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Patologie reumatiche Francesca Galeazzi
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 Azienda Ospedale-Università Padova
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G.I. motility and Rheumatic diseases
GI motor abnormalities: clinical impact prognostic value progression Clinical manifestation +/- Altered motor function Suspected Rheumatic disease
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G.I. involvement in autoimmune diseases
100 % SSc Wegener Sjogren Beçhet RA LES Poli/Derma Mixed Others (mucosal, vascular, side effects) Motility Adapted: Schneider A et al, Gastrointest Endoscopy Clin N Am 2006
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Systemic sclerosis Mucosa Submucosa Serosa Smooth muscle ENS Vascular
Normal Oedema Endothelial oedema Neural Inflammatory cells in l propria Collagen + inflammatory cells around vessels Muscular Collagen Patchy fibrosis atrophy mm Thickness of vascular wall Fibrosis of glands Collagen Fibrotic Degeneration epithelium Fibrosis Extensive fibrosis of submucosa Serosal thickening Fibrosis, atrophy of muscular wall thinning Extensive axonal degeneration Fibrotic Patchy fibrosis (mainly circular) intercellular gap junction Collagen Axonal degeneration Muscular normal Axonal degeneration Neural Vascular Smooth muscle ENS Adapted: Sallam H et al, Aliment Pharmacol Ther 2006
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Systemic sclerosis Direct neural damage (antiAch Abs) Cells of Cajal
Sakkas LI, Arthritis & Rheumatism 2004 Roberts GC et al, Gut 2006
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G.I. motility in SSc Peristalsis Dysphagia LES pressure GERD
Accomodation EGG abnormalities Delayed empying Vomiting Malnutrition Pseudoobstruction Bacterial overgrowth Malabsorption Contractility Colon Anus-Rectum Constipation Diarrhea
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G.I. motility in SSc % 100 Esophagus Stomach Small bowel Colon
100 Esophagus Stomach Small bowel Colon Ano-rectum % Forbes A, Rheumatology 2008
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? Systemic sclerosis Esophagus Uncoord perist LES Normal /
Aperistalsis, LES pressure Reflux - Impaired clearance In symptomatic pts: Esophagitis: 56-60% Strictures: > 40% Asymptomatic pts suspected Barrett: 37% Disease subtype Duration Symptoms ? Zamost BJ et al, Gastroenterol 1987 Basilisco G et al, Gut 1993 Katzka DA et al, Am J Med 1987
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(II-III) Uncoord perist LES Normal /
Systemic sclerosis 133 pts SSc; duration 1-38 yrs (M 6 yrs) PPI standard dose Upper GI endoscopy, Manometry 9.8% 14.3% 77.4% Nausea/Vomiting Dysphagia Heartburn 7% 6.8% 32% Candidiasis Barrett Esophagitis 24% 28% 48% (I) Normal (II-III) Uncoord perist LES Normal / (IV) Aperistalsis LES pressure Marie I et al, Alimen Pharmacol Ther 2006
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Systemic sclerosis Esophagitis/Barrett: No relation with
133 pts Esophagitis/Barrett: No relation with Symptoms! subtype (diffuse, localized) duration age Marie I et al, Alimen Pharmacol Ther 2006
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SSc: esophagus and lung
133 pts Severe esophageal motor abnormalities No association with subtype duration age Association with lung disease! Marie I et al Alimen Pharmacol Ther 2006
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SSc: esophagus and lung
40 consecutive SSc pts 15 dcSSc 25 lcSSc 45% pulmonary fibrosis HRCT pH-impedance More severe reflux (acid and non-acid) in pts with interstitial lung disease Savarino E et al, Am J Resp Crit Care 2008
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Proximal reflux in pts with ILD
SSc: esophagus and lung 5 cm above LES Proximal reflux in pts with ILD 15 cm above LES ILD pts no relation subtype duration age GERD symptoms Savarino E et al, Am J Resp Crit Care 2008
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Juvenile Localized Scleroderma
14 consecutive pts Juvenile Localized Scleroderma Age 6-17; Disease duration: 4.7 yrs ( ) 7 1 Symptoms Pathological 24 hrs pH–monitoring Esophagitis No major motor abnormalities Asymptomatic Low LES basal pressure Guariso G et al, Clin Exp Rheumatol 2007
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Systemic sclerosis Esophagus
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
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G.I. motility in SSc Small bowel 100 Esophagus Stomach Small bowel
100 Esophagus Stomach Small bowel Colon Ano-rectum %
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Systemic sclerosis Small bowel
10 pts with altered esophageal motility: 8/10 impaired SB motility (neuropathy + myopathy) Diffuse motor alterations Sjolund K et al, Eur J Gastroenterol Hepatol 2005
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Systemic sclerosis Small bowel
8 SSc pts SB manometry at diagnosis and 5 yrs 5 yrs Onset: 75% pts abnormal SB manometry 5 yrs: 100% worsening of SB motor activity Marie I et al, Rheumatology 2007
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Small bowel bacterial overgrowth
55 pts vs 60 HV LBT Rifaximin 10 days SIBO +ve SIBO -ve SSc pts Controls Small bowel involvement: Common Progressive Bacterial overgrowth >50% Malabsorption Pseudobstruction Diarrhea Upper abd pain Lower abd pain Bloating Tenesmus Abd tenderness Emesis Fever Dysuria General iIlness Nausea Parodi A et al, Am J Gastroenterol 2008 Marie I et al, Rheumatology 2009
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Systemic sclerosis and GI motility
Subgroup of patients? 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 Subgroup GI as main early manifestation (esophagus / SB) ILD less frequent! 50% ANA +ve nucleolar pattern Nishimagi E et al, J Rheumatol 2007
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G.I. involvement in autoimmune diseases
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 Others (mucosal, vascular, side effects) Motility Adapted: Schneider A et al: Gastrointest Endoscopy Clin N Am 2006
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Sjogren 27 pts dysphagia 76% (40.6% severe) Xerostomia?
Simultaneous contractions distal (22%) and proximal (11%) esophagus No relation with salivary function Salivary outflow (gr/2 min) Anselmino M et al, Dig Dis Sci 1997
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Chronic musculo-skelatal pain without tissue inflammation or damage
Fibromyalgia Chronic musculo-skelatal pain without tissue inflammation or damage Stressors IBS Fibromyalgia Pain processing FD Irritable bladder Intestinal permeability TMD Pamuk ON et al, J Rheumatology 2009
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Fibromyalgia Pamuk ON et al, J Rheumatology 2009
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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?)
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