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George NA, Surendran S, Paulose RR, Pradeep M. Hyperacute reactivation of cytomegalovirus-induced gastroduodenitis during remission induction in a young male patient with granulomatosis with polyangiitis: a case report and review of literature. J Med Case Rep 2025; 19:68. [PMID: 39994816 PMCID: PMC11849236 DOI: 10.1186/s13256-025-05103-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Accepted: 01/31/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND Cytomegalovirus is a pathogen known to aggravate the inflammatory response in autoimmune diseases via molecular mimicry. Although it is recognized that cytomegalovirus activation can happen during extended but variable periods of immunosuppression (14-90 days), it is rarely reported in conjunction with an acute flare-up of an autoimmune disease. Currently, there is no consensus on cytomegalovirus prophylaxis for patients initiating remission induction. CASE PRESENTATION Here, we present the case of a 31-year-old male patient of South Indian ethnicity, presenting with a 2-month history of fever, conductive hearing loss, and ear discharge. This was associated with symmetrical inflammatory polyarthritis for 1 month, unilateral painful conjunctivitis, and skin erythema for 5 days. Blood analyses showed elevated inflammatory markers; strongly positive anti-proteinase 3 and cytoplasmic antineutrophil cytoplasmic antibody levels; normal procalcitonin and complement levels; and negative anti-myeloperoxidase and perinuclear antineutrophil cytoplasmic antibody levels. A nasal endoscopy revealed a midline granuloma with vasculitis features on biopsy. Imaging revealed pulmonary nodules and otomastoiditis. Now diagnosed with granulomatosis with polyangiitis, the patient developed signs of gastroduodenitis within a day of initiation of immunosuppression with high-dose "pulse" intravenous methylprednisolone. We evaluated him for mesenteric ischemia/gastrointestinal vasculitis. However, the duodenal biopsies from the bleeding ulcers revealed a probable cytomegalovirus infection, confirmed with high serum viral loads. We treated him with a ganciclovir regimen and transitioned him to steroid-sparing immunosuppressant therapy with mycophenolate mofetil, which was selected over cyclophosphamide for its noninferior effectiveness and better safety profile in non-life-threatening granulomatosis with polyangiitis disease. The patient recovered uneventfully and is currently in remission. CONCLUSION Cytomegalovirus reactivation is possible during short-term steroid pulse therapy. Further research is needed to evaluate whether routine cytomegalovirus screening is warranted before starting immunosuppressive treatment with high-dose steroids in autoimmune conditions.
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Affiliation(s)
- Nisha Annie George
- Department of Infectious Diseases and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Sandeep Surendran
- Department of Rheumatology and Clinical Immunology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India.
| | - Roopa Rachel Paulose
- Department of Pathology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
| | - Manu Pradeep
- Department of Rheumatology and Clinical Immunology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India
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Kondo M, Torisu T, Ihara Y, Kawasaki K, Umeno J, Kawatoko S, Tsuchimoto A, Nakano T, Okabe Y, Kitazono T. Clinical Features of Gastroduodenal Ulcers in Kidney Transplant Patients. Intern Med 2023; 62:3437-3443. [PMID: 37062748 PMCID: PMC10749817 DOI: 10.2169/internalmedicine.1508-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Accepted: 02/26/2023] [Indexed: 04/18/2023] Open
Abstract
Objective The risk of developing peptic ulcers and gastrointestinal bleeding is high in patients with chronic kidney disease (CKD). Whether or not kidney transplant patients, who are treated with multiple medications, including immunosuppressive drugs, are at an increased risk of developing peptic ulcers is unclear. Methods In this retrospective study, we compared the clinical and endoscopic features of gastroduodenal ulcers between kidney transplant patients and CKD patients. The subjects underwent upper gastrointestinal endoscopy between January 2015 and March 2021. Results Gastroduodenal ulcers were observed more frequently (6.5%) in kidney transplant patients than in CKD patients (2.1%) (p=0.026). Due in part to the lower median age in the kidney transplant ulcer group than in the CKD ulcer group (59 vs. 70 years old, p=0.016), the rates of atrophic gastritis and Helicobacter pylori infection were also lower in the kidney transplant ulcer group than in the CKD ulcer group. Significantly more kidney transplant patients were treated with acid secretion inhibitors than CKD ulcer patients (100% vs. 34.8%, p=0.0005). Peptic ulcers were observed frequently in kidney transplant patients, even though common risk factors for gastroduodenal ulcers other than immunosuppressive drugs were few. All kidney transplant patients were taking immunosuppressive medications, and tacrolimus, mycophenolate mofetil, and methylprednisolone were taken more frequently than others. Conclusion Kidney transplant patients have a high risk of developing gastroduodenal ulcers. All kidney transplant patients take immunosuppressive medications, so there may be an association between immunosuppressive medications and gastroduodenal ulcer development.
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Affiliation(s)
- Masahiro Kondo
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Takehiro Torisu
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Yutaro Ihara
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Keisuke Kawasaki
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Junji Umeno
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Shinichiro Kawatoko
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
- Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Akihiro Tsuchimoto
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Toshiaki Nakano
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Yasuhiro Okabe
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Japan
| | - Takanari Kitazono
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Japan
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Kreidieh M, Gurala D, Amarnath S, Philipose J, Colef R, Yassine AA, Gumaste V. The Unmasking of Cytomegalovirus as an Accomplice to Helicobacter pylori-Induced Severe Acute Gastroenteritis in a Healthy Host. ACG Case Rep J 2023; 10:e01181. [PMID: 37899956 PMCID: PMC10602490 DOI: 10.14309/crj.0000000000001181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Accepted: 09/19/2023] [Indexed: 10/31/2023] Open
Abstract
Cytomegalovirus (CMV) belongs to the Herpesviridae family, and it is considered the largest virus to infect humans. Primary CMV infection frequently targets immunodeficient patients and is often symptomatic. However, it may remain latent or clinically unapparent for years in immunocompetent individuals. CMV infection rarely presents as an invasive disease in the latter group of individuals, in which case, the most common site of involvement in the gastrointestinal tract. When CMV affects the gastrointestinal tract, the colon and stomach are the 2 frequently involved sites. This case report describes a unique case of an immunocompetent patient who presented with acute excruciating periumbilical pain and was diagnosed with acute gastritis secondary to CMV infection and possible Helicobacter pylori-associated chronic active gastritis. Symptoms resolved entirely soon after treatment with antimicrobials that cover for both infections. The diagnosis was based on histopathologic findings from biopsies taken from the stomach during the endoscopic evaluation combined with positive CMV serology and positive CMV-deoxyribonucleic acid.
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Affiliation(s)
- Malek Kreidieh
- Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY
| | - Dhineshreddy Gurala
- Division of Gastroenterology, Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY
| | - Shivantha Amarnath
- Division of Gastroenterology, Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY
| | - Jobin Philipose
- Division of Gastroenterology, Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY
| | - Robert Colef
- Department of Pathology, Staten Island University Hospital, Northwell Health, Staten Island, NY
| | - Ahmad Abou Yassine
- Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY
| | - Vivek Gumaste
- Division of Gastroenterology, Department of Internal Medicine, Staten Island University Hospital, Northwell Health, Staten Island, NY
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Hamada N, Maeda R, Suyama A, Yuzurio S, Oda W, Suwaki T. Acute Hemorrhagic Rectal Ulcer Complicated by Cytomegalovirus Enteritis following Steroid Pulse Therapy for Acute Exacerbation of Interstitial Pneumonia. Intern Med 2023; 62:2335-2339. [PMID: 36543211 PMCID: PMC10484779 DOI: 10.2169/internalmedicine.0823-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 11/10/2022] [Indexed: 12/24/2022] Open
Abstract
We herein report a rare case of acute hemorrhagic rectal ulcer (AHRU) complicated by cytomegalovirus enteritis following steroid pulse therapy for interstitial pneumonia. An 86-year-old woman underwent steroid pulse therapy for interstitial pneumonia. She was bedridden with dyspnea and suddenly developed melena. Colonoscopy revealed AHRU, which did not improve with conservative treatment, but did improve with ganciclovir administration for cytomegalovirus enteritis. This gastrointestinal complication has not received much attention by pulmonologists who perform steroid pulse therapy for interstitial pneumonia. Delayed treatment of this complications can be fatal. Caution should be taken when administering steroid pulse therapy to bedridden patients with interstitial pneumonia.
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Affiliation(s)
- Noboru Hamada
- Department of Respiratory Medicine, Okayama City Hospital, Japan
| | - Ruri Maeda
- Department of Respiratory Medicine, Okayama City Hospital, Japan
| | - Atsuhito Suyama
- Department of Respiratory Medicine, Okayama City Hospital, Japan
| | - Shouta Yuzurio
- Department of Respiratory Medicine, Okayama City Hospital, Japan
| | - Wakako Oda
- Department of Pathology, Okayama City Hospital, Japan
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Yamawaka T, Kitamoto H, Nojima M, Kazama T, Wagatsuma K, Ishigami K, Yamamoto S, Honzawa Y, Matsuura M, Seno H, Nakase H. The association between antigenemia, histology with immunohistochemistry, and mucosal PCR in the diagnosis of ulcerative colitis with concomitant human cytomegalovirus infection. J Gastroenterol 2023; 58:44-52. [PMID: 36287269 PMCID: PMC9825535 DOI: 10.1007/s00535-022-01931-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Accepted: 10/12/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Human cytomegalovirus (HCMV) colitis can be involved in active ulcerative colitis (UC) in patients refractory to steroid and immunosuppressive drugs. Histological examination with colonic biopsy specimens and antigenemia assays are the standard tests for diagnosing HCMV enterocolitis, and we have previously reported the usefulness of mucosal polymerase chain reaction (PCR) methods. However, the associations among histopathological tests, antigenemia assays, and mucosal PCR are unknown. METHODS We retrospectively analyzed 82 UC patients who underwent mucosal biopsy from inflamed colonic tissues for histological evaluation and mucosal PCR to detect HCMV. We analyzed the relationships between the HCMV-DNA copy number in colonic mucosa and other HCMV tests. RESULTS In total, 131 HCMV mucosal PCR tests from 82 UC patients were positive. The HCMV-DNA copy number was significantly higher in patients with positive immunohistochemistry (IHC) (p < 0.01) and was correlated with the number of positive cells for the antigenemia (C7-HRP, p < 0.01; C10/11, p < 0.01). Receiver operating characteristic curve analysis confirmed 1300 copies/μg of HCMV-DNA as the best diagnostic cut-off value to predict positive results of antigenemia (area under the curve = 0.80, 95% CI 0.68-0.93). HCMV-DNA copy number also correlated with the total UCEIS score (p = 0.013) and the bleeding score (p = 0.014). For each individual patient, a positive correlation between the change in total UCEIS score and HCMV-DNA copy number was observed (p = 0.040). CONCLUSION The antigenemia assay and histopathological test with IHC were significantly associated with the HCMV-DNA copy number in colonic tissues. Moreover, endoscopic examination with the UCEIS can help diagnose the HCMV colitis in UC patients.
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Affiliation(s)
- Tsukasa Yamawaka
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-Ku, Sapporo, 060-8543, Japan
| | - Hiroki Kitamoto
- Department of Gastroenterology and Hepatology, Kyoto University School of Medicine, Kyoto, Japan
| | - Masanori Nojima
- Center for Translational Research, Institute of Medical Science Hospital, University of Tokyo, Tokyo, Japan
| | - Tomoe Kazama
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-Ku, Sapporo, 060-8543, Japan
| | - Kohei Wagatsuma
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-Ku, Sapporo, 060-8543, Japan
| | - Keisuke Ishigami
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-Ku, Sapporo, 060-8543, Japan
| | - Shuji Yamamoto
- Department of Gastroenterology and Hepatology, Kyoto University School of Medicine, Kyoto, Japan
| | - Yusuke Honzawa
- Department of Gastroenterology and Hepatology, Kyoto University School of Medicine, Kyoto, Japan
| | - Minoru Matsuura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan
| | - Hiroshi Seno
- Department of Gastroenterology and Hepatology, Kyoto University School of Medicine, Kyoto, Japan
| | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-Ku, Sapporo, 060-8543, Japan.
