Nausea and vomiting, appetite loss, abdominal pain, and watery diarrhea are common symptoms of GI-GVHD. Watery diarrhea appears in almost all cases of GI-GVHD and occasionally becomes chronic or causes bleeding. Therefore, this symptom is a major factor that reduces patient QoL[11
]. Moreover, after HSCT, CMV infection of the GI mucosa and GI-GVHD can both cause diarrhea[12,13
Diseases characterized by the development of GI symptoms after HSCT include not only CMV and GI-GVHD infection but also virus infections caused by enterovirus, adenovirus, rotavirus, and Epstein-Barr virus, complications with bacterial and fungus infections, and colitis associated with thrombotic microangiopathy and regimen-related toxicity. In routine clinical examination, differentiating among these diseases is difficult[14
], particularly because GI-GVHD is frequently associated with CMV infection[15,16
]. In this case, because of the severe GI-GVHD accompanied by CMV infection, the patient developed frequent and long-term bloody diarrhea and abdominal pain, which appeared to have led to serious symptoms such as anemia, malnutrition, and dehydration.
The endoscopic findings reflected the severity of the clinical symptoms. The lower GI tract exhibited severe signs of multiple deep ulcers, edema, and erythema, with no normal mucosa observed. The upper GI endoscopy revealed diffuse sloughing of the mucosa in the stomach, except for the antrum. Although the endoscopic findings of chronic GI-GVHD may include the characteristic esophageal web and strictures[2
], various endoscopic findings are associated with acute GI-GVHD depending on the severity of the inflammation. We reviewed the English literature in the MEDLINE database by searching with “gastrointestinal”, “GVHD”, and “endoscopy” as key words (Table ). Although there are some reports of normal mucosal findings, a large number of studies reported findings of erythema, erosions, and edema. Because the symptoms were generally mild in the upper GI tract, the lower GI tract often had relatively severe inflammatory symptoms, with occasional actively bleeding ulcers. In addition, although tortoise shell-like mucosa and pseudomembrane formation are occasionally observed, no particular findings are reportedly associated with the colorectal mucosa. Moreover, even though some papers report mucosal sloughing and ulceration[8
], a wide area of sloughing mucosa along with ulcers and inflamed mucosa, as observed in the present case, has never been reported. We believe that a combination of severe GVHD and CMV infection is the pathogenesis responsible for these symptoms[13
]. According to He et al[17
], GI-GVHD accompanied by CMV infection causes deep, discrete ulcers. The ischemic consequences of occluded blood vessels caused by enlarged vascular endothelial cells due to CMV infection are thought to be the mechanism underlying the GI mucosal damage[18
]. Similarly, ischemic alteration, in addition to the cytotoxicity caused by GVHD[19
], is a likely cause of the severe symptoms in our patient.
Literature review of the endoscopic findings in gastrointestinal graft-versus-host disease
The early and accurate diagnosis of CMV infection in the GI tract is the key to preventing severe symptoms, such as perforation and bleeding[20
]. In this case, even though immunostaining with an anti-CMV antibody was negative, the quantitative PCR results of the biopsy specimens were positive, with a high value of 1.0 × 104
copies/μg DNA, which enabled the diagnosis of CMV-GID. The diagnostic accuracy of the quantitative PCR method using biopsy samples is reportedly superior to that of immunostaining to determine the involvement of CMV in the GI symptoms[21
]. This case showed that the results of the CMV quantitative PCR were closely correlated with the post-treatment improvement of the mucosa, suggesting the usefulness of the technique for evaluating the effects of CMV treatment.
In conclusion, when endoscopic observation is performed on HSCT patients with postoperative GI symptoms, it is necessary to look for signs of mucosal sloughing and ulcers. In addition to a detailed endoscopic observation, biopsy samples should be examined for the characteristic pathological features of GVHD[22
] and for signs of CMV infection. The course of this case suggests that the quantitative PCR of biopsy samples is useful for revealing CMV infection in the GI tract.