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

IBD Facts Approx 1,000,000 Americans have IBD men and women affected equally first peak occurs between the ages of a later peak occurs in the 7th decade

Histology

Normal Intestine Vs. IBD Environmental triggers (infection, bacterial products) Moderately inflamed Failure to down- regulate Chronic uncontrolled inflammation = IBD Down-regulate Normal gut controlled inflammation Normal gut controlled inflammation

Evidence of Genetic Influence Prevalence varies among different populations risk in increased among first degree relatives greater concordance among monozygotic than diazygotic twins recent identification of “susceptibility genes” (NOD2/CARD 15)

Proportion of Patients with Family History of IBD by Age of Diagnosis * * *p<0.005 % Patients with Positive Family History of IBD 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

Erythema Nodosum

Pyoderma Gangrenosum

Crohn’s Disease

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 Small Intestine Large Intestine (Colon) Appendix Esophagus Stomach Rectum

Crohn’s Disease: Fistula

Fibrostenotic Crohn’s Disease

Crohn’s Disease Histology

Ulcerative Colitis

History 1859, Samuel Wilks described “simple idiopathic colitis” 1909 –Hawkins described the natural history of UC –Hurst describe the sigmoidoscopic appearance

Disease Distribution at Presentation n= % 17% 46% Farmer RG. Dig Dis Sci;38:

Ulcerative Colitis Complications Massive Bleeding Perforation Acute Dilation Pseudopolyps Colonic Cancer Extraintestinal manifestations

Ulcerative Colitis Histology

Medical Treatment

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

Oral 5-ASA Release Sites Stomach Small Intestine Large Intestine Azo bond COLAZAL ™ Mesalamine in microgranules Pentasa ® Mesalamine w/ eudragit-S Mesalamine w/ eudragit-S Asacol ® Sulfasalazine Olsalazine

Mesalamine Side Effects Nausea/vomiting Heartburn Diarrhea Headache Allergic Reaction

Antibiotic Side Effects Flagyl –metallic taste –headache –nausea/vomiting –dizziness –diarrhea –peripheral neuropathy Cipro –headache –rash –nausea/vomiting –dizziness –Achilles tendon rupture

Steroid Side Effects GI upset Acne Moon face Fluid Retention Diabetes HTN Striae Weight gain Cataracts Glaucoma Depression Osteoporosis Infection Growth retardation

Outcome of Steroid Therapy for Patients with CD No response 20% Remission 54% Relapse 46% Improved 57% Relapse 43% Remission 48% Improved 32% 1-Month Outcomes (n=109) 12-Month Outcomes (n=87) 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 AZA 6MP6TGN 6Methyl Mercaptopurine 6Thiouric Acid Xanthine oxidase TPMT HPRT

Immunosuppressant Side Effects AZA/6MP –Bone marrow suppression –pancreatitis –hepatitis –allergic reaction –lymphoma –infections MTX –hepatotoxicity –pneumonitis –teratogenic –alopecia –allergic reaction

Infliximab

Infliximab Side Effects Reactivation of TB Headache Nausea Upper respiratory tract infection Other serious infections Fatigue Fever

Referral to Surgeon Symptoms not relieved by medications Serious complications –abscesses –fistula –intestinal blockage –uncontrolled bleeding

Conclusion Crohn’s Disease and Ulcerative Colitis are the two major types of IBD The inflammatory bowel diseases are chronic diseases the are caused by genetic, environmental factors and immunologic abnormalities Medical treatment options should be tailored based of disease type, distribution and pattern

Conclusion Medical treatment will usually relieve symptoms but relapse is common and therefore treatment is lifelong