Diagnostic, présentation clinique et histoire naturelle...
Transcript of Diagnostic, présentation clinique et histoire naturelle...
Diagnostic,
présentation clinique et
histoire naturelle des MICI
Prof Yoram Bouhnik
Gastroentérologie et Assistance Nutritive
Université Paris VII
Hôpital Beaujon, Clichy
DU Médecine interne, Novembre 2013
The burden of IBD
• Prevalence of IBD is 1% in North America and some European countries
• Incidence of Crohn’s disease is still increasing in these countries
• Rapid increases in the incidence of IBD are now being observed in Japan, South Korea, Australia, New Zealand and some regions of India and China
• IBD will emerge as a worldwide epidemic in the coming years
Elkjaer M et al. Gut 2010;59:1652–61 Molodecky NA, et al. Gastroenterology 2012;142:46–54
global map of inflammatory bowel disease
Worldwide IBD incidence and/or prevalence rates for countries reporting
data (A) before 1960; (B) from 1960 to 1979; (C) after 1980.
Before 1960
1960-1979
≥ 1980
Molodecky et al. Gastroenterology 2012;142 (Jan):46-54
UC CD
Molodecky et al. Gastroenterology 2012
Temporal trends of incidence rates for studies that reported at least 10 years
of data and with at least 3 time points for CD
Data from France The EPIMAD registry: Northern France
6 million inhabitants (9.3% of french population)
242 adult gastroenterologists, 12 pediatric gastroenterologists, 6733 GPs
22,976cases recorded by the Registry (1988-2012)
4
5
6
7
8
9
Total
Femmes
Hommes
Incidence /105
Incidence of Crohn’s disease in Northern France (1988-2008)
Chouraki V et al. Aliment Pharmacol Ther 2011 (maj 2012)
5,3
4,5
6,1
7,6
6,4
8,8
0
2
4
6
8
10
12
0-19
0-9
10-19
Age at diagnosis
Incidence /105
Incidence variation for CD in children and adolescents in Northern France (1988-2008)
Chouraki V et al. Aliment Pharmacol Ther 2011 (maj 2012)
3,5
0,5
6,5 7,1
1,2
12,9
Crohn’s Disease Incidence according to gender & age
0
2
4
6
8
10
12
14
16
18
20
0-9
10-19
20-29
30-39
40-49
50-59
60-69
70-79
>=80
Age
incid
en
ce
Males
Females
Incidence /100 000 26 years (median age at diagnosis)
0%
20%
40%
60%
80%
100%
< 17 ans 17-39 ans 40-59 ans > 60 ans
E3 (PANCOLITE)
E2 (COLITE GAUCHE)
E1 (RECTITE)
Présentation de la RCH selon l'âge
• Étude prospective
• 5 253 cas incidents en population
• Registre EPIMAD de 1988 et 2010
Incidence
Localisation au diagnostic
Symptômes au diagnostic
0
20
40
60
80
100
douleurs abdominales perte de poids syndrome rectal manifestations
extraintestinales
< 17 ans
17-39 ans
40-59 ans
> 60 ans
ATCD Familiaux
13 % 3 % p < 10-4 * p < 10-4
• Conclusion : Présentations cliniques différentes en fonction de l’âge probablement reflet d’une pathogénie différente (poids des facteurs environnementaux et génétiques)
Charpentier C et al. DDW 2012. Abstract 102
p < 10-4
Facteurs environnementaux protecteurs
RR de développer une RCH :
•fumeur = 0,4
•ex-fumeur = 1,7
Ex-fumeur :
•aggravation de la maladie
•extension des lésions
•augmentation du risque de RCH
réfractaire et de colectomie.
Facteurs Causalité
Tabac +++
Appendicectomie +++
Infections intestinales ++
Antibiothérapie +
Hygiène +
OP ou THS +
Alimentation +
Polluants ?
Soleil ?
Chaîne du froid ?
Ulcerative colitis Crohn’s disease
Crohn’s disease
• CD is a relapsing, transmural inflammatory disease of the GI mucosa that can affect the entire GIT from the mouth to the anus.
