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Inflammatory Bowel Disease. Kimberly Persley, MD Digestive Disease Associates of Dallas Presbyterian Hospital of Dallas. What is IBD?. Chronic Inflammation of the bowel Idiopathic Relapsing course. IBD Spectrum. Ulcerative colitis. Crohn’s Disease. Indeterminant colitis. Epidemiology.
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Inflammatory Bowel Disease Kimberly Persley, MD Digestive Disease Associates of Dallas Presbyterian Hospital of Dallas
What is IBD? • Chronic • Inflammation of the bowel • Idiopathic • Relapsing course
IBD Spectrum Ulcerative colitis Crohn’s Disease Indeterminant colitis
IBD Facts • Approx 1,000,000 Americans have IBD • men and women affected equally • first peak occurs between the ages of 15-30 a later peak occurs in the 7th decade
Normal Intestine Vs. IBD Environmental triggers (infection, bacterial products) Failure to down- regulate Chronic uncontrolled inflammation = IBD Moderately inflamed Down-regulate Normal gut controlled inflammation Normal gut controlled inflammation
Proportion of Patients with Family History of IBD by Age of Diagnosis * % Patients with Positive Family History of IBD * *p<0.005 Polito JM et al. Gastro.1996;111:580
Diagnosis • Clinical history • Physical examination • Laboratory tests • Endoscopic findings • Radiographic findings • Histology
Differential Diagnosis • Lymphoma • Infectious etiologies • Appendicitis • Diverticulitis • Carcinoma • Celiac Disease • Ischemic colitis • Irritable Bowel Syndrome
History • In 1932, Drs. Crohn, Oppenheimer and Ginzburg at Mount Sinai Medical Center described a subacute inflammatory process affecting the distal ileum • “terminal ileitis” • “granulomatous ileitis” • In 1952, Dr. Wells reported colonic involvement
What is Crohn’s Disease? • Crohn’s disease (CD) is an inflammatory bowel disorder that may affect any part of the gastro-intestinal (GI) tract • The inflammation penetrates the lining of the GI tract and often causes ulcers Esophagus Small Intestine Stomach Large Intestine (Colon) Rectum Appendix
History • 1859, Samuel Wilks described “simple idiopathic colitis” • 1909 • Hawkins described the natural history of UC • Hurst describe the sigmoidoscopic appearance
37% 46% 17% Disease Distribution at Presentation n=1116 Farmer RG. Dig Dis Sci;38:1137-1146
Goals of Therapy • Relieve symptoms • Prevent recurrence of symptoms • Prevent or cure complications • Control inflammation of the GI tract • Improve quality of life • Steroid sparing • Reduce the need for surgery
Disease Activity • Number of bowel movements a day • presence of blood in stool • abdominal exam (tenderness) • Weight loss • Extraintestinal manifestation • Overall well-being • Vitals: fever, tachycardia • Labs: anemia,
Medications for Mild-Moderate Disease • Aminosalicylates • Sulfasalazine • Mesalamine (Pentasa, Asacol, Colazal, Rowasa enema and Canasa Suppositories) • Antibiotics • Metronidazole (Flagyl) • Quinolones (Cipro)
Medications for Moderate-Severe Disease • Steroids • Prednisone • Solumedrol • Budesonide (Entocort) • Immunosuppressives • Azathioprine (Imuran) • 6-mercaptopurine (Purinethol) • Methotrexate • Cyclosporin
Medications for Moderate-Severe Disease • Biologics • Infliximab (Remicade)
Side Effects of Sulfasalazine • Fever • Headache • Rash • Nausea/vomiting • Diarrhea • Loss of appetite
Pentasa® Asacol® COLAZAL™ Stomach Small Intestine Large Intestine Mesalamine in microgranules Mesalamine w/ eudragit-S Azo bond Oral 5-ASA Release Sites Olsalazine Sulfasalazine
Mesalamine Side Effects • Nausea/vomiting • Heartburn • Diarrhea • Headache • Allergic Reaction
Flagyl metallic taste headache nausea/vomiting dizziness diarrhea peripheral neuropathy Cipro headache rash nausea/vomiting dizziness Achilles tendon rupture Antibiotic Side Effects
GI upset Acne Moon face Fluid Retention Diabetes HTN Striae Weight gain Cataracts Glaucoma Depression Osteoporosis Infection Growth retardation Steroid Side Effects
Outcome of Steroid Therapy for Patients with CD No response20% 1-Month Outcomes (n=109) Remission 48% Improved 32% 12-Month Outcomes (n=87) Remission54% Relapse46% Improved57% Relapse43% Summary Outcomes (n=109) Steroid Dependent 36% (n=39) Prolonged Response 44% (n=48) Steroid Resistant 20% (n=22) Munkholm P et al. Gut 1994;35:360
Purine Metabolism 6Methyl Mercaptopurine TPMT HPRT AZA 6MP 6TGN Xanthine oxidase 6Thiouric Acid
AZA/6MP Bone marrow suppression pancreatitis hepatitis allergic reaction lymphoma infections MTX hepatotoxicity pneumonitis teratogenic alopecia allergic reaction Immunosuppressant Side Effects