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BCS Lectures > Preena Joshi > Flashcards

Preena Joshi Flashcards

1
Q

Genetic susceptibility factors for SLE

A
  1. More common in people with early complement protein deficiency - (c1q, c2, c4 - results in lack of clearance of immune complexes)
  2. Histocompatibility genes (6p21.33; 6p21.32). HLA B8, DR2, DR3
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2
Q

Which finding would suggest drug induced SLE?

A

Anti-histone antibody

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3
Q

What are the major subcategories of SLE pathophysiology

A
  1. Type II hypersensitivity reaction (cytotoxic antibody mediated attack) mainly
  2. Type III hypersensitivity reaction (immune complex mediated) to a lesser degree
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4
Q

Describe the type II pathophysiology in SLE

A

Type II Hypersensitivity

  1. Autoantibodies binding directly to surface of blood cells - especially erythrocytes but all leukocytes to lesser extent
  2. Results in pancytopenia and increase susceptibility to infection
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5
Q

Effect of SLE on the kidneys

A
  1. Can be nephrotic (>3.5 g/day protein) or nephritic (bleeding and inflammation) - usually nephritis doe
  2. IC deposition results in activation of complement (classical) via a type III hypersensitivity reaction
  3. Most commonly results in diffuse proliferative glomerulonephritis seen as subendothelial,intramembranous and/or mesangial deposition of IgG with C3 deposition
  4. LM will show wire looping in kidneys and granular immunofluorescence
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6
Q

Effect of SLE on the heart?

A
  1. LSE disease (Libman Sacks Endocarditis)
  2. Verrucous thrombi (nonbacterial vegetations on both sides of the mitral and aortic valves)
  3. These vegetation may result form immune complex deposition.
  4. The condition may progress to valve fibrosis resulting in regurgitation or possible stenosis.
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7
Q

Signs and symptoms of SLE with justification

A

Rash (malar or discoid) - Skin infiltration by leukocytes and other immune cells in response to UV light are crucial to the development of CLE lesions.

Arthritis (inflammatory, migratory, nonerosive - monoarthritis is rare in SLE)

Serositis (pericarditis, pleuritis - manifests as chest pain and SOB

Haematoligcal dysfuction - pancytopenia - manifests as fatigue

Oropharyngeal/mouth ulcers - painless but prolonged and recurrent

Renal impairment - manifests as edema, hematuria, proteinura, oliguria

Photosensitivity

Antinuclear antibodies

Immunoligic disorder

Neuroligcal disroder (seizure, psychosis)

Other:

Alopecia

Cardiovascular: HTN, dysrhytmias, venous/arterial thrombosis

Fibronyalgia

Raynaud’s phenomenin - colour changes of the digits induced by cold or emotion

  • Triphasic colour change from white to blue to red in fingers and toies
  • Bilateral
  • Fever
  • Weight loss
  • Lymphadenopathy
  • peripheral that is regional rather than generalised (cervical and axillar regions)
  • Non tender around 3-4 cm
  • Abdominal pain and diarrhoea
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8
Q

First line investigations of SLE

A

1st to order:

  1. FBC and differential:
    anaemia, leukopenia, thrombocytopenia; rarely pancytopenia
    - Leukopenia is usually caused by lymphopenia rather than neutropenia.
  2. Activated PTT:
    May be prolonged in patients with antiphospholipid
  3. U & E:
    Elevated due to renal manifestations
  4. ESR and CRP:
    Non specific
    ESR due to increase immunoglobulins
  5. ANA, anti dsDNA, Smith antigen
    - Anti dsDNA suggestive of renal impairment
    - ANA most sensitive
    Clinically relevant ANA are IgG
    - Positive ANA in itself may also indicate other connective tissue disease such as RA, Sjogren’s, thyroid disease and certain drugs
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9
Q

Ddx of SLE

A
  1. RA
    Joint X ray would show symmetrical erosive arthrtis in RA but non erosive in SLE
  2. Antiphospholipid syndrome
    Recurrent venous or arterial thrombosis
    Recurrent miscarriages
    Anticardiolipin IgG or IgM present in moderate or high levels on >2 occasions at leat 6 weeks apart
    Lupus anticoagulant detected >2 occasiona at least 6 weeks apart
    B glycoprotein positive
    Veneral disease research labortaty test: flase positive due to cardiolipin (Syphillis)
  3. Systemic sceloris
    Raynouds phenomenon that ulcerates (does not ulcerate in SLE)
    Patients with systemic sclerosis have characteristic sclerodactyly and calcinosis, not present in SLE.
    positive anti-centromere antibodies or anti topoisomerase antibodies
  4. Mixed connective tissue disease
    Tend to lack anti-Sm, anti-Ro and anti dsDNA
  5. Adult Still’s disease
    Variant of juvenile RA characterised by seronegative chronic polyarthritis with systemic manifestations
    Elevated ferritin
    Rash is usually only seen in febrile peroids and is usually salmon coloured
  6. Lyme disease
    Exposure to ticks
    Lyme specific IgM or IgG
    Presence of ANA common but dsDNA and Smith are not
  7. HIV
    HIV ELISA positive
    ANA may be present but dsDNA and Smiths are not
    CMV
    Serology positive
    ANA may be present but dsDNA and Smiths are not
8. Infectious Mononucleosis
In patients with EBV 
Positive agglutination
Septic arthritis
Positive culture joint aspiration
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10
Q

Genes associated with SLE

A

HLA B8, DR2, DR3

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11
Q

Which virus may trigger SLE?

