Habif Ch 16 - Vesicular And Bullous Dz

Front 1

What is the most common autoimmune blistering disorder?

Back 1

Bullous Pemphigoid

Front 2

What is the split for Pemphigoid d/o vs Pemphigus?

Back 2

Pemphigoid - impaired epidermis to BM connection
Pemphigus - impaired cell to cell adhesion

Front 3

Diseases that affect the Spinous Layer (upper and mid epidermis)

Back 3

Dermatophyte fungus infection
Dyshidrosis
Eczematous blister
Friction blister
Insect bites and scabies
Miliaria rubra
Viral blisters (HSV, VZV)

Front 4

Diseases that affect the Granular cell layer (aka subcorneal)

Back 4

Bullous ichthyosiform erythroderma
Pemphigus foliaceus
Pemphigus erythematosus

Front 5

Diseases that affect the Subcorneal

Back 5

Candida albicans infection
Impetigo
Miliaria crystallina
Staph Scalded Skin Syndrome
Subcorneal pustular dermatosis

Front 6

Diseases that affect the Basal Cell Area

Back 6

Erythema multiforme (epidermal type)
Epidermolysis bullosa simplex
Fixed drug eruption
Kerosene necrosis
Lichen Planus
TEN

Front 7

Diseases that affect the Spinous layer (lower epidermis and suprabasal area)

Back 7

Benign Familial Chronic Pemphigus
Keratosis follicularis
Pemphigus vulgaris
Transient acantholytic dermatosis

Front 8

Diseases that affect the Lamina Lucida

Back 8

Bullous Pemphigoid
Cicatrical Pemphigoid
Dermatitis herpetiformis
Epidermolysis bullosa acquista
Epidermolysis bullosa letalis
Herpes gestationis
Suction blister
Thermal lesions (LN2, burns)

Front 9

Diseases that affect the Basal Lamina and sublaminar connective tissue

Back 9

Bullous dermatosis of hemodialysis
Bullous eruption of SLE
Epidermolysis bullosa dystrophica
Erythema multiforme (dermal type)
Ischemic bullae (drug overdoses)
Lichen sclerosus et atrophicus
Porphyria cutanea tarda

Front 10

What is the role of the hemidesmisome in the epidermal basement membrane?

Back 10

Binds the keratin intermediate filaments to the anchoring filaments that attach the epidermal cells to the lamina densa (basement membrane).

Front 11

Target of autoantigens in Pemphigus Foliaceus?

Back 11

Desmoglein 1

Front 12

Target of Ab in Pemphigus vulgaris

Back 12

Desmoglein 3 - in mucosal dominant PV
Desmoglein 1 & 3 in mucocutaneous PV

Front 13

Target of Ab in Paraneoplastic pemphigus

Back 13

1) Desmoglein 1
2) Desmoglein 3
3) desmoplakin 2 (desmosomal plaque protein)
4) BP230
envoplakin
priplakin

Front 14

What type of collage forms the anchoring fibrils in the lamina lucida ?

Back 14

Collagen type VII

Front 15

In what diseases is the target BP 180?

Back 15

herpes gestationis
cictricial pemphigoid
linear IgA disease

Front 16

What dz targets the laminin 5?

Back 16

cictricial pemphigoid

Front 17

What dz targets Type VII collagen?

Back 17

epidermolysis bullosa acquista

Front 18

What protein is targeted in IgA pemphigus?

Back 18

Subcorneal Pustular Dermatosis variant: Desmocollin 1
Intra-Epidermal Neutrophilic (IEN) variant: Desmoglein 1 or 3

Front 19

Target of Bullous pemphigoid

Back 19

BP 180, BP 230 (hemidesmosome and lamina lucida)

Front 20

Target of Herpes gestationis

Back 20

BP 180, BP 230 (hemidesmosome and lamina lucida)

Front 21

Target of cicatricial pemphigoid

Back 21

BP 180, laminin V (hemidesmosome and lamina lucida)

Front 22

Target of Epidermolysis bullosa acquisita

Back 22

Type VII collagen (anchoring fibrils)

Front 23

Target of Bullous SLE

Back 23

Type VII collagen (anchoring fibrils)

Front 24

Target of of Linear IgA disease

Back 24

Type I (childhood variant) = LAD1 (97k) =
Cleaved ectodomain of BP2 - 180kD = also called ladinin
Type 2

Front 25

Target of Dermatitis herpetiformis

Back 25

Tissue Transglutaminase

Front 26

Prevalence of dermatitis herpetiformis

Back 26

1.2 to 39.2 per 100,000;
avg age 41.8 y/o, rare in children

Front 27

What type of enteropathy is assoc with Dermatitis Herpetiformis?