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Lin SH, Wu KT, Wang CC, Liu TT, Eng HL, Chiu KW. Immunohistochemistry Staining-Proven Cytomegalovirus Colitis in Living Donor Liver Transplantation. Viruses 2022; 15:115. [PMID: 36680155 PMCID: PMC9862431 DOI: 10.3390/v15010115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 12/22/2022] [Accepted: 12/27/2022] [Indexed: 01/04/2023] Open
Abstract
Background and Aims: Cytomegalovirus (CMV) infection is a common occurrence in liver transplantation (LT) even in an era of preventive strategies. However, the diagnosis of CMV colitis remains challenging. This study aimed to focus on the clinical significance of endoscopic biopsy-proven CMV colitis in patients following living donor liver transplantation (LDLT). Methods: From January 2007 to December 2021, a total of 55 CMV colitis cases were retrospectively enrolled and divided into a non-LDLT group in 53 and an LDLT group in 2 cases. Clinical demographics, diagnostic measurement, histopathology, and anti-viral therapy were investigated. Results: There were 1630 cases undergoing LDLT in the period 2007-2021, with only 2 recipients being confirmed to have CMV colitis in 2021 (2/114, 1-year incidence: 1.75%). Comparisons between the 53 non-LDLT cases and 2 LDLT cases are as follows: Serum anti-CMV immunoglobulin M (IgM) was shown to be positive (n = 3, 5.5% vs. n = 0, p = 1.0) and negative (n = 20, 37.7% vs. n = 2, 100%, p = 0.16); anti-CMV immunoglobulin G (IgG) was positive (n = 19, 35.8% vs. n = 2, 100%, p = 0.14) and none were negative; CMV DNAemia was shown to be detectable (n = 14, 26.4% vs. n = 1, 50%, p = 0.47) and undetectable (n = 14, 26.4% vs. n = 1, 50%, p = 0.47). Among the two recipients with CMV colitis, one had CMV DNAemia and the other had no CMV DNAemia upon the development of symptoms; negative anti-CMV-IgM and positive anti-CMV-IgG were observed both pre-transplant and post-transplant; finally, CMV colitis was documented based on the presence of inclusion bodies and positive immunohistochemistry (IHC) staining in histology. Conclusion: Patients with immunocompromised status, in particular organ transplantation, may have positive serum anti-CMV IgM/IgG antibodies both before and after transplantation. This study emphasized the fact that endoscopic biopsy with IHC staining may be a more powerful tool for making an accurate diagnosis of CMV colitis in the setting of living donor liver transplantation.
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Affiliation(s)
- Shu-Hsien Lin
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan 123 Ta-Pei Road, Niao-Sung District, Kaohsiung 833, Taiwan
- Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Kun-Ta Wu
- Division of General Surgery, Department of Surgery, E-Da Hospital, Kaohsiung 833, Taiwan
| | - Chih-Chi Wang
- Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- Division of General Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Ting-Ting Liu
- Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Hock-Liew Eng
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
- Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - King-Wah Chiu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan 123 Ta-Pei Road, Niao-Sung District, Kaohsiung 833, Taiwan
- Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
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Human cytomegalovirus: a survey of end-organ diseases and diagnostic challenges in solid organ transplant recipients. Curr Opin Organ Transplant 2022; 27:243-249. [PMID: 36354249 DOI: 10.1097/mot.0000000000000992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
PURPOSE OF REVIEW Human cytomegalovirus (CMV) infection is one of the most important infectious complications in solid organ transplant (SOT) recipients, leading to significant morbidity and mortality. Therefore, early detection and prompt treatment are imperative to improve transplant outcomes. This article highlights the clinical characteristics of the most common CMV end-organ diseases in SOT recipients and their diagnostic modalities and challenges. RECENT FINDINGS CMV can cause a variety of end-organ diseases in SOT recipients. Although CMV nucleic acid amplification by polymerase chain reaction (PCR) is frequently employed to detect CMV reactivation or infection, its predictive value for various CMV end-organ diseases remains uncertain. Given the limitation of PCR or other noninvasive tests, confirmation of CMV end-organ disease may require tissue biopsy, which may not be feasible or available, or may cause untoward complications. SUMMARY The utility of PCR to diagnose CMV end-organ disease is limited. As CMV can infect any organ system(s), clinicians caring for SOT recipients need to maintain vigilance for any signs and symptoms of end-organ disease to allow early recognition and prompt treatment. Invasive procedures might be needed to confirm the diagnosis and minimize the empirical use of antiviral therapy that may have substantial drug toxicities.
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Jung KH, Jung J, Kim MJ, Chong YP, Lee SO, Choi SH, Kim YS, Kim SH. Optimal duration of antiviral treatment in patients with gastrointestinal cytomegalovirus disease at a low and high risk of relapse. Medicine (Baltimore) 2022; 101:e28359. [PMID: 35029881 PMCID: PMC8735784 DOI: 10.1097/md.0000000000028359] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 12/01/2021] [Indexed: 11/26/2022] Open
Abstract
We evaluated the association between antiviral treatment duration and relapse of gastrointestinal (GI) cytomegalovirus (CMV) disease by analyzing the risk factors for relapse.Patients who were diagnosed with GI CMV disease at a tertiary hospital from January 2008 to April 2019 were retrospectively enrolled. Patients with relapsed disease were those with a recurrence of GI CMV disease at least 4 weeks after the initial antiviral treatment.Of 238 participants, including 145 (51.9%) with upper and 93 (48.1%) with lower GI CMV diseases, 27 (11.3%) had experienced relapses. The difference in antiviral treatment duration between the relapsed and nonrelapsed GI CMV groups was not significant (median days, 21.0 vs 17.0, P = .13). Multivariate analysis revealed that hematologic malignancy (odds ratio, 3.73; P = .026) and ulcerative colitis (odds ratio, 4.61; P = .003) were independent risk factors for relapse. Participants with at least one of these risk factors and those with no independent risk factors were classified under the high- (relapse rate, 25.9%) and low-risk of relapse groups (relapse rate, 6.7%), respectively. Accordingly, we further stratified 180 (75.6%) and 58 (24.4%) participants under the low- and high-risk of relapse groups, respectively. There was no significant difference in relapse rates between the high- and low-risk groups according to antiviral treatment duration.Approximately 10% of the participants experienced relapses after antiviral treatment, with hematologic malignancy and ulcerative colitis featuring as risk factors. Therefore, prolonged antiviral treatment might not be helpful in preventing GI CMV disease relapse.
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Affiliation(s)
- Kyung Hwa Jung
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
- Department of Infectious Diseases, Uijeongbu Eulji Medical Center, University of Eulji College of Medicine, Uijeongbu, Republic of Korea
| | - Jiwon Jung
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Min Jae Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yong Pil Chong
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang-Oh Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sang-Ho Choi
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yang Soo Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sung-Han Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Cytomegalovirus gastroenteritis in patients with acute graft-versus-host disease. Blood Adv 2021; 6:574-584. [PMID: 34788389 PMCID: PMC8791573 DOI: 10.1182/bloodadvances.2021005885] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 10/26/2021] [Indexed: 11/20/2022] Open
Abstract
A pre-emptive strategy has successfully decreased cytomegalovirus (CMV) disease after allogeneic hematopoietic cell transplantation (HCT). However, some recipients still develop CMV gastroenteritis, especially after acute graft-versus-host disease (aGVHD), and its incidence, risk factors, and prognostic impact remain to be elucidated. We retrospectively analyzed 3759 consecutive adult patients who developed grade II-IV aGVHD using a Japanese registry database. The cumulative incidence of CMV gastroenteritis was 5.7% by day 365 from the development of grade II-IV aGVHD. Advanced age (hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.16-2.22; P = 0.004), GVHD prophylaxis with mycophenolate mofetil and calcineurin inhibitor (HR, 1.73; 95% CI, 1.08-2.77; P = 0.024), lower-gut aGVHD (HR, 2.17; 95% CI, 1.58-2.98; P < 0.001), and the use of systemic steroids (HR, 1.78; 95% CI, 1.16-2.74; P = 0.008) were independent risk factors for CMV gastroenteritis. Development of CMV gastroenteritis was associated with an increased risk of nonrelapse mortality (HR, 1.89; 95% CI, 1.50-2.39; P < 0.001). Moreover, letermovir prophylaxis significantly reduced both the incidence of CMV gastroenteritis (HR, 0.50; 95% CI, 0.25-0.99; P = 0.047) and the risk of nonrelapse mortality (HR, 0.72; 95% CI, 0.52-0.99; P = 0.043). In summary, CMV gastroenteritis is a life-threatening complication that sets the need for preventive strategies with letermovir and targeted surveillance.
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Ochiai Y, Hoteya S, Kono K, Takazawa Y, Matsui A, Kikuchi D. Cytomegalovirus ileitis with protein-losing enteropathy in an immunocompetent adult. Clin J Gastroenterol 2021; 14:1060-1066. [PMID: 33745065 DOI: 10.1007/s12328-021-01382-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 03/08/2021] [Indexed: 11/30/2022]
Abstract
Symptomatic cytomegalovirus (CMV) infection in immunocompetent hosts has traditionally been considered to have a benign, self-limited course, and those who need intensive therapy are rare. Moreover, there are few reports of CMV infection with protein-losing enteropathy (PLE). We present an immunocompetent 74-year-old woman with CMV ileitis with PLE, which was diagnosed due to severe hypoalbuminemia and edema of the lower extremities. The patient was not immunocompromised, because a human immunodeficiency virus (HIV) antibody test was negative and she had not been taking immunosuppressants. Imaging tests including colonoscopy revealed ileitis with shallow widespread ulcers. 99mTc-human serum albumin (HAS-D) scintigraphy suggested a possibility of protein loss in the ileum based on selective accumulation of nuclides in the right abdomen. Histological findings of the biopsy showed ulcerative mucosa with abnormal cells, which had enlarged nuclei with intranuclear inclusion bodies, including typical Cowdry A type. In immunohistochemistry, these cells were positive for anti-CMV staining. She was successfully treated with medical treatments including intravenous injection of ganciclovir (GCV) (500 mg/day). We described an extremely rare case of CMV ileitis with PLE in an immunocompetent adult who was treated successfully with medical treatments, including GCV.
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Affiliation(s)
- Yorinari Ochiai
- Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
| | - Shu Hoteya
- Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Kei Kono
- Department of Pathology, Toranomon Hospital, Tokyo, Japan
| | | | - Akira Matsui
- Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
| | - Daisuke Kikuchi
- Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan
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11
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Chen YJ, Huang HC, Chen TC, Cheng HT. Cytomegalovirus esophagitis with symptoms of gastroesophageal reflux disease in a kidney transplant recipient. Kaohsiung J Med Sci 2020; 36:859-860. [PMID: 32671960 DOI: 10.1002/kjm2.12264] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 05/23/2020] [Accepted: 06/07/2020] [Indexed: 11/11/2022] Open
Affiliation(s)
- Yu-Jhou Chen
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Hsin-Chih Huang
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Tse-Ching Chen
- Department of Anatomical Pathology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Hao-Tsai Cheng
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
- Chang Gung University College of Medicine, Taoyuan, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, New Taipei Municipal Tucheng Hospital, New Taipei City, Taiwan
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12
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Noguchi T, Nishikawa T, Ishihara S. Rectocolic and colocolic fistulas accompanied by cytomegalovirus infection: Two case reports. Asian J Surg 2020; 43:783-784. [PMID: 32199669 DOI: 10.1016/j.asjsur.2020.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 03/04/2020] [Indexed: 10/24/2022] Open
Affiliation(s)
- Tatsuki Noguchi
- Department of Surgical Oncology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Takeshi Nishikawa
- Department of Surgical Oncology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Soichiro Ishihara
- Department of Surgical Oncology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
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13
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Liu Y, Sun LY, Zhu ZJ, Qu W. Novel approach for the diagnosis of occult cytomegalovirus cholangitis after pediatric liver transplantation: A case report. World J Clin Cases 2020; 8:2597-2602. [PMID: 32607337 PMCID: PMC7322438 DOI: 10.12998/wjcc.v8.i12.2597] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 05/09/2020] [Accepted: 05/21/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) infection is a common infection in liver transplant recipients, which is related to chronic rejection and biliary complications. It is often diagnosed based on serum CMV-DNA or CMV pp65. To our knowledge, this is the first report of the successful treatment of occult CMV cholangitis in a pediatric liver transplantation (LT) recipient.
CASE SUMMARY A 7-mo-old baby girl received LT due to biliary atresia and cholestasis cirrhosis. At 1 mo following LT, the patient suffered from aggravated jaundice with no apparent cause. As imaging results showed intrahepatic and extrahepatic bile duct dilatation, the patient was diagnosed with biliary complications and percutaneous cholangiography and biliary drainage was performed. However, there was little biliary drainage and her liver function deteriorated. CMV-DNA was isolated from the bile with the surprising outcome that 3 × 106 copies/mL were present, whereas the CMV-DNA in serum was negative. Following antiviral therapy with ganciclovir, she gradually recovered and bilirubin decreased to normal levels. During the 4-year follow-up period, her liver function remained normal.
CONCLUSION Bile CMV sampling can be used for the diagnosis of occult CMV infection, especially in patients with negative serum CMV-DNA and CMV pp65. Testing for CMV in the biliary tract may serve as a novel approach for the diagnosis of cholestasis post-LT. Timely diagnosis and treatment will decrease the risk of graft loss.
