Bullous Diseases

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Bullous Diseases ?????
????? ?????? ?????
07-31211012755
yukkwa_at_kmu.edu.tw
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1. Lever WE Histopathology of the skin. 7th ed.,
p. 116-31 2. Sapp JP Contemporary Oral
Maxillofacial Pathology, p. 254-60 3. Kaohsiung
Medical University, Oral Pathology Department 4.
http//byebyedoctor.com/bullous-pemphigoid 5.
Bagan J et al Mucous membrane pemphigoid. Oral
Dis 200511197-218 6. Black M et al Pemphigus
vulgaris. Oral Dis 200511119-30 7. Ruocco R et
al Life-threatening bullous dermatoses
Pemphigus vulgaris. Clin Dermatol
200523223-6 8. Robinson RA et al Desquamative
gingivitis A sign of mucocutaneous disorders a
review. Aus Dent J 200348206-11 9.
Tilakaratne WM et al. Paraneoplastic pemphigus a
case report and review of literature. Oral Dis
200511326-9 10. www.umm.edu/imagepages/17280.h
tm 11. Williams DM. Vesiculobullous mucocutaneous
disease pemphigus vulgaris. J Oral Pathol Med
198918544-53 12. www.ispub.com/ostia/ijd/vol2
n1/bullous.xml 13. www.dermnet.org.nz/immune/linea
r-iga.html 14. www.immcodiagnostics.com/Products/v
b.php 15. www.pemphigus.org/content/view/24/38/lan
g,en/ 16. Dent Clin N Am 200549107-125 17.
http//jpkc.fimmu.com/pfb/all/photo15.htm 18.
http//www.twword.com/wiki/ 19. High Yield
Dermatopathology20. dermpedia.org
4
?????????

• ?? blister(?), bullous(?)?????
  (intraepithelial)???? (subepithelial)???????,?????
  ??????????????

??
??
Ref. 3
5
?????????

• 1.????? (spongiosis)
• 2.???? (acantholysis)
• 3.???? (cytolysis)
• 4.???? (reticular degeneration)
• 5.???????? (basement
• membrane zone destruction)

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1. ????? (spongiosis)

• ???????? (intercellular edema),????????????,??????
  (keratinocyte) ??,????(desmosome) ??,?????

en.wikipedia.org/wiki/Spongiosis
visualphotos.com
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2. ???? (acantholysis)

• ??????????????
• ???????,?????

,????,?????,?????
Refs. 1, 11
8
2. ???? (acantholysis)
Primary Pemphigus Dariers disease Transient
acantholytic dermatosis Warty (?) dyskeratoma
Secondary Impetigo (???) Viral infections Carcinom
a
Ref. 6
9
3. ???? (cytolysis)

• ???????????????????? (??????) ???????? (?????)?

Ref. 2
10
3. ???? (cytolysis)
Ref. 3
11
4. ???? (reticular degeneration)

• ????? (intracellular edema),??
• ????? (ballooning degeneration) ?
• ???????????,
• ???????????
• ??????????
• ??,??????
• ?????

Ref. 11
12
5????????? (basement membrane zone destruction)

• ???????? ???????,???? (lamina lucida),????
  (lamina densa),??????IV???????,??????(sublamina
  dense zone) ?

Ref. 2
13
? ? ? (Pemphigus)

• ????????????????,???????,??????
• ?????? ??????????(acantholysis)?
• ?????,???
• ??70???
• ???????
• 40?60???,
• ?????????

Ref. 3
14
? ? ? (Pemphigus)
Ref. 5
15
1.?????? (pemphigus vulgaris)
???????? (indirect immunofluorescent, IF)
?????????? (DIF)
Ref. 16
16
? ? ? (Pemphigus)

• ? ?
• (1) ?????? (pemphigus vulgaris)
• /?????? (pemphigus vegetans)
• (2) ????? (pemphieus foliaceus)
• /??????(pemphigus erythematosus)
• (3) ??????? (drug-induced pemphigus)
• (4) IgA??? (IgA-pemphigus)
• (5) ?????? (paraneoplastic pemphigus)

17
1.?????? (pemphigus vulgaris)

• ???? ????????????
• ??????????,??????????????
• ????????,??????
• Nikolskys sign ???????????????????????

Nikolskys Sign skin reddens, fluid collects
underneath, skin rubs off, leaving raw red base
Refs. 2, 10
18
1. ?????? (pemphigus vulgaris)

• Beutner Jordon(1964)????????IgG???????????,?????
  ??????,??????????????(autoimmune)?
• ???????? (indirect immunofluorescent staining,
  IF),?????????
• ?????????? (DIF),???????????????????????????????Ig
  G???C3 ?

