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Cytomegalovirus colitis masquerading as an indeterminate colitis flare-up: Case report and review of the literature
*Corresponding author: Krishnasree Sasikumar, Department of Internal Medicine, Manipal Hospital, Sarjapur, Bengaluru, Karnataka, India. krishnasreesasikumar@gmail.com
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Received: ,
Accepted: ,
How to cite this article: Sasikumar K, Havannavar S. Cytomegalovirus colitis masquerading as an indeterminate colitis flare-up: Case report and review of the literature. Karnataka Med J. 2025;48:26-9. doi: 10.25259/KMJ_58_2024
Abstract
This case report describes a 63-year-old female who presented with severe, refractory lower gastrointestinal bleeding. An initial colonoscopy was inconclusive, and due to ongoing massive bleeding unresponsive to conservative treatment, she underwent a subtotal colectomy. Histopathological examination of the colectomy specimen revealed indeterminate colitis (IC), and she was managed with conventional inflammatory bowel disease (IBD) therapies. However, her symptoms persisted post-surgery, including decreased appetite, weight loss, abdominal pain, and fatigue. Further evaluation revealed active indeterminate IBD associated with cytomegalovirus (CMV) colitis and refeeding syndrome. Sigmoidoscopy confirmed active colitis with CMV inclusions. The patient was treated with antiviral therapy using ganciclovir, aggressive management of refeeding syndrome, and concurrent IBD therapy. She showed significant clinical improvement following this multidisciplinary approach. This case highlights the importance of considering CMV infection, even in immunocompetent individuals with refractory IBD, and demonstrates that antiviral treatment can be critical to recovery when standard therapies fail. It also emphasizes the need to evaluate the role of steroids and biologics in managing IC with CMV coinfection.
Keywords
Cytomegalovirus
Cytomegalovirus colitis
Ganciclovir
Indeterminate colitis
Inflammatory bowel disease
INTRODUCTION
Cytomegalovirus (CMV) infection is commonly asymptomatic in immunocompetent individuals, This report presents a case of a 63-year-old female with a history of type 2 diabetes mellitus, hypertension and cerebrovascular accident (CVA), with severe refractory lower gastrointestinal (GI) bleeding, previously inconclusive colonoscopy who was ultimately treated with subtotal colectomy in view of uncontrolled massive lower GI bleed but had persistent symptoms. She presented with persistent symptoms of decreased appetite, vomiting, bloody diarrhoea, weight loss, abdominal pain and fatigue post-surgery.
The patient was diagnosed with indeterminate colitis (IC) histopathological examination [HPE] who continued to have refractory bloody diarrhoea even after subtotal colectomy and abdominal pain that did not respond to standard medical management. She was evaluated further and colonoscopic biopsy revealed CMV colitis. The patient ultimately improved only after treatment with ganciclovir. Although unusual, it is important to consider CMV in patients with inflammatory bowel disease (IBD) flare-ups refractory to conventional therapy, as appropriate anti-viral therapy may spare the patient surgery and helps inthe complete recovery of symptoms.
The patient’s presentation was complicated by an indeterminate diagnosis of IBD, where conventional medical management proved ineffective. The subsequent diagnosis of CMV colitis highlights the need for awareness of this infection in immunocompetent patients with indeterminate IBD.
Objectives
To provide an overview of the diagnostic and therapeutic approach for a patient with IBD associated with CMV colitis and refeeding syndrome, while addressing the challenges in managing such a complex case. To provide an overview of the diagnostic and therapeutic approach for a patient with indeterminate IBD where biopsy is non-conclusive and the role of steroids and immunosuppressants and surgical management in indeterminate IBD with primary CMV colitis.
