Chronic Blistering Disease Part I

1
Chronic Blistering Disease Part I

• Rick Lin, DO MPH
• SECOND year resident

2
(No Transcript)
3
(No Transcript)
4
(No Transcript)
5
(No Transcript)
6
(No Transcript)
7
(No Transcript)
8
(No Transcript)
9
(No Transcript)
10
(No Transcript)
11
(No Transcript)
12
Pemphigus Vulgaris

• Easily rupture bullae
• Bulla is clear at first but may become
  hemorrhagic or even seropurulent then form
  erosion
• Appear first in the mouth and them commonly in
  the groin, scalp, face, neck, axillae, or
  genitals
• Nikolsky sign is present

13
Nikolsky sign vs. Asboe-Hansen

• Nikolsky sign absence of cohesion in the
  epidermis, upper layers are easily made to slip
  laterally by slight pression or rubbing.
• Asboe-Hansen sign direct pression on intact
  bulla leading to bulla-spread phenomenon

14
Pemphigus Vulgaris

• Mouth lesion first appear in 60 of the case
• Mucosa with painful erosion
• Mouth odor is offensive and penetratingly
  unpleasant
• Esophagus may be involved and sloughing of entire
  lining to form a cast (esophagitis dissecans
  superficialis)

15
Pemphigus Vulgaris

• Epidemiology MF, usually 5th and 6th decades,
  rare in young person
• Etiology autoimmune blistering disease mediated
  by intercellular antibodies
• IgG throughout epidermis, C3 reliably found
• Desmoglein-3 antibody detected

16
Pemphigus Vulgaris

• Drugs which induces pemphigus
• Penicillamine for treatment of RA, most often for
  foliaceous type
• Captopril, penicillin, thiopronine,
  interleukin-2, rifampin

17
(No Transcript)
18
(No Transcript)
19
(No Transcript)
20
(No Transcript)
21
The hallmark of pemphigus is the finding of IgG
autoantibodies directed against the cell surface
of keratinocytes. A Pemphigus vulgaris sera
containing anti-desmoglein 3 IgG alone stain the
cell surfaces in the lower epidermis. B
Pemphigus vulgaris sera containing both
anti-desmoglein 3 IgG and anti-desmoglein 1 IgG
stain the cell surfaces throughout the epidermis.
C Pemphigus foliaceus sera, which contain only
anti-desmoglein 1 IgG, stain the cell surfaces
throughout the epidermis, but more intensely in
the superficial layers.
22
(No Transcript)
23
(No Transcript)
24
Pemphigus Vulgaris

• Treatment
• Topical Silvadene, Maalox for mouth
• Systemic Prednisone 60mg to 100mg daily
• Systemic Azathioprine (Imuran), cyclophasphamide
  (Cytoxin), Mexotrexate maybe used in combination
• Repeat pemphigus antibody titer in 4-8 weeks
  after treatment. If not improving, increase
  prednisone up to 150mg/day
• Solu-medrol IV pulse therapy at 1g/day over 2-3
  hour period, repeat for 5 days if patient is not
  responding orally.

25
Pemphigus Vulgaris

• Use of an immunosuppresant is helpful in
  diminishing the need for corticosteroids.
• Imuran is one of the best
• Risk of death in pemphigus from side effect of
  oral prednisone is greater than the risk of death
  from the disease itself

26
(No Transcript)
27
Pemphigus Vegetans

• A variant of pemphigus vulgaris
• Characterized by flaccid bullae that become
  erosions and form fungoid vegetation or
  papillomatous proliferations, especially in body
  folds
• Histology finding are identicla with those of
  pemphigus vulgaris, but there is an increased
  papillary proliferations and marked epidermal
  hyperplasia.

28
(No Transcript)
29
(No Transcript)
30
(No Transcript)
31
Pemphigus Foliaceus

• Mild, chronic variety of pemphigus characterized
  by flaccid bullae and generalized or localized
  exfoliation.
• Nikolsky sign present. Oral lesions rarely seen.
• Desmoglein-1 antibody.
• Patient with Pemphigus Foliaceus are not severely
  ill.

