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Oral medicine > Autoimmune diseases > Flashcards

Autoimmune diseases Flashcards

1
Q

name 2 blistering diseases

A

pemphigus

pemphigoid

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2
Q

name 2 CT diseases

A

Sjogrens Syndrome

SLE

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3
Q

name 2 vasculitis

A

erythema multiforme

Behcets disease

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4
Q

give 4 causes of blistering diseases

A 
trauma
extreme temp
chemical exposure
medical conditions
-infective
-genetic
-autoimmune
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5
Q

definition of AMBDs

A

Ig-mediated diseases with autoantibodies against desmosomal or basement membrane zone molecules

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6
Q

what is the classification of pemphigus based on?

A

different clinical and histopathological features

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7
Q

give the 5 broad types of pemphigus

A 
pemphigus vulgaris
pemphigus foliaceus
drug-induced pemphigus
paraneoplastic pemphigus
IgA pemphigus
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8
Q

which is the most common type of pemphigus and the one that gives oral lesions?

A

pemphigus vulgaris

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9
Q

give a subtype of pemphigus vulgaris

A

pemphigus vegetans

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10
Q

give 2 subtypes of pemphigus foliaceus

A

pemphigus erythematosus - localised

fogo selvagem - endemic

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11
Q

pathogenesis of pemphigus

A

autoantibodies against proteins that constitute desmosomes
intraepithelial blister and acantholysis
autoantibodies deposited in epithelium - complement activated and plasmin

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12
Q

2 types of intraepithelial blister in pemphigus

A 
supra basal (lower)
sub corneal (higher)
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13
Q

what is acantholysis?

A

when desmosomes separate

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14
Q

why are there different types of pemphigus?

A

because desmosomes are complex - attack against a specific desmosome protein gives you a specific type of pemphigus
not just a single attack on a single protein

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15
Q

anti-Dsg3 IgG

A

autoantibodies against Dsg3 attack desmosomes

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16
Q

how many self-antigens are recognised by IgGs in patients with PV and/or PF?

A

more than 50

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17
Q

what does the severity and exact clinical picture of pemphigus depend on?

A

ratio of different kinds of autoantibodies in each particular pt

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18
Q

what type of surface does pemphigus affect?

A

any stratified squamous epithelium

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19
Q

pemphigus epidemiology

A

uneven geographic and ethnic distribution

high incidence in Ashkenazi jews and those of mediterranean origin

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20
Q

what age group does pemphigus usually affect?

A

40-60 years

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21
Q

gender distribution of pemphigus

A

M=F

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22
Q

where does the mucosal phenotype of pemphigus typically begin and progress to?

A

usually begins oral cavity

can spread to skin - face, back, chest, genitals

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23
Q

pemphigus features in the oral cavity

A

desquamative gingivitis
soreness, blistering, erosions
can be covered by yellow fibrinous slough
rare to see intact blisters in oral cavity (trauma) - see erosions
lesions can be painful to brush, but plaque irritates lesions
can easily peel off - leaves haemorrhagic erosion underneath

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24
Q

which sites in the oral cavity are most affected by pemphigus?

A

buccal mucosa

tongue

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25
Q

pemphigus - what is spongiosis?

A

blister about to form

cells in epithelium full of fluid

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26
Q

does the mucosal phenotype of pemphigus affect just the skin?

A

rarely

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27
Q

pemphigus prognosis

A

untreated often fatal due to dehydration/infection

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28
Q

pemphigus prognosis mucosal lesions

A

may persist even though skin lesions are controlled

topical CS/tacrolimus may then help

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29
Q

BM zone

A

hemidesmosomes
lamina lucida
lamina densa - sub epithelial split
sublamina densa

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30
Q

pathogenesis of pemphigoid

A

autoantibodies against hemidesmosomes deposited in epithelium
complement activated, leukocytes recruited - damage to BM
sub epithelial blister or sub-lamina densa (deeper) split

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31
Q

what age group is pemphigoid most common in?

A

> 75s

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32
Q

is pemphigoid common?

A

no

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33
Q

gender distribution of pemphigoid

A

F>M

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34
Q

epidemiology of MM pemphigoid

A

extremely rare

prevalence 25 per million

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35
Q

clinical presentation of MM pemphigoid

A

mostly affects mucosae - conjunctiva, nasal, oral, genital

occasionally skin

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36
Q

why do blisters in pemphigoid persist longer?

A

blister has thicker roof and is more attached to the floor of blister

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37
Q

which areas of the oral cavity are often affected by MM pemphigoid?

A

interface of hard and soft palate soft palate
uvula
gingivae

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38
Q

pemphigoid prognosis without treatment?

A

may persist with periods of remission and flare ups for many years

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39
Q

pemphigoid prognosis with treatment?

A

immune response and inflammation can be suppressed

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40
Q

is pemphigoid fatal?

A

no

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41
Q

what is Nikolsky’s sign?

A

induce an erosion by rubbing on the skin

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42
Q

2 types of Nikolsky sign sites?

A

marginal - next to blister

direct - perform on healthy skin

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43
Q

Nikolsky’s sign in oral cavity

A

PD probe/spatula under roof - can extend and peel roof off v easily

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44
Q

positive Nikolsky sign

A

indicator you might be dealing with blistering diseases

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45
Q

sensitivity and specificity of Nikolsky sign

A

poor sensitivity - means you miss a lot of cases

good specificity - pts with no disease test negative

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46
Q

aim of biopsy of suspected AMBDs and why is this difficult?

A

aim for intact blister to send to pathologist so they can determine whether intra or sub epithelial
difficult as tissues fragile

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47
Q

biopsy procedure for suspected AMBDs

A

2 parallel incisions

hold blister with tweezers and cut underneath

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48
Q

why is biopsy of suspected AMBDs easier on attached gingiva?

A

there is bone underneath

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49
Q

what is needed in addition to biopsy/Nikolsky sign to confirm diagnosis of AMBDs?

A

autoimmmune diagnosis

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50
Q

What is direct immunofluorescence done on?

A

specimen - pts perilesional oral mucosa
- you send some for H and E and some for DIF
added primary antibody labelled with a fluorescent probe - intercellular epithelial staining

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51
Q

aim of DIF

A

to detect tissue bound immunodeposits

  • inside epithelium if pemphigus vulgaris
  • along BM zone if pemphigoid
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52
Q

what is indirect immunofluorescence done on?

A

pts sera - take blood

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53
Q

aim of IIF?

A

to detect circulating IgG antibodies in bloodstream - identify immunologic signal

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54
Q

procedure of IIF

A

on specific substrate

added a secondary antibody labelled with fluorochrome to recognise a primary antibody from patients serum

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55
Q

substrates used in IIF

A

monkey oesophagus, normal skin or rat uroepithelium

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56
Q

diagnosis of pemphigus - DIF

A

fishnet like pattern
presence of IgG and/or C3 as well as IgA deposition within the intercellular spaces throughout the epithelium

may also get IgM or IgA (in the IgA variant get this expression)

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57
Q

diagnosis of pemphigus - IIF

A

high % will be positive

IgG, C3, IgM, IgA

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58
Q

histopathology of pemphigus

A

intraepithelial blisters

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59
Q

if DIF in pemphigus shows intercellular epithelial staining and IgA, what is the diagnosis?

A

IgA pemphigus

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60
Q

if DIF in pemphigus shows intercellular epithelial staining and DSG1?

A

PF

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61
Q

if DIF in pemphigus shows intercellular epithelial staining and DSG-3?

A

OPV

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62
Q

if DIF in pemphigus shows intercellular epithelial staining and DSG-1 and 3?