A

EBV

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12
Q

Antibodies in SLE and % of times that they wil be positive in people with SLE

A
  1. ANA (most sensitive) 95%
  2. Anti dsDNA (highly specific) - 60%
  3. Anti Rf - 40%
  4. Anti ENA - (Anti RO, La, Sm RNP) - 20-30%
  5. Antiphospholipid Ab’s (lupus anticoag and anticardiolipin) - also assocaited with Shogrens (15-20% ) autoimmune thyroid disease (5-10%)
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13
Q

Best tests for monitoring SLE activity

A
  1. Anti dsDNA
  2. C3 and C4 (denotes consumption of complement, hence C3 and C4 low, and
    C3d and C4d high, their degradation products).
  3. ESR
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14
Q

Relationship between ESR and CRP

A

if ESR high but CRP normal think about SLE whenever someone has a multisystem disorder

If CRP is high think of infection, serositis or arthritis

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15
Q

Which drugs may worsen idiopathic SLE

A
  1. Sulphonamides

2. OCP

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16
Q

Tx of SLE acute flares
(eg haemolytic anaemia, nephritis, severe pericarditis
or CNS disease)

A
  1. IV Cyclophosphamide

2. High dose prednisolone

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17
Q

Tx of SLE cutaneous symtoms

A
  1. Topical steroids

2. High factor sunblock

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18
Q

Maintenance Mx of SLE

A
  1. NSAIDs
  2. Hydrochloroquine (joint and sin)
  3. Low does steroids for chronicity
  4. Azathioprine,
    methotrexate and mycophenolate are used as steroid sparing treatment
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19
Q

Tx of lupus nephritis

A

May require more intensive immunosuppression with steroids

and cyclophosphamide or mycophenolate

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20
Q

What is the injury in a”floating shoulder injury”

A

Fracture of the distal clavicle and neck of the scapula

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21
Q

What is the common mechanism of injury in a floating shoulder injury

A

Occurs due to high energy trauma such as motor vehicle accidents, fall from height, crush injury, gunshot wound

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22
Q

What is the artery at most risk in a floating shoulder injury

A

Axillary - see pics in joint anatomy sheet

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23
Q

What are the main componeNts of anasTAmoses around the scapula?

A

SEE IMAGE IN JOINT ANAT. SHEET

  • The Arterial Anastomosis around Scapula is principally created between the branches of the first part of the subclavian and the third part of the axillary arteries.
    1. Suprascapular artery (from the thyrocervical trunk)
    2. Circumflex scapular artery (subscapular artery, from axillary)
    3. Dorsal scapular artery (of the subclavian)
    4. Intercostal arteries (thoracic aorta)
  • SEE IMAGE IN JOINT ANATOMY SHEET
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24
Q

What is the clinical significance of the scapular anatamoses

A

The Arterial Anastomosis around Scapula is principally created between the branches of the first part of the subclavian and the third part of the axillary arteries.

If the subclavian and axillary arteries are blocked anywhere between 1st part of subclavian artery and 3rd part of axillary artery, the scapular anastomosis acts as a potential pathway (collateral circulation) between the first part of the subclavian artery and the third part of the axillary artery, to ensure the adequate circulation to the upper limb.

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25
Q

Which nerve is most likely to be damage in an anterior dislocation of the shoulder? How would this present?

A

Axillary nerve damage

Inability to abduct >15 degrees (deltoid)
flattened deltoid
loss of sensation over deltoid muscle and lateral arm

Also might have damage to the radial nerve since it is tightly bound in the radial groove

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26
Q

Which muscles attach to the glenohumeral capsule?

A

Rotator cuff muscles

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27
Q

Another name for adhesive capsulitis

A

Frozen shoulder

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28
Q

What is the function of the glenohumeral joint capsule?

A

a fibrous sheath which encloses the structures of the joint. It extends from the anatomical neck of the humerus to the border of the glenoid fossa. The joint capsule is lax, permitting greater mobility (particularly abduction).

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29
Q

What is the function of the synovial membrane and its associated bursae?

A

The synovial membrane lines the inner surface of the joint capsule, and produces synovial fluid to reduce friction between the articular surfaces.
To reduce friction in the shoulder joint, several synovial bursae are present. A bursa is a synovial fluid filled sac, which acts as a cushion between tendons and other joint structures.

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30
Q

What changes occur in the joint capsule in adhesive capsulitis/frozen shoulder

A

Thickening and contraction of the glenohumeral joint capsule and formation of adhesions cause pain and loss of movement

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31
Q

Which muscles attach to the lateral supracondylar ridge

A
  1. Brachioradialis
  2. Extensor carpi radialis longus
  3. Triceps brachii
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32
Q

Pronators of the forearm

A
  1. Brachioradialis
  2. Pronator teres
  3. Pronator quadratus
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33
Q

Supinators of the arm

A
  1. Supinator

2. Biceps brachi

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34
Q

How are the medial and lateral epicondyles related to the flexors and extensors of the forearm? How might flexor/extensor muscle movement create pain for people suffering from lateral/medial epicondylitis?

A

flexors on medial epicondylitis = golfers elbow

extensors on lateral epicondyle = tennis elbow

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35
Q

Borders of the cubital fossa

A

Lateral border – The medial border of the brachioradialis muscle.

Medial border– The lateral border of the pronator teres muscle.

Superior border – An imaginary line between the epicondyles of the humerus.

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36
Q

Contents of the cubital fossa

A

From lateral to medial

“Really Need Beer To Be At My Nicest.”

