4 Medical course – Medical options? Hypertension (3 drug) Osteopenia DVT Persistent pancolitisMedical options?
5 Medical Therapy Medical treatment options? IV steroids? Infliximab? Tacrolimus?Fecal transplant?
6 Surgical Options?Optimization for surgery?IPAA candidate?
7 Clinical CourseAge two - Total abdominal colectomy with plan for delayed reconstructionPersistent bleeding from rectumCompletion proctectomy with J-pouch reconstructionPouchitis responsive to antibiotics
8 Patient 2 – refractory UC 18 year old male – 3 weeks bloody diarrhea8 BM per dayCultures and C. difficile negativeColonoscopy –pancolitis, normal ileumPlaced on prednisone (60 mg daily) with improvementMesalamine maintenance1600 mg bidSymptoms rapidly recurred as soon as prednisone tapered despite mesalaminePrednisone dose increased
9 What would you do for maintenance therapy? Azathioprine or mercaptopurineMethotrexateInfliximabAdalimumab
10 One year remission rates in UC Thiopurine - Pediatric IBD registry %*Infliximab - ACT 1 clinical trial 30%**Adalimumab - ULTRA 2 clinical trial 22%***Methotrexate - retrospective VA 30%*****Hyams AJ Gastro 2011** ACT 1 and 2 NEJM 2006*** Sandborn, Gastroenterology 2012****Khan, IBD Journal 2012
11 Management Patient started on mercaptopurine Dose increased to 2 mg/kg/dayStill steroid dependent after 3 monthsLevel – 6TG 168, 6MMP – 4200Infliximab and surgery discussed but reluctant6MP – 37.5 mg dailyAllopurinol, 100 mg dailyAfter 2 months – 6TG 306, MMP 0, improvement but still requires low dose steroid (10-15 mg daily)3-5 BM per day
12 Management 2Repeat colonoscopy – active disease from transverse to rectum (Mayo score 1-2)Begun on infliximabContinued allopurinol / 6MPImprovement after 3 monthsSteroid free2-3 BM per day
13 QuestionsWould you continue the mercaptopurine in addition to the infliximab?Would you continue the allopurinol?What about the risk of hepatosplenic T cell lymphoma?Is surgery preferable to all this immunosuppression?What information would surgeons give to help this patient weigh risks and benefits?
14 Outcome Allopurinol discontinued, but disease worsened Infliximab dose increased to 10 mg/kg every 6 weeks, but disease remained activeReferred to a surgeon for information, but not interested in surgerySecond opinionRestart allopurinol, continue 6MPDisease enters remission, continues combination therapy for UC
16 Presenting history 16 year old male Presented with bloody diarrhea EGD normal; colonoscopy with normal TI and pan-colitisResponded to IV steroidsFlared during oral prednisone taperReceived infliximab 5 mg/kg x 2 seven days apartSecond opinion, admittedPUCAI 80, Cdiff negative
18 Diagnostic Tests CTE: pan-colitis, normal small bowel Flex Sig: severe colitis, CMV PCR negativeInfliximab level 9 days after second 5 mg/kg dose: 18 mcg/mL, neg. antibodies
19 Medical Therapy Medical treatment options? IV steroids? Higher dose infliximab?Tacrolimus?Vedolizumab?Fecal transplant?
20 Clinical courseIV steroids and infliximab 10 mg/kg x 2 seven days apartTPNPUCAI 75
21 Medical or Surgical Therapy? Tacrolimus?Vedolizumab?Diverting ileostomy?Subtotal colectomy with end ileostomy?Procto-colectomy with J-pouch and ileostomy?
22 Clinical course Subtotal colectomy with end ileostomy Colectomy specimen: no creeping fat, terminal ileum normal, severe chronic active colitisNo granulomas or transmural inflammationDischarged home, feeling wellTwo months later developed mouth sores, otherwise feels well, with second stage J-pouch planned soonTests?
23 Diagnostic TestsEGD: Antrum with apthous ulcers – mild chronic active gastritis and duodenitisIleum: first 5 cm friable with chronic active ileitis, remainder normalFlex Sig: inflamed rectum with chronic active colitis
24 What Now? Does he have Crohns or UC ? Other tests ? Proceed with procto-colectomy with J-pouch and ileostomy?Treat proctitis and then proceed with ileo-rectal anastomosis if healed?Wait?