A

MCPV

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63
Q

if DIF in pemphigus shows intercellular epithelial staining and desmocollins 1-3?

A

PNP/PAMS

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64
Q

diagnosis of pemphigoid - DIF

A

linear pattern at BM zone - u or n serrated

IgG and/or C3 as well as IgA deposition along the BM zone

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65
Q

DIF in pemphigoid - u serrated

A

EBA

bullous lupus

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66
Q

DIF in pemphigoid - n serrated

A

bullies pemphigoid
MM pemphigoid
P200 pemphigoid

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67
Q

pemphigoid - IIF salt split

A

mucosal sample incubated at 4 degrees in 5cc NaCl for 24-48hrs
NaCl acts like scissors at lamina lucida - get roof and floor

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68
Q

pemphigoid IIF - floor blister (dermal)

A

bullous lupus
deeper MM pemphigoid
epidermolysis bullosa

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69
Q

pemphigoid IIF - mixed floor and roof blister

A

MM pemphigoid - autoantibody attack between lamina lucida and lamina dura (middle of BP180)

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70
Q

pemphigoid IIF - roof blister (epidermal)

A

bullous pemphigoid
MM pemphigoid
LP pemphigoid

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71
Q

pemphigoid histopathology

A

sub epithelial blister

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72
Q

pemphigoid - if DIF shows IgA pattern at BM zone

A

linear - LAD

granular - DH

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73
Q

what is ELISA?

A

enzyme-linked immunosorbent assay

detects anti-Dsg antibodies

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74
Q

advantages of ELISA

A

quantitative method for measuring specific circulating antibody levels
plates read automatically and results do not depend on observer

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75
Q

disadvantages of ELISA

A

may not detect all subtypes of autoantibodies involved in the pathogenesis of AMBDs
e.g. negative result for anti-Dsg1 and 3 does not rule out possibility of other auto antigens in different subtypes of pemphigus

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76
Q

how should ELISA be used?

A

as a complementary test to IIF and not as a substitute

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77
Q

ELISA process

A

plates precoated with recombinant antigen (Dsg1, 3, BP230, BP180)
add pt sera (containing antibodies)
antigen-antibody complex formed
add enzyme (HRPO) conjugated anti-antibody
antigen-antibody-antiantibody complex formed
add substrate (TMB) to enzyme
substrate converted by enzyme to detectable coloured product

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78
Q

why is early diagnosis of AMBDs important?

A

may not be AMBDs
- mucocutaneous side effect of meds e.g. sunitinib for breast cancer
- secondary syphilis
prevent mucosal spread
-nasal, anogenital, ocular, voice box, oesophagus (dysphagia)
prevent mucocutaneous spread
mucosal scarring phenotype of MMP

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79
Q

which AMBD can cause scarring and why?

A

pemphigoid

subepithelial so BM zone affected - get scar tissue

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80
Q

does pemphigus cause scarring?

A

no as intraepithelial

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81
Q

consequences of mucosal scarring phenotype of MMP

A

oesophageal stricture if scarring
eye scarring - if reaches corneal limbus (contains corneal SCs) pt will develop blindness. opacification of iris and pupil, inflammation of conjunctiva

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82
Q

what type of syndrome is Paraneoplastic Autoimmune Multiorgan Syndrome?

A

mucocutaneous

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83
Q

what is PAMS?

A 
a distinct clinical entity characterised by heterogeneous group of S+S including
-severe desquamative stomatitis
-a polymorphous cutaneous eruption
-ofren a progressive respiratory failure
develop due to an underlying malignancy
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84
Q

when may PAMS occur?

A

well before the discovery of occult malignancy or lymphoproliferative disorder
need extended clinical follow-up

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85
Q

haematological malignancies that can cause PAMS

A

NHL
chronic lymphocytic leukaemia
Castleman disease

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86
Q

non-haematological malignancies that can cause PAMS

A

carcinomas
sarcomas
malignant melanoma

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87
Q

pathogenesis of PAMS

A

cancer cells activate a wide number of immune cells

activated auto reactive T cells induce both humeral and cell-mediated immunity

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88
Q

PAMS - how do humoral and cell-mediated immunity cause its features?

A

humoral immunity (mostly autoantibodies) - acantholysis (resembles pemphigus)
cell-mediated immunity - lichenoid dermatitis (resembles lichenoid)
both - bronchiolitis obliterates (life-threatening)

get these features based on % of 2 types of immunity

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89
Q

what is the major antigenic target in PAMS?

A

plakins

- desmoplakin 1 and 2, envoplakin, periplakin, pectin, BP230

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90
Q

how many clinical phenotypes of PAMS

A

may have at least 5 - both humoral and cytotoxic immunities involved in development of PAMS

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91
Q

give some clinical phenotypes of PAMS

A

autoantibody mediated cytotoxicity

pemphigus like (aka PNP)
bullous pemphigoid like
EM like
GvHD like
LP like

cell-mediated cytotoxicity

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92
Q

clinical features of PAMS

A

ocular - inflammation of conjunctiva, ectropion (eyelid turns outward)
lip lesions
oral lesions

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93
Q

is there a diagnostic criteria for PAMS?

A

no generally accepted diagnostic criteria

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94
Q

Components of the suggested diagnostic criteria for PAMS

A 
clinical signs
histopathology
DIF
IIF
detection of circulating autoantibodies against
detection of a neoplasm
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95
Q

suggested diagnostic criteria for PAMS - clinical signs

A

severe stomatitis - MANDATORY
blisters
LP like plaques
bronchiolitis obliterans

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96
Q

suggested diagnostic criteria for PAMS - histopathology

A

supra basal blistering, acantholysis, lichenoid interface dermatitis with keratinocyte necrosis

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97
Q

suggested diagnostic criteria for PAMS - DIF

A

IgG intercellular in epithelium / and IgG/C3 at BM zone

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98
Q

suggested diagnostic criteria for PAMS - IIF

A

IgG intercellular in epithelium

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99
Q

suggested diagnostic criteria for PAMS - detection of circulating autoantibodies against

A

envoplakin or periplakin - MANDATORY
Dsg 1, 3
desmoplakin 1+2, plectin, BP230, 170-KDa protein

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100
Q

suggested diagnostic criteria for PAMS - detection of a neoplasm

A

MANDATORY

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101
Q

mandatory components of suggested diagnostic criteria for PAMS

A

severe stomatitis
detection of circulating autoantibodies against envoplakin or periplakin
detection of a neoplasm

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102
Q

suggested diagnostic criteria for PAMS - if specific detection of antibodies against envoplakin or periplakin is not available what do you use as mandatory criterion?

A

DIF or IIF - needs to be positive

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103
Q

why is PAMS usually non-responsive to immunosuppressive therapies?

A

related to an underlying neoplasm

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104
Q

treatment of PAMS

A

treat underlying malignancy

not always sufficient

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105
Q

why is early diagnosis of PAMS essential?

A

early diagnosis and treatment of underlying malignancy - more favourable prognosis

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106
Q

coordinated MDT in AMBDs

A 
oral med
dermatology
ENT
ophthalmology
gynecology
gastroenterology
infectivology
endocrinology
urology
psychiatry
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107
Q

what should you do before making a treatment plan for AMBDs?

A

determine the extent of disease

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108
Q

determining the extent of disease in AMBDs

A 
routine lab work
screening for infections
tumour markers and instrumental exams - EKG, CT, DEXA
medical consults
additional exams for biologic therapies
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109
Q

why do you need to screen for infections before treating AMBDs?

A

don’t want to reactivate any silent infections as you will be using immunosuppressive meds

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110
Q

why do you need to carry out instrumental exams and tumour markers before treating AMBDs?

