,

Allergy: 2006: 61: 969-987

The Journal of Allergy and Clinical Immunology: 2006: 118: 1: 152-169

the touch of uniqueness

 2006 ,

DOI: 10.1111/j. 1398-9995.2006.01153.x

Allergy 2006: 61: 969-987

, ,
:

,
/

. 7 ,

/PRACTALL:

C. A. Akdis , M. Akdis , T. Bieber ,

C. Bindslev-Jensen , M. Boguniewicz ,
P. Eigenmann , Q. Hamid , A. Kapp ,

D. Y.
M. Leung
, J. Lipozencic
,
T. A.
Luger , A. Muraro , N.
Novak
,

.
. ,
T.A.E.
Platts-Mills
, L. Rosenwasser

,
A. Scheynius , F. E. R. Simons ,

. 10
J. Spergel , K. Turjanmaa ,
,
U. Wahn , S. Weidinger , T. Werfel ,
,
T. Zuberbier for the European
Academy of Allergology and Clinical
Immunology/American Academy of
, . .
Allergy, Asthma and Immunology/
PRACTALL Consensus Group*
1

4,5

10

11

12

13

14

15

16

17

18

19

17

, -

,
The Swiss Institute of Allergy and Asthma Research, Davos,
, PRACTALL.
Switzerland; The University
of Bonn, Bonn, Germany;

/ The Odense University Hospital, Odense, Denmark; The

National Jewish Medical and
Research
Center, Denver,
CO, USA; The University of Colorado School of Medicine,

Denver, CO, USA; The University
Childrens Hospital Geneva, Geneva, Switzerland; The McGill University,

. 10-11
Montreal, QC, Canada; The
Hannover Medical
University,
1

Hannover, Germany; 9The Zagreb Hospital Center and

School of Medicine University of Zagreb, Zagreb, Croatia;
10
The Munster University, Munster, Germany; 11The
University of Padua, Padua, Italy; 12The Asthma and
Allergic Diseases Center, Charlottesville, VA, USA; 13The
Karolinska University Hospital Solna, Stockholm, Sweden;
14
The University of Manitoba, MB, Canada; 15The Childrens
Hospital of Philadelphia and the University of Pennsylvania
School of Medicine, USA; 16The Tampere University
Hospital, Finland; 17The Charite University of Berlin, Berlin,
Germany; 18The Technical University Munich, Munich, Italy;
19
The Hannover Medical School, Hannover, Germany.

: , (atopic dermatitis). APT,

(atopy patch test). CyA, A (cyclosporine A). DC: (dendritic cell). IDEC, (inflammatory
dendritic epidermal cell). LC, langerhans (langerhans cell). MnSOD,
(manganese superoxide dismutase). pDC, (plasmacytoid dendritic cell). SPT,
(skin prick test). TCI, (topical calcineurin
inhibitors). TReg, T (T regulatory).

. ,
,

,
: atopic dermatitis;
children;
adults; risk
factors; immunopathology; diagnosis; systemic treatment;

topical treatment.
EAACI/AAAAI/PRACTALL Consensus Group . 12* Ulrich
Wahn.
Ulrich Wahn, MD
Charite-Universitatsmedizin Berlin
Augustenburger Platz 1
D-13353 Berlin
Germany
31 2006.

PRACTALL ,
. Novartis.
The Journal of Allergy and Clinical Immunology Allergy

 2006 ,

DOI: 10.1111/j. 1398-9995.2006.01153.x

Allergy 2006: 61: 969-987

:
/ ,
/PRACTALL:
C. A. Akdis , M. Akdis , T. Bieber ,
C. Bindslev-Jensen , M. Boguniewicz ,
P. Eigenmann , Q. Hamid , A. Kapp ,
D. Y. M. Leung , J. Lipozencic ,
T. A. Luger , A. Muraro , N. Novak ,
T.A.E. Platts-Mills , L. Rosenwasser ,
A. Scheynius , F. E. R. Simons ,
J. Spergel , K. Turjanmaa ,
U. Wahn , S. Weidinger , T. Werfel ,
T. Zuberbier for the European
Academy of Allergology and Clinical
Immunology/American Academy of
Allergy, Asthma and Immunology/
PRACTALL Consensus Group*
1

