Autoimmune blistering Flashcards
1
Q
Associations of EBA
A
IBD (esp crohns), myeloma, SLE, RA, thyroiditis, dermatomyositis, amyloidosis, lymphoma, carcinoma, drug induced.
2
Q
Types of EBA
A
1) classic - acral with alopecia and nail dystrophy
2) BP like (no milia or scarring): widespread with accentuation in skin folds
3) mucous membrane including bursting-perry with scarring alopecia. oesophageal strictures, laryngeal stenosis, ocular scarring, blindness.
3
Q
DIF of EBA
SSS
A
Continuous, linear, IgG at BMZ, can have C3, IgA or M
SSS: dermal side.
4
Q
EBA can occur at any age
A
T
5
Q
EBA is more common in asians
A
T
6
Q
Antibodies in EBA
A
alpha-chain 290kDa NC1 domain (collagen VII) 145kDa
7
Q
Where is the blister in EBA
A
sublamina densa
PMN predominant
8
Q
BP antigens
A
BPAg1 230kDa
BPag2 NC16A 180kDa
9
Q
BP IF
A
Linear C3 and IgG at BMZ
IgG4>G1
10
Q
Drugs associated with BP
A
Fluid Sores Caused by Prescription
Frusemide, Spironolactone/sulphasalazine, Captopril, Betablockers, PCN, penicillamine.
11
Q
Potential associations with BP
A
Psoriasis, LP, parkinsons, dementia, stroke, MS
12
Q
Triggers for BP
A
trauma, burns, radiotherapy, UV irradiation
13
Q
BP oral cavity in %
A
30%
14
Q
Eosinophilia in BP %
A
50%
15
Q
Gender predominance in BP
A
M>F
16
Q
BP in children - where
A
acral and vulvar
17
Q
EM in BP where is the blister
A
Lamina lucida blister
18
Q
Variants of BP
A
Localised variants: pretibial, vulva, peristomal, umbilical, distal end of amputated limb, sites of radiotherapy, burns
Unusual: palmo/plantar, vegetans, nodularis, vesicular TEN like, papular, eczematous, erythrodermic, LP pemphigoides
19
Q
Drugs associated with MMP
A
penicillamine, clonidine
20
Q
Antibodies and MMP
A
Group 1 = laminin332=5, laminin 6
Group 2= just ocular: integrin beta4
Group 3: mucosa + skin BPAG2/BP/collagen XVII/BP230
Group 4: heterogenous. variable mucosa, no skin
21
Q
% of oral mucosa in MMP
A
85%
22
Q
skin involvement in MMP
A
25-30%
23
Q
Associations with MMP
A
Anti-laminin 5 (332) and adenocarcinoma,
autoimmune disease: LS
24
Q
DIF MMP
A
linear deposits of immunoglobulins and/or complement along epithelial BMZ. Linear IgG and C3 at BMZ
Mucosa 50-90% > skin 20-50%
25
SSS MMP
epidermal roof mostly
| but anti-laminin 5 (332): dermal
26
histo MMP
blister in lamina lucida with mixed infiltrate: may have plasma cells, Eos, PMNs
27
Ddx of cicatricial pemphigoid
PV, erosive LP, ocular pseudopemphigoid, SJS/TEN, BP, EBA, linear IgA
28
Herpes gestationis DIF
linear C3 at BMZ
29
Associations with pemphigus gestationis
Graves, hydatidiform mole, choriocarcinoma.
30
Pemphigus gestationis antigens
BPAg2 NC16A
31
Pemphigus gestationis DIF
linear C3 at BMZ
32
Pemphigus gestationis - mucosal involvement?
No
33
Pemphigus gestationis - when
4 weeks to 5 weeks post part
34
Pemphigus gestationis who
father more often HLA-DR2
| 50% 1st pregnancy, 8% of subsequent pregnancies are spared.
