Bod: Dermatology: Blistering Disease

Front 1

What is the difference between a vesicle and a bulla?

Back 1

A vesicle is a blister that is < 1 cm

A bulla is a blister that is > 1 cm

Front 2

c/c desmosomes and hemidesmosomes

Back 2

Desmosomes connect adjacents keratinocytes in the epidermis. Contain keratin, E-cadherins, desmoplakins

Hemidesmosomes: tether cells in the basal zone to the basement membrane zone. Contain integrin and laminins

Front 3

Blistering disease: give an example of a genetic cause

Back 3

Genetic:
- Epidermolysis bullosa: caused by mutations in basal layer keratins and hemidesmosomal proteins

Front 4

Blistering disease: give an example of infectious causes

Back 4

Infectious:
- SSSS
- Bullous cellulitis
- Herpes simplex virus
- Varicella zoster virus

Front 5

Blistering disease: give an example of a traumatic/physical cause

Back 5

Friction blisters, coma bulla (from passing out and staying in one position for awhile), burns, cryotherapy

Front 6

Blistering disease: give an example of a contact-driven cause

Back 6

Contact dermatitis, chemical burns, vesicants (blister beetle juice)

Front 7

Blistering disease: give an example of a drug-related cause

Back 7

Stevens-Johnson Syndrome
Toxic epidermal necrolysis

Front 8

Blistering disease: give an example of a metabolic cause

Back 8

Porphyria cutanea tarda (blistering and skin fragility when exposed to sunlight)

Front 9

Blistering disease: give an example of a autoimmune cause

Back 9

Pemphigus vulgaris
Pemphigus folaceus
Bullous pemphigoid
Dermatitis herpetiformis
Linear IgA bullous dermatosis

Front 10

Blisters in the subcorneal region

Back 10

Subcorneal pustular dermatosis of Sneddon and Wilkinson (rare)

Front 11

Blisters in the granular layer

Back 11

SSSS

Front 12

Blisters in the upper spinous layer

Back 12

Pemphigous foliaceus

Front 13

Blisters in the spinous layer

Back 13

Friction blisters

Front 14

Blisters in the lower spinous layer

Back 14

Pempigous vulgaris

Front 15

Blisters in the basal layer

Back 15

Epidermolysis bullosa simplex (inherited)

Front 16

Blisters in the subepidermal layer

Back 16

- Bullous pemphigoid
- Dermatitis herpetiformis
- Linear IgA bullous dermatosis
- Epidermolysis bullosa acquisita
- Junctional and dystrophic

Front 17

Staphylococcal Scalded Skin Syndrome: clinical features

Back 17

- Children < 5 y.o. (often neonates)
- May have preceeding URI
- Prodrome of malaise, fever, irritability and very tender skin

- Rapid course: erythema spreads from head to entire body within hours

- Scaling and desquam in 3-5 days

- Spares palms, soles, and mucous membranes

- Heals in 1-2 weeks w/o scarring

Front 18

Staphylococcal Scalded Skin Syndrome: pathophysiology

Back 18

- S. aureus at a DISTANT FOCUS in nose, pharynx, ear, umbilicus

- Blisters are STERILE (unlike bullous impetigo)

- Epidermolytic toxins A and B are produced by Group II S. aureus phages

- Toxins cleave desmoglein 1 a desmosomal protein in the upper spinous layer

- Toxins are cleared by the kidneys (poor function in neonates, elderly)

Front 19

Staphylococcal Scalded Skin Syndrome: DDX

Back 19

TEN
Kawasaki's
Viral exanthem (usually not as severe as SSSS)
TSS

Front 20

Nikolsky's Sign

Back 20

lateral pressure on a blister causes a new one to be formed

Front 21

Asboe-Hansen's sign

Back 21

Pressure on top of the blister causes blister to extend into normal appearing skin

Front 22

Staphylococcal Scalded Skin Syndrome: histopath

Back 22

- Skin separation seen in high epidermis, within or below the granular layer

- May see acantholytic (free-floating) cells

- NO inflammatory infiltrate

- Remainder of epidermis is unaffected

- Note that TEN causes the entire epidermis to become necrotic

Front 23

Staphylococcal Scalded Skin Syndrome: treatment

Back 23

Oral treatment with a beta-lactamase resistant penicillin or cephalosporin ABX for 1 week

Bland emollients to skin

Isolate patient from other infants to prevent spread of Staph

Front 24

Pemphigus: definition

Back 24

A group of autoimmune blistering disorders of the skin and mucous membranes characterized by lack of cohesion bet keratinocytes (acantholysis) and mediated by IgG antibodies to desmosomal proteins

Front 25

Pemphigus: what are the three main types?