A

ensure no underlying malignancy

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111
Q

what do you need to screen for before using biologic therapies to treat AMBDs?

A

thrombophilia

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112
Q

conventional therapy in PV

A

attack phase - CSs immunosuppressive

+/- adjuvant CS sparing agents

CHX 0.12% alcohol free rinse

topical and/or systemic anti-mycotic agents if you see candidiasis overgrowth

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113
Q

PV - first line attack phase of treatment

A

corticosteroids: prednisolone 1-2.5mg/kg

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114
Q

PV - adjuvant corticosteroid sparing agents

A 
azathioprine
mycophenolic acid
cyclophosphamide
methotrexate
cyclosporine
dapsone
tetracycline
nicotinamide (vitB3)
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115
Q

PV - adjuvant corticosteroid sparing agents - dose of azathioprine

A

1-2.5 mg/kg

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116
Q

PV - adjuvant corticosteroid sparing agents - dose of mycophenolic acid

A

35-40 mg/kg

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117
Q

PV - adjuvant corticosteroid sparing agents - dose of cyclophosphamide

A

2-2.5 mg/kg

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118
Q

PV - adjuvant corticosteroid sparing agents - dose of methotrexate

A

10-20 mg/wk

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119
Q

PV - adjuvant corticosteroid sparing agents - dose of cyclosporine

A

3-5 mg/kg

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120
Q

PV - adjuvant corticosteroid sparing agents - dose of dapsone

A

50-200mg

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121
Q

PV - adjuvant corticosteroid sparing agents - dose of tetracycline

A

2g

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122
Q

PV - adjuvant corticosteroid sparing agents - dose of nicotinamide (vit B3)

A

1.5g

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123
Q

intra and perilesional injections of triamcinolone in PV

A

often used if stubborn remnant lesions and you want to taper the systemic corticosteroids
reduces healing time

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124
Q

indications for advanced therapeutic options in AMBDs

A
  1. pts non-responders to at least one standard regimen inc the combination of systemic glucocorticoids (at min dose of 1mg/kg body weight prednisolone equivalent) and other immunosuppressants or immunomodulators
  2. pts who developed significant SE from conventional systemic therapies
  3. pt unable to achieve a sustained clinical remission on standard regimens
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125
Q

types of advanced therapeutic options in AMBDs

A 
IV IgG
rituximab
antiTNFa
plasmapheresis
immunoadsorption
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126
Q

IvIgG in AMBDs

A

anti-inflammatory properties
increases catabolism of autoantibodies
decreases synthesis of autoantibodies
neutralises pathogenic autoantibodies

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127
Q

AMBDs - rituximab contraindications

A

active severe infections
severely immunocompromised
severe heart failure/uncontrolled cardiac disease
pregnancy

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128
Q

AMBDs - rituximab action

A

anti-CD20 medication - monoclonal antibodies that attack molecule on B cells

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129
Q

2 ways in which rituximab works as an anti-CD20 medication

A
  1. directly targets CD20+ autoreactive B cells as progenitors of autoantibody secreting plasma cells
    - B cells destroyed so don’t get autoantibodies produced - ADCC cytotoxicity, complement-dependent cytotoxicity, apoptosis
  2. indirectly decreases the freq of autoreactive T cells, which initiate and perpetuate the autoimmune response in pemphigus
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130
Q

effectiveness of rituximab in AMBDs

A

low rate of relapses and side effects

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131
Q

what is the issue with treating MM pemphigoid?

A

lack of evidence

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132
Q

low risk MM pemphigoid

A

oral mucosa only
oral mucosa and limited skin
no ocular, genital, oesophageal, laryngeal

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133
Q

high risk MM pemphigoid

A

diffuse oral mucosa
progressive oral mucosa
ocular, genital, oesophageal, laryngeal

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134
Q

initial treatment of low risk MM pemphigoid

A 
topical CS
dapsone
tetracycline and nicotinamide
sulphametoxypyridazine
sulphapyridine

can also use high risk txs if needed

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135
Q

initial treatment of high risk MM pemphigoid

A

CS +/- (0.5-1.5mg/kg)
azathioprine\cyclophosphamide
mycophenolic acid

can also use low risk txs

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136
Q

tx of MM pemphigoid if partial response or progressive disease

A

IvIgG

RTX

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137
Q

IvIgG dose in MM pemphigoid

A

2-3g/kg/day diluted on 3-5 days, monthly

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138
Q

RTX dose in MM pemphigoid

A

375mg/sqm²/day, 4 weekly infusions
or
1g/day, 2 infusions (TO-TIS)

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139
Q

MMP treatment - biologics as a first line adjuvant indications

A

contraindication to systemic CS
paediatric/young pts
rapid progression (ocular, laryngeal, oesophageal)

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140
Q

Primary SS triad

A

exocrinopathy (often results in dryness of mouth and eyes)
fatigue
joint pain

  • main features but there are others
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141
Q

what does the prevalence of SS vary depending on?

A

classification criteria used

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142
Q

most common age for SS

A

40-60yrs

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143
Q

incidence of SS

A

4 per 100 000

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144
Q

gender distribution of SS

A

much higher in F

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145
Q

proposed immunopathogenic mechanisms of SS

A

microbial trigger
destroys salivary gland epithelium
produces autoantigens - nucleic acid and T1 interferon
triggers reaction of B cell and CD4 T cell
differentiation of B cells in plasma cells
produce autoantibodies - form immunocomplex with autoantigens
captured by DCs - produces T1 interferon amplifying immune response
activation of cytotoxic CD8 - directly destroys salivary gland epithelium through cytotoxic granules
produces new neoantigens and amplifies immune response
innate and adaptive immunity pathways

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146
Q

SS env factors

A

no single causative env factor identified
data continue to support infections as an important risk factor
biological factors
organic chemical factors
inorganic chemical factors
lots interact in a temporal contribution

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147
Q

SS biological factors

A 
bacteria
viruses
vaccination
hormones
vit D
stress
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148
Q

SS organic chemical factors

A

alcohol
smoking
solvents

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149
Q

SS inorganic chemical factors

A

silicone

silica

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150
Q

SS genetic factors

A

may both determine the baseline disease susceptibility and disease phenotype as well as interact with the different types of env factors

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151
Q

what 2 broad factors may contribute to the development of SS?

A

env factors

genetic factors

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152
Q

in what % of SS pts do systemic manifestations occur?

A

about 30-40%

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153
Q

systemic manifestations of SS

A 
constitutional symptoms
lymph nodes
renal
articular
cutaneous
peripheral neuropathy
muscular
pulmonary
glandular
CNS
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154
Q

systemic manifestations of SS - constitutional symptoms

A

fever
weight loss
night sweats

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155
Q

systemic manifestations of SS - LNs

A

benign lymphadenopathy/lymphoma

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156
Q

systemic manifestations of SS - renal

A

interstitial nephritis

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157
Q

systemic manifestations of SS - articular

A

arthralgia with morning stiffness or synovitis

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158
Q

systemic manifestations of SS - cutaneous

A

purpura
vasculitis
subacute cutaneous lupus

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159
Q

systemic manifestations of SS - muscular

A

myositis

pain/weakness

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160
Q

systemic manifestations of SS - pulmonary

A

chronic bronchitis/bronchiolitis

interstitial lung disease

161
Q

systemic manifestations of SS - glandular

A

palpable parotid, submandibular or lacrimal swelling

162
Q

systemic manifestations of SS - CNS

A

cerebral vasculitis
transverse myeltiis
demyelinating lesions

163
Q

what does ESSDAI stand for?

A

EULAR Sjogren’s Syndrome Disease Activity Index

164
Q

what is ESSDAI?

