 Fever
 Mouth ulcers
 Lymphadenopathy
2. Skin
 Malar (butterfly) rash: Spares nasolabial folds
 Discoid rash
Scaly, Erythematous, well demarcated rash in sun-exposed areas.
May progress to be pigmented and Hyperkeratotic before becoming atrophic
 Photosensitivity
 Reynaud's phenomenon
 Livedo Reticularis
 Non-scarring alopecia
 3. Musculoskeletal
 Arthralgia
 Non - Erosive arthritis
4. Cardiovascular
 Pericarditis: the most common cardiac manifestation
 Myocarditis
5. Respiratory
 Pleurisy
 Fibrosing alveolitis
6. Renal
 Proteinuria
 Glomerulonephritis (diffuse proliferative glomerulonephritis is the most common type)
7. Neuropsychiatric
 anxiety and depression
 psychosis
 seizures

Investigations
1. Sensitivity
99% are ANA positive
2. Specificity
 Anti-dsDNA  highly specific (> 99%), but less sensitive (70%) highly associated with glomerulonephritis in SLE.
 Anti-Smith  Most specific (> 99%), sensitivity (30%),

3. Special Condition
 SS-A (anti-Ro) associated with congenital heart block (detect fetal
 and SS-B (anti-La)
 Anti-histone is associated with drug-induced lupus.
 4. 20% are rheumatoid factor positive
5. also: anti-U1 RNP,

Monitoring
1. ESR: during active disease the CRP is characteristically normal - a raised CRP may indicate underlying infection
2. ↓↓(C3, C4)  during active disease (formation of complexes leads to consumption of complement)
3. anti-dsDNA titres can be used for disease monitoring (but note not present in all patients)

Drug-induced lupus
Not all the typical features of SLE are seen (Kidney and CNS involvement are unusual) It usually resolves on stopping the drug.
1. Arthralgia, myalgia
2. skin (Malar Rash)
3. Pulmonary involvement (pleurisy) are common
4. Antibodies Association
 Sensitivity  ANA (100%)
 Specify  Anti-Histone (80-90%)
 Anti-Ro, Anti-Smith  around 5%
 dsDNA negative
Most common causes Less common causes
 Procainamide  Isoniazid
 Hydralazine  Minocycline
 Phenytoin
Discoid lupus erythematosus
 A benign disorder seen in younger females.  Follicular keratin plugs and is thought to be autoimmune in aetiology
 Very rarely progresses to SLE (< 5%). Features
1. Rash  raised Erythematous 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), and pigmentation

 Management
1. Topical steroid cream
2. Oral antimalarials may be used second-line e.g. hydroxychloroquine
3. Avoid sun exposure

Systemic lupus erythematosus: pregnancy

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

Antiphospholipid syndrome
 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 (most commonly (SLE)
 A key point for the exam is to appreciate that antiphospholipid syndrome 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
 Lupus anticoagulant is the strongest risk factor for thrombosis of all the listed options  Odds ratio for thrombosis 5 to 16 times higher than controls.
 Anticardiolipin antibodies, Beta-2-glycoprotein are not as prothrombotic as lupus anticoagulant. Features
1. venous/arterial thrombosis
2. recurrent fetal loss
3. livedo reticularis
4. thrombocytopenia
5. prolonged APTT
6. other features: pre-eclampsia, pulmonary hypertension
7. Associations other than SLE
  other autoimmune disorders
 Lymphoproliferative disorders
 Phenothiazines (rare)
Management
1. initial venous thromboembolic events:  warfarin with a target INR 2-3 for 6 months
2. Recurrent venous thromboembolic  lifelong warfarin; if occurred whilst taking warfarin then increase target INR to 3-4
3. arterial thrombosis  lifelong warfarin with INR 2-3

Raynaud's phenomena
1ry (Raynaud's disease" young women (30 years old) with bilateral symptoms".) OR 2ry (Raynaud's phenomenon)
Factors suggesting underlying connective tissue disease
1. onset > after 40 years
2. unilateral symptoms
3. Rashes
4. +Ve autoantibodies
5. features suggests RA or SLE (arthritis OR Recurrent miscarriages)
6. Digital ulcers  Calcinosis
7. very rarely: chilblains  (pernio) itchy, painful purple swellings on the fingers and toes after cold exposure.
2ry causes
1. C.T disorders
 Systemic Sclerosis (2%) of women and (6%) of men with Raynaud's phenomenon develop systemic sclerosis (most common),
 RA, SLE
2. Leukaemia
3. Type I cryoglobulinaemia, cold agglutinins
4. Use of vibrating tools
5. Drugs  Oral Contraceptive Pill, Ergot
6. Cervical rib
 Management
 all patients with suspected secondary Raynaud's phenomenon should be referred to secondary care
 first-line calcium channel blockers (Nifedipine)
 IV Prostacyclin (Epoprostenol) infusions: effects may last several weeks/months

Sjogren's syndrome
 Autoimmune disorder affecting exocrine glands  dry mucosal surfaces.
 1ry (PSS) or 2ry to RA OR other C.T disorders, where it usually develops around 10 years after the initial onset.
 Much more common in females (ratio 9:1). There is a marked increased risk of Lymphoid malignancy (40-60 folds)
 Features
1. Dry Eyes  Keratoconjunctivitis Sicca
2. Dry Mouth (Xerostomia)
3. Recurrent episodes of Parotitis
4. Vaginal Dryness
5. Reynaud's
6. Sensory Polyneuropathy
7. Renal tubular Acidosis (usually subclinical)

Investigation
 Rheumatoid Factor (RF) positive in nearly 100% of patients
 ANA positive in 70%
 Anti-Ro (SSA) Abs in 70% of patients with PSS
 Anti-La (SSB) Abs 30% of patients with PSS
 Schirmer's test: filter paper near conjunctival sac to measure tear formation
 Histology  focal lymphocytic infiltration
 Hypergammaglobulinaemia, Low C4

Management
 Artificial saliva and tears
  Pilocarpine may stimulate saliva production

Still's disease in adults

Bimodal age (15-25 yrs and 35-45. Features
1. Arthralgia
2. ↑↑ serum ferritin
3. Rash  Salmon-pink, maculopapular
4. Pyrexia  rises in the late afternoon/early evening in a daily pattern and accompanies a worsening of joint symptoms and rash
5. Lymphadenopathy
6. RF & ANA  -Ve
7. The Yamaguchi criteria is the most widely used criteria and has a sensitivity of 93.5%.

Management
1. NSAIDs
 first-line to manage fever, joint pain and serositis
 at least a week before steroids are added.
2. Steroids
 may control symptoms but won't improve prognosis
3. If symptoms persist, the use of Methotrexate or Anti-TNF therapy can be considered
Anakinra  "IL1 inhibitor" competitively inhibits IL-1 by binding to the IL-1 receptor
 Plasma levels correlate well with IL-1 in synovial fluid and presence of synovitis.
Rituximab is usually instigated in patients who fail to respond to anakinra.