CASE REPORT
The 63-year-old female patient presented with 2-week history of decreased appetite, weight loss, abdominal pain, vomiting, bloody diarrhoea and fatigue. There is no history of fever. She is a known case of type 2 diabetes mellitus and hypertension for 10 years, CVA in February 2023: Left-sided hemiplegia due to right basal ganglia bleed and laparoscopic cholecystectomy in 2023. Physical examination revealed pallor, hypotension (blood pressure [BP] 80/60 mmHg), tachycardia (pulse rate [PR] 108 bpm) and abdominal tenderness. No icterus, pedal oedema or lymph node enlargement and other systemic examination was normal. She had undergone a subtotal colectomy with ileorectal anastomosis on 30 March 2024 for massive refractory lower GI bleeding and HPE of colectomy specimen showed acute severe IC. Ileostomy closure was done on 19 June 2024. Post-surgery, she continued to have symptoms such as abdominal pain, vomiting and bloody diarrhoea and extreme fatigue, which were affecting her daily routine.
Relevant investigations showed that low haemoglobin of 6, total leucocyte count and platelets were normal. Renal function was normal. Hypokalaemia and hypoalbuminaemia were present. Stool occult blood was positive. Computed tomography abdomen showed grossly distended rectum, sigmoid colon, descending colon, transverse colon up to hepatic flexure and part of ascending colon [Figure 1a and b]. Mild wall thickening of the ascending colon with mild pericolic fat stranding. Mild wall thickening in whole length of distended rectum. Multiple small mesorectal lymph nodes.
- (a and b) Computed tomography abdomen images showing dilated bowel loops (blue arrows) with thickening.
Sigmoidoscopy was done which revealed multiple erosions and ulcers in the proximal sigmoid colon [Figure 2] and biopsy revealed active colitis, favouring infective colitis with CMV inclusions-CMV colitis (positive immunohistochemistry [IHC] for CMV) [Figure 3a and b]. Serum CMV polymerase chain reaction (PCR) was also positive (57.1 copies).
- Colonoscopy showing mutiple ulcers and erosions in the sigmoid colon (blue arrow) with active oozing.
- (a) Shows endothelial cells with intranuclear cytomegalovirus (CMV) inclusions, (40x) (blue arrow), scale 50 um, H and E Stain. (b) CMV inclusion bodies show endothelial cells with intranuclear CMV inclusions (100x), (blue arrow) scale 50 um, H and E Stain. H and E: Hematoxylin and Eosin stain.
She was started on IV ganciclovir along with conventional medical management for IBD (mesalamine iv ciprofloxacin, metronidazole, sulfasalicylic acid and proper nutritional support). Aggressive management of the refeeding syndrome, which she developed after initiation of feeding through NG tube (she had hypokalaemia, hypomagnesaemia and hypophosphatemia with peripheral oedema) was done with electrolyte correction (IV MgSO4, IV KCl and IV phosphate) and with IV albumin, thiamine, vitamin C and micronutrients.
Main dilemma was the initiation of steroid plus or minus immunomodulators/anti-TNF alpha agents in the setting of underlying severe active CMV colitis. We started her on a budesonide tablet along with IV ganciclovir for 14 days.
Follow-up and outcomes
The patient’s condition drastically improved with IV ganciclovir, proper nutritional support, electrolyte and micronutrient correction and concurrent IBD management. She was discharged after 14 days of intravenous ganciclovir therapy, continuing with oral therapy at home.
DISCUSSION
This case highlights the complexities of managing active CMV colitis with concurrent IC and refeeding syndrome. CMV colitis, while more common in immunocompromised patients, can occur in immunocompetent individuals and must be considered in patients with unexplained GI symptoms and refractory GI bleeding.[1]
Key points
IC represents a diagnostic challenge and requires careful management
CMV should be a consideration in refractory IBD cases not responding to conventional treatment modalities and may avoid unnecessary surgical interventions
Refeeding syndrome is a significant concern in postoperative care and requires proactive management of electrolytes.
Literature review
CMV colitis is typically associated with immunocompromised states but can also occur in immunocompetent individuals, complicating diagnosis and management.[1] The presence of post-operative refeeding syndrome further increases morbidity, underscoring the need for vigilant electrolyte and nutritional management.
IC
The term IC was originally used by pathologists to describe colectomy specimens that lacked the classic features of either ulcerative colitis (UC) or Crohn’s disease (CD).[2] Clinically, it now refers to patients in whom a clear diagnosis cannot be established using standard endoscopic, histologic or radiologic criteria. Approximately 10% of IBD patients fall into this category.[3] Diagnostic clarity is critical, especially when surgical intervention is considered, since operative choices and outcomes vary significantly between UC and CD.