32
(No Transcript)
33
(No Transcript)
34
(No Transcript)
35
(No Transcript)
36
Fogo Selvagem

• AKA Brazilian Pemphigus
• Endemic form of pemphigus foliaceus found in
  tropical regions
• Histologically and immunohistologically identical
  to pemphigus foliaceus

37
Pemphigus Erythematosus

• Senear-Usher Syndrome
• Resemble lupus erythematosus
• Positive for lupus band in 80 of patients
• Histologically resemble Pemphigus foliaceus
• Dosage of prednisone required for control usually
  is much lower than that of Pemphigus Foliaceus

38
(No Transcript)
39
Paraneoplastic Pemphigus

• Mucosal lesions may present as lichenoid with
  Stevens-Johnson-like presentation
• Skin lesions may appear as erythematous macules,
  lichenoid lesions, erythema multiforme-like
  lesion, flaccid bullae, and erosion.
• Immunohistopathologic reveals IgG and C3.

40
The characteristic clinical feature is severe
intractable stomatitis that extends onto the
vermilion lip.
41
(No Transcript)
42
Intraepidermal Neutrophilic IgA Dermatosis

• Generalized flaccid bullae, which may rapidly
  ruptured and crusted
• Histological finding shows neutrophilic
  exocytosis and in some areas neutrophils arranged
  in a linear fashion at the dermal-epidermal
  junction.
• Direct IF showed an intrercellular deposition of
  IgA with in epidermis with minimal staining of
  basal layer.

43
Intraepidermal Neutrophilic IgA Dermatosis

• Second subset of patients develop disease that
  more closely simulates subcorneal pustular
  dermatosis
• Present much more like Sneddon-Wilkinson patient
  with serpiginous and annular pustules
• Treatment with Dapsone is often effective at as
  low as 25mg per day.

44
(No Transcript)
45
(No Transcript)
46
Bullous Pemphigoid

• Large bullae
• When rupture, shows large denuded area and do not
  materially increase in size.
• Denuded areas show a tendency to heal
  spontaneously
• Begins at a localized site, frequently the shin
• Young girls maybe initially seen with localized
  vulvar erosion and ulcers that resemble signs of
  child abuse.

47
Bullous Pemphigoid

• Occurs most frequently in the elderly.
• Age of average onset is 65 to 75 years
• Etiology circulating basement membrane zone
  antibodies of the IgG class present 70.
• Site of IgG binding has been localized to the
  lamina lucida, with accentuation near
  hemidesmosome
• Bullous pemphigoid antigen 1 (BPAg1) and 2
  (BPAg2) identified in 90 of patients

48
(No Transcript)
49
(No Transcript)
50
(No Transcript)
51
(No Transcript)
52
(No Transcript)
53
(No Transcript)
54
(No Transcript)
55
(No Transcript)
56
(No Transcript)
57
(No Transcript)
58
(No Transcript)
59
(No Transcript)
60
(No Transcript)
61
(No Transcript)
62
(No Transcript)
63
(No Transcript)
64
A Direct immunofluorescence microscopy studies of
perilesional skin demonstrating linear continuous
deposits of IgG along the epidermal basement
membrane zone (arrow). The same pattern of
labeling is observed in cicatricial pemphigoid
and epidermolysis bullosa acquisita. B Indirect
immunofluorescence microscopy study utilizing
salt-split normal human skin as a substrate.
Patient's IgG autoantibodies are bound to the
epidermal side (roof) of the split (arrow). The
level of the artificial separation is indicated
by asterisk. Cell nuclei are stained blue. The
same pattern of labeling is observed in a subset
of patients with cicatricial pemphigoid .
65
Treatment

• Same treatment for pemphigus, with the
  expectation that disease will respond readily
  with lower dose of corticosteroid.
• In severe case, pulse therapy with
  methylprednisolone giving 15mg/kg in 16 ml
  bacteriostatic water over period of 30 to 60
  minutes daily for 3 doses.
• Imuran is commonly used in resistant cases

66
Treatment

• Additional treatment options include mexotrexate
  and mycophenolate mofetil.
• Nicotinamide 500mg three times daily combined
  with tetracycline 500mg four times daily works 10
  out of 14 patients.

67
(No Transcript)
68
(No Transcript)
69
(No Transcript)
70
(No Transcript)
71
(No Transcript)
72
(No Transcript)
73
(No Transcript)