A

a clinical index designed to measure disease activity in pts with primary SS
each has a weighting - give score for each depending on severity

165
Q

ESSDAI clinical factors

A 
constitutional
lymphadenopathy
glandular
articular
cutaneous
pulmonary
renal
muscular
PNS
CNS
haematological
biological
(Raynaud associated in 15% cases)
166
Q

oral S+S in primary SS

A 
salivary hypofunction
caries
fungal infections
oral trauma
lip dryness
orofacial pain
dysphagia
dysgeusia
swollen salivary glands
gastroesophageal reflux
oral lesions of autoimmune aetiology
167
Q

primary SS - salivary hypofunction/dysfunction

A

diminished secretions on palpation
thicker, opaque or viscous secretions
recurrent salivary gland infection

168
Q

primary SS - why is there enlarged salivary glands?

A

initial acute inflammation of glands, then chronic inflammation with fibrosis, decrease in volume of gland due to progressive destruction of the parenchyma - also lacrimal gland

169
Q

primary SS - caries

A

pts with hyposalivation also have decreased secretion of IgA - antibody responsible for oral mucosal immunity that prevents caries
also saliva in primary SS does not act as an effective buffer therefore increases risk of caries
cervical caries and other atypical sites e.g. lingual surface, incisal edge and cusps

170
Q

primary SS - fungal infection

A 
pts with pSS have higher prevalence of oral fungal infections
mainly candidiasis
- erythematous
- angular cheilitis
- atrophic
- pseudomembranous
171
Q

primary SS - which is the most common enlarged salivary gland?

A

parotid
30-40% pts
bilateral swelling can be found in 25-60% pts - acute or chronic
(submandibular can also be affected but less frequently)

172
Q

primary SS - acute salivary gland enlargement

A

can be unilateral/bilateral

usually painful

173
Q

primary SS - salivary gland enlargement inflammatory infiltrate

A

mixed - T,B cells, abundant cytokine secretion that promote local chemotaxis, exacerbating the gland inflammation

174
Q

primary SS - autoimmune/immunomediated lesions

A

oral lichen planus/lichenoid lesions
RAS
MM pemphigoid
pemphigus vulgaris

175
Q

what is the other major organ affected in primary SS?

A

eye

176
Q

primary SS - ocular manifestations

A 
dry eye
extraglandular ocular complications
- corneal inflammation
- conjunctival inflammation
- uveitis
- scleritis/episcleritis
- optic neuritis
- retinal vasculitis
177
Q

secondary SS

A

when pt already has another autoimmune disease then presents with extreme dryness of eyes and mouth

178
Q

diagnosis of SS - lab testing

A

anti-SSA antibodies - anti-Ro
anti-SSB antibodies - anti-La
present in 2/3 pts and should be assessed when SS is suspected

other autoantigens

  • muscarinic receptors
  • vasoactive intestinal peptide receptor
  • platelet(p)-selectin
  • kallikreins
179
Q

What classification criteria is used for the diagnosis of SS?

A

American College of Rheumatology European League against Rheumatism

180
Q

SS diagnosis- inclusion criteria

A

at least one symptom of ocular or oral dryness (answer yes to 1 or more Qs):

have you had daily, persistent, troublesome dry eyes for >3m?
do you have a recurrent sensation of sand/gravel in the eyes?
do you use tear substitutes >3 times a day?
have you had a daily feeling of dry mouth for >3m?
do you freq drink liquids to aid in swallowing dry food?

or when there is suspicion of SS from the European League Against Rheumatism SS Disease Activity index questionnaire (1 or more domain with a + item)

181
Q

SS diagnosis - exclusion criteria

A 
history of H+N radiation tx
active hep C infection (confirm by PCR)
AIDS
sarcoidosis
amyloidosis
GvHD
IgG4-related disease
182
Q

SS - if the patient meets inclusion criteria, doesn’t have. any exclusion criteria, what do they need to score for diagnosis?

A

4 or more

183
Q

SS diagnosis - what are the aspects of the scoring system?

A 
biopsy
anti-SSA/Ro positive
ocular staining score
Schirmer's test
unstimulated whole saliva flow rate
184
Q

SS diagnosis - biopsy

A

labial salivary gland with focal lymphatic sialadenitis and focus score of 1 or more foci/4mm²
- presence of 1 or more dense aggregates of 50 or more lymphocytes usually located in perivascular or periductal locations

score = 3

185
Q

SS diagnosis - biopsy technique

A

5 or more minor glands
L lip in paramedian region
incision parallel to labial frenum, identify minor gland, lift, remove, suture

186
Q

SS diagnosis - antiSSA/Ro positive

A

score = 3

187
Q

SS diagnosis - ocular staining score

A

5 or more
(or Van Bijsterveld score 4 or more in at least 1 eye)
lissamine green or fluorescein

score = 1

188
Q

SS diagnosis - Schirmer’s test

A

5 or less mm/5min in at least one eye
filter paper in lower eyelid - tears

score = 1

189
Q

SS diagnosis - unstimulated whole saliva flow rate

A

0.1ml/min or less
don’t eat or drink 90mins before

score = 1

190
Q

SS diagnosis - scores

A 
biopsy - 3
antiSSA/Ro positive - 3
ocular staining score - 1
Schirmer's test - 1
unstimulated whole saliva flow rate - 1
191
Q

what could the classification criteria of primary SS be extended to?

A

could be applicable to secondary SS

192
Q

SS - what do you do before starting therapeutic interventions?

A

baseline evaluation of salivary gland function by measuring whole salivary flows
always rule out SS-unrelated conditions - candidiasis, burning mouth syndrome
may consider salivary scintigraphy

193
Q

SS - what would you measure if the UWSF is less than 0.1ml/min?

A

SWSF

194
Q

SWSF SS - normal/mild dysfunction

A

> 0.7ml/min

195
Q

SWSF SS - mod dysfunction

A

0.1-0.7ml/min

196
Q

SWSF SS - severe dysfunction

A

<0.1ml/min

197
Q

SS - normal/mild salivary dysfunction treatment

A

non-pharmacological
if no response/intolerance - pharmacological stimulation

rescue therapies

198
Q

SS - mod salivary dysfunction treatment

A

non-pharmacological and pharmacological stimulation
if no response/intolerance - saliva substitutes

rescue therapies

199
Q

SS - severe salivary dysfunction treatment

A

saliva substitutes

rescue therapies

200
Q

SS - salivary dysfunction rescue therapies

A

mucolytic (NAC)
choleretic
electrostimulation

201
Q

non-pharmacological saliva stimulation

A 
gustatory stimulants (sugar-free acidic candies, lozenges)
and/or
mechanical stimulants (sugar-free chewing gum)
202
Q

lozenges containing malic acid

A

increase saliva production and xerostomia relief

203
Q

pharmacological saliva stimulation

A

pilocarpine
cevimeline
both licensed to treat oral dryness (but only pilocarpine licensed worldwide)

204
Q

cevimeline dose

A

30mg 1-3x day

205
Q

what not to recommend as pharmacological saliva stimulation

A

hydroxychloroquine
oral corticosteroid
immunosuppressive agents
rituximab

206
Q

ideal saliva substitute properties

A

neutral pH
contain F and other electrolytes
-mimics composition of natural saliva

207
Q

give 3 forms of saliva substitute

A

spray
gel
rinse

208
Q

why is pilocarpine not always useable?