Steric hindrance
Refs. 2, 6
19
1. ??????(pemphigus vulgaris)

• ????? 130 kDa ???????????????????????????,?????
  50,68?210 kDa??

????? ??????? (anti-intercellular substance
antibody)?IgG???
Ref. 2
20
1. ??????(pemphigus vulgaris)

• ???? ????,???????,???,???????????????????????????
  ??,???????,??????????????????????,??????
• IgG????????,?????????????

21
1. ?????? (pemphigus vulgaris)

• ????(titer)????????????,?????????????,????????????
  ??
• ???? ?????????,???????,???????,??????????,?????
• ????????,
• ??????????
• ??????,???
• ??????????

???
?????
Ref. 6
22
1. ?????? (pemphigus vulgaris)
Ref. 19
23
1. ??????(pemphigus vulgaris)
Refs. 6, 19
24
1. ??????(pemphigus vulgaris)
Ref. 7
25
1. ??????(pemphigus vulgaris)

• ????????,1969????????methotrexate?azathioprine?cyc
  lophosphamide???????
• ?????????,??????,?????????????????
• Penney(1973)?????,?????
• ?1978?1979??????????,??????????????????

26
1. ??????(pemphigus vulgaris)

• ?? ?????????????????????
• ????????????,?????????????????????????????????,???
  ???????????,??????????????

27
1. ??????(pemphigus vulgaris)

• Painful oral ulcer
• Blister at the most basal layer of the epidermis,
  loss of cell-cell adhesion with maintenance of
  attachment to BM
• DIF IgG, C3 on the keratinocyte, Ab to desmoglein

28
1. ??????(pemphigus vegetans)

• ??????????? (variant) (5)?
• ?? ???????????????????
• Neumann?Hallopeau
• ???
• ???????, ???????????
• ?,????????,???????
• ?????????????,?????

Ref. 1
29
1. ??????(pemphigus vegetans)

• ???????????????????
• ???????,???????????,???????

Ref. 17
30
1. ??????(pemphigus vegetans)

• ???? ????????????????????????????

Ref. 19
31
1. ??????(pemphigus vegetans)
Ref. 3
32
1. ??????(pemphigus vegetans)

• ???????? ??????IgG?C3????????
• ?? ?????????,????????,????

Ref. 1
33
2. ?????(pemphigus foliaceus)

• ??????????,?????????????,????????
• Nikolskys sign ??,?????????????????????
• ?? ??????160 kD???????,???????????,??????????????
  ????
• ?? ???????,???????????????

Refs. 18, 19
34
2. ????? (pemphigus foliaceus)

• ???? (a) ?????????,(b) ????????????????,(c)
  ????????????????????
• ?? ???????????, ????????????

Ref. 1
35
2. ????? (pemphigus foliaceus)
????????
Ref. 19
36
2. ????? (pemphigus foliaceus)
????????
Ref. 3
37
2. ????? (pemphigus foliaceus)

• Subcorneal blister on head neck
• Seldom involve mucosal surface
• Ab to desmoglein
• DIF IgG fishnet pattern

On the face, scalp upper trunk, lesions are
often scaly crusty on a red inflamed base.
Burning sensation or localized pain may be felt
Ref. 13
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2. ?????? (pemphigus erythematosus)

• ???,????????? (variant),?????????78?
• Dr. Senear?Usher(1962)??????,??Senear-Usher
  syndrome?
• ?? ????????????????
• ??????,????1585???

39
2. ??????(pemphigus erythematosus)

• ?? ????????????????????????,?????????????
• ???? ?????????????,???????????

Ref. 1
40
2. ??????(pemphigus erythematosus)

• ???? ???????,??????,????????,?????????

• ????
• (a)???????????????????????????(b)??????????
  ????????????(c)?????? ???????

Ref. 1
41
2. ?????? (pemphigus erythematosus)

• ????? ??????????????????lgG??,IgM????????????????
  ????????????????????

????????
????????
Ref. 1
42
2. ?????? (pemphigus erythematosus)

• ???? ??????????,?????????????????
• ?? ??????????????????,?????(?????????????)?

Ref. 1
43
2. ?????? (pemphigus erythematosus)

• Well-circumscribed lesions on malar (?) area
• DIF IgG,C3 in both BM intercelluar
• 30 positive ANA associated with other
  autoimmune diseases

44
3. ??????? (drug-induced pemphigus)

• ???????????,???
• 1. penicillamin ?2. capatopril?
• penicillamine??sulhydryl (SH) group
  ????????????,???????

Ref. 1
45
3. ??????? (drug-induced pemphigus)

• ???????DIF?90???????
• ???????? ??????????70 IgG???
• ???? ???????
• ,????????????????????,??????????????????

Ref. 20
46
4. IgA??? (lgA-pemphigus)

• ???? ??????????
• ?? ????????,?????????????,???????

