Cytomegalovirus Colitis Research Articles

1469. Drug-resistance associated mutations of Human Cytomegalovirus (CMV) UL97 and UL54 genes in immunocompromised patients. Experience in Colombia, South America.

Abstract Background Cytomegalovirus (CMV) infection is a significant disease in immunocompromised patients, particularly transplant patients. The wide use of antivirals for prophylaxis and treatment has decreased the incidence and impact of this disease. Although, this exposure can lead to mutations in CMV UL54 and UL97 genes, which are associated with antiviral resistance. Little is known of the frequency of these mutations in Latin America, despite an increase in the transplant population. Methods We performed a prospective observational study. Patients with suspected CMV resistance based on the persistence of CMV DNAemia despite treatment were included from April to December 2019 in Fundación Valle del Lili. The blood samples were processed for DNA extraction, amplification, and sequencing for molecular characterization of (UL97) and (UL54) genes. Laboratory and clinical data were recollected from the clinical laboratory database and clinical charts. Results We enrolled 50 patients with CMV DNAemia, 32 amplified for gene sequencing. The median age was 31.7 years old, and 46.8% were males. 65.6% had a stem cell transplant, and 28.1% had a solid organ transplant. Only 65.2% had previous antiviral exposure. 93.7% manifested with CMV DNAemia alone, and 6.2% had CMV disease, hepatitis, and colitis. According to our findings, 56.2% had only UL54 mutations, 6.25% had only UL97 mutations, and 37.5% had both. The mutations associated with antiviral resistance were D605E and A594V for UL97 and A692S for UL54. The most common UL97 polymorphisms were V355A and F396L, while for UL54 were N898D, N685S, and S655L. On day 14 of treatment, 21.8% (7/32) had treatment failure. No canonic resistance mutations were found. 15.6% (5/32) of patients died; none had UL97 mutations, two had UL54 mutations associated with antiviral resistance, and three had polymorphisms of this gene. Conclusion Our study is the first one performed in Colombia. Although resistance was low, it was present in a few patients and related to mortality. It is important to study this evolving resistance as the use of antivirals increases in the transplant population in Latin America. Disclosures Olga Agudelo, n/a, Fundación valle del lili: Board Member.

S47 Combined Therapy With Ustekinumab and Vedolizumb in Severe Colitis in HIV Patients

Background: Combined therapy as well as drug sequencing, using induction and maintenance with different therapeutic classes, are possibilities of treatment in inflammatory bowel diseases. Among the different combined biological therapy options, the combination of ustekinumab and vedolizumab is among the most cited since they use different mechanisms of action with a good safety profile. Combined biological therapy has been suggested as an option to achieve better results in cases that are refractory to previous biological treatments or with a high risk of developing complications, and in the concomitance of uncontrolled extra-intestinal manifestation. There is a scarcity in the literature regarding the treatment of IBD and HIV, however, in individuals with controlled disease, there seems to be no restriction on any of the available options. In the presence of severe UC and a history of infections, the ideal therapeutic agent should have a rapid onset of action and a good safety profile in the maintenance treatment. Methods: The present study is a clinical case followed at the Oswaldo Cruz University Hospital, Recife-PE, during the period from February to August 2022, with data collected from the medical records. Results: A 53-year-old male patient with HIV for 14 years, on antiretroviral treatment for 10 years, currently with CD4 308 and an undetectable viral load. He was diagnosed with ulcerative colitis (UC), Montreal E2, in march 2021, with irregular follow-up, frequent hospitalizations until readmission in december 2021 with severe UC activity. He remained dependent on high doses of corticosteroids for about 5 months and presented several infectious complications, such as neurotoxoplasmosis and CMV colitis. He was discharged with disease under clinical control but readmitted for urinary infection and severe UC activity after 4 days of undue corticosteroid suspension. Given the severity and availability of intravenos ustekinumab per donation, it was decided to administer the dose of induction (260 mg). After 2 weeks, there was little clinical improvement, at which time he had access to vedolizumab by the public health system. UC became mildly active at week 2 of induction and the patient was discharged. He is currently in clinical and biomarker remission, on regular maintenance infusions of vedolizumab and steroid-free since week 6 of induction. Conclusion: In the present report, we considered that prolonged and recurrent hospitalizations, prolonged use of corticosteroids and previous infectious complications in patients with severe UC and HIV justified the combination of biological agents. A rapid induction strategy with ustekinumab followed by reinduction and maintenance with vedolizumab was chosen, given its best safety profile. Such association proved to be safe and effective. Although the results are attractive, there is still no formal indication in clinical practice for its use. Thus, combined biological therapy should be prescribed with caution, under consent, with close monitoring and individually indicated.

