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Treating the Challenging Inpatient with Complicated IBD: Case Studies Peter D.R. Higgins, MD, PhD, MSc University of Michigan Slide 2 Todays Cases Difficult inpatients The kind that are NOT eligible for clinical trials Limited, if any, RCT data available There are frequently NO right answers Management through general principles, art, analogy, and a bit of science Slide 3 COMPLICATED CROHNS DISEASE CASE 1 Slide 4 Case 1: Crohns Disease 23 year old male with CD x 4 years Ileal and segmental colonic location Failed 5-ASA x 8m, Aza x 3 years, now referred after starting IFX monotherapy x 4m Slowly worsening RLQ pain, fevers x 2 months CT Scan ordered Admitted with CRP 4.3, ESR 78, Albumin 2.2, Prealbumin 3 after scan result. Slide 5 Long arrows: Active inflammatory TI stricture Short yellow arrow: retroperitoneal abscess cavity medial to the cecum Slide 6 Coronal images Long arrows: Active inflammatory TI stricture Short yellow arrows: retroperitoneal abscess cavity medial to the cecum Slide 7 Consultant Notes Radiology: 2.6 cm abscess medial to cecum, adjacent to long (15 cm) TI stricture with active inflammation. Unable to drain safely. Upstream SB dilated to 3.6 cm. Surgery: No emergent indication for surgery. Recommend maximize medical therapy to eliminate inflammation and eradicate all infection before elective surgery. Follow up in surgery clinic in 8 weeks. Slide 8 Options? Continue anti-TNF? What are the anti-inflammatory options? Anti-microbial therapy? Surgical therapy? Will this situation recur? Will this damaged bowel be responsive to therapy? Discuss Slide 9 Medical Therapies Anti-TNF Systemic steroids Topical steroids Entocort Immunomodulators Methotrexate Azathioprine Abscess fertilizers Slide 10 Anti-microbial therapy Drainage Would be optimal, not always possible 60-84% can be drained in case series with 2+ attempts Antibiotics Cover gut bugs broadly Consider iv for best bioavailability Consider early re-image (3-5d) if incomplete drainage Long term, re-image in 4-6 weeks Waljee, Chapter 135, Advanced Therapy of IBD text, ed. Bayless and Hanauer Feagins, Kane, et al, CGH 2011:842 Slide 11 Is Surgery Avoidable? Usually not Penet rating complications occur close to strictures Increased pressure within and upstream Inflammation weakens walls Likely to recur unless stricture fixed There are exceptions inflammatory strictures Can you drain and start anti-TNF? 31% recur @5y N=55 Goal is generally to get patient to ELECTIVE surgery Nguyen, Sandborn, et al. CGH 2012: 400-4 Slide 12 Goals for pre-op visit Eradicate infection Control mucosal inflammation Even better, control transmural inflammation Limit/reduce length of resection neoadjuvant anti-TNF therapy? Prevent new fistulas, abscesses Boost nutritional status Prealb, Alb Boost functional status Pre-hab Slide 13 Hans Herfarth, MD, PhD University of North Carolina at Chapel Hill Chapel Hill, North Carolina Treating the challenging inpatient with complicated IBD: Case studies Slide 14 27 yo female patient, hospitalized for refractory ulcerative colitis PMHx: Diagnosis of ulcerative pancolitis 2.5 years ago Initial therapy with steroids and 5-ASA without improvement, start of infliximab. Allergic reaction with shortness of breath, chest pain during maintenance therapy Start of 6-MP, remission for 18 months until 3 weeks before hospitalization. 2 weeks before hospitalization start of oral steroids (40 mg prednisolone) without success Case 2 Slide 15 Time of consult: 8-10 bloody bowel movements/day, no fever Physical exam: Abdomen soft, non-tender Medication: Start of 60 mg methylprednisolone iv yesterday. Labs: WBC 11.9 x10 9 th /L, HGB 8.9 g/dl, platelets 550,000 x10 9 th /L, CRP 9.4 mg/dl. Case 2 (cont'd) Slide 16 Rectum Sigmoid Colon Slide 17 Case 2 (cont'd) Slide 18 Therapeutic options in the setting of no response to steroids in active UC and pregnancy: Infliximab Adalimumab Golimumab Cyclosporine Colectomy with ileostomy Case 2 (cont'd) Slide 19 8 patients 7-Pan-UC 1 Left sided UC Pregnancy week 6-27 3 case reports, 3 case series with 2, 5 and 8 patients Cyclosporine Therapy of UC in Pregnancy Iv cyclosporine for 5-17 days (1 patient oral), then switch to oral cyclosporine (2 patients + AZA 7/8 patients with response to therapy. One patient after 17 days switch to IFX with response (later on Dx of CD) 7/8 pregnancies conducted to term. 1 death at week 22 (cyclosporine started week 10; mother with protein-S defect). Two newborns premature. Branche et al. 2009 Slide 20 Surgical management of Therapy Refractory UC in Pregnancy 11 case reports with 1 or 2 patients, 4 case series with 4, 5, 7 and 9 patients Case series before 2000, especially around the 1970s significant mortality of mothers or infants Case series Mayo 2006 (Dozois et al. 2006): 5 patients with UC. All with subtotal colectomy at first (1), second (3) and third trimester (1) No complications after surgery or during delivery. Slide 21 Time period 1989-2001: 11 patients with UC, 6 patients with CD, 1 patient with IC Hospitalization and treatment with hydrocortisone n=18, cyclosporine n=5, start of 6-MP/AZA n=3. 15 pat. 83% response to medical therapy, 3 (17%) colectomy. 1 patient in cyclosporine group spontaneous abortion week 15. Reddy et al. 2008 In-Hospital Management and Birth Outcomes in Pregnancy in 2 Tertiary Care Centers (Mount Sinai, NYC, Chicago) p Outcome case UC pregnancy Start of cyclosporine 2 mg/kg bw. Aim trough level >200Slide 23 SEVERE ULCERATIVE COLITIS CASE 3 Slide 24 Case 3: Severe Ulcerative Colitis 19 year old female with UC x 4 months 3 m on 5-ASA, various types and doses 1 m on Aza 2.5 mg/kg TPMT 13.2 C diff infection found 3 weeks ago Flagyl x 10 days, better on days 5-10 Then worsened 22 bloody BM daily, low-grade fevers Slide 25 Admitted CDTOX negative WBC 12.2, ESR 33, CRP 9.2 HR 95, BP 122/78 IV methylprednisolone 60 mg daily Small improvements Day 2 scope - severe UC, no CMV End of day 3: 15 BM/day, CRP 6.9 Slide 26 Options? Prognosis? What are the rescue therapy options? How to dose/frequency of dosing? Where will drug go? How to monitor levels? Implications of surgery on fertility? What are long-term risks/benefits? Discuss. Slide 27 An Extreme Paucity of Data A fair amount of trial and error Trial and failure, learn from your mistakes IFX can leak out of colon into stool in surprisingly large amounts CRP is invariably high, and falls with therapy Retrospectively developed prognostic indices help If steroids are not working by day 3, will not work In the CYSIF trial, IFX ~ Cyclo at 90 days Slide 28 What Various IBD Centers Do Operate at Day 4 Rescue with Cyclosporine (decreasing) Rescue with IFX Dose high (10 mg/kg) Dose often (5 mg/kg q 72h until CRP