scholarly journals A195 A RARE CAUSE OF SEVERE REFRACTORY DIARRHEA IN A PATIENT WITH COMMON VARIABLE IMMUNE DEFICIENCY ASSOCIATED INTESTINAL ENTEROPATHY

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 217-219
Author(s):  
B Markandey ◽  
M J Beyak ◽  
S Perez ◽  
P Manley ◽  
M Ropeleski

Abstract Background CVID is the most common type of severe antibody deficiency. Gastrointestinal manifestations affect approximately 20–50% of patients. Boland et al. described in a case series that 2/3 CVID patients were able to achieve clinical and endoscopic remission with Vedolizumab. This α4β7 integrin antagonist inhibits intestinal T cell translocation by blocking integrin interactions with mucosal vascular addressin cell adhesion molecule 1, reducing lymphocyte mediated inflammation. However, despite its novel use for this indication, limited data is available on the consequences of this therapy in patients with CVID. Aims To report on a case assessing the efficacy and outcomes of Vedolizumab for the treatment of CVID associated autoimmune enteropathy. Methods We present the case of a 50-year-old male presenting with severe refractory diarrhea and malnutrition. A colonoscopy demonstrated patchy ulceration and biopsies revealed ulcerated active colitis, negative for CMV. He was treated with Vedolizumab and Total Parental Nutrition (TPN). His diarrhea resolved, he gained 20 kg and he was weaned off TPN. In 2019, he re-presented with severe diarrhea. Subsequently endoscopic evaluation revealed patchy edematous colonic mucosa and biopsies demonstrated minimally active colitis, negative for CMV. He again responded to Vedolizumab re-induction, however shortly after, his diarrhea returned aggressively. CT enterography demonstrated active jejunal inflammation. Subsequently, an EGD revealed multiple duodenal ulcers and luminal narrowing. Biopsies of the small bowel were sent to histopathology. Results CMV superinfection was diagnosed on pathology (image 1). This patient’s diarrhea completely resolved with IV Gancyclovir and he was discharged on maintenance treatment with oral Valganciclovir. Conclusions This represents the first reported case of CMV enteritis secondary to Vedolizumab for the treatment of CVID associated autoimmune enteropathy. In this case, clinical and endoscopic remission was observed with Vedolizumab, however subsequently hampered by CMV reactivation. Hommel et al., published a positive correlation in a single centre retrospective cohort study of CMV reactivation in patients with ulcerative colitis treated with Vedolizumab. A large retrospective review of data from a multicenter consortium database of over 1000 Vedolizumab treated IBD patients reported CMV colitis in only 4 patients. CMV reactivation appears to be an exceptionally rare but important event in patients treated with Vedolizumab. Based on this report, patients with CVID associated enteropathy and refractory diarrhea should be carefully screened for CMV when treated with Vedolizumab. Further prospective data assessing the incidence of CMV reactivation in patients with Vedolizumab therapy is required to further define these findings. Funding Agencies None

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4567-4567 ◽  
Author(s):  
Mudussara A. Khan ◽  
Terri Walling ◽  
Aaron Cumpston ◽  
Michael Craig

