Zentrum für Kinderheilkunde und Jugendmedizin, Giessen

ĞůŝĂĐŝƐĞĂƐĞ K.-P. ZIMMER  =HQWUXPIU.LQGHUKHLONXQGHXQG-XJHQGPHGL]LQ $OOJHPHLQH3lGLDWULHXQG1HRQDWRORJLH

ĂǀŝĚZE^/E͊ ͻ DĂůĂďƐŽƌƉƚŝŽŶ ͻ ĞůĂLJŝŶƐŽŵĂƚŝĐΘƉƐLJĐŚŽƐŽĐŝĂůĚĞǀĞůŽƉŵĞŶƚ ͻ /ŵƉĂŝƌĞĚůŝĨĞƋƵĂůŝƚLJ ͻ /ŶĨĞƌƚŝůŝƚLJ͕ƉƌĞŵĂƚƵƌŝƚLJͬĂďŽƌƚŝŽŶƐϭ͕^'ϭ ͻ KƐƚĞŽƉŽƌŽƐŝƐ ͻ ƵƚŽŝŵŵƵŶŝƚLJ;/DͿϮ͍ ͻ '/DĂůŝŐŶĂŶĐLJ;dĞůů>LJŵƉŚŽŵĂͿ ͻ DŽƌƚĂůŝƚLJϯ

EAP / Lyon, 22.9.13

ϭ

,ƵŵĂŶZĞƉƌŽĚƵĐƚŝŽŶϮϱ͗ϱϮϴ͕ϮϬϭϬ

Ϯ

'ĂƐƚƌŽĞŶƚĞƌŽůŽŐLJϭϭϳ͗Ϯϵϳ͕ϭϵϵϵ ŝĂďĞƚĞƐĂƌĞ͕ƉƵďϮϬϭϭ

ϯ

'ĂƐƚƌŽĞŶƚĞƌŽůŽŐLJϭϯϳ͗ϴϴ͕ϮϬϬϵ Ƶƌ:ƉŝĚĞŵŝŽůϮϭ͗ϯϱϵ͕ϮϬϬϲ EĂƚZĞǀ'ĂƐƚƌŽĞŶƚĞƌŽů,ĞƉĂƚŽůϳ͗ϭϱϴ͕ϮϬϭϬ K.-P. Zimmer, Gießen

- 34 -

*OXWHQ)UHH'LHWÄ2YHUNLOO䇾 䇾" Celiac Disease

„Wheat sensitivity䇾 䇾

Dyspepsia

Permeability

Ĺ

Ļ

N

Claudin 4

N

Ĺ

N

IL-6

Ĺ

N

N

IFN-J

IL-21

Ĺ Ĺ

N N

N N

TLR-2

N

Ĺ

N

FOXP3

N

Ļ

N

IEL/CD3

75-80

30-50

18-25 6DSRQHHWDO%0&0HG

• seronegative / latent celiac disease ? • double-blind placebo controlled food challenge (DBPCFC) ! EAP / Lyon, 22.9.13

K.-P. Zimmer, Gießen

- 35 -

ESPGHAN - 2011 1a

Symptoms (+ extraintestinal)

3

IgA anti-TG2

+

4

Histology (Marsh 2-3)

+ Gluten free Diet

-

+

Remission Sympt. + Serol.

Compliance? Refractory CD DD

CELIAC DISEASE lifelong strict GFD

(63*+$1&'JXLGHOLQH-3*1

EAP / Lyon, 22.9.13

K.-P. Zimmer, Gießen

- 36 -

ESPGHAN - 2011 1a

Symptoms

1b

(+ extraintestinal)

2a

+ 3

IgA anti-TG2

+

4

-

Risk Patient

(asymptomatic)

HLA-DQ2/8

([FOXVLRQRI&HOLDF'LVHDVH &DYH\HDURIO,IH GDLO\JOXWHQLQWDNH GUXJV GLIIHUHQWLDOGLDJQRVLV

Histology (Marsh 2-3)

+ Gluten free Diet

-

+

Remission Sympt. + Serol.