35
Pemphigus gestationis flares
post partum, menstruation, OCP
36
Pemphigus gestationis more likely to be prolonged if:
older age, multiparity, mucosal involvement
37
Pemphigus gestationis fetal prognosis
worse when early onset. Risk of low birth weight and premature
neonatal PG in 3%
38
SSS MMP
Epidermal (roof) except anti-laminin 5 (332): floor
39
MMP antigens
BPAg2 - NC16A, BPAg1, Laminin 5, type VII collagen, alpha 6integrin beta 4
40
MMP M>F
F
41
DIF MMP
Linear IgG +/- complement along epithelial BMZ (mucosa >skin). Less commonly IgA and IgM
42
%+ve IIF MMP
20-30% usually IgG +/-IgA
43
What gives a worse prognosis in children with MMP
IgA
44
Associations with MMP
LS
antiliminin 5 - adenoca
Drugs: penicillamine, clonidine, NSAIDS
45
Which HLA is MMP associated with
HLA DQ7, DQB1*0301
46
MMP H&E vs BP
MMP: subepidermal blister with usually fewer eosinophils in the cutaneous lymphochistiocytic infiltrate than in bullous pemphigoid. Later stage: fibrosis
47
All patients with MMP will have +ve DIF
false
48
Most commonly +ve DIF site for MMP
Conjunctiva
49
T/F in mmp SSS increases sensitivity of autoantibodies and is more likely to detect IgA
T
50
MMP - genitals involved in half of female patients
t
51
2 types of skin lesions in MMP `
Generalised blistering (looks like BP) or localised blisters on an erythematous plaque
52
% sites involved in MMP
85% oral
Skin 25-30%
Genitals of females in 50%
Conjunctiva
53
Pemphigoid gestationis occurs when
Pregnancy, hydatidiform mole, choriocarcinoma. Male more likely HLA-DR2
54
Pemphigoid gestationis - target antigens
BP180 >BP230
| IgG and C3 (as IgG1 avidly binds C3, C3 is sometimes more often detected than the IgG themselves)
55
Pemphigoid gestationis - other associations
14% other autoimmune disease
Graves 10%
Hypothyroidism
vitiligo, alopecia, autoimmune thrombocytopenia
56
Linear IgA antigens
BP180 (shed ectodomain LAD1) , BP230, LAD285 Collagen VII
57
Least satisfactory DIF site for linear IgA
forearm
58
t/f mucosal biopsies but not necessarily the conjunctiva are positive in linear IgA
t
59
SSS with linear IgA usually shows the binding to the dermal side
F epidermal> dermal (dermal more likely collagen VII)
60
IIF in linear IgA is more commonly +ve in adults than children t/f
F children 80% vs 30% adults
61
Linear IgA - how to do IIF
Can use blister fluid, or serum
62
T/F in linear IgA, IIF can use urine
F
63
In chronic bullous disease of childhood, the mucosa is rarely involved
F - common. However if conjunctiva scarring - consider this to be MMP
64
What age does chronic bullous disease of childhood usually occur?
Less than 5
65
Associations with linear IgA
Drugs: vancomycin, frusemide, penicillin, diclofenac, lithium
Infection, IBD
Presence of building work in home, (50% adults and 75% children)
Increase in lymphoproliferative disease in adults. Case reports of increased risk of bladder and renal cancer
66
Prognosis of linear IgA
Spontaneous remission after 3-6 years. Often improvement in pregnancy, but relapse post partum. No fetal problems
67
Treatment of linear IgA
Dapsone
68
Which type of EBA has the best prognosis
BP like
69
Bullous SLE - target antigen
Collagen VII
70
H&E bullous SLE
subepidermal blister with neutrophlic infiltrate, occasionally resulting in microabscesses resembling DH.
71
DIF bullous SLE
Linear bands of IgG, IgA, IgM and C3
72
T/F bullous SLE occurs when SLE flares
F
73
SSS bullous SLE
Floor
74
Tx of bullous SLE
Capstone, MTX, rituxumab
75
DH: family hx of coeliac disease or DH in what %
10%
76
DH: HLA associations
HLA DQ2, HLADR3, DQw2, HLAB8
77
DIF DH
Granular IgA in papillary dermis
78
IIF in DH
Negative for BMZ or dermal autoantibodies. But if monkey oesophagus used - IgA endomysial abs may be detected.
79
Usual onset of DH
20-55
80
T/F oral lesions do not occur in DH
F - common but asymptomatic
81
Associations with DH
Gluten
Thyroid disease in 30%
Lymphoma (GI)
DM, SLE, vitiligo, sjogrens
82
Prognosis of DH
10% remission
| Do not have a reduced life expectancy, despite increased risk of lymphoma, likely due to reduced IHYD
83
Tx of DH
```
dapsone
sulfapyridine
Topical steroids
Heparin +/-tetracyclines + nicotinamide
Gluten free diet
Avoid iodine products
Gluten free after 2 years, maybe be able to reduce dapsone and diet after 5-10 years, protects from lymphoma.
```
84
% of PNP with an existing neoplasm
2/3
85
PNP IIF is +ve in what sort of epithelial
Simple, transitional and stratifying.
86
Associations with PNP
40% NHL, 30% CLL, 10% castlemans, 6% thymomas, 6% sarcomas, 6% waldenstroms macroglobulinaemia
87
Clinical features of PNP
Intractable stomatitis, pseudomembranous conjunctivitis, oesophageal, nasopharyngeal, vaginal, labia, penile, mucosal lesions. EM like lesions palms and soles.
