Bullous pemphigoid

58

Clinical practice guideline

for Bullous pemphigoid
$%$&'( ' )(*&
$%$&( +& ,-('
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%$&./(- $ 5)06)7(8$&
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($:
Bullous pemphigoid (BP)  !"#$%!&'( )$*+ ,-./( ,0!1/2%!30'! %*4)
"5!2 6- &'$.2786-49+2! 2 :*.2)$*+ #8*3221'; ,  $ *9.9+%4* #:<%678* 
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;1
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Bullous pemphigoid &'%*4)"?#6&'&2 6- **#. 60 B 2%, * *++6<7&'6 6 -7
,.2 1 7 ,.2B +62%, * *+'F0/ 300 . )"&'&2 6- **#. 90 B 1'2&64&64
*%4"&'2 6-26*#. 60 B 49+26 *)+I* 4)JK 6 **#. J$L! ) caucasian 4
# 5%%PQ*%4* *+*%4 HLA DQ B 0301 78)L&'-?4# 5%%PQ*%4 HLA DRB 104 DRB
11101 DQ B 10302 : ** J0*= )8J964#. "?#62 6-<7&'6 69.3 B K 6,.2$L! 2.7:1 78&
# 5%%PQ*%44 $# 78 !84485 5!*#. 8K *%'#926. !&%65( %L !5>,1
)<.80
"?#6 bullous pemphigoid *124-* 6& autoantibody ,.2 BP 180 antigen 78 BP 230 antigen
K1'2#. *+: * autoreactive T- cell &',2452!,.2* *8,-: * BP 180 78 BP 230 antigen *8,-)$
B cell 5 ! antibody F0/
$7%!: *&' autoantibody :%4*%4 target antigens &' dermo-epidermal junction :8*+*84#* 
,. !;,  K. * *8,-844 complement * $7%'! chemoattractants ( )$& neutrophils 78
59

eosinophils 'F0/ &* 7.26 proteolytic enzymes #%/!* 4*#* 5 ! hemidesmosome
*84#* +%!*7. #.#*%4 proinflammatory cytokines $7 6K+( )$*+* 6*K%/8$#. ! epidermis
*%4 dermis *+ subepidermal blister F0/
 (('= $
1. - ;- )
((
"?#6:8&2 * % 78&"1'5&+! 4#7 6"1'7= ,.2 :8*+ ,-./( )5,0!F0/4"1'+!
$124"#*, ,( $.!&'44.26 12 $ 2! ,F 78,F+ ) 426&'61'24-9+8 g
2678 30 $7%!: *,-./( ,* "7>72*5.#)$L.:8$ 69++69.*+"7 ,.2 :4267/( 9+
2.  8 '.5-AB(1 8(
2.1  4 TzanckFs smear +#6* : 8,-./( F+&'h F2!,-./( 4 ; i 67!4597+Q 7#(
597+Q962 Wrightks stain $12 Giemsa stain :84 eosinophils +. +69.4 acantholytic cells
2.2  8
3(G<HG-8 '%$*(($ #,%+K/1/2: *26&',-./( 30'!*+F0/)$.; :8
46 P5  subepidermal separation 78 mixed dermal inflammatory infiltration 30'!%*:84
eosinophils :( # *
2.3  8 ' 8'-(::%$*(($
2.3.1 * J0*= Direct Immunofluorescence (DIF)+6)K"#$%!4#gF24F2!26
)$. ; (perilesional skin) :84 C3 78/$12 IgG * 8&' basement membrane )44&' linear
pattern
2.3.2 * J0*= Indirect Immunofluorescence (IIF)+6)K clotted blood rs6*2 serum
5.!,#: :84 circulating IgG :%4*%4 basement membrane F2! squamous epithelial substrate ()K"#$%!
*,$12$72+2 $ F2!7!) )44 linear pattern #P&* ,#:+%!*7. #)$"74#*8 g2678
70-80 F2!"?#6 788+%4F2! antibody 9."%, *%42 * F2!"?#6 :0!9.5  >)KK.#6)* 
,+, * %*= 9+
2.3.3 * J0*= Salt-split immnofluorescence ( +6( K/1/2 9 incubate *%4 1 M NaCl &'
0
4 C *.21'2)$ epidermis 6*22*: * dermis &',( $.! lamina lucida 30'!( 9+%/! direct 78 indirect
technique 1'2)K)* 6*)*7-. bullous systemic lupus erythematosus 78 epidermolysis bullosa
acquisita 22*9
2.3.4 * ,#: BP180 autoantibody titer +#6#P& ELISA 1'2$ antibodies ,.2 NC-16A
domain F2! BP180 $12 extracellular domain F2! BP180 %/!$+ 8+%4F2! antibody &'#%+9+%*:8
"%, # -!F2! 785  >)KK.#6)* ,+, * %*= " ?#69+