A quick guide to diagnosis and treatment of cytomegalovirus infection in the gut: current dilemmas

Abstract Cytomegalovirus is a ubiquitous herpesvirus, which, after often asymptomatic primary infection, establishes a life-long latency in different organs, including gut. As there is a close synergistic relationship between mucosal inflammation and viral expression, particularly in patients suffering from inflammatory bowel disease, it is often challenging to distinguish subclinical cytomegalovirus replication from cytomegalovirus-mediated colitis. The outcome for patients with cytomegalovirus reactivation appears to be worse than that for patients without reactivation, but the true role of cytomegalovirus is not entirely clear, as is the dilemma whether specific treatment with antivirals alters the course of inflammatory bowel disease. This review focuses on gastrointestinal tract cytomegalovirus disease, with special emphasis on diagnostic and treatment considerations of cytomegalovirus colitis in patients with inflammatory bowel disease.

Cytomegalovirus Colitis in COVID-19 Patient: a Case Report

Human cytomegalovirus (CMV) is a double-stranded DNA virus with high seroprevalence and is common in developing countries. The ability to cause a lifelong latent infection is established, and it can be reactivated later in life in both immunocompetent and especially in immunosuppressed carriers. We report a case of CMV colitis in an elderly gentleman who was initially admitted for COVID-19 pneumonia.

Letermovir use to treat complex cytomegalovirus reactivations in two heart transplant recipients.

Letermovir, an anti-cytomegalovirus (CMV) drug, is recommended as a prophylactic agent in patients at risk of CMV infection/reactivation after allogeneic hematopoietic stem cell transplant. We report the curative and pre-emptive use of letermovir in two heart transplant recipients. In one patient with ganciclovir-resistant CMV, letermovir was successfully used to treat CMV colitis. In the second patient, letermovir was used as pre-emptive therapy for CMV reactivation, but did not prevent CMV esophagitis. In both cases, letermovir was successful for secondary prophylaxis. Curative use of letermovir may be considered if resistance or major adverse effect of other antivirals therapy is suspected.

Acute cytomegalovirus infection modulates the intestinal microbiota and targets intestinal epithelial cells.

Primary and recurrent cytomegalovirus (CMV) infections frequently cause CMV colitis in immunocompromised as well as inflammatory bowel disease (IBD) patients. Additionally, colitis occasionally occurs upon primary CMV infection in patients who are apparently immunocompetent. In both cases, the underlying pathophysiologic mechanisms are largely elusive - in part due to the lack of adequate access to specimens. We employed the mouse cytomegalovirus (MCMV) model to assess the association between CMV and colitis. During acute primary MCMV infection of immunocompetent mice, the gut microbial composition was affected as manifested by an altered ratio of the Firmicutes to Bacteroidetes phyla. Interestingly, these microbial changes coincided with high-titer MCMV replication in the colon, crypt hyperplasia, increased colonic pro-inflammatory cytokine levels, and a transient increase in the expression of the antimicrobial protein Regenerating islet-derived protein 3 gamma (Reg3γ). Further analyses revealed that murine and human intestinal epithelial cell lines, as well as primary intestinal crypt cells and organoids represent direct targets of CMV infection causing increased cell death. Accordingly, in vivo MCMV infection disrupted the intestinal epithelial barrier and increased apoptosis of intestinal epithelial cells. In summary, our data show that CMV transiently induces colitis in immunocompetent hosts by altering the intestinal homeostasis.

Gas Leak in the Port: Portal Venous Gas Associated With Congenital Cytomegalovirus Colitis.

Gas Leak in the Port: Portal Venous Gas Associated With Congenital Cytomegalovirus Colitis.

The association between antigenemia, histology with immunohistochemistry, and mucosal PCR in the diagnosis of ulcerative colitis with concomitant human cytomegalovirus infection

BackgroundHuman 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.MethodsWe 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.ResultsIn 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).ConclusionThe 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.