Back 25

Pemphigus vulgaris
Pemphigus foliaceous
Paraneoplastic pemphigus

Front 26

Asboe-Hansen's sign

Back 26

Pressure on top of the blister causes blister to extend into normal appearing skin

Front 27

Staphylococcal Scalded Skin Syndrome: histopath

Back 27

- Skin separation seen in high epidermis, within or below the granular layer

- May see acantholytic (free-floating) cells

- NO inflammatory infiltrate

- Remainder of epidermis is unaffected

- Note that TEN causes the entire epidermis to become necrotic

Front 28

Staphylococcal Scalded Skin Syndrome: treatment

Back 28

Oral treatment with a beta-lactamase resistant penicillin or cephalosporin ABX for 1 week

Bland emollients to skin

Isolate patient from other infants to prevent spread of Staph

Front 29

Pemphigus: definition

Back 29

A group of autoimmune blistering disorders of the skin and mucous membranes characterized by lack of cohesion bet keratinocytes (acantholysis) and mediated by IgG antibodies to desmosomal proteins

Front 30

Pemphigus: what are the three main types?

Back 30

Pemphigus vulgaris
Pemphigus foliaceous
Paraneoplastic pemphigus

Front 31

Pemphigus vulgaris: clinical features

Back 31

- Rare, often fatal

- 50-60s, Jewish/Medit, HLA-DR4, DR6, DQ1

- Oral and mucous membrane involvement (most serious sx bc pts can't eat)

- Also develop large, bullous blisters arising from normal appearing skin, rapidly rupture

- Nikolsky's sign POSITIVE

Front 32

Pemphigus vulgaris: histopath

Back 32

- Characteristic: acantholysis or free-floating dissociated keratinocytes (in lower spinous level)

- No inflamm

- Only basal cell layer remains at the floor of the blister: a row of tombstones (indicates that hemidesmosomes are functional)

Front 33

Pemphigus vulgaris: direct Immunofluorescence

Back 33

fluorescently labeled abs applied directly to skin bx

- detect pt's own IgGs to DSG 3 (and often 1) in the epidermis.

- Intercellular staining throughout epidermis appears as a "chicken wire fence"

Front 34

Pemphigus vulgaris: indirect Immunofluorescence

Back 34

Patient's serum to DSG-3 (and often DSG-1) is applied to a substrate like monkey esophagus

Can show level of circulating abs?

Levels of circulation correlate with disease activity

Front 35

Pemphigus vulgaris: tx

Back 35

- systemic corticosteroids (prednesone 1 mg/kg/day)

- Steroid sparing agents: azathioprine, cyclophosphamide, mycophenolate moffetil

- Plasmaphoresis, IVIG

- Rituxan: an anti-CD20 mAb that decreses pathogenic IgG production

Front 36

Pemphigus foliaceous: clinical

Back 36

- Adults 40-50 y.o.

- endemic type in Brazil (Fogo selvagem, assoc with a type of black fly)

- Small flaccid bullae, rupture as soon as they appear --> crusting and bleeding

- Scalp, face, trunk

- NO MUCOSAL LESIONS

- evolves into localized or generalized exfoliation, burning, pruritus

- Nikosky's sign is POSITIVE

Front 37

Pemphigus foliaceus: histopath

Back 37

Subcorneal blister - Acantholysis in UPPER epidermis at the granular layer

IF:
- Direct IF: see Igg in the upper epidermis
- ELISA: Abs to DSG 1 NOT DSG 3 (vs PV, which is DSG 1 +/- DSG 3)

Front 38

Pemphigus: abs profiles

Back 38

Pemphigus foliaceous: DSG 1
Pemphigus vulgaris (oral lesions only): DSG 3
Pemphigus vulgaris (oral and skin lesions): DSG 1 and 3

Front 39

Pemphigus foliaceous: tx

Back 39

similar to PV
topical steroids

Front 40

Bullous Pemphigoid: definition

Back 40

An autoimmune blistering disease involving abs to hemidesmosomal proteins

Front 41

c/c Bullous Pemphigoid and Pemphigus Vulgaris: prognosis

Back 41

BP is more common and better prognosis than PV

Front 42

Bullous Pemphigoid: epi

Back 42

elderly

HLA class II DQB1*0301 in Caucasians

Front 43

Bullous Pemphigoid: Clinical

Back 43

- generilized, symmetric

- intensely pruritic eruption with widespread tense blisters (vs. pemphigus which has flaccid blisters)