88
H&E of PNP
Suprabasal acantholysis and individual keratinocytes necrosis with lymphocytes in the epidermis. Basal cell liquefactive degeneration.
89
PNP DIF
Intercellular and subepidermal IgG + C3.
90
PNP target antigens
Plains (desmoplakin, envoplakin, BP230, periplakin. ) and desmogleins
91
Complications of PNP
bronchiolitis obliterans - RFTs and CXray or CT
92
T/F the intracellular location of plakin proteins makes it unlikely that antiplakin autoabs initiate pathology in PNP because IgG cannot penetrate cell membranes.
T
93
After castlemans or thymoma removed, how long will it take to clear completely (PNP)
6-18/12
94
Drug induced pemphigus - mechanism
thiol: provoke acantholysis by increasing the activity of plasminogen activators.
Non thiol: active amide group
95
% of drug induced pemphigus that remits
40-50% thiols when drug withdrawn, only 15% non thiol group
96
Thiol drugs (sulfhydryl group)
Captopril, penicillamine
97
Non thiol causes of pemphigus
angiotensin II blockers, enalapril, ramapril, nifedipine, penicillin, cephalosporin, rifampicin, montelukast, hydroxychloroquine.
98
Susceptibility allele to drug induced pemphigus
HLADR4
99
Non drug triggers of pemphigus
allium family of veggies (onion, garlic, shallot, leek)
| Radiotherapy, thermal burns and electrical injury
100
Where does fogo selvagem occur?
Brazil, Columbia, el Salvador, Paraguay and Peru, Tunisia and Libya
101
bg prevalence of antidesmoglein 1 abs in general population of endemic pemphigus
20% antidesmoglein 1 with non pathogenic subclasses or a non pathogenic domain of dsg1
43% have antidesmoglein 3 but significance is unknown
102
Risk factor for endemic PF
Black flies at the end of the rainy season. Simuliidae bites
103
Age group affected by endemic PF
Children and young adults.
104
Endemic PF - sites affected and clinical features
head and neck first. Burning sensation (wild fire), spreads aurally and may become generalised.
105
Endemic PF is often transferred via the placenta T/F
F - although the abs transfer, rarely does the disease occur in neonates. Desmoglein3 is more highly expressed in neonatal than adult skin and this may be protective.
106
World wide PV is more common than PF
T
107
Areas of the world where PF is more common than PV
Mali, Libya, south Africa.
108
DIF PF
Intercellular IgG and C3, may be restricted to upper epidermis.
109
IIF in PF = %
85%
110
Areas which PF tends to occur
seborrhoeic areas - scalp, face, chest, upper back.
111
Clinical variants of PF
```
Pemphigus resembling DH (pemphigus herptiformis)
Pemphigus erythematosus(senear usher)
```
112
senear usher DIF
Granular IGG and C3 at BMZ, intercellular IGG and C3 in epidermis
113
Tx of PF
```
Potent or IL steroids
Prod 20-40mg/day
aza, cyclophosphamide
HCQ as adjuvant
IVIg
MTX
Dapsone
MMF
Nicotinamide 1.5mg + minocycline 100mg daily
Rituximab.
```
114
H&E PF
Dyskeratotic cells in the granular layer of older lesions with a mixed inflammatory infiltrate of eosinophils and Neutrophils in the superficial dermis.
115
T/F people with PV in India tend to be older than those elsewhere
F younger
116
Types of pemphigus
```
PV - variant: veterans
PF - vary: PH, PE
Drug induced
Intercellular IGA
PNP
```
117
% of pemphigus that is PV
70%
118
Races that more susceptible to PV
Ashkenazi Jews, Indians, eastern countries
119
HLA and PV
DRB1*0402 and DRB1*1401
120
IN Iranian pemphigus, epidemiology
Increase in OCP, pesticides, protective effect from smoking
121
In PV patients, Indian patients are more likely to have what
Dsg 1
122
Clinical features PB
Oral lesions 50-70%
Scalp, face, axillae, groins and pressure points.
Nail dystrophy and paronychia
123
PV - poor prognostic factors
Jews, older patients
124
PV, most relapse occur when
First 2 years after Dx.
125
2 subtypes of pemphigus vegetans
Neumann (severe) and hallopeau (mild)
126
Pemphigus veterans antigens
desmocollins 1 and 2 and dig 3
127
2 types of IgA pemphigus
1) subcorneal pustular (desmocollin 1) - associated with monoclonal IgA gammopathy
2) intraepidermal neutrophilic type (sometimes desmocollin1)
128
Associations with IgA pemphigus
IgA monoclonal gammopathy, HIV, IBD, gluten sensitive enteropathy, RA, thiol drugs