S2176 Co-Occurrence of Two Rare Diseases: CMV Colitis in a Patient With Clozapine-Included Ischemic Colitis

Introduction: CMV (Cytomegalovirus) colitis is a well-recognized disease in immunocompromised patients, however, there are case reports and series describing the disease in immunocompetent hosts. Given its rarity, its characteristics are yet to be well defined. We present a case of CMV colitis in an immunocompetent patient who likely had concomitant ischemic colitis from clozapine. Case Description/Methods: A 68-year-old female with PMH of Schizophrenia on Clozapine, chronic constipation presented to the emergency department with 1 day of bloody diarrhea and NBNB vomiting. On arrival, she was noted to be tachycardic and tachypneic with a physical exam revealing diffuse abdominal tenderness and hypoactive bowel sounds. Initial labs were notable with leukocytosis of 19 K/ul with bands. Serum lactate, renal function, and liver function tests were normal. Clozapine level was elevated at 1143 ng/dl. Computed Tomography Angiography of the abdomen showed severe colitis of the entire descending colon. Working diagnosis at that point was Infectious colitis, inflammatory colitic, and ischemic colitis. She completed 5 days of antibiotics despite negative Gastrointestinal panel PCR with some relief of symptoms. Colonoscopy planned on day 6 was postponed due to acute delirium, which required the initiation of a new anti-psychotic. Colonoscopy on day 28 showed a 10 cm area of non-bleeding ulcerated mucosa at the splenic flexure. Histopathology reports which became available 1 week later showed colonic mucosa with ulceration, granulation tissue, acute inflammation, and rare CMV-positive cells. HIV test which was then obtained was negative, and CMV DNA PCR was 52 IU/ml. She was subsequently started on Valgancyclovir and discharged without any acute events with a plan for a follow-up colonoscopic examination. Discussion: CMV is a common virus with positive serology in upwards of 2-thirds of the general population. However, it rarely manifests in immunocompetent hosts. CMV colitis in immunocompetent hosts has been described mostly as a superinfection in patients with primary gastrointestinal disorders. Destruction of colonic mucosa from the ischemic colitis caused by clozapine likely allowed for CMV to establish the infection in our patient. It is thought that the anticholinergic manifestation in the gastrointestinal tracts which causes constipation and luminal dilation leads to decreased capillary circulation. Treatment usually involves discontinuation of the drug and supportive care.

S2018 Concurrent CMV Colitis and GI Amyloidosis as Initial Presentation of Multiple Myeloma: A Case Report

Introduction: Prior associations with Cytomegalovirus (CMV) colitis and multiple myeloma (MM) or amyloidosis are only described in immunocompromised patients undergoing treatments like transplantation, monoclonal antibodies, or chemotherapy. The concurrent presentation of gastrointestinal (GI) amyloidosis with CMV colitis is rarely reported and should be considered more readily in the hospital. Case Description/Methods: 67-year-old male was admitted to the hospital with bilateral lower extremity deep vein thromboses after transurethral resection of the prostate 8 days prior. He was started on anticoagulation, but due to onset of hematuria, anticoagulation was stopped and an IVC filter was placed. The patient then developed bright red blood per rectum with diarrhea and GI was called. On exam, vitals were stable, and abdomen was non-distended and non-tender. Digital rectal exam showed brown stool. A colonoscopy displayed discontinuous areas of ulcerated, erythematous mucosa with loss of vascular pattern (Figure A). A histologic examination showed terminal ileal mucosa with lymphoid aggregates (Figure B), positive Congo red stain with apple green birefringence and cytomegalovirus inclusions in the colon (Figure C). Subsequent immunology testing demonstrated elevated free lambda light chains with a free kappa to lambda ratio of 0.019. A bone marrow biopsy confirmed lambda restriction and >20% CD138-positive plasma cells, consistent with MM. The patient was started on valganciclovir but showed no improvement of symptoms, which was attributed to his confounding amyloidosis. The patient’s clinical status continued to worsen, and he ultimately expired from cardiac causes. Discussion: It is noteworthy that CMV colitis occurred concurrently with amyloidosis. Immune dysfunction and hypogammaglobinemia in amyloidosis lead to susceptibility to infection, but the inciting organisms usually are H. influenzae, S. pneumoniae, and E. coli. The use of immunosuppressing therapies such as transplantation or chemotherapy increases the likelihood of opportunistic infections. Besides these scenarios, CMV has rarely been reported in patients with amyloidosis or MM. We suggest GI amyloidosis and CMV should be considered and treated rapidly in patients presenting with non-specific GI symptoms. However, our case also highlights the difficulty in measuring effectiveness of antiviral treatment for CMV in GI amyloidosis due to overlap of symptoms between both conditions.Figure 1.: A) skiped areas of ulcerated, friable colon. B) immunohistochemistry CMV viral inclusions, C) Colonic epithelium with amyloidosis.

