Pemphigus/ other blistering diseases

Question 1

Pemphigus foliaceous antigen vs.pemphigus vulgaris antigen

Answer 1

PF Ag - Desmoglein 1
PV Ag - Desmoglein 3

Question 2

Desmoglein 1 is found in ____ layers of the epidermis
Desmoglein 3 on the contrary is found

Answer 2

DG1 is in ALL layers, so loss of it CANNOT be compensated for - pemphigus foliaceous
DG3 3 loss can be compensated for as it is found mostly in the lower layer of the epidermis

If DG1 is targeted, the skin can develop blisters
if ONLY DG3 is targeted, the skin remains intact (however the mucous membranes blister easily - as seen in mucosal type PV)

Note: DSG3 is strongly expressed in mucosal tissue, not much DSG1

Question 3

Strength of adherens junctions versus desmosomes

Answer 3

Adherens - quick but weak
Desmosomes - slow and strong

Question 4

In patients with only Anti-Dsg1 IgG, you see what type of blisters

Answer 4

superficial without mucosal involvement
because DSG3 can compensate for deep epidermis

Question 5

Bonus fact for understanding, why does Anti-DSG1 antibodies in mother not affect baby

Answer 5

Because babies skin has DSG3 strongly expressed everywhere (similar to mucosa)

Question 6

Staph scalded skin syndrome toxin cleaves which antigen

Answer 6

DSG1 (superficial blisters)
Remember DSG3 is deep
Histologically these lesions are similar to those seen in PF

Question 7

Desmoglein 4 has an important role where?

Autosomal recessive localized hypotrichosis and monilethrix

Answer 7

Hair follicles

Question 8

Auto-Ab’s to DG3 __
Auto-Ab’s to DG1 and DG3 ___

Answer 8

DG3 - ___ Mucosal-dominant pemphigus
DG1/ DG3 - ____ Mucocutaneous pemphigus

Question 9

Describe and what antigen?

Answer 9

pruritic urticarial plaques with crusted vesicles in a grouped, herpetiform arrangement
Ag is commonly desmoglein 1, chronic and not usually severe

Question 10

Which medications can cause drug induced pemphigus?

Answer 10

Penicillamine
CAptopril (other prils)
Pyrazones
Abx - PCN, ceph, rifampicin, nifedipine

Question 11

Paraneoplastic pemphigus
Which neoplasms a/w>?
Which autoantibodies (numerous)
Involvement where?
Diagnose how?

Answer 11

A/W non-hodgkins lymphoma, CLL, castelmans disease, thymoma, sarcoma
Ab’s vs -> desmoplakin 1, 3, BPAG1, plectin, periplakin, envoplakin, desmoglein 1/3
severe mucosal involvement

diagnose with DIF -> IgG and C3 along BMZ

Question 12

How do you differentiate PV and paraneoplastic pemphigus on IIF?

Answer 12

pemphigus antibodies bind stratifed squamous epithelia → monkey esophagus

paraneoplastic abs react with simple/ transitional epithelia AS WELL

Question 13

What is this?

Answer 13

IgA pemphigus

Elderly → pruritic, flaccid vesicles/ pustules with annular pattern/ central crust (axilla/ groin)

NO mucous membrane

dx: DIF +100% IgA

Tx: Dapsone

Remember CAT PISS: candida, acropustulosios of infancy, transient neonatal pustular melanosis, pustular psoriaiss, impetigo , senddone-0wilkinson (and IGA pemphigus), Staph scalded skin

Question 14

Which other autoimmune diseases are associated with PV?

Answer 14

Myasthenia gravis, autoimmune thryoiditis, thymoma

Question 15

What disease are you concerned for

Answer 15

Pemphigus vulgaris, think of suprabasilar acantholysis AND TOMBSTONING

Look for eosinophilic abscesses within dermis also

This is in comparison with Hailey Hailey disease which shows ACANTHOLYSIS of HAIR FOLLICLES ONLY

Question 16

Which antigen is associated with LABD?

