Chronic active Epstein-Barr virus-associated infection (CAEBV) is one of the many subtypes of Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (EBV-LPD) and comprises a range of lymphoid tissue diseases including hyperplastic, borderline, and neoplastic diseases [
Chronic active EBV-associated enteritis (CAEAE) was first described in 2005 by Joan Robinson et al. [
This study was conducted with the approval of the ethics committee of The First Affiliated Hospital of Anhui Medical University, and the requirement for written informed consent was waived in this retrospective study. All cases were obtained from the Department of Pathology and the Department of Radiology at The First Affiliated Hospital of Anhui Medical University in China. From January 2018 to May 2019, the pathology records and medical records of three patients with pathologically and clinically confirmed CAEAE were reviewed. The diagnostic criteria for CAEAE were based on a previous study [
All patients were required to fast overnight prior to CTE examination. The patients achieved adequate bowel distension with the oral administration of 1.5-2 L of iso-osmotic polyethylene glycol solution 1 h before CT scanning.
CTE was conducted using a 64-slice multidetector (Revolution CT, GE Healthcare, Waukesha, WI, USA). The CT scan was performed from the diaphragmatic dome to the symphysis pubis with the following parameters: tube voltage 120 kV, tube current 400 mAs, collimation
All CTE images were retrospectively reviewed by two experienced radiologists with 5 and 10 years’ experience in CTE, respectively. All image analyses were performed using an AW 4.7 workstation (GE Healthcare), and the radiologists were blinded to the patients’ clinical information. Multiplanar reconstruction was performed to visualize and measure the location and morphology of lesions. The following CTE imaging characteristics were evaluated: (1) pattern of mural thickening: a small bowel wall >3 mm or colonic wall >2 mm was defined as bowel wall thickening (asymmetric thickening or symmetric thickening) [
Clinical data, including sex, age, clinical symptoms, endoscopic records, laboratory examinations, and pathologic findings, were collected from the electronic medical records.
Among the 3 included patients, there were 2 males and 1 female aged 28-42 years (median age, 39 years). The clinical features and laboratory findings of CAEBV enteritis are summarized in Tables
Clinical data of the three CAEAE patients.
Case | Sex | Age | Clinical symptoms | EBV DNA (copies/mL) | Organ involvement | HB (g/L) | Inflammatory indicators | Coagulation function | Misdiagnose |
---|---|---|---|---|---|---|---|---|---|
1 | M | 39 | Abdomin al pain, fever, adenopathy, diarrhea, hematochezia | Colon | 12 | Increased | Altered | UC | |
2 | M | 28 | Abdominal pain, fever, adenopathy, retrosternal pain, diarrhea, splenomegaly | Colon, esophagus | 92 | Increased | Altered | IBD | |
3 | F | 42 | Abdominal pain, fever, adenopathy, | NA | Colon | 105 | Increased | Altered | CD |
M: male; F: female; UC: ulcerative colitis; IBD: inflammatory bowel disease; CD: Crohn’s disease.; NA: not available.
Endoscopic and pathologic findings of the three CAEAE patients.
Case | Endoscopy | Biopsy samples | HE stain | Immunohistochemistry | EBER |
---|---|---|---|---|---|
1 | Numerous irregular ulcers in the colon | Hepatic flexure of colon, transverse colon, descending colon, sigmoid colon | Lymphatic follicles in the lamina propria, crypt abscess in some glands, aggregation of atypical lymphoid cells | CD3, CD7+ Ki-67+<5% | Colon positive |
2 | Numerous shallow and small ulcers in the colon | Ascending colon, transverse colon, descending colon, rectum, esophagus, throat | Tissue granulation, atypical lymphocyte infiltration | Colon:CD2, CD3, CD4, CD8, TIA-1, GrB+. Ki-67(+, 20%). Throat:CD2, CD3, CD7, CD56(+). Ki-67(+, 40%). | Colon and esophagus positive |
3 | Numerous irregular ulcers in the colon | Ileocecal junction, ascending colon, transverse colon, descending colon | Granulomatous tissue and lymphoid tissue hyperplasia, atypical lymphocyte infiltration | CD3, CD20, Pax-5, CD4, CD8(+), Ki-67(+, 20%). | Colon positive |
Numerous irregular and shallow ulcers in colon.
Activity chronic inflammation with ulcer formation in the mucosa, and diffuse inflammatory cell infiltrate within the lamina propria and submucosa, and granulation tissue.
In situ hybridization for Epstein-Barr virus-encoded RNA positive expression in the esophagus and colon.
The CTE features of all cases are summarized in Table
CTE findings of the three CAEAE patients.