Relapsing polychondritis
A multi-systemic condition  episodes of inflammation of cartilage (Commonest Pinna ears, other parts (nose and joints).
May be associated with autoimmune diseases (SLE and systemic vasculitis). Features:
1. Ears  Auricular chondritis/ Hearing loss/ Vertigo
2. Nasal nasal chondritis → saddle-nose deformity
3. Respiratory tract  hoarseness, aphonia, wheezing, inspiratory stridor
 4. Ocular  Episcleritis, scleritis, iritis, and keratoconjunctivitis sicca
5. Joints arthralgia
6. Less commonly  Valvular regurgitation, cranial nerve palsies, peripheral neuropathies, renal dysfunction

Diagnosis:
 Various scoring systems (clinical + pathological + radiological criteria)

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

Chronic fatigue syndrome

 Diagnosed after ≥ 4 months of disabling fatigue (Mental + Physical) function > 50% of the time in the absence of other disease which may explain symptoms
 ↑↑ females , Better prognosis in children
 past psychiatric history has not been risk factor
 Features include
1. Fatigue is the central feature
2. Sleep problems (insomnia, hypersomnia, unrefreshing sleep, a disturbed sleep-wake cycle)
3. muscle and/or joint pains
4. Headaches
5. painful lymph nodes without enlargement
6. Sore throat
7. cognitive dysfunction (difficulty thinking, ↓↓concentrate, ↓↓short-term memory, and difficulties with word-finding)
8. physical or mental exertion makes symptoms worse
9. general malaise or 'flu-like' symptoms
10. dizziness, nausea, palpitations
Investigation
 large number of screening blood tests FBC, U&E, LFT, glucose, TFT, ESR, CRP, calcium, CK, ferritin(, coeliac screening and also urinalysis
 Management
 CBT - 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

Fibromyalgia
widespread pain throughout the body + tender points at specific anatomical sites. The cause of fibromyalgia is unknown. ↑↑↑ 30-50 Ys Women (5Times)
Features
1. Chronic pain: at multiple site, sometimes 'pain all over'  neck, elbow regions, and knees.
2. lethargy
3. Cognitive impairment: 'fibro fog'
4. Sleep disturbance, headaches, dizziness are common

Diagnosis
1. Clinical
2. Classification criteria  9 pairs of tender points on the body. (least 11/ 18 points  diagnosis of fibromyalgia more likely)

Management
Often difficult and needs to be tailored to the individual patient  psychosocial and multidisciplinary approach is helpful.
1. explanation
2. aerobic exercise Strongest evidence base
3. CBT
4. Medication pregabalin, duloxetine, amitriptyline

Myopathies
  symmetrical muscle weakness (proximal > distal)
 common problems are rising from chair or getting out of bath
 sensation normal, reflexes normal, no fasciculation
 Causes
1. Inflammatory  polymyositis
2. Inherited  Duchenne/Becker muscular dystrophy, myotonic dystrophy
3. Endocrine  Cushing's, Thyrotoxicosis
4. Alcohol
5. Anti-synthetase syndrome diagnosis is (Proximal Myopathy + Mechanic Hands +/- Lung Symptoms) association W interstitial lung disease -
particularly non-specific interstitial pneumonia or NSIP.

Polymyositis
 inflammatory disorder causing Symmetrical Proximal Muscle weakness  T-cell mediated cytotoxic process directed against muscle fibres
 may be idiopathic or associated (C.T OR Malignancy)
 Dermatomyositis is a variant ( Skin manifestations are prominent, purple (heliotrope) rash on the cheeks and eyelids
 Middle-aged, (F : M 3). Features
1. Proximal muscle weakness +/- Loss of mucle mass
2. Raynaud's
3. Respiratory Muscle weakness
 Major risk factor for premature death
 The anti-Jo-1 antibody with up to 70% of patients having concurrent ILD  5-year survival (60 -80%)
4. Interstitial lung disease fibrosing alveolitis or organising pneumonia
5. Dysphagia, Dysphonia
Investigations
 ↑↑ CK (Weakness)
 ↑↑ Muscle enzymes (lactate dehydrogenase (LD), aldolase, AST and ALT) 85-95%
 EMG
 muscle biopsy
 Anti-Jo-1 antibodies  associated with lung involvement, Raynaud's and fever
Dermatomyositis
 an inflammatory disorder causing Symmetrical, Proximal Muscle Weakness + Skin Lesions
 idiopathic or C.T disorders or underlying malignancy
 Screening for malignancy  following a diagnosis of dermatomyositis (typically Ovarian/ Breast/ Lung cancer, (20-25%) ↑↑W age
EX: presentation with weakness of UL + macular rash over his back. He is a heavy smoker and his sodium is 121 mmol/l  small cell lung cancer
 Polymyositis variant of the disease where skin manifestations are not prominent
 Features
 Skin features
1. Photosensitive
2. Macular rash over back and shoulder
3. Gottron's papules  roughened red papules over extensor surfaces of fingers
4. Nail fold capillary dilatation
5. Heliotrope rash in the Periorbital region
 Muscle features
1. proximal muscle weakness +/- tenderness
2. Raynaud's
3. Respiratory muscle weakness
4. interstitial lung disease  Fibrosing alveolitis or organising pneumonia
5. Dysphagia, Dysphonia

Investigations
 ↑↑ CK
 EMG
 muscle biopsy
 Antibodies
 1. Majority of patients (around 80%) ANA positive
2. Highly specific Anti-Mi-2 antibodies, but are only seen in around 25% of patients
3. "Polymyositis" Subtypes  anti-Jo-1 antibodies
 Not common in dermatomyositis
 ↑↑common in Polymyositis disease associated with (lung involvement + Raynaud's + fever)
Management
Prednisolone

around 30% of patients have antibodies to aminoacyl-tRNA synthetases (anti-synthetase antibodies), including:
 antibodies against histidine-tRNA ligase (Anti- Jo-1) (also with polymiocytis and moresensitive)
 antibodies to signal recognition particle (SRP)
 anti-Mi-2 antibodies

Mixed connective tissue disease (MCTD, Sharp's syndrome)

 Heterogeneous, multi-system autoimmune disorder. It is a distinct clinical entity, but
 features of ((SLE) + Systemic Sclerosis (SSc) + Myositis may all be present.
 It is associated with anti-U1 Ribonucleoprotein (RNP) antibodies (not completely specific and may also be seen in definite SSc and SLE)
 DD. 'undifferentiated connective tissue disease'.  features of ≥ 1'classical' C.T disease, but do not meet diagnostic criteria. Anti-U1 RNP is absent

Epidemiology
 Male:female ratio 1:3  30-40 Ys may present in children

Presentation: (Bone, Muscle. Vessels)

1. Raynaud's phenomenon often precedes other symptoms and occurs in 90% of cases
2. Polyarthralgia/arthritis
3. Myalgia
4. 'Sausage fingers'(dactylitis)
 5. Other clinically important features:
Dermatological  photosensitive rash, scleroderma-like changes, alopecia
GIT Oesophageal dysfunction
Respiratory  pleuritis, pulmonary hypertension, interstitial lung disease
Haematological  anaemia, lymphadenopathy, splenomegaly, rarely TTP
CVS  Pericarditis, Pericardial effusion, accelerated coronary artery disease
Renal  glomerulonephritis (tends to be milder than SLE)
CNS : 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,  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.