4,5

10

11

12

13

14

15

. ,
-

16

17

18

19

17

The Swiss Institute of Allergy and Asthma Research, Davos,

Switzerland; 2The University of Bonn, Bonn, Germany;
3
The Odense University Hospital, Odense, Denmark; 4The
National Jewish Medical and Research Center, Denver,
CO, USA; 5The University of Colorado School of Medicine,
Denver, CO, USA; 6The University Childrens Hospital
Geneva, Geneva, Switzerland; 7The McGill University,
Montreal, QC, Canada; 8The Hannover Medical University,
Hannover, Germany; 9The Zagreb Hospital Center and
School of Medicine University of Zagreb, Zagreb, Croatia;
10
The Munster University, Munster, Germany; 11The
University of Padua, Padua, Italy; 12The Asthma and
Allergic Diseases Center, Charlottesville, VA, USA; 13The
Karolinska University Hospital Solna, Stockholm, Sweden;
14
The University of Manitoba, MB, Canada; 15The Childrens
Hospital of Philadelphia and the University of Pennsylvania
School of Medicine, USA; 16The Tampere University
Hospital, Finland; 17The Charite University of Berlin, Berlin,
Germany; 18The Technical University Munich, Munich, Italy;
19
The Hannover Medical School, Hannover, Germany.
1

: atopic dermatitis; children; adults; risk

factors; immunopathology; diagnosis; systemic treatment;
topical treatment.
Ulrich Wahn, MD
Charite-Universitatsmedizin Berlin
Augustenburger Platz 1
D-13353 Berlin
Germany
31 2006.

,

,
, . . ,
, PRACTALL.

: , (atopic dermatitis). APT,

(atopy patch test). CyA, A (cyclosporine A). DC: (dendritic cell). IDEC, (inflammatory
dendritic epidermal cell). LC, langerhans (langerhans cell). MnSOD,
(manganese superoxide dismutase). pDC, (plasmacytoid dendritic cell). SPT,
(skin prick test). TCI, (topical calcineurin
inhibitors). TReg, T (T regulatory).

* EAACI/AAAAI/PRACTALL Consensus Group Ulrich Wahn.

PRACTALL ,
. Novartis.
The Journal of Allergy and Clinical Immunology Allergy

Akdis et al.

()
,
.
11 ,

(Global International Study of Asthma and Allergies in Childhood
trial), 1% 20%,
1.
45% 6 , 60%
85%
5 2. 2 , 20%
17%
7 ( 1)3. , 16,8%
4,5.
.
, ,
. 2 .

, , ,
.
. , ,
, , .
,

.

, , .

1-2

100%

37%

34%

31%

36%

37%

1.
, Multicenter Atopy Study
( )3.

2 :
,
,

- (case-control
association studies).
,
. 6.
200 ,
3q217.
148 ,
,
IgE, 5 ,
1q21, 17q25, 20p, 16q, 5q3 8.
197 4 , 11 , , IgE
9. ,
3
10. (robust)
(genome-wide
screens) .
17-10. 2
11-13
.

, 14.

4 15,
3 .

. ,
. , (, )

16-18. ,

. (
)
.
3.
( 33%
) ,
(food challenge studies)19.

PRACTALL

1.

Lee et al.7
(2000)
Cookson et al.8
(2001)

199 ()

148

IgE

Bradley et al.9

(2002)

109 (197 ,
9 )

IgE

Haagerup et al.10
(2004)

23 ()

.

. 2 , 50%
20.
,
, 3,21.

. , ,
.
, , .
,
IgE,
,
,

22.


23.

, ,
, 24.

IgE

3q21
3q21
1q21
17q25
20p
16q-tel
5q31
3p24-22
5p13
6q16
10p13-12
18q21
4q24-26
6p
1p32
18p
21q21
7p14
13q14
15q14-15
17q21
3q14
3p26-24
4p15-14
18q11-12

, (DC), , , .

.
. -
, ( 2)25.