Radial nerve

Biceps tendon

Brachial artery

Median nerve

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37
Q

Boundaries of Guyons canal

A

Floor: T
ransverse carpal ligament, hypothenar muscles

Roof: Volar carpal ligament

Ulnar border: Pisiform and pisohamate ligament, abductor digiti minimi muscle belly

Radial: border Hook of hamate

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38
Q

What runs through Guyons canal

A

Ulnar nerve and artery

ulnar nerve bifurcates into the superficial sensory and deep motor branches

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39
Q

What does the deep branch of the ulnar nerve innervate

A
  • Innervates all of the interosseous muscles and the 3rd and 4th lumbricals.
  • Innervates the hypothenar muscles, the adductor pollicis, and the medial head (deep) of the flexor pollicis brevis (FPB)
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40
Q

What is the ulnar paradox and why does it occur

A

Ulnar claw: Distal to the elbow, proximal to the wrist
1. Ulnar nerve innervated the lumbrical which flex at MCP joint and extend at IP joints. Damage to ulnar nerve results in extension at this joint due to unopposed action of extensor digitorium and extensor digiti minimi
2. Loss of extension of IP joints results in flexion of IP of ulnar two fingers due to the lack of opposition of the FDP = claw appearance
Ulnar paradox: closer to the elbow.
- Ulnar nerve lesion closer to the elbow reduces action of FDP = less flexion = less claw like. Seems like the injury is better but its actually worse!

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41
Q

How to test for collateral blood supply in the hand

A

Allens Test

radial and ulnar are collateral circulation for one another for the hand - if you occlude one the other will take over provided it is in a healthy condition
If color returns as described, Allen’s test is considered to be normal. If color fails to return, the test is considered abnormal and it suggests that the ulnar artery supply to the hand is not sufficient.[2] This indicates that it may not be safe to cannulate or needle the radial artery.

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42
Q

Carpal tunnel structure

A

Median nerve

4 x FDP

4 x FDS

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43
Q

Cells in the epidermis

A

Keratinocytes

Also melanocytes and langerhans cells

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44
Q

Cells in the dermis

A

skin’s next layer, is a thick
layer of fibrous and elastic tissue made
mostly of collagen, elastin, and fibrillin

Contains blood vessels, nerves and
specialized structures such as sweat glands
and hair follicles

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45
Q

Difference between UVA and UVB

A

UVA - long wave and causes photoageing (wrinkles and ageing) - 320-400nm

UVB - burns and skin cancer 290-320

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46
Q

Skin phenotypes

A

SPT I

Always burns, never tans – pale white

SPT II

Burns easily, tans minimally - white

SPT III

Burns moderately, tans gradually to light
brown - white

SPT IV

Burns minimally, always tans well to
moderately brown – light brown

SPT V

Rarely burns, tans profusely to dark
brown – brown (e.g. Asian)

SPT VI

Never burns, deeply pigmented – black
(e.g. African)

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47
Q

Describe sunburn and risk factors associated with it

A

Acute inflammatory response to UV radiation

More frequently seen in individuals with SPT I
and II

Repeated sunburns lead to photoageing and
increased risk of skin cancer

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48
Q

Tx for sunburn

A
  • cool wet dressings
  • topical steroids
  • systemic steroids / NSAIDs
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49
Q

Features of action/solar keratoses

A

Marker of chronic sun damage

Back of hands, forearms, forehead, scalp,
temples, nose, cheeks and ears

Pre – Malignant; Increased risk of
developing non-melanoma skin cancer

Poorly defined scaly areas, erythematous
base

Discrete yellow-brown keratotic lesions

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50
Q

Mc of actinic/solar keratoses

A
  • Cryotherapy (light spray of liquid nitrogen)
  • Cauterization
  • 5-FU cream (Efudix) for multiple lesions
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51
Q

Desribe polymorphous light eruption

A

Idiopathic & acquired reaction to UV radiation

5% population, female predilection, 23 years

Lesions appear in Spring/Summer

Pruritic erythematous macules, papules, plaques
and vesicles

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52
Q

Prevention of polymorphous light eruption

A

Sunscreen

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53
Q

Mx of polymorphous skin eruption

A

Topical/systemic sterioids

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54
Q

Examples of drug induced photo sensitivity

A

Phototoxicity

Photoallergy

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55
Q

What cuases phototoxicity

A

psoralen

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56
Q

Features of phototoxicity

A

More common

Changes noted within hrs
of exposure

UV ‘activates’ the agent
which then destroys cell
membranes or DNA

Limited to sun-exposed
sites

Looks like severe sunburn

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57
Q

Drugs that cause photoallergy

A

Thiazides, Amiodarone (causes skin to become blue),
Tetracyclines,
Sulfonamides

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58
Q

Features of photoallergy

A

Less common

Changes noted 1-3 days
after exposure

UV changes the ‘shape’ of
the substance so that it
gets recognized by the
immune system

Looks like contact
dermatitis mainly at
exposed sites

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59
Q

Which conditions are exacerbated by sunlight

A

SLE

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60
Q

What differentiates a malar rash from other butterfly rashes

A

Spares the nasolabial folds - LUPUS

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61
Q

Conditions improved by sunlight

A
  1. Psoriasis

2. Atopic dermatitis

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62
Q

Treatment for psoriasis

A

Narrow band UVB (reduces risk of skin cancer)

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63
Q

Describe porphyria cutanea tarda

A

UROGEN decarboxylase deficiency

Bullae are seen after sun exposure (dorsum of hands and face)
which resolve with scarring. Condition

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64
Q

What is PCT assocaited with ?