Compliance? Refractory CD DD

CELIAC DISEASE lifelong strict GFD

(63*+$1&'JXLGHOLQH-3*1

EAP / Lyon, 22.9.13

K.-P. Zimmer, Gießen

- 37 -

ESPGHAN - 2011 1a

Symptoms

1b

(+ extraintestinal)

2a

Risk Patient

(asymptomatic)

HLA-DQ2/8

+ 3

IgA anti-TG2

+

([FOXVLRQRI&HOLDF'LVHDVH &DYH\HDURIO,IH GDLO\JOXWHQLQWDNH GUXJV GLIIHUHQWLDOGLDJQRVLV

+ 2b

4

Histology (Marsh 2-3)

+ Gluten free Diet

-

-

HLA-DQ2/8

-

+ NO Biopsy, if: • Malabsorption • anti-TG2 > 10x Cutoff • EMA pos. • Pediatric Gastroenterologist

+

Remission Sympt. + Serol.

Compliance? Refractory CD DD

CELIAC DISEASE lifelong strict GFD

(63*+$1&'JXLGHOLQH-3*1

EAP / Lyon, 22.9.13

K.-P. Zimmer, Gießen

- 38 -

ESPGHAN - 2011 1a

Symptoms

1b

(+ extraintestinal)

2a

Risk Patient

(asymptomatic)

HLA-DQ2/8

+ 3

IgA anti-TG2

+

4

Histology

([FOXVLRQRI&HOLDF'LVHDVH &DYH\HDURIO,IH GDLO\JOXWHQLQWDNH GUXJV GLIIHUHQWLDOGLDJQRVLV

+

Continuation of gluten containing nutrition

2b

HLA-DQ2/8

-

+

(Marsh 2-3)

+ Latent Celiac Disease Gluten free Diet

-

-

NO Biopsy, if: • Malabsorption • anti-TG2 > 10x Cutoff • EMA pos. • Pediatric Gastroenterologist

+

Remission Sympt. + Serol.

Compliance? Refractory CD DD

CELIAC DISEASE lifelong strict GFD

(63*+$1&'JXLGHOLQH-3*1

EAP / Lyon, 22.9.13

K.-P. Zimmer, Gießen

- 39 -

ESPGHAN - 2011 1a

Symptoms

1b

(+ extraintestinal)

2a

Risk Patient

(asymptomatic)

HLA-DQ2/8

-

+ 3

IgA anti-TG2

+

4

Histology

([FOXVLRQRI&HOLDF'LVHDVH &DYH\HDURIO,IH GDLO\JOXWHQLQWDNH GUXJV GLIIHUHQWLDOGLDJQRVLV

+

Continuation of gluten containing nutrition

2b

HLA-DQ2/8

-

+

(Marsh 2-3)

+ Latent Celiac Disease Gluten free Diet

-

NO Biopsy, if: • Malabsorption • anti-TG2 > 10x Cutoff • EMA pos. • Pediatric Gastroenterologist

+

Remission Sympt. + Serol.

+

Gluten Challenge - Doubts on Diagnosis - incomplete criteria

-

([FOXVLRQ&HOLDF'LVHDVH

(if HLA-DQ2/8 positive!)

Compliance? Refractory CD DD

CELIAC DISEASE lifelong strict GFD

(63*+$1&'JXLGHOLQH-3*1

EAP / Lyon, 22.9.13

K.-P. Zimmer, Gießen

- 40 -

ESPGHAN - 2011 1a

Symptoms

1b

(+ extraintestinal)

2a

Risk Patient

(asymptomatic)

HLA-DQ2/8

-

+ 3

IgA anti-TG2

+

4

Histology

([FOXVLRQRI&HOLDF'LVHDVH &DYH\HDURIO,IH GDLO\JOXWHQLQWDNH GUXJV GLIIHUHQWLDOGLDJQRVLV

+

Continuation of gluten containing nutrition

2b

HLA-DQ2/8

-

+

(Marsh 2-3)

+ Latent Celiac Disease Gluten free Diet

-

NO Biopsy, if: • Malabsorption • anti-TG2 > 10x Cutoff • EMA pos. • Pediatric Gastroenterologist

+

Remission Sympt. + Serol.

+

Gluten Challenge - Doubts on Diagnosis - incomplete criteria

-

([FOXVLRQ&HOLDF'LVHDVH

(if HLA-DQ2/8 positive!)

Compliance? Refractory CD DD

CELIAC DISEASE lifelong strict GFD

фϮ>:͗DĂƌƐŚ///нDͬd'нƐLJŵƉƚŽŵƐ EŽŐůƵƚĞŶĐŚĂůůĞŶŐĞ

(63*+$1&'JXLGHOLQH-3*1

EAP / Lyon, 22.9.13

tŽůƚĞƌƐͬ,ŽƵǁĞŶ͗:W'Eϰϴ͗ϱϲϲ͕ϮϬϬϵ

K.-P. Zimmer, Gießen

- 41 -

„Three of four criteria䇾 䇾

Symptoms

12 ELRSV\

ÅVHURQHJ䇾 䇾 =|OLDNLH

Å+/$QHJ䇾 䇾 =|OLDNLH

VLOHQWH =|OLDNLH

ODWHQWH =|OLDNLH

+

+

+

-

+/-

+

+

-

+

+

+++

-

+

+

+

[+]

+

+

+

-

(gluten sensitive)

HLA-DQ 2/8 TG2/EMA (gluten sensitive)

Histology

(Marsh 1)

䚒 Gluten EAP / Lyon, 22.9.13

-

-

-

-

+ K.-P. Zimmer, Gießen

- 42 -

„Three of four criteria䇾 䇾 very rare

Symptoms

12 ELRSV\

ÅVHURQHJ䇾 䇾 &'

Å+/$QHJ䇾 䇾 =|OLDNLH

VLOHQWH =|OLDNLH

ODWHQWH =|OLDNLH

+

+

+

-

+/-

+

+

-

+

+

+++

-

+

+

+

+

+

-

(gluten sensitive)

HLA-DQ 2/8 TG2/EMA (gluten sensitive)

Histology

[+]

(Marsh 1)

䚒 Gluten EAP / Lyon, 22.9.13

-

-

-

-

+ K.-P. Zimmer, Gießen

- 43 -

„Three of four criteria䇾 䇾 very rare

Symptoms

12 ELRSV\

ÅVHURQHJ䇾 䇾 &'

Å+/$QHJ䇾 䇾 =|OLDNLH

VLOHQWH =|OLDNLH

ODWHQWH =|OLDNLH

+

+

+

-

+/-

+

+

-

+

+

+++

-

+

+

+

[+]

+

+

+

-

(gluten sensitive)

HLA-DQ 2/8 TG2/EMA (gluten sensitive)

Histology

(Marsh 1)

䚒 Gluten EAP / Lyon, 22.9.13

-

-

-

-

+ K.-P. Zimmer, Gießen

- 44 -

„Three of four criteria䇾 䇾 very rare

Symptoms

12 ELRSV\

ÅVHURQHJ䇾 䇾 &'

Å+/$QHJ䇾 䇾 =|OLDNLH

VLOHQWH =|OLDNLH

ODWHQWH =|OLDNLH

+

+

+

-

+/-

+

+

-

+

+

+++

-

+

+

+

[+]

+

+

+

-

(gluten sensitive)

HLA-DQ 2/8 TG2/EMA (gluten sensitive)

Histology

(Marsh 1)

䚒 Gluten

-

-

-

-

+

gluten challenge EAP / Lyon, 22.9.13

K.-P. Zimmer, Gießen

- 45 -

„Three of four criteria䇾 䇾 very rare

Symptoms

very rare

12 ELRSV\

ÅVHURQHJ䇾 䇾 &'

Å+/$QHJ䇾 䇾 &'

VLOHQWH =|OLDNLH

ODWHQWH =|OLDNLH

+

+

+

-

?

+

+

-

+

+

+++

-

+

+

+

[+]

+

+

-

(gluten sensitive)

HLA-DQ 2/8 TG2/EMA (gluten sensitive)

Histology

(Marsh 1)

䚒 Gluten

-

-

-

-

+

gluten challenge EAP / Lyon, 22.9.13

K.-P. Zimmer, Gießen

- 46 -

„Three of four criteria䇾 䇾 very rare

Symptoms

very rare

12 ELRSV\

ÅVHURQHJ䇾 䇾 &'

Å+/$QHJ䇾 䇾 &'

VLOHQWH =|OLDNLH

ODWHQWH =|OLDNLH

+

+

+

-

?

+

+

-

+

+

+++

-

+

+

+

[+]

+

+

+

-

(gluten sensitive)

HLA-DQ 2/8 TG2/EMA (gluten sensitive)

Histology

(Marsh 1)

䚒 Gluten

-

-

-

-

+

gluten challenge EAP / Lyon, 22.9.13

K.-P. Zimmer, Gießen

- 47 -

„Three of four criteria䇾 䇾 very rare

Symptoms

very rare

12 ELRSV\

ÅVHURQHJ䇾 䇾 &'

Å+/$QHJ䇾 䇾 &'

VLOHQW &'

ODWHQWH =|OLDNLH

+

+

+

-

+/-

+

+

-

+

+

+++

-

+

+

+

[+]