,
. CD4+ .
( ,
Langerhans [LCs],
[IDECs] )
, IgE26. ,
, .
(tissue remodeling),
. (),
.
. , ,
,
.

Akdis et al.

2.

TLR2

Toll-like receptor 2

4q32

Arg753Gln

IRF2
CSF2

Interferon regulatory factor 2

Colony-stimulating factor 2

4q35
5q31

IL4

IL-4

5q31

-467 G/A
-677 A/C
3606 T/C, 3928 C/T
-590 C/T

IL13

IL-13

5q31

Arg130Gln

12 24

( )

IgE

( )

IgE

13

11

-111C/T
IL5
IL1811

IL-5
IL-18

5q31
11q22

CARD412

Caspase recruitment
domain-containing protein 4

7p14-p15-

CD14

Monocyte differentiation antigen CD14

5q31

IL12B
SPINK5

IL-12B
Serine protease inhibitor, Kazal-type 5

5q31-33

1188 A/C
Glu420Lys

FCER1B
GSTP1

High-affinity IgE receptor, -chain

Glutathione-S-transferase, PI

11q13
11q13

PHF11

Plant homeodomain zink finger

11 protein
Mast cell chymase

13q14

RsaIin2, RsaIex7
Ile105Val
Haplotypes
T/C intron3, G/A 3 UTR

14q11

BstXI

CMA1

-703 C/T
-137 G/C, -133 C/G
113 T/G, 127 G/T
rs2736726
rs2075817
rs2975632
rs2075822
rs2907749
rs2907748
-159 C/T

-1903 G/A
IL4RA

IL-4 Receptor chain

16p12

Gln551Arg

-3223 C/T
CARD15
RANTES
EOTAXIN
TGFb1
SCCE

Caspase recruitment domaincontaining protein 15

Regulated on activation, normally
T cell expressed plus secreted
Eotaxin
TGF-
Stratum corneum chymotryptic enzyme

16q12

2722 G/C

17q11-q12

-403 A/G

17q21
19q13.1
19q13

-426 C/T, -384 A/G

Arg25Pro
AACCins

27. , TNF-a IL-1 (, DC),
,

,
(NF) kB,
.
(process of tethering),
,

PRACTALL

2. . Leung DY. Atopic dermatitis: new insights and opportunities for therapeutic
intervention. J Allergy Clin Immunol 2000;105:860-76. LC, Langerhans. MC, . TSLP, . Ag,
. SAg, . AICD, . CLA, . MO, .

. o , , , .

.
TH2 , IL-4 IL-13,

28.
(isotype switching) IgE
,
IL-4 IL-13
, TH2 IL-5, ,
28. GM-CSF
,
29.
, , TH1- IL-12 IL-18,
(remodeling) ,
IL-11 TGF-1,
30.
C-C ( -4 [monocyte chemoattractant protein 4],
eotaxin, RANTES) ,

31. (CCL27) -
- [cutaneous T cell-attracting chemokine] , . , -

(selective recruitment) CCR4-

TH2
,
27.

32. , , (fractalkine)33,
IFN-- 10, IFN-
IFN-- a,
34 TH1 .

IgE IgE
80% ,
IgE (>150 kU/L),
/
35,36. , 20%

IgE. (>20
) IgE 35,36. ,
IgE , Staphylococcus aureus
Candida albicans Malassezia sympodialis ( Pityrosporum ovale)37,38. ,

(APT)39.
IgE
, /-

Akdis et al.

IgE
40 .
IgE ( ,
IgE [FcRI]) D.
IgE DC
FcRI DC - 41.

,
, . ,


, 42,43.
,
, . pH

44.
, ,
45.
, ,

, .
, ,
.

.
(immune effector T cells) -
IgE ,
24,46. ,
47. ,
(TCI), ,
48.
TH1 TH2
,
. , (transgenic)
IL-4

, TH2
49.
IL-5, , -

IL-4
47. ,
IFN-,
, TH2
TH2 50.

51.
, (TReg)
,
TH1
TH2 52-54. TReg
TH1 TH2 .
TReg , Foxp3,
- ,
-IgE, 55. ,
TReg
56.
(DC). FcRI (DC)
, LC IDEC.

