1. Case Presentation 34 y/o male34 y/o male 5 years Crohn’s disease of ileum and Rt. colon5 years Crohn’s disease of ileum and Rt. colon 10 days – Fever, chills10 days – Fever, chills Watery diarrhea Watery diarrhea RLQ abdominal pain RLQ abdominal pain

2. Medical History Last exacerbation 6m agoLast exacerbation 6m ago No surgical historyNo surgical history Treatment: Azathioprine 150 mgTreatment: Azathioprine 150 mg

3. Physical Examination Fever –38.6, HR-90 Tenderness – RLQ, Without hepatosplenomegaly or ascitis PR- normal No lymphadenpathy Heart & lungs- normal

4. Laboratory Data Hb-11.5, MCV-81,WBC- 3400, Neu- 62%Hb-11.5, MCV-81,WBC- 3400, Neu- 62%PLT-197 ALK.P, T Bill- normal, ALT-71, GGT- 110, LDH-746ALK.P, T Bill- normal, ALT-71, GGT- 110, LDH-746 Total Protein - 63,ALB - 29Total Protein - 63,ALB - 29 Folic acid, B12-normalFolic acid, B12-normal Blood, urine, fecal culture, CDT -negativeBlood, urine, fecal culture, CDT -negative

5. Management Treatment 7 days with PO metronidazole and IV hydrocortisone – without improvement

6. CMV IgG – negativeCMV IgG – negative CMV IgM – positiveCMV IgM – positive CMV antigenemia – negativeCMV antigenemia – negative

7. NEXT STEP? CMV COLITIS AZATHIOPRINEHYDROCORTISONE START

8. CMV IgM? 63 patient –Active IBD63 patient –Active IBD Evaluated for CMV :Evaluated for CMV : IgM CMV IgM CMV PCR – Colonic biopsy PCR – Colonic biopsy H&E – Inclusion body H&E – Inclusion body Kishore et al. J med microbiol 2004;53

10. ILEOCECAL VALVE

11. H&E STAINING

12. ?

13. Diagnosis IHC vs H&E Kambham et al. Am J Surg pathol 2004; 28:3

14. Diagnosis IHC vs H&E Kambham et al. Am J Surg pathol 2004; 28:3

15. CMV-IHC STAINIG

16. CMV COLITIS Defective cell-mediated immunity:Defective cell-mediated immunity: AIDS, organ transplant recipients, immunosuppressionAIDS, organ transplant recipients, immunosuppression Old age, cancer, CRF, alcoholismOld age, cancer, CRF, alcoholism Immunocompetent hosts :Immunocompetent hosts : Mucosal damage Mucosal damage

17. EPIDEMIOLOGY IN IBD More common in UCMore common in UC - Prevalence: 4.6% in UC, 0.8 % in Crohn’s disease - Prevalence: 4.6% in UC, 0.8 % in Crohn’s disease - 12% of patients with intestinal CMV infection - 12% of patients with intestinal CMV infection Kaufman et al. Dis Colon Rectum 1999; 42: 24 Kaufman et al. Dis Colon Rectum 1999; 42: 24 Usually reactivation of latent virusUsually reactivation of latent virus

18. PREDISPOSING FACTORS Duration of IBDDuration of IBD Active inflammationActive inflammation TreatmentTreatment - Steroids with other immunosuppression - Steroids with other immunosuppression Often in a patient who had long been stable Kishore et al. J med microbiol 2004;53

19. CLINICAL CHARACTERISTICS Exacerbation of the underlying IBDExacerbation of the underlying IBD Mononucleosis-like syndromeMononucleosis-like syndrome Steroid -refractory colitisSteroid -refractory colitis Additional GI manifestations – oral lesions, odynopagiaAdditional GI manifestations – oral lesions, odynopagia Papadakis et al. Am J Gastroenetrolgy 2001; 96:7 Kambham et al. Am J Surg pathol 2004; 28:3

20. DIAGNOSIS SerologySerology CMV antigenemiaCMV antigenemia PCR for CMVPCR for CMV Endoscopic appearanceEndoscopic appearance - Erosions, ulcerations, mucosal hemorrhage - Erosions, ulcerations, mucosal hemorrhage Mucosal biopsyMucosal biopsy - Large cells with intranuclear and intracytoplasmic inclusions - Large cells with intranuclear and intracytoplasmic inclusions - Immunostaining - Immunostaining - Submucosal vasculitis or microvascular thrombosis - Submucosal vasculitis or microvascular thrombosis

21. TREATMENT GancyclovirGancyclovir 5 mg/kg bid5 mg/kg bid 6 weeks of intravenous treatment6 weeks of intravenous treatment Marked improvement usually noted within a weekMarked improvement usually noted within a week

22. TREATMENT STOP! Steroids (rapid tapering) Cyclosporin Azathioprine 6-MP

23. IMMUNOSUPPRESSION THERAPY RENEWAL?