Systemic sclerosis
 Unknown aetiology characterised by hardened, sclerotic skin and other connective tissues. It is ↑↑ 4* 1 females.
There are three patterns of disease:
Limited cutaneous + systemic sclerosis Diffuse cutaneous + systemic sclerosis Scleroderma (without internal organ
 Raynaud's "first sign"  Scleroderma trunk and proximal limbs  ightening and fibrosis of skin
 Scleroderma  face and distal limbs predominately predominately  may be manifest as plaques
 anti-Centromere antibodies
 scl-70 antibodies (morphoea) or linear
 Commonest cause of death  respiratory
 CREST syndrome
involvement,
 a subtype of limited systemic sclerosis  (80%) interstitial lung disease (ILD)
 Calcinosis, Raynaud's phenomenon, oEsophageal and PAH
dysmotility, Sclerodactyly, Telangiectasia  Other complications  Renal disease and
 Malabsorption can develop in these patients secondary to HTN
bacterial overgrowth of the sclerosed small intestine  Poor prognosis
 PHTN  one of the more common late complications

Antibodies
1. ANA positive in 90%
2. RF positive in 30%
3. anti-scl-70 antibodies associated with diffuse cutaneous systemic sclerosis
4. anti-centromere antibodies associated with limited cutaneous systemic sclerosis

Behcet's syndrome
Multisystem disorder with presumed autoimmune-mediated inflammation of the arteries and veins. Triad (oral ulcers + genital ulcers + anterior uveitis)

Epidemiology
 more common in the eastern Mediterranean (Turkey)
 More common and severe in men 20 - 40 years old ) (complicated gender distribution which varies according to country.
  associated with HLA B51
 30% of patients have a positive family history

Features
 1) oral ulcers
 2) genital ulcers
 3) anterior uveitis not Conjunctivitis
 Ocular involvement is the most feared complication
 Conjunctivitis is rare and is much less common than anterior uveitis. Others (Retinal vasculitis, Iridocyclitis and Chorioretinitis)
 Thrombophlebitis and deep vein thrombosis
 arthritis
 neurological involvement (aseptic meningitis)
 GI  abdo pain, diarrhoea, colitis
 Erythema nodosum

Diagnosis
 no definitive test
 diagnosis based on clinical findings
 +Ve 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

McArdle's disease
 AR  type V glycogen storage disease  caused by Myophosphorylase deficiency  ↓↓ muscle glycogenolysis
Features
1. muscle pain and stiffness following exercise  'second-wind' phenomenon and present
2. Muscle cramps  Distal muscle
3. Myoglobinuria  Dark Urine after exercise
4. low lactate levels during exercise
 DD. Polymyositis and dermatomyositis  cause a more marked ↑↑↑ CK which can be up to 100 times the upper limit of normal.

Polyarteritis nodosa
Vasculitis of medium-sized arteries with necrotizing inflammation (Aneurysm formation. ↑↑Middle-aged men, Associated with hepatitis B. Features
1. Fever, malaise, arthralgia
2. Weight loss
3. Hypertension
4. Mononeuritis Multiplex  sensorimotor polyneuropathy (Pt Ulner palsy  radial  facial new foot drop or wrist drop ….)
5. Testicular pain
6. livedo reticularis
7. Haematuria, renal failure
8. Perinuclear-antineutrophil cytoplasmic antibodies (ANCA) are found in around 20% of patients with 'classic' PAN
9. hepatitis B serology +Ve  30% of patients

Diagnosis
 No ↑↑ correlated Abs is likely to be positive

 Confirmed Diagnosis  Biopsy showing necrotizing arteritis

 Escaped lesions  disease is focal (biopsy should target sites suggested by clinical evaluation)
 Samples of subcutaneous tissue, sural nerve, and muscle are preferred to samples from the kidneys or liver; kidney and liver biopsies
 Might be falsely negative and may cause bleeding from unsuspected microaneurysms.

 Arteriography  Typical aneurysms in medium-sized arteries.

 MRA may show microaneurysms, but some abnormalities may be too small for it to detect.
 Labs
 ↑↑ (ESR, Platlet & TLC up to 20,000 to 40,000/L)
 Anaemia caused by blood loss or renal failure
  Proteinuria, and microscopic haematuria are the most common abnormalities.
 Liver  low serum albumin AST and ALT are often mildly elevated. Testing for hepatitis B and C should be done.
Temporal arteritis
Large vessel vasculitis (polymyalgia rheumatic) PMR W 'skips' certain affected artery. Features
1. > 60ys old
2. Rapid onset (< 1 month)
3. Headache (found in 85%)
1. Jaw claudication (65%)  very specific sign for temporal arteritis.
4. Visual disturbances secondary to anterior ischemic optic neuropathy
5. Tender, Palpable temporal artery
6. Around 50% have PMR  Aching, Morning stiffness in proximal limb muscles (not weakness)
7. lethargy, depression, low-grade fever, anorexia, night sweats

Criteria requires 3 of the following for GCA diagnosis:

1. Age > 50 y/o
2. New onset localised headache
3. Temporal artery tenderness or ↓↓pulsation
4. ESR > 50mm/hr
5. Temporal artery biopsy positive

Investigations
2. ↑↑ ESR > 50 mm/hr (note ESR < 30 in 10% of patients). CRP may also be elevated
3. Temporal artery biopsy  skip lesions may be present
4. –Ve Temporal artery  biopsy can occur in up to 50 % of patients
5. CK & EMG normal

Treatment
1. Uncomplicated GCA  No visual involvement and/or jaw/tongue claudication)
  Oral prednisolone 40-60mg daily until symptoms and investigations normalise.

2. Complicated GCA (Visual involvement and/or jaw/tongue claudication)

 IV Methylprednisolone 500-1000mg for 3 days before starting oral prednisolone.

3. Urgent ophthalmology review  visual symptoms should be seen the same-day by an ophthalmologist. Visual damage is often irreversible

Long term therapy

1. long-term steroid + Bone sparing agents (a bisphosphonate and vitamin D) + Gastroprotective drug (e.g omeprazole).
2. Low dose aspirin  ↓↓ rate of visual loss and cerebrovascular accidents in GCA.

Polymyalgia rheumatica
 overlaps with Temporal arteritis
 Histology  Vasculitis + giant cells W 'Skips' certain sections  Muscle bed arteries affected most in Polymyalgia Rheumatic
Features
1. > 60 years old
2. usually rapid onset (< 1 month)
3. Aching/ Morning stiffness in proximal limb muscles (not weakness)
4. Mild polyarthralgia, lethargy, Depression, low-grade fever, anorexia, Night sweats

Investigations
 ESR > 40 mm/hr
 CK and EMG normal

Treatment
 Prednisolone  15mg/od - dramatic response
ANCA
2 types of anti-neutrophil cytoplasmic antibodies (ANCA) - Cytoplasmic (cANCA) & Perinuclear (pANCA)
For the exam, remember:
 cANCA - granulomatosis with polyangiitis (Wegener's granulomatosis)
 pANCA - Churg-Strauss syndrome + others (see below)
Canca pANCA
 Most common target Serine Proteinase 3 (PR3)  Myeloperoxidase ( most common) neutrophil protein whose primary
 Some correlation between cANCA levels and disease activity role is the generation of oxygen free radicals. (MPO)
1. Granulomatosis with polyangiitis, positive in > 90%  Others  Lysosome, Cathepsin G and elastase
2. Microscopic polyangiitis, positive in 40%  cannot use level of pANCA to monitor disease activity.
1. Immune Crescentic GN (positive in c. 80% of patients)
2. Microscopic polyangiitis, positive in 50-75%
3. Churg-Strauss syndrome, positive in 60%
4. 1ry sclerosing cholangitis, positive in 60-80%
5. Granulomatosis with polyangiitis, positive in 25%

Other causes of positive ANCA (usually pANCA)

 IBD  (UC > Crohn's
 C.T disorders: RA, SLE, Sjogren's
 Autoimmune hepatitis

Testing for ANCA

 Enzyme-linked immunosorbent assay (ELISA) or immunofluorescence.
The former detects anti-MPO or anti PR3 antibodies in the blood.
 Immunostaining would show different patterns depending on the condition

Marfan's syndrome
AD C.T disorder  defect FBN1 gene on Chromosome 15 that codes for the protein fibrillin-1A Glycoprotein structure wraps around Elastin.
It affects (1 in 3,000) people.Features
1. Tall stature with Arm span to height ratio > 1.05
2. high-arched palate
3. Arachnodactyly
4. pectus excavatum
5. pes planus
6. scoliosis of > 20 degrees
7. HEART  Dilation of the aortic sinuses (90%)  aortic aneurysm, aortic dissection, aortic regurgitation, mitral valve prolapse (75%),
8. Lungs  Repeated pneumothoraces
9. Eyes  upwards lens dislocation (50%) (superotemporal ectopia lentis), blue sclera, myopia, Glucoma, Retinal dislocation.