Abstract Introduction: CMV generally produces an asymptomatic or minimally symptomatic acute illness in immunocompetent patients. CMV reactivation commonly occurs in patients with CML after allogeneic transplant but has not been described in those who are treated with tyrosine kinase inhibitors. We report a case of a patient with CML in lymphoid blast phase treated with dasatinib to cytogenetic remission that presented with CMV Colitis. Method: 73-year-old male diagnosed with CML in lymphoid blast crisis 2/2006 treated with chemotherapy and imatinib with good response. He relapsed in 2/2007 with leukostasis and underwent leukopharesis. His BCR/ABL mutation analysis was positive for F359V mutation conferring resistance to imatinib. He was started on dasatinib 70 mg twice daily and had a cytogenetic remission within four months. He presented five months after starting therapy with four weeks of recurrent fevers, chills, malnutrition and diarrhea. Results: CBC and differential revealed only mild thrombocytopenia, Absolute CD4 count of 209; absolute CD8 count of 1495. CMV DNA PCR Quantification of 1500 copies/ml. CT chest abdomen and pelvis showed right sided pleural effusion but no pneumonitis. Flex sigmoidoscopy showed inflamed edematous mucosa with submucosal hemorrhages scattered throughout colon and rectum. Pathology showed chronic colitis, focal viral cytopathic changes consistent with CMV presence. Presence of CMV was confirmed by immunoperoxidase stain for CMV. Treatment was started with IV ganciclovir then switched to oral valganciclovir with good response and resolution of CMV infection. Conclusion: CMV colitis is a well-known complication in immunocompromised hosts after HCT. We are reporting a case of CMV colitis in a patient with CML and had hematologic and cytogenetic remission on a novel tyrosine kinase inhibitor - dasatinib. CMV reactivation may occur in patients who are receiving dasatinib. Furthur evaluation is necessary to determine the incidence of this complication.


2021 ◽  
Vol 10 (13) ◽  
pp. 2792
Author(s):  
Patrícia Moniz ◽  
Sérgio Brito ◽  
Pedro Póvoa

The SARS-CoV-2 pandemic has placed great strain on the most developed of health care systems, especially in the context of critical care. Although co-infections with cytomegalovirus (CMV) are frequent in the critically ill due to underlying immune suppression of multiple causes, the impact on COVID-19 patients remains unclear. Furthermore, severe COVID-19 has recently been associated with significant immune suppression, and this may in turn impact CMV reactivation, possibly contributing to clinical course. Nevertheless, multiple confounding factors in these patients will certainly challenge upcoming research. The authors present a case series of five patients admitted to the intensive care unit (ICU) in the context of respiratory failure due to severe COVID-19. All patients evolved with CMV reactivation during ICU stay.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3161-3161
Author(s):  
Yuriko Morita ◽  
Mami Hosokawa ◽  
Yuji Heike ◽  
Tohru Sasaki ◽  
Michiko Ebisawa ◽  
...  

Abstract Previous studies on the tetramer-based quantification of CMV-specific CTL have shown that the reconstitution of CMV-specific CTL to levels greater than 10/μL may protect against CMV reactivation. To evaluate the usefulness of CMV-specific tetramer for monitoring the number of CMV-specific CTL, assays with CMVpp65 495–503 tetramer were performed in 34 patients with HLA-A02 while CMVpp65 328–336 tetramer was used in 47 HLA-A24 patients who received non-T-cell-depleted SCT from a serologically full-matched donor after a myeloablative or nonmyeloablative regimen without ATG. Patients were assessed after recovery from CMV reactivation. Although the average number of CTL detected in patients with HLA-A02 [23.5/μL (1.33%/lymphocytes)] was significantly higher than that in patients with HLA-A24 [0.48/μL (0.02%)], the CMV reactivation rate was similar (67.6% and 62.5% in HLA-A02 and A24, respectively). This result demonstrates that these assays are of limited value since the number of CTL detected varies among different HLA-restricted epitopes. To further evaluate whether there is any relationship between CMV-specific CTL and CMV reactivation, the number of CTL in HLA-A02 patients was assessed in detail. The average number of CTLs in 11 patients without CMV reactivation, 23 with CMV reactivation, 13 with a peak CMV antigenemia of >10/50000, and 3 who developed CMV disease was 12.3/μL (0.85%), 29.3/μL (1.35%), 13.8/μL (0.8%) and 16.3/μL (1.33%), respectively. No significant correlation was observed between the number of CTL and CMV reactivation after the reconstitution of CMV immunity. Since CMV reactivation usually occurs within 100 days after SCT, tetramer was assessed biweekly until day 100 in 13 HLA-A02 patients. In those who had CMV reactivation, simultaneous intracellular IFN-γ staining was performed with the same peptide used for tetramer. CMV reactivation was observed in 10 patients between day 23 and day 56 (median, day 34); among them, 5 had a peak antigenemia of >10/50000, and required GCV therapy, and 3 developed CMV colitis. The average number of CTL at CMV reactivation was 5.67 (0.08–22.65) /μL in 10 patients who had reactivation, with 3 showing >10/μL, while this was 1.08 (0–1.98) /μL at day 30 in those who did not. Two of the 3 patients who developed CMV colitis had >10/μL CTL at the time of disease onset, while among 8 who did not require GCV therapy, only 1 and 2 patients recovered CTL >10/μL at day 30 and day 60, respectively. The number of intracellular IFN-γ-secreting cells among those with CMV colitis was 18.2/μL (1.8%) at the time of disease onset, and this increased to 47.3/μL (3.5%) after recovery from CMV disease. These results suggest that tetramer-based monitoring of CTL is of limited value in predicting CMV reactivation compared to intracellular IFN-γ assay that assesses the functional properties of CTL.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3417-3417 ◽  
Author(s):  
Pierluigi Porcu ◽  
Robert A. Baiocchi ◽  
Thomas S. Lin ◽  
Kristie A. Blum ◽  
Patricia Curtis ◽  
...  