A

Condition associated with
chemicals and drugs (alcohol, estrogen, iron), liver disease
(hepatitis C) and diabetes mellitus

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65
Q

Features of PCT

A

hypertrichosis(hair growth) (sides of face and
between eyebrows), hyperpigmentation of the facial skin

In this condition there is an hepatic
enzyme abnormality with a genetic predisposition. It presents with
bullous eruption which heals with scarring and milia formation

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66
Q

Diagnosis of PCT

A

Urine test with Wood lamp examination: orange-red

fluorescence due to increased uroporphirin in urine

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67
Q

Features of xeroderma pigmentosa

A

Rare autosomal recessive disorder

Cellular hypersensitivity to UV radiation
due to defect in DNA repair

Photosensitivity, pigmentary changes,
premature skin aging & malignant tumour
development.

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68
Q

Management of xeroderma pigmentosa

A

Management: sun-avoidance, surveillance

for early skin cancer detection.

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69
Q

Basal cell carcinoma lesions

A

Sun-exposed sites

Raised, pearly or translucent papule

Telangiectasia

Central ulceration

Rolled edge

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70
Q

Does BCC metastasise?

A

rarely

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71
Q

Tx of BCC

A

Surgical excision ( consider MOHS for difficult sites)

Curettage + Cautery

Radiotherapy

Topical Imiquimod - superficial BCC’s

Topical 5-FU - superficial BCC’s

Cryotherapy – superficial BCC’s

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72
Q

Diagnosis of squamous CC

A

Presence of thick keratin layer contained within squamous cells

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73
Q

Features of SCC

A

Second commonest form of skin cancer

Malignant tumour of keratinocytes

Begin as keratotic nodules

Firm indurated base

Ulcerating as enlarge

Invades deeply and may metastasise if untreated (to the LNDs)

74
Q

Mx of SCC

A

Excision

75
Q

Describe Bowen’s disease

A

Dysplastic changes are confined to the
epidermis i.e. no invasion

They usually occur in sun exposed sites
(especially lower leg)

Usually will be a lesion that has been there or a number of years

76
Q

Tx of Bowens disease

A

Monitor the lesion - it will be increasing in size

It can be treated with cryotherapy,
curettage and cautery or radiotherapy.
Topical 5 fluorouracil is helpful in multiple
lesions

77
Q

Features of lentigo

A

“Sun spots”
Benign

Flat, pigmented areas

Composed of increased numbers of
melanocytes

78
Q

Features of lentigo maligna

A

Melanoma in situ
ie: patch of malignant melanocytes, in
sun-damaged skin, which proliferate along
dermo-epidermal junction.

Malignant transformation may take years!

Lesion flat, irregular outline and pigment

Management: Excision

79
Q

Skin surveillance steps

A

A symmetry (in colour and shape)

B order

C olour

D iameter (<6mm benign)

E volution (elevation – enlargement)

  • More than two signs you should be monitored or have the lesion excised
80
Q

Types of malignant melanomas and who/where they present

A

Various Forms:

Lentigo Maligna = elderly patient

Superficial Spreading = commonest

Nodular = invasive pattern

Acral = on sole or palm

Subungual = beneath the nail

Amelanotic = often late presentation

81
Q

Melanoma prognosis

A

Prognosis directly related to tumour
thickness on histology (Breslow thickness)

<1.5mm~ excellent prognosis

> 3.5mm~ normally metastasise despite wide
resection margins - bad prognosis

82
Q

Mx of malignant melanoma

A

Surgical excision with wide margin

Plastic surgery consult often required

83
Q

Types of immunoflouresence

A

Direct: single Ab linked to a fluorophore
(tissue-bound Abs)

Indirect: primary and secondary (which
carry the fluorophore) Abs (circulating Abs)

84
Q

Autoimmune iseases of the skin

A

Pemphigus

Bullous pemphigoid

Dermatitis herpetiformis

Psoriasis

Vitiligo

Alopecia areata

Epidermal necrolysis

85
Q

Features of pemphigus

A

Bullous autoimmune disease of skin and mucous membranes
based on acantholysis – loss of the normal cell-to-cell adhesion in
the epidermis

Circulating IgG antibodies that bind to desmosomes

Vescicles – bullae formation, superficial, flaccid → erosions

86
Q

Who does pemphigus affect

A

Affects adults 40-60s, more common in Ashkenazi Jews

87
Q

Investigations of pemphigus

A

Biopsy shows intraepidermal vesicles with keratinocytes floating
free in the blister cavity (acantholysis)

Immunofluorescence
shows IgG fixed against intercellular desmosomes between
keratinocytes.

88
Q

Tx of pemphigus

A

Treatment is initially with high dose systemic steroids and in the
long-term a steroid sparing agent e.g. Methotrexate, Azathioprine

89
Q

S+S of pemphigus

A 
It usually begins in the oral
mucosa and is characterised
by flaccid vesicles which
are fragile and burst readily
producing eroded areas on
the face, scalp, neck and
chest
Nikolsky sign positive: by
applying lateral pressure to
normal skin, there is a
resulting shearing of the
epidermis→ erosion
formation
90
Q

Pathophys of bulous pemphigoid

A

The most common autoimmune blistering disease
Affects the older patients
Circulating IgG antibodies that bind to hemidesmosomes
Large, tense bullae

91
Q

Diagnostic features of pemphigus

A

Histologically there are subepidermal blisters with the defect in the dermo-epidermal junction.
Immunofluorescence shows IgG and C3 binding to the dermo-epidermal junction in a linear fashion.
Circulating IgG is present in the serum

92
Q

Tx of bullous pemphigoid

A

Treatment is initially with moderate doses of systemic steroids and sparing agents e.g Azathioprine, Methotrexate, Dapsone, Minocycline

93
Q

Differene between pemphigous and bullous pemphigous

A

SEE SLIDE 26 IN AUTOIMMUNE SKIN LECTURE MUSTKNOW THIS

  • know the different layers that they affect
94
Q

What is Dermatitis Herpetiformis assoc with

A

Gluten sensitive enteropathy

95
Q

Who is Dermatitis Herpetiformis

seen in

A

white peeps 20-30

96
Q

Histological features of Dermatitis Herpetiformiss

A

Histologically there are subepidermal blisters and immunofluorescence shows fixed IgA (between dermis and epidermis) in dermal papillae
There is no circulating autoantibody

97
Q

Tx of Dermatitis Herpetiformis

A

Treatment is lifelong with a gluten free diet

Dapsone can also be given to these patients (side effects include methaemoglobinaemia and haemolytic anaemia)

98
Q

Features of D.H.

