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XVI Congresso della Federazione Nazionale delle Malattie Digestive (FISMAD) Verona, 6-9 Marzo 2010. Joint Meeting GISMAD-AIGO-SIED-SIGE DISTURBI DELLA MOTILITA ’ GI NELLE PATOLOGIE SISTEMICHE. Patologie reumatiche. Francesca Galeazzi UOC Gastroenterologia - PowerPoint PPT Presentation
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Patologie reumatiche
Francesca Galeazzi
UOC GastroenterologiaAzienda Ospedale-Università Padova
Joint Meeting GISMAD-AIGO-SIED-SIGE
DISTURBI DELLA MOTILITA’ GI NELLE PATOLOGIE SISTEMICHE
XVI Congresso della Federazione Nazionale delle Malattie Digestive (FISMAD)
Verona, 6-9 Marzo 2010
G.I. motility and Rheumatic diseases
Rheumatic disease
GI motor abnormalities:• clinical impact• prognostic value• progression
• Clinical manifestation
+/-• Altered motor function
Suspected
Rheumatic disease
100
SSc Wegener Sjogren Beçhet RA LES Poli/Derma Mixed
%
Adapted: Schneider A et al, Gastrointest Endoscopy Clin N Am 2006
0
G.I. involvement in autoimmune diseases
Others (mucosal, vascular, side effects)
Motility
Systemic sclerosisMucosa Submucosa Serosa
Vascular NormalOedema
Endothelial oedemaNormal
NeuralInflammatory cells
in l propria
Oedema
Collagen + inflammatory cells around vessels
Normal
MuscularCollagen
Patchy fibrosis atrophy mm
Thickness of vascular wall
Fibrosis of glands
Collagen
FibroticDegeneration epithelium Fibrosis
Extensive fibrosis of submucosa
Serosal thickening
Adapted: Sallam H et al, Aliment Pharmacol Ther 2006
Fibrosis, atrophy of muscular
wall thinningExtensive axonal degenerationFibrotic
Patchy fibrosis (mainly circular)
intercellular gap junction
Collagen
Axonal degenerationMuscular
normal Collagen
Axonal degenerationNeural
normalnormalVascular
Smooth muscleENS
Sakkas LI, Arthritis & Rheumatism 2004Roberts GC et al, Gut 2006
Systemic sclerosis
• Direct neural damage (antiAch Abs)• Cells of Cajal
G.I. motility in SSc
PeristalsisLES pressure
AccomodationEGG abnormalities Delayed empying
Contractility
ColonAnus-Rectum
Dysphagia GERD
VomitingMalnutrition
PseudoobstructionBacterial overgrowthMalabsorption
ConstipationDiarrhea
G.I. motility in SSc
0
100
Esophagus Stomach Small bowel Colon Ano-rectum
%
Forbes A, Rheumatology 2008
Uncoord perist LES Normal / Aperistalsis, LES pressure
Reflux - Impaired clearance
In symptomatic pts:Esophagitis: 56-60%Strictures: > 40%
Asymptomatic ptssuspected Barrett: 37% Zamost BJ et al, Gastroenterol 1987
Basilisco G et al, Gut 1993Katzka DA et al, Am J Med 1987
Disease subtype
Duration
Symptoms?
Systemic sclerosis
Esophagus
133 pts SSc; duration 1-38 yrs (M 6 yrs) PPI standard dose
Upper GI endoscopy, Manometry
Marie I et al, Alimen Pharmacol Ther 2006
9.8%14.3%77.4%
Nausea/VomitingDysphagiaHeartburn
7%6.8%32%
CandidiasisBarrettEsophagitis
24%28%48%
(I) Normal(II-III) Uncoord perist LES Normal /
(IV) Aperistalsis
LES pressure
Systemic sclerosis
Marie I et al, Alimen Pharmacol Ther 2006
Esophagitis/Barrett: No relation with
Symptoms!
133 pts
•subtype (diffuse, localized)
•duration
•age
Systemic sclerosis
Marie I et al Alimen Pharmacol Ther 2006
Severe esophageal motor abnormalities
133 pts
• subtype
• duration
• ageAssociation with lung disease!