. LC
naive-T
TH2 IL-4, 57. , FcRI LC
IDEC T in vitro.
FcRI IDEC
,

.
,
, DCs (pDCs),
, 58. pDCs

FcRI
, IgE. pDCs ,
FceRI- ,
pDCs
I IFNs ,
- 59.
.
Toll-like
60.

.
RANTES TNF-a IFN-61. TSLP (
), DC -

PRACTALL

naive T IL-4 IL-1362.

34,63.
Fas
/
63. IFN- Fas , IL-1a,
IL-1, TNF-a
GM-CSF, 34,64.
E-cadherin -cadherin (desmosomal cadherin contacts)
65.
34,62,66.
. ,
, 67,68.
69.
,
IL-5 GM-CSF,
70.
, , TH2 , IL-5 IL-1368. , (eotaxin
RANTES)
. ,
1 (endothelial cells vascular
cell adhesion molecule 1)
1 (intercellular adhesion molecule 1)
.

TH1 IL-12 71. ,

,
, 67,68. ,

72.

, ,
, 73.
,
, 74.
.
,

, 75. TCI
,
76,77.

, , ,
78-81.

. -
, 69. , ,

LC . P

82. - .
-
in vitro72.
. placebo

83,84. ,
-
.
IgE
, , , , .
,
. ,
- . ,
( ,
) .
3 , , .
. (
, , ,
) APT ,
85. .

(patch test)
Dermatophagoides pteronyssinus (Der p 1)
,
.

Akdis et al.

. S. aureus
86.
,
. S.
aureus ,
,
.
IgE
, 87.
, 88.
S. aureus .
tacrolimus S. aureus . , ,
,
89,90. -
TH2 .
,
TNF-a IFN-,


90.

. ,
(eczema herpeticum) (eczema vaccinatum),
91. , ()

92.
Malassezia / 37,93.
IgE , (SPT-skin prick test) APT Malassezia
37. IgE
Malassezia
94,95.
. - 96,97. IgE

1 DC ,
98. ,
IgE
(MnSOD) M sympodialis
, MnSOD99.

MnSOD M sympodialis
MnSOD,
MnSOD .
. ,

. , , ,
.

,
,
.
Hanifin Rajka
( 3)100.
101 Hanifin
Rajka,

. ,

, .

. ,
, .

. . ,
. ,
: ,
Netherton, ,
, - - 102. ,
,
(cutaneous T cell lymphoma/mycosis fungoides).

,
,

( 4).

.
.

83,103.
, 104.
SPT g
-

PRACTALL

Hanifin & Rajka

UK Working Party
Schultz Larsen
DARC

Scorad
Easi

IV

Malassezia

3.
.

4. .

.
, .
( [gold standard])
IgE SPT ,
, 105-107.
(decision point) . ,
.
,
,
IgG ( -) .
APT . , APT
-
.

APT 108.

.
, 103.
, 24 .
, ,
104.
, .

, APT
. ,

.

,
IgE
,
7 94,109-111.

110.

.
, .
SPT (
) IgE . -

,
, . ,
.
.

,

,
. ,

112.

. ,
pH (
pH 5.5-6.0,
) 113.

Akdis et al.

( CyA) UV

- TCS / TCI*
* 2 .
- TCS / TCI*
* 2 .
:

1 / , ,

5. (). TCS, . TCI, . CyA, A. . Cheiron Pharma: / .

,
( )108,114.
, , ( 5). .
, . ,
,
.
, ,
.

.
115.
.

116,117.
,
118.
,
, ,
, .
(w/o) (o/w)
.
(polidocanol) .
. Cheiron Pharma:

,
119.
. 120,121. ,


/ , prednicarbate,
mometasone furoate, fluticasone methyl-prednisolone
aceponate77,122,123. . (
)

124. ( ) .
,
(fluticasone)

125. ,
S. aureus
126,127.
,
, , ,

.
,
.
-

. 3-4 . PRUZAX cream

PRUZAX ULTRA cream.
LACUREX ointment ( 10% + 12%), PRUZAX ULTRA cream ( 5%) AQUATOPIX
PLUS cream ( 10%).