A

Intensely pruritic, symmetrically distributed, erythematous papules and vesicles over the extensor surfaces of elbows, knees, forearms, buttocks and face/scal

99
Q

Pathophys and presentation of vitiligo?

A

This is an autoimmune condition affecting the melanocytes (in basal layer of the skin) which may be associated with other autoimmune and/or endocrine conditions

Common worldwide – 1% of the population
Hypopigmentary macules, sharply marginated that coalesce

Face orifices, digits and sites of pressure (elbows, knees) are the first affected

Hair depigmentation (poliosis)

100
Q

Features of vitiligo

A

Areas of pigment loss are symmetrical and are often annular in outline, but can be various shapes

Usually initially affect fingers, hands, face and genitalia

Exhibits the Koebner reaction, with the development of lesions at traumatized sites e.g. soles of feet when you walk a lot

101
Q

What is vitiligo assoc with

A

Graves disease

alopecia areata

102
Q

Features of alopecia areata

A

There is patchy hair loss over any part of the scalp but often the occipital area extending into the scalp is usually affected Pathognomonic “exclamation-mark” hairs are broken hairs which indicates disease activity
Hair loss can occur anywhere else and there may be associated nail pitting

103
Q

Pathophys of epidermal necrolysis

A

Cell-mediated cytotoxic reaction against keratinocytes leading to massive apoptosis

Acute, life-threatening mucocutaneous reaction characterized by extensive necrosis and detachment of the epidermis

Idiopathic or drug induced (anticonvulsants, antibiotics, NSAIDS, allopurinol)

Overall mortality: 20-25%

104
Q

Difference between Stevens-Johnson Syndrome

Toxic Epidermal Necrolysi

A

Variants of epidermal necrolysis, differ only in the percentage of body surface involved.
SJS < 10%
SJS/TEN overlap – 10-30%
TEN > 30%

105
Q

Clinicalfeatures of epidermal necrolysis

A

Prodromes: fever, malaise, arthralgias

Skin tenderness, burning sensation, conjuctival burning, mouth tenderness
s include conjunctivitis, uveitis and corneal ulceration, so its important to ask for early ophthalmology review

Macular/target-like lesions → flaccid blisters → necrosis and epidermal detachment

Nikolsky sign

106
Q

Complications of epidermal necrolysis

A

Infection predisposition

Sepsis

Fluid loss

Impaired thermoregulation

Visceral involvement (GI bleeding, bronchial erosions & ARDS)

Nutritional deficiencies – impaired oral intake

107
Q

Mx of epidermal necrolysis

A

Withdraw the offending drug

Supportive care in hospital setting

Fluid replacement

Early nutritional support

Skin, blood, urine cultures→ antibiotics

Pain management

Mouth antiseptics

Ophthalmological evaluation

108
Q

Features of skin sclerosis

A

Classically there is beaking of the nose, furrowing of the lips and facial telangiectasia (they are mainly on the cheeks and nose) - sclerodactyly

Other organ sclerosis
Most organs may be affected but most frequently the oesophagus and patients can present with dysphagia

109
Q

Describe sclerodactyly

A

The skin of the fingers appear tightened and shiny due to fibrosis. There are telangiectasia also seen here affecting the hands

110
Q

Features of sclerderma

A

hickening of the skin which if only confined to the skin is called morphea (localized scleroderma)
This picture shows a smooth, waxy plaque which has a sclerotic feel. In active morphea there is a purplish border (lilac ring) as is seen here

111
Q

What presents with thickening of collagen throughout the dermis with loss of appendages (hair follicles, sweat glands, sebaceous glands)

A

Morphea/systemic sclerosis

112
Q

Skin manifestations of RA

A

Rheumatoid nodules
Vasculitis
Vasculitic rash (“palpable purpura”) -PAINFUL
Skin ulceration

113
Q

Describe the features of dermatomyositis

A

Heliotrope/Violaceous rash- eyelids

Erythema of the face, neck and upper trunk

Knuckles: Gottron’s papules ( seen here as purple streaky lesions affecting the extensor aspect of the fingers)

Fingernail: periungual telangiectasias

Photosensitivity

Polymyositis (if not: amyopathic DM)

Underlying malignancy

  • Patients >40y – investigation is recommended
  • Breasts, ovary, lungs, GI, prostate Ca
114
Q

Types of immunochemical tests

A

Based on Ab-Ag complexed using enzyme flouresence

Immunofluorescence

Nephelometry

ELISA

Electrophoresis

Flow cytometry

115
Q

Use of immunochemistry

A
  1. Aid in clinical diagnosis (thyroid abs)
  2. Severity of disease (high RF and CCP)
  3. Prognosis of the condition (high anti DNA)
  4. Monitor-relation to disease activity
    treatment, relapse, remission (ANCA)
116
Q

Most common detection method

A

Indirect immunofluorescence

117
Q

What does immunochemistry measure

A
  1. normal and abnormal immunoglobulins
  2. Acute phase proteins e.g. CRP
  3. Complement components
  4. Complement activity
118
Q

What is ANA present in?

