CM- Blistering Disorders

Question 1

What is spongiosis?

What is an example of something that would cause this?

Answer 1

Widening of the intercellular space between the epidermal cells causing sponge-like appearance. The cells will start to appear star-shaped because the desmosomes still work until they finally break

ex. allergic contact dermatitis

Question 2

What term describes the loss of coherence between epidermal or epithelial cells that results in the “rounding up” of cells and a fried egg appearance of cells in clear blister cavities?

Answer 2

Acantholysis

Question 3

Primary acantholysis occurs among _______cells as a result of _________ of the intercellular substance.

_______describes a group of autoimmune diseases in which antibodies are directed against cadherin molecules [desmosomes] responsible for keratinocyte adhesion to each other.

Answer 3

1 acantholysis is among unaltered cells as a result of dissolution of intercellular substance.

Pemphigus describes autoimmune diseases where Ab against cadherin lead to lack of coherence amongh epidermal and epithelial cells

Question 4

Describe ballooning degeneration. What is the result?

What happens if it is acute and severe?

Answer 4

It is epidermal cell degeneration resulting in swelling of cells and secondary acatholysis [herpes simplex].

If it is acute and severe, it can cause bursting of epithelial cells and formation of multilocular bullae [reticular degeneration]

Question 5

What is epidermolysis bullosa simplex?

Answer 5

absent or defective keratin leads to intraepithelial blister formation

Question 6

What is epidermolysis bullosa dystophica?

Answer 6

Absent or defective type 7 collagen causes a defect in the anchoring of the basement membrane to the papillary dermis

Question 7

What is the difference between primary acatholysis and pemphigus?

Answer 7

Primary acantholysis is the dissolution of intercellular substance when the cell was unaltered.
Pemphigus is an autoimmune condition where Ab are directed against cadherin [of desmosomes] dissolving adhesion between keratinocytes to each other

Question 8

What connects keratinocytes to each other?

What blistering diseases destroys this bond?

Answer 8

Desmosomes connect keratinocytes to each other.

Pemphigus vulgaris has Ab against cadherin [component of desmosome]

Question 9

What connects the basal keratinocytes to the basement membrane zone?
What 3 proteins is this made of?
What blistering disease destroys the connection?

Answer 9

Hemidesmosomes

• laminin
• plectin
• integrin

Bullous pemphigoid has antigens against the hemidesmosome

Question 10

What tethers the epidermis to the dermis?

The absence of what protein disrupts this connection, forming blisters?

Answer 10

Anchoring fibrils tether epidermis to the dermis.

Absence of collagen 7 [epidermolysis bullosa dystrophica]

Question 11

What are the 4 things that should be considered when classifying a blister?

Answer 11

1. size [less than 1cm = vesicle, greater = bulla]
2. content
   - serum [clear]
   - blood [red]
   - leukocytes [cloudy]
3. Inflammatory vs. non-inflammatory
   - inflam = bullous pemphigoid, erythema multiforme]
   - non = epidermolysis bullosa simplex, pemphigus
4. histological level of blistering
   - sub stratum corneum
   - stratum lucidum
   - stratum granulosum [lose nuclei, get keratin granules]
   - stratum spinosum
   - stratum basale

Question 12

What is the main way to tell the difference between pemphigus and pemphigoid ?

Answer 12

GUS is non-inflammatory and GOID is inflammatory so pemphigus will be more cell-poor on histology

Question 13

What main diseases are associated with each layer of the epidermis?

Answer 13

1. sub-stratum corneum
   - bullous impetigo
   - pemphigus foliaceous/erythematous
2. stratum spinosum
   - herpes simplex and other viral blisters
3. Supra-basal
   - pemphigus vulgaris/vegetans
4. Basal Cell
   - erythema multiforme
   - SJS, toxic epidermal necrolysis

Question 14

What main diseases are associated with each layer of the dermis?

Answer 14

1. junctional
   - bullous pemphigoid
2. sublamina densa
   - dermatitis herpitiformis
   - porphyria cutanea tarda

Question 15

What 4 skin disorders are considered “immune-mediated” disorders?

Answer 15

1. bullous pemphigoid
2. dermatitis herpetiformis
3. herpes gestationis
4. pemphigus

Question 16

What 3 skin disorders are non-immune mediated?

Answer 16

1. bullous impetigo
2. herpes infection
3. porphyria cutanea tarda

Question 17

What is the Nikolsky sign?