Abstract BACKGROUND: T-cell lymphoproliferative disorders (T-LPD) are heterogeneous and highly chemoresistant malignancies without standard therapy. With few exceptions, cure rates with combination chemotherapy do not exceed 25–30%. We have shown that alemtuzumab (A), a humanized IgG1 targeting the CD52 antigen expressed on most human leukocytes, is cytotoxic for malignant T-cells in vitro and in vivo, regardless of p53 mutational status (Blood106: 3380–3382, 2005). We initiated a Phase I study with A and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in T-LPD. METHODS: Accrual goal: 18–21 pts with untreated (u) or relapsed (r)T-LPD, excluding untreated ALK-1-positive or primary cutaneous anaplastic large cell lymphoma. CD52 expression was not assessed. Other exclusion criteria: pregnancy, HIV+, HCV+, or HBV+. Primary objective: A maximal tolerated dose (MTD). DLT defined as grade (G) ≥ 3 (or non-reversible grade 2) non-hematologic toxicity or G4 neutropenia or thrombocytopenia requiring >7 day delays in therapy for > 3 times. All pts received single agent SQ A loading (3, 10, 30 mg) over 5 days followed by one SQ A dose with each cycle of CHOP every 21 days for a total of 8 cycles. A dose levels: 3, 10, 20, 30 mg. All pts received valacyclovir, trimethoprim-sulfamethoxasole prophylaxis and G-CSF. Erythropoietin was given according to published guidelines. RESULTS: 18 pts were enrolled (uPTCL=11, uT-PLL=2, rCTCL=3, uSezary Syndrome=2). Enrollment according to dose level: 3mg = 6 pts; 10mg = 3 pts; 20 mg = 6 pts; 30 mg = 3 pts. Median age: 62 years. All pts completed single agent SQ A loading on time with minimal local reactions. Ten pts completed all planned therapy. Six pts did not complete therapy: 2 rCTCL=stable disease, 1 uPTCL=poor compliance, 2 PTCL=pt witdrew, 1 uT-PLL=progression. Two pts (30 mg dose level) are receiving therapy. Toxicity: G4 febrile neutropenia=1; G3 fatigue=2, G3 anemia=2, G3 dyspnea=1, G3 emesis=2, G3 CMV infection=1. Cohort 1 was expanded due to asymptomatic CMV reactivation requiring hospitalization for thrice daily foscarnet. Subsequent asymptomatic CMV reactivations (N=4) were treated with oral valganciclovir until clearance. No symptomatic CMV reactivation or other viral or fungal infections were seen. Out of 107 cycles of A/CHOP given, only 3 had to be delayed. Four pts (1 PTCL, 1 T-PLL and 2 Sezary) are in continuous clinical and molecular (PCR) complete response at 36, 28, 18 and 12 months respectively. CONCLUSIONS: SQ A was safely administerd up to 20 mg with each cycle of CHOP chemotherapy and growth factor support without excessive myelosuppression or infectious AEs. Treatment at 30 mg dose level is in progress. Asymptomatic CMV reactivation can be managed with oral valganciclovir without discontinuation of therapy. Durable responses have been seen, including molecular clearance of the malignant T-cell clone.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5011-5011
Author(s):  
ZiYi Lim ◽  
Gordon Cook ◽  
Peter R. Johnson ◽  
Anne Parker ◽  
Mark Zuckerman ◽  
...  