10. CNS  Dural ectasia (ballooning of the dural sac at the lumbosacral level)
lower back pain associated with neurological problems such as bladder and bowel dysfunction

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 CVS problems remain the leading cause of death however.

Inferonasal ectopia lentis is characteristic of homocystinuria

Pseudoxanthoma elasticum
AR(AD in minority)  Abnormality in Elastic Fibres. Features
 1. Earliest sign "Skin Changes"  'plucked chicken skin' appearance (Small Yellow Papules on the neck, antecubital fossa and axilla)
2. Retinal Angioid streaks  small breaks in Bruch's membrane ( Elastic tissue containing membrane of the retina)
3. CVS  MV prolapse, ↑↑↑ IHD
4. GIT Hge

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

Ehler-Danlos syndrome
AD  C.T disorder that mostly affects type III collagen.  tissue being more elastic than normal  joint hypermobility and increased elasticity of the skin.
Features and complications
1. Elastic, fragile skin  Bruises
2. joint hypermobility: recurrent joint dislocation
3. AR , MV prolapse and aortic dissection
4. Subarachnoid Hge
5. Angioid retinal streaks

DD
Collagen type I  Osteogenesis imperfecta
Collagen type IIIEhler Danlos
Collagen type IVGoodposture
Collagen type V Less common Ehler Danlos

Gout
 Microcrystal Synovitis (deposition of Monosodium urate monohydrate in the synovium). predominantly "Superficial Portions of the Articular cartilage
 Chronic hyperuricaemia (uric acid > 0.45 mmol/l)
 Decreased excretion of uric acid
 Chronic kidney disease ↓↓renal excretion (90%) 1ry gout.
 2ry risk factors such as alcohol intake and medications should also be investigated
 Drugs
 Diuretics  Thiazides, Furosemide, Indipamide
 Ciclosporin
 Alcohol
 Cytotoxic agents
 Pyrazinamide
 Aspirin  balanced against the cardiovascular benefits of aspirin and the study showed patients coprescribed allopurinol were not at an
increased risk
 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  only seen in boys
 Gout / Renal failure / Neurological deficits / Learning difficulties / Self - Mutilation
Features
1. Episodes  days maximal intensity with 12 hs , often symptom-free between episodes. The main
 Pain: this is often very significant 1st metatarsophalangeal (MTP) joint (70%) (ankle, wrise, knee)
 Swelling
 Erythema
Investigations
XR, CT, MRI and bone scintigraphy  inability to assess early soft tissue changes. not seen radiographically until 6-12 yrs after the initial acute attack.
1. Radiological features
 Joint effusion is an early sign
  "Double-contour sign" Most Ch.Ch. lesion"  Hyperechoic, irregular band over the superficial margin of the joint cartilage" produced by
deposition of monosodium urate crystals on the surface of the hyaline cartilage, ↑↑interface of the cartilage surface, reaching a thickness
similar to the subchondral bone.
 Well-defined 'Punched-out' Erosions + Sclerotic Margins  ina juxta-articular distribution, often with overhanging edges
 Relative preservation of joint space until late disease
 Eccentric erosions
 Periarticular osteopenia (in contrast to rheumatoid arthritis)
 Soft tissue Tophi (Roentgenography) may be seen

1. The most reliable method  Needle aspiration  Monosodium urate crystals.

Acute management
st
1. 1 Line
 NSAIDs or Colchicine
 Maximum dose of NSAID  prescribed until 1-2 days after the symptoms have settled.
 Gastroprotection (e.g. a proton pump inhibitor) may also be indicated
 Colchicine
 (- -) Microtubule polymerization by binding to tubulin, interfering with mitosis. Also (- -) Neutrophil motility and activity
 Slower onset of action. The main S/E diarrhea
 CKD
↓↓ dose or ↑↑ the dosage interval if eGFR 10-50ml/minute/1.73m²;
Avoid if eGFR < 10mL/minute/1.73m².
nd
2. 2 Line
 Oral steroids
 NSAIDs and colchicine are contraindicated
 Prednisolone 15mg/day is usually used
3. intra-articular steroid injection
 4. if the patient is already taking allopurinol it should be continued

Urate-lowering therapy (ULT)

 All patients after their first attack of gout, ULT is particularly recommended if:
1. ≥ 2 attacks in 12 months
2. Tophi
3. Renal disease
4. Uric acid renal stones
5. Prophylaxis if  Cytotoxics or diuretics

 1st Line  Allopurinol

 Should not be started until 2 weeks after an acute attack, as starting too early may precipitate a further attack.
 Better for a patient to make long-term drug decisions whilst not in pain
 Initial dose of 100 mg/ Day  ↑↑every few weeks (aim serum uric acid of < 300 µmol/l.)
 Lower initial doses  reduced eGFR
 Colchicines cover  starting allopurinol. NSAIDs can be used if colchicine cannot be tolerated. may need to be continued for 6 months
 2nd-line  Febuxostat (Xanthine Oxidase inhibitor)
 in refractory cases other agents may be tried:
 Uricase (Urate Oxidase)  enzyme catalyzes conversion of urate to the degradation product allantoin (in certain mammals but not huma
 Pegloticase
Polyethylene glycol modified mammalian uricase
Used in persistent symptomatic and severe gout despite the adequate use of urate-lowering therapy.
Achieve rapid control of hyperuricemia.
It is given as an infusion once/ 2 weeks
Lifestyle modifications
 1. reduce alcohol intake and avoid during an acute attack
2. lose weight if obese
3. avoid food high in purines (Liver, kidneys, seafood, oily fish (mackerel, sardines) and yeast products)

Other points
 stopping precipitating drugs (thiazides)
 losartan has a specific uricosuric action  coexistent hypertension
 ↑↑ vitamin C intake (either supplements or through normal diet) may also ↓↓serum uric acid levels

Pseudogout
Microcrystal synovitis  caused by the deposition of Ca++ pyrophosphate dihydrate crystals in the synovium. Risk factors
1. ↑↑PTH Hyperparathyroidism
++ )
2. ↑↑ (Fe Haemochromatosis
3. ↑↑ (Copper) Wilson's disease
4. ↑↑ (GH) Acromegaly
+
5. ↓↓ (Mg, P )

Features
 knee, wrist and shoulders most commonly affected
 joint aspiration: weakly-positively Birefringent Crystals
 ↑↑ Transferrin Saturation (confirm Haemochromatosis)
 X-Ray
 Non-specific changes such as loss of joint space
 Chondrocalcinosis in the knee  linear calcifications of the meniscus and articular cartilage (DD. pseudogout from gout)