Back 27

subclinical gluten-sensitive enteropathy (rice and corn are okay. Avoid Wheat and Barley)

Front 28

HLA links for dermatitis herpetiformis?

Back 28

*** HLA-DQw2 (100%) ***
HLA-B8 (60%)
HLA class II antigens HLA-DR3 (95%)

Front 29

Difference b/tw IgA Bullous dermatosis and dermatitis herpetiformis

Back 29

Linear IgA has no assoc bowel dz and is different histologically

Front 30

Common areas for dermatitis herpetiformis

Back 30

elbows, knees, scalp and nuchal area, shoulders and buttocks;
63% c/o of oral symptoms
Rarely see an intact bullous

Front 31

Describe teeth defects in dermatitis herpetiformis

Back 31

Celiac-type permanent tooth enamel defects (in 53% of pts)

Front 32

What drugs can cause linear IgA bullous dermatosis (LABD)?

Back 32

**V=Vancomycin**
In general, may develop 24 hours to 15 days after first dose
S = Somatostatin/Sulfa
A = Amiodarone
D = Diclofenac
C = Captopril
L = Lithium/Lasix
I = IFgamma, IL2
P = Phenytoin, PCN, PUVA, Piroxicam

Hint 32

"Very SAD CLIP"

Front 33

How do you confirm Linear IgA Bullous dermatosis?

Back 33

DIF shows linear deposition of IgA at the epidermal BMZ.
Some pts have both IgA and IgG at the BMZ.
No gluten-sensitive enteropathy.

Front 34

What antibody can be found in patients with dermatitis herpetiformis that can correlate with jejenal damage?

Back 34

IgA-EmA
IgA antiendomysial antibodies

Front 35

What type of cancer has been linked to dermatitis herpetiformis?

Back 35

Small bowel lymphoma and nonintestinal lymphoma
All cases in patients who did not adhere to a Gluten Free Diet!
*Hypothyroidism (hashimoto's) is another assoc d/o*

Front 36

In LABD, what deposits are seen in DIF?

Back 36

IgA in the BMZ

Front 37

In DH, what are the DIF deposits?

Back 37

IgA deposits in the dermal papillae

Front 38

What type of circulating antibodies have been seen in patients with gluten sensitive enteropathy?

Back 38

Abs to Endomysium, tissue tranglutaminase, reticulin, and gliadin

Front 39

Treatment for dermatitis herpetiformis

Back 39

Dapsone & Sulfapyridine
Other treatments: Gluten-Free diet, elemental diet
Tetracylcine + Nicotinamide

Front 40

What medication interaction with Dapsone is important to know?

Back 40

Probenicid blocks renal excretion
Rifampin incrases rate of plasma clearance

Front 41

Side Effects of Dapsone

Back 41

Hemolysis/Hypersensitivity
Elevated Liver Enzymes
Leukopenia
Peripheral Neuropathy
Psychosis
Methemoglobinemia
Agranulocytosis/Aplastic Anemia

Hint 41

"HELPP MA"

Front 42

Describe Bullosis diabeticorum

Back 42

may be huge, tense on non-erythematous base; Painless ulcer.
No immunopathologic feature found.
Tx: wound care

Front 43

Common drug assoc with drug-induced pemphigus

Back 43

Penicillamine

Front 44

HLA assoc with pemphigus?

Back 44

HLA-DR4, DQ8 haplotypes in Jewish pts, HLA DR6, DQ5 in non-jewish

Front 45

Name for endemic form of pemphigus foliaceus in rural S. America?

Back 45

Fogo Selvagem

Front 46

Where are Dsg1 and Dsg3 restricted to?

Back 46

Stratified squamous epithelia

Front 47

What is the most common form of Pemphigus?

Back 47

Pemphigus vulgaris

Front 48

Describe Pemphigus vulgaris lesions

Back 48

mucosal involvement
thin blisters -- scalp, face, axilla, and oral cavities

Front 49

What is Pemphigus vegetans?