Abstract The advent of reduced intensity conditioning(RIC) protocols for allogeneic haematopoietic stem cell transplantation(HSCT) has reduced the incidence of early transplantation related morbidity largely due to the attenuation of the conditioning intensity. Nevertheless, the incidence of CMV reactivation in these patients remains high. Herein we report the results of a multi-centre randomised prospective study to assess the bioavailability(auc0–12) of ganciclovir in the population of patients undergoing alemtuzumab-based RIC HSCT after oral administration of valganciclovir and secondly, the efficacy and safety of valganciclovir in the treatment of a CMV infection following allogeneic SCT. Recipients of allogeneic bone marrow or peripheral blood stem cell transplants with related or unrelated donors following reduced intensity conditioning, without proven graft versus host disease were eligible for this study. RIC protocols approved for the purposes of this study were FBC(fludarabine, busulphan, alemtuzumab) and FMC(fludarabine, melphalan,alemtuzumab). For inclusion into the study, patients had to have a detectable CMV DNA load in two consecutive blood specimens up to 120 days after transplant. Eligible patients were randomized to 1 of 2 treatment groups: group A received 900 mg oral valganciclovir(2 x 900 mg/d) for 14 days and group B received intravenous ganciclovir 5mg/kg/d twice daily for 14 days. All patients were monitored for 84 days(safety follow-up). pK profiles of ganciclovir were obtained after administration of the study drug in each study arm. pK assessments were scheduled at days 4 and 11. 27 patients were recruited into the study over a 24-month period from Jan 2005 to Dec 2006. The median age was 51 years(range:34–68). The median time to CMV reactivation was 43 days post-HSCT(range:20–114). 18 patients(67%) completed the allocated treatment resulting in CMV DNA load <10 copies/ml at a median of 14 days post-HSCT(range:7–28). In 9 cases, there were changes to the primary treatment regimen. In group A, treatment was modified in 5 cases; 3 due to rising CMV levels, 1 due to drug rash, 1 due to neutropenia. In group B, 4 patients had treatment modification; 3 patients due to rising CMV DNA levels, 1 had neutropenia. None of the patients in the study developed CMV invasive disease. The median value of the systemic clearance of ganciclovir was 11.8 l/h(95%CI: 8–15.6 l/h). The bioavailability of ganciclovir from valganciclovir(expressed as equivalents of ganciclovir) was 73%(95%CI, 34%–112%). The average exposure in the valganciclovir group(36.9 ± 14.9μg.h/ml) was significantly higher than in the ganciclovir cohort(27.9 ±7.5μg.h/ml). As a result, ganciclovir bioavailability in the subjects who received valganciclovir was 79%. In summary, when compared with intravenous ganciclovir, oral valganciclovir had high bioavailability with equivalent efficacy and safety in patients undergoing RIC HSCT. Use of valganciclovir can facilitate the out-patient treatment of patients with CMV reactivation post-HSCT with a potential reduction in hospitalization costs.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7594-7594 ◽  
Author(s):  
P. Porcu ◽  
R. A. Baiocchi ◽  
J. Lee ◽  
T. S. Lin ◽  
K. Blum ◽  
...  