A

Sensitive but not specific

SLE,
MCTD,
Sjogren’s,
Scleroderma

ANA can also be positive in juvenile chronic
arthritis, RA and other autoimmune diseases and
infections.

ANA also found in a percentage of healthy
individuals and in the elderly.

119
Q

Significance of a homogeneous pattern

A 
A uniform diffuse
fluorescence of the entire
nucleus of interphase cells.
Fluorescence intensity more
pronounced in the
chromosomal region in mitotic cells
120
Q

Clinical assoc. of homogeneous pattern

A
  1. SLE,
  2. drug induced lupus,
  3. RA,
  4. juvenile
    chronic arthritis
121
Q

Confirmatory test for dsDNA abs

A

Crithidia test (strongly suggestive of SLE)

specificity of 95% , sensitivity
of 70%
antigen: dsDNA

122
Q

Use of direct IF

A

Detection of Immune complexes (IC) on
tissue biopsy from patient.

Tissue sections eg skin or kidney are mounted onto slides

Incubated with anti-human IgG-FITC (fluorescein IsoThioCyanate) which binds to the IgG from the IC.

Lumpy bumpy pattern seen on renal biopsy from lupus patient, ICxes on basement membrane

123
Q

Relationship between anti-dsDNA Ab and renal disease

A

The presence of anti - dsDNA ab is closely related to renal disease and an increase in levels alerts to a possible flare of disease.

Important to measure C3 / C4 (low in renal
involvement)

124
Q

Diagnostic criterIa for SLE

A

ANA (almost always but not specific)

Anti ds DNA (Almost always – specific)

Anti Smith (not always but VERY specific)

Ro, La,RF, Anticardiolipin (non specific)

125
Q

Features of antiphospholipid syndrome

A
  1. lupus anticoagulant and/or
  2. antibodies to cardiolipin, ( and anti - β2 GPI antibodies)
  3. Arterial / venous thrombosis
  4. Recurrent foetal loss (>3months)
  5. Migraine
  6. Livedo reticularis -
    the things white girls get when they are cold (and rarely other rashes / skin ulceration)
  7. Sometimes ‘catastrophic antiphospholipid syndrome’ with
    multi-organ failure
126
Q

Key features of APL

A
  1. ANA
  2. Anticardiolipin antibodies
  3. Anti – b2 GPI antibodies
  4. Lupus anticoagulant
127
Q

Features of Sjogren syndrome

A

Autoimmune condition affective mostly women

  • Primary – no other underlying disease
  • Secondary - RA, SLE, systemic sclerosis, mixed connective tissue disease,
    Hashimoto’s thyroiditis, primary biliary cirrhosis, or chronic autoimmune
    hepatitis
  • Sicca symptoms (Lymphocytes infiltrate the glands that secrete fluids,
    such as the salivary and tear glands and injure the glands, resulting in a dry
    mouth, dry eyes and gynae dryness - the hallmark symptoms of this
    syndrome)
  • ANA (upto 70%), Ro (SSA), La (SSB), RF
  • High serum immunoglobulins
  • Salivary gland biopsy
  • Rarely other features (Arthritis, vasculitis, renal tubular acidosis etc)
128
Q

Key diagnostic features of Sjogren

A
  1. ANA
  2. Anti –Ro (SSA)
  3. Anti La (SSB)
  4. Rheumatoid factor (often fools people)
129
Q

What is the next thing we look for after finding positive ANA?

A

ENA - extractable nuclear antigen

130
Q

What is ENA

A

soluble nuclear and cytoplasmic components

Over 100 different antigens have been described

On a routine basis, however, the following are screened for:

Sm, U1-sn RNP, SSA (Ro), SSB (La), Scl-70, Jo-1

131
Q

Types of ENA

A

Each individual antigen is used to specify the antibody:

  1. Sm,
    - Diagnostic for SLE and indicates severe disease
  2. U1 RNP,
  3. SSA (Ro),
    - Sjogren, lupus and RA
    - High titre in pregnancy cause neonatal lupus syndrome and neonatal heart block
  4. SSB (La),
    - ssa, ss, LESS IN sle
  5. Anti Histone
    - Drug induced lupus
  6. Anti-RNP
    - Marker antibody for mixed connective tissue disorders which comprise overlap features fromseveral
    rheumatic diseases and tend to be less severethan SLE,
    also found in 30-40% of lupus
  7. Scl-70
    - (diffuse) systemic sclerosis
  8. Anticentromere : (limited – & ‘old name CREST’) systemic sclerosis
  9. Jo-1
    - Polymyositis, dermatomyositis
132
Q

Another name for scleroderma

A

Systemic sclerosis

133
Q

Types of scleroderma (ss)

A
  1. Generalised
    - Diffuse (scl-70 Abs but not always)
    - Limited morphea including ‘CREST’ (anticentromere Abs)
  2. Localised
    - Linear
    - No autoAbs usually no organ involvement
134
Q

Features of scleroderma

A
  • Chronic disorder characterised by degenerative
    changes and scarring.
  • Affects the skin, joints, internal organs and blood vessel
  • Thickened skin most striking feature, although confusingly, sometimes there is little or no skin involvement!

Symptoms
- The usual initial symptom of scleroderma is swelling, then thickening and tightening of the skin at the ends of the fingers.

Raynaud’s is a must!

The fingertips are taut, shiny, and thickened

135
Q

Features of systemic sclerosis

A

1 .Common symptoms include Raynaud’s phenomenon,
polyarthralgia, dysphagia, heartburn, and swelling and
eventually skin tightening and contractures of the fingers.