- Early stage may be urticarial or eczematous instead of bullous

- Lower legs, groin area, flexor surfaces of forearms

- 20-30% have mucosal involvement

- Does not scar
- Nikolsky's sign NEGATIVE
- Often self limited (5-6 years), may come and go for years
- Typically not life-threatening

Front 44

Bullous Pemphigoid: histopath

Back 44

SUBepidermal split
INFLAMMATORY blister with eosinophils
No basal cells left

Front 45

Bullous Pemphigoid: Immunofluorescence

Back 45

Direct: Linear staining for IgG and C3 along the basement membrane zone

Indirect:
70% have circulating IgG
The level of IgG does NOT correlate with disease activity (unlike Pemphigus)

Front 46

Bullous Pemphigoid: antigens

Back 46

Bullous Pemphigoid antigen 1: 230 kd protein in a hemidesmosomal plaque

Bullous Pemphigoid antigen 2: also called type XVII collagen, makes up anchoring filaments

Front 47

Bullous Pemphigoid: txt

Back 47

Suppress inflammation, wait for remission (Unlike pemphigus)

- Oral and topical steroids
- Tetracycline/niacinamide (tetracyclines have an anti-inflammatory effect)
- Immunosuppressive agents (azathioprine, mycophenidate moffetil [suppresses lymphocytes])

Front 48

Dermatitis herpetiformis: clinical features, pathogenesis

Back 48

An intensely pruritic subepidermal blistering disease asociated with GLUTEN sensitivity (Celiac disease) and IgA abs agains tissue transglutaminase

Symmetrical, grouped vesicles (often excoriated) on extensor surfaces, scalp, neck, posterior axillary folds, buttocks

- No mucous membrane involvement

- Intense burning and itching

- Nikolsky's sign negative

- 90% of pts have gluten-sensitive enteropathy on small bowel biopsy

- 20% are symptomatic with Celiac disease

Front 49

Dermatitis herpetiformis: epi

Back 49

Most common in Northern Europeans

Associated with HLA-DQ2A1*05B1*02

Usual onset at 20-40

Front 50

Dermatitis herpetiformis: increased risk of what?

Back 50

Intestinal lymphoma (3%)
Thyroid disease

Front 51

Dermatitis herpetiformis: pathogenesis

Back 51

Gluten ingestion --> IgA abs and inflammation --> IgA binds to epidermal transglutaminase --> form IgA-immune complexes that are deposited in the skin. Complement activation leads to neutrophils in the dermal papillae.

Front 52

Dermatitis herpetiformis: histopath

Back 52

Subepidermal vesicles
Neutrophils in groups at the dermal papillae +/- eosinophils

Front 53

Dermatitis herpetiformis: pattern on immunofluorescence

Back 53

granular IgA deposits (as opposed to bullous pemphigoid, which is linear)

Front 54

Dermatitis herpetiformis: txt

Back 54

Dapsone (highly effective)

Gluten-free diet can cause remission, though this may take months to years - this also reduces the risk of intestinal lymphoma

Front 55

Epidermolysis bullosa: definition

Back 55

A group of inherited blistering disorders

CP varies widely from mild localized variants (Weber-Cockayne) to universally fatal generalized types (Herlitz Junctional types)

Herlitz comes with an increased risk of developing SCC (often the cause of death)

Front 56

Epidermolysis bullosa: simplex type

Back 56

- Simplex: Split occurs in the basal layer (mildest form, keratin 5, 14, intermediate filament proteins expressed in basal layer)

Front 57

Epidermolysis bullosa: Junctional

Back 57

- Junctional: Split within basement membrane zone

- laminin 5, alpha-6, beta-4 integrins; type XVII collagen (anchoring fibers)

Front 58

Epidermolysis bullosa: Dystrophic

Back 58

- Dystrophic: Split beneath basement membrane

Type VII collagen (anchoring fibrils)

Front 59

Epidermolysis bullosa: txt

Back 59

Supportive, specialized dressings and wound care

Front 60

Tell me what the characteristic findings of each are:

1. Epidermolysis bullosa
2. Dermatitis herpetiformis
3. Toxic epidermal necrolysis
4. Pemphigus vulgaris
5. Bullous pemphigoid

Back 60

1. Epidermolysis bullosa - genetic
2. Dermatitis herpetiformis - neutrophils in dermal papillae
3. Toxic epidermal necrolysis - necrosis of epidermis
4. Pemphigus vulgaris - acantholysis
5. Bullous pemphigoid - inflammatory blisters with eosinophils

Front 61

c/c Stevens Johnson Syndrome and toxic epidermolyic necrosis

Back 61

SJS is < 10% body surface involvement

Between 10 and 30 is a TEN/SJS mix

TEN is > 30% involvement