S4885 No Stone Left Unturned: Rapid Induction of Remission With Upadacitinib Followed by Cytomegalovirus-Colitis in a Hospitalized Patient With Crohn’s Disease

Introduction: Patients with Crohn’s disease (CD) who develop severe symptoms often require hospitalization for rapid induction of remission to improve symptoms and prevent progression of complications. Case Description/Methods: A 60-year-old woman with ulcerative proctitis (diagnosis changed to CD due to penetrating perianal disease) on mesalamine, hydrocortisone enemas, and prednisone 20 mg (taper) presented with severe rectal pain and bloody diarrhea. Her hemoglobin was 10 g/dL, C-reactive protein (CRP) 27 mg/dL, albumin 2.6 mg/dL, and fecal calprotectin 3173 mg/kg. Serum cytomegalovirus (CMV) polymerase chain reaction was positive with viral load <50 IU/mL. Magnetic resonance imaging pelvis showed an intersphincteric perianal fistula with a 3.3 cm horseshoe abscess and active proctocolitis. She was started on intravenous methylprednisolone. Flexible sigmoidoscopy revealed large, deep ulcers in the rectum and sigmoid (extent reached); histology showed chronic active colitis with negative CMV immunostain. Given severe inflammation and low albumin, high-intensity, off-label upadacitinib (30 mg BID) was initiated. After 8 days of upadacitinib, her symptoms and CRP normalized. Despite improved stool frequency, she developed new onset hematochezia and her hemoglobin dropped to 5.8 g/dL. Colonoscopy showed mucosal healing and improved fecal calprotectin (285 mg/kg), with histology revealing regenerative changes and quiescent colitis. Upadacitinib was decreased to 45 mg daily, and she transitioned to oral prednisone. Unfortunately, less than 2 weeks following the improved colonoscopy, she developed recurrent abdominal pain, worsening bloody stools, and rising CRP. She was deemed medically refractory and underwent total colectomy. Surgical pathology revealed CMV colitis, without any active Crohn’s disease. CMV polymerase chain reaction viral load was 2236 IU/mL. CMV infection resolved with ganciclovir. Discussion: While this patient had a rapid initial response to off-label, high-intensity upadacitinib, she subsequently demonstrated clinical deterioration ultimately undergoing colectomy for suspected refractory CD. Surgical pathology unexpectedly revealed quiescent CD with CMV colitis despite no initial endoscopic evidence of infection. This highlights the importance of considering repeat endoscopy to evaluate for alternative causes (especially treatable causes, such as CMV) when a patient with inflammatory bowel disease initially improves with treatment then suddenly worsens.