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Affiliation(s)
- Ying Liu
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Li-Ying Sun
- Intensive Care Unit, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Zhi-Jun Zhu
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Wei Qu
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
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14
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Oh EH, Kim J, Ham N, Hwang SW, Park SH, Yang DH, Byeon JS, Myung SJ, Yang SK, Ye BD. Long-term Outcomes of Adalimumab Therapy in Korean Patients with Ulcerative Colitis: A Hospital-Based Cohort Study. Gut Liver 2020; 14:347-356. [PMID: 31530738 PMCID: PMC7234882 DOI: 10.5009/gnl19137] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 06/08/2019] [Accepted: 06/20/2019] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND/AIMS Studies on long-term outcomes of adalimumab therapy in non-Caucasian patients with ulcerative colitis (UC) are lacking. METHODS We analyzed long-term outcomes of Korean UC patients treated with adalimumab at the Asan Medical Center, Seoul, Korea. RESULTS Between July 2013 and October 2018, adalimumab therapy was started in a total of 100 patients with UC (65 males [65.0%]; median age, 39.5 years [interquartile range, 23.3 to 49.8 years]; and median disease duration, 3.0 years [interquartile range, 1.0 to 7.0 years]). The median duration of adalimumab therapy was 13.5 months (interquartile range, 4.0 to 32.0 months). Eight of 100 patients (8.0%) received induction therapy only, four (4.0%) of whom ultimately underwent colectomy. Of 92 patients who received adalimumab maintenance therapy, 30 (30.0%) stopped adalimumab therapy due to loss of response, and one patient (1.0%) was lost to follow-up. Among the 92 patients who received adalimumab maintenance therapy, the cumulative proportions of patients remaining on adalimumab maintenance therapy were 70.0% at 1 year and 48.9% at 5 years. High partial Mayo score after 8 weeks of adalimumab therapy (hazard ratio [HR], 1.217; 95% confidence interval [CI], 1.040 to 1.425; p=0.014) and a history of exposure to two biologic agents before adalimumab therapy (HR, 4.722; CI, 1.033 to 21.586; p=0.045) were predictors of adalimumab discontinuation. CONCLUSIONS Long-term outcomes of adalimumab therapy in Korean UC patients appear to be comparable to those in previously published Western studies. Furthermore, previous exposure to multiple biologic agents before adalimumab therapy and disease activity after 8 weeks of adalimumab therapy were predictors of adalimumab discontinuation.
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Affiliation(s)
- Eun Hye Oh
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeongseok Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Namseok Ham
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Wook Hwang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang Hyoung Park
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dong-Hoon Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong-Sik Byeon
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung-Jae Myung
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Byong Duk Ye
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Correspondence to: Byong Duk Ye, Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea, Tel: +82-2-3010-3181, Fax: +82-2-476-0824, E-mail:
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15
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Chen D, Zhao R, Cao W, Zhou W, Jiang Y, Zhang S, Chen Y, Fei G, Li J, Qian J. Clinical characteristics of cytomegalovirus gastritis: A retrospective study from a tertiary medical center. Medicine (Baltimore) 2020; 99:e18927. [PMID: 32000406 PMCID: PMC7004595 DOI: 10.1097/md.0000000000018927] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Cytomegalovirus (CMV) gastritis is a rare opportunistic infection with diverse clinical manifestations. Our study aimed to investigate the clinical features of Chinese patients with CMV gastritis.Six inpatients diagnosed with CMV gastritis were retrospectively enrolled, based on the finding of inclusion bodies in routine hematoxylin and eosin staining or positive anti-CMV monoclonal antibodies under immunohistochemistry in the gastric biopsy. Data, including demographics, diagnostic measurements, and medications, were collected.Abdominal pain was the most frequently reported symptom, occurring in 4 patients. Five patients were immunocompromised with associated underlying diseases, and 3 patients had decreased leukocyte differentiation antigen 4 positive (CD4) T lymphocyte counts. Only 3 patients had either positive cytomegalovirus (CMV)-immunoglobulin (Ig) M or increased copies of CMV-DNA peripherally. All patients had gastric lesions in the antrum of the stomach, including ulcers or erosions observed by gastroscopy. All patients received ganciclovir by intravenous injection (IV) as the first line anti-CMV therapy, and attained complete (4) or partial remission (2) during the follow-up.CMV gastritis should be taken into consideration in patients with immunocompromised status who have abdominal pain, nausea, or vomiting. Gastroscopy and necessary biopsy are the major diagnostic methods for CMV gastritis. Early diagnosis leads to a better prognosis for these patients.
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Affiliation(s)
| | | | - Wei Cao
- Department of Infectious Diseases
| | | | | | - Shangzhu Zhang
- Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | | | | | - Ji Li
- Department of Gastroenterology
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16
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CMV-Reactive NK Cells in Pediatric Post-Hematopoietic Stem Cell Transplant. Transplant Proc 2020; 52:353-359. [DOI: 10.1016/j.transproceed.2019.11.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 10/21/2019] [Accepted: 11/10/2019] [Indexed: 12/19/2022]
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17
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McDonald GB, Sarmiento JI, Rees-Lui G, Myerson D. Cytomegalovirus hepatitis after bone marrow transplantation: An autopsy study with clinical, histologic and laboratory correlates. J Viral Hepat 2019; 26:1344-1350. [PMID: 31315152 DOI: 10.1111/jvh.13176] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Revised: 06/03/2019] [Accepted: 06/13/2019] [Indexed: 02/06/2023]
Abstract
Mortality from cytomegalovirus disease after marrow transplantation can be reduced by treatment with antiviral drugs based on the detection of viremia and organ involvement. We examined autopsy liver specimens to determine the frequency, extent and outcome of cytomegalovirus hepatitis and whether cytomegalovirus hepatitis occurred in the absence of cytomegalovirus disease elsewhere. Autopsy specimens from 50 transplant patients were evaluated for cytomegalovirus-infected cells, in five groups of 10, according to extent of CMV during life and at autopsy. Liver sections were examined by routine light microscopy, immunohistochemistry and in situ DNA hybridization. Clinical and laboratory data collected during the last 30 days of life were analysed as markers of liver cytomegalovirus infection. Cytomegalovirus-infected cells were detected in the livers of 10/10 patients with cytomegalovirus infection during life and widespread cytomegalovirus at autopsy; in 3/20 livers from patients with cytomegalovirus infection during life but negative liver cultures at autopsy; and in 1/10 livers from cytomegalovirus-seropositive patients who had been without other evidence of cytomegalovirus infection. Histology detected a lower density of cytomegalovirus-bearing cells per unit area of liver, compared to immunohistochemistry and in situ hybridization. No cytomegalovirus-infected cells were detected in livers from cytomegalovirus-seronegative controls. No distinctive clinical or laboratory findings correlated with liver cytomegalovirus detection. CMV liver disease is common in allografted patients with disseminated CMV but may rarely be isolated to the liver, best demonstrated with IHC and ISH. Massive hepatic necrosis from CMV was not seen in any autopsy liver in this study.
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Affiliation(s)
- George B McDonald
- Gastroenterology/Hepatology and Pathology Sections, Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, Washington
| | | | | | - David Myerson
- Gastroenterology/Hepatology and Pathology Sections, Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, Washington
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18
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Lim CC, Tan BH, Tung YT, Huang H, Hao Y, Mok IYJ, Lee PH, Choo JCJ. Risk-stratified approach to anti-viral prophylaxis against cytomegalovirus disease in glomerulonephritis and renal vasculitis treated with potent immunosuppressants. Infect Dis (Lond) 2019; 51:745-752. [PMID: 31407631 DOI: 10.1080/23744235.2019.1648855] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
Abstract
Aim: Cytomegalovirus (CMV) reactivation and disease in immunocompromised individuals is associated with significant morbidity and mortality. Preventive measures such as anti-viral prophylaxis or surveillance and pre-emptive therapy effectively reduced CMV disease in solid organ transplant but have not been evaluated among patients with glomerulonephritis at-risk for CMV disease after immunosuppressive therapy. We evaluated the utility and outcomes of a risk-stratified approach to anti-viral prophylaxis for adults with glomerulonephritis treated with potent immunosuppressants. Methods: Single-center retrospective cohort study of adults with glomerulonephritis and renal vasculitis prescribed methylprednisolone, cyclophosphamide or rituximab in a tertiary referral centre. A risk-stratified approach to CMV anti-viral prophylaxis was implemented in March 2015. We compared the incidence of CMV disease in the pre-implementation (January 2008-December 2014) and post-implementation (June 2015-June 2017) groups. Results: We studied 119 individuals: 85 in the pre-implementation group and 34 in the post-implementation group. The post-implementation group had worse kidney function, greater proteinuria, higher prednisolone dose and more received intravenous methylprednisolone and plasma exchanges but CMV disease within 6 months was similar to the pre-implementation group (2.9% vs. 3.5%, p = 1.00). Among individuals in the post-implementation group who satisfied criteria to receive anti-viral prophylaxis (n = 21), CMV disease was more frequent in the group not given prophylaxis compared to those given prophylaxis as recommended (8.3% versus 0%, p = 1.00). Adverse events related to anti-viral prophylaxis occurred in 40%. Conclusion: This study provided pilot data for future randomized controlled trials to evaluate CMV preventive strategies in selected high-risk patients with glomerulonephritis or renal vasculitis.
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Affiliation(s)
- Cynthia Ciwei Lim
- Department of Renal Medicine, Singapore General Hospital , Singapore
| | - Ban Hock Tan
- Department of Infectious Diseases, Singapore General Hospital , Singapore
| | - Yu Tzu Tung
- Department of Pharmacy, Singapore General Hospital , Singapore
| | - Huijun Huang
- Yong Loo Lin School of Medicine, National University of Singapore , Singapore
| | - Ying Hao
- Health Service Research Unit, Division of Medicine, Singapore General Hospital , Singapore
| | - Irene Y J Mok
- Department of Renal Medicine, Singapore General Hospital , Singapore
| | - Puay Hoon Lee
- Department of Pharmacy, Singapore General Hospital , Singapore
| | - Jason C J Choo
- Department of Renal Medicine, Singapore General Hospital , Singapore
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19
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Ljungman P, de la Camara R, Robin C, Crocchiolo R, Einsele H, Hill JA, Hubacek P, Navarro D, Cordonnier C, Ward KN. Guidelines for the management of cytomegalovirus infection in patients with haematological malignancies and after stem cell transplantation from the 2017 European Conference on Infections in Leukaemia (ECIL 7). THE LANCET. INFECTIOUS DISEASES 2019; 19:e260-e272. [PMID: 31153807 DOI: 10.1016/s1473-3099(19)30107-0] [Citation(s) in RCA: 286] [Impact Index Per Article: 47.7] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 06/03/2018] [Revised: 01/05/2019] [Accepted: 03/05/2019] [Indexed: 12/11/2022]
Abstract
Cytomegalovirus is one of the most important infections to occur after allogeneic haematopoietic stem cell transplantation (HSCT), and an increasing number of reports indicate that cytomegalovirus is also a potentially important pathogen in patients treated with recently introduced drugs for hematological malignancies. Expert recommendations have been produced by the 2017 European Conference on Infections in Leukaemia (ECIL 7) after a review of the literature on the diagnosis and management of cytomegalovirus in patients after HSCT and in patients receiving other types of therapy for haematological malignancies. These recommendations cover diagnosis, preventive strategies such as prophylaxis and pre-emptive therapy, and management of cytomegalovirus disease. Antiviral drugs including maribavir and letermovir are in development and prospective clinical trials have recently been completed. However, management of patients with resistant or refractory cytomegalovirus infection or cytomegalovirus disease is a challenge. In this Review we summarise the reviewed literature and the recommendations of the ECIL 7 for management of cytomegalovirus in patients with haematological malignancies.
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Affiliation(s)
- Per Ljungman
- Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital, and Division of Hematology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
| | | | - Christine Robin
- Assistance Publique-Hopitaux de Paris, Department of Hematology, Henri Mondor Hospital and Université Paris-Est Créteil, Créteil, France
| | - Roberto Crocchiolo
- Servizio Immunoematologia e Medicina Trasfusionale, Azienda Socio Sanitaria Territoriale di Bergamo Ovest, Treviglio, Italy
| | - Hermann Einsele
- Medizinische Klinik und Poliklinik II, Julius Maximilians Universitaet, Würzburg, Germany
| | - Joshua A Hill
- Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Petr Hubacek
- Department of Medical Microbiology and Department of Paediatric Haematology and Oncology, Second Faculty of Medicine of Motol University Hospital and Charles University, Prague, Czech Republic
| | - David Navarro
- Microbiology Service, Hospital Clínico Universitario, Instituto de Investigación INCLIVA, Valencia, Spain; Department of Microbiology, School of Medicine, University of Valencia, Valencia, Spain
| | - Catherine Cordonnier
- Assistance Publique-Hopitaux de Paris, Department of Hematology, Henri Mondor Hospital and Université Paris-Est Créteil, Créteil, France
| | - Katherine N Ward
- Division of Infection and Immunity, University College London, London, UK
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20
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Ito K, Okuno T, Sawada A, Sakai K, Kato Y, Muro K, Yanagita M, Teramoto Y, Yamasaki T, Inoue T, Ogawa O, Kobayashi T. Recurrent Aphthous Stomatitis Caused by Cytomegalovirus, Herpes Simplex Virus, and Candida Species in a Kidney Transplant Recipient: A Case Report. Transplant Proc 2019; 51:993-997. [PMID: 30979493 DOI: 10.1016/j.transproceed.2019.01.058] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Revised: 11/20/2018] [Accepted: 01/17/2019] [Indexed: 12/13/2022]
Abstract
Recipients of organ transplants are immunosuppressed and at high risk of oral infection. Oral diseases are often neglected compared with infections of other organs that typically confer higher morbidity. However, severe local symptoms hinder oral intake, decrease quality of life, and are sometimes lethal. Here we describe a case of a 57-year-old woman who developed recurrent aphthous stomatitis after kidney transplantation; the cause of the infection was complex and included cytomegalovirus, herpes simplex virus, and Candida species. Since misdiagnosis of oral diseases impairs patient quality of life and increases morbidity, clinicians should be aware of possible etiologies of oral infections in renal transplant recipients.