• Typical presentations include the discontinuous involvement
of various portions of the GIT and the development of complications including strictures, abscesses, or fistulas.
• The clinical presentation is largely dependent on disease
location and can include diarrhoea, abdominal pain, fever, clinical signs of bowel obstruction, as well as passage of blood or mucus or both.
From mouth to anus
Rare
Perianal fistula:
One fourth of patients
after 20 years
Small bowel and colon (30%)
Colon (40%)
Small bowel (30%)
Upper GI tract (<5 %)
Ulcerative colitis
• UC is a relapsing non-transmural inflammatory disease that is restricted to the colon
• Patients typically present with bloody diarrhoea (often nocturnal and postprandial), passage of pus, mucus, or both, and abdominal cramping during bowel movements.
• Severe symptoms are less common in left-sided colitis and proctitis.
Left sided
colitis
(20%) Extensive
colitis
(30%)
Proctitis (50%)
Differential diagnosis of UC and CD
Up to 25% patients with CD and UC will develop EIM
Ileocolonoscopy with biopsies is the 1st
line investigation to diagnose IBD
Le diagnostic repose sur l’endoscopie et les biopsies
Small intestinal Crohn’s disease
as seen by capsule endoscopy
Detects erosions in suspected Crohn’s disease with negative SBFT /
colonoscopy
Recent imaging to explore the SB in IBD
CT-based (left) and MRI-based (right) enterography showing an ileocaecal-sigmoid fistula in patient with Crohn’s disease
Histoire naturelle RCH
Représentation de l’histoire naturelle
de la rectocolite hémorragique
Torres J et al. Inflamm Bowel Dis 2012 ; 18 : 1356-63
Ac
tivité
infla
mm
ato
ire
(Ma
yo
sco
re, U
CEIS
)
Premiers
Symptômes
Diagnostic RCH
précoce
RCH
tardive
De
stru
ctio
n in
test
ina
le
Atteinte
Epithéliale
Dysplasie
/Cancer
Extension
Perte de
compliance
Chirurgie
Poussées
sévères
Profil évolutif de la RCH
Solberg, Scand J Gastro 2009; 44: 431
amélioration
progressive
aggravation
progressive
chronique
continu
chronique
intermittent
55% 1% 37% 6%
Cohorte d'inclusion danoise (IBSEN study), n=423/519, suivi 10 ans
Principales complications
associées à la RCH
Complications Commentaires
Colite grave 15%
Hémorragie 10%, cause fréquente d’anémie
Mégacôlon toxique,
perforation
5%
Sténose colique 2 -10%, avec risque tumoral +++
Hépatobiliaires CSP avec risque de cholangiocarcinome (X
100-800)
Thrombovasculaires FDR indépendant accident + récidive (x 3,5
vs population générale (veineuses+++)
– Risque de complications/mégacolon toxique,
péritonite, hémorragie
– Risque de chirurgie / Risque morbimortalité
– Risque de cancer colorectal
– Qualité de vie / handicap fonctionnel
Risques particuliers des formes
sévères/compliquées de RCH
(E3 > E1-E2)
Cu
mu
lati
ve p
rob
abili
ty (
%)
Cohorte de 1161 patients au Danemark (1962–87)
Langholz E et al. Scand J Gastroenterol 1996;31:260–6
Recto-sigmoidite
L’étendue des lésions progresse avec le temps
chez 50% des patients atteints de RCH
0
20
40
60
80
100
0 2 4 6 8 10 12 14 16 18 20 22 24
Années après le diagnostic
Progression
Une maladie destructrice au cours du temps
• Relation entre augmentation de la largeur de
l’espace présacré et la durée de la maladie :
– augmentation du dépôt de graisse en avant
du sacrum
– rétrecissement de la lumière rectale
