Pemphigoid

Question 1

FEATURES OF PEMPHIGOID?

Answer 1

-autoimmune disease
-subepidermal
-mostly cutaneous manifestaion but can involve the oral mucosa in 30 %
- severe pruritus (unlike pemphigus)

Question 2

do you see peripheral eosinophilia iin BP?

Answer 2

yes in 50%

Question 3

what about the epidemiology of the disease?

Answer 3

מופיע לרוב לאחר גיל 60, עם שכיחות גוברת ככל שהגיל עולה. באופן נדיר- מופיע

בילדים

או

בנשים בהריון

Question 4

how do you call bullous pemphigoid when it appears in the pregancy

Answer 4

pemphigoid gestationis

Question 5

explain the pathogenesis of BP?

Answer 5

BP is basically a combined humoral - antibodies against portions of the hemidesmosomes BP180 ( NC16A domain) or BP230

as well as cellular immune response in which T cells (CD4) produce cytokines of Th1 type (Interferon Gamma) and Th2 (IL4,IL5 and IL13).

the binding of the Ab produces a response that causes the recruitment of inflammatory cells that result in the breakdown of ECM and BP180–> subepidermal cleavage –> the innate system also takes part *recuiting macrophages neutrophils eosinophils and mast cells)

Question 6

how is the pathophysiology of BP different from mmp

Answer 6

Bp targets the NC16A domain of the BP180 hemidesmosome

MMP the Ab targets the C terminal of BP180

Question 7

CLinical presentation

Answer 7

Pruritus ! can also appear prior to the disease

initially there is the prodromal Urticarial stage or Eczematous presentation prior to the bullous phase .

another presentation could be excoriation only .

next is the bullous phase - containing tense bullae (up to 4 cm, containing seorus or hemorrhagic content ) usually the appearance is symmetrical
- mucosal involvemt is seldom 30 % ( and if there is its ostly oral )

Question 8

Clinical variant of Pemphigoid ? other clinical variant ( more extensve)

Answer 8

Childhood pemphigoid
Drug induced

other
-Dyshidrosiform pemphigoid- palmoplantar vesicles and bullae

-Pemphigoid nodularis- prurigo nodularis-like lesions

• Vesicular pemphigoid- DH-like with small-grouped vesicles
• Large erosive TEN-like lesions
• Papular pemphigoid
• Eczematous pemphigoid
• Erythrodermic pemphigoid
• Lichen planus pemphigoides -

אופייני בעיקר באזורי קפלים -Pemphigoid vegetans -

Question 9

mention the other atypical loclaized BP presentations?

Answer 9

• pretebial
• vulvar
• stump pemphigoid
• radiotherapy site
• brunsting perry
• prestromal
• umbilical
• paralyzed limb

Question 10

Triggers for the disease?

Answer 10

• TRAUMA
• RADIOTHERAPY AND UV including PHOTOTHERAPY
• DRUGS
  -BURNS

Question 11

WHAT KIND OF DRUGS CAN INDUCDE BP ? what is the time lag

Answer 11

usually when its drug induced the time lag is up to 3 months - in case of immunotherapy it can be abit longer

• DIURETICS (SPIRONALACTONE AND FUROSEMIDE)
  -NSAIDS (SYSTEMIC AND LOCALIZED E.G DICLOFENAC GEL)
  -ANTIBIOTICS (CIPRO +AMOXICILLIN
  -ACEI
  -TNF INHIBITORS
• POTASSIUM IODINE
  -IMMUNIZATIONS
• DPP4 INHIBITORS
• CHECKPOINT INHIBITORS (PD1 INHIBITORS )

Question 12

IS THERE A CORRELATION WITH NEURLOGICAL DISEASE?

Answer 12

YES , More commonly seen in patients with dementia, Psychiatric diseases, MS , CVA

• Not clear how and why but the presumption is that its secondary to Bp230 which also exist in the Nervous system

Question 13

is there any correlation between BP , Pso and lichen?