Management
 Aspiration of joint fluid  exclude septic arthritis
 NSAIDs or intra-articular, intra-muscular or oral steroids as for gout
Langerhans cell histiocytosis
A rare condition associated with the abnormal proliferation of histiocytes  formation of multiple granulomas. It presents in childhood with bony lesions.
Features
1. Bone pain, typically in the skull or proximal femur
2. Recurrent otitis media/Mastoiditis
3. Cutaneous nodules
 proliferative condition of the dendritic cells in the skin
 Skin Biopsy  Tennis racket-shaped Birbeck granules on electromicroscopy
Paget's disease of the bone
"Osteitis deformans"  ↑uncontrolled bone turnover. disorder of Osteoclasts, ↑↑ osteoclastic resorption followed by ↑↑ osteoblastic activity.
It is common (UK prevalence 5%) but symptomatic(1 in 20) patients.↑↑↑ skull, spine/pelvis, and long bones of the lower extremities
Predisposing factors
1. increasing age
2. male sex
3. northern latitude
4. family history

Clinical features - only 5% of patients are symptomatic

1. typically  older male + bone pain + isolated ↑↑ ALP
2. bone pain (pelvis, lumbar spine, femur)
3. classical, untreated features  bowing of tibia, bossing of skull
4. calcium* and phosphate are typically normal (↑↑ prolonged immobilization)
5. other markers of bone turnover include
 pro-collagen type I N-terminal propeptide (PINP),
 serum C-telopeptide (CTx),
 urinary N-telopeptide (NTx)
 ↑↑ Blood & urinary Hydroxyproline
 6. X-ray:
 Skull thickened vault, Osteoporosis Circumscripta
 Osteolytic lesions + patch sclerosis

Indications for treatment

 bone pain
 skull or long bone deformity
 Fracture
 periarticular Paget's
1. Bisphosphonate (either oral risedronate or IV zoledronate) + Ca and Vit D.
2. Calcitonin is less commonly used now

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

Osteoarthritis (OA)
 Trapeziometacarpal joint (base of thumb) is the most common site of hand osteoarthritis. Management
1. all offered (weight loss, local muscle strengthening exercises and general aerobic fitness).
2. first-line
 Analgesics Paracetamol and Topical NSAIDs are.
 Topical NSAIDs  Only knee or hand)
3. 2nd-line treatment
 oral NSAIDs/COX-2 inhibitors
 Opioids
  Capsaicin cream and
 intra-articular corticosteroids.
4. A proton pump inhibitor should be co-prescribed with NSAIDs and COX-2 inhibitors.
5. These drugs should be avoided if the patient takes aspirin
6. Non-pharmacological treatment options include supports and braces, TENS and shock absorbing insoles or shoes
7. if conservative methods fail then refer for consideration of joint replacement

What is the role of glucosamine?

1. Normal constituent of glycosaminoglycans in cartilage and synovial fluid
2. Significant short-term symptomatic benefits including significantly ↓↓ joint space narrowing and improved pain scores
Osteomalacia
 Normal bony tissue but ↓↓mineral content
 Rickets if when growing  Osteomalacia if after epiphysis fusion

Types
 Vit D deficiency e.g. malabsorption, lack of sunlight, diet
 Renal failure
 Drug  anticonvulsants
 Vit D resistant  inherited
 liver disease  Cirrhosis

Features
 Rickets  knock-knee, bow leg, features of hypocalcaemia
 Osteomalacia  bone pain, fractures, muscle tenderness, proximal myopathy

Investigation
 ↓↓ 25(OH) vitamin D (in 100% of patients, by definition)
 ↑↑ ALP (95-100%)
  ↓↓ (Ca++, P) (in around 30%)
 X-Ray
 Children  Cupped, Ragged Metaphysical surfaces
 Adults  Translucent Bands (Looser's zones OR Pseudo fractures)

Treatment
 Ca with vitamin D tablets

DD. Osteoporosis blood values are normal

1ry hyperparathyroidism ('Refer for a technetium-MIBI subtraction scan') are associated with↑↑Ca++

Vitamin D supplementation
 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 should be treated anyway so again testing is not necessary.
1. all pregnant and breastfeeding women should take a daily supplement containing 10µg of vitamin D
2. all children aged (6 months - 5 years). Babies fed with formula milk do not need if they are taking > 500ml of milk (fortified with vitamin D)
3. Adults > 65 years
4. 'people who are not exposed to much sun should also take a daily supplement' (housebound patients)

Testing for vitamin D deficiency

Testing may be appropriate in the following situtations:
1. patients with bone diseases may be improved with vitamin D (known osteomalacia or Paget's disease)
2. patients with bone diseases, prior to specific treatment where correcting vitamin deficiency is appropriate (IV zolendronate or denosumab
3. patients with musculoskeletal symptoms could be attributed to vitamin D deficiency ( bone pain ?osteomalaci)

Measurement of serum 25-OH vitamin D is the best way of estimating vitamin D status.
 < 30 nmol/l Deficiency  treatment recommended
 30-50 nmol/l Insufficiency  treatment for patients with
1. fragility fracture,
 2.Osteoporosis.
3.symptoms suggestive of vitamin D deficiency,
4.↓↓ exposure to sunlight,
5.↑↑ PTH,
6.conditions associated with malabsorption
 50- 75 nmol/l Adequate  reassurance and advice on maintaining adequate vitamin D ( safe sunlight exposure and diet)

Treatment
1. Load with vitamin D and then continue on maintenance.
2. In patients with good calcium intake and normal serum calcium, giving oral calcium may actually be detrimental.
3. This is due to adverse CVS outcomes (↑↑ tissue and vascular calcification  CI  IHD

Osteopetrosis
 "Marble Bone Disease"  rare disorder of Defective osteoclast function  failure of normal bone resorption  dense, thick bones prone to fracture
 Bone pains and neuropathies are common.
 Ca++, P+ & ALP are normal
 Treatment  Stem cell transplant and interferon-gamma.

Osteoporosis
Advancing age and female sex are significant risk factors for osteoporosis.
Prevalence (2% at 50 ys) & > 25% at 80 y
risk factors and 2ry causes the most 'important' ones (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. ↓↓ BMI
6. current smoking
 Other risk factors
1. Sedentary lifestyle
2. premature menopause
3. Caucasians and Asians
4. Endocrine  DM, hyperthyroidism, hyperparathyroidism, ↓↓↓GH, Hypogonadism (Turner's, Testosterone deficiency)
5. Multiple myeloma, Lymphoma
6. GIT disorders: IBD, Malabsorption (Coeliac's), Gastrectomy, Liver disease
7. Chronic kidney disease
8. Osteogenesis imperfecta, Homocystinuria

Medications that may worsen osteoporosis (other than glucocorticoids):

1. SSRIs
2. Antiepileptic
3. Proton pump inhibitors
4. Glitazones
5. Long term heparin therapy
6. Aromatase inhibitors e.g. Anastrozole

Investigations for secondary causes

If a patient is diagnosed with osteoporosis or has a fragility fracture testing for the following reasons:
1. exclude diseases that mimic osteoporosis (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. CB, ESR or CRP, Serum Ca
3. Albumin, Creatinine, phosphate, ALPand liver transaminases
 4. Thyroid function tests
5. Bone densitometry ( DXA)