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Affiliation(s)
- K Ito
- Department of Urology, Kyoto University Hospital, Kyoto, Japan
| | - T Okuno
- Department of Urology, Kyoto University Hospital, Kyoto, Japan
| | - A Sawada
- Department of Urology, Kyoto University Hospital, Kyoto, Japan
| | - K Sakai
- Department of Nephrology, Kyoto University Hospital, Kyoto, Japan
| | - Y Kato
- Department of Nephrology, Kyoto University Hospital, Kyoto, Japan
| | - K Muro
- Department of Nephrology, Kyoto University Hospital, Kyoto, Japan
| | - M Yanagita
- Department of Nephrology, Kyoto University Hospital, Kyoto, Japan
| | - Y Teramoto
- Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan
| | - T Yamasaki
- Department of Urology, Kyoto University Hospital, Kyoto, Japan
| | - T Inoue
- Department of Urology, Kyoto University Hospital, Kyoto, Japan
| | - O Ogawa
- Department of Urology, Kyoto University Hospital, Kyoto, Japan.
| | - T Kobayashi
- Department of Urology, Kyoto University Hospital, Kyoto, Japan
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21
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Del Moral-Hernández O, Castañón-Sánchez CA, Reyes-Navarrete S, Martínez-Carrillo DN, Betancourt-Linares R, Jiménez-Wences H, de la Peña S, Román-Román A, Hernández-Sotelo D, Fernández-Tilapa G. Multiple infections by EBV, HCMV and Helicobacter pylori are highly frequent in patients with chronic gastritis and gastric cancer from Southwest Mexico: An observational study. Medicine (Baltimore) 2019; 98:e14124. [PMID: 30653141 PMCID: PMC6370051 DOI: 10.1097/md.0000000000014124] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The chronic inflammation and damage to the gastric epithelium induced by Helicobacter pylori (H. pylori) are the main risk factors for gastric cancer development. Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) induce chronic inflammation and have been found in gastric tumors. The objectives this observational study were to determine the frequency of multiple infections by Helicobacter pylori, Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) and to relate the infection by EBV and HCMV with H. pylori vacA/cagA genotypes in patients with chronic gastritis or gastric cancer. DNA from H. pylori, EBV and HCMV was detected by PCR in biopsies from 106 Mexican patients with chronic gastritis and 32 from gastric cancer. The cagA status and the vacA genotypes of H. pylori were determined by PCR. In chronic gastritis and gastric cancer EBV was found in 69.8% and 87.5%, HCMV in 52.8% and 53.1%, and H. pylori in 48.1% and 40.6%, respectively. In chronic gastritis, 53% of H. pylori patients were EBV and 33% were both EBV/HCMV; in gastric cancer, 92.3% of H. pylori-infected individuals were EBV and 46.1% were EVB/HCMV. All the intestinal- and mixed-type tumors and the 83.3% of diffuse-type tumors were EBV. No significant differences were found between single infections or coinfections with the diagnosis or the cancer type. The H. pylori genotypes were not related to EBV or HCMV infection. The frequency of dual infections by H. pylori, EBV and HCMV is higher in patients from southwest Mexico than other populations. It is likely that these pathogens act synergistically to induce inflammation and gastric cancer.
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Affiliation(s)
- Oscar Del Moral-Hernández
- Laboratory of Virology and Epigenetics of Cancer, Faculty of Chemical-Biological Sciences, Autonomous University of Guerrero, Chilpancingo, Guerrero
| | | | | | | | | | - Hilda Jiménez-Wences
- Laboratory of Clinical Research, Faculty of Chemical-Biological Sciences, Autonomous University of Guerrero
| | - Sol de la Peña
- Postdoctoral Fellow CONACYT in Laboratory of Clinical Research, Faculty of Chemical-Biological Sciences, Autonomous University of Guerrero
| | - Adolfo Román-Román
- Laboratory of Bacteriology Research, Faculty of Chemical-Biological Sciences, Autonomous University of Guerrero, Chilpancingo, Guerrero, Mexico
| | - Daniel Hernández-Sotelo
- Laboratory of Virology and Epigenetics of Cancer, Faculty of Chemical-Biological Sciences, Autonomous University of Guerrero, Chilpancingo, Guerrero
| | - Gloria Fernández-Tilapa
- Laboratory of Clinical Research, Faculty of Chemical-Biological Sciences, Autonomous University of Guerrero
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22
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Real-time quantitative PCR analysis of endoscopic biopsies for diagnosing CMV gastrointestinal disease in non-HIV immunocompromised patients: a diagnostic accuracy study. Eur J Clin Microbiol Infect Dis 2018; 37:2389-2396. [PMID: 30255430 DOI: 10.1007/s10096-018-3387-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Accepted: 09/19/2018] [Indexed: 12/27/2022]
Abstract
Cytomegalovirus gastrointestinal diseases (CMV-GIDs) are end-organ diseases of the gastrointestinal (GI) tract caused by CMV in immunocompromised patients. We aimed to evaluate the performance of quantitative polymerase chain reaction (qPCR) on endoscopic biopsies. We retrospectively reviewed the qPCR data on endoscopic biopsies in nonhuman immunodeficiency virus (HIV) immunocompromised patients between January 2009 and May 2015. The performance of the qPCR for CMV-GID was evaluated with the sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). A total of 195 patients were included, and 28 patients with confirmed CMV-GID were identified. The AUROC of the qPCR was 0.935 (95% confidence interval [CI], 0.885 to 0.985), the sensitivity was 89.3% (95% CI, 71.8 to 97.7%), and the specificity was 85.6% (95% CI, 79.4 to 97.6%) with a cutoff value of 180 copies/μg DNA. The proportion of patients with inflammatory bowel disease in the histopathology-negative, PCR-positive group was smaller than that in the histopathology-positive group (10.7 vs 35.0%, p = 0.026), but other characteristics were not significantly different. The use of qPCR on endoscopic biopsies demonstrated good diagnostic performance for detecting CMV in non-HIV immunocompromised patients. It may increase the diagnostic yield when combined with a conventional histopathology.
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Cytomegalovirus Associated Duodenal Ulcer and Duodenitis in a Malnourished Pediatric Patient. Case Rep Pediatr 2017; 2017:2412930. [PMID: 29119032 PMCID: PMC5651128 DOI: 10.1155/2017/2412930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Revised: 08/21/2017] [Accepted: 09/07/2017] [Indexed: 12/01/2022] Open
Abstract
Cytomegalovirus (CMV) duodenitis is a rare occurrence, especially in pediatric patients. A thirteen-month-old female presented to the Emergency Department for a febrile seizure. She was incidentally admitted for severe malnutrition with an initial workup remarkable for only a slight elevation in her ALT at 48. The patient was found to have an oral aversion requiring nasogastric tube feeds for adequate caloric intake. She continued to fail to gain weight and underwent an EGD that demonstrated a duodenal ulcer. She was consequently started on sucralfate and omeprazole. Post-EGD lab work demonstrated a pronounced increase in AST and ALT. Pathology from the EGD biopsies later demonstrated viral inclusion bodies consistent with CMV duodenitis. Apart from malnutrition, other causes of immune deficiency were eliminated from the differential diagnosis due to negative HIV PCR and normal immunoglobulins. While on antiviral treatment, her viral load of 1080 IU/mL trended to resolution and her liver enzymes normalized. The patient was ultimately discharged home demonstrating adequate weight gain via gastrostomy tube feeds. This case advocates for pediatricians to include immunodeficiency and infectious etiologies in their differential for malnourished patients in order to lead to earlier diagnosis and management of this treatable condition.
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Kim SH, Lee HS, Lee HJ, Kim SM, Shin S, Park SH, Kim KJ, Kim YH, Sung H, Lee SO, Choi SH, Yang SK, Kim YS, Woo JH, Han DJ. Clinical applications of interferon-γ releasing assays for cytomegalovirus to differentiate cytomegalovirus disease from bystander activation: a pilot proof-of-concept study. Korean J Intern Med 2017; 32:900-909. [PMID: 28830137 PMCID: PMC5583447 DOI: 10.3904/kjim.2015.354] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Revised: 02/05/2016] [Accepted: 02/22/2016] [Indexed: 01/24/2023] Open
Abstract
BACKGROUND/AIMS We evaluated the proposed clinical application of the combined interpretation of host factors and viral factors in two different cytomegalovirus (CMV) co-infection models. METHODS We prospectively enrolled all human immunodeficiency virus non-infected patients with confirmed Pneumocystitis jirovecii pneumonia (PCP) and those with suspected gastrointestinal CMV disease in a tertiary hospital. All patients underwent CMV interferon-γ releasing assay (IGRA) for CMV (T-track CMV, Lophius Biosciences). We created the 2-axis model with the CMV IGRA results as the x-axis and the results for CMV virus replication as the y-axis, and hypothesized that cases falling in the left upper quadrant (high viral load and low CMV-specific immunity) of the model would be true CMV infections. The CMV IGRA results were concealed from the attending physicians. RESULTS Of 39 patients with PCP, four (10%) were classified as combined CMV pneumonia, 13 (33%) as bystander activation, and the remaining 22 (56%) as no CMV infection. The data for all four patients with PCP and CMV pneumonia fell in the left upper quadrant of the 2-axis model. Of 24 patients with suspected gastrointestinal CMV disease, 12 (50%) were classified as gastrointestinal CMV disease and the remaining 12 (50%) as bystander activation with no gastrointestinal CMV disease. The data for 11 of the 12 patients (92%) with gastrointestinal CMV disease were located in the left upper quadrant of the 2-axis model. CONCLUSIONS Cases yielding low CMV IGRA results and high CMV viral replication appear to be true CMV infections. Further studies with large number of cases in different types of CMV disease should be proposed.
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Affiliation(s)
- Sung-Han Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Correspondence to Sung-Han Kim, M.D. Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea Tel: +82-2-3010-3305 Fax: +82-2-3010-6970 E-mail:
| | - Ho-Su Lee
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyun-Jung Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sun-Mi Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Shin
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang-Hyoung Park
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyung-Jo Kim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Hoon Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Heungsup Sung
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang-Oh Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang-Ho Choi
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yang Soo Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jun Hee Woo
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Duck-Jong Han
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Seo H, Chang K, Lee SH, Song EM, Kim GU, Seo M, Lee HS, Hwang SW, Yang DH, Kim KJ, Ye BD, Byeon JS, Myung SJ, Yang SK, Park SH. Long-term outcomes of infliximab treatment and predictors of response in 195 patients with ulcerative colitis: a hospital-based cohort study from Korea. Scand J Gastroenterol 2017; 52:857-863. [PMID: 28502189 DOI: 10.1080/00365521.2017.1323229] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Large-scale studies regarding the long-term efficacy of infliximab (IFX) treatment in non-Caucasian patients with ulcerative colitis (UC) are lacking. STUDY We analyzed the long-term outcomes of IFX in 195 Korean UC patients who received scheduled IFX treatments at Asan Medical Center. IFX failure was defined as IFX discontinuation due to colectomy or non-response to IFX, and additionally UC-related hospitalization or a need for rescue corticosteroids during the course of IFX. RESULTS Between December 2006 and October 2016, a total of 3101 infusions of IFX were administered to 195 patients over a median period of 21 months. At the end of the follow-up, 86 patients (44.1%) were still receiving IFX without failure. IFX was stopped in 73 (37.4%) patients due to colectomy (23 patients, 11.8%), non-response to IFX (35 patients, 17.9%) or other reasons such as adverse events or patients' preferences (15 patients, 7.7%). An additional 36 (18.5%) patients experienced IFX failure during follow-up due to a need for rescue corticosteroids (13 patients, 6.7%), UC-related hospitalization (8 patients, 4.1%), or both (15 patients, 7.7%). The survival free of IFX failure was 58.1% at 1 year, 50.7% at 3 years and 44.8% at 5 years. In a multivariate regression analysis, cytomegalovirus colitis within 3 months before IFX initiation was a predictor of IFX failure (hazard ratio 1.57; 95% confidence interval 1.04-2.37; p = .032). CONCLUSIONS The long-term efficacy of IFX in a large, real-life cohort of Korean UC patients appears to be comparable to that in previously published Western studies.