Answer 13

Inflammatory conditions such as psoriasis and lichen planus may predispose the development of BP lesions on top of the inflammatory primary lesion probably due to exposure of epitopes

Question 14

is there any corrlation to malignancy?

Answer 14

most probably not

Question 15

Mention 4 features the differ BP from other Vesicullobullous diseases?

Answer 15

1- lack of atrophy
2- lack of Mucosal involvment
3- lack of Head and neck Involvement
4- age above 70

Question 16

Histopathology of BP?

Answer 16

שלפוחית עם היפרדות סאבאפידרמלית ותסנין בדרמיס השטחי מעורב של
לימפוציטים ואאוזינופילים.
. בשלב המוקדם הלא-בולוזי
תסנין דרמלי של אאוזינופילים
eosinophilic spongiosis או יכול רק

Question 17

what do you see in the electron microscopy in case of BP?

Answer 17

• ידגים היפרדות בשכבת ה-lamina lucida (שם נמצא החלק החוץ-תאי של B180- ה-NCA16 domain).

Question 18

what about DIF?

Answer 18

נלקח מעור בריא סמוך, לא מעורב. מדגים שקיעה ליניארית רציפה בשכבת
הבסיס מורכבת מ IgG
או ו c3

Question 18

what is the patten immuno deposition in case of Bullous Pemphigoid?

Answer 18

N serrated

The U-serrated and N-serrated patterns in dermatology immunofluorescence refer to distinct patterns of immunodeposition observed at the basement membrane zone (BMZ) during direct immunofluorescence (DIF) microscopy,

Question 19

mention the conditions by which we can see N serrated pattern?

Answer 19

it is commonly observed in other subepidermal bullous diseases, such as

• bullous pemphigoid (BP), - mucous membrane pemphigoid (MMP)
  -linear IgA disease

. The N-serrated pattern corresponds to the localization of autoantibodies in the hemidesmosomes, lamina lucida, or lamina densa

Question 19

when do you see u Serrated pattern, explain why?

Answer 19

in the case of epidermolysis bullosa acquisita

DIF shows a U-serrated pattern of immunodeposits along the basement membrane zone (BMZ).

This pattern is indicative of autoantibodies targeting type VII collagen located in the sublamina densa zone

• u serrated pattern is also seen in Bullous SLE

Question 20

if bullous pemphighoid and Linear IgA and MMP shows the same patten then how can you differentaite between the 3?

Answer 20

while the N-serrated pattern on DIF is common to BP, LABD, and MMP, differentiation is achieved through clinical presentation, IIF on salt-split skin, and specific autoantibody profiles detected by ELISA or immunoblotting.

BP-

• Clinical Features: BP typically presents with tense blisters on erythematous or normal skin, primarily affecting the elderly.
• Indirect Immunofluorescence (IIF): IIF on salt-split skin shows IgG binding to the epidermal side of the split.
• ELISA: Positive for BP180 and BP230 autoantibodies

Linear IgA Bullous Dermatosis (LABD):
* Clinical Features: LABD presents with annular or grouped vesicles and bullae, often described as a “string of pearls” appearance.
* Indirect Immunofluorescence (IIF): IIF on salt-split skin shows IgA binding to the epidermal side of the split.
* ELISA/Immunoblotting: Positive for IgA autoantibodies against BP180 or LAD-1

Mucous Membrane Pemphigoid (MMP):
* Clinical Features: MMP predominantly affects mucous membranes, leading to scarring and strictures, with common sites including the oral cavity, conjunctiva, and genital mucosa.
* Indirect Immunofluorescence (IIF): IIF on salt-split skin shows IgG binding to the dermal side of the split.
* ELISA/Immunoblotting: Positive for autoantibodies against BP180, BP230, and laminin-332. Laminin-332 positivity is associated with an increased risk of malignancy