A

need residual secretory capacity - still need functioning parenchyma

209
Q

disadvantages of pilocarpine

A

£ (useful galenic preparations)
several 5mg lozenges needed each day (3-6)
several disease interactions
may have no protective effect on caries, periodontitis or candidiasis in pSS patients

210
Q

pilocarpine dose

A

3-6 5mg lozenges each day

211
Q

contraindications for pilocarpine

A 
uncontrolled asthma
uncontrolled COPD
uncontrolled cardiorenal diseases
narrow-angle closure glaucoma
gall bladder stones
acute iritis
212
Q

SS - caries prevention

A 
frequent recall (4-6m)
meticulous OH
F
non-F remineralising agents
salivary stimulation
antimicrobial agents e.g. CHX
213
Q

what malignancy does SS carry a risk of?

A

haematological - lymphoma

214
Q

what origin are most lymphomas in SS?

A

B cell origin

215
Q

3 subtypes of lymphoma account for what % of cases in pSS pts?

A

> 90%

216
Q

3 main subtypes of lymphoma in SS?

A

Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma
Diffuse Large B-Cell Lymphoma (DLBCL)
Marginal Zone Lymphoma (MZL)

217
Q

what % of haematological neoplasias in pSS pts do MALT lymphomas account for?

A

63%

218
Q

where is the most common localisation of MALT lymphomas in SS?

A 
salivary glands (mainly parotids)
but other mucosal sites can also be affected
219
Q

what may MALT lymphomas transform into over the course of disease?

A

DLBCL

220
Q

what other malignancy can a small number of SS pts get?

A

non-B cell haematological cancers

myeloid leukaemia, Hodgkin disease or T/NK cell lymphoma

221
Q

main primary sites of lymphoma in pSS

A 
SALIVARY GLANDS (parotid)
lungs, gastric, ocular, oral/ENT, spleen
222
Q

what risk do SS pts have of developing lymphoma compared to the general population?

A

22-260x higher risk of parotid gland B cell lymphoma

90-1000x higher risk for parotid gland MALT lymphoma

223
Q

risk factors for developing lymphoma in pSS

A 
recurrent swelling of parotid glands
splenomegaly, lymphadenopathy or both
purpura
>5 score on ESSDAI
RF
cryoglobulinemia
low C4 level
CD4 T cell lymphocytopenia
presence of ectopic germinal centres
focus score of >3
germinal mutations in TNFAIP3
224
Q

what tests can be done to monitor for lymphoma development in SS?

A 
lymphocyte count
protein electrophoresis
RF
C3+4 protein
cryoglobulin
225
Q

how often should simple monitoring tests for malignancy in SS pts be carried out?

A

every 1-2yrs

pts considered higher risk - every 6m

226
Q

if lymphoma is suspected in SS pts, what should be done?

A

tissue biopsy

imaging studies such as positron-emission tomography may also be helpful

227
Q

give 2 ways of treating SS by targeting innate immunity pathways

A

inhibit pro inflammatory cytokines

interfere with T1 interferon production

228
Q

treating SS by targeting innate immunity pathways - inhibiting proinflammatory cytokines - drugs

A

tocilizumab
anakiura
infliximab/etanercept
iguratimod

229
Q

treating SS by targeting innate immunity pathways - interfering with T1 interferon production - drugs

A

hydroxychloroquine

230
Q

SS treatment - adaptive immunity therapeutic targets

A 
antigen presentation/costimulation
B-cell activation
germinal centre formation
T cell proliferation
immunobiologics
231
Q

SS treatment - adaptive immunity therapeutic targets - immunobiologic targets

A

anti-B cell
anti-TNFa
costimulatory signal inhibitors
anti-CD40

232
Q

SS treatment - adaptive immunity therapeutic targets - immunobiologic targets - anti B cell

A 
rituximab
high evidence level
improve USFR
effect on xerostomia not indicated
significant improvement in glandular parenchyma in 2 studies
233
Q

SS treatment - adaptive immunity therapeutic targets - immunobiologic targets - anti-TNFa

A

infliximab

234
Q

SS treatment - adaptive immunity therapeutic targets - immunobiologic targets - costimulatory signal inhibitors

A

abatacept

235
Q

SS treatment - adaptive immunity therapeutic targets - immunobiologic targets - anti-CD40

A

CFZ533

236
Q

definition of SLE

A

the prototype of an autoimmune multisystem disorder which clinically presents with a broad spectrum of clinical manifestations involving almost all organs and tissues, and serologically the appearance of antinuclear antibodies

237
Q

what 2 processes contribute to the clinical picture of SLE?

A

systemic inflammation

tissue damage

238
Q

what are the potential severe outcomes of SLE?

A

disability or death

239
Q

which continent does SLE tend to be lower in?

A

europe

240
Q

gender distribution of SLE?

A

F>M

241
Q

factors contributing to SLE

A

can act either sequentially or simultaneously on the immune system

  1. genetic predisposition
  2. env
  3. hormonal
  4. epigenetic
  5. immunoregulatory factors
242
Q

SLE genetic predisposition

A

have identified genes - cellular functions that have lupus susceptibility genes related to them

  • priming/autoantigen presentation
  • lymphocyte activation
  • cell survival/apoptosis
  • innate response/IFN-1
  • apoptotic clearance
  • immune-complex-dependent response
243
Q

SLE environmental factors

A

smoking
UV exposure
EBV
exposure to silica dust, petroleum, organic solvents and mineral oils

244
Q

SLE hormonal factors

A

mainly affects women in their reproductive age, F:M 9:1 - suggests role for female hormones

245
Q

SLE epigenetic factors

A

DNA methylation

histone modifications

246
Q

SLE immunoregulatory factors

A 
presentation of unknown antigens by MHC molecules leads to priming of CD4+ T cells
these cells activate B cells in auto reactive germinal centres; undergo class switching, affinity maturation and differentiation into plasma cells
PCs secrete high levels of soluble autoantibodies of the IgG isotype. form immune complexes by binding autoantigens
- autoantibodies: anti-nuclear, anti-cardiolipin
this can support inflammation and tissue destruction through the recruitment of inflammatory cells to tissues - complement fixation
apoptotic cells from damaged tissues can be taken up by phagocytes, which present novel autoantigens, supporting further priming and autoreactivity
env triggers e.g. viral infection or DNA damage by UV rays contribute by inducing secretion of IFN-1 and other cytokines, supporting lymphocyte autoreactivity as well as tissue destruction
247
Q

SLE-DAS factors

A 
arthritis
localised skin rash
generalised skin rash
alopecia
mucosal ulcers
systemic vasculitis
mucocutaneous vasculitis
neuropsychiatric involvement
cardiac/pulmonary involvement
serositis
myositis
proteinuria
hypocomplementaemia
increased anti-dsDNA
thrombocytopenia
leucopenia
haemolytic anaemia
  • then use formula to work out score
248
Q

Constitutional S and S of SLE - broad factors which contribute to fatigue

A

disease related factors
psychosocial factors
others

249
Q

Constitutional S and S of SLE - disease related factors which contribute to fatigue

A

disease activity and inflammation
history of neuropsychiatric lupus
co-morbidities: AI hypothyroidism, anaemia

250
Q

Constitutional S and S of SLE - psychosocial factors which contribute to fatigue

A

depression
poor sleep pattern
personality traits
low perceived social support

251
Q

Constitutional S and S of SLE - other factors which contribute to fatigue

A 
vit D deficiency
obesity
physical inactivity
meds
fibromyalgia
252
Q

SLE - investigations if pt presents with fatigue

A

FBC
serum iron/B12/folic acid (if anaemic)
thyroid fct
serum vit D

253
Q

what are the 2 most common constitutional symptoms of SLE?