– épaississement de la paroi rectale
– affaissement de la graisse périrectale
Torres J et al. Gut 2011;Jul 11:Epub ahead of print
% cumulé de CCR
Risque élevé de cancer colorectal
dans la RCH
Double méta-analyse : CCR et RCH
Lutgens et al. Gut 2008 ; 57 :A131. Eaden et al. Gut 2001;48:526-35
1% à 10 ans 4% à 20 ans 14% à 30 ans
Adherence to endoscopy guidelines
CESAME cohort: prevalence of colonoscopic surveillance of IBD in patients with longstanding (>7 years) extensive colitis
0
20
40
60
80
100
Pro
po
rtio
n o
f p
atie
nts
su
rvey
ed
(%
)
Study centre (academic)
All UC + IBDU Crohn’s colitis
1 2 3 4 5 6 7 8 All 9
Vienne A, et al. Aliment Pharmacol Ther 2011;34:188–95
Vingt et 30% des patients RCH ont une
colectomie après 10 et 25 ans d’évolution
Langholz E et al. Gastroenterology. 1994
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 2 4 6 8 10 12 14 16 18 20 22 24
Années après le diagnostic
% d
e p
ati
en
ts
Colectomie
Maladie active
Rémission
Status at any given timepoint
Méthode : étude en population (Manitoba) depuis 1984 (suivi maximal de 25 ans)
– facteurs de risque de colectomie • sexe masculin : HR = 1,34, p < 0,0064 • âge > 65 ans : HR = 0,63, p < 0,0001 • hospitalisation au diagnostic : HR = 2,01, p < 0,0001
Chirurgie au cours de la RCH
DDW 2011 – Targownik L.E. et al. CO631
0 0 2 4 6 8 10 12 14 16 18 20
5
10
15
Taux global de colectomie
(%)
15,4
10,5
7,7 1,8
à 90 jours
Années après le diagnostic
0 0 5 10 15 20
5
10
15
20 1987-91 1992-96 1997-2001 2002-08
(%) Taux de colectomie par périodes
Années après le diagnostic
p<0.0001
Meucci G, et al. Gastroenterology 2006;130(4 Suppl. 2):Abstract S1302
% R
ech
ute
à 1
2 m
ois
90
80
70
60
50
40
30
20
10
0 Rémission clinique
et endoscopique à S6
(n=54)
Rémission clinique
mais non endoscopique à S6
(n=5)
L’objectif thérapeutique dans la RCH est la rémission clinique et endoscopique
ECCO consensus
La rémission endoscopique est définie
par le score Mayo endoscopique
RE = sous-score
endoscopique ≤ 1
Pineton de Chambrun, G. et al. NRGH 2010; 7:15–29
La cicatrisation muqueuse à un an
diminue le risque de colectomie
Froslie K.F et al Gastroenterology, 2007; 133: 412-22
Suivi prospectif d’une cohorte
Norvégienne recrutée entre 1990-94
(avant biothérapies)
354 RCH avec évaluation
endoscopique à 1 an : 175 MH+, 163
MH -
Réévaluation clinique à 5 ans
MH+: 3 colectomies /178 (2%)
MH -:13 colectomies /176 (7%)
p= 0,02
MH-
MH+
Colombel JF et al. Gastro 2011;141:1194–1201
Une colon d’aspect normal est associé à un risque
plus faible de dysplasie/cancer au cours de la RCH
À l’endoscopie Groupe OR (IC95% ) p
Pseudo-polypes inflammatoires
NON
OUI
1
2, 29 (1,28-4,11) 0,005
Sténose du colon NON
OUI
1
4,62 (1,03-20,08) 0,05
Inflammation histologique sévère
NON
OUI
1
5,13 (2,36-11,14) 0,001
Colon d’aspect normal NON
OUI
1
0, 38 (0,19-0,73) 0,003
Rutter MD et al. Gut 2004 ; 53 : 1813-6
Rutter MD et al. Gastroenterology 2004 ; 56 : 451-9
Histoire naturelle MC
Crohn’s disease as a progressive disease
Progression of digestive damage and inflammatory activity in a theoretical patient with Crohn’s disease
Pariente B, et al. Inflamm Bowel Dis 2011;17:1415–22
Inflam
mato
ry activity (C
DA
I, CD
EIS, CR
P)
Surgery
Stricture
Stricture
Fistula/abscess
Disease onset
Diagnosis Early disease
