Case PresentationCase Presentation

• 34 y/o male 34 y/o male

• 5 years Crohn’s disease of ileum and Rt. 5 years Crohn’s disease of ileum and Rt. colon colon

• 10 days – Fever, chills10 days – Fever, chills

Watery diarrhea Watery diarrhea

RLQ abdominal pain RLQ abdominal pain

MedicalMedical HistoryHistory

• Last exacerbation 6m agoLast exacerbation 6m ago

• No surgical historyNo surgical history

• Treatment: Azathioprine 150 mgTreatment: Azathioprine 150 mg

Physical ExaminationPhysical Examination

Fever –38.6, HR-90Fever –38.6, HR-90

Tenderness – RLQ , WithoutTenderness – RLQ , Without

hepatosplenomegaly or ascitishepatosplenomegaly or ascitis

PR- normal PR- normal

No lymphadenpathyNo lymphadenpathy

Heart & lungs- normalHeart & lungs- normal

Laboratory DataLaboratory Data• Hb-Hb-11.511.5, MCV-81,WBC- 3400, Neu- 62%, MCV-81,WBC- 3400, Neu- 62%PLT-197PLT-197

• ALK.P, T Bill- normal, ALT-ALK.P, T Bill- normal, ALT-7171, GGT- , GGT- 110110, , LDH-LDH-746746

• Total Protein - 63 ,ALB - Total Protein - 63 ,ALB - 2929

• Folic acid, B12-normalFolic acid, B12-normal • Blood, urine , fecal culture , CDT -negativeBlood, urine , fecal culture , CDT -negative

ManagementManagement

Treatment 7 days with PO metronidazole Treatment 7 days with PO metronidazole and IV hydrocortisone – without and IV hydrocortisone – without improvementimprovement

• CMV IgG – negativeCMV IgG – negative

• CMV IgM – CMV IgM – positivepositive

• CMV antigenemia – negativeCMV antigenemia – negative

NEXT STEP?NEXT STEP?

CMV COLITISCMV COLITIS AZATHIOPRINEAZATHIOPRINEHYDROCORTISONEHYDROCORTISONE

STARTSTART

CMV IgMCMV IgM??

• 63 patient –Active IBD63 patient –Active IBD

• Evaluated for CMV :Evaluated for CMV :

IgM CMVIgM CMV

PCR – Colonic biopsyPCR – Colonic biopsy

H&E – Inclusion bodyH&E – Inclusion body

Kishore et al. J med microbiol 2004;53

Kishore et al. J med microbiol 2004;53

ILEOCECAL VALVEILEOCECAL VALVE

H&E STAININGH&E STAINING

?

Diagnosis IHC vs H&EDiagnosis IHC vs H&E

Kambham et al. Am J Surg pathol 2004; 28:3

Diagnosis IHC vs H&EDiagnosis IHC vs H&E

Kambham et al. Am J Surg pathol 2004; 28:3

CMV-IHC STAINIGCMV-IHC STAINIG

CMV COLITISCMV COLITIS

• Defective cell-mediated immunity: Defective cell-mediated immunity: • AIDS, organ transplant recipients, AIDS, organ transplant recipients,

immunosuppressionimmunosuppression

• Old age, cancer, CRF, alcoholismOld age, cancer, CRF, alcoholism

• Immunocompetent hosts : Immunocompetent hosts :

Mucosal damageMucosal damage

EPIDEMIOLOGY IN IBDEPIDEMIOLOGY IN IBD

• More common in UCMore common in UC - Prevalence: 4.6% in UC, - Prevalence: 4.6% in UC, 0.80.8% in Crohn’s % in Crohn’s

diseasedisease - 12% of patients with intestinal CMV - 12% of patients with intestinal CMV

infectioninfection Kaufman et al. Dis Colon Rectum 1999; 42: 24Kaufman et al. Dis Colon Rectum 1999; 42: 24

• Usually reactivation of latent virusUsually reactivation of latent virus

PREDISPOSING FACTORSPREDISPOSING FACTORS

• Duration of IBDDuration of IBD• Active inflammationActive inflammation• TreatmentTreatment - - Steroids with other immunosuppressionSteroids with other immunosuppression

Often in a patient who had long been Often in a patient who had long been stablestable

Kishore et al. J med microbiol 2004;53

CLINICAL CHARACTERISTICSCLINICAL CHARACTERISTICS

• Exacerbation of the underlying IBDExacerbation of the underlying IBD• Mononucleosis-like syndromeMononucleosis-like syndrome• Steroid -refractory colitisSteroid -refractory colitis• Additional GI manifestations – oral Additional GI manifestations – oral

lesions, odynopagialesions, odynopagia

Papadakis et al. Am J Gastroenetrolgy 2001; 96:7Kambham et al. Am J Surg pathol 2004; 28:3

DIAGNOSISDIAGNOSIS

• SerologySerology• CMV antigenemiaCMV antigenemia• PCR for CMV PCR for CMV • Endoscopic appearanceEndoscopic appearance - Erosions, ulcerations, mucosal hemorrhage- Erosions, ulcerations, mucosal hemorrhage

• Mucosal biopsy Mucosal biopsy -- Large cells with intranuclear and intracytoplasmic inclusionsLarge cells with intranuclear and intracytoplasmic inclusions

- Immunostaining- Immunostaining - Submucosal vasculitis or microvascular thrombosis- Submucosal vasculitis or microvascular thrombosis

TREATMENT

• Gancyclovir Gancyclovir • 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

TREATMENTTREATMENT

STOP!• Steroids (rapid tapering)• Cyclosporin• Azathioprine• 6-MP

IMMUNOSUPPRESSION IMMUNOSUPPRESSION THERAPY RENEWALTHERAPY RENEWAL??