Pemphigus

Question 1

Subtypes of Pemphigus

Answer 1

Pemphigus Vulgaris
- Mucosal Dominant
- Mucocutaneous
- Pemphigus Vegetans

Pemphigus Foleacous
- inc Fogo Selvagem

Paraneoplastic Pemphigus

Pemphigus Erythematosus

IgA Pemphigus

Question 2

Histology Findings Pemphigus Vulgaris

Answer 2

Intraepidermal Blister
Suprabasilar acantholysis (without keratinocyte necrosis)
- acantholysis extends down hair follicles
Epidermal cells and eosinophils within the blister cavity

Perivascular mononuclear infiltrates with eosinophils
Dermal papillae are maintained

Question 3

DIF findings pemphigus Vulgaris

Answer 3

IgG +/- C3 intercellular staining - giving a chickenwire appearance.

Staining may be more prominent are the basilar / supreabasilar layer compared to the granular layer

Question 4

IF findings for pemphigus vulgaris

Answer 4

Best demonstrated on Monkey Eosophagus

IgG staining throughout the epidermis

Question 5

ELISA results of pemphigus vulgaris

Answer 5

DSG 3 +/- DSG 1

Question 6

Histopathology of pemphigus vegetans

Answer 6

Similar to P. Vulgaris
- intraepidermal blister, acantholysis, eposinophils

With acanthosis and papilomatosus
More intense inflammatory cell infiltrate continaing eosinophils

Question 7

Pemphigus Foliaceous Histology findings

Answer 7

Acanthosis at the level of teh granular layer
(often wihtout keratinocyte necrosis)
Stratum corneum often lost
Eosinophils and neutrohils

Mononuclear perivascular infiltrate with eosinophils

Question 8

What are the DIF findings with Pemphigus Foliaceous?

Answer 8

Intercellular staining of IgG +/- C3 - chickenwire apeparance

More prominent at the stratum corneum / granulosum compared to the basal layer

Question 9

IF findings for Pemphigus Foliaceous?

Answer 9

Human skin OR Guinea Pig eosphagus

Intercellular IgG staining +/- C3

Question 10

Elisa results of Pemphigus Foliaceous?

Answer 10

DSG 1

Question 11

Paraneoplastic pemphgigus most common malignancies?

Answer 11

Non-hodgkins lymphoma
CLL
Castlman disease

Question 12

Paraneoplastic pemphigus histology findings?

Answer 12

Variable findings - intraepidermal blister formation / acantholysis

Oft ass wtih lichenoid inflamation - band like lymphocytic infiltarte abuting the dermo-epidermal junction

Basal vacuolar change and keratinocyte necorsis

Question 13

DIF findings for paraneoplastic pemphigus

Answer 13

intercellular staining of IgG +/- C3

+ Prominent stainng along the dermoepidermal junction

Question 14

ELISA findings for paraneoplastic pemphigus?

Answer 14

Envoplakin
Periplakin
Desmocollin 1 / 3
BP 230

Question 15

IF findings for paraneoplastic pemphigus?

Answer 15

Best demonstrated on Monkey or guinea pig esophagus or rat bladder

IgG

intercellular staining of IgG +/- C3
AND
Prominent stainng along the dermoepidermal junction

Question 16

Histology findings in pemphigus erythematosus?

Answer 16

Intraepithelial blister formation / acantholysis around the granular layer
Eosinophils

Plus lichenoid inflammation:
- band like perivascular inflammaiton
- mucin
- basal vaculoar change
- keratinocyte necorsis

Question 17

What are the DIF findings of pemphigus erythematosus/

Answer 17

Intercellular deposits of IgG and C3 in the epidermis

+ granular staining of IgG and/or C3 along the dermal-epidermal junction

Question 18

What are the histology findigns of IgA pemphigus?

Answer 18

Intraepidermal pustule or vesicle
- Predominant cell type = neutrophils
- May be subcroneal or intraepidermal

No acantholysis

Question 19

What are the DIF findings of igA pemphigus?

Answer 19

IgA +/- C3 positive granular and intercellular, resembling a “chicken wire” pattern

On keratinocyte cell surfaces

Question 20

IgA pemphigus has what associations?

Answer 20

Inflammatory bowel disease
IgA myeloma

Question 21

Paraneoplastic Pemphigus is ass. with which conditions?

Answer 21

1. Malignancy - Non-hodgkins lymphoma, CLL, castelmans, Sarcoma etc
2. Benign tumours - e.g Thymoma
3. Bronchiolitis Obliterans

Question 22

What drugs are commonly associated with pemphigus?

Answer 22

ACEi
Penicillamines
Gold
Pyritinol
Antibiotics (penicillins)
ICIs (pembrolizubmab)
Topical Imiquimod
Propranolol

Question 23

Subtuypes of IgA pemphigus? and the associated antigens?