String of beads sign
Ref. 13
47
4. IgA??? (lgA-pemphigus)

• ??????
• ????
• (a) ??????????????
• (b) ??????????

Ref. 3
48
4. IgA??? (lgA-pemphigus)
Refs. 3, 19
49
4. IgA??? (lgA-pemphigus)

• ??????DIF
• ????????IgA? ??

????????
No deposition of IgG
Linear deposition of IgA
Ref. 13
50
5. ?????? (Paraneoplastic pemphigus)

• ??
• ?????,
• ????,??????????????????

Refs. 2, 14, 19
51
5. ?????? (Paraneoplastic pemphigus)

• ??????? ???????????????,??????????????????,??????
  ??
• ?? ????,????????

52
5. ?????? (Paraneoplastic pemphigus)

• ????
• (a) ??????????????????
• (b) ???????
• ??????
• ????????
• ???

a
???
???????
b
Ref. 1
53
5. ?????? (Paraneoplastic pemphigus)
Ref. 19
54
5. ?????? (Paraneoplastic pemphigus)

• ??????DIF
• (a) ???????IgG?????
• (b) ?????????????????,???IgG ?
• (c) ???????,?lgG?IgM?

a
b
c
Ref. 2
55
5. ?????? (Paraneoplastic pemphigus)

• Five diagnostic criteria
• 1. Painful mucosal ulcerations blisters a
  polymorphous skin eruption, with papular lesions
  progressing to blisters and erosive lesions
  affecting the trunk, extremities, palms, and
  soles, in the context of an occult or confirmed
  underlying neoplasm.
• 2. Histologic findings of vacuolar interface
  change, keratinocyte necrosis, intraepidermal
  acantholysis.
• 3. Deposition of IgG C3 in epidermal
  intercellular spaces, granular-linear
  complement deposition along epidermal basement
  membrane zone on direct immunofluorescence

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5. ?????? (Paraneoplastic pemphigus)

• Five diagnostic criteria (continue)
• 4. Serum autoantibodies that bind not only to
  cell surfaces of skin mucosa in a pattern
  typical of pemphigus, but also to simple,
  columnar, and transitional epithelia.
• 5. Serum autoantibodies that recognize
  epidermal antigens of 250, 230, 210, 190 kD by
  immunochemical techniques such as
  immunoprecipitation.

57
5. ?????? (Paraneoplastic pemphigus)

• Neoplasia-induced pemphigus
• Major criteria
• 1. Polymorphous mucocutaneous
• eruption
• 2. Concurrent internal neoplasia
• 3. Characteristic serum
• immunoprecipitation findings

58
5. ?????? (Paraneoplastic pemphigus)

• Minor criteria
• 1. Positive cytoplasmic staining of rat
  bladder
• epithelium by indirect immunofluorescence
  
• 2. Intercellular and basement membrane zone
• immunoreactants on direct
• immunofluorescence of perilesional tissue
  
• 3. Acantholysis in biopsy specimen from at
• least one anatomic site of involvement
• Patients have neoplasia-induced pemphigus all 3
  major or 2 major ?2 minor criteria

59
5. ?????? (Paraneoplastic pemphigus)

• Occurs exclusively in the neoplasm
• Complex set of autoAb to one or more proteins
  that play key roles in cell-cell adhesion
• Significant variability in histologic features
• IF intercelluar staining

Ref. 9
60
? ? ? (Pemphigus)
Variants Antigens location Main antigens Antibody class Oral lesions
Pemphigus vulgaris Desmosomes Dsg3 IgG Common
Pemphigus foliaceus Desmosomes Dsg3 IgG Uncommon
Drug-induced pemphigus Desmosomes Dsg1 IgG Common
IgA pemphigus Desmosomes Dsg3 Desmocollin 1 Desmocollin 2 IgA Uncommon
Paraneoplastic pemphigus Desmosomes or hemidemosomes Dsg3 Desmocollin 1Desmocollin 2 BP230 Periplakin IgG or IgA Common
Ref. 6
61
? ? ? (Pemphigus)
Ref. 6
62
???? (Pemphigoid)

• Two major forms of pemphigoid
• 1. Mucous Membrane Pemphigoid/Cictricial
  Pemphigoid (MMP/CP)
• 2. Bullous Pemphigoid (BP)The type of pemphigoid
  depends on which autoantibodies are produced,
  in which layer of skin blister occurs

Ref. 15
63
???????? (Benign mucous membrane pemphigoid)

• ?????????(1/3 of patients)/??????(3/4 of
  patients),????????
• Intense erythema with erosion, features of
  desquamative gingivitis (most common)