Profil évolutif des MICI maladie de Crohn
Solberg, CGH 2007; 5: 1430
amélioration
rapide
aggravation
tardive
chronique
continue
chronique
intermittente
43% 3% 32% 19%
Cohorte d'inclusion danoise (IBSEN study), n=197/237, suivi 10 ans
Peyrin-Biroulet L, et al. Gut 2010;59:141–7
Genetic and environmental
factors, intestinal microflora Symptoms Criteria for diagnosis of
Crohn’s disease fulfilled
Time
Early Crohn’s disease
Inflammation (clinical, biological,
endoscopic, radiologic evidence
of disease activity)
No fistula, abscess or stricture
Late Crohn’s disease
Bowel damage (stricture, fistula,
abscess,
Impairment of GI functioning
Colorectal cancer
Preclinical phase
Subclinical inflammation
(immune response and
histologic lesions)
Early CD
Rutgeerts P, et al. Gastroenterology 1990;99:956-63
Endoscopic lesions precede clinical
relapse • Prospective trial with 89 patients having had ileal resection
• Endoscopical diagnosis 1 year after surgery predicts future relapse
i0: no lesions
i1: <5 aphthous lesions
i2: >5, but normal
mucosa between lesions
i3: diffuse and diffusely
inflamed between lesions
i4: diffuse inflammation
and large ulcers,
narrowing, etc.
0
0.2
0.4
0.6
0.8
1.0
Sym
pto
m-f
ree s
urv
ival (%
)
0 1 2 3 4 5 6 7 8
i4
i3
i2
i0 + i1
Follow up (years)
Anatomic Evolution
Rutgeerts P, et al. Gastroenterology 1990;99:956-63
Inflammation
Stricture
Fistula/
abscess
At diagnosis After 10 years
80% 50%
20% 50%
Disease behaviour over time
Montreal classification
Montreal
Age at diagnosis A1 below 16 y
A2 between 17 and 40 y
A3 above 40 y
Location L1 ileal
L2 colonic
L3 ileocolonic
L4 isolated upper
disease*
Behaviour B1 non‐stricturing,
non‐penetrating
B2 stricturing
B3 penetrating
p perianal disease
modifier†
*L4 is a modifier that can be added to L1–L3 when concomitant upper gastrointestinal disease is present.
†“p” is added to B1–B3 when concomitant perianal disease is present.
Cumulative rate of remaining free of intestinal penetrating or stricturing complications in ileal (left) and colonic (right) CD
Data were obtained from the studies at St-Antoine hospital that included 1448 patients with ileal disease (L1) and 1129 patients
with colonic disease (L2).
CD evolution relates to disease location
Long term disease course in CD
Ileal
Colon
Ileocolon
Proximal
Penetrating
Stricturing
Inflammatory
Louis E et al Gut 2001; 49:777-32
%
years years
Behaviour Location
Schwartz et al. Gastroenterology 2002
Perianal fistulas
Penetrating complications
0.0
0.2
0.4
0.6
0.8
1.0
0 5 10 15 20 25 30
Years from Crohn’s disease diagnosis
Cu
mu
lati
ve p
rob
ab
ilit
y
of
co
mp
licati
on
s
Penetrating or stricturing complications
Stricturing complications
52
Long-term evolution of Crohn’s disease behaviour
(population-based study)
Thia KT, et al. Gastroenterol 2010;139:1147–55
American population-based cohort of individuals diagnosed with Crohn’s disease 1970–2004 (n=306);
evaluated for initial phenotype and cumulative probability of complications estimated using Kaplan-Meier
Hospitalisations Taux annuel: 20 %
Chirurgie abdominale majeure
(Comté d’Olmsted, 1970-2004, n=310)
Peyrin-Biroulet L et al. Soumis
Perc
en
t
0
20
40
60
80
100
Years
0 5 10 15 20 25 30
310 166 92 54 33 20 7# at risk
Cumulative Probability of First Major Abdominal Surgery