Answer 23

Subcorneal pustular dermatosis type - Desmocollin 1
Intraepidermal neutrophillic type - unknown antigen
PF type - DSG1
PV type - DSG3

Question 24

Classification of pemphgus

Answer 24

Question 25

Causes of eosinophillic spongiosis?

Answer 25

Question 26

Descirbe?

Answer 26

Question 27

Describe

Answer 27

Question 28

What the recommended IF subtrates for PV, PF, PP and BP, LABP and MMP?

Answer 28

PV = Monkey Eosphagus PF = Human skin of Guinea Pig Esophagus PP = Monkey Eosphagus (DSG3) Guinea pig esophagus (DSG1) and Rat bladder (anti-plakin) BP = Human, split Skin LAPD = Human, split skin MMP = Huma, split skin or norneal, genital or oral mucosa

Question 29

DDx of Pemphigus Vegetans/

Answer 29

Question 30

How is IgA pemphigus treated?

Answer 30

Dapsone - first line

Question 31

What are the target antigens in the different types of pemphigus?

Answer 31

Question 32

In IgA pemphigus, what is the target antigen in the subcorneal pustular dermatosis type, and how does DIF differ from classic PV?

Answer 32

**Target antigen: 👉 Desmocollin 1 (a cadherin protein similar to desmogleins)** Found in the superficial epidermis **DIF (Direct Immunofluorescence): Shows intercellular deposition of IgA (not IgG!)** Usually most intense in the upper epidermis May resemble the “chicken-wire” pattern but limited to superficial layers

Question 33

A patient presents with pruritic annular and vesicular plaques on the trunk, minimal mucosal involvement, and histology shows eosinophilic spongiosis with early acantholysis. What is the most likely pemphigus subtype, and which desmoglein is typically involved?

Answer 33

Pemphigus herpetiformis Eosinophilic spongiosis with early acantholysis = hallmark for pemphigus herpetiformis Most commonly: Desmoglein 1 (DSG1) Occasionally: antibodies to DSG3, desmocollins, or periplakin Pemphigus herpetiformis mimics dermatitis herpetiformis or linear IgA disease — but DIF shows intercellular IgG in a fishnet pattern.

Question 34

What treatment in first line for first-line for IgA pemphigus?

Answer 34

Dapsone

Question 35

In pemphigus vulgaris, what is the rationale for rituximab as first-line therapy, and how does its mechanism differ from IVIg?

Answer 35

Monoclonal antibody against CD20 Targets pre-B cells to mature B cells Spares plasma cells (which lack CD20) but prevents further antibody generation Leads to long-term remission in many patients **Demonstrated superiority to steroids alone in the Ritux 3 trial: ** * Faster remission * Reduced cumulative steroid dose * Fewer relapses Now included in international consensus as first-line for moderate–severe PV

Question 36

What histologic feature distinguishes early pemphigus foliaceus from impetigo or staphylococcal scalded skin syndrome (SSSS)?

Answer 36

Early Pemphigus Foliaceus (PF): Acantholysis in the upper epidermis — usually subcorneal * Eosinophils often infiltrate the epidermis and blister cavity * Minimal or absent neutrophils * No significant inflammation in the dermis early on Caused by staph exotoxins (esp. exfoliative toxin A) * Also show subcorneal splitting BUT: * Rich neutrophilic infiltrate, often with crust * No eosinophils In SSSS, the split occurs without significant inflammation (toxin-mediated cleavage of desmoglein 1)

Question 37

You're shown a biopsy from a flaccid blister. It reveals suprabasilar acantholysis, scattered eosinophils, and rare dyskeratotic keratinocytes. What pemphigus variant must be considered in the differential, and what histologic clue would confirm it?

Answer 37

**Pemphigus Vulgaris VS Pemphigus Erythematosus VS Paraneoplastic pemphigus ** To confirm **Pemphigus Erythematosus:** Look for: Suprabasilar acantholysis (as in pemphigus foliaceus) Basal vacuolar change (interface dermatitis) Band-like lymphocytic infiltrate Dermal mucin Direct immunofluorescence (DIF) may show: Intercellular IgG (chicken wire) + linear or granular basement membrane IgG (like LE)

Question 38

What is the most commonly used substrate for indirect IF in the diagnosis of pemphigus vulgaris, and why is it preferred?

Answer 38

Monkey Esophagus in Pemphigus Vulgaris: Reason for use: High expression of desmoglein 3 in the lower epidermis Closely mimics human mucosa Ideal for detecting circulating IgG antibodies against DSG3 Produces classic intercellular "chicken-wire" pattern More sensitive than normal human skin for mucosal-dominant PV

Question 39

Rat bladder is a preferred IIF substrate for detecting antibodies in paraneoplastic pemphigus

Answer 39

T Why rat bladder? It expresses plakin family antigens (e.g. envoplakin, periplakin) in the urothelium These are the dominant autoantigens in PNP Human skin and monkey esophagus may miss these reactivities, especially early