Introduction
Painless rectal bleeding, or haematochezia, particularly when low in volume, often points towards a bleeding source in the distal gastrointestinal tract, below the ligament of Treitz. In patients with a history of portal hypertension and known internal haemorrhoids, this is frequently the initial presumed cause. However, the discovery of a solitary ulcer in the proximal colon during colonoscopy can present a diagnostic surprise, necessitating a broader differential diagnosis. This article delves into the differential diagnosis of colonic ulcers, emphasizing the often-overlooked role of cytomegalovirus (CMV), particularly in patients who may not present with classic risk factors for immunosuppression.
Uncommon Cause: Isolated Proximal Colon Ulcers
The finding of a solitary ulcer in the proximal colon during colonoscopy is not a common occurrence. Studies suggest that such findings are observed in only one to two out of every thousand colonoscopies. This figure may even be an overestimation when considering only patients undergoing colonoscopy for anaemia or blood loss, highlighting the relative rarity of this specific presentation. When encountered, a systematic approach to differential diagnosis is crucial to determine the underlying etiology and guide appropriate management.
Differential Diagnosis of Solitary Proximal Colon Ulcer
The differential diagnosis for a solitary proximal colon ulcer is broad and encompasses several key categories. It is essential to consider and rule out conditions such as:
- Malignancy: Colorectal cancer, particularly in its ulcerative form, must always be considered.
- Inflammatory Bowel Disease (IBD): Crohn’s disease can manifest with colonic ulcers, although it often involves more diffuse or discontinuous lesions.
- Medication Side Effects: Certain medications, notably non-steroidal anti-inflammatory drugs (NSAIDs), are known to be associated with colonic ulceration.
- Chemical Injury: Though less common in the proximal colon, chemical injury should be considered in specific clinical contexts.
- Infections: Infectious agents are important considerations, particularly in the context of colonic ulcers. Besides CMV, other infectious causes include amoebiasis and tuberculosis.
In the context of infections, Cytomegalovirus (CMV) colitis emerges as a critical, albeit sometimes under-recognized, entity. While initial investigations may focus on more common causes, the possibility of CMV infection, especially in certain patient populations, should be actively explored.
CMV Colitis: A Key Consideration
Gastrointestinal (GI) CMV disease, although classically associated with immunocompromised states like AIDS and organ transplantation, can also present in individuals with less overt forms of immunosuppression. Isolated ulcerations, including large solitary ulcers, are recognized endoscopic features of GI CMV disease. While CMV is known to cause ulceration throughout the GI tract, from the oesophagus to the small intestine, its manifestation as a solitary proximal colon ulcer warrants specific attention.
Patients with isolated proximal colon ulcers due to CMV may present with symptoms such as right lower quadrant abdominal pain, haematochezia, and constipation. This symptom profile, while not specific, should raise suspicion in the appropriate clinical setting.
Diagnosis of CMV Colitis
Diagnosing CMV colitis requires a multi-faceted approach, integrating clinical findings with laboratory and pathological evidence. Key diagnostic modalities include:
- Biopsy and Immunohistochemistry: Tissue biopsy with immunohistochemical (IHC) staining for CMV is considered the gold standard. The characteristic finding of intracellular inclusions with an “owl’s-eye” appearance on microscopy is highly sensitive and specific for CMV infection.
- Serological Testing: IgM antibody testing for CMV can indicate recent infection but does not definitively confirm active disease.
- Viraemia Detection (PCR): Polymerase chain reaction (PCR) testing for CMV DNA in blood can detect viraemia, although its sensitivity can vary, and thresholds for positivity may differ between institutions.
In clinical practice, biopsy with IHC remains the most crucial diagnostic step for confirming CMV colitis in tissue specimens.
Risk Factors for GI CMV Disease Beyond Classic Immunosuppression
While traditionally associated with profound immunosuppression, it is increasingly recognized that GI CMV disease can occur in patients without classic risk factors. Factors that can predispose individuals to CMV reactivation and subsequent GI disease include:
- Chemotherapy: Recent chemotherapy administration, even without overt signs of immunosuppression like neutropenia, is a significant risk factor. The diverse range of chemotherapy agents and their varying degrees of immunosuppressive effects highlight the need for vigilance.
- Age and Comorbidities: Advanced age and underlying comorbidities, such as chronic kidney disease, can also contribute to a state of relative immunosuppression, increasing susceptibility to CMV reactivation.
The growing body of literature documenting CMV colitis in immunocompetent individuals underscores the importance of considering this diagnosis even in the absence of apparent immunodeficiency. Patients who have received chemotherapy within a recent timeframe should be particularly considered at risk, even if they do not exhibit typical laboratory markers of immunosuppression.
Clinical Implications and Learning Points
The case of isolated proximal colon ulceration leading to the diagnosis of CMV colitis highlights several critical learning points for clinicians:
- Consider CMV in the Differential Diagnosis: In patients presenting with haematochezia and isolated proximal colon ulcers, especially after recent chemotherapy, CMV infection should be actively considered in the differential diagnosis, even in the absence of profound immunosuppression.
- Chemotherapy as a Risk Factor: Recognize recent chemotherapy as a significant risk factor for GI CMV disease, expanding the traditional risk profile beyond classic immunocompromised states.
- Need for Further Research: Further research is needed to better define the specific chemotherapy regimens, patient comorbidities, and degrees of immunosuppression that most significantly elevate the risk of clinically apparent CMV reactivation.
Until more definitive risk stratification is available, clinicians should maintain a heightened awareness of CMV infection as a potential cause of diarrhoea and lower GI bleeding in patients with a history of recent chemotherapy. Prompt consideration of CMV in the differential diagnosis and appropriate diagnostic testing can lead to timely management and improved patient outcomes.
References
[1] Reference 1 from original article
[2] Reference 2 from original article
[3] Reference 3 from original article
[4] Reference 4 from original article
[5] Reference 5 from original article
[6] Reference 6 from original article
[7] Reference 7 from original article
[8] Reference 8 from original article
[9] Reference 9 from original article
[10] Reference 10 from original article
[11] Reference 11 from original article
[12] Reference 12 from original article
[13] Reference 13 from original article
[14] Reference 14 from original article
[15] Reference 15 from original article
[16] Reference 16 from original article
