Dermatitis herpetiformis/ LABD chapter Flashcards
Describe the classic lesions of what is seen here
Most commonly we see urticarial plaques, papules and vesicles that can be grouped/ herpetiform on an erythematous base, symmetric dist. favoring the elbows, knees, extensor forearms, back and buttocks’
pruritic papulovesicles or excoriated papules on extensor surfaces
neutrophilic infiltration of the dermal papillae with vesicle formation at DEJ
granular IgA deposition within dermal papillae in clinically normal skin adjacent to lesion
a response to dapsone therapy (but not the intestinal disease)
What is the strong genetic association with DH?
HLA DQ2
topical iodide on normal skin of patients with a history of DH (or ingestion of iodide) can cause what?
DH is associated with which two other autoimmune conditions commonly?
new lesions / neutrophil chemotaxis! (follicular neutrophilic pustules)
a/w insulin dependent DM and hashimoto’s thyroid dz
H&E, explain what you see
This is DH
Subepidermal clefts beneath which are collections of neutrophils within dermal papillae. Scattered eosinophils are also present.
For routine histology, it is optimal to capture a small, intact vesicle. If this is not available, an area of erythema should be biopsied. Areas of erythema will show dermal papillary edema and neutrophil infiltration associated with a superficial perivascular lymphocytic infiltrate. Dermal papillae filled with neutrophils, with relative sparing of the lowermost tips of the intervening rete ridges, is a characteristic finding. When an intact vesicle is biopsied, a subepidermal blister containing predominantly neutrophils will be seen
Why is it optimal to biopsy adjacent, but not inside a lesion of DH for DIF?
which autoantibodies can be found in labs?
A false-negative DIF can occur if lesional skin is biopsied, since the inflammatory infiltrate can destroy the IgA
IgA anti-TTG3 Anti-endomysial antibodies = specific for CD/ DH
Granular IgA is pathognomonic
Ddx for DH?
Top row= arthropod bite (hypersensitivity rxn to bug bite)
bottom row = papular urticaria
DH Ddx
top left = BP
top mid = LABD
top right = urticarial vasculitis
EM
bullous LE
Granulomatosis w/ ?
Front/ back - which disease?
Discuss epidemiology/ main causative agent?
LABD
F> M
bimodal → 4-5 yo and >60yo
MCC is Vanco
What is primary IgA autoantibody target?
BP180 / BPAG2 (specifical LAD-1/ LABD97)
Difference between LABD and DH on DIF?
Linear IgA along BMZ in LABD and granular IgA deposition in DH - both in adjacent skin
Also note: Can have mucosal involvement with LABD
LABD treatment
Dapsone, Sulfapyridine, colchicine
Starting from top left to top right
- EBA
- Localized EBS
- Friction blister
- Bullous diabetacorum
- Coma blister (pt had some phenobarbital
- bullous insect bites (immunosuppressed HIV/hematologic malignancy//kids)
- bullous impetigo-edema blisters (person has anasarca)
- localized BP
- postburn blisters
– self induced (bullous dermatitis artefacta)
What do you think of here?
Which drug can cause LABD?
How about BP?
How about PV?
Vanco > B-Lactams
BP = Diuretics/ abx
PV = captopril/ penicillamine, b lactams
How do you know this is coma blister?
epidermal necrosis, sweat gland necrosis (characteristic), focal necrosis of epithelium of pilosebaceous follicles
no distinct cellular infiltrate
no Ig’s on DIF
Describe basic pathology of a friction blister?
intraepidermal blister resulting from necrosis of keratinocytes, usually at the level of the stratum spinosum just below stratum granulosum, the roof of blister forms in stratum corneum
sparse perivascular infiltrate
Back of teh hands blisters makes you think of?
What variation is seen here?
porphyria
drug induced here → NSAIDS, thiazides, furosemide, tetracyclines
What do you see here? What else on ddx?
What medication likely caused this?
This is AGEP
Pustular psoriasis on ddx
Caused by -Beta lactams, macrolides, pristinamycin, CCB, plaquenil, etc. etc.
Acute onset, usually occurring within 2 days of drug exposure
Areas of erythema studded with pustules; occasionally vesicles
Fever, malaise, leukocytosis
What is seen here
Photo distributed rash
Resembles exaggerated sunburn
Phototoxic drug eruption
think doxycycline (tetracyclines), quinolones, psoralens, nsaids, diuretics
What the heck is going on here
Bromoderma/ iododerma
Acneiform lesions, papulopustules, nodules, or even vegetating lesions simulating pemphigus vegetans
Clear or hemorrhagic blisters can develop (more common in iododerma)
What is seen here?
