CM: Blistering Disorders

Question 1

What are the pathogenic mechanisms that lead to blistering?

Answer 1

spongiosis
acantholysis: primary or secondary
ballooning degeneration
minor: absent or defective keratin (leads to intraepidermal blister formation) or type VII collagen (causes defect anchoring BM to papillary dermis)

Question 2

What is spongiosis?

Answer 2

widening of intercellular space between epidermal cells causing sponge-like appearance of epidermis
keratinocytes get fluid in b/w them - hang on by desmosomes until they finally break apart

Question 3

What is acantholysis?

Answer 3

loss of coherence b/w epidermal or epithelial cells
primary is due to dissolution of intercellular substance
keratinocytes have a fried egg appearance

Question 4

What is ballooning degeneration?

Answer 4

epidermal degeneration resulting in marked swelling of cells and secondary acantholysis, common in Herpes
intracellular edema can cause bursting of cells and formation of multilocular bullae = reticular degeneration

Question 5

What is the difference in pathology b/w pemphigus vulgaris and bullous pemphigoid?

Answer 5

pemphigus vulgaris - antibodies against cadherins in desmosomes
bullous pemphigoid - antibodies against hemidesmosomes
pemphigus has cell-poor appearance on histology

Question 6

What are examples of inflammatory blistering disorders?

Answer 6

bullous pemphigoid

erythema multiforme

Question 7

What are examples of non-inflammatory blistering disorders?

Answer 7

epidermolysis bullosa simplex

pemphigus

Question 8

What are important features of pemphigus vulgaris?

Answer 8

flaccid bullae that break easily and leave denuded areas that increase in size
oral lesions - do not involve vermillion border (herpes does)
Nikolsky sign

Question 9

What are important features of pemphigus foliaceus?

Answer 9

flaccid bullae on erythematous base, leaves more superficial erosions, in seborrheic distribution
usually no oral lesions
Nikolsky sign
better prognosis than pemphigus vulgaris

Question 10

What is the Nikolsky sign?

Answer 10

lateral pressure applied to normal skin at periphery of active lesions causes skin to shear away

Question 11

What are the histologic features of pemphigus?

Answer 11

supra-basal blisters in vulgaris w preservation of basal cell layer
more superficial sub-corneal blisters in foliaceus
intercellular edema w acantholysis
little inflammation - lymphocytes and eosinophils

Question 12

What does immunofluorescence of pemphigus show?

Answer 12

direct: IgG antibodies between keratinocytes (chicken-wire)
indirect: circulating IgG in blood

Question 13

What are important features of bullous pemphigoids?

Answer 13

large, tense bullae esp on extremities, which upon breakage leave denuded areas that DON’T increase in size
more often in elderly pts than pemphigus - also more inflammation, no Nikolsky, itchy

Question 14

What is herpes gestationis?

Answer 14

variant of bullous pemphigoid during pregnancy that starts on distended abdominal skin
usually goes away after birth

Question 15

What is the histology of bullous pemphigoid?

Answer 15

mixed infiltrate - lymphocytes and eosinophils in papillary dermis
subepidermal blister

Question 16

What does immunofluorescence of bullous pemphigoid show?

Answer 16

direct and indirect: linear IgG in epidermal-dermal jxn

Question 17

What are important features of dermatitis herpetiformis?

Answer 17

pruritic, symmetrical grouped papules and vesicles surrounded by erythema
extensor surfaces of extremities, shoulders, buttocks
oral mucosa NOT affected
may be associated with celiac sprue

Question 18

What does histology of dermatitis herpetiformis show?

Answer 18

sub-lamina densa blisters

Question 19

What does immunofluorescence of dermatitis herpetiformis show?

Answer 19

granular IgA along dermoepidermal jxn w concentration at papillary tips

Question 20

What are important features of erythema multiforme?

Answer 20

can manifest as many different skin conditions
characteristic lesions are target-like
includes erythema multiforme minor, erythema multiforme, major, stevens johnsons, and toxic epidermal necrolysis
= hypersensitivity rxns

Question 21

What is erythema multiforme minor?

Answer 21

self limited or recurrent, skin lesions only, no mucous membrane involvement
less than 10% of BSA involved
most common cause is Herpes

Question 22

What is erythema multiforme major?

Answer 22

less than 10% BSA involved
mucous membranes ARE involved - erythematous macules or erosions
same causes as EM minor

Question 23

What is Stevens Johnson syndrome?

Answer 23

affects skin and 2 or more mucous membranes
up to 30% BSA involved
most common cause is drugs

Question 24

What is toxic epidermal necrolysis?

Answer 24

more than 30% BSA involved
erythema and sloughing of large sheets of skin
2 or more mucous membranes involved
most common cause is drugs

Question 25

What is the histology of erythema multiforme?

Answer 25

epidermal (basal layer) blisters

Question 26

What is porphyria cutanea tarda?

Answer 26

dominantly inherited def of uroporphyrin decarboxylase (required for synthesis of heme)
accumulation of porphyrin metabolites that become active after exposure to UVA light = photosensitive

Question 27

What are the clinical manifestations of porphyria cutanea tarda and what can trigger an attack?

Answer 27

acquired factor damaging to liver (estrogen, ethanol)
80% antibody positive for HCV
vesicles and bullae on sun-exposed skin
hypertrichosis = increased facial hair

Question 28

What is the histology of porphyria cutanea tarda?

Answer 28

subepidermal (sublamina densa) blisters

Question 29

What are important features of herpes simplex virus?

Answer 29

type 1 = orofacial, type 2 = genital
recurrence can be triggered be exposure to sunlight, febrile illnesses or arise spontaneously
grouped vesicles on erythematous base
Tzanck prep or gram stain shows multinucleated giant cells and acantholytic keratinocytes

Question 30

What is the histology of herpes?

Answer 30

intraepidermal (stratum spinosum) vesicle w profound ballooning of keratinocytes resulting in secondary acantholysis
multi-nucleated epithelial giant cells and necrotic keratinocytes
maybe eosinophilic inclusion bodies in center of enlarged nuclei of balloon cells

Question 31

What are the clinical manifestations of varicella zoster (chicken pox)?

Answer 31

fever, malaise, generalized vesicular eruption
lesions begin as erythematous vesicle (dew drops on rose petals) and progress to larger vescile, umbilicated pustule, superficial erosion and crusted papule

Question 32

What are the clinical manifestations of herpes zoster (shingles)?

Answer 32

painful grouped vesicles along dermatome
usually elderly patient
due to varicella virus dormant in dorsal root ganglia
lesions resolve in 2-3 wks but post-herpetic neuralgia may remain for months or years

Question 33

What is the histology of herpes zoster and varicella zoster?

Answer 33

stratum spinosum blisters

Question 34

What is bullous impetigo?

Answer 34

toxins produced during inf w S. aureus cause vesicles and bullae
more common in neonates and older infants
no Nikolsky sign
bullae contain clear yellow fluid that then becomes dark yellow and turbid
well circumscribed and non-erythematous, rupture in 2-3 days, leave light brown or golden yellow crust
diabetics more prone to dev bullae

Question 35

What is the histology of bullous impetigo?

Answer 35

sub stratum corneum blisters