7594 Background: T-cell lymphomas are highly chemoresistant. Cure rates with combination chemotherapy do not exceed 25–30%. We showed that A, a humanized IgG1 targeting the CD52 antigen expressed on most human leukocytes, is cytotoxic for malignant T-cells in vitro and in vivo, regardless of p53 mutational status (Blood 106, 3380, 2005). Thus, we initiated a Phase I study with A and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) in T-cell lymphoma. Methods: Accrual goal: 15–18 patients (pts) with untreated (u) or relapsed (r) peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL), excluding ALK-1-positive anaplastic large cell lymphoma. Primary objective: maximal tolerated dose (MTD). All pts receive single agent SQ A loading (3, 10, 30 mg) over 5 days, followed by one SQ A dose with each CHOP every 21 days for a total of 8 cycles. A dose levels: 3, 10, 20 and 30 mg. All pts receive valacyclovir and trimethoprim-sulfamethoxasole, plus G-CSF and erythropoietin according to guidelines. Results: Eight of the nine enrolled pts on cohort 1 (A=3 mg) and cohort 2 (A=10 mg) are evaluable for toxicity (uPTCL= 4, rPTCL=1, rCTCL=3). All pts completed single agent A loading on time and tolerated well further SQ A. No cycle was delayed due to myelosuppression. There were no opportunistic infections or neutropenic fevers. Four pts completed all planned therapy. Three pts did not complete therapy due to progression (2) or toxicity (1). One pt remains on study after 4 cycles. There were no Grade 4 adverse events (AEs). Grade 3 AEs included fatigue (1), anemia (1), dyspnea (1) and emesis (1). Cohort 1 was expanded due asymptomatic cytomegalovirus [CMV] reactivation requiring hospitalization for thrice daily foscarnet, thus resulting in Grade 3 AE. Protocol was amended and subsequent asymptomatic CMV reactivations (2) were treated with oral valganciclovir. No symptomatic CMV reactivation occurred. Conclusions: At current dose levels, SQ A can be easily and safely administered with CHOP chemotherapy and growth factor support, without excessive myelosuppression or infectious AEs. Asymptomatic CMV reactivation can be managed with oral valganciclovir. Further A dose escalation is in progress. [Table: see text]


Reumatismo ◽  
2015 ◽  
Vol 67 (1) ◽  
Author(s):  
M. S. Dag ◽  
I. H. Turkbeyler ◽  
Z. A. Ozturk ◽  
B. Kısacık ◽  
E. Tutar ◽  
...  

Rheumatoid arthritis (RA) is an autoimmune, systemic, chronic, inflammatory disease generally treated with various immunosuppressive drugs. Cytomegalovirus (CMV) is an opportunistic, viral infection that is commonly seen in immunosuppressed patients. A sixty-four-year old female diagnosed with RA and treated with immunosuppressive agents was admitted to our rheumatology outpatient service with complaints of diarrhea and abdominal pain, which had lasted longer than four weeks. The patient’s colonoscopy revealed inflamed and ulcerated areas in the colon and in the terminal ileum. A biopsy showed intra-nuclear inclusion particles consistent with CMV. We started an oral valganciclovir therapy in this serum-CMV-polymerase chain reaction-positive patient. The concomitant use of immunosuppressive agents and anti-viral drugs eased the patient’s complaints, and the endoscopic picture improved. Consequently, cytomegalovirus ileocolitis in immunosuppressed patients admitted with severe diarrhea must be considered in the differential diagnosis.


2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S270-S271
Author(s):  
I Spigarelli De Rábago ◽  
C Suárez Ferrer ◽  
J Poza Cordón ◽  
E Martín Arranz ◽  
M Sánchez Azofra ◽  
...  