Total proctocolectomy with ileal pouch–anal anastomosis remains the gold-standard surgical approach for UC, but it carries higher complication rates in CD. Patients with IC experience intermediate outcomes – better than CD but worse than UC – with about half eventually reclassified as either UC or CD.[4] Serologic markers such as anti-Saccharomyces cerevisiae antibody and perinuclear antineutrophil cytoplasmic antibody may aid in differentiation, although most IC patients test negative.[5] Clinically, management often parallels that of UC, but distinguishing backwash ileitis from Crohn’s involvement can be difficult.
CMV colitis in IBD
CMV is a ubiquitous herpesvirus that typically remains latent in immunocompetent hosts. Reactivation may occur in the GI tract under conditions of severe inflammation, mucosal disruption or immunosuppressive therapy.[6]
Endoscopic features of CMV colitis vary and may include well-demarcated ulcerations, ulceroinfiltrative lesions or pseudomembranes. Histopathologic examination remains the diagnostic gold standard, revealing large cells (25–35 μm) with basophilic intranuclear inclusions, pathognomonic for CMV infection.
Diagnosis requires both serologic and histologic confirmation. IHC using CMV-specific monoclonal antibodies or PCR assays for viral DNA enhances sensitivity and specificity.[7] Positive CMV IgM titres or antigenaemia correlate with histopathologic findings and support the diagnosis.
Therapeutic considerations
Ganciclovir remains the first-line antiviral therapy for CMV colitis, including in immunocompetent patients, as untreated disease is associated with poor outcomes. Although adverse effects such as myelosuppression, hepatotoxicity and nephrotoxicity can occur, careful monitoring enables safe and effective therapy.[8] In the present case, prompt administration of intravenous ganciclovir led to significant clinical and endoscopic improvement without detectable toxicity.
The continuation of immunomodulators and biologic therapy during CMV infection remains controversial. The European Crohn’s and Colitis Organisation guidelines recommend temporary cessation of all immunosuppressive therapy until CMV colitis is controlled.[9] In contrast, Ciccocioppo et al. suggested tapering corticosteroids rapidly but maintaining long-acting immunosuppressants or biologics in patients with high mucosal viral loads.[10] Sager et al. proposed that conventional corticosteroid therapy may be continued with concurrent antiviral treatment when clinically necessary.[11]
Emerging evidence suggests that anti-tumour necrosis factor (anti-TNF) therapy may be safe – and possibly beneficial – in CMV-associated colitis. Lavagna et al.[12] found that infliximab did not induce CMV reactivation in refractory CD patients. Subsequent studies reported similar CMV reactivation rates in UC patients treated with anti-TNF agents or azathioprine, with no increase in viral load during biologic therapy.[12] TNF-a blockade may even reduce CMV replication by lowering mucosal inflammation, making anti-TNF therapy preferable to other immunosuppressants for managing CMV-associated UC flare-ups.
CONCLUSION
CMV colitis can present in immunocompetent patients and should be considered when encountering unexplained rectal bleeding or GI symptoms. Timely diagnosis and treatment are crucial for improving outcomes, particularly in elderly patients or those with significant comorbidities. Standard treatment for the flare-up in IBD, which included intravenous corticosteroids, bowel rest, topical salicylates and ultimately colectomy, was not effective. Th e pa tient did no t improve until therapy with intravenous ganciclovir was initiated. The diagnosis is not frequently entertained and, if not made, leads to a high rate of colectomy (67%) and mortality (33%). Appropriate antiviral therapy appears to eliminate these complications; thus, a high index of suspicion for CMV superinfection/primary infection in cases of IBD refractory to traditional therapy is warranted. However, a large-scale study is required to explore the utility of immunomodulators as treatments for CMV colitis complicating UC.
Authors' contributions:
KS, SH: Case evaluation, work-up, investigation, data gathering, manuscript drafting, editing, literature review.
Ethical approval:
Institutional Review Board approval is not required.
Declaration of patient consent:
Patient’s consent not required as patients identity is not disclosed or compromised.
Conflicts of interest:
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
Financial support and sponsorship: Nil.
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