Answer 16

LAD-1 / LABD97

Look for linear IgA at BMZ + IgG/C3

lesions are pruritic, symmetrical on extensors, 70% of patients have oral lesions

VANCOMYCIN***

Question 17

Mucous membrane pemphigoid autoantigen ?

Anti-Epiligrin MMP autoantigen?

Occular predominant MMP?

Answer 17

BPAG2 = mucous membrane pemphigoid

Laminin 332 = anti-epiligrin

B4 integrin (from a6b4) = Occular predominant

Question 18

Three characteristic histological patterns in pemphigus foliaceus/ pemphigus erythematosus

Answer 18

1. eosinophilic spongiosis and abscesses
2. subcorneal/ granular layer blisters with few acantholytic keratinocytes
3. subcorneal / granular blisters with dyskeratotic granular cells

Look for linear or granular IgG and possible c3 at epidermal BMZ

Question 19

Two most common drugs for drug induced pemphigus?

Answer 19

penicillamine and captopril

Question 20

histopathologic features of drug induced pemphigus

Answer 20

early you see acute/ subacute eczematous dermatitis

Eosinophils present → spongiosis

blister separation plane is either subcorneal or suprabasal zones

Question 21

Autoantigen for IgA pemphigus?

Histological features?

Answer 21

Desmocolin 1 and/or desmogleins -→ this leads to characteristic annular appearing blisters

Either a subcorneal pustular pattern (with minimal acantholysis) or intraepidermal pustular pattern (pustules contain neutrophils throughout the breadth of epidermis)

Needs IgA intercellular deposition on IIF

Question 22

Describe the classic lesions of Hailey-Hailey disease

What gene is associated with it?

Describe some histopathologic features

Answer 22

This autosomal dominant genodermatosis presents in adolescence or adulthood with localized, recurrent vesicles arising on erythematous bases . The vesicles often become eroded and develop scale crust. The plaques expand serpiginously, with healing or ensuing vegetation. Lesions are usually limited to the intertriginous areas, sides of the neck, and less commonly, the antecubital, perianal, and inframammary zones. Lesions may extend elsewhere and in rare cases become widespread. Maceration and fissuring may be prominent, particularly intertriginous areas

On chromosome 3q, ATP2C1 gene

Full thickness acantholysis of the stratum spinosum develops, epidermal hyperplasia as well

Question 23

Paraneoplastic pemphigus involves palms soles?

Main autoantigens?

Answer 23

Yes

desmoplakin 1, BPAG1

Suprabasilar acantholysis with basilar layer apoptosis, interface dermatitis like LP

Question 24

Which blistering diseases are associated with a6b4?

Answer 24

ocular and oral cicatricial pemphigoid

also junctional EB with pyloric atresia

Question 25

EBA, linear IgA bullous disease and bullous lupus have which autoantigen in common? Is histopath the same or different between BP and cicatricial pemphigoid?

Answer 25

collagen 7 The same!

Question 26

BPAG 1 and BPAG 2 are both equally found in sera from BP patients?

Answer 26

BPAG1 is actually in 90% of patients BPAG2 is only found in 50%, so BPAG1 is more representatitve!! However in herpes gestationis and LP pemphigoides, expect BPAG2 \> BPAG1

Question 27

Where is the blister in BP? What other histopathologic features?

Answer 27

Subepidermal mod-dense infiltrate of lymphocytes (*tho can have cell poor bp)* numerous eosinophils few neutrophils DEJ vacuolar degradation may have neutrophilic collections in the papillary dermis → neutrophilic microabscesses **note, early urticarial BP lesions are characterized by superficial perivascular infiltrate of lymph, eos, neuts sometimes** also look for eos/ neuts at DEJ + vacuolar changes, spongiosis is common **EARLY BP looks like eosinophilic spongiosis differential**

Question 28

How does DIF differ between EBA and BP?

Answer 28

IgG deposition in roof of blister in BP Floor of the blister in EBA

Question 29

Paraneoplastic pemphigus clinical features Which malignancy associations? Histo features?