What 3 skin disorders show + Nikolsky signs?

Answer 17

When lateral pressure is applied to normal skin at the periphery of an active lesion, the skin shears right off.

1. pemphigus vulgaris/foliaceous
2. toxic epidermal necrolysis
3. staph scalded skin syndrome

Question 18

A patient presents with flaccid bulla that break easily leaving denuded areas that increase in size by progressive peripheral detachment.
He has oral lesion that do NOT involve the vermillion border but were the first manifestation of the blistering.

What is the most likely disorder?
What causes it?

Answer 18

Pemphigus vulgaris- Ab against cadherin in desmosomes of the supra-basal layer

Question 19

A patient presents with a flaccid bullae that arises on an erythematous base. When the blisters pop, they leave erosions and accumulation of hyperkeratotic scales.
The lesions are in seborrheic distribution.

There are NO oral lesions.

What is the most likely disorder? What causes it?

Answer 19

Pemphigus foliaceous- Ab against cadherin in desmosomes in the sub-stratum corneum.

Question 20

Describe the histology seen with pemphigus vulgaris.

Answer 20

1. suprabasal blisters with
   - intracellular edema
   - acantholysis
2. preservation of the basal cell layer
3. LITTLE if any inflammation with mixed eosino/lympho

Question 21

For what 3 blistering diseases is direct immunoflourescence indicated?
How would each appear?

Answer 21

1. Pemphigus - IgG deposited in between keratinocytes giving it a chicken wire appearance
2. bullous pemphigoid - IgG deposit in the epidermal-dermal juction showing up linearly
3. dermatitis herpetiformis- granular IgA along dermoepidermal junction with concentration at the papillary tips.

Question 22

An elderly patient presents with large, tense bullae on the extremities. They complain of itching on/around the blisters. When they break, they leave denuded areas that do NOT increase in size. There is a negative Nikolsky sign.

What is the likely cause of the blister?
What is the pathology behind how it occurs?
Why is there pruritis?

Answer 22

Bullous pemphigoid which is an autoimmune disorder where Ab are directed against hemidesmosomes [that attach epidermis to basement membrane.

Pruritis because of the inflammation [GOID is inflammatory, GUS is non-inflammatory]

Question 23

A pregnant woman comes in with tense bullae on her distended abdomen skin. She complains that they are itchy. When they break, they leave a denuded area that does not get larger.

What does she have?
What is it a variant of? What is the underlying problem?

Answer 23

She has herpes gestationis which is a variant of bullous pemphigoid where IgG attack hemidesmosomes

Question 24

Describe the histology of bullous pemphigoid.

Answer 24

1. mixed infiltrate of lymphocytes, eosinophils in the PAPILLARY DERMIS with subepidermal vesiculation
2. late bulla regenerating in the epidermis can be confused with intraepidermal vesicles

Question 25

A patient presents with pruritic, chronic blistering disease with symmetric distribution of grouped papules and vesicles, surrounded by erythema. The predilection is extensor surfaces, shoulders and buttocks. The oral mucousa is NOT involved. On histology, you note sub-lamina densa blisters. What is the likely diagnosis? What is thought to be the cause?

Answer 25

Dermatitis herpetiformis [dermal layer, herpetic distribution] It is though to be associated with gluten-sensitive celiac enteropathy

Question 26

You do direct immunoflorescense on a skin lesion and notice IgA granular deposition along the dermoepidermal junction with concentrations in the papillary tips of the dermis. What is the likely diagnosis?

Answer 26

Dermatitis herpetiformis

Question 27

You do direct immunofluorescence and see linear deposition of IgG in the epidermal-dermal junction. Indirect immunofluorescence shows the same thing. What is the likely problem?

Answer 27

Bullous pemphigoid - autoantibody attack on hemidesmosomes between the basal layer and BM

Question 28

You do direct immunofluorescence of a skin lesion and see IgG deposited like chicken wire between keratinocytes. Indirect immunofluorescence shows IgG Ab circulating in the blood stream. What is the likely diagnosis?

Answer 28

pemphigus vulgaris or foliaceous

Question 29

What is erythema mulitforme?

Answer 29

A group of reactive disorders to the skin that result in macules, papules, vesicles, bullae or a combination. Characteristic lesions are target-like with a dark center and lighter outside or papule inside surrounded by a plaque, etc

Question 30

Erythema multiforme minor self-limited, recurrent dermatosis that involves what type of lesions? What area of the body NEVER has involvement? What % of the body surface area is involved in EM?

