Azathioprine-induced toxoplasma gondii infection in a patient with Crohn's disease with NUDT15 variation: A case report.

INTRODUCTION: Azathioprine (AZA) has been widely used for the treatment of various immune-related diseases and has become a mainstay in the treatment of inflammatory bowel disease. However, patients with genetic mutations may experience severe adverse events when treated with azathioprine. Most of the previous literature focused on the TPMP gene-related adverse reactions, herein, we report a case of Crohn's disease patient with nucleoside diphosphate-linked moiety X motif 15 gene (NUDT15) variation and wild-type TPMP gene who developed toxoplasma gondii infection after azathioprine treatment. PATIENT CONCERNS: A 56-year-old Crohn's disease patient developed toxoplasma gondii infection within 2 months after the administration of azathioprine; however, he had no relevant high-risk factors. DIAGNOSIS: Subsequent genetic testing revealed that the patient was heterozygous for NUDT15. Therefore, it was reasonable to consider that the patient's genetic mutation resulted in reduced tolerance to azathioprine, leading to low immunity and eventually toxoplasma infection. INTERVENTIONS: AZA was then discontinued; after anti-infection, antipyretic and other supportive treatments were administered, the patient's condition gradually improved. OUTCOMES: The patient was followed up at 1, 3, and 6 months after discharge; fortunately, he was in good health. CONCLUSION: We report a case of Crohn's disease in a patient who developed severe pneumonia caused by toxoplasma gondii infection due to the administration of AZA, with normal TPMP gene but NUDT15 gene mutation. This indicates that NUDT15 variation may contribute to severe adverse events in patients treated with azathioprine, and we suggest that NUDT15 genotype be detected before the use of azathioprine in order to provide personalized therapy and reduce side effects.

Four Variants of SLCO2A1 Identified in Three Chinese Patients with Chronic Enteropathy Associated with the SLCO2A1 Gene.

BACKGROUND: Chronic enteropathy associated with the SLCO2A1 gene (CEAS) is an enteropathy characterized by multiple small intestinal ulcers of nonspecific histology, also known as chronic nonspecific multiple ulcers of the small intestine. The SLCO2A1 gene encodes a prostaglandin transporter (PGT). AIMS: The aim of this study was to investigate the clinical characteristics of ten Chinese patients with intestinal ulcers of unknown origin, screen them for variants of SLCO2A1, and to investigate the expression of PGT in the small intestinal mucosa of patients with CEAS. METHODS: Ten Chinese patients with intestinal ulcers of unknown origin were included in this study. Blood samples were collected for whole-exome sequencing and Sanger sequencing of candidate gene variants. Immunohistochemical staining was used to investigate the expression of PGT. RESULTS: These ten patients were clinically diagnosed with intestinal ulcers of unknown origin based on criteria established according to earlier publications. Three of them were genetically diagnosed as having CEAS and four candidate variants of the SLCO2A1 gene were identified, among which c.941-1G>A, c.178G>A and c.1681C>T were detected in patients with CEAS for the first time. The terminal ileum was involved in all three patients with CEAS in our study, which was different from the results of Japanese patients. The expression of PGT in the vascular endothelial cells of the intestinal mucosa tissues of patients with CEAS was negative or intermediate. CONCLUSION: We summarized the clinical data of ten Chinese patients with intestinal ulcers of unknown origin and identified three novel SLCO2A1 variants from three patients with CEAS. This study improves our understanding of CEAS and broadens the spectrum of SLCO2A1 variants known to cause CEAS.

Intestinal ulcers as an initial finding in EBV-associated lymphoproliferative disorder: A case report.