60

 
 11A ; 1A ;- ( +684"7+#6 burow's solution $12/( *712#%78 2 %/!
 <=%;2-4
1. $)<8- -$
& * )K6  5,226+Q &'&{P|! (Level of evidence 1, Strength of
recommendations A) #%78 2 %/! : g )K6 $7%*)"?#6&'"1'< 8&'$12# -!26
>0! *7 ! (&,-./( F0/)$.26*#. 10 ,-.,.2#%) $122 :)K* %*= .#*%4* %*= 21'
2. $ 1A ;
2.1 6 5,226+Q (Level of evidence 1, Strength of recommendations A) )K)"?#6&'&# 
-! *7 !>0! * (&,-./( )$. **#. 10 ,-.,.2#%) K. prednisolone )F + 0.5 -0.75 *./**./
#%
2.2 6 K&#8K+ tetracyclines F +6 500 2,000 *./#% (Level of evidence 2,
Strength of recommendations B) : g )K)"?#6&'"1'< 8&'$12# -!26>0! *7 !
$122 :)K.#*%46 nicotinamide )F + 500 2,500 */#% * )K minocycline $12 doxycycline
 tetracycline 6%!9.&* #:%6&'+&5%45-
2.3 6 *+-*%
2.3.1 Azathioprine (Level of evidence 2, Strength of recommendations B)
* )K6 azathioprine F + 2-3 *./**./#% .#*%46 %48 5,226+Q)K* 
%*= 2%+%42!
1'2%*= +#66 %48 5,226+Q26. !+&6#9.9+"7
$12&"7F !&6!: *
6 5,226+Q : ** J0*= 4#. 9+"7,*,. !: * * )$6 %48 5,226+Q26. !+&6#&6!7I*26
+64#. &"7F !&6! **#. :0!#: g )K)"?#6&'&2 * -!4 ! 6. %/
2.3.2 Methotrexate (Level of evidence 3, Strength of recommendations C)
6 methotrexate F + 2.5-17.5 *./5%+ $Q )K* %*= 2%+%42! 2 :)K6 ,%#
+&6#$12.#*%46 %48 5,226+Q*9I +5
2.3.3 Cyclophosphamide (Level of evidence 4, Strength of recommendations C)
K+%48  * )$6 %48  1-2 *./**./#% 9.4#. & steroid sparing effect
,.*7%44#. & drug-related mortality 78 morbidity "7F !&6!&'#8#%! 12 * *+9F*8+*78
*8 8r55 #82%*54 (hemorrhagic cystitis) )"?#64 ! 6&'&2 * -!2 :)K* <&+F  !5
712+6
2.3.4 Mycophenolate mofetil (Level of evidence 2, Strength of recommendations B)
F +6 0.5-1 *% #%78 2 %/! 2 :)K6 +&6# $12.#*%46 %48 5,226+Q

61

2.3.5 Cyclosporine (Level of evidence 4, Strength of recommendations C)

F +6
2.5-5 *./**./#% 5.#)$L.%*:8,2452!) 6&'%*= .#*%46
%48 5,226+Q
2.3.6 Chlorambucil (Level of evidence 3, Strength of recommendations C)
F +6 Chlorambucil 0.1-0.15 *./**./#% +6)$.#*%46 Prednisolone 40-60 *./#%
"7F !&6!&'#8#%! 12 * *+9F*8+*
2.4 6 21'; &'& 6! #. 9+"72 :)K6 K++&6#)* %*= "?#6&'&# -!26
>0! *7 ! * ,2452!:8K *#. 6 )*7-.5,226+Q 2-3 5%+ $Q $122 :)K6 %*= .#*%46
 5,226+Q )*g&&'"?#69+%46 %48 5,226+Q $126 azathioprine 7#9.9+"72 :
: g '6 )*7-.&/ (Level of evidence 4, Strength of recommendations C)
2.4.1 Dapsone (Level of evidence 3, Strength of recommendations C)
)F +* %*= 50-200 *./#%7-8
2.4.2 Sulfonamides (Level of evidence 3, Strength of recommendations C)
sulfapyridine $12 sulfmethoxypyridazine F + 1-1.5 *./#% 2 :)K6 K++&6#)
* %*= "?#6&'&# -!26>0! *7 ! #8#%!* )K6 &/)"?#65!2 6- 78$ )K)"?#6
Glucose-6 phosphate dehydrogenase (G6PD) deficiency
3.
 (*K-HLM KL:K. N-5-( 2 :: g )K6 $7. &/ )*g&&'* %*= #P&21';
7$7# $12&F2$ : ** )K6 F !,
3.1 Intravenous immunoglobulin (IVIG) (Level of evidence 3, Strength of recommendations
C)F +6 0.4 *./**./#% )$,.21'2!*%#7 5 #% 2 :* %* = ,%#+&6 # $12)K.#*% 4
6 5,226+Q "?#62 :,2!9+%4* %*= 2-4 cycles -*; 3-4 5%+ $Q
3.2 Plasmapheresis (Plasma exchange) (Level of evidence 2, Strength of recommendations B)
: g )K.#*%46 5,226+Q ) 6&'-! *$12+1/2,.2* %*= * %*= +#6#P&
&/ &# 6-.!6 * 3%432 )K#7     ! 9+"7K%'# # 78,2!8#%!"7F !&6!
 8(
8: 
1'2!: * bullous pemphigoid 1/2%! :0!#,+, * +( F2! : ** J0*=
)8J964#. "?#6&'9+%4* %*= 5  >$6-+6 9+ (remission) 2678 66  6)#7 3 B1 )
8$#. !* %*= #i 8#%!78,+, "7F !&6!&'2 :*+: ** %*= 78*32

