In UC, the Mayo score and Montreal classification work together to comprehensively assess the disease. The Mayo score, calculated from stool frequency, bleeding, urgency, and endoscopic findings, reflects disease severity. Meanwhile, the Montreal classification categorizes the location of inflammation (rectum only, left colon, or beyond), guiding treatment decisions. By combining these tools, healthcare professionals gain a clearer picture of UC activity and location, allowing for more personalized treatment plans and disease monitoring [12, 13]. The recent increase in the use of innovative immunosuppressive drugs, notably biologics, has altered the therapy landscape for IBD. However, this therapeutic progress raises a critical safety concern: an increased risk of opportunistic infections. These infections provide a distinct challenge to doctors. They can be severe, resulting in considerable morbidity and death, but are frequently difficult to detect due to unique symptoms. Furthermore, opportunistic infections in IBD patients might be more difficult to treat effectively than in the general population [1]. Immunosuppressed IBD patients must be particularly cautious about a variety of opportunistic infections. This includes, but is not limited to, bacterial illnesses like Tuberculosis (TB) and Clostridium difficile, as well as viral infections like hepatitis A, B, and C, CMV, varicella zoster virus (VZV), and even Human Immunodeficiency Virus (HIV). These opportunistic infections might be minor or life-threatening [1]. Based on the positive result of CMV IgG, there is no difference in the prevalence between IBD patients and healthy individuals. Notably, there is a remarkable rise in the prevalence of positive CMV IgM and CMV replication among steroid-resistance IBD patients [14]. For a variety of reasons, UC patients are more vulnerable to CMV reactivation than Crohn’s disease (CD) patients, including (1) dysfunction of the innate immune system; (2) dysfunction of the adaptive immune system; (3) dysfunction of mucosal immunity; and (4) increased production of cytokines, particularly TNF, which has been found to promote CMV [15]. In Crohn’s disease, CD4 + T cells produce interferon alpha, which prevents CMV reactivation and may explain the difference in CMV prevalence between CD and UC [16]. Many risk factors were noted to be associated with an increased risk of CMV reactivation in IBD patients, especially in UC, which included female sex, pancolitis, being older than 30 years, and immunosuppressive treatment, particularly steroids and azathioprine, like our patient [5, 17,18,19]. The association between long-term infliximab treatment and CMV colitis is debatable and not conclusive. Some studies have shown the absence of a correlation [20, 21], while other reports have suggested an association [22], while in our case, the CMV colitis developed within four weeks of initiating the first induction dose. CMV infection may cause a recurrence, modify the natural history and outcome of UC patients, and also affect treatment responsiveness, but the role of CMV infection in worsening the severity of UC remains uncertain [23,24,25]. Individuals with CMV infection and acute severe colitis tend to be resistant to steroids, unlike latent CMV infection, which was not identified as a risk factor for steroid resistance [14]. Like our case, which was resistant to steroids and anti-TNFα, failure to treat acute severe ulcerative colitis may result in colectomy, which may be more common in CMV colitis patients [26]. The difficulty is distinguishing between acute-severe UC and CMV colitis, as both exhibit the same clinical characteristics such as malaise, fever, diarrhea, haematochezia, abdominal pain, and weight loss. Furthermore, it is critical to distinguish between CMV infection and CMV disease. CMV infection or exposure is indicated by CMV serology and may not always result in CMV disease, which is characterized by symptoms or CMV-related tissue damage [1, 9, 27]. Serological assays, including CMV viral load detected by PCR, were not used to diagnose CMV colitis. The diagnosis, however, is based on CMV DNA in colonic tissue or viral inclusion bodies on routine H&E stains or, better yet, immunohistochemistry, and even those have various criteria [23, 28, 29], which are associated with the colitis severity, resistance to steroid treatment, response to antivirals, or colectomy rate [23, 28]. The location of biopsies is very important to increase the probability of diagnosis, there are no clear diagnostic endoscopic signs that may distinguish, though specific endoscopic findings, such as punched-out ulcers, are more frequent in CMV colitis patients [4]. It was proposed that no less than 11 biopsies be collected from the sigmoid colon of individuals with UC flares to reach an 80% likelihood of a positive biopsy [30]. Positive results are more likely when biopsies are taken from the ulcer base [30]. Unlike in our situation, where there were no obvious ulcers and many biopsies had shown negative results about four weeks prior, patients with a true CMV colitis infection may benefit from antiviral therapy alone, but patients with a CMV infection may benefit from escalating therapy. However, the rates of hospitalization, re-hospitalization, surgery, and mortality are higher for true CMV colitis [23, 28, 29]. Starting antiviral treatment for CMV colitis requires careful consideration. Doctors will weigh clinical symptoms, endoscopic findings, CMV tests, disease duration, patient preferences, and potential side effects. The chosen antiviral agent is intravenous ganciclovir, but there is no agreement about its duration, regardless of the low quality of the evidence, the British Society of Gastroenterology (BSG) strongly recommends treatment with intravenous ganciclovir (5 mg/kg) twice daily for two weeks, while continuing with corticosteroids or rescue therapy with infliximab or cyclosporine. Alternatively, the European Crohn’s and Colitis Organisation (ECCO) suggested treatment with intravenous ganciclovir 5 mg/kg twice daily for 5 days, followed by oral valganciclovir 900 mg twice daily for 2–3 weeks [1]. The primary side effect of valganciclovir is bone marrow suppression, which occurs in up to 40% of individuals [6]. Post-antiviral therapy, studies report colitis remission rates exceeding 67%, however, data on the frequency and significance of CMV reactivation during or following treatment remain unclear. Additionally, patients with confirmed CMV colitis demonstrate a higher colectomy rate [6, 31]. Corticosteroids that are frequently used in IBD patients induce viral replication and increased production of cytokines, which causes more inflammation and increased migration of infected monocytes and macrophages into inflamed tissue, generating more virus replication and a vicious process with deteriorating colon inflammation [1, 32]. It is currently widely recognized that steroids, even short courses, immunomodulators and cyclosporine are associated with an increased risk of CMV reactivation, However, using corticosteroids is controversial; it is uncertain whether they should be stopped or not in patients with CMV colitis who are getting antiviral therapy [1, 27, 33, 34]. Theoretically, TNFα and azathioprine promote CMV reactivation [1, 32], while anti-TNFα has no deleterious effect on the outcome of CMV reactivation patients. However, no research has directly examined the effect of anti-TNFα antagonists on CMV viral replication in UC and CMV colitis patients. Other biological treatments, such as vedolizumab and ustekinumab, may raise the risk of CMV reactivation [35, 36]. CMV colitis remains a diagnostic challenge in IBD management. The lack of a gold standard, coupled with the heterogeneity of diagnostic modalities including histology, immunohistochemistry, and PCR, often results in diagnostic delays. Endoscopic findings, while suggestive, are not pathognomonic, further complicating accurate and timely identification of this clinically significant condition [2, 6, 7]. Therapeutic management of CMV colitis is complex due to multiple factors. Corticosteroids, commonly used in IBD, may exacerbate CMV replication, necessitating careful consideration of their continuation during antiviral therapy. The role of biologics, such as infliximab, in CMV colitis remains uncertain, with potential associations between its use and CMV development further complicating treatment decisions, especially in early-onset CMV infection [3, 37, 38]. The absence of standardized follow-up protocols for CMV colitis hinders the understanding of long-term outcomes, including recurrence rates and the overall impact on IBD disease progression. This knowledge gap necessitates further research to establish optimal post-treatment care strategies for CMV colitis patients [39,40,41].
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