Transcript Asymptomatic PCD

«Gloriosa scuola medica che, affondando le radici nel secolo scorso, ha
creato la vera clinica moderna intesa come studio del malato su basi
scientifiche e logiche»
La Malattia Celiaca Potenziale nell’adulto:
caratteristiche cliniche e storia naturale
Presentata da: Dott. Giacomo P.I. Caio
Relatore: Prof. Roberto De Giorgio
Correlatore: Dott. Umberto Volta
Direttore della Scuola di Specializzazione: Prof. Mauro Bernardi
Background
Celiac Disease
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•
•
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Autoimmune disease triggered by gluten ingestion
Genetic predisposition (HLA DQ2/DQ8+)
Prevalence worldwide 1%
Onset at any age: from childhood to oldness
Challenging clinical presentation: intestinal and extraintestinal symptoms
Diagnostic gold standards: serology and duodenal biopsy
Volta U, Caio et al. BMC Gastroenterol. 2014
Potential Celiac Disease
Endomysial Abs (EmA)
Marsh 0-1 lesion
HLA-DQ2 / -DQ8
DQ2
a5
DQA1*05
b2
DQB1*02
TG2 antibodies
DQ8
a3
DQA1*03
b302
DQB1*0302
Although diagnostic criteria are well-defined, PCD is still a grey area
with little knowledge, particularly in adults
AIMS
This study was designed to:
• shed light on the natural history of adult
PCD
• assess the evolution of asymptomatic
PCD cases
Patients & Methods
• Prospective cohort study on 735 consecutive CD patients diagnosed
from 2004 to 2013
• PCD patients criteria: positivity of serology (EmA and tTGA), HLA DQ2 and/or
DQ8, Marsh 0-1
• PCD patients were subdivided in symptomatic and asymptomatic subgroups
• Symptomatic PCD  GFD + periodic follow-up to assess their clinical
and serological response to GFD
• Asymptomatic PCD  GCD + clinical and serological follow up every 6
months + duodenal biopsy every 2 years
PCD vs Active CD
735 consecutive CD
patients
10.5%
PCD
77 PCD vs 658 ACD
F/M = 3.2:1 vs 3.5:1
Mean age: 25 vs 36
years
6
5
6
14
7
18
18
Clinical features of 77 PCD
patients at onset
%
classical phenotype
non classical phenotype
16 (21%)
61 (79%)
Serology, genetics, histology and
autoimmunity
in symptomatic vs. asymptomatic PCD
HLA-DQ2%
HLA-DQ8%
Biopsy
Autoimmune
disorders %
EmA°
IgA%
TG2°°
IgA%
Symptomatic
98*
98*
98
3
25
75
36**
Asymptomatic
100
100
94
6
31
69
5
P
ns
ns
ns
ns
M0
M1
ns
<0.05
°EmA at low titre (mean titre 1:20, range 1:5 to 1:40); TG2 : mean titre 1.5 cut-off (range 0.2-3.0)
*One patient with IgA deficiency positive for EmA and TG2 of IgG class
**Autoimmune disorders (including autoimmune thyroiditis, type 1 DM, alopecia, dermatitis herpetiformis ) in
symptomatic vs asymptomatic PCD P <0.05, Fisher’s exact test
Gluten-free or gluten-containing diet?
A tough challenge
Symptomatic
Potential
Celiac
Disease
malabsorption, anemia,
miscarriages, short stature,
cerebellar ataxia,
hypertransaminasaemia,
unexplained osteoporosis
Asymptomatic
GFD
GCD +
serology / biopsy
follow-up
Kurppa K et al, Gastroenterology 2009;
Auricchio R, et al, Am J Gastroenterol 2014
Management of the PCD patients
n= 77
PCD patients
n= 61
SYMPTOMATIC
n= 16
ASYMPTOMATIC
Gluten free diet
Gluten containing
diet
Clinical / serological
follow-up every 6 months
to assess the response to
gluten free diet
Clinical / serological
follow-up every 6 months;
biopsy every 2 years to assess the progression
to overt celiac disease
3-year mean follow-up (range 1-10 yrs)
of asymptomatic PCD cases
16 cases on
GCD
1 with diarrhea/anemia
and raised antibody
titers
Biopsy: subtotal
villous atrophy
Active CD
Only 6% of asymptomatic adult
PCD patients developed active CD
during follow-up
15 patients
persistently
asymptomatic
4 with EmA/tTG
disappearance
Biopsy every 2 years:
No villous atrophy
IgA-TG2 deposits in PCD patients
A
B
C
IgA deposits to TG2 (A), indicated by white arrows, were positive in a
proportion of PCD cases
They did not predict the evolution towards ACD
Comparison between
adult and pediatric PCD
Adult PCD
Pediatric PCD
 Estimated prevalence: 11% of total
CD diagnoses
 Estimated prevalence: 12% of total
CD diagnoses
 More symptomatic (79%) than
asymptomatic (21%)
 More asymptomatic (83%) than
symptomatic (17%)
 25% with antibody disappearance
 20% with antibody disappearance
 6% with development of active CD at
3-year follow-up
 13% with development of active CD
at 3-year-follow-up
G.Caio Tesi Specializzazione
Auricchio R et al, AJG 2014
Conclusions
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Adult PCD is a growing clinical entity with an increasing rate in latest years
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Most of the adult PCD patients are symptomatic and they should be treated
with a GFD which causes a significant improvement of their clinical picture
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Conversely, asymptomatic PCD should be maintained on a GCD and monitored
by clinical, serological and histological assessment
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Only a minority of asymptomatic PCD developed histologically proven CD
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Antibody follow-up disclosed that not only anti-TG2, but also EmA may
spontaneously disappear in asymptomatic PCD on GCD
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Based on our data, caution should be recommended before prescribing a GFD
in adults with asymptomatic PCD.
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Ringraziamenti
Dott. Umberto Volta
Prof. Roberto De Giorgio
Prof. Mauro Bernardi
Prof. Massimo Campieri
Dott. Magda Frisoni
Prof. Enrico Roda
Prof. Alessio Fasano
Dr. Anna Sapone
Dr. M. Rosaria Fiorentino
Prof. Luigi Bolondi
Prof. Giovanni Barbara
Prof. Daniela Zauli
Dott. Alessandro Granito
Dott. Cesare Cremon
Dott. Alessandro Venturi
Antibodies fluctuation