Palmoplantar erythrodysesthesia
- Acral variant of toxic erythema of chemotherapy
- Cytarabine, doxorubicin, capecitabine, 5-fluorouracil (especially prolonged infusions), multikinase inhibitors (e.g. sorafenib, sunitinib), busulfan, taxanes, clofarabine, pralatrexate
Bullous insect bite rxns
epidemiology
Hematologic malignancy associations?
Pathogenesis
What do you seen on H&E
•Epidemiology–Children–
Hematologic malignancy = CLL > mantle cell lymphoma, NK/T-cell lymphoma
Path = immune response t oinsect Ag (IgE mediated and delayed/ cell mediated)
Path → eosinophilic spongiosis, Intraepidermal > subepidermal blister (may occur if dermal edema severe), –Superficial and deep perivasc/periadnexal lympho-eosinophilic inflammation (+/- flame figures), Superficial dermal edema
What type of bulla?
Delayed posburn/ post graft blisters
- happen at site of prev. trauma/ >30% involvement increases reoccurence rate
-
tense vesicles/ bulla appearing wks/months after original wound has healed, d/t fragility of new DEJ
- path shows cell-poor subepidermal blister, NO DIF findings
What do you see here?
bullous dermatitis artefacta
LABD → IgA autoantibodies directed at _____, which is broken into two antigens: 1) ____ and 2) ____
BPAG2
Broken into LAD-1 and LABD97
can linear IgA have mucosal involvement?
Yes, similar to MMP
Histopath of LABD
Early versus late?
Fully developed lesions show subepidermal blisters with infiltrates of lymphocytes, eos and neuts
Expect more Neuts than others
vacuolar degeneration at the BM zone
Neutrophilic dermal papilla accumulation, similar to DH
DIF shows linear IgA deposits along BMZ
Salt split shows binding to epidermal side of the split
EBA is acquired or genetic?
Adults or kids?
Associated conditions?
Acquired
Adults
Crohns/ IBD > Myeloma, SLE, RA,
Which autoantibody for EbA
Which MHC association?
IgG against Collagen 7 NC1 domain
Class 2 HLA-DR2
Where does mechanobullous EBA affect?
Inflammatory EbA
Acral/ trauma prone sites ( may result in mitten deformities) → syndactyly, nail dystrophy/ loss, bullous lesions heal w/ atrophic scars, milia, dyspigmentation
Inflammatory → widespread (BP LIKE), indistinguishable from BP, widespread vesicles/ bulla with NO scarring/ millia after healing (mechanical EBA heals with scarring)
Inflammatory also has eye/ mouth involvement, also esophageal
DIF for EBA shows →
Borad linear band of IgG with a U serrated pattern along BMZ
Opposite of BP (Linear C3 with an N-Serrated pattern)
Salt split skin shows DERMAL side staining
Mechanical EBA vs. Inflammatory EBA on Histology>?
Which substrate for EBA?
Mech → cell poor sub epidermal blister (occasional EOs)
Inflammatory → moderately dense lymphocytic infiltrates with eos’/ neuts
Early urticarial lesions are not distinguishable from early lesions from other disease (BP?), vacuolar degeneration of BMZ, eosinophilic spongiosis common
Blisters localize to sublamina densa region
Monkey Esophagus
In contrast to DH, bullous Lupus lymphocytic inflitrate is more concentrated around the ____
Bullous Lupus DIF shows
Hair Follicles versus dermal papilla (DH)
Linear AND or granular IgG, IgA, IgM and C3 (full house)
HistoPathology of friction blisters
intraepidermal split, necrosis of keratinocytes
Split usually mid spinosum
pale and degenerated keratinocytes
Think of localized EB → weber cockayne
Which autoantibody for GUT involvement of DH?
How about skin involvement?
GUT → Anti TTG2 IgA ab
Skin → Anti TTG3 IgA ab
DH a/w which other autoimmune diseases?
–Hashimoto’s thyroiditis (>50%) > IDDM > pernicious anemia >> Addison’s, AA, myasthenia gravis, vitiligo, SLE
What DIF pattern do you expect to see in DH?
Granular IgA deposited within the dermal papilla
Which HLA types for DH?
DQ2 >90%
DQ8 <10%
bullous arthropod assault bugs associated? (2)
fleas and bed bugs
think kids and people with cancer (CLL)
delayed postgraft burns appear when
how much TBSA is usually seen?
30-37 days after
TBSA >30%
which stain for neonatal cephalic pustulosis
giemsa stain
looks like neonatal cephalic pustulosis but isn’t just on the head?
ETOX/ ETN
TNPM or ETN first???
TNPM