62

O
P5AQ$   Bullous Pemphigoid

63

<-) -5-(
1. Kulthanan K, Chularojanamontri L, Tuchinda P, Sirikudta W, Pinkaew S. Prevalence and Clinical
features of Thai patients with bullous pemphigoid. Asian Pac J Allergy Immunol 2011; 29: 66-72.
2. Mutasim DF. Management of autoimmune bullous diseases: pharmacology and therapeutics. J Am
Acad Dermatol 2004; 51: 859-77.
3. Wojnarowska F, Kirtschig G, Highet AS, Venning VA, Khumalo NP. Guidelines for the
management of bullous pemphigoid. Br J Dermatol 2002 147: 214-21.
4. Kirtschig G, Middleton P, Bennett C, Murrell DF, Wojnarowska F, Khumalo NP. Interventions for
bullous pemphigoid. Cochrane Database Syst Rev 2010 Oct6; (10): CD 002292.
5. Heilborn JD, Stahle-Backdahl M, Albertioni F, Vassilaki I, Peterson C, Stephansson E. Low- dose
oral pulse methotrexate as monotherapy in elderly patients with bullous pemphigoid. J Am Acad
Dermatol 1999; 40:741-9.
6. Itoh T, Hosokawa H, Shirai Y, Horio T. Successful treatment of bullous pemphigoid with pulsed
intravenous cyclophosphamide. Br J Dermatol 1996; 134: 931-3.
7. Venning VA, Millard PR, Wojnarowska F. Dapsone as first line therapy for bullous pemphigoid. Br
J Dermatol 1989; 120: 83-92.
8. Bouscarat F, Chosidow O, Picard-Dahan C, et al. Treatment of bullous pemphigoid with dapsone:
retrospective study of thirty-six cases. J Am Acad Dermatol 1996; 34: 683-4.
9. Joly P, Roujeau JC, Benichou J, Picard C, Dreno B, Delaporte E, et al. A comparison of oral and
topical corticosteroids in patients with bullous pemphigoid. N Engl J Med 2002; 346: 321-7.
10. Fiverson P, Breneman L, Rosen B, Hersh S, Cardone S, Mutasim D. Nicotinamide and tetracycline
therapy of bullous pemphigoid. Arch Dermatol 1994; 130: 753-8.
11. Morel P, Guillaume JC. Treatment of bullous pemphigoid with prednisolone only: 0.75 mg/kg/day
versus 1.25 mg/kg/day. A multicenter randomized study. Ann Dermatol Venereol 1984; 111: 925-8.
12. Dreno B, Sassolas B, Lacour P, Montpoint S, Lota I, Giordano F, et al. Methylprednisolone versus
prednisolone methylsulfobenzoate in pemphigoid: a comparative multicenter study. Ann Dermatol
Venereol 1993; 120: 518-21.
13. Piamphongsan T. Dapsone for the treatment of bullous pemphigoid. Asain Pac J Allergy Immunol
1983; 1: 19-21.
14. Burton JL, Harman RR, Peachey RD, Warin RP. Azathioprine plus prednisone in treatment of
pemphigoid. Br Med J 1978; 2:1190-1.

64

15. Guillaume JC, Vaillant L, Bernard P, Picard C, Prost C, Labeille B, et al. Controlled trial of
azathioprine and plasma exchange in addition to prednisolone in the treatment of bullous
pemphigoid. Arch Dermatol 1993; 129: 49-53.
16. Roujeau JC, Guillaume JC, Morel P, et al. Plasma exchange in bullous pemphigoid Lancet. 1984; 2:
486-8.
17. Hofmann S, Thoma-Uszynski S, Hunziker T, et al. Severity and phenotype of bullous pemphigoid
relate to antibody profile against the NH2- and COOH-terminal regions of the BP180 ectodomain. J
Invest Dermatol 2002; 119: 1065-73.
18. Tsuji-Abe Y, Akiyama M, Yamanaka Y, Kikuchi T, Sato-Matsumura KC, Shimizu H. Correlation of
clinical severity and ELISA indices for the NC16A domain of BP180 measured using BP180 ELISA
kit in bullous pemphigoid. J Dermatol Sci 2005; 37: 145-9.
19. Schmidt E, Obe K, Brocker EB, Zillikens D. Serum levels of autoantibodies to BP180 correlate with
disease activity in patients with bullous pemphigoid. Arch Dermatol 2000; 136: 174-8.

65

Drug

Level of evidence

Strength of recommendation

Topical steroid (Clobetasol propionate)

Systemic steroid 3,4

Immunosuppressants Azathioprine 8,9

Tetracyclines nicotinamide

Dapsone / Sulfonamides 5-7

IVIG

Plasmapheresis

Methotrexate 10

Cyclophosphamide

Mycophenolate mofetil

Cyclosporine

Chlorumbucil

66