Récidive post-opératoire
(Comté d’Olmsted, 1970-2004, n=310)
Peyrin-Biroulet L et al. DDW 2010
Phenotype recurrence after surgery
Indications for first
resection
Perforating
(n=195)
Non-
perforating
(n=150)
Indications
for second
resection
Perforating 64(77%) 24(29%)
Non-
perforating
19(23%) 60(71%)
Total 83 84
Greenstein et al. Gut, 1988, 29, 588-592
Work disability in IBD C
D p
atie
nts
re
ceiv
ing
DP
(%
)
0
10
20
30
50
18–29 40–49 60–67 50–59 30–39
40
Age (years) U
C p
atie
nts
re
ceiv
ing
DP
(%
) 0
10
20
30
50
18–29 40–49 60–67 50–59 30–39
40
DP because of CD
DP because of other diagnosis
DP in background population
DP because of UC
DP because of other diagnosis
DP in background population
Age (years)
Norwegian population-based study of IBD patients (n=518) receiving disability pension (DP)
RR for DP: 2.0 (95% CI 1.4–2.7)
RR for DP: 1.8 (95% CI 1.4–2.3)
Hoivik M, et al. Gut 2012 [Epub ahead of print: doi:10.1136/gutjnl-2012-302311]
Crohn’s disease Ulcerative colitis
Estimates of mortality in IBD
Mortality increased in the first year after diagnosis
Intermediate and long-term mortality increased by 10% in UC and 50% in CD
Mortality from UC decreased from 1982 to 2010, because of reduced mortalities from gastrointestinal disorders and colorectal cancer
Mortality from CD did not change
Risk of dying according to age at, and time since, IBD diagnosis (Denmark 1982–2010) 36,080 UC and 15,361 CD vs 2,858,096 matched controls
Jess T, et al. Clin Gastroenterol Hepatol 2013;11:43–8
0 25 50
100
0 5 10 15 20 25
80+ years old
0 25 50
100
0 5 10 15 20 25
60–79 years old
0
20
40
0 5 10 15 20 25
40–59 years old
0 5
10 15
0 5 10 15 20 25
20–39 years old
0
2
4
0 5 10 15 20 25
0–19 years old
Time since IBD diagnosis / date of matching (years)
Ris
k o
f d
eat
h (
%)
Control persons
Ulcerative colitis
Crohn’s disease
Inflam
mato
ry activity
Surgery
Stricture
Stricture
Fistula/abscess
Disease onset
Dig
est
ive
dam
age
Diagnosis Early disease
New goal of treatment: Blocking disease progression and damage
Adapted from Pariente B, et al. Inflamm Bowel Dis 2011;17:1415–22
New goal of treatment: Blocking disease progression and damage
Adapted from Pariente B, et al. Inflamm Bowel Dis 2011;17:1415–22
Inflam
mato
ry activity
Disease onset
Dig
est
ive
dam
age
Diagnosis Early disease
Réponse
clinique
Rémission
clinique Réponse ET
rémission
clinique
Rémission
clinique Rémission
clinique
sans
corticoïdes
1997
Targan
2006
Hanauer
CLASSIC-I
2002
Hanauer
ACCENT 1
2007
Colombel
CHARM
2010
Colombel
SONIC
Cicatrisation
muqueuse
2012
Rutgeerts
EXTEND
Critère de jugement principal dans les
essais randomisés contrôlés dans la MC
Emerging concepts in IBD therapy
Treat to target (beyond symptoms)
Early intervention
Monitoring (tight control)
Profiling disease course
Personalizing (precision medicine)
Take home messages • Incidence et prévalence des MICI ont augmenté ces 4
dernières décades, parallèlement à l’industrialisation du mode de vie
• Maladies chroniques inflammatoires à manifestations digestives et extradigestives évoluant par poussées de pronostic imprévisible
• Diagnostic relativement facile si on y pense (iléocoloscopie+++)
• Risque chirurgical majeur
• Objectif thérapeutique actuel = rémission profonde soutenue pour modifier histoire naturelle