A

fatigue

fever

254
Q

Overall management of SLE - 5 features

A

treat active disease - hydroxychloroquine and immunosuppressants
treat anaemia/hypothyroidism
address co-morbid psychosocial factors
exercise
behavioural therapy, psychoeducational intervention

255
Q

SLE - possible aetiology of fever

A

infection - viral, bacterial, mycobacterial, fungal, protozoal, haematodes
malignancy - lymphoma, primary carcinoma, metastatic carcinoma, myeloma

256
Q

differential diagnosis of splenomegaly in SLE

A 
neoplastic and lymphoproliferative disease
hepatic
vascular occlusive
immunological
infection
inherited haemoglobinopathies
257
Q

differential diagnosis of weight loss in SLE

A 
infection
malignancy
GI
organ damage
meds
258
Q

SLE renal manifestations

A

lupus nephritis
- immune-complex glomerulonephritis, which is defined by a combination of clinical and lab features (proteinuria, high level of creatinine and blood urea nitrogen)

259
Q

SLE classification of LN - categories

A 
1
2
3
4
5
6
260
Q

SLE classification of LN - 1

A

minimal mesanginal LN

261
Q

SLE classification of LN - 2

A

mesanginal proliferative LN

262
Q

SLE classification of LN - 3

A

focal lupus nephritis (<50% of glomeruli)

- active/active and chronic/chronic

263
Q

SLE classification of LN - 4

A 
diffuse LN (>=50% of glomeruli
- active/active and chronic/chronic
264
Q

SLE classification of LN - 5

A

membranous LN

265
Q

SLE classification of LN - 6

A

advanced sclerosing LN (>=90% globally sclerosed glomeruli without residual activity)

266
Q

SLE musculoskeletal manifestations

A 
arthritis/arthropathy (most common)
tendon rupture (rare)
myalgia/myositis
avascular bone necrosis
osteopenia/osteoporosis
267
Q

SLE musculoskeletal manifestations - arthritis/arthropathy

A

non-erosive non-deforming arthritis primarily affecting small joints of hands, wrists, knees
5-15% progresses to deforming arthropathy, may show as erosive on X-ray, rhupus syndrome, or non-erosive the Jacoud’s arthropathy

268
Q

SLE musculoskeletal manifestations - tendon rupture

A

rare

patellar and Achilles tendon

269
Q

SLE musculoskeletal manifestations - myalgia/myositis

A

generalised myalgia and muscle tenderness common

more rarely, myositis involving proximal muscles +/- elevated muscle enzymes, typically creatinine phosphokinase (CPK)

270
Q

SLE musculoskeletal manifestations - avascular bone necrosis

A

asymptomatic with abnormal findings on imaging
severe disease with pain and disability from advanced cortical destruction
most common site hip, but most pts will have multisite involvement

271
Q

SLE CV manifestations

A 
pericarditis (most common)
myocarditis (rare)
cardiomyopathy
CAD
valvular disease
272
Q

SLE CV manifestations - pericarditis

A

most common

typically present with tachycardia, substernal or precordial chest discomfort, dyspnea and positional pain

273
Q

SLE CV manifestations - myocarditis

A

rare
can present with symptoms of HF inc resting tachycardia and dyspnea, also sometimes chest discomfort, fever and/or myopericarditis

274
Q

SLE CV manifestations - cardiomyopathy

A

can be directly caused by SLE or secondary to CAD

275
Q

SLE CV manifestations - CAD

A

most common cause of death in pts with late-onset or long-standing SLE
risk of fatal MI increases with time from SLE diagnosis

276
Q

SLE CV manifestations - valvular disease

A

most common - a sterile endocarditis/Libman-Sacks endocarditis, which usually affects mitral valve (but any can be affected)
clinically significant valvular dysfunction secondary to L-S is rare

277
Q

CV risk factors in SLE

A

traditional risk factors
inflammatory risk factors
lupus-related risk factors

278
Q

neuropsychiatric manifestations of SLE

A

wide spectrum - can affect all levels of the NS inc brain and spinal cord, as well as PNS
CNS - myelitis
PNS - myasthenia

279
Q

neuropsychiatric manifestations of SLE - CNS

A

myelitis

  • NV disease
  • seizures
  • menngitis
  • movement disorders
  • psychiatric disease
  • cognitive dysfunction
280
Q

neuropsychiatric manifestations of SLE - PNS

A

myasthenia

  • cranial neuropathy
  • mononeuritis multiplex
  • inflammatory demyelinating neuropathy
  • axonal polyneuropathy
281
Q

pulmonary manifestations of SLE

A

lung parenchyma - acute lupus pneumonitis, interstitial lung disease
pleura - lupus pleuritis +/- effusion
airways - laryngeal involvement, bronchiectasis, small airways disease
vessels - alveolar haemorrhage; pulmonary arterial hypertension, anti phospholipid syndrome
muscles - shrinking lung syndrome
infectious pneumonia
lung cancer

282
Q

SLE GI manifestations

A 
lupus mesenteric vasculitis
protein losing gastroenteropathy (PLGE)
SLE-related intestinal pseudo-obstruction (IPO)
SLE-related acute pancreatitis
celiac disease
IBD
eosinophilic enteritis
pneumatosis cystoides intestinalis
283
Q

SLE GI manifestations - lupus mesenteric vasculitis

A

acute ischaemic enteritis - mainly SI
chronic multiple ulcers - mainly colon
mild, non-specific abdominal pain, bloating, loose stool - necrosis and intestinal perforation

284
Q

SLE GI manifestations - PLGE

A

oedema and severe hypoalbuminemia secondary to excessive loss of serum protein from GIT

285
Q

SLE GI manifestations - IPO

A

ineffective intestinal propulsion with clinical features of intestinal obstruction without an identifiable organic obstructive lesion and an abdominal distension with a very sluggish or absent peristalsis

286
Q

SLE GI manifestations - SLE-related acute pancreatitis

A

acute inflammation of pancreas presenting in 83% of cases with also pain, in only 23% pain radiates to back
diagnosis based on lab evidence of elevated serum amylase or lipase levels
clinical symptoms and suggestive tomographic findings are helpful
may have nausea and vomiting

287
Q

ocular manifestations of SLE

A 
keratoconjunctivitis sicca
mild lupus retinopathy
mild retinal artery and vein occlusion
6th nerve palsy
neovascular glaucoma
uveitis
scleritis
ischaemic optic neuropathy/neuritis
vasculitis
288
Q

SLE cutaneous manifestations - specific

A

derma-epidermal LE - acute, subacute, chronic/discoid

289
Q

SLE cutaneous manifestations - non-specific signs

A

dermal LE
hypodermal (subcutaneous) LE
signs indicative of a thrombotic vasculopathy
neutrophilic cutaneous LE
other, of yet uncertain pathogenic significance

290
Q

Acute Cutaneous Lupus Erythematosus (ACLE)

A

can be first sign of SLE, preceding onset of systemic disease by weeks or months
classic malar/butterfly rash
in generalised ACLE, may affect arms, elbows, shoulders, knees and trunk
oral lesions - ulcerations - mainly hard palate, intense erythema +/- petechiae

291
Q

ACLE - classic malar/butterfly rash

A

discrete erythematous macules, papules and plaques in central areas of face, without typically affecting nasolabial folds and periorbital regions
lesions may become confluent with scaling, erosions and crusting

292
Q

Subacute Cutaneous Lupus Erythematosus (SCLE)

A

erythematous macules or papules, evolve into either
-scaly papulo-squamous psoriasiform lesions
-annular patches and plaques
in 50% cases

mixed form lesions also found
oral lesions rare and clinically similar to CCLE

293
Q

SCLE healing

A

post-inflammatory hyper and/or hypo pigmentation, greyish atopic scarring and telangiectasias

294
Q

Discoid or Chronic Cutaneous Lupus Erythematosus (CCLE)

A

most common clinical manifestation of CLE, usually affects ears, face, scalp and/or neck
annular erythematous and violaceous plaques with follicular hyperkeratosis, can progress to scars and atrophy
if scalp involved, scarring alopecia can develop
oral mucosa can be affected by lichenoid lesions

295
Q

what is the most common clinical manifestation of CLE?