No association with
SSc: esophagus and lung
Savarino E et al, Am J Resp Crit Care 2008
40 consecutive SSc pts15 dcSSc25 lcSSc45% pulmonary fibrosis
• HRCT• pH-impedance
SSc: esophagus and lung
More severe reflux (acid and non-acid) in pts with interstitial lung disease
Savarino E et al, Am J Resp Crit Care 2008
Proximal reflux in pts with ILD
SSc: esophagus and lung
ILD pts no relation
•subtype
•duration
•age
•GERD symptoms
5 cm above LES
15 cm above LES
Juvenile Localized Scleroderma
14 consecutive pts Juvenile Localized SclerodermaAge 6-17; Disease duration: 4.7 yrs (0.2-13.2)
Guariso G et al, Clin Exp Rheumatol 2007
•Symptoms
•Pathological 24 hrs pH–monitoring
•Esophagitis
•No major motor abnormalities
•Asymptomatic•Low LES basal pressure
7
1
Systemic sclerosis
High prevalence of esophageal lesions in SSc on therapy (Pts on PPI: > 75% heartburn; 30% esophagitis)
No relation with disease subtype, duration, age
Esophageal involvement associated with interstitial lung disease
Esophagus
G.I. motility in SSc
0
100
Esophagus Stomach Small bowel Colon Ano-rectum
%
Small bowel
Systemic sclerosis
Small bowel
Sjolund K et al, Eur J Gastroenterol Hepatol 2005
10 pts with altered esophageal motility: 8/10 impaired SB motility (neuropathy + myopathy)
Diffuse motor alterations
Systemic sclerosis
Small bowel
Marie I et al, Rheumatology 2007
Onset: 75% pts abnormal SB manometry
5 yrs: 100% worsening of SB motor activity
5 yrs
8 SSc pts SB manometry at diagnosis and 5 yrs
Parodi A et al, Am J Gastroenterol 2008Marie I et al, Rheumatology 2009
Small bowel bacterial overgrowth
SIBO +ve SIBO -ve
SSc pts Controls
55 pts vs 60 HVLBTRifaximin 10 days
Small bowel involvement:Common Progressive
• Bacterial overgrowth >50%• Malabsorption• Pseudobstruction
Dia
rrhe
aU
pper
abd
pai
nLo
wer
abd
pai
nB
loat
ing
Ten
esm
us
Abd
ten
dern
ess
Em
esis
Fev
er
Dys
uria
Gen
eral
iIln
ess
Nau
sea
•14 pts severe GI involvement within 2 yrs of onset
•288 pts No GI involvement
•117 pts No GI involvement within 2 yrs of onset
Nishimagi E et al, J Rheumatol 2007
Systemic sclerosis and GI motility
Subgroup of patients?
Subgroup GI as main early manifestation (esophagus / SB)• ILD less frequent!• 50% ANA +ve nucleolar pattern
Adapted: Schneider A et al: Gastrointest Endoscopy Clin N Am 2006
G.I. involvement in autoimmune diseases
Others (mucosal, vascular, side effects)
Motility
RA: impaired esophageal peristalsis, reduced LES pressure (up to 58% pts)
SLE: segmentary or diffuse altered esophageal motility
Polymyositis/Dermatomyositis: esophagus, small bowel
Mixed connective tissue disease: Smooth muscle involvement
100
SSc Wegener Sjogren Beçhet RA LES Poli/Derma Mixed
%
0
Sjogren
27 pts -dysphagia 76% (40.6% severe)
Xerostomia?
•Simultaneous contractions distal (22%) and proximal (11%) esophagus
•No relation with salivary function
Anselmino M et al, Dig Dis Sci 1997
Sal
ivar
y o
utf
low
(g
r/2
min
)
Fibromyalgia
Chronic musculo-skelatal pain without tissue inflammation or damage
Fibromyalgia
IBS
Irritable bladder
FD
TMD Intestinal permeability
Stressors
Pain processing
Pamuk ON et al, J Rheumatology 2009
Fibromyalgia
Pamuk ON et al, J Rheumatology 2009
GI motility and
Rheumatic diseases GI motility alterations commonly described in rheumatic
diseases, affecting > 90% pts in SSc
Except for SSc, specific pattern of motor abnormalities unclear
In SSc GI motility impairment may represent the most relevant internal manifestation, with potentially severe complications
Difficult to identify patients and to predict severity of motor alterations only on the basis of clinical symptoms and in absence of specific “markers” (subgroups of patients?)
Recommended