  1. GI disturbances (eg, heartburn, dysphagia) or respiratory
    complaints (eg, dyspnea) are occasionally the first
    manifestations.
  2. Lung, heart, and kidney involvement.
  3. Diagnosis is clinical, but laboratory tests help with
    confirmation.
136
Q

Features of the two types of generalised systemic sclerosis

A
  1. Limited systemic sclerosis, tends to stay restricted to the skin
    of the hands and feet / face with occasional other skin /organ features, old
    acronym → CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia.) syndrome
  • anti-centromere antibodies (present in 60%).
  • Could result in Pulmonary hypertension or less commonly other organ
    involvement.
  1. Diffuse systemic sclerosis
    the disorder progresses
  • extensive skin disease
  • scl-70 abs
  • could involve lungs (fibrosis), kidney (renal crisis), heart (pulm hypertension,
    etc)
137
Q

Most important point for scleroderma

A

No Raynaud’s NO GENERALISED

SCLERODERMA!

138
Q

Diagnostic features of scleroderma

A

1 .ANA

  1. Scl 70 antibodies
  2. Anti centromere antibodies

We are suspicious of ANA –ve
scleroderma (malignancy)

139
Q

Features of Polymyositis / Dermatomyositis

A

Limb weakness in general may be due to
neuropathy or myopathy

  • In myositis → proximal weakness (can’t
    stand from sitting or walk up stairs) and
    upper limbs (lift arms / brush hair)
  • Characteristic rash (Heliotrope or Gottron’s
    papules)
140
Q

Types of dermatomyositis

A
  1. Primary idiopathic polymyositis can occur at any age and does
    not involve the skin.
  2. Primary idiopathic dermatomyositis is similar to primary
    idiopathic polymyositis but also involves the skin.
  3. Polymyositis or dermatomyositis associated with cancer can occur
    at any age but is most common among older adults; the cancer can
    develop up to 2 yr before or after the myositis.
  4. Childhood dermatomyositis can be associated with systemic
    vasculitis.
  5. Polymyositis or dermatomyositis can occur with an associated
    disorder such as progressive systemic sclerosis, mixed connective
    tissue disease, RA, SLE, or sarcoidosis.
141
Q

Features of dermatomyositis

A

Skin –various rashes / vasculitis /
calcinosis

Lung – muscle weakness / interstitial lung
disease

Heart – Heart block / Arrhythmias /
Cardiomyopathy

Gut – Dysphagia / intestinal hypomobility

Musculoskeletal – Proximal weakness /
arthritis

142
Q

Diagnostic criteria of polymyositis/dermatomyositis

A

Diagnostic criteria

  1. Progressive, symmetrical, proximal muscle weakness
  2. Muscle biopsy showing typical features (necrosis, phagocytosis,
    regeneration, inflammation)
  3. Elevated Creatine Kinase or Aldolase

4.Electromyography typical findings (myopathic potentials,
fibrillations and complex repetitive discharges) (MRI…)

  1. Rash of Dermatomyositis (blue –red to violet papules on dorsum
    of hands, elbows, ankles, neck and trunk Gottron’s papules)

All of 1-4 = Polymyositis

All of 1-5 = Dermatomyositis

143
Q

Key diagnostic features of poly/dermatomyositis

A

ANA (often but not always)

From ENA- Jo-1 or other anti-synthetase
antibodies

‘myositis specific antibodies’ (rare –don’t
need to know)

144
Q

Features of MCTD

A

Often Raynaud’s before other symptoms

Early, often like SLE, scleroderma, myositis or
even RA.

Often the limited disease and the whole picture
change with time.

145
Q

Diagnosis of MCTD

A
  1. MCTD should be suspected when additional
    overlapping features are present in patients
    appearing to have SLE, systemic sclerosis,
    polymyositis, or RA.
  2. ANA positive
  3. Anti - RNP antibodies
  4. Rheumatoid factor frequently positive, and titers are
    often high.
  5. Occasionally others e.g scleroderma ones etc
  6. The ESR is frequently elevated.
146
Q

Key diagnostic features of MCTD

A
  1. ANA
  2. Anti RNP (most specific)
  3. Occasionally various others
147
Q

Anticardiolipin diseases

A

primary and secondary antiphospholipid sy. SLE, RA

and other conditions

148
Q

Antiparital cell diseases

A

(Pernicious anaemia , but also autoimmune hepatitis and

chronic liver disease)

149
Q

Tissue transglutaminase, Gliadin and Endomysial diseases

A

coeliac disease

150
Q

Anitmitochondrial diseases

A

(PBC but chronic infections, chronic liver disease and other

conditions)

151
Q

AntiACh resecptor disase

A

Myesthenia gravis

152
Q

ANCA disease

A

vasculitis (p and c – VS
myeloperoxidase or proteinase 3
respectively)

153
Q

Anti GBM disease

A

good pastures

154
Q

Examples of NSAIDs

A

(ibuprofen, naproxen, etoricoxib)

155
Q

Indications of NSAIDs

A
  1. Mild to moderate pain
    - Alternative or in addition to paracetamol
2. Regular treatment for pain related inflammatio
#
156
Q

MOA of NSAIDs

A
  • Non selective COX inhibitor
  • Role of COX 1:
    Mediated platelet aggregation
    Produces cytoprotective prostaglandins - protect gastric mucosa
  • Role of COX 2:
    Inhibits platelet aggregation
  • Recruits inflammatory mediators which induce pain
  • Sensitive skin pain receptors
  • Regulate hypothalamic temperature control
  • Therefore aspirin mainly mediates its effects through
    COX 2
157
Q