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Affiliation(s)
- Hyungil Seo
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Kiju Chang
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Sun-Ho Lee
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Eun-Mi Song
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Gwang-Un Kim
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Myeongsook Seo
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Ho-Su Lee
- b Health Screening and Promotion Center , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Sung-Wook Hwang
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
- c Inflammatory Bowel Disease Center , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Dong-Hoon Yang
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Kyung-Jo Kim
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
- c Inflammatory Bowel Disease Center , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Byong Duk Ye
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
- c Inflammatory Bowel Disease Center , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Jeong-Sik Byeon
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Seung-Jae Myung
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Suk-Kyun Yang
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
- c Inflammatory Bowel Disease Center , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Sang Hyoung Park
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
- c Inflammatory Bowel Disease Center , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
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Hong SI, Kim T, Park SY, Jung J, Lee JY, Chong YP, Sung H, Lee SO, Choi SH, Kim YS, Woo JH, Kim SH. Sensitivity of the Cytomegalovirus Antigenemia Assay to Diagnose Cytomegalovirus Retinitis. Infect Chemother 2016; 48:302-308. [PMID: 27883376 PMCID: PMC5204009 DOI: 10.3947/ic.2016.48.4.302] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2016] [Accepted: 09/02/2016] [Indexed: 12/04/2022] Open
Abstract
Background Cytomegalovirus (CMV) retinitis is one of the most important tissue-invasive CMV diseases in immunocompromised patients. Since 1980, non-invasive diagnostic methods, notably the CMV antigenemia assay, have been widely used as adjunct tests to diagnose tissue-invasive CMV diseases. However, there are limited data on the diagnostic value of the CMV antigenemia assay for diagnosing CMV retinitis. Materials and Methods We performed a retrospective review of all cases of CMV retinitis at Asan Medical Center, Seoul, South Korea over a 9-year period. The diagnosis of CMV retinitis was made by experienced ophthalmologists according to medical history and an ophthalmoscopic appearance of typical retinopathy, together with absence of an alternative diagnosis. Results We analyzed 44 patients with CMV retinitis (affecting 57 eyes) for whom the CMV antigenemia assay was performed. Of the 44 patients, 31 (70%) were HIV-uninfected and 13 (30%) were HIV-infected. The overall sensitivity of the CMV antigenemia assay was 66% (95% confidence interval [CI] 50–80%). The test’s sensitivity showed a non-significant trend towards being higher in HIV-infected patients than in HIV-uninfected patients (sensitivity 85% vs 58%, respectively, P = 0.16). In a subgroup analysis of the 35 patients without other concurrent tissue-invasive CMV disease, the sensitivity of the CMV antigenemia assay was 57% (95% CI 40–74%). Conclusions The CMV antigenemia assay has limited value as a non-invasive diagnostic adjunct test for CMV retinitis. Therefore, the results of the assay need to be interpreted in the context of underlying disease, clinical presentation, and ophthalmoscopic findings.
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Affiliation(s)
- Sun In Hong
- Department of Infectious Diseases, Gyeongsang National University Changwon Hospital, Gyeongsang National University School of Medicine, Changwon, Korea.,Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Taeeun Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Se Yoon Park
- Division of Infectious Diseases, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Jiwon Jung
- Division of Infectious Diseases, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
| | - Joo Yong Lee
- Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yong Phil Chong
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Heungsup Sung
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang Oh Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang Ho Choi
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yang Soo Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jun Hee Woo
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Han Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
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Kim T, Lee YM, Lee SO, Choi SH, Kim YS, Woo JH, Sung H, Jung JH, Shin S, Kim YH, Kang YA, Lee YS, Lee JH, Lee JH, Lee KH, Park SK, Han DJ, Kim SH. Differences of cytomegalovirus diseases between kidney and hematopoietic stem cell transplant recipients during preemptive therapy. Korean J Intern Med 2016; 31:961-70. [PMID: 27055664 PMCID: PMC5016278 DOI: 10.3904/kjim.2015.079] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Revised: 05/22/2015] [Accepted: 06/30/2015] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND/AIMS Cytomegalovirus (CMV) surveillance and preemptive therapy is a widely-used strategy for preventing CMV disease in transplant recipients. However, there are limited data on the incidence and patterns of CMV disease during the preemptive period. Thus, we investigated the incidence and pattern of tissue-invasive CMV disease in CMV seropositive kidney transplantation (KT) and hematopoietic stem cell transplantation (HCT) recipients during preemptive therapy. METHODS We prospectively identified patients with tissue-invasive CMV disease among 664 KT (90%) and 496 HCT (96%) recipients who were D+/R+ (both donor and recipient seropositive) during a 4-year period. RESULTS The incidence rates of CMV disease were 4.1/100 person-years (4%, 27/664) in KT recipients and 5.0/100 person-years (4%, 21/496) in HCT recipients. Twenty-six (96%) of the KT recipients with CMV disease had gastrointestinal CMV, whereas 17 (81%) of the HCT recipients had gastrointestinal CMV and 4 (19%) had CMV retinitis. Thus, CMV retinitis was more common among HCT recipients (p = 0.03). All 27 KT recipients with CMV disease suffered abrupt onset of CMV disease before or during preemptive therapy; 10 (48%) of the 21 HCT recipients with CMV disease were also classified in this way but the other 11 (52%) were classified as CMV disease following successful ganciclovir preemptive therapy (p < 0.001). CONCLUSIONS The incidence of CMV disease was about 4% in both KT and HCT recipients during preemptive therapy. However, CMV retinitis and CMV disease as a relapsed infection were more frequently found among HCT recipients.
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Affiliation(s)
- Tark Kim
- Division of Infectious Diseases, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yu-Mi Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Department of Infectious Diseases, Inje University Busan Paik Hospital, Busan, Korea
| | - Sang-Oh Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang-Ho Choi
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yang Soo Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jun Hee Woo
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Heungsup Sung
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Joo Hee Jung
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Shin
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young Hoon Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Ah Kang
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Shin Lee
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jung-Hee Lee
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Je-Hwan Lee
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyoo-Hyung Lee
- Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Su-Kil Park
- Department of Nephrology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Duck Jong Han
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung-Han Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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CMV in Hematopoietic Stem Cell Transplantation. Mediterr J Hematol Infect Dis 2016; 8:e2016031. [PMID: 27413524 PMCID: PMC4928522 DOI: 10.4084/mjhid.2016.031] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Accepted: 06/06/2016] [Indexed: 12/12/2022] Open
Abstract
Due to its negative impact on the outcome of stem cell transplant (SCT) and solid organ transplant patients (SOT) CMV has been called “the troll of transplantation”. One of the greatest advances in the management of SCT has been the introduction of the preemptive strategy. Since its introduction, the incidence of the viremia, as expected, remains unchanged but there has been a marked decline in the incidence of early CMV disease. However, in spite of the advances in prevention of CMV disease, CMV is still today an important cause of morbidity and mortality. Late CMV disease is still occurring in a significant proportion of patients and the so-called indirect effects of CMV are causing significant morbidity and mortality. Fortunately there have been several advances in the development of new antivirals, adoptive immunotherapy and DNA-CMV vaccines that might transform the management of CMV in the near future.
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Fisher C, Alexander J, Bhattacharya R, Rakita R, Kirby K, Boeckh M, Limaye A. Sensitivity of blood and tissue diagnostics for gastrointestinal cytomegalovirus disease in solid organ transplant recipients. Transpl Infect Dis 2016; 18:372-80. [DOI: 10.1111/tid.12531] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Revised: 12/17/2015] [Accepted: 01/21/2016] [Indexed: 12/12/2022]
Affiliation(s)
- C.E. Fisher
- Divisions of Allergy & Infectious Disease; Department of Medicine; University of Washington; Seattle Washington USA
- Vaccine and Infectious Disease Division; Fred Hutchinson Cancer Research Center; Seattle Washington USA
| | - J. Alexander
- Gastroenterology; Department of Medicine; University of Washington; Seattle Washington USA
| | - R. Bhattacharya
- Gastroenterology; Department of Medicine; University of Washington; Seattle Washington USA
| | - R.M. Rakita
- Divisions of Allergy & Infectious Disease; Department of Medicine; University of Washington; Seattle Washington USA
| | - K.A. Kirby
- Division of Geriatrics; San Francisco VA Medical Center and University of California; San Francisco California USA
| | - M. Boeckh
- Divisions of Allergy & Infectious Disease; Department of Medicine; University of Washington; Seattle Washington USA
- Vaccine and Infectious Disease Division; Fred Hutchinson Cancer Research Center; Seattle Washington USA
| | - A.P. Limaye
- Divisions of Allergy & Infectious Disease; Department of Medicine; University of Washington; Seattle Washington USA
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Seo M, Kim DH, Gong EJ, Ahn JY, Lee JH, Jung KW, Choi KD, Song HJ, Lee GH, Jung HY, Kim JH, Lee SO, Choi SH, Kim YS, Woo JH, Kim SH. Is Follow-Up Endoscopy Necessary in Upper Gastrointestinal Cytomegalovirus Disease? Medicine (Baltimore) 2016; 95:e3389. [PMID: 27175637 PMCID: PMC4902479 DOI: 10.1097/md.0000000000003389] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Gastrointestinal (GI) cytomegalovirus (CMV) disease is a major cause of morbidity and mortality in immunocompromised patients. Diagnosis of GI CMV disease mostly relies on endoscopy examination and histopathologic findings. There are limited data on the need for follow-up endoscopy with histopathologic examination in patients with upper gastrointestinal (UGI) CMV disease. All adult patients with confirmed and probable UGI CMV disease at a tertiary hospital over a 16-year period whose follow-up endoscopy was available were enrolled. The patients were classified as endoscopic responders if they showed complete or partial improvement on follow-up endoscopy, and as endoscopic nonresponders if there was no improvement or worsening. CMV tissue clearance was defined as absence of any visible CMV inclusion bodies, negative CMV immunohistochemistry and negative CMV polymerase chain reaction in follow-up biopsy tissues. During the study period, 77 patients with UGI CMV disease were analyzed. The median time to follow-up endoscopy was 19 days (interquartile range, 14-27). Of these 77 patients, 52 (68%) were classified as responders, and the remaining 25 (32%) as nonresponders. GI bleeding was more common in the nonresponders than the responders (36% vs 12%, respectively; P = 0.02). There was no significant difference in CMV tissue clearance between the responders and nonresponders (56% vs 69%, respectively; P = 0.38), median durations of treatment (20 days vs 21 days, respectively; P = 0.48), and relapse rates (10% vs 8%, respectively; P > 0.99). Multivariate analysis showed that the only independent predictive factor for relapse of CMV antigenemia or CMV GI disease was multiorgan CMV disease (odds ratio = 12.4, 95% confidence interval 1.6-97.9; P = 0.02). Endoscopic responses were obtained in about two-thirds of patients with UGI CMV disease 2 or 3 weeks after antiviral therapy. However, these follow-up endoscopic findings neither reflected CMV tissue clearance nor predicted disease relapse. These findings suggest that the routine follow-up endoscopy may not be warranted in patients with UGI CMV disease.
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Affiliation(s)
- Myeongsook Seo
- From the Department of Gastroenterology (MS, DHK, EJG, JYA, JHL, KWJ, KDC, HJS, GHL, H-YJ, J-HK) and Department of Infectious Diseases (S-OL, S-HC, YSK, JHW, S-HK), Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
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Lee HS, Park SH, Kim SH, Kim J, Choi J, Lee HJ, Kim WS, Lee JM, Kwak MS, Hwang SW, Yang DH, Kim KJ, Ye BD, Byeon JS, Myung SJ, Yoon YS, Yu CS, Kim JH, Yang SK. Risk Factors and Clinical Outcomes Associated with Cytomegalovirus Colitis in Patients with Acute Severe Ulcerative Colitis. Inflamm Bowel Dis 2016; 22:912-918. [PMID: 26829410 DOI: 10.1097/mib.0000000000000675] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Cytomegalovirus (CMV) colitis can contribute to an unfavorable outcome of acute severe ulcerative colitis (ASUC). The purpose of this study was to evaluate the clinical outcomes of ASUC according to the CMV status and identify risk factors for CMV colitis in patients with ASUC. METHODS We retrospectively analyzed patients with ASUC from 2011 to 2014 according to the criteria of Truelove and Witts. CMV colitis was diagnosed by histopathological and/or immunohistochemical analysis of tissue samples. The risk factors for CMV colitis were investigated and clinical outcomes were assessed using the rate of rescue therapy and colectomy. RESULTS Of 149 patients with ASUC, 50 (33.6%) were diagnosed with CMV colitis. During admission, 16 of 149 patients (10.7%) underwent colectomy: 7 of 50 (14.0%) in the ASUC-CMV group versus 9 of 99 (9.1%) in the ASUC-only group (P = 0.364). The need for rescue therapy was 2.28-fold higher in the ASUC-CMV group than in the ASUC-only group in multivariate analysis (95% confidence interval, 1.10-4.72). Multivariate analysis also revealed that recent use of high-dose steroids (odds ratio, 3.30; 95% confidence interval, 1.33-8.19) and a higher Mayo score (odds ratio, 1.58; 95% confidence interval, 1.05-2.38) were risk factors for CMV colitis. CONCLUSIONS CMV colitis often occurs in ASUC, particularly in patients who have recently been treated with high-dose steroids and have a higher Mayo score on admission. Patients with ASUC and CMV colitis seem to have a poorer prognosis, as indicated by the greater need for rescue therapy.