Abstract Background Fecal calprotectin (FC) has become a fundamental tool in the non-invasive monitorization of activity in patients with inflammatory bowel diseases (IBD). However, there is still debate over the choice of the optimal cut-off point for the different clinical settings. The aim of this study is to analyze whether the presence of pseudopolyps and their characteristics have an impact on the value of FC and should therefore be taken into account when deciding the optimal cutoff values. Methods A single-centered, retrospective analysis including data from patients with colonic Crohn′s disease or Ulcerative colitis who underwent colonoscopy for dysplasia screening at our center between 2018 and 2019. Patients that did not have a FC registered within 8 months from to the colonoscopy, or that did not maintain clinical remission between the colonoscopy and the measurement of the FC, were excluded. Patients that had activity in the colonoscopy (Mayo endoscopic score &gt;0, SESCD &gt;0) were also excluded. Results 73 patients were included. 26 (35.6%) of them had pseudopolyps in the colonoscopy. The median value of the FC was significantly different in patients with pseudopolyps (110.1 µg/g, CI 95% [48.6–171.5]) compared to those without them (52.5 µg/g, CI 95% [29.9–75.1]). In 11 (42.3%) of the patients with pseudopolyps, biopsies were taken, observing histological activity in 3 of them (27.3%) and no inflammatory activity in the other 8 (72.7%). We found that FC was higher in patients with inflammatory polyps (119.0 µg/g) in comparison to those without histological activity in their pseudopolyps (96.9 µg/g); however, these results were not statistically significant. The location of the pseudopolyps had no influence over the FC in our study. In addition, no correlation was found between the presence of polyps or diverticula and FC. Conclusion In our study, the presence of pseudopolyps is associated with significantly higher levels of FC. Moreover, our results suggest a tendency towards higher FC in patients who had active colitis in the histological samples of their pseudopolyps.


2019 ◽  
Vol 2 (1) ◽  
pp. 01-03
Author(s):  
Ajda Altinoz ◽  
Huda Gasmelseed ◽  
Katharina Kessler

This is a case of a 74 years old immunocompetent female who developed severe diarrhea after haemorrhoidopexy for 2 months duration. Investigations to find the cause of persistent diarrhea were done, including colonoscopy showed ulcers from which biopsy was taken and the presence of CMV-DNA was identified. She got treated with IV and oral Ganciclovir and repeated colonoscopy showed improvement of the ulcers with gradually improvement of diarrhea.


2019 ◽  
Vol 14 (5) ◽  
pp. 624-629
Author(s):  
Rita Vale Rodrigues ◽  
Margaret Sladek ◽  
Konstantinos Katsanos ◽  
C Janneke van der Woude ◽  
Juan Wei ◽  
...  

Abstract Background and Aims Crohn’s disease [CD] can involve any part of the gastrointestinal tract. We aimed to characterize the clinical, endoscopic and histological features and treatment outcomes of CD patients with oesophageal involvement. Methods We collected cases through a retrospective multicentre European Crohn’s and Colitis Organisation CONFER [COllaborative Network For Exceptionally Rare case reports] project. Clinical data were recorded in a standardized case report form. Results A total of 40 patients were reported (22 males, mean [±SD, range] age at oesophageal CD diagnosis: 25 [±13.3, 10–71] years and mean time of follow-up: 67 [±68.1, 3–240] months). Oesophageal involvement was established at CD diagnosis in 26 patients [65%] and during follow-up in 14. CD was exclusively located in the oesophagus in two patients. Thirteen patients [32.2%] were asymptomatic at oesophageal disease diagnosis. Oesophageal strictures were present in five patients and fistulizing oesophageal disease in one. Eight patients exhibited granulomas on biopsies. Proton-pump inhibitors [PPIs] were administered in 37 patients [92.5%]. Three patients underwent endoscopic dilatation for symptomatic strictures but none underwent oesophageal-related surgery. Diagnosis in pre-established CD resulted in treatment modifications in 9/14 patients. Clinical remission of oesophageal disease was seen in 33/40 patients [82.5%] after a mean time of 7 [±5.6, 1–18] months. Follow-up endoscopy was performed in 29/40 patients and 26/29 [89.7%] achieved mucosal healing. Conclusion In this case series the endoscopic and histological characteristics of isolated oesophageal CD were similar to those reported in other sites of involvement. Treatment was primarily conservative, with PPIs administered in the majority of patients and modifications in pre-existing inflammatory bowel disease-related therapy occurring in two-thirds of them. Clinical and endoscopic remission was achieved in more than 80% of the patients.


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