Back 49

Variant form of pemphigus with large verrucous confluent plaques and pustules localized to flexural areas in the axilla and groin

Front 50

Pemphigus foliaceus rash

Back 50

gradually on the face in a butterfly distribution -- seb derm distribution;
mucous membrane is rarey involved (desmoglein compensation theory*);
tends to be localized, better prognosis than PV

Front 51

DDX for Pemphigus foliaceus?

Back 51

Pemphigus foliaceus
IgA pemphigus -- has IgA ab and circulating IgA anti-cell surface Ab
Pemphigus erythematosus

Front 52

Pemphigus erythematosus aka?

Back 52

Senear-Usher syndrome
Combo of pemphigus foliaceus and SLE

Front 53

Ways to Dx of Pemphigus

Back 53

Bx for light microscopy
DIF
Indirect IF (to DSG1, 2, 3)

Front 54

Treatment of PV

Back 54

High dose systemic glucocorticoids
Topical Steroids
Adjuvants: Cyclophosphamide, Azathiaprine. MTX not used due to high incidence of infections reported.
Others: Plasmapheresis, extracorporeal photophoresis, or IVIG
Case reports: hydroxychloroquine
Combo of nicotinamide and TCN or MCN
Dapsone

Front 55

Sfx of Cyclophosphamide

Back 55

bone marrow suppression
hemorrhagic cystitis
bladder fibrosis
reversible alopecia
incrased risk of bladder carcinoma and lymphoma

Front 56

Sfx of Azathioprine

Back 56

bone marrow suppression
hepatotoxicity, increased risk of malignancy

Front 57

Remission criteria

Back 57

Can stop treatment when negative DIF or lower ab levels

Front 58

What other diseases have been reportedly assoc with pemphigus?

Back 58

Myasthenia gravis, thymoma, malignancy of the lymphoid or reticuloendothelial system

Front 59

Drug induced vs drug triggered pemphigus?

Back 59

Drugs with sulfhydryl radical (thiol drugs or SH drugs) induce PV (50% recovery when drug is discontinued)
Other drugs trigger the dz in predisposed people (only 15% recovery seen)

Front 60

Criteria for the Dx of Neoplasia-Induced Pemphigus

Back 60

All three major, or two major + two minor criteria.
Major Criteria:
Polymorphous mucocutaneous eruption
Concurrent internal neoplasia
Characteristic serum immunoprecipitation findings
Minor Criteria:
Postitive cytoplasmic staining of rat bladder epithelium by indirect immunofluorescence
Intercellular and BMZ immunoreactants on DIF of perilesional tissue
Acantholysis in biopsy specimen from at least one anatomic site of involvement

Front 61

Clinical appearance of Neoplasia induced pemphigus

Back 61

mucosal ulcerations
conjunctival reactions
polymorphous skin lesions on the trunk and extremities

Front 62

DIF findings in Neoplasia induced pemphigus

Back 62

- surface deposits of IgG and C3
- granular basement membrane deposits of C3

Front 63

How can you differentiate PNP from PV?

Back 63

Indirecti IF with rat bladder for PNP
(monkey for PV)

Front 64

List the subepidermal blistering diseases (vs. intraepidermal)

Back 64

Bullous Pemphigoid
Herpes gestationis
Cicatricial pemphigoid

Front 65

Demographics of BP?

Back 65

benign, autoimmune, subepidermal bullous dz of the elderly

Front 66

Target of BP autoantibodies?

Back 66

BP1 (230kD) & BP2 (180kD, aka type XVII collagen)

Front 67

What is a bad predictive factor in BP?

Back 67

generalized disease

Front 68

Clinical picture of BP

Back 68

Oral blisters (24%)
starts like an urticarial rash, then becomes dark and/or cyanotic, then becomes blistered
Areas: abdomen, groin, genital regions, flexor surfaces of arms and legs
palms and soles are affected
NEGATIVE NIKOLSKY'S SIGN

Front 69

What lab tests correlate with disease remission in BP?

Back 69

blood eosinophilia (in 50% of patients)

Front 70

Histo of BP

Back 70

subepidermal bullae w/ eos

Front 71

DIF findings in BP

Back 71

linear band at the BMZ (IGG, C3, IGA, IGM, AND FIBRIN CAN BE SEEN)

Front 72

What diseases can linear band of IgG at BMZ be seen?