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Affiliation(s)
- Ho-Su Lee
- *Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; and Departments of †Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, ‡Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, §Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, and ‖Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Kim SH, Lee HJ, Kim SM, Jung JH, Shin S, Kim YH, Sung H, Lee SO, Choi SH, Kim YS, Woo JH, Han DJ. Diagnostic Usefulness of Cytomegalovirus (CMV)-Specific T Cell Immunity in Predicting CMV Infection after Kidney Transplantation: A Pilot Proof-of-Concept Study. Infect Chemother 2015; 47:105-10. [PMID: 26157588 PMCID: PMC4495268 DOI: 10.3947/ic.2015.47.2.105] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2015] [Revised: 03/24/2015] [Accepted: 03/25/2015] [Indexed: 11/24/2022] Open
Abstract
Background Cytomegalovirus (CMV) is one of the most important opportunistic infections in transplant recipients. Currently sero-positivity for CMV IgG before solid organ transplantation is the laboratory test of choice for stratifying the risk of CMV reactivation after solid organ transplantation. Theoretically, CMV-specific cell-mediated immune responses before solid organ transplantation should further categorize patients as high or low risk of CMV development. We therefore evaluated the usefulness of the CMV-specific enzyme-linked immunospot (ELISPOT) assay in kidney transplant (KT) candidates for predicting the development of CMV infections after transplantation. Materials and Methods All adult CMV IgG (+) recipients admitted to the KT institute between March 2014 and June 2014 were enrolled, and CMV infections after KT were observed between March 2014 and December 2014. All patients underwent CMV pp65 and IE1-specific ELISPOT assays before transplantation. CMV infection was defined in the presence of CMV antigenemia, CMV syndrome, or tissue-invasive CMV disease. We used the data to select optimal cut-off values for pp65 and IE1, respectively, on ROC curves. Results A total of 69 transplant recipients involving 54 (78%) living-donor KT, 9 (13%) deceased-donor KT, 3 (4%) kidney-pancreas transplants, and 3 (4%) pancreas transplants were enrolled. Of the 69 patients, 27 (39%) developed CMV infections. There was no association between the IE1-specific ELISPOT assay and CMV infection. However, only 15 (31%) of the 48 patients with positive pp65-specific ELISPOT results (>10 spots/2.0 × 105 cells) developed CMV infections, whereas 12 (57%) of the 21 patients with negative pp65-specific ELISPOT results developed CMV infection (P = 0.04). Conclusion Negative pp65-specific ELISPOT assay results before transplantation appear to predict the subsequent development of CMV infections after transplantation in CMV IgG (+) KT recipients. Therefore, risk stratification of CMV IgG (+) recipients using the CMV-specific ELISPOT, together with preventive strategies, may further reduce CMV development.
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Affiliation(s)
- Sung-Han Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyun-Jeong Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sun-Mi Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Joo Hee Jung
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Shin
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young Hoon Kim
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Hungseop Sung
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang-Oh Lee
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang-Ho Choi
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yang Soo Kim
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jun Hee Woo
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Duck Jong Han
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Chun J, Lee C, Kwon JE, Hwang SW, Kim SG, Kim JS, Jung HC, Im JP. Usefulness of the cytomegalovirus antigenemia assay in patients with ulcerative colitis. Intest Res 2015; 13:50-9. [PMID: 25691843 PMCID: PMC4316222 DOI: 10.5217/ir.2015.13.1.50] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2014] [Revised: 05/28/2014] [Accepted: 06/30/2014] [Indexed: 12/13/2022] Open
Abstract
Background/Aims Patients with ulcerative colitis (UC) are at high risk for cytomegalovirus (CMV) reactivation. The usefulness of the CMV antigenemia assay in active UC patients has rarely been studied. We assessed whether the assay detects CMV colitis and predicts clinical outcomes in patients with UC. Methods We retrospectively reviewed the medical records of patients hospitalized for moderate-to-severe UC from 2003 to 2012. Positive CMV antigenemia was defined as ≥1 pp65-positive cell per 2×105 polymorphonuclear neutrophils. CMV colitis was defined as the presence of inclusion bodies and/or positive immunohistochemistry in the colonic mucosa. The primary outcome was steroid refractoriness, defined as the absence of clinical improvement after intravenous high-dose steroid administration. Results A total of 43 patients were enrolled. CMV antigenemia was detected in 12 (27.9%) patients. Positive CMV antigenemia was significantly associated with CMV colitis (P =0.001). The sensitivity and specificity of positive CMV antigenemia for diagnosing CMV colitis were 66.7% and 87.1%, respectively. Steroid refractoriness was found in 11 of 12 (91.7%) and 12 of 31 (38.7%) patients with positive and negative CMV antigenemia, respectively (P =0.002). The independent predictors for steroid refractoriness were positive CMV antigenemia (adjusted odds ratio [OR], 7.73; 95% confidence interval [CI], 1.22-49.19; P =0.030) and a shorter duration from the diagnosis of UC (adjusted OR, 0.99; 95% CI, 0.98-0.99; P =0.025). Conclusions The CMV antigenemia assay shows low sensitivity but high specificity for detecting CMV colitis and may predict steroid-refractory UC. Early rescue therapy might be considered in UC patients positive for CMV antigenemia.
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Affiliation(s)
- Jaeyoung Chun
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Changhyun Lee
- Department of Internal Medicine and Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Korea
| | - Ji-Eun Kwon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Sung Wook Hwang
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Sang Gyun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Joo Sung Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hyun Chae Jung
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jong Pil Im
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Chang S, Cheon JH. A clinical significance of assessing cytomegalovirus infection status in patients with ulcerative colitis. Intest Res 2015; 13:2-3. [PMID: 25691836 PMCID: PMC4316218 DOI: 10.5217/ir.2015.13.1.2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2014] [Revised: 12/03/2014] [Accepted: 12/03/2014] [Indexed: 12/28/2022] Open
Affiliation(s)
- Sooyun Chang
- Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Hee Cheon
- Institute of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Ko JH, Peck KR, Lee WJ, Lee JY, Cho SY, Ha YE, Kang CI, Chung DR, Kim YH, Lee NY, Kim KM, Song JH. Clinical presentation and risk factors for cytomegalovirus colitis in immunocompetent adult patients. Clin Infect Dis 2014; 60:e20-6. [PMID: 25452594 DOI: 10.1093/cid/ciu969] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) colitis is a common manifestation of CMV end-organ disease, which has typically been described in immunocompromised hosts. Recently, it has been noted that this also occurs in immunocompetent patients. To gather relevant data about clinical presentation, prognosis, and risk factors for development of CMV colitis in immunocompetent hosts, we analyzed all cases that occurred during a 19-year period at our institution. METHODS A case-control study was performed to identify risk factors for CMV colitis in immunocompetent hosts. Electronic medical records of individuals who were admitted and diagnosed with CMV colitis between January 1995 and February 2014 at a tertiary care university hospital were reviewed. Two non-CMV colitis patients who were age- and sex-matched were selected as controls for each case. RESULTS A total of 51 patients with CMV colitis were included in this study along with 102 control patients. Certain conditions including renal disease on hemodialysis, neurologic disease, rheumatologic disease, intensive care unit admission, and exposure to antibiotics, antacids, steroids, or red blood cell (RBC) transfusions within 1 month of diagnosis of colitis were associated with CMV colitis on univariate analysis. Among these, steroid use and RBC transfusion within 1 month were identified as independent risk factors for developing CMV colitis on multivariate analysis. The 30-day mortality rate was 7.8% without any attributable mortality. CONCLUSIONS Steroid use and RBC transfusion within 1 month of the diagnosis of colitis were independent risk factors for development of CMV colitis in immunocompetent hosts.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Kyoung-Mee Kim
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Kim JW, Boo SJ, Ye BD, Kim CL, Yang SK, Kim J, Kim SA, Park SH, Park SK, Yang DH, Jung KW, Kim KJ, Byeon JS, Myung SJ, Kim JH. Clinical utility of cytomegalovirus antigenemia assay and blood cytomegalovirus DNA PCR for cytomegaloviral colitis patients with moderate to severe ulcerative colitis. J Crohns Colitis 2014; 8:693-701. [PMID: 24405983 DOI: 10.1016/j.crohns.2013.12.014] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Revised: 12/16/2013] [Accepted: 12/17/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Clinical usefulness of cytomegalovirus (CMV) antigenemia assay and blood CMV polymerase chain reaction (PCR) in patients with ulcerative colitis (UC) needs to be evaluated. METHODS Medical records of moderate to severe UC patients between January 2001 and December 2012 were reviewed retrospectively. Diagnostic performances of CMV antigenemia assay and blood PCR to predict CMV colitis, and clinical outcome according to the results were analyzed. CMV colitis was diagnosed by H&E staining and/or CMV immunohistochemistry. RESULTS Of the 229 study subjects, 83 patients (36.2%) had CMV colitis. The sensitivity and specificity of CMV antigenemia assay were 47.0% and 81.7%, and those of blood CMV DNA PCR were 44.3% and 87.9%, respectively. If either CMV antigenemia or PCR was positive in the presence of significant ulcers, the sensitivity and specificity of having CMV colitis were 67.3% and 75.7%, respectively, with the area under the receiver operating characteristic curve value of 0.717. Among patients with significant ulcers, positive CMV antigenemia (33/50 [66.0%] vs. 31/102 [30.4%]; p<0.001) and positive blood CMV PCR (25/37 [67.6%] vs. 24/86 [27.9%]; p<0.001) showed significantly higher probability of CMV colitis than blood test-negative patients. UC-CMV colitis patients with positive CMV antigenemia showed significantly higher rate of colectomy than those with negative antigenemia (13/39 [33.3%] vs. 5/44 [11.4%]; p=0.015). CONCLUSIONS Although CMV antigenemia and blood CMV PCR showed low sensitivity for diagnosing CMV colitis, the specificity values were high. Among UC-CMV colitis patients, CMV antigenemia showed significant association with subsequent colectomy.
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Affiliation(s)
- Jong Wook Kim
- Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Republic of Korea
| | - Sun-Jin Boo
- Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Republic of Korea
| | - Byong Duk Ye
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea; Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
| | - Chang Lae Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Suk-Kyun Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea; Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jihun Kim
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Sun A Kim
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Sang Hyoung Park
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea; Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Soo-Kyung Park
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Dong-Hoon Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Kee Wook Jung
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Kyung-Jo Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea; Inflammatory Bowel Disease Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jeong-Sik Byeon
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Seung-Jae Myung
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jin-Ho Kim
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
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Lee YM, Kim Y, Han D, Park SK, Park J, Sung H, Hong HL, Kim T, Kim SH, Choi SH, Kim Y, Woo J, Lee SO. Cytomegalovirus infection after acute rejection therapy in seropositive kidney transplant recipients. Transpl Infect Dis 2014; 16:397-402. [DOI: 10.1111/tid.12227] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Revised: 12/17/2013] [Accepted: 01/20/2014] [Indexed: 11/29/2022]
Affiliation(s)
- Y.-M. Lee
- Department of Infectious Diseases; Asan Medical Center; University of Ulsan College of Medicine; Seoul Korea
- Department of Infectious Diseases; Busan Paik Hospital; Inje University College of Medicine; Busan Korea
| | - Y.H. Kim
- Department of Surgery; Asan Medical Center; University of Ulsan College of Medicine; Seoul Korea
| | - D.J. Han
- Department of Surgery; Asan Medical Center; University of Ulsan College of Medicine; Seoul Korea
| | - S.-K. Park
- Department of Nephrology; Asan Medical Center; University of Ulsan College of Medicine; Seoul Korea
| | - J.S. Park
- Department of Nephrology; Asan Medical Center; University of Ulsan College of Medicine; Seoul Korea
| | - H. Sung
- Department of Laboratory Medicine; Asan Medical Center; University of Ulsan College of Medicine; Seoul Korea
| | - H.-L. Hong
- Department of Infectious Diseases; Asan Medical Center; University of Ulsan College of Medicine; Seoul Korea
| | - T. Kim
- Department of Infectious Diseases; Asan Medical Center; University of Ulsan College of Medicine; Seoul Korea
| | - S.-H. Kim
- Department of Infectious Diseases; Asan Medical Center; University of Ulsan College of Medicine; Seoul Korea
| | - S.-H. Choi
- Department of Infectious Diseases; Asan Medical Center; University of Ulsan College of Medicine; Seoul Korea
| | - Y.S. Kim
- Department of Infectious Diseases; Asan Medical Center; University of Ulsan College of Medicine; Seoul Korea
| | - J.H. Woo
- Department of Infectious Diseases; Asan Medical Center; University of Ulsan College of Medicine; Seoul Korea
| | - S.-O. Lee
- Department of Infectious Diseases; Asan Medical Center; University of Ulsan College of Medicine; Seoul Korea
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Gotthardt DN, Senft J, Sauer P, Weiss KH, Flechtenmacher C, Eckerle I, Schaefer Y, Schirmacher P, Stremmel W, Schemmer P, Schnitzler P. Occult cytomegalovirus cholangitis as a potential cause of cholestatic complications after orthotopic liver transplantation? A study of cytomegalovirus DNA in bile. Liver Transpl 2013; 19:1142-1150. [PMID: 23894112 DOI: 10.1002/lt.23713] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2013] [Accepted: 06/30/2013] [Indexed: 12/29/2022]
Abstract
Cholestatic complications, important causes of morbidity and mortality after orthotopic liver transplantation (OLT), often have an unclear etiology. Human cytomegalovirus (CMV) infections occur in immunosuppressed patients and can be detected in blood samples. However, CMV analyses of body fluids and biopsies are more sensitive. Here we evaluated whether a CMV analysis of bile could reveal occult CMV cholangitis. We evaluated OLT patients undergoing endoscopic retrograde cholangiography (ERC) for suspected biliary complications after OLT at a tertiary care center. Biliary CMV DNA levels were measured with real-time polymerase chain reaction. A nonanastomotic biliary lesion (NABL) group consisted of patients with nonanastomotic strictures (NASs) at the time of ERC (n = 59) and patients with normal ERC findings but microscopic biliary lesions in biopsy samples (n = 12). The anastomotic stricture (AS) group comprised patients with ASs only (n = 53). In all, 124 OLT patients underwent 240 ERC procedures. Biliary CMV DNA was detected in 14 of the 124 patients and was more frequently found in the NABL group (12/71 for the NABL group versus 2/53 for the AS group, P = 0.02). Concurrent sampling of CMV DNA in blood yielded negative results. Biliary CMV was more frequently detected in patients with a positive recipient status (13/73 or 17.8% versus 1/44 or 2.3%, P < 0.05). There was no significant difference in the incidence of biliary CMV between patients with a high-risk CMV status and patients with a low-risk CMV status. The median interval between OLT and biliary CMV detection was 8.4 months (range = 0.4-212.8 months). In conclusion, biliary CMV was detected in a substantial number of patients after OLT and was significantly associated with NASs or microscopic biliary lesions. A potential occult CMV infection could, therefore, be considered as a contributory etiological factor in the development of biliary complications.