S2722 Cytomegalovirus Colitis in an Immunocompetent Patient Presenting With New Onset Ulcerative Colitis: A Clinical Vignette

Introduction: Cytomegalovirus (CMV) colitis is a rare disease among immunocompetent patients presenting with inflammatory bowel disease (IBD). CMV can cause steroid-refractory IBD, which may require antiviral and infliximab (IFX) combination therapy. Case Description/Methods: A 23-year-old woman was admitted for dehydration and poor oral intake in the setting of eight bloody bowel movements per day, tenesmus, and weight loss. She presented to an outside hospital 5-weeks prior with abdominal cramps and bright red blood per rectum. The CT scan showed bowel wall thickening and mucosal enhancement in the rectosigmoid and descending colon. A colonoscopy 2-weeks prior to admission was suggestive of severe ulcerative colitis (UC) and she was started on mesalamine/budesonide. Due to poor clinical response, she was switched to prednisone 40 mg for 5 days. Outpatient medical management failed and, upon admission, she was converted to methylprednisolone 20 mg every eight hours. Serum CMV PCR was positive at 1,758 IU/mL and colonic biopsies showed scattered CMV inclusions by immunohistochemical staining. She was started on ganciclovir 5mg/kg/dose IV in addition to the steroid regimen and IFX infusions were deferred. By day 2 of ganciclovir IV and day 7 of methylprednisolone IV, IBD symptoms began to resolve. On discharge at hospital day 12, patient was transitioned to twice daily oral valganciclovir 900 mg for a 3-week course and an oral prednisone taper. CMV PCR was 1,185 IU/mL on discharge and < 100 IU/mL at one week follow up. IFX therapy was initiated 45 days post discharge with improved symptoms, as characterized by a 17-lb weight gain at 3-month follow-up. (Figure) Discussion: CMV colitis is a rare diagnosis in immunocompetent patients with early, steroid naïve IBD. Serum PCR positive infection has been reported more commonly after 2-3 weeks of steroid therapy. CMV infection is a recognized complication and marker of poor prognosis in moderate to severe UC, especially those who present with steroid refractory disease. It is believed that the inflammatory mediators associated with UC play a synergistic role in CMV reactivation and subsequent disease. In addition, local corticosteroid induced immunosuppression may further facilitate CMV gene transcription, resulting in disease progression and poor steroid response. There remains no consensus for management of UC with concomitant CMV colitis however, in our patient the use of antiviral and biologic therapy (IFX) promoted disease regression and clinical improvement.Figure 1.: H&E Stain (20x) demonstrating active chronic colitis (left). Immunohistochemical staining (40x) showing CMV immunoreactivity (right).

S2716 CMV in IBD: An Innocent Bystander, or Active Pathogen?

Introduction: Ulcerative Colitis (UC) is a gastrointestinal inflammatory disease that affects over 6 million people worldwide. Clinical manifestations of UC such as bloody diarrhea and abdominal pain can often mimic an infectious colitis, such as cytomegalovirus (CMV) colitis. Often a silent infection, CMV has a worldwide seroprevalence of 83%. We present an interesting case of a UC patient with biopsy positive CMV colitis, who symptomatically improved on steroids and mesalamine alone. Case Description/Methods: A 66 year old African American female with a history of well-controlled UC was evaluated for acute onset bloody diarrhea and abdominal pain. Following negative stool studies for infection, the patient underwent colonoscopic evaluation. Preliminary imaging and results demonstrated a left-sided UC flare extending from the rectum to the splenic flexure. The patient was started on pulse dose steroids with instructions to taper as an outpatient and experienced resolution of symptoms. Biopsy revealed CMV with subsequent serologic testing showing a CMV viral load of < 390 cpy/mL, IgM level of 45.4 AU/mL and negative IgG levels. Interestingly, the patient's acute gastrointestinal symptoms resolