DEBRA INTERNATIONAL Congress - debraitaliaonlus.org Annichiarico.pdf · L’epidermolisi bollosa distrofica: altri fattori predisponenti In conclusion, in the present study we have

“Sensibilità al glutine e malattie rare: i positivi

riscontri della gluten free diet nelle disfunzioni

evolutive della Epidermolisi Bollosa.”

Giuseppina Annicchiarico

Coordinamento Regionale Malattie Rare Puglia

[email protected]

DEBRA INTERNATIONAL Congress

Living with EB : the voice of patients and families

Le malattie rare

Orphanet ne ha censite 8 300; Colpiscono tra il 6% e l’8% della popolazione (tra i 27 e i 36 milioni di persone nell’Unione europea).

La definizione è fondata sulla sola prevalenza: patologie di origini e tipologie assai diverse.

Predominante la trasmissione genetica : l’80 % di tutte le malattie rare.

Possono colpire tutti i distretti e sistemi

del corpo umano (l’apparato digerente

o quello respiratorio, la pelle, il sistema

nervoso e così via), e a volte anche

più (approccio interdisciplinare).

Ridotte aspettative di vita in termini di tempo e qualita!!!!!

Le epidermolisi bollose:

E’ una malattia rara che affligge circa 1 su 17.000 nuovi nati

In italia la stima è di 1:82.000/100.000

Nel mondo esistono circa 500.000 malati

Le epidermolisi bollose ereditarie sono un gruppo

clinicamente e geneticamente eterogeneo di malattie rare,

caratterizzate da fragilità della cute e delle mucose e da

formazione di lesioni bollose in seguito a traumatismo.

L’epidermolisi bollosa: classificazione

Fonte: LG diagnosi delle epidermolisi bollose ereditarie- CNMR-marzo 2011

L’epidermolisi bollosa distrofica

Complicanze:

Iposomia

Grave anemia sideropenica

Sindattilia

Insufficenza renale da

depositi lineari di IgA


L’epidermolisi bollosa distrofica : le complicanze

non sono sempre presenti


L’epidermolisi bollosa: distrofica


Forme clinicamente gravi / gravissime

Forme clinicamente lievi

Cosa fa la differenza??????

L’epidermolisi bollosa: distrofica


Forme clinicamente gravi / gravissime

Forme clinicamente lievi

Cosa fa la differenza??????

L’epidermolisi bollosa: case report

1

caso

E.B. is a male 22 year old patient diagnosed of recessive dystrophic form

of EB genetically confirmed. When he was six years old, he underwent to

surgical procedure for correction of hand sindactyly. Skin was removed

from tights, the only body part showing no damage or scars from EB. After

this procedure, a chronic flogistic phenomena was evident at tight level.

Chronic inflammation was treated and resolved with high dose 16 mg/die

of the leukotriene receptor antagonist montelukast. At the age of 17 blood

tests showed severe anaemia (Hb< 8 g/dl and albumin 2.5 g/dl) along

with hyposideraemia (5 µg/ml) with normal transferrin, elevated platelet

count (731 x 103/µl), prolonged coagulation time and microcytosis.


1

caso

….

He showed moderate renal failure (creatinine 0,69 mg/dl, creatinine

clearance 50–60 ml/min per m2 body surface area), proteinuria (2.5 g/24

h) and increased levels of serum γ-globulins (IgG 29,500 g/l, IgA 4,900

g/l, normal IgM and IgE) and inflammatory markers [erythrocyte

sedimentation rate (ESR) 93 mm/h, C-reactive protein (CRP) 39.2 mg/dl].

More detailed analysis evidenced the presence of auto-antibody against

COL7 and pemphigoid bullous 180 (BP180) antigen . Like many EB

subjects, he was hyposomic, with 25-hydroxy-vitamin D deficiency and

delayed puberty.


1

caso

….

One year later, the patient was admitted for severe vasculitis Henoch–

Schönlein purpura-like. He presented abdominal cramps, melena, and

haematemesis. Blood test confirmed the early pattern with a more severe

thrombocytosis (826 x 103/µl), high ESR (107 mm/h), CRP (112.7 mg/dl)

and IgG, IgM and IgA levels. Renal function was still compromised

(creatinine 0,61 mg/dl) with proteinuria (30 mg/dl). He was treated with

betametasone, 2 mg/bidie, and the intestinal symptoms along with high

IgA presence, suggested a concomitant disease, such as celiac disease

or gluten sensitivity, and thus a gluten free diet (GFD) was started. Further

analyses showed positive anti-gliadin IgG and anti-endomysium. After

5 months of GFD and betametasone treatment, proteinuria was resolved

and the general state of the patient was improved. He underwent puberty

and hyposomia was resolved. Betametasone was lately reduced to

0.5mg/bidie.


Limite:

L’impossibilità ad eseguire

una

biopsia intestinale


L’epidermolisi bollosa: la ricerca

Definizione del protocollo di studio:

studio retrospettivo-studio caso controllo

Ipotesi di lavoro:

Ricerca della componente autoimmune nell’EB

L’epidermolisi bollosa: studio caso controllo

Coinvolti 36 pazienti

14 maschi e 22 femmine

24 pazienti con EBDR

12 pazienti con EBS

L’epidermolisi bollosa distrofica: severity score

Moss et al, 2009


Moss et al, 2009

Limite:

L’uso della

medesima scala

per ogni età


Moss et al, 2009

Abbiamo scelto di dividere il gruppo di

pazienti per fascia d’età, perché in un

bambino lo score è comunque più

basso non essendo presenti le

complicanze.

Ciò ha dato la possibilità di distinguere

più agevolmente le forme più gravi da

quelle meno gravi.

L’epidermolisi bollosa: severity score

sex age nails % area

damaged mouth eye Lar

Oes

.

Hand

scarr.

Skin

cancer

Chro

nic

woun

d

(>50

%)

Scarr.

alopecia

Nutr.

Compr. total

M 1 2 30 3 2 0 2 1 x x x 0 40

F 2 3 40 5 5 0 5 1 x x x 5 64

F 3 4 35 3 3 0 3 3 x x x 5 56

F 6 5 30 3 3 0 2 4 0 2 0 4 53

Età 0-6 anni


sex age nails

%

area

dama

ged

mouth eye Lar Oes. Hand

scarr.

Skin

cance

r

Chro

nic

woun

d

(>50

%)

Scarr

.

alope

cia

Nutr.

Compr

.

total

F 9 2 2 0 0 0 0 0 0 1 0 0 5

M 12 5 40 3 3 0 5 5 0 x 1 5 67

F 15 5 35 4 5 0 2 3 0 2 1 3 60

F 16 3 5 0 0 0 4 0 0 1 4 0 17

M 15 3 0 0 2 3 x x x 5 5 40 40

Età 7-17 anni


sex age nails

% area

damag

ed

mouth eye Lar Oes. Hand

scarr.

Skin

cance

r

Chroni

c

wound

(>50%)

Scarr.

alopec

ia

Nutr.

Compr

.

total

F 19 5 40 4 3 0 2 3 0 2 1 3 63

M 19 5 40 3 3 0 2 5 0 3 1 3 65

F 25 5 40 3 3 0 3 5 0 5 3 5 72

F 25 5 40 5 5 0 5 5 0 4 4 5 78

F 27 5 35 5 5 0 4 5 0 4 3 3 69

F 28 5 40 5 5 5 0 5 5 0 4 4 78

F 28 5 35 5 5 0 4 5 0 4 3 3 69

F 32 5 50 5 5 0 5 5 0 5 5 5 90

M 33 5 40 5 5 0 4 5 3 5 4 3 79

M 33 5 20 0 0 0 2 1 0 2 3 0 33

M 42 5 20 4 0 0 1 2 3 2 0 1 38

F 44 5 20 0 0 0 4 1 3 4 0 2 39

F 49 1 5 2 0 0 3 0 0 0 0 0 11

F 55 3 20 2 0 0 4 0 0 2 0 5 36

Età 18 anni in poi


Moss et al, 2009

In tutti gli ammalati

Abbiamo dosato gli Ac anti penfigoide

bolloso (i cui valori avevamo verificato

essere alti nel caso descritto, ma

presenti anche in altre malattie).