Answer 29

generalized polymorphous eruption of blisters and lichenoid papules, oral ulcers (similar to SJS)/ eyes, palms/soles involved (which helps rule out PV) Hodgkin lymphoma, thymoma, CLL Histo: suprabasilar acantholysis, interface dermatitis

Question 30

EBA Histological features

Answer 30

Sub epidermal blisters (remember collagen 7, subLamina densa No or sparse perivascular intersittial infiltrates (occasional eos/ neuts) \> classic variant -→ Ddx included PCT and cell poor BP in the inflammatory variant, expect moderate density lymphocytic infiltrates with eos/neuts the infiltrate is at the DEJ, so expect vacuolar change

Question 31

bullous lupus antigen and histo features?

Answer 31

collagen 7 similar to DH (dermal papillary neutrophilic infiltrate) however, subepidermal blisters/ infiltrate of lymphocytes/ neuts around hair follicles is more common Mucin deposits

Question 32

Hailey Hailey disease clinical features Histo findings

Answer 32

autosomal dominant genoderm, adolescence/ adulthood → localized, recurrent vesicles arising on an erythematous base, vesicles are eroded/ scaled/ crusted, plaques expand serpiginously, intertriginous locations only ATP2c4 gene Full thickness acantholysis of the stratum spinosum, hyperplastic epidermis, no follicular involvement of the acantholysis

Question 33

Darrier disease clinical features histology findings

Answer 33

autosomal dominant genoderm in 1st two decades of life Red borwn papules with scale coalesce into larger plaques - chest, back, head and groin cobblestone papules in mouth warty papules acrally **ATP2A2 Gene** Large acantholytic suprabasal cleft with **intact basilar layer** elongated retes ortho/parakeratotic debris above stratum corneum **numerous dead keratinocytes, large keratinocytes with perinuclear halos, clumped keratohyalin granules in eosinophilic cytoplasm, small seed shaped cells with pyknotic neuclei and dense eosinophilic cytoplasm**

Question 34

Summary of bullous diseases

Answer 34

Question 35

summary of antigens/ autoantibody targets

Answer 35

Question 36

salt split skin antigens

Answer 36

Question 37

is SSSS pauci inflammatory?

Answer 37

yes

Question 38

is bullous impetigo pauci inflammatory??

Answer 38

No!! expect neuts

Question 39

Two subtypes of IgA Pemphigus How to differentiate from sneddon wilkinson?

Answer 39

Differentiate from SW with DIF (chicken wire)

Question 40

DIF for Paraneoplastic pemphigus?

Answer 40

Question 41

Darier disease -→ think ______ \_\_\_\_\_\_\_

Answer 41

Acantholytic dyskeratosis (suprabasilar split) (core ronds/ grains) ronds = lower in epidermis, round pyknotic dying keratinocytes grains, look like parakeratosis

Question 42

hailey hailey disease - think ______ \_\_\_\_\_\_

Answer 42

Acantholysis WITHOUT dyskeratosis

Question 43

What should I see here

Answer 43

multinucleation, margination, molding

Question 44

BP would show what on salt split skin?

Answer 44

Binding above the lamina lucida, BP230/180 (n16a domain of bpag2) localizes to the roof!

Question 45

cicatricial pemphigoid varieties

Answer 45

Laminin 332 binds to the floor on salt split skin (dungeons, yucky, awful, cancer - paraneoplastic) the rest bind to the roof of the blister

Question 46

subepidermal bulla with neutrophil differential dx (4 options)

Answer 46

LIPS Lupus → expect lots of neuts, interface like intradermal changes, DIF shows IgG, IgA, IgM, and c3 (chicken wire, linear pattern and granular), binds to floor in Salt split skin → **collagen 7 antigen** linear IgA → expect neuts along entire BMZ, not just papillae Pemphigoid Sweet's

Question 47

what disease is here

Answer 47

EBA - \> pauci inflam subepidermal clean split salt split skin binds to the floor, type 7 collagen cicatricial, PCT, bullous lupus (not pauci immune)

Question 48

What is shown here

Answer 48

Festooning of the dermal papilla, caterpillar bodies **porphyrin** deposits around vessels cause IgG complement attack and bullas