Case | Pattern of mural thickening | Length of involvement | Pattern of attenuation | Perienteric abnormalities |
---|---|---|---|---|
1 | 11 mma, | 25 cm | Layered attenuation | Fat stranding, |
Asymmetric thickening | Adenopathy | |||
2 | NF | NF | NF | NF |
3 | 8 mma, | 30c m | Layered attenuation | Fat stranding |
Asymmetric thickening | Adenopathy |
aMaximum thickness; NF: not found.
CT enterograph features of case 1 (a, b) and case 3 (c, d): asymmetric thickening (small arrow), layered attenuation (big arrow), fat stranding (triangle).
EBV is not only prevalent in healthy individuals as a latent infection but also plays an important role in some infectious and neoplastic diseases, such as infectious mononucleosis, Burkitt’s lymphoma, NK/T cell lymphoma, and Hodgkin’s lymphoma. Besides, EBV has been associated with some lymphoproliferative disorders that may vary between nonneoplastic and neoplastic diseases, such as CAEBV. Primary infections are usually asymptomatic and often occur in infants and young children. Adolescents and adults with EBV infection often manifest self-limited infectious mononucleosis-like symptoms with a good prognosis. However, a few individuals present with chronic or recurrent transmissible mononucleosis, including persistent or intermittent fever with abnormal liver function, hepatosplenomegaly, and adenopathy, accompanied by increased peripheral blood serum EBV DNA load and abnormal changes in EBV antibody [
In recent years, multislice computed tomography has been developed as an important tool for detecting intestinal lesions, enabling the acquisition of isotropic data and facilitating the ability to perform high-resolution multiplanar reconstruction [
Comparison of CTE features between CAEAE and IBD.
Main involved location | Pattern of mural thickening | Length of involvement | Pattern of attenuation | Perienteric abnormalities | |
---|---|---|---|---|---|
CAEAEa | All segmental colons may be involved | Asymmetric thickening | Segmental involvement | Layered attenuation | Fat stranding, adenopathy |
CDb | Terminal ileum, ascending colon | Asymmetric thickening | Focal involvement | Layered or white attenuation (acute, active disease), grey attenuation (chronic disease) | Fat stranding, adenopathy, prominent vasa recta, fistulas and abscesses |
UCb | Rectum, descending colon | Symmetric thickening | Segmental or diffuse involvement | Layered attenuation | Not common |
aBased on our study findings.
bCommon and typical CTE features based on literature review.
If the thickness of the bowel is 6-40 cm or >40 cm, it is defined as a segmental or diffuse thickening, respectively [
Segmental or diffuse thickening is more common in inflammatory and vascular diseases, including ulcerative colitis, infectious microenteritis, hypoproteinemia, and portal hypertension-induced intestinal wall edema and hypoperfusion-induced ischemia [
In terms of clinical data, we found that the clinical symptoms were abdominal pain, fever, hepatosplenomegaly, diarrhea, hematochezia, and adenopathy, consistent with other reports [
With regard to endoscopic findings, we found there were no integrative continuous mucosal damage, cobble-like appearance, and longitudinal ulcers; however, there were numerous irregular, variously sized ulcers in the colon, mucosal erythema, edema, and erosion accompanied by purulent secretion, while in patients with ulcerative colitis, endoscopy typically revealed a uniform, continuous inflammation extending proximally from the rectum, but limited to the colon [
CAEAE and IBD are similar in endoscopic and pathological morphology. The key to differential diagnosis is that CAEBV infection usually presents with fever or hepatosplenomegaly, and adenopathy, with rare manifestations of ulcerative colitis such as purulent stool and tenesmus. Compared with ulcerative colitis, diffuse disturbed crypt architecture and crypt abscesses are rare. Although CAEAE may also present with a transmural inflammatory fissure ulcer and occasionally granulomatous structure, which is easily confused with Crohn’s disease, it generally lacks typical chronic interstitial changes such as granuloma, mucosal muscle hyperplasia, and nerve hyperplasia and hypertrophy [
The treatment of CAEBV infection is difficult. Antiherpesvirus drugs such as acyclovir and ganciclovir do not respond to active EBV infection. Glucocorticoid immunosuppressants (cyclosporine), immunomodulators, and cytotoxic chemotherapy drugs (cyclophosphamide, anthracyclines, vincristine, etoposide, and prednisone) can provide short-term relief from active EBV infection, but there is no cure. Hematopoietic stem cell bone marrow transplantation is a surgical treatment method for CAEBV infection; however, there are also risks associated with transplant complications [
In summary, the differential diagnosis of CAEAE from IBD may be difficult, because these two conditions share similarities in terms of imaging, clinical signs, endoscopic manifestations, laboratory examinations, and pathology. The presence of segmental and asymmetric bowel wall thickening, layered attenuation, and fat stranding in the CTE image may provide some valuable information to help differentiate CAEAE from IBD.
The data used to support the findings of this study including the CTenterography images, and the clinical data are available from the corresponding author upon request.
The authors declare that they have no conflicts of interest.