Refractory Cytomegalovirus Colitis in Common Variable Immunodeficiency Requiring Total Colectomy

Cytomegalovirus (CMV) colitis is an uncommon infection in immunocompetent hosts, usually occurring in the presence of an underlying immunodeficiency condition that allows for the reactivation of latent CMV infection. CMV colitis typically presents with persistent diarrhea, sometimes accompanied by bloody stools and nonspecific abdominal pain. We present the case of a 76-year-old woman known to have chronic CMV colitis, which was diagnosed in the context of underlying common variable immunodeficiency (CVID). Despite multiple attempts at managing CMV colitis, her symptoms persisted over the years. Ultimately, the patient required a pan colectomy due to refractory CMV colitis.


Introduction
Cytomegalovirus (CMV) is a double-stranded DNA virus that belongs to the herpesvirus family.It is a virulent virus that can afect multiple organs, including the colon, retina, esophagus, and the central nervous system (CNS) [1].However, most of these infections occur in the context of underlying immunodefciency conditions, such as acquired immunodefciency syndrome (AIDS), organ transplant patients, patients undergoing chemotherapy, and individuals with underlying immunodefciency diseases like common variable immunodefciency (CVID) [2,3].Healthy individuals can also contract CMV infections; however, the complications are more severe in immunodefcient hosts when compared to healthier individuals.
CMV colitis is an infection of the colon that typically presents with nonspecifc symptoms such as diarrhea, unexplained weight loss, and fever.Diagnosing CMV colitis can be challenging due to its clinical presentation, which is similar to other common gastrointestinal conditions.Furthermore, CMV colitis may exhibit endoscopic features resembling other infammatory diseases, such as infammatory bowel disease (IBD), leading to potential misdiagnosis.However, when considering the entire clinical picture, particularly in cases of known immunocompromised patients, a high suspicion of CMV colitis, after excluding other common conditions, is a reasonable diferential diagnosis.Accurate diagnosis is crucial, given the distinct management approaches for CMV colitis compared to similar conditions like IBD [4,5].

Case Report
A 76-year-old woman, known to have cytomegalovirus (CMV) colitis diagnosed through a colonoscopy with colonic biopsy that tested positive for CMV, presented with ongoing diarrhea and rising CMV titers despite medical treatment with ganciclovir, foscarnet, and weekly IgG infusions.Over the course of four years, the patient had multiple hospital admissions.Ganciclovir resistance testing revealed a mutation, D843D/V, in the UL54 region, possibly causing resistance to ganciclovir, foscarnet, and cidofovir.Subsequently, she underwent various frst-line, second-line, and investigational therapies, including interferon alpha, intravenous foscarnet, intravenous ganciclovir, valganciclovir, letermovir, lefunomide, and multiple cycles of interleukin-2 (aldesleukin) injections.Despite receiving multiple lines of treatment, her symptoms persisted, with worsening diarrhea and abdominal pain that required multiple emergency room visits.Her CMV titers remained elevated (Figure 1).Repeat CT scans of the abdomen and pelvis showed progression and worsening colon thickening, involving the entire colon and cecum compared to earlier scans that indicated involvement of only the ascending colon and cecum.A repeat colonoscopy (Figure 2) revealed pan colitis with ulceration, and the biopsy confrmed severe colitis with positive CMV inclusion bodies and immunohistochemistry from multiple sites of ulceration and infammation (Figures 3(a) and 3(b)).Te patient underwent a trial of fresh frozen plasma, which was unsuccessful.After exhausting all medical treatment options and due to the worsening of CMV colitis, a multidisciplinary decision was made to proceed with a pan colectomy, which was performed around mid-2021, as indicated by an arrow on Figure 1.Initial postoperative CMV titers remained elevated (Figure 1), but subsequent measurements ranged between 1000 and 2000 copies/ml, resulting in signifcant clinical improvement.

Discussion
In our case, the patient had been diagnosed with common variable immunodefciency (CVID) at the age of 60 and had been receiving weekly IgG injections without antibiotic prophylaxis.Te diagnosis of CVID was made in the context of recurrent pneumonia episodes occurring 3-4 times per year.Given the patient's known CVID and ongoing care under an immunologist, the medical team suspected an underlying CMV colitis.During the initial colonoscopy, there was still suspicion of a concomitant infammatory condition, such as ulcerative colitis or Crohn's disease, as the initial biopsies suggested idiopathic infammatory bowel disease with fndings like cryptitis and architectural distortion.   2 Case Reports in Gastrointestinal Medicine However, subsequent biopsies, along with immunohistochemistry, confrmed CMV colitis, and the possibility of underlying IBD could not be ruled out.Te pathologist suggested repeating the biopsy once the CMV infection was treated.After consulting with infectious disease experts, the decision was made to actively treat the patient.Multiple lines of management, as mentioned earlier, were attempted.Unfortunately, poor clinical response, increasing CMV titers, disease progression on imaging, and endoscopic evidence of active infammation led the medical team to approach this case in a multidisciplinary manner.Te decision was made to proceed with a pan colectomy and end ileostomy, which resulted in a favorable outcome.Tis decision was based on several factors.First, the patient had an exceptionally resistant form of CMV colitis that did not respond to any medical management, as evidenced clinically, biochemically, on imaging, and endoscopically.Second, the benefts of surgical intervention outweighed the risks, primarily the risk of perforation and eventual death [6].Furthermore, no other medical management options were available, as all potential treatments had been exhausted without success.Based on this case report, we would recommend considering pan colectomy with end ileostomy as a viable option when all medical management options have been exhausted and there is no improvement in the patient's condition.

Figure 3 :
Figure 3: Inclusion bodies on colonic biopsy with positive immunohistochemistry for CMV.