RATIONALE: Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disorder (LPD) usually occurs in children and young adults. Gastrointestinal involvement is rare. EBV-associated T-cell lymphoproliferative disorder manifesting as intestinal ulcers poses diagnostic challenges clinically and pathologically because of the atypical manifestations. We concluded that some indicators according to our case and literatures, which might be helpful to the diagnosis of EBV-associated LPD manifested as intestinal ulcers. PATIENT CONCERNS: Here we present a 26-year-old man with complaints of diarrhea and abdominal pain that had persisted for 1 year. Multiform and multifocal deep ulcers were discovered in the colonoscopy. Cell atypia was not obvious but colitis with crypt distortion was found in pathology. DIAGNOSES: According to the symptoms, laboratory examinations, colonoscopy and pathology results, Crohn Disease was diagnosed. INTERVENTIONS: Infliximab therapy was initiated based on the diagnosis of Crohn Disease. OUTCOMES: After the fifth course of therapy, intermittent fever and hematochezia occurred. Physical examination revealed swollen tonsils and ulcers, and purulent exudate from the right tonsil and palatoglossal arch were observed. Biopsies obtained through colonoscopy and nasopharyngoscopy demonstrated EBV-associated T-cell proliferation disease (level 3). After that, the tissue sample from the first colonoscopy was reexamined immunohistochemically. The result suggested EBV-associated T-cell proliferation disease (level 1). LESSONS: When we confront with patients with multiform and multifocal deep intestinal ulcers, not only the common diseases such as Crohn Disease and intestinal tuberculosis should be considered, EBV-associated T-cell proliferation disease should be considered as well. Repeated multiple biopsy, gene rearrangement, EBV DNA quantitative analysis result, EBV-encoded RNA(EBER) and experienced pathologists might be helpful to the diagnosis.

[Safety and efficacy of carbon dioxide insufflation during colonoscopy].

OBJECTIVE: To assess the safety and efficacy of carbon dioxide (CO(2)) in colonoscopy examination. METHODS: We randomized 349 patients to undergo colonoscopy with insufflation of air (n=175) or CO(2) (n=174). At colonoscopy, p (ET CO(2)) was observed at 4 time points: before the exam, arrived caecum, back rectum, and after the exam. Patient's experience of pain in the end and after the examination at 1, 3, 6, and 24 h was registered using a visual analog scale (VAS). Sedation was not used routinely. RESULTS: The groups were similar in age, sex, inspection time, and caecal intubation rate (all P>0.05). There were no significant differences in p (ET CO(2)) values between the 2 groups before and after the procedure (all P>0.05). VAS scores in the CO(2) group at various time points after the examination were significantly lower than those in the air group (all P<0.05). The percent of VAS scores of 0 in the CO(2) group after 1, 3, 6, and 24 h was significantly higher than that in the air group (all P<0.01). CONCLUSION: Injection of CO(2) for colonoscopy will not cause CO(2) retention, and it may significantly reduce the pain, which is safe and effective.

[Endoscopic band ligation versus endoscopic hemoclip placement for bleeding due to Dieulafoy lesions in the upper gastrointestinal tract].

OBJECTIVE: To compare the hemostatic efficacy and safety of endoscopic band ligation(EBL) and endoscopic hemoclip placement(EHP) for bleeding due to Dieulafoy lesions in the upper gastrointestinal tract. METHODS: Between February 2004 and October 2006, 34 patients with Dieulafoy lesions in the upper gastrointestinal tract were prospectively enrolled,including 22 cases of lesions in the stomach,10 in gastrointestinal stoma,and 2 in duodenal, who were randomly assigned to undergo EBL (n=16) or EHP (n=18). The therapeutic results of these 2 groups were compared. RESULTS: The median number of O-ring or hemoclip required in the EBL group and the EHP group was similar. The rate of primary haemostasis,recurrent bleeding,transfer into surgery, complications, and average stay and blood transfusion requirements did not significantly differ in the 2 groups (P>0.05). CONCLUSION: In this study, no significant differences are detected in the efficacy and the safety of EBL vs. EHP for bleeding due to Dieulafoy lesions in the upper gastrointestinal tract.