Abbiamo dosato gli Ac anti coll VII

L’epidermolisi bollosa: valutazione degli autoanticorpi

0 50 100 150 200

80

70

60

50

40

30

20

10

0

BP180

Coll

VII

0 50 100 150

80

70

60

50

40

30

20

10

0

BP230

Coll

VII

Ab anti-BP180 Ab anti-BP230

R2 0.87

Slope P < 0.0001

R2 0.69

Slope P < 0.0001

Alti valori degli auto anticorpi anti BP ed anche degli auto

anticorpi anti Coll VII nelle forme cliniche più gravi!!

E non solo……………


EB BP PV Other Healty

0

20

40

60

80

100A

nti

-Coll

agen

VII

lev

els

(UA

/mL

)

….. e non solo…..

auto anticorpi anti Coll VII e specifici

dell’Epidermolisi Distrofica


EBS

EBD

Ab anti-type VII collagen Ab anti-BP180 e anti-BP230

0

17(77%)

3 (25%)

18(82%)


Presenza degli

autoanticorpi specifici

nei soggetti

clinicamente più gravi malattia autoimmune

o

epifenomeno????

L’epidermolisi bollosa distrofica: altri fattori predisponenti

Ci siamo chiesti che relazione ci potesse

essere tra epidermolisi e celiachia/ gluten

sensitivity.

Nello stesso gruppo di pazienti abbiamo

studiato l’HLA.


controls EB Controls% EB%

DQ2.5 DQA1*0105/DQB1*0201 27 3 7.92% 8.1%

DQ2.2 DQA1*0201/DQB1*0202 20 8 5.87% 21.62%*

DQ2T DQA1*0201/DQB1*0202

DQA1*0505/DQB1*0301

39 2 11.44% 5.41%

DQ8 DQA1*0301/DQB1*0302 9 2 2.64% 5.41%

DQ2-8 DQB1*02/DQB10302 3 0 0.88% 0

DQ7 DQA1*0505/DQB1*0301 138 14 40.47% 37.83%

Neg X/X 105 7 30.79% 18.91%

total 341 37

Significativa la presenza di DQ2.2 nei pazienti con EB


In conclusion, in the present study we have reported that in EB

patients a possible association with gluten sensitivity, non celiac

disease, can be hypothesized. Moreover, we believe that in these

subjects the use of gluten free diet might result beneficial in order

to reduce the organ damage risk. Indeed, the exposure to

gluten in these patients may contribute to worsen organ

damage, in particular renal function, leading to

hospitalization up to loss of capacity to freely deambulate. To

screen for gluten sensitivity and an early administration of

gluten free diet in the population of EB patients with high

score for pathology (BEBS) and in particular to those with

higher nutritional compromise, should be considered as a

novel therapeutic approach and might help to change the

course of the disease as well as EB extracutaneous

complications.


HLA TYPING IN EPIDERMOLYSIS BULLOSA PATIENTS: RELEVANCY TO GLUTEN

SENSITIVITY

G. Annicchiarico1, M. G. Morgese2,3, T. Fiore4, S Mauro5, L. Garofalo6, G. Aceto7, M. Tampoia8,

D. Bonamonte6, M. Minelli9 and L. Brunetti7

«Jornal of genetic syndromes & gene therapy»

---- Original Message -----

From: "OMICS Publishing Group-OMICS" <[email protected]>

To: "Giuseppina Annicchiarico"

<[email protected]>

Sent: Wednesday, September 18, 2013 3:47 PM

Subject: Your PDF HLA TYPING IN EPIDERMOLYSIS BULLOSA PATIENTS: RELEVANCY TO

GLUTEN SENSITIVITY has been built and requires approval

> Dear Annicchiarico,

>

> The PDF for your submission, "HLA TYPING IN EPIDERMOLYSIS BULLOSA

> PATIENTS: RELEVANCY TO GLUTEN SENSITIVITY" is ready for viewing.

>

Grazie per l’attenzione!

DEBRA INTERNATIONAL Congress - debraitaliaonlus.org Annichiarico.pdf · L’epidermolisi bollosa distrofica: altri fattori predisponenti In conclusion, in the present study we have

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