A

CCLE - Discoid or Chronic Cutaneous Lupus Erythematosus

296
Q

Discoid or Chronic Cutaneous Lupus Erythematosus - oral lesions

A

lichenoid lesions
-well-demarcated, round or irregular red lesions, atrophic/ulcerated with a white radiating keratitis striae
-can have verrucous aspect or be linear fissured or have ulcerative lesions
-asymmetrically distributed mainly on hard palate, followed by lips
oral DLE (or CLE) is an OPMD, though malignant transformation is extremely rare

297
Q

SLE oral manifestations

A 
oral mucosa
-ulcerations
-lichenoid lesions
-erythematous lesions
-leukoplakias
-petechia
-cheilitis with erythema
salivary gland involvement - low flow rate - SLE associated with SS
caries
TMJ involvement - pain, crepitus, difficulty opening
PDDs
298
Q

SLE diagnosis - lab testing

A

positive ANA mandatory entry criterion
99% cases present

anti-Sm and anti-dsDNA

299
Q

SLE diagnosis - ANA specificity and sensitivity

A

v high sensitivity for SLE but limited specificity - occur in other CT diseases

300
Q

SLE diagnosis - anti-Sm and anti-dsDNA specificity and sensitivity

A

highly specific but less sensitive

301
Q

is SLE classification criteria diagnostic?

A

no

302
Q

entry criterion for SLE

A

ANA titre >=1:80

303
Q

SLE additive criteria

A

don’t count a criterion if there is a more likely explanation than SLE
one occasion sufficient
don’t need to occur simultaneously
need at least one clinical criterion and >=10 points
in each domain only count highest criterion

304
Q

SLE classification - clinical domains (each has a different weighting)

A

constitutional - fever
haematological - leukopenia, thrombocytopenia, AI hemolysis
neuropsychiatric - delirium, psychosis, seizure
mucocutaneous - non-scarring alopecia, oral ulcers, subacute discoid/cutaneous, acute cutaneous
serosal - pleural/pericardial effusion, acute pericarditis
MS - joint involvement
renal
-proteinuria >0.5g/24 hr
-renal biopsy class 2 or 5 LN
-renal biopsy class 3 or 4 LN

305
Q

SLE classification - immunology domains (each has a different weighting)

A

antiphospholipid antibodies

  • anticardiolipin OR
  • anti-B2GPI OR
  • lupus anticoagulant

complement proteins

  • low C3 OR C4
  • low C3 AND C4

SLE-specific antibodies

  • anti-dsDNA OR
  • anti-Sm
306
Q

what is the pharmacological treatment for SLE mainly guided by?

A

individual patient manifestations

307
Q

SLE pharmacological treatment

A 
corticosteroids - prednisolone
antimalarials - hydroxychloroquine
immunosuppressive agents
-azathioprine
-mycophenolic acid
-methotrexate
-cyclophosphamide
-cyclosporine
-tacrolimus
-sirolimus (rapamycin)
308
Q

SLE treatment prednisolone dose

A

1-2mg/kg

309
Q

SLE treatment hydroxychloroquine dose

A

400-800mg

310
Q

SLE treatment - pharmaceuticals targeting B cells in different developmental stages

A

if SEs to conventional immunosuppressive therapy/may not respond
monoclonal antibodies against a specific molecule
anti-CD22 - epratuzumab
anti-CD20 - rituximab
target different receptors in mature and memory B cells

311
Q

is there an increased cancer risk with SLE?

A

overall slightly increased risk

312
Q

SLE - which cancers are patients at an increased risk for?

A

haematological (lymphoma, leukaemia, multiple myeloma)
NHL
H+N cancer

313
Q

possible factors suggested as mediating cancer risk in SLE

A

lupus-related meds e.g. cyclophosphamide
inherent immune system abnormalities e.g. high levels of IL6+10 high risk of NHL
overlap with SS
viral infections e.g. HPV and EBV
traditional cancer risk factors e.g. smoking

314
Q

when was Behect disease first described and how?

A

1937

triad

315
Q

Behcet disease triad

A

oral ulcers
genital ulcers
uveitis

316
Q

how is Behcet disease recognised now in contrast to the triad?

A

involvement of most organ systems recognised

systemic vasculitis which can involve arteries and veins of all sizes

317
Q

why is the diagnosis of Behcet disease often delayed by several years?

A

because the diagnostic features may present over months/years

318
Q

why is Behcet disease known as the “Silk Road Disease”?

A

strikes people with this bloodline more frequently

e.g. high incidence in Turkey

319
Q

pathogenesis of Behcet disease - overall

A

genetic predisposition
disruption of innate immunity
disruption of adaptive immunity

= tissue damage + vasculitis

320
Q

pathogenesis of Behcet disease - genetic predisposition

A

HLA B51 association

321
Q

pathogenesis of Behcet disease - disruption of innate immunity

A

hyperactivation of neutrophils (neutrophilic vasculitis, enhance chemotaxis, secrete cytokines able to induce a Th1-mediated immune response)
alterations in both number and function of peripheral NK cells
enhanced activation of ydT cells

322
Q

pathogenesis of Behcet disease - disruption of adaptive immunity

A

Treg downregulation = less of IL-10
Th1 upregulation = increased IFNy, IL2, IL12 and IL18
Th17 upregulation = increase in IL17

323
Q

clinical manifestations of Behcet disease

A

oral ulcers
genital ulcers
eye lesions - uveitis, blindness
skin lesions - palpable purpura, subcutaneous nodules

324
Q

Behcet disease - pathargy test

A

needle prick
24-48 hours
exaggerated inflammatory reaction

325
Q

Behcet disease differential diagnosis

A 
RAS
infections
skin diseases
Crohns
SJS
pemphigoid
pemphigus
SLE
IBD
sarcoidosis
326
Q

Behcet disease more extensive clinical manifestations

A 
mucocutaneous involvement
ocular involvement
MS involvement
vascular involvement
cardiac involvement
GI involvement (entero-Behcet disease)
neurologic involvement
pulmonary involvement
327
Q

Behcet disease diagnosis

A

difficult
no diagnostic lab test, mostly clinical
history key - RAS plus other characteristic clinical manifestations should raise suspicions for BD

328
Q

Consensus Classification of Paediatric Behcet Disease

A

recurrent oral aphtosis - >=3 attacks pa
genital ulceration and aphtosis - typically scar
skin involvement - necrotic folliculitis, acneiform lesions, erythema nodosum
ocular involvement - uveitis, retinal vasculitis
neurological signs - with exception of isolated headaches
vascular signs - venous thrombosis, arterial thrombosis, arterial aneurysm

need to score >=3

329
Q

Behcet Disease ISG criteria

A 
ROU >=3 in a year
plus 2 of:
-recurrent genital ulceration
-eye lesions
-cutaneous lesions
-+pathergy test

findings applicable only in absence of other clinical explanation

330
Q

International Criteria for Behcets disease

A

score >=4

  • if do pathergy test add 1 to score
  • ocular lesions 2
  • genital aphthosis 2
  • oral aphthosis 2
  • skin lesions 1
  • neurological manifestations 1
  • vascular manifestations 1
331
Q

ISG and ICBD criteria limitations

A

helpful for diagnosis
but the criteria were described to categorise pts for study purposes and were not developed to diagnose disease in individuals

332
Q

conventional immunosuppressive therapies for Behcet disease

A

corticosteroids

- topical for mucocutaneous

333
Q

biologic therapies for Behcet disease

A 
infliximab, rituximab, tocilizumab
multiple different targets
-TNFa
-interleukins
-CD cells
334
Q

EM definition

A

an acute immune-mediated inflammatory mucocutaneous disease

clinically polymorphic lesions triggered by hypersensitivity reactions to various antigens with a tendency to recur

335
Q

what surfaces does EM affect?