Inhibiton of which COX is the cause of the adverse affects of NSAIDs

A
  • Adverse effects of aspirin are due to the inhibition of COX 1
  • Selective COX 2 inhibitors e.g. etoricoxib have less adverse effects but COX -2 more associated with CV complications since their normal role is to inhibit platelet aggregation
158
Q

Adverse affects of NSAIDs

A
  1. GI toxicity
  2. Renal impairment
  3. Increased risk of MI and stroke
  4. Hypersensitivity reactions (bronchospasm, angioedema)
  5. Fluid retention (worsening HTN and heart failure)
159
Q

NSAID CI

A

. Severe renal impairment

  1. Heart failure
  2. Liver failure
  3. NSAID hypersensitivity
  4. Peptic ulcer disease
  5. GI bleed
  6. CV disease
  7. Renal impairmen
160
Q

NSAID important intereractions

A 
Low dose aspirin
Corticosteroids 
Anticoagulants
SSRIs
Venflaxine
ACE inhibits
Diuretics
Warfarin - NSAIDs increase the risk of bleeding and reduce effects of antihypertensice and diuerti
161
Q

Antimalarial (hydroxychloroquine)

A
  1. SLE
    - Skin, arthralgias, arthritis flares
  2. Malria
  3. Rheumatoid arthritis
162
Q

MOA of antimalarials

A
  • Exact mechanism unknown
  • Immunomodulator - inhibits rheumatoid factor and acute phase reactiants
  • Binds and alters DNA via alkylation
  • Accumulated in WBCs to stabilise lysosomal membranes, preventing activity of enzymes like collagenase and protease
163
Q

Adverse affects of antimalarials

A

GI disturbance
Headache
Skin reactions
Pruritis

164
Q

CI of antimalarials

A
  1. May exacerbate myasthenia gravis and psoriasis
  2. Severe GI disorders
  3. Can use in pregnancy but avoid in breastfeeding
165
Q

Examples of DMARDs

A

Methotrexate and cyclophosphamide

166
Q

MOA of cyclophosphamide

A
  • Alkylation of DNA - prevents DNA synthesis and RNA transcription
  • Induction of mispairing of nucleotides
  • Cross linking of DNA
167
Q

Indications for cyclophosphamide

A
  1. RA

2. SLE (renal and CNS manifestations)

168
Q

CI to cyclophosphamide

A
  1. Haemorrhagic cysticits
  2. Avoid in acute prophyrias
  3. Diabetes mellitu
169
Q

Adverse affected of cyclophosphamide

A
  1. Anorexia
  2. Cardiotoxicity (high doses)
  3. Carbohydrate metabolism dysfunction
  4. Interstitial pulmonary fibrosis
  5. Pigmentation of palms
170
Q

Indications for corticosteroids

A
  1. Allergic or inflammatory disorder
  2. Suppression of AI disease
  3. Cancer chemotherapy
  4. Hormone replacement in adrenal insufficiency or hypopituitarism
171
Q

MOA of corticosteroids

A
  1. Bind to glucocorticoid receptors which translocate to the nucleus and bind glucocorticoid response elements which regulate gene expression
  2. Modify immune response
  3. Upregulate anti inflammatory gene
  4. Down regulate proinflammatory genes
  5. Directly suppress monocytes and eosinophils
  6. Increased gluconeogenesis
    mineralocorticoid effects - stimulate na and water retention and k excretion
172
Q

Adverse effects of corticosteroids

A
  1. Infection - immunosuppression
  2. DM and OP
  3. Proximal muscle weakness, skin thinning, easy bruising gastritis
  4. Insomnia, confusion, psychosis, suicidality
  5. HTN
  6. Hypokalemia
  7. Edema
  8. Adrenal atrophy - idf withdrawn suddenly = addisonian crisi
173
Q

CI of infection

A
  1. Infection

2. Children (Suppress growth)

174
Q

Important corticosteroid interactions

A
  1. Increased risk of peptic ulceration and GI bleed when used with NSAIDS
  2. Enhance hypokalemia when used with beta blockers, theophylline, loop/thiazide diuretics
175
Q

DDx of swollen joints

A

See table in Preena Joshi LOB sheet

176
Q

Processes involved in immunologial tolerance

A
  1. Clonal deletion
  2. Clonal anergy

Clonal deletion predominates in the elimination of T lymphocytes whilst clonal anergy (or clonal inactivation) predominates for B cells. There are additional mechanisms which can suppress T cell help.

177
Q

Locations of tolerance

A

Tolerance can be induced centrally (for the T cell, in the thymus; for the B cell in the bone marrow) or peripherally.

178
Q

Pathways of tolerance

A

Central selection: occurs in the thymic cortex

Peripheral selection: continuously in the tissue

T regulatory cells

179
Q

Describe central selection

A

Positive selection: occurs in the thymic cortex. cells that don’t bind to MHC are apoptosed

Negative selection: cloncal deletion mainly in the cortex but also in the medulla of cells that bind STRONGLY to self antigen

180
Q

Describe immunological ignornace

A

T cells cannot be activated by self antigens which are either sequestered in immuno-privileged sites (eg lens proteins in the eye), or present in too small a concentration to stimulate a response.

Alternatively, though B cells may recognise an antigen they require T cell help and, if that is missing because there are no T cells capable of recognising the presented peptide, then the B cell will become unresponsive.

Key Topic created and reviewed by Terry Poult

181
Q

Read St Geroges Key topics on AI and immune tolerance

A

Read St Geroges Key topics on AI and immune tolerance

BCS Lectures (8 decks)

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