Pediatric GI Update 2006
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Poop Pourri of Oral Manifestations of Pediatric Gastrointestinal Disease 13th Annual Fall Pediatric Conference Susan Maisel MD St. Vincent PMCH Pediatric Gastroenterology 317 338-9450
Objective • To provide an update for three pediatric gastrointestinal diseases that can initially manifest themselves in, and profoundly affect the oral cavity.
Dermatitis herpetiformis
Endoscopic Findings • Frequently normal appearing endoscopy • Can be associated with mild gastritis
Dental Enamel Defects and Celiac Disease • Affects 89% • Childhood onset of disease occurs during enamel formation • Characterized by: – – – –
demarcated opacities undersized teeth yellowing grooves and pitting
• Can occur in asymptomatic Celiacs
Dental Enamel Defects and Celiac Disease • Involves permanent dentition • Symmetrical – incisors – Molars
• Damage is irreversible • Treatment is cosmetic – bonding – veneers
Celiac Disease Histology
Normal
Partial atrophy I
Partial atrophy II
Partial atrophy III
Subtotal atrophy
Total atrophy
Oral Cavity and Celiac Disease • Cavities – Calcium and vitamin D deficiencies common
• • • •
Aphthous stomatitis Atrophic glossitis Dry mouth syndrome Squamous carcinoma
Iritis/Uveitis
Erythema Nodosum
Pyoderma Gangrenosum
Inflammatory Bowel Diseases (IBDs) INFLAMMATORY BOWEL DISEASE
Ulcerative Colitis (UC)
Crohn’s Disease (CD)
Mucosal Ulceration in Colon
Transmural Inflammation
Proctitis
Left-sided Extensive Colitis Colitis
Upper Small Bowel Colonic Gastrointestinal
Anorectal
Stenson WF, et al. Inflammatory bowel disease. In: Yamada T et al., eds. Textbook of Gastroenterology Philadelphia, PA: Lippincott Williams & Wilkins;4th Ed. 2003:1699.
Worldwide Geographical Prevalence of IBD
High Intermediate Low Loftus EV. Gastroenterology. 2004;126:1504.
Epidemiology of IBD in North America • Incidence (per 100,000 person-years) – UC: 2.2 to 14.3 cases – CD: 3.1 to 14.6 cases
• Prevalence (per 100,000 persons) – UC: 37 to 246 cases – CD: 26 to 199 cases
• New diagnoses (per year) – UC: 7,000 to 46,000 cases – CD: 10,000 to 47,000 cases Loftus EV. Gastroenterology. 2004;126:1504. • Population experiencing IBD – 1,400,000
Demographic Features of IBD in North America • Slight male predominance in UC – Incidence of UC seems to have stabilized overall but continues to rise in males
• Slight female predominance in CD – Especially in late adolescence and early adulthood – Hormonal factors might play a part
• Mean age at diagnosis 15 – 35 • Late onset 50’s-60’s Loftus EV. Gastroenterology. 2004;126:1504.
Recurrent Aphthous Ulcers • 48-80% incidence in Crohn’s, less in UC • Parallel or predate intestinal disease • Biopsies can often diagnose Crohn’s • Treatment – topical, intralesional, systemic steroids; aminosalycilate preps
•
Orofacial granulomatosis • Chronic swelling of the lips and lower half of the face • Oral lesions • Hyperplastic gingivitis
Potential Risk Factors Associated With IBD Risk Factors With IBD Association
• Cigarette smoking – + risk factor for CD – - risk factor for UC
• Appendectomy – + risk factor for CD – - risk factor for UC
Risk Factors With Questionable IBD Association
• Perinatal and childhood factors • Measles infection or vaccination • Mycobacterial infection
• Oral contraceptives – Weak association with IBD
• Diet – Increased sugar intake
Loftus EV. Gastroenterology. 2004;126:1504.
Evolution of Crohn's Disease Behavior Over Time Cumulative probability %
100 90 80 70
Penetrating
60 50 40 30
Stricturing Inflammatory
20 10 0
years 1
3
5
7
9
11
13
15
17
19
Established percentage of CD patients remaining free of penetrating complications (upper curve) and free of stricturing and/or penetrating complication (lower curve) in 2002 patients with Crohn’s disease since onset (diagnosis) of the disease. Adapted from Cosnes J, et al. Inflammatory Bowel Dis. 2000;8:244.
The Role of Proinflammatory Cytokines in Crohn’s Disease IL- 6
Inflammation and Tissue Damage
B Cell
Plasma Cell IL- 12 Antigenpresenting Cell
Activation of T cells
Inflammatory Cell Adhesion
Humoral Immune Response
TNF IL- 1
Antigen
IL- 8
GM-CSF Leukotrienes, Superoxides, Nitric Oxide, and Prostaglandins
Sands BE. Inflammatory Bowel Diseases. 1997; 3:95-113. Feldman M, et al. Advances in Immunology. 1997; 64:283-350.
Key Actions Attributed to TNF
Mechanism for Antibody Neutralization of TNF
van Deventer S. Gut. 1997; 40:443-48. Scallon BJ. Cytokine. 1995; 7:251-59. Feldman M. et al. Advances in Immunology. 1997; 64:283-350.
Results of Infliximab Use The use of Infliximab is no longer restricted to patients who have severe disease, not responsive to conventional therapy. 1.
A single infusion can induce remission in ~60% of patients with active Crohn’s Disease (Targan et al., 1997).
2.
Three infusions over six weeks led to closure of fistulae in 50% of patients (Present et al., 1999).
3.
Before Treatment
Week 2
Repeated infusions maintains remission in >60% of patients (Hanauer et al., 2002).
Figure: Closure of an abdominal fistula in a 60year old man with treatment of Infliximab (5mg/kg). Present et al., 1999.
Week 18
Ringed Esophagus
Esophageal nodules
Whitish exudates
Esophageal Stricture with Food Impaction
Diagnosis: Endoscopic Features of EE Vertical Lines Rings
White Specks
Epidemiology • Described in 1978; not recognized until late 1990’s • 15 fold increase in last 16 years • Male to female 2:1
(Allergic) Eosinophilic Esophagitis • 50 – 75% atopic • Food sensitization common • Aero-allergens may also play a role
GERD and Dental Erosions
4/7/2015
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Dental Erosions and GERD • Critical pH of enamel – 5.5 • Gastric refluxate - 2.2 • Salivary protective factors vary – rate of salivary flow – pH – viscosity – protein and mineral content
• Fluoride – unproven to help • Brushing after GERD without rinsing first
Diagnosis: Clinical symptoms in EE Symptom
Median Age of Presentation (years)
Feeding disorders
2
Vomiting/reflux
8
Abdominal pain
12
Dysphagia
13.4 and adults
Food impaction
16 and adults Noel NEJM;351, 2004
EE vs. GERD Characteristic Atopy Food sensitization Histology Peripheral eosinophilia Esophageal pH PPI Steroids Food allergen elimination
EE High High >24 eos/hpf ~50% Normal Usually not helpful Helpful Sometimes helpful
GERD Nml Nml 0-7 eos/hpf rare Abnormal Helpful Not helpful Not helpful
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