+

+

(gluten sensitive)

HLA-DQ 2/8 TG2/EMA (gluten sensitive)

Histology

(Marsh 1)

䚒 Gluten

-

-

-

-

+

gluten challenge EAP / Lyon, 22.9.13

K.-P. Zimmer, Gießen

- 48 -

„Three of four criteria䇾 䇾 very rare

Symptoms

very rare

12 ELRSV\

ÅVHURQHJ䇾 䇾 &'

Å+/$QHJ䇾 䇾 &'

VLOHQW &'

ODWHQWH =|OLDNLH

+

+

+

-

+/-

+

+

-

+

+

+++

-

+

+

+

[+]

+

+

+

-

(gluten sensitive)

HLA-DQ 2/8 TG2/EMA (gluten sensitive)

Histology

(Marsh 1)

䚒 Gluten

-

-

-

-

+

gluten challenge EAP / Lyon, 22.9.13

K.-P. Zimmer, Gießen

- 49 -

„Three of four criteria䇾 䇾 very rare

Symptoms

very rare

12 ELRSV\

ÅVHURQHJ䇾 䇾 &'

Å+/$QHJ䇾 䇾 &'

VLOHQW &'

ODWHQW &'

+

+

+

-

+/-

+

+

-

+

+

+++

-

+

+

+

[+]

+

+

+

-

(gluten sensitive)

HLA-DQ 2/8 TG2/EMA (gluten sensitive)

Histology

(Marsh 1)

䚒 Gluten

-

-

-

-

gluten challenge EAP / Lyon, 22.9.13

K.-P. Zimmer, Gießen

- 50 -

„Three of four criteria䇾 䇾 very rare

Symptoms

very rare

12 ELRSV\

ÅVHURQHJ䇾 䇾 &'

Å+/$QHJ䇾 䇾 &'

VLOHQW &'

ODWHQW &'

+

+

+

-

+/-

+

+

-

+

+

+++

-

+

+

+

[+]

+

+

+

-

(gluten sensitive)

HLA-DQ 2/8 TG2/EMA (gluten sensitive)

Histology

(Marsh 1)

䚒 Gluten

-

-

-

-

+

gluten challenge EAP / Lyon, 22.9.13

K.-P. Zimmer, Gießen

- 51 -

Å2YHUNLOO䇾 䇾 ‡ Å:KHDW6HQVLWLYLW\´ *)'IRUODWHQW&' ‡ %DGTXDOLW\FRQWURORIVHURORJ\ ‡ 1RXVHRI+/$'4 ‡ ''YLOORXVDWURSK\ ‡ (63*+$1PLVLQWHUSUHWDWLRQ

EAP / Lyon, 22.9.13

K.-P. Zimmer, Gießen

- 52 -

Å8QGHUNLOO´ ‡ ‡ ‡ ‡

EAP / Lyon, 22.9.13

1RXVHRIVHURORJ\DQG+/$'4 1RTXDOLW\FRQWURORIVHURORJ\$*$ 1RELRSV\VROH\0DUVK (63*+$1PLVLQWHUSUHWDWLRQ

K.-P. Zimmer, Gießen

- 53 -

(63*+$1    

EAP / Lyon, 22.9.13

6\PSWRPV 6HURORJ\ +/$'4 'XRGHQDOELRSV\ *)'

K.-P. Zimmer, Gießen

- 54 -

d:;DͿ͕ŶŽƚŝĨ,>ͲYϮͬϴŶĞŐĂƚŝǀĞ͊ 䚜 ŽŵƉůĞdžŝƚLJŽĨ^W',EĂůŐŽƌŝƚŚŵ;ƌĞĨĞƌƚŽƉĞĚŝĂƚƌŝĐŐĂƐƚƌŽĞŶƚĞƌŽůŽŐŝƐƚͿ 䚜 'ůƵƚĞŶĨƌĞĞĚŝĞƚ͗ĞĨĨŝĐŝĞŶƚ͕ƐĂĨĞ;ďĞǁĂƌĞŽĨĂƌƚŝĨŝĐŝĂůůLJƉƌŽĐĞƐƐĞĚĨŽŽĚͿ 䚜 ŚĞĐŬĐƌŝƚŝĐĂůůLJ͞tŚĞĂƚ^ĞŶƐŝƚŝǀŝƚLJ͟ ;W&Ϳ EAP / Lyon, 22.9.13

K.-P. Zimmer, Gießen

- 55 -

d,E