Back 72

BP
Epidermolysis bullosa acquisita
Cicatricial pemphigoid
Herpes gestationis
Bullous eruption of SLE

Front 73

Which Dz can you monitor activity using IIF?

Back 73

IIF in Pemphigus (monkey esophagus)
You can not use IIF to monitor BP

Front 74

Treatment of BP

Back 74

Atarax for itching
Systemic steroids combined with immunosuppressor (azathioprine, cyclophosphamide, MTX, or chlorambucil)
Antibiotics, dapsone and topical steroids are an option

Front 75

cyclophosphamide aka?

Back 75

Cytoxan

Front 76

What enzyme do you need to check prior to starting azathioprine?

Back 76

Thiopurine methyltransferase (TPMT) activity

Front 77

Azathioprine aka?

Back 77

Imuran

Front 78

List variants of localized pemphigoid

Back 78

Cicatricial pemphigoid (aka Mucous membrane pemphigoid - MMP)
Localized childhood vulvar pemphigoid
Pretibial Pemphigoid (nonscarring bullous lesions on legs of women)
Chronic pemphigoid of Brunsting-Perry (crops of grouped blisters on the head and neck that heal with atrophic scars)
dyshidrosiform pemphigoid (vesiculobullous hemorrhagic lesions of the palms and soles)
Pemphigoid vegetans (erosive and vegetating plaques)

Front 79

Cicatricial pemphigoid

Back 79

aka MMP
Pts older than 40;
2:1 women.
Oral disease 85% of cases -- spares the vermilion border in contrast to pemphigus
Eye Dz 65% -- relapse is common, fibrosis of the conjunctival sac leads to scarring and blindness in 20% of cases
Cutaneous lesions - 25%
Remission uncommon.

Front 80

Target of antigens in Mucous Membrane Pemphigoid?

Back 80

BMZ antigens: BP2 (180kD), Epiligrin (subunit of laminin 5), and B4-integrin.

All in lamina lucida and involved in keratinocyte adhesion to extracellular matrix

Front 81

Brunsting-Perry type of cicatricial pemphigoid

Back 81

cutaneous MMP involvement of the head and neck, but NOT the mucous membrane

Front 82

Treatment of MMP

Back 82

Topicals, IM injections
Systemic:
Dapsone & Corticosteroids first
Immunosuppressives -- cyclophosphamide is better than Azathioprine

Front 83

Benign Chronic Bullous dermatosis of childhood aka?

Back 83

Linear IgA type 1

Front 84

Herpes gestationis

Back 84

aka Pemphigoid gestationis
appears in pregnancy, usu 2nd or 3rd trimester, and recurs with subsequent pregnancy;
mucous membrane involvement is RARE

Front 85

HLA assoc with H. gestationis?

Back 85

Class II angigens HLA DR3 &
HLA DR4
Class III antigen (C4)

Front 86

AutoAb target in H. Gestationis?

Back 86

IgG1 specific for BP2 (180kD), the NC16A domain

Front 87

Histology of H. gestationis?

Back 87

bandlike deposit of C3 and IGG at BMZ
circulating IgG (this is what can cause lesions in newborns - 10% incidence)

Front 88

Treatment of H. Gestationis?

Back 88

topical corticosteroids or oral
*Dz has risk of morbidity for child, unlike PUPPP*

Front 89

Target of Ab in Epidermolysis Bullosa Acquisita (EBA)

Back 89

Type VII collagen (anchors fibrils) -- same target as bullous SLE
Salt Skin - Ab on Floor

Front 90

Classic EBA presentation

Back 90

skin fragility, heals with scar and milia formation;
tense blisters on a noninflammatory base in trauma prone areas;
may have alopecia or nail dystrophy

Front 91

BP-like EBA presentation

Back 91

50% of pts w/EBA
Tense blisters on an inflammatory base on trunk and flexural surfaces
pruritis, minimal skin fragility, healing of some of the lesions w/o scarring and milia

Front 92

Differentiating BP from EBA

Back 92

Look the same on DIF
On salt-split -- IgG is on dermal side in EBA (vs epidermal side in BP)

Front 93

Treatment of EBA

Back 93

topical and/or systemic steroids
colchicine, cyclosporine, IVIG

Front 94

Benign Familial Chronic pemphigus aka?