Other procedures, if indicated

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

So from the first list we should order the following bloods as a minimum for all patients:
1. full blood count
2. urea and electrolytes
3. liver function tests
4. bone profile
5. CRP
6. thyroid function tests
7. DEXA scan
1. T score  means the number of SDs above or below the mean for a healthy 30Ys adult of the Same sex and Ethnicity as the patient
T score (-1)  bone mass of one standard deviation < that of young reference population.
 -1.0 = normal
 -1.0 to -2.5 = osteopaenia
 < -2.5 = osteoporosis
 2. Z score  comparing the patients bone density to individuals of a /similar age /gender and ethnic factors
 Diagnosing of 2ry osteoporosis  used for children, young adults, pre-menopausal women and men < 50 Ys
 Abnormal Z-scores confirm a diagnosis of 2ry osteoporosis.
Management
Treatment is indicated following
 Osteoporotic fragility fractures in postmenopausal women confirmed to have osteoporosis (a T-score of - 2.5 SD or below).
 In women ≥ 75 years, a DEXA scan may not be required 'if clinically inappropriate or unfeasible'

1. Vit D and calcium  all women unless the clinician is confident they have adequate calcium intake and are vitamin D replete
2. Alendronate is first-line
3. 25% of patients cannot tolerate alendronate, (upper GIT problems)  Risedronate OR Etidronate (see treatment criteria below)
4. Strontium Ranelate and Raloxifene  if patients cannot tolerate bisphosphonates (see treatment criteria below)

Treatment criteria for patients not taking alendronate

 Age, T-score and risk factors:
1. Parental history of hip fracture
2. Alcohol intake ≥ 4 units per day
3. Rheumatoid arthritis

 T-score criteria for Risedronate or Etidronate < others ( So, 2nd line drugs)
 If Alendronate, Risedronate or Etidronate cannot be taken Strontium ranelate or Raloxifene (based on strict T-scores (60Y  T-score < -3.5)
 The strictest criteria are for Denosumab

Supplementary notes on treatment

1. Bisphosphonates
 Analogues of pyrophosphate ((- -) osteoclasts  by ↓↓ recruitment and ↑↑ apoptosis  ↓↓ demineralisation in bone
 alendronate, risedronate and etidronate  prevention and treatment of post-menopausal and glucocorticoid-induced osteoporosis
1. all three shown to ↓↓ risk (Vertebral & Non - Vertebral Fractures)
2. Alendronate & Risedronate > superior to Etidronate in preventing Hip Fractures
 3. Ibandronate  once-monthly oral bisphosphonate
4. Zoledronic Acid is another type of bisphosphonate.
 It attaches to bone cells and ↓↓ rate of bone change.
 Treatment of osteoporosis & fracture prevention in cancer such as multiple myeloma and prostate cancer.
 Clinical uses
1. Prevention and treatment of osteoporosis
2. Hypercalcaemia
3. Paget's disease
4. pain from bone metastases

 Adverse effects
1. Oesophageal reactions  oesophagitis, oesophageal ulcers (especially alendronate)
2. Osteonecrosis of the jaw
3. ↑↑ risk of atypical stress fractures of the proximal femoral shaft in patients taking alendronate
4. acute phase response: fever, myalgia and arthralgia may occur following administration
5. Hypocalcaemia: ↓↓calcium efflux from bone. Usually clinically unimportant

 Precautions with oral bisphosphonates

1. 'Tablets should be swallowed whole with plenty of water while sitting or standing; to be given on an empty stomach at least 30 minute
before breakfast (or another oral medication); patient should stand or sit upright for at least 30 minutes after taking tablet'
2. Hypocalcemia/vitamin D deficiency should be corrected before giving bisphosphonates.
 when starting bisphosphonate treatment for osteoporosis, calcium should only be prescribed if dietary intake is inadequate.
 Vitamin D supplements are normally given.

4. The duration of bisphosphonate  according to the level of risk. 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
  Alendronate  first-line treatment  Not tolerated then (Risedronate or Etidronate).
Following this the advice becomes more complicated with the next-line medications

2. Vitamin D and calcium

 ↓↓ fracture rates in the general population at risk of osteoporotic fractures - may reduce rates in frail, housebound patients

3. Raloxifene - selective Oestrogen Receptor Modulator (SERM)

 (based on strict T-scores (60Y  T-score < -3.5)
 Prevent bone loss and to ↓↓ risk of vertebral fractures, NOT ↓↓ risk of non-vertebral fractures
 ↑↑ bone density in the spine and proximal femur
 may worsen menopausal symptoms
 ↑↑ risk VTE
 ↓↓ risk of breast cancer

4. Strontium ranelate
 (based on strict T-scores (60Y  T-score < -3.5)
 'Dual action bone agent' ↑↑deposition of new bone by osteoblasts (++ differentiation of pre-osteoblast to osteoblast) and ↓↓ resorption
of bone by↓osteoclasts
 ↑↑ Safety concerns  only be prescribed by a specialist in secondary care
 Only when other treatments for osteoporosis
 ↑↑ CVS  History of CVS
 ↑↑ thromboembolic events it is not used in patients with a history of venous thromboembolism
 may cause serious skin reactions such as Stevens Johnson syndrome

5. Denosumab
 Human monoclonal antibody inhibits RANK Ligand,  (- -) maturation of osteoclasts
 Dose
 single S.C injection/ 6 months
 Larger dose (120mg) /1 month  prevention of skeletal-related events (Pathological fractures) (bone metastases from solid tumours
 Effective and well tolerated
 Indication
Only if certain T score and other risk factor criteria being met.
 Side-effects
Dyspnoea and diarrhea "two most common 1 in 10 patients"|.↓ Ca++ and URTI.
Cases of atypical femoral fractures (look out for patients complaining of unusual thigh, hip or groin pain.
6. Teriparatide
 recombinant form of PTH
 very effective ↑↑bone mineral density but role in the management of osteoporosis yet to be clearly defined

7. Hormone replacement therapy

 ↓↓ incidence of vertebral fracture and non-vertebral fractures
 ONLY if vasomotor symptoms (Risk CVS and breast cancer)
8. Hip protectors
 ↓↓hip fractures in nursing home patients  compliance is a problem
9. Falls risk assessment
 no evidence to ↓↓fracture rates
 however, ↓↓ rate of falls and should be considered in management of high risk patients
10. Glucocorticoid-induced
 ↑↑↑ risk if dose = prednisolone 7.5mg a day for ≥ 3 Ms.
 manage patients in an anticipatory (steroids for at least 3 months + start bone protection straight) until 3 months has elapsed.
 Patient with newly diagnosed polymyalgia rheumatica prednisolone > 3 months bone protection should be commenced
 Management of patients at risk of corticosteroid-induced osteoporosis
 > 65 years OR previous fragility fracture  bone protection.
 < 65 years  bone density scan
T score Management
> 0 Reassure
Between 0 and -1.5 Repeat in 1-3 years
< -1.5 Offer bone protection
  Treatment  Alendronate + calcium + vitamin D replete.

