Pemphigus/ other blistering diseases Flashcards
Pemphigus foliaceous antigen vs.pemphigus vulgaris antigen
PF Ag - Desmoglein 1
PV Ag - Desmoglein 3
Desmoglein 1 is found in ____ layers of the epidermis
Desmoglein 3 on the contrary is found
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
Strength of adherens junctions versus desmosomes
Adherens - quick but weak
Desmosomes - slow and strong
In patients with only Anti-Dsg1 IgG, you see what type of blisters
superficial without mucosal involvement
because DSG3 can compensate for deep epidermis
Bonus fact for understanding, why does Anti-DSG1 antibodies in mother not affect baby
Because babies skin has DSG3 strongly expressed everywhere (similar to mucosa)
Staph scalded skin syndrome toxin cleaves which antigen
DSG1 (superficial blisters)
Remember DSG3 is deep
Histologically these lesions are similar to those seen in PF
Desmoglein 4 has an important role where?
Autosomal recessive localized hypotrichosis and monilethrix
Hair follicles
Auto-Ab’s to DG3 __
Auto-Ab’s to DG1 and DG3 ___
DG3 - ___ Mucosal-dominant pemphigus
DG1/ DG3 - ____ Mucocutaneous pemphigus
Describe and what antigen?
pruritic urticarial plaques with crusted vesicles in a grouped, herpetiform arrangement
Ag is commonly desmoglein 1, chronic and not usually severe
Which medications can cause drug induced pemphigus?
Penicillamine
CAptopril (other prils)
Pyrazones
Abx - PCN, ceph, rifampicin, nifedipine
Paraneoplastic pemphigus
Which neoplasms a/w>?
Which autoantibodies (numerous)
Involvement where?
Diagnose how?
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
How do you differentiate PV and paraneoplastic pemphigus on IIF?
pemphigus antibodies bind stratifed squamous epithelia → monkey esophagus
paraneoplastic abs react with simple/ transitional epithelia AS WELL
What is this?
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
Which other autoimmune diseases are associated with PV?
Myasthenia gravis, autoimmune thryoiditis, thymoma
What disease are you concerned for
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
Which antigen is associated with LABD?
LAD-1 / LABD97
Look for linear IgA at BMZ + IgG/C3
lesions are pruritic, symmetrical on extensors, 70% of patients have oral lesions
VANCOMYCIN***
Mucous membrane pemphigoid autoantigen ?
Anti-Epiligrin MMP autoantigen?
Occular predominant MMP?
BPAG2 = mucous membrane pemphigoid
Laminin 332 = anti-epiligrin
B4 integrin (from a6b4) = Occular predominant
Three characteristic histological patterns in pemphigus foliaceus/ pemphigus erythematosus
- eosinophilic spongiosis and abscesses
- subcorneal/ granular layer blisters with few acantholytic keratinocytes
- subcorneal / granular blisters with dyskeratotic granular cells
Look for linear or granular IgG and possible c3 at epidermal BMZ
Two most common drugs for drug induced pemphigus?
penicillamine and captopril
histopathologic features of drug induced pemphigus
early you see acute/ subacute eczematous dermatitis
Eosinophils present → spongiosis
blister separation plane is either subcorneal or suprabasal zones
Autoantigen for IgA pemphigus?
Histological features?
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
Describe the classic lesions of Hailey-Hailey disease
What gene is associated with it?
Describe some histopathologic features
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
Paraneoplastic pemphigus involves palms soles?
Main autoantigens?
Yes
desmoplakin 1, BPAG1
Suprabasilar acantholysis with basilar layer apoptosis, interface dermatitis like LP
Which blistering diseases are associated with a6b4?
ocular and oral cicatricial pemphigoid
also junctional EB with pyloric atresia
EBA, linear IgA bullous disease and bullous lupus have which autoantigen in common?
Is histopath the same or different between BP and cicatricial pemphigoid?
collagen 7
The same!
BPAG 1 and BPAG 2 are both equally found in sera from BP patients?
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
Where is the blister in BP?
What other histopathologic features?
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
How does DIF differ between EBA and BP?
IgG deposition in roof of blister in BP
Floor of the blister in EBA
Paraneoplastic pemphigus clinical features
Which malignancy associations?
Histo features?
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
EBA Histological features
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
bullous lupus antigen and histo features?
collagen 7
similar to DH (dermal papillary neutrophilic infiltrate)
however, subepidermal blisters/ infiltrate of lymphocytes/ neuts around hair follicles is more common
Mucin deposits
Hailey Hailey disease clinical features
Histo findings
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
Darrier disease clinical features
histology findings
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
Summary of bullous diseases
summary of antigens/ autoantibody targets
salt split skin antigens
is SSSS pauci inflammatory?
yes
is bullous impetigo pauci inflammatory??
No!!
expect neuts
Two subtypes of IgA Pemphigus
How to differentiate from sneddon wilkinson?
Differentiate from SW with DIF (chicken wire)
DIF for Paraneoplastic pemphigus?
Darier disease -→ think ______ _______
Acantholytic dyskeratosis
(suprabasilar split)
(core ronds/ grains)
ronds = lower in epidermis, round pyknotic dying keratinocytes
grains, look like parakeratosis
hailey hailey disease - think ______ ______
Acantholysis WITHOUT dyskeratosis
What should I see here
multinucleation, margination, molding
BP would show what on salt split skin?
Binding above the lamina lucida, BP230/180 (n16a domain of bpag2)
localizes to the roof!
cicatricial pemphigoid varieties
Laminin 332 binds to the floor on salt split skin (dungeons, yucky, awful, cancer - paraneoplastic)
the rest bind to the roof of the blister
subepidermal bulla with neutrophil differential dx (4 options)
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
what disease is here
EBA - > pauci inflam subepidermal clean split
salt split skin binds to the floor, type 7 collagen
cicatricial, PCT, bullous lupus (not pauci immune)
What is shown here
Festooning of the dermal papilla, caterpillar bodies
porphyrin deposits around vessels cause IgG complement attack and bullas