Back 94

Hailey-Hailey Dz

Front 95

Genetics of Hailey-Hailey

Back 95

AD
ATP2C1 (Ca2+ pump ATPase)

Front 96

Describe clinical picture of Hailey-Hailey

Back 96

grouped (in an annular pattern) pruritic vesicles from a red or noninflmaed base.
usu appears in adolescents, usu in the summer.
areas exposed to UV light or friction/heat/sweating
Longitudinal white bands in fingernails seen

Front 97

Treatment for Hailey-Hailey blisters

Back 97

Oral Abx can help along with topical steroids
For groin/axilla: add anti-yeast.
Other Rx: excision, topical cyclosporine, CO2 laser, grafting

Front 98

Name the three major groups of Epidermolysis Bullosa

Back 98

Epidermolysis Bullosa Simplex (92%) - epidermal, nonscarring
Dystrophic Epidermolysis Bullosa (5%) - dermal, atrophy and scarring
Junctional Epidermolysis bullosa (1%) -- junctional, atrophy

Front 99

Where is the split in Epidermolysis Bullosa groups?

Back 99

Epidermolysis Bullosa Simplex - epidermal basal cells
Dystrophic Epidermolysis Bullosa (5%) - split through upper dermis
Junctional Epidermolysis bullosa -- split through basement membrane area

Front 100

Epidermolysis Bullosa Simplex

Back 100

Target: K5 & 14 defect, AD.
May be sporadic; seen in childhood;
blisters seen especially on the palms and soles;
Biggest complication is infection

Front 101

Junctional epidermolysis bullosa

Back 101

AR: Laminin 5 or BP2 (Type XVII collagen)
"exuberant granulation"

Front 102

Dystrophic epidermolysis bullosa

Back 102

Collagen VII defect (same as EBA target) - "mitten deformities"
Hallopeau-Siemens (AD)
Non-Hallopeu (AR):
1. Cockayne-Touraine: acral, hypertrophic scars
2. Pasini: "albopapuloid" lesions on trunk

Front 103

Dx of Epidermolysis Bullosas

Back 103

Electron Microscope

Front 104

Treatment of Epidermolysis bullosa?

Back 104

avoid trauma
Dilantin - a collagenase inhibitor
Genetic counseling

Front 105

What are the Main causes of benign transient neonatal pustulosis?

Back 105

Erythema toxicum neonatorum
Transient neonatal pustular melanosis
Neonatal acne

Front 106

First step for dx newborns with blisters?

Back 106

Tzank smear
then, gram stain & KOH

Front 107

Describe rash in Erythema Toxicum Neonatorum

Back 107

LESIONS NOT PRESENT AT BIRTH.
Begins on face, trunk, proximal extremities and buttocks;
palms and soles not affected;
20-50% of term infants

Front 108

What stain shows eos in ETN?

Back 108

Wright's stain

Front 109

Describe Transient neonatal pustular melanosis

Back 109

LESIONS PRESENT AT BIRTH, but may be overlooked;
in 2-5% of blacks, 0.6% of whites;
Rash: forehead, behind hears, under the chin, on the neck & back, and on hands and feet;
palms and soles are affected;

Front 110

Treatment for TNPM?

Back 110

none -- resolves with hyperpigmented macules

Front 111

What does Wright's stain show in TNPM?

Back 111

PMNs & Eos

Front 112

Difference b/tw miliaria crystallina and miliaria rubra

Back 112

Occlusion levels -- crystallina is at the skin surface, so sweat is under the stratum corneum
rubra is in the intraepidermal section of the sweat duct which causes a diffuse erythema from inflammation

Front 113

Causes of Drug-Induced Pemphigus?

Back 113

I - Indocin
C - Captopril
R - Rifampin
A - Ampicillin
P - Penicillamine

Hint 113

" I CRAP"

Front 114

IIF for Pemphigus Foliaceus with what?

Back 114

Guinea Pig Esophagus

Front 115

Asboe-Hansen and Nikolsky signs in PV? vs. BP?

Back 115

Positive in PV
Negative in BP

Front 116

Ab in BP are what part of the salt split?

Back 116

Roof