Osteogenesis imperfect
"Brittle bone disease"
AD  abnormality in type 1 collagen due to ↓↓ synthesis of pro-alpha 1 or pro-alpha 2 collagen polypeptides  bone fragility and fractures.
The most common, and milder, form is type 1. Features
1. presents in childhood
2. fractures following minor trauma
3. blue sclera
4. deafness secondary to otosclerosis
5. dental imperfections are common
Investigations
 adjusted calcium, phosphate, parathyroid hormone and ALP results are usually normal in osteogenesis imperfecta

Ankylosing spondylitis
HLA-B27 associated spondyloarthropathy. Young man sex ratio 3:1 aged 20-30 years  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
1. ↓↓ (lateral flexion & forward flexion)
2. loss of lumbar lordosis
3. 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 ↑↑ by > 5 cm
when the patient bends as far forward as possible
4. ↓↓ chest expansion, ↑↑ thoracic kyphosis
5. Other features - the 'A's
 Anterior Uveitis
 Apical Fibrosis
 AR
 AV node block
  Amyloidosis
 Cauda Equina syndrome
 Achilles tendonitis
 Peripheral Arthritis (25%, more common if female)
Investigations
BLOOD
 ↑↑ (ESR, CRP) 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

BACK
 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. Sacroiliitis  Subchondral erosions, Sclerosis
2. squaring of lumbar vertebrae
3. 'bamboo spine' (late & uncommon)  Complete fusion of anterior and posterior elements
4. Dagger sign  bamboo spine with a single central radiodense line related to ossification of supraspinous and interspinous ligaments
5. syndesmophytes: due to ossification of outer fibers of annulus fibrosus
 If the x-ray is negative for sacroiliac joint involvement in ankylosing spondylitis but suspicion for AS remains high,  MRI Signs of early
inflammation involving sacroiliac joints (bone marrow oedema) confirm the diagnosis of AS and prompt further treatment.

Chest
 x-ray apical fibrosis
 Spirometry may show a restrictive defect due to a combination (pulmonary fibrosis + kyphosis + Ankylosis) of the costovertebral joints.

Management
1. encourage regular exercise such as swimming
 2. NSAIDs are the first-line treatment
3. physiotherapy
4. Disease-modifying drugs
 (Sulphasalazine) only really useful if there is peripheral joint involvement

5. Anti-TNF Therapy
Persistently ↑↑↑disease activity despite conventional treatments'
 Etanercept and Adalimumab should be used earlier in the course of the disease (Under trial)
 It improves Quality of life, Spinal mobility, Extra-articular features, Early morning stiffness.
 It does not affect Radiological progression

Lower back pain:

common presentations with non-specific muscular nature, but there are some possible causes which may need specific treatment.
Red flags for lower back pain
1. age < 20 years or > 50 years
2. systemically unwell e.g. weight loss, fever
3. history of previous malignancy
4. history of trauma
5. Night pain
  acute or chronic
Pain worse in the morning and on standing
On examination pain over the facets. The pain is typically worse on extension
Facet joint the back
Spinal stenosis  Usually gradual onset
 Unilateral or bilateral 'aching', 'crawling' leg pain ± back pain, numbness, and weakness is worse on walking.
 ↓↓ sitting down, leaning forwards and crouching down
Clinical examination is often normal
Requires MRI to confirm diagnosis  narrowing of the spinal canal
Ankylosing Typically a young man with lower back pain and stiffness
spondylitis Stiffness is usually worse in morning and improves with activity
Peripheral arthritis (25%, more common if female)
Peripheral Pain on walking, relieved by rest
arterial disease Absent or weak foot pulses and other signs of limb ischaemia
prolapsed lumbar disc Past history may include smoking and other vascular diseases
usually produces
clear dermatomal leg pain associated with neurological deficits.

Features
 unilateral leg pain usually worse than back (Back Pain  LL)
 pain often worse when sitting DD. Spinal stenosis

Site of compression Features

L3 nerve root compression 1. Sensory loss over anterior thigh
2. Weak quadriceps
3. ↓↓ knee reflex
4. Positive femoral stretch test
L4 nerve root compression 1. Sensory loss anterior aspect of knee
 Site of compression Features
2. Weak quadriceps
3. ↓↓ knee reflex
4. Positive femoral stretch test
L5 nerve root compression 1. Sensory loss dorsum of foot
2. Weakness in foot and big toe dorsiflexion
3. Reflexes intact
4. Positive sciatic nerve stretch test
S1 nerve root compression 1. Sensory loss posterolateral aspect of leg and lateral aspect of foot
2. Weakness in plantar flexion of foot
3. ↓↓ ankle reflex
4. Positive sciatic nerve stretch test

Management
 similar to that of other musculoskeletal lower back pain: analgesia, physiotherapy, exercises
 if symptoms persist (after 4-6 weeks) then referral for consideration of MRI is appropriate

iliopsoas abscess
A collection of pus in iliopsoas compartment (iliopsoas and iliacus).

Primary Secondary
 Mortality 2.4%  Mortality ↑↑ 19-20%
1. Haematogenous spread of bacteria 1. Crohn's (commonest cause in this category)
2. Staphylococcus aureus: most common 2. Diverticulitis, colorectal cancer
3. UTI, GU cancers
4. Vertebral osteomyelitis
 5. Femoral catheter, lithotripsy
Endocarditis
Clinical features
Fever/back pain with pain on extension of the hip → iliopsoas abscess (Not resolver by Antibiotics)
1. Fever
2. Back/flank pain
3. Limp
4. 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:
 Place hand proximal to the patient's ipsilateral knee and ask patient to lift thigh against your hand pain due to contraction of Psoas muscle.
 Lie the patient on the normal side and hyperextend the affected hip pain as the psoas muscle is stretched.
Investigation
CT is the gold standard

Management
 Antibiotics
 Percutaneous drainage  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
Septic arthritis
 most common organism  Staphylococcus auras, young adults sexually active Neisseria Gonorrhoeae should also be considered
 ↑↑ in knee
 The Kocher criteria for the diagnosis of septic arthritis:
1. fever >38.5 degrees C
2. Non-weight bearing
 3. ↑↑ ESR
4. ↑↑ WCC
 The three classic differentials for this presentation  Septic arthritis, Gout and Pseudogout
 Culture will enable a positive diagnosis of septic arthritis,
 microscopy and gross appearance the diagnosis of crystal arthropathy.

Management
1. synovial fluid should be obtained before starting treatment
2. IV antibiotics cover Gram-positive cocci are indicated ( flucloxacillin or clindamycin if penicillin allergic) (6-12 weeks)
3. Needle aspiration should be used to decompress the joint (Even w ↑↑ INR)
4. arthroscopic lavage may be required
Reactive arthritis
 Following infection (organism not recovered from joint).  Post-STI (Chlamydia Trachomatis) "Acquired reactive arthritis" SARA) OR GIT "Salmonella"
 One of the HLA-B27 associated seronegative spondyloarthropathies.
 It encompasses Reiter's syndrome (urethritis, conjunctivitis and arthritis) following a dysenteric

Epidemiology
 Post-STI  men > Females (10:1)
 Post-dysenteric  form equal sex incidence
Features
1. within 4 weeks of initial infection  lasts around 4-6 months
2. Arthritis
 Asymmetrical Oligoarthritis of lower limbs
 Dactylitis
3. Urethritis
4. Eye
 Conjunctivitis (10-30%)
  Anterior uveitis
5. Skin
 Circinate balanitis (Painless vesicles on the coronal margin of the Prepuce)
 keratoderma Blenorrhagica (Waxy yellow/brown papules on palms and soles)

25% of patients  recurrent episodes, 10% of patients  chronic disease:

6.
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 & Methotrexate are sometimes used for persistent disease
3. symptoms rarely last > 12 months

Osteomyelitis
Infection of bone  Staph. aureus is the most common cause except in patients with sickle-cell anaemia and hemoglobinopathies  Salmonella (usually
preceded by GIT upset. Predisposing conditions
1. D.M
2. Sickle cell anaemia
3. I.V drug user
4. Immunosuppression due to either medication or HIV
5. Alcohol excess

Investigations
MRI is the imaging modality of choice, with a sensitivity of 90-100%
 Management
1.Flucloxacillin  6 weeks
2.Clindamycin if penicillin-allergic

Avascular necrosis of Hip(AVN)

death of bone tissue 2ry to loss of blood supply  bone destruction and loss of joint function  most commonly affects the epiphysis of long bones ( femur).
Causes
1. long-term steroid use
2. chemotherapy
3. alcohol excess
4. trauma

Features
1. initially asymptomatic
2. Pain in the affected joint  might referred to groin
3. Limping and limited range of joint mobility

Investigation
 Plain X- Ray
 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

DD. Bone metastasis  X-ray lesions + bone pain.