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Affiliation(s)
- Daniel Nils Gotthardt
- Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg, Germany
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Durand CM, Marr KA, Arnold CA, Tang L, Durand DJ, Avery RK, Valsamakis A, Neofytos D. Detection of cytomegalovirus DNA in plasma as an adjunct diagnostic for gastrointestinal tract disease in kidney and liver transplant recipients. Clin Infect Dis 2013; 57:1550-9. [PMID: 23956167 DOI: 10.1093/cid/cit521] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) disease is the most common infectious complication after solid organ transplantation, frequently affecting the gastrointestinal (GI) tract. There are limited data on quantitative polymerase chain reaction (qPCR) for plasma CMV DNA as an adjunct diagnostic method for GI tract disease in kidney and liver transplant recipients. METHODS We reviewed all records of adult kidney and liver transplant recipients with a GI tract biopsy and plasma CMV qPCR result within 15 days of biopsy during a 6.5-year period at our center. CMV GI tract disease was defined as histopathologic evidence of CMV on biopsy by immunohistochemistry or visualization of inclusion bodies. RESULTS GI tract biopsy and qPCR results were available for 81 kidney and liver transplant recipients; 20 cases of confirmed CMV GI tract disease were identified. Overall, the sensitivity of qPCR for diagnosing CMV GI tract disease was 85% (95% confidence interval [CI], 61%-96%), and the specificity was 95% (95% CI, 85%-99%). For CMV-seronegative recipients (R(-)) with CMV-seropositive donors (D(+)), the sensitivity of qPCR was 100% (95% CI, 59%-99%), and the specificity was 80% (95% CI, 30%-99%). The lowest sensitivity was observed in CMV D(+)/R(+) cases (72.7%; 95% CI, 39%-93%). The mean plasma CMV copy number in patients with GI tract disease was 3.84 log10 (38 334 copies/mL). CONCLUSIONS Plasma CMV qPCR had good sensitivity and excellent specificity for CMV GI tract disease in kidney and liver transplant recipients. Its sensitivity was 100% in CMV D(+)/R(-) cases but 72.7% in CMV D(+)/R(+) cases. This variation in assay performance according to host serostatus may reflect differences in disease pathogenesis.
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Ozaki T, Yamashita H, Kaneko S, Yorifuji H, Takahashi H, Ueda Y, Takahashi Y, Kaneko H, Kano T, Mimori A. Cytomegalovirus disease of the upper gastrointestinal tract in patients with rheumatic diseases: a case series and literature review. Clin Rheumatol 2013; 32:1683-90. [PMID: 23942768 DOI: 10.1007/s10067-013-2363-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2013] [Accepted: 07/31/2013] [Indexed: 02/06/2023]
Abstract
Cytomegalovirus disease of the upper gastrointestinal tract (CMV-UGT) is a rare but significant complication in patients with rheumatic diseases. We reviewed records for January 2004 to December 2012 and investigated the occurrence of CMV-UGT in patients with rheumatic diseases to evaluate clinical characteristics, the value of the CMV antigenemia assay, and the association between immunosuppressive therapy and CMV-UGT. Ten CMV-UGT events (six gastric ulcer, two esophagitis, one gastritis, and one duodenal ulcer) in nine patients (three rheumatoid arthritis, three systemic lupus erythematosus, one dermatomyositis, one systemic sclerosis, and one overlap syndrome) were identified based on pathology. Mean age was 66.5 (range, 53-76) years. The CMV antigenemia assay was negative in five cases (50 %). All ten cases received glucocorticoids and six (60 %) received pulsed glucocorticoids. Mean prednisolone dose was 31.3 (range, 7.5-40) mg/day at diagnosis. Concomitant immunosuppressive agents were used in eight cases (80 %). Considering other published cases, the most common immunosuppressive drug was cyclophosphamide (ten cases; 45 %). Notably, two of our patients who were treated with low-dose glucocorticoids plus other milder immunosuppressive drugs (methotrexate and cyclosporine) also developed CMV-UGT. Life-threatening complications such as massive bleeding or perforated ulcer occurred in two patients. These results suggest that patients receiving intensive immunosuppressive therapy such as high-dose glucocorticoids and cyclophosphamide are at higher risk for developing CMV-UGT. Moreover, CMV-UGT can occur even with low-dose glucocorticoid therapy and relatively mild immunosuppressive agents. The value of the CMV antigenemia assay for predicting CMV-UGT appears to be limited.
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Affiliation(s)
- Takashi Ozaki
- Division of Rheumatic Diseases, National Center for Global Health and Medicine, 1-21-1, Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan,
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Hamada Y, Nagata N, Shimbo T, Igari T, Nakashima R, Asayama N, Nishimura S, Yazaki H, Teruya K, Gatanaga H, Kikuchi Y, Akiyama J, Ohmagari N, Uemura N, Oka S. Assessment of antigenemia assay for the diagnosis of cytomegalovirus gastrointestinal diseases in HIV-infected patients. AIDS Patient Care STDS 2013; 27:387-91. [PMID: 23799239 DOI: 10.1089/apc.2013.0115] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
We conducted a single-center prospective study to evaluate the utility of cytomegalovirus (CMV) antigenemia assay for the diagnosis of CMV-gastrointestinal disease (GID). The study subjects were HIV-infected patients with CD4 count ≤200 μL/cells who had undergone endoscopy. A definite diagnosis of CMV-GID was made by histological examination of endoscopic biopsied specimen. CMV antigenemia assay (C10/C11 monoclonal antibodies), CD4 count, HIV viral load, history of HAART, and gastrointestinal symptoms as measured by 7-point Likert scale, were assessed on the same day of endoscopy. One hundred cases were selected for analysis, which were derived from 110 cases assessed as at high-risk for CMV-GID after endoscopy screening of 423 patients. Twelve patients were diagnosed with CMV-GID. Among the gastrointestinal symptoms, mean bloody stool score was significantly higher in patients with CMV-GID than in those without (2.5 vs. 1.7, p=0.02). The area under the receiver-operating characteristic curve of antigenemia was 0.80 (95%CI 0.64-0.96). The sensitivity, specificity, positive likelihood ratio (LR), and negative LR of antigenemia were 75.0%, 79.5%, 3.7, and 0.31, respectively, when the cutoff value for antigenemia was ≥1 positive cell per 300,000 granulocytes, and 50%, 92.0%, 5.5, and 0.55, respectively, for ≥5 positive cells per 300,000 granulocytes. In conclusion, CMV antigenemia seems a useful diagnostic test for CMV-GID in patients with HIV infection. The use of ≥5 positive cells per 300,000 granulocytes as a cutoff value was associated with high specificity and high positive LR. Thus, a positive antigenemia assay with positive endoscopic findings should allow the diagnosis of CMV-GID without biopsy.
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Affiliation(s)
- Yohei Hamada
- AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Naoyoshi Nagata
- Department of Gastroenterology and Hepatology, National Center for Global Health, Tokyo, Japan
| | - Takuro Shimbo
- Department of Clinical Research and Informatics, International Clinical Research Center Research Institute, National Center for Global Health, Tokyo, Japan
| | - Toru Igari
- Department of Pathology Division of Clinical Laboratory, National Center for Global Health, Tokyo, Japan
| | - Ryo Nakashima
- Department of Gastroenterology and Hepatology, National Center for Global Health, Tokyo, Japan
| | - Naoki Asayama
- Department of Gastroenterology and Hepatology, National Center for Global Health, Tokyo, Japan
| | - So Nishimura
- Department of Gastroenterology and Hepatology, National Center for Global Health, Tokyo, Japan
| | - Hirohisa Yazaki
- AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Katsuji Teruya
- AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Hiroyuki Gatanaga
- AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan
- Center for AIDS Research, Kumamoto University, Kumamoto, Japan
| | - Yoshimi Kikuchi
- AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Junichi Akiyama
- Department of Gastroenterology and Hepatology, National Center for Global Health, Tokyo, Japan
| | - Norio Ohmagari
- Division of Infectious Diseases, Disease Control and Prevention Center, National Center for Global Health, Tokyo, Japan
| | - Naomi Uemura
- Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Kohnodai Hospital, Chiba, Japan
| | - Shinichi Oka
- AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan
- Center for AIDS Research, Kumamoto University, Kumamoto, Japan
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Cho BS, Yahng SA, Kim JH, Yoon JH, Shin SH, Lee SE, Choi SM, Lee DG, Eom KS, Park G, Kim YJ, Kim HJ, Lee S, Min CK, Cho SG, Kim DW, Lee JW, Min WS, Park CW. Impact of cytomegalovirus gastrointestinal disease on the clinical outcomes in patients with gastrointestinal graft-versus-host disease in the era of preemptive therapy. Ann Hematol 2012. [PMID: 23180439 DOI: 10.1007/s00277-012-1632-x] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Cytomegalovirus gastrointestinal (CMV-GI) disease in GI graft-versus-host disease (GI-GVHD) has not been properly evaluated in the era of preemptive therapy for CMV infection. We investigated 103 patients with GI-GVHD who underwent endoscopic biopsies with immunohistochemical staining for CMV. All recipients and/or donors were seropositive for CMV and monitored with a strategy of preemptive therapy based on real-time quantitative polymerase chain reaction. Twenty-six patients (25 %) developed CMV-GI disease, especially in HLA-mismatched transplants (P = 0.023) and with initial gut involvement of GVHD (P = 0.009). The CMV-GI diseases were diagnosed at follow-up endoscopies (n = 10, 39 %), comprising 19 % of 52 patients who underwent follow-up endoscopies, as well as initial endoscopies (n = 16, 61 %), comprising 16 % of all GI-GVHD patients. In seven cases, either at initial (n = 5) or follow-up endoscopies (n = 2), CMV-GI disease was diagnosed in the absence of histopathologic evidence for GI-GVHD. Notably, only 11 patients (42 %) had prior CMV DNAemia before the diagnosis of CMV-GI disease, while 12 (46 %) and three (12 %) had concurrent and no CMV DNAemia, respectively. Sixty-five percent of CMV-GI disease was resolved by additional antiviral therapies, but CMV-GI disease (P = 0.032) as well as severity of GVHD (P = 0.001) negatively affected GVHD-specific survival. In conclusion, our data demonstrate that CMV-GI disease was a cause of initial or persistent GI manifestations after the initiation of therapy in a considerable proportion of GI-GVHD. These suggest the necessity of novel strategies to reduce CMV-GI disease as well as an effort to confirm CMV with repeated endoscopies.