10

PRACTALL

128. , ,
/

.
TCI. pimecrolimus tacrolimus
, .
,
129.
, pimecrolimus (1%)
tacrolimus (0,03%) 2 130 131. tacrolimus
(0,1%) .
0,1% tacrolimus
132,
1% pimecrolimus 133.
,
pimecrolimus 1% . ,
2 pimecrolimus134 4
tacrolimus135.

TCIs .

0,03% tacrolimus 1% pimecrolimus
, pimecrolimus
tacrolimus136.
TCI
137. , ,
.
, eczema herpeticum
eczema molluscatum,
TCI138.
TCI 134.

TCI, (FDA) black-box pimecrolimus (Elidel, Novartis, Basel,
) tacrolimus (Protopic, Astellas, Deerfield,
Il, ) 139,140. ,

2 .
TCI ,
, 134.
. ,
141
142,
143.
144.

.
S. aureus, . S. aureus
, ,
,
145,146. ,
triclosan (2,4,4-trichloro-2-hydroxydiphenyl ether) ,
146.

. triclosan

S.aureus
147. , ,
, triclosan148.

S. aureus 149,150. .

151.

152.
,
.

.
, S.
aureus
153.
S.
aureus
154. ,
155. ,
2 156. S. aureus,
mupirocin 157.
,
158. ,
.

, ( S.
aureus).

. Cheiron Pharma:
... 12% ,
. LACUREX ointment 12% . (A SUPPLEMENT TO SKIN & ALLERGY
NEWS: Vol. 39: No. 11: Nov.2008)

11

Akdis et al.

7 10 . ,
159. ,
.
, 160. ,

.
eczema
herpeticum ( Kaposi)
,
( , valacyclovir)138.

37,96,99. 161,162
163,
.

,
164.
.
( , ,
, ). ,
,

.

A
TCI, A (CyA) ,
, IL-2
IFN-. CyA
.
, 165-167.
CyA , , , CyA
,

.

(3-5 mg/kg/) (2.5 mg/kg/),
168,169.

12

, .
.

,
170. , 171.
-,
, ,
172-174. , ,
, , ,
.
(thiopurine
methyltransferase),
174.
1 3 mg/kg
,
thiopurine methyltransferase175. 173.
2 3
176.

. 177,178.
, , , -
177.

179. ,
.
: UVB (280-320 nm), UVB (311-313 nm), UVA (320-400 nm), UVA1 (340-400
nm), PUVA, Balneo-PUVA. , UVB UVB
UVA, UVA1 ,
180-182.
UV
12 , .
UV

PRACTALL

, - .


,

183.
-

184. , - .

, .
, ( , TNF
)185,186, (
)187
- (alefacept
efalizumab)86.

, ,

.
, ,
,
.
. ,
,
-

.

188.
,
189-191.

80%
Staab .192.
12 192
1 , .
, 820 (n = 443)
(n = 377)193. 12
.
1 , (SCORAD-Severity Score for Atopic Dermatitis),
,
.
,
.
,
.

,
, ,

.

,

.
.
IgE- 194-197.
6 , 50%
198,199.
(Lactobacillus
GG) .
200.

.
, .


. -
, 50%20.
500 20.

,
16.
pimecrolimus

.
(consensus)

13

Akdis et al.

, .


.

T. Bieber Novartis
Schering. C. Bindslev-Jensen Schering-Plough. A. Kapp / Novartis, Astellas, UCB,
ALK, DPO Novartis, Astellas, UCB, ALK. K. Turjanmaa -

Ansell. U. Wahn

Novartis, MSD, GSK, UCB-Pharma, ALK Stallergenes.
T. Zuberbier
Novartis, Schering-Plough, UCB, Schering, MSD, Staller-genes
Leti. M. Boguniewicz /
Novartis, Astellas, Sinclair
Novartis
Astellas. D. Y. M. Leung /
Novartis
Novartis Astellas. L. Rosenwasser
Novartis Genentech. J.
Spergel /
Novartis NIH
GSK Astellas. .

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21

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