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

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

pain syndrome  Pain and tenderness over the lateral side of thigh
(Trochanteric bursitis)  ↑↑ (Night & when ling on the affected side.
 ↑↑ women aged 50-70 years.
 No limitation of movement
 X- Ray might reveal mild space narroing
Referred lumbar spine  Femoral nerve compression 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

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
 Condition Features
 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 pregnancy
osteoporosis  Groin pain associated with a limited range of movement in the hip
 atients may be unable to weight bear
 ESR may be elevated
Meralgia paraesthetica
 Greek words "Meros"  thigh and "Algos"  pain  syndrome of paraesthesia 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
 1ry Sensory Nerve, (No motor fibres) 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),  subject to repetitive trauma or pressure.
 Compression of this nerve anywhere along its course can lead to the development of meralgia paraesthetica.

Epidemiology
 30 and 40 W men > women
 In some, both legs may be affected.
 ↑↑ D.M .

Risk factors
1. Obesity
2. Pregnancy
3. Tense ascites
 4. Trauma
5. Iatrogenic,  pelvic osteotomy, spinal surgeries, laparoscopic hernia repair and bariatric surgery abduction splints (management of Perthe's D
6. Various sports  gymnastics, football, bodybuilding and strenuous exercise.
7. Some cases are idiopathic.

Presentation with the following symptoms in the upper lateral aspect of the thigh:
 Burning, tingling, coldness, or shooting pain
 Numbness
 Deep muscle ache
 ↑↑↑standing, and ↓↓↓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.
 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
 Nerve conduction studies may be useful.

Rotator cuff muscles

SItS - small t for teres minor  ↑↑Pain (Movement, at night and when lying on the affected side)
1. Supraspinatus
2. Infraspinatus
3. teres minor
4. 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
Condition Notes
Lateral  45-55 years  dominant arm activity (house painting or playing tennis)
epicondylitis  Pain and tenderness localised to the lateral epicondyle
(Tennis elbow)  ↑↑ ( resisted wrist extension + elbow extended) OR (Supination of the forearm + elbow extended)
 Attacks  ( 6 Ms -2 years) W acute pain for 6-12 weeks
 Management options
1. advice on avoiding muscle overload
2. simple analgesia
3. steroid injection
4. physiotherapy
Radial tunnel  Compression of the posterior interosseous branch of the radial nerve. overuse.
syndrome  symptoms are similar to lateral epicondylitis making it difficult to diagnose
 DD. 4-5 cm distal to the lateral epicondyle
↑↑ by extending the elbow + Pronating the forearm
Medial  pain and tenderness localised to the medial epicondyle
epicondylitis  ↑↑ wrist flexion and pronation
(golfer's elbow)  numbness / tingling in the 4thfourth and 5th finger due to ulnar nerve involvement
Cubital tunnel  Compression of the ulnar nerve.
syndrome  ↑↑ elbow is resting on a firm surface OR flexed/ bent for extended periods
 Condition Notes
 later numbness in the 4th and 5th finger with associated weakness
Olecranon bursitis  Swelling over the posterior aspect of the elbow. middle-aged male patients
 pain, warmth and erythema.

Adhesive capsulitis
 (frozen shoulder) is a common cause of shoulder pain. It is most common in middle-aged females. The aetiology is not fully understood.
 Associations  D.M up to 20% of diabetics may have an episode of frozen shoulder
 Features typically develop over days
1. External rotation is affected > internal rotation or abduction
2. ↓↓( active and passive movement)
3. Painful freezing phase  Adhesive phase  Recovery phase
4. Bilateral (20%)
5. Episode  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

Carpal tunnel syndrome (Thumb and index)

Compression of median nerve in the carpal tunnel. Features
1. pain/pins and needles in Thumb, index, middle finger
2. unusually the symptoms may 'ascend' proximally
3. patient shakes his hand to obtain relief, classically at night

Examination
 1. weakness of thumb abduction (abductor pollicis brevis)
2. wasting of thenar eminence (NOT hypothenar)
3. Tinel's sign  Tapping causes paraesthesia
4. Phalen's sign  flexion of wrist causes symptoms

Causes
1. idiopathic
2. pregnancy
3. oedema  heart failure
4. Obesity independent risk factor in those < 63 years
5. lunate fracture
6. rheumatoid arthritis

Electrophysiology
motor + sensory: prolongation of the action potential

Treatment
1. corticosteroid injection
2. wrist splints at night
3. surgical decompression (flexor retinaculum division)

C6 entrapment neuropathy More proximal (weakness of the biceps muscle or reduced biceps reflex).

Cubital Tunnel Syndrome(little &Ring finger)

Due to compression of the ulnar nerve as it passes through the cubital tunnel. Features
1. Tingling and numbness of the 4th and 5th finger which starts off intermittent and then becomes constant.
2. Over time patients may also develop weakness and muscle wasting
3. Pain  worse on leaning on the affected elbow
4. 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

Radial tunnel syndrome  aching and paraesthesia of the hand with forearm pain distal to the lateral epicondyle

De Quervain's tenosynovitis Base of thumb/Radial styloid

common condition  Inflammation of sheath containing the extensor pollicis brevis and abductor pollicis longus tendons. females 30 - 50 years
Features
1. pain on the radial side of the wrist
2. tenderness over the radial styloid process
3. abduction of the thumb against resistance is painful
4. Finkelstein's test  the examiner pulls the thumb of the patient in ulnar deviation and longitudinal traction.  pain over the radial styloid process and
along the length of extensor pollisis brevis and abductor pollicis longus

Management
1. analgesia
2. steroid injection
3. immobilisation with a thumb splint (spica) may be effective
4. surgical treatment is sometimes required

Ankle injury: Ottawa rules

 The Ottawa Rules with for ankle X-Rays (sensitivity 100%)
An ankle x-ray  only if there is any pain in the malleolar zone + 1 of the following findings:
1. Bony tenderness  lateral malleolar zone (tip of the lateral malleolus to include the lower 6 cm of posterior border of the fibular)
2. bony tenderness  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

Familial Mediterranean Fever

 "Recurrent Polyserositis"  AR (2nd decade. ↑↑↑Turkish, Armenian and Arabic descent)
 Features - attacks typically last 1-3 days
1. pyrexia
2. abdominal pain (due to peritonitis)
3. pleurisy
4. pericarditis
5. arthritis
6. Erysipeloid rash on lower limbs

 Management
Colchicine may help

DD. Other Polyserositis

1. Pancreatitis
2. 1ry effusion lymphoma  Lymphadenopathy, 1ry effusion lymphoma
3. SLE
4. Castleman's