Severe conjunctivitis. corneal scarring is
evident and keratotic scar is present lateral to
iris (2/3 of patients )
Refs. 5, 8, 19
64
???????? (Benign mucous membrane pemphigoid)
Ref. 5
65
???????? (Benign mucous membrane pemphigoid)
Ref. 19
66
???????? (Benign mucous membrane pemphigoid)
Strong linear C3 deposition along the
dermalepidermal junction
Ref. 19
67
???????? (Benign mucous membrane pemphigoid)
Principal treatment modalities Principal treatment modalities
Topical corticosteroids Beclomethasone dipropionate Betamethasone valerate Clobetasol propionate Fluocinonide
Systemic corticosteroids Prednisone
Other immunosuppressives Azathioprine Cyclophosphamide Cyclosporine Methotrexate Thalidomide Mycophenolate mofetil Leflunomide Mitomycin C Etanercept
Dapsone
Sulphonamides Sulfapyridine Sulfamethoxypyridazine Sulfasalazine
Tetracyclines Tetracycline Doxycycline Minocycline
Intravenous immunoglobulin therapyPlasmapheresis
68
???????? (Benign mucous membrane pemphigoid)
Extensive moderately severe
Localized
Ref. 5
69
??????? (Bullous pemphigoid)

• Lever(1953) ???????(pemphigus),??????????(pemphig
  us vulgaris)?????,?????????????
• ????
• ???????,????60???,????????
• ?????????????

70
??????? (Bullous pemphigoid)

• ?????? ??????(epidermal basement membrane
  zone)?C3?IgG????
• ??????????,???????????????

Refs. 2, 3
71
??????? (Bullous pemphigoid)

• ????????
• ????? ??????????????(lamina
  densa)??????(lamina lucida),????(anchoring
  filament)??????
• (hemidesmosome)????
• ??????????
• ???????

Ref. 2
72
??????? (Bullous pemphigoid)

• ?????
• (a) ?????? ?????????????(C3?IgG).?????IgD?IgE?
  ?IgA?IgG?????????
• (b) ??????
• 70-80??????
• ??????????
• ?????IgG,
• ????????
• ??? ???

IgG
Collagen type IV
C3
Ref. 2
73
??????? (Bullous pemphigoid)

• ?????
• (a) ?????????????????,???????????????(mast
  cell)??????
• (b) ????????????????????
• (c) ??????????????????????????

Ref. 11
74
??????? (Bullous pemphigoid)

• ????
• (a) ???? ??????
• ,????????????
• ???,????,???
• ?????
• (b) ?????????,?
• ???????????,??????,?????,?????

Refs. 4, 12
75
??????? (Bullous pemphigoid)

• (c) ?? ?????,???????????????????????????,????
  ??? ???????,???????
• (d) ???? 10-35???,
• ??????,??????
• ,??????,?????
• ,???????,????
• ????
• (e) ?????????
• ????? ???????,
• ???????????

Ref. 3
76
??????? (Bullous pemphigoid)

• ????
• (a) ??????,???????,???????????????????????psora
  len?????????
• ?????
• (a) ?????????IgE??,??? lgG??????,????????
• (b) ????????????????,???lgG??????

77
??????? (Bullous pemphigoid)

• ????
• (a) ???????????,??lichen planus
  pemphigoides????????????????????????????????T?????
  ?????,??????????????
• (b) ?????????
• ???????????
• (?????)?????
• (c) ?????????
• ???????????

T?????
Ref. 2
78
??????? (Lichen planus pemphigoid)
Ref. 3
79
??????? (Bullous pemphigoid)

• ???
• (a) ????????????????????
• (b) ?????,?????,?????,??????????????????,??????
  ?,???????????

Refs. 2, 19
80
??????? (Bullous pemphigoid)

• (c) ??????????,?????????(microabscess),????????
  ???????????????????????
• (d)
  ???????
• 
  ??????????

Refs. 2, 3
81
??????? (Bullous pemphigoid)
Ref. 19
82
??????? (Bullous pemphigoid)

• ?????
• (a) ??????????,??????????
• (b) ?????????????30????,?8????15?????(3-38???)?
  ????,??????8???(??65?)??????,???65??16????????????
  ??,?????????????

83
??????? (Bullous pemphigoid)

• (c) ?????????,?2???6??????,???????10????
• (d) ??????????azathioprine??,??????????????????
  ??????????????
• (e) ???????????????????
• (f) ?????????????

84
??????? (Bullous pemphigoid)

• (g) ???????????? ??????????????,???????
• ??????
• 1. ??????????????
• 2. ??????????????????,?azathioprine
  (????cyclophosphamide)?????????????????

85
??????? (Bullous pemphigoid)

• (h) ?????????????????????????????
• (i) Sulfone??????????????dapsone?sulfayridin???
  15-44????
• (j) ???????????tetracycline?niacinamide,chloram
  bucil??????(plasmapheresis)?

86
SUMMARY