Answer 30

It involves SKIN LESIONS ONLY and no mucous membrane involvement. Less than 10% of the body surface area is involved

Question 31

What is the most common cause of erythema multiforme?

Answer 31

Herpes simplex infection esp. for recurrent cases [Others: mycoplasma, yersinia, drugs]

Question 32

What is the difference between erythema multiforme minor and EM major?

Answer 32

Minor- self limited, recurrent, less than 10% body surface area, NO mucous membranes Major - less than 10% body surface area but DOES have mucous membrane involvement

Question 33

How does Stevens Johnson syndrome present? What is REQUIRED for diagnosis? What % body surface area is involved? What is the most common cause?

Answer 33

1. target or maculopapular lesions on the skin 2. vesicles, bullae erosions 3. involvement of 2 OR MORE MUCOUS MEMBRANES*** required for diagnosis Involves 30% of body surface area Most common cause = drugs

Question 34

Describe the presentation of toxic epidermal necrolysis. What % body surface area is involved? What is the most common cause?

Answer 34

1. erythema and sloughing of large sheets of skin [+Nikolosky]. 2. involvement of 2 OR MORE MUCOUS MEMBRANES 30% body surface area is involved Most common cause = drugs

Question 35

What is the inheritance pattern of porphyria cutanea tarda? | What is deficient in these patients?

Answer 35

It is a dominantly inherited disorder of uroporphyrin decarboxylase in the liver that is necessary for the synthesis of heme. Deficiency leads to increased porphyrin metabolites in the skin

Question 36

Describe the pathogenesis of porphyria cutanea tarda. | What areas of the skin will be most affected?

Answer 36

It is an AD disorder with deficient uroporphyrin decarboxylase. Porphyrin metabolites built up in the skin and when it is exposed to UVA light, it becomes metabolically active. Sun-exposed skin will have bullae or vesicles esp. on hands and forearms

Question 37

What 3 things can precipitate attacks of porphyria cutanea tarda?

Answer 37

1. Hep C [80% are positive] 2. enthanol 3. estrogen

Question 38

A man presents with vesicles and blisters on sun-exposed skin. He has hypertrichosis where his beard connects with his eye brows. On histology you notice sub lamina densa blisters. What skin condition does this man likely have? What other disease is associated with this skin condition? What should you tell him to do?

Answer 38

Porphyria cutanea tarda Associated with Hep C. Tell him to give blood once a week, and to cut back on alcohol

Question 39

What causes recurrence of herpes simplex infection? What will it look like on PE? What test can confirm that it is herpes simplex?

Answer 39

sunlight, fever, spontaneous It will be grouped vesicles on an erythematous base. Tzanck prep of the roof of the blister will show: 1. multi-nucleated giant cells 2. acantholytic keratinocytes

Question 40

A person presents with a group of vesicles on an erythematous base. This has happened before and it "hurts in the same place every time". What will you likely see on histology/Tzanck stain?

Answer 40

Tzanck: 1. multinucleated giant cells 2 acantholytic keratinocytes Histology: 1. blisters in the stratum spinosum with - ballooning - secondary acantholysis 2. multinucleated giant cells 3. necrotic keratinocytes

Question 41

A child presents with fever, malaise and generalized vesicular eruption. The lesions look like dewdrops on rose petals. Some have progressed to larger vesicles, umbilicated pustules, superficial erosions, and crusted papules. What is the likely diagnosis? What is the child prone to later in life?

Answer 41

Varicella zoster [chicken pox] He acquired lefelong immunity, but it can recurr in a dermatome distribution as herpes zoster [shingles]

Question 42

An elderly patient has painful grouped vesicles lining a dermatome on one side of his body. It has happened before and the pain/vesicles lasted 2-3 weeks, but then he had pain in the area for months. What does he have? What layer of the epidermis are the blisters arising?

Answer 42

Herpes Zoster [shingles] Rising from stratum spinosum

Question 43

What causes bullous impetigo? | What age group is frequently affected?

Answer 43

Exfoliative toxins from S. aureus which leads to vesicles and bullae. It affects neonates and older infants.

Question 44

A neonate has bullae with clear yellow fluid that have become turbid and darker yellow. The lesions are well-circumscribed and non-erythematous. After they rupture [2-3 days] they leave yellow crust. What is this and what layer of the skin is affected?

Answer 44

Bullous impetigo [from staph infection] | It affects substratum corneum