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Affiliation(s)
- Byung-Sik Cho
- Division of Hematology, Department of Internal Medicine, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Martín-Gandul C, Pérez-Romero P, Sánchez M, Bernal G, Suárez G, Sobrino M, Merino L, Cisneros JM, Cordero E. Determination, validation and standardization of a CMV DNA cut-off value in plasma for preemptive treatment of CMV infection in solid organ transplant recipients at lower risk for CMV infection. J Clin Virol 2012; 56:13-8. [PMID: 23131346 DOI: 10.1016/j.jcv.2012.09.017] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2012] [Revised: 09/04/2012] [Accepted: 09/06/2012] [Indexed: 12/17/2022]
Abstract
BACKGROUND Valganciclovir preemptive therapy guided by the viral load is the current strategy recommended for preventing CMV disease in CMV-seropositive Solid Organ Transplant Recipients (SOTR) at lower risk for developing CMV infection. However, universal viral load cut-off has not been established for initiating therapy. OBJECTIVES Our goal was to define and validate a standardized cut-off determined in plasma by real-time PCR assay for initiating preemptive therapy in this population. STUDY DESIGN A prospective cohort study of consecutive cases of CMV-seropositive SOTR was carried out. The cut-off value was determined in a derivation cohort and was validated in the validation cohort. Viral loads were determined using the Quant CMV LightCycler 2.0 real-time PCR System (Roche Applied Science) and results were standardized using the WHO International Standard for human CMV. RESULTS A viral load of 3983 IU/ml (2600 copies/ml) was established as the optimal cut-off for initiating preemptive therapy in a cohort of 141 patients with 982 tests and validated in a cohort of 252 recipients with a total of 2022 test. This cut-off had a 99.6% NPV indicating that the great majority of patients at lower risk will not develop CMV disease without specific antiviral therapy. The high sensitivity and specificity (89.9% and 88.9%, respectively) and the relatively small numbers of patients with CMV disease confirm that real-time PCR was optimal. CONCLUSIONS We have established a cut-off viral load for starting preemptive therapy for CMV-seropositive SOT recipients. Our results emphasized the importance of a mandatory follow-up protocol for CMV-seropositive patients receiving preemptive treatment.
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Affiliation(s)
- C Martín-Gandul
- Unit of Infectious Disease, Microbiology and Preventive Medicine, Instituto de Biomedicina de Sevilla, University Hospital Virgen del Rocío/CSIC/University of Sevilla, Spain.
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44
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Abstract
Cytomegalovirus (CMV) infection is common worldwide, but the majority are asymptomatic. However, during initial infection or reactivation, CMV can cause tissue-invasive end-organ damage including in the gastrointestinal tract, especially in immunocompromised individuals. Gastrointestinal CMV disease can present with myriad of symptoms and be highly variable endoscopically. In this article we review the manifestations of CMV infection within the luminal gastrointestinal tract and discuss the options for diagnosis and management.
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Affiliation(s)
- David M You
- Department of Gastroenterology, Naval Medical Center, San Diego, CA 92134, USA.
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Abstract
Cytomegalovirus infection remains a serious threat to solid transplant recipients. Despite advances in this field, there are still difficulties in the diagnosis of the disease and there are questions about the best and most cost-effective strategy to prevent infection and its direct and indirect consequences in the short and long term. All these points are discussed and updated in this chapter.
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46
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Park SY, Lee SO, Choi SH, Kim YS, Woo JH, Baek S, Sung H, Kim MN, Kim DY, Lee JH, Lee JH, Lee KH, Kim SH. Efficacy and safety of low-dose ganciclovir preemptive therapy in allogeneic haematopoietic stem cell transplant recipients compared with conventional-dose ganciclovir: a prospective observational study. J Antimicrob Chemother 2012; 67:1486-92. [PMID: 22354954 DOI: 10.1093/jac/dks043] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVES We performed a prospective observational study comparing the efficacy and safety of low-dose ganciclovir (5 mg/kg/day) as initial preemptive therapy in allogeneic haematopoietic stem cell transplantation (HSCT) recipients with conventional-dose ganciclovir (10 mg/kg/day). METHODS All adult patients undergoing allogeneic HSCT were enrolled at a transplant centre over a 24 month period. The decision to use low-dose or conventional-dose ganciclovir was at the discretion of each attending haematologist. A logistic regression model with inverse probability of treatment weighting (IPTW) using propensity scores was performed to reduce the effect of the selection bias in assignment for ganciclovir preemptive therapy. RESULTS Of the 252 HSCT recipients, 97 (38%) received preemptive ganciclovir therapy. Of these, 53 (55%) and 44 (45%) received low-dose and conventional-dose ganciclovir, respectively. The viral clearance rate was higher in the low-dose ganciclovir group [98% (52/53)] than in the conventional-dose ganciclovir group [86% (38/44), P = 0.04], while the low-dose ganciclovir group exhibited a longer viral clearance time (median 21.0 days) than the conventional-dose ganciclovir group (median 14.0 days, P = 0.05). The rate of discontinuation of therapy due to neutropenia or nephrotoxicity was similar in the two groups, although conventional-dose ganciclovir was changed to another regimen more frequently than low-dose ganciclovir. There were three cases of cytomegalovirus (CMV) disease in each group after the initial preemptive therapy. The logistic regression models using propensity scores also revealed that there were no significant differences in viral clearance, secondary episodes of CMV infection, CMV disease and overall mortality between the two groups. CONCLUSIONS Low-dose ganciclovir appears to be safe, and to be at least as effective as conventional-dose ganciclovir for CMV viraemia in allogeneic HSCT recipients.
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Affiliation(s)
- So-Youn Park
- Department of Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul, Republic of Korea
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47
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Lemonovich TL, Watkins RR. Update on cytomegalovirus infections of the gastrointestinal system in solid organ transplant recipients. Curr Infect Dis Rep 2012; 14:33-40. [PMID: 22125047 DOI: 10.1007/s11908-011-0224-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Cytomegalovirus (CMV) infection of the gastrointestinal tract is the most common manifestation of tissue-invasive CMV disease, and is a significant cause of morbidity and mortality in the solid organ transplantation (SOT) recipient. In addition to the direct effects of the infection, its indirect effects on allograft function, risk for other opportunistic infections, and mortality are significant in this population. The most common clinical syndromes are esophagitis, colitis, and hepatitis; however, infection can occur anywhere in the gastrointestinal tract. Diagnosis is usually by histopathology or viral culture of tissue specimens; molecular assays also often have a role. Antivirals are the cornerstone of therapy for gastrointestinal tract CMV disease and complications such as recurrent infection and antiviral resistance are not uncommon. Prevention with antiviral prophylaxis or preemptive therapy is important. This review summarizes recent data regarding the clinical manifestations, diagnosis, treatment, and prevention of gastrointestinal tract CMV infection in the SOT population.
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Affiliation(s)
- Tracy L Lemonovich
- Division of Infectious Disease and HIV Medicine, University Hospitals Case Medical Center, Case Western Reserve University, 11100 Euclid Ave., Cleveland, OH, 44106, USA,
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Moon S, Sung H, Kim MN, Lee SO, Choi SH, Kim Y, Woo J, Kim SH. Diagnostic yield of the cytomegalovirus (CMV) antigenemia assay and clinical features in solid organ transplant recipients and hematopoietic stem cell transplant recipients with CMV pneumonia. Transpl Infect Dis 2012; 14:192-7. [DOI: 10.1111/j.1399-3062.2011.00703.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2011] [Revised: 08/23/2011] [Accepted: 10/06/2011] [Indexed: 12/29/2022]
Affiliation(s)
- S.M. Moon
- Department of Infectious Diseases; Asan Medical Center; University of Ulsan College of Medicine; Seoul Republic of Korea
- Graduate School of Kyung Hee University; Seoul Republic of Korea
| | - H. Sung
- Department of Laboratory Medicine; Asan Medical Center; University of Ulsan College of Medicine; Seoul Republic of Korea
| | - M.-N. Kim
- Department of Laboratory Medicine; Asan Medical Center; University of Ulsan College of Medicine; Seoul Republic of Korea
| | - S.-O. Lee
- Department of Infectious Diseases; Asan Medical Center; University of Ulsan College of Medicine; Seoul Republic of Korea
| | - S.-H. Choi
- Department of Infectious Diseases; Asan Medical Center; University of Ulsan College of Medicine; Seoul Republic of Korea
| | - Y.S. Kim
- Department of Infectious Diseases; Asan Medical Center; University of Ulsan College of Medicine; Seoul Republic of Korea
| | - J.H. Woo
- Department of Infectious Diseases; Asan Medical Center; University of Ulsan College of Medicine; Seoul Republic of Korea
| | - S.-H. Kim
- Department of Infectious Diseases; Asan Medical Center; University of Ulsan College of Medicine; Seoul Republic of Korea
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Paradoxical rising cytomegalovirus antigenemia during preemptive ganciclovir therapy in hematopoietic stem cell transplant recipients: incidence, risk factors, and clinical outcomes. J Clin Microbiol 2011; 49:4179-84. [PMID: 22031700 DOI: 10.1128/jcm.05464-11] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Preemptive ganciclovir (GCV) therapy is adopted increasingly in hematopoietic stem cell transplant (HCT) recipients, but occasional cases of increasing cytomegalovirus (CMV) antigenemia levels occur during preemptive GCV therapy. This prospective study investigated the incidence, risk factors, and clinical outcomes of paradoxical responses during GCV therapy. Adult patients receiving allogeneic HCTs during a 24-month period were enrolled. Patients were prospectively monitored for CMV antigenemia once a week until 3 months after engraftment. Paradoxical responders were defined as patients exhibiting CMV antigenemia levels elevated from the baseline after the first week of preemptive GCV therapy. Of 252 HCT recipients, 97 (38%) received preemptive GCV therapy due to CMV infection. Of these 97 patients, 23 (24%) were classified as paradoxical responders. Risk factors for paradoxical response were a low white blood cell (WBC) count (P = 0.02) and a prolonged duration of CMV antigenemia (P = 0.04) before preemptive therapy. There were no significant differences in rates of successful viral clearance and secondary episodes of CMV infection between paradoxical responders (87% [20/23] and 26% [6/23]) and nonparadoxical responders (95% [70/74] and 23% [17/74], respectively). However, breakthrough CMV disease during preemptive GCV therapy was significantly more frequent in paradoxical responders (17% [4/23]) than in nonparadoxical responders (3% [2/74], P = 0.03). Paradoxical responses occurred in one-quarter of the HCT recipients receiving preemptive GCV therapy. A low WBC count and a long duration of CMV antigenemia before GCV therapy were associated with paradoxical responses, and breakthrough CMV disease during preemptive GCV therapy occurred more frequently in paradoxical responders.
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Marashi SM, Raeiszadeh M, Workman S, Rahbar A, Soderberg-Naucler C, Klenerman P, Chee R, Webster AD, Milne RSB, Emery VC. Inflammation in common variable immunodeficiency is associated with a distinct CD8(+) response to cytomegalovirus. J Allergy Clin Immunol 2011; 127:1385-93.e4. [PMID: 21536322 DOI: 10.1016/j.jaci.2011.04.001] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2010] [Revised: 03/31/2011] [Accepted: 04/01/2011] [Indexed: 02/09/2023]
Abstract
BACKGROUND Common variable immunodeficiency is the most common primary immunodeficiency. A subset of patients has debilitating inflammatory complications. OBJECTIVES We investigated the role of cytomegalovirus (CMV), and the T-cell response targeted at this virus, in this inflammatory disease. METHODS Phenotypic and functional assays were used to profile CMV-specific T cells in patients with common variable immunodeficiency with and without inflammatory complications. Highly sensitive immunohistochemistry was used to detect CMV antigens at sites of inflammation. RESULTS Cytomegalovirus was significantly associated with inflammatory disease, which occurred in 31 of 43 (72%) virus-exposed patients and 8 of 31 (26%) naive patients (P = .0001). CMV pp65-NLVPMVATV epitope-specific CD8(+) T-cell frequencies were significantly elevated in inflammatory patients, but these cells did not show evidence of exhaustion, with low levels of programmed death-1 and high T-cell receptor avidity. Rather, they showed features consistent with high in vivo functionality and proliferative activity including reduced levels of the anti-inflammatory marker CD73 (1.67% of NLV(+) cells were CD73(+) vs 42.01% in noninflammatory patients; P = .004) and increased Ki-67 expression (37% vs 2% in noninflammatory patients; P < .0001). In vitro, the CMV-specific T cells showed high antigen-specific proliferative potential compared with cells from noninflammatory patients. By using sensitive immunohistochemistry, we detected for the first time viral antigen at the sites of inflammation, indicative of active viral replication. CONCLUSION Our data strongly support a direct role for CMV and a hyperreactive CMV-specific immune response in the debilitating chronic inflammatory complications of common variable immunodeficiency.
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Affiliation(s)
- Sayed Mahdi Marashi
- Medical Research Council Centre for Medical Molecular Virology, Division of Infection and Immunity, Royal Free Campus, University College London Medical School, London, United Kingdom
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