A

mucous membranes and skin

336
Q

what age group does EM typically affect?

A

young adults 20-4yrs

337
Q

EM gender distribution

A

more common F 1.5:1

338
Q

estimated annual incidence of EM

A

<1% (but unknown)

339
Q

prevalence of EM

A

<1%

340
Q

what is the estimated prevalence of oral EM lesions among patients with cutaneous lesions?

A

35-65%

341
Q

causes of EM

A

infections and drugs

other conditions

342
Q

EM mortality rates

A

not documented

343
Q

infections as a cause of EM

A

HSV infection most commonly identified cause of EM

most commonly identified cause in children - mycoplasma pneumoniae infection

344
Q

drugs as a cause of EM

A 
antibiotics
sulfonamides
anti epileptics
barbiturates
NSAIDs
345
Q

other conditions that can cause EM

A

IBD
malignancy
menstruation

346
Q

what is the most commonly identified cause of EM?

A

HSV

347
Q

what is the most commonly identified cause of EM in children?

A

mycoplasma pneumoniae infection

in this context, a new entity of EM named MIRM (mycoplasma induced rash and mucositis) was described

348
Q

basic pathogenesis of EM

A

T3 hypersensitivity reaction

T4 hypersensitivity reaction

349
Q

T3 hypersensitivity reaction

A

immune complex reaction of antigen and antibody
1 form antigen-antibody complex in circulation
2 deposit of immune complex in blood vessels
3 appearance of inflammatory reaction with subsequent vasculitis

350
Q

what does a biopsy on the blood vessel wall of EM patients show?

A

an increasing level of IgM, complement and fibrin deposits

351
Q

T4 hypersensitivity reaction

A

T cell mediated immune reaction to precipitating agent

352
Q

what does HAEM stand for?

A

HSV-associated EM

353
Q

when does HAEM occur?

A

7-21 days after primary or recurrent viral infection

354
Q

pathogenesis of HAEM

A

circulating PBMCs, macrophages and CD34+ Langerhans cells engulf HSV-DNA
migrate to epidermis to transfer these antigens to keratinocytes
expression of HSV-DNA in keratinocytes leads to activation of HSV-specific CD41 Th1 cells, which produce IFN-y
in turn this will up regulate cytokines and chemokine that autoreactive attack cytotoxic T cells, NK cells, and monocytes, responsible of keratinocytes lysis and subsequent epithelial damage

355
Q

what does DIEM stand for?

A

Drug-induced EM

356
Q

DIEM

A

no IFN-y is found but have TNFa, produced by macrophages, which along with perforin and granzyme B, will induce keratinocytes apoptosis with subsequent epithelial destruction

357
Q

differences between HAEM and DIEM - aetiology

A

HAEM - HSV1/2

DIEM - drugs

358
Q

differences between HAEM and DIEM - clinical

A

HAEM - no/mild prodromal S+S, acute, self-limiting, recurrent
DIEM - flu-like prodrome, acute, self-limiting, not recurrent

359
Q

differences between HAEM and DIEM - predilection site

A

HAEM - skin, mucosal lesions absent/minimal

DIEM - skin, mucosal lesions prominent

360
Q

differences between HAEM and DIEM - histopathology

A

HAEM - focal keratinocyte necrosis, edema, predominant mononuclear infiltration CD4+
DIEM - extensive keratinocyte necrosis, less edema, predominant mononuclear infiltration CD4+

361
Q

differences between HAEM and DIEM - immunochemistry

A

HAEM - +HSV DNA PCR, +IFNy

DIEM - -HSV DNA PCR, +TNFa

362
Q

differences between HAEM and DIEM - mortality

A

HAEM - not reported

DIEM - 5-15%

363
Q

three EM subtypes

A

isolated
recurrent
persistent

364
Q

isolated EM

A

occurs just once

infections, drugs

365
Q

recurrent EM

A

frequent occurrence of EM over a period of years, usually >6 episodes p.a.
infections, menstruation

366
Q

persistent EM

A

continuous occurrence of typical and atypical lesions without interruption
infections, IBD, malignancy

367
Q

EM clinical forms

A

minor

major

368
Q

EM minor form

A

skin <10% BSA

mucosa uncommon, 1 site only, usually oral

369
Q

EM major form

A

skin <10% BSA
mucosa >=2 different mucosal sites
oral and genital, ocular, laryngeal, oesophageal or a combination

370
Q

EM typical target lesion

A

centre is dusky or dark red with a blister or crust
next ring is a paler pink and is raised due to oedema
outermost ring bright red

371
Q

EM atypical target lesion

A

raised, oedematous lesion with two zones of colour change and a poorly defined border

372
Q

EM diagnosis - criteria

A

no standardised criteria

373
Q

what is EM diagnosis based on - broad categories?

A

clinical history
clinical exam
biopsy (skin)
lab studies

374
Q

EM diagnosis - clinical history

A

acute, episodic, self-limiting
symptoms of HSV, mycoplasma pneumoniae and other infections
thorough meds history (often started 2-3 days prior)

375
Q

EM diagnosis - clinical exam

A

skin lesions: typical, atypical

morphology: pleomorphic appearance of oral lesions
location: U/L lip and anteriorly in mouth - erythematous, erosions, fibrin, haemorrhagic

376
Q

EM diagnosis - biopsy

A

skin
H+E
DIF

377
Q

EM diagnosis - lab studies

A

test for ESR, WCC, LFT, electrolytes

IIF to rule out AI blistering disease

378
Q

basis of EM treatment

A

treating underlying infection/medication paramount
symptomatic treatment, guided by clinical severity
prevent infections and local symptom control

379
Q

treatment of mild EM

A

topical antiseptics
oral antihistamines
analgesics
topical CS

380
Q

treatment of EM affecting MM

A

high potency CS gel, oral anaesthetic solutions, topical ophthalmic preparations

381
Q

treatment of severe mucosal EM

A

oral prednisolone 40-60mg

taper 2-4 wks

382
Q

treatment of recurrent EM

A

6m trial of continuous antiviral therapy

383
Q

are the lesions raised or flat in EM major?

A

raised

384
Q

distribution of lesions in EM major?

A

mostly extremities

in children often affects trunk

385
Q

does EM major progress to TEN?

A

no

386
Q

features of SJS - skin detachment

A

<10%

387
Q

features of SJS - target lesions

A

atypical

388
Q

features of SJS - raised lesions?

A

no

389
Q

features of SJS - distribution of lesions

A

mostly trunk

390
Q

features of SJS - progression to TEN?

A

possible

391
Q

features of TEN with macules - skin detachment

A

> 30%

392
Q

features of TEN with macules - target lesions

A

atypical

393
Q

features of TEN with macules - raised lesions?

A

no

394
Q

features of TEN with macules - distribution of lesions?

A

mostly trunk

395
Q

features of TEN with no macules - skin detachment

A

> 10%

396
Q

features of TEN with no macules - target lesions?

A

none

397
Q

features of TEN with no macules - raised lesions?

A

no

398
Q

features of TEN with no macules - distribution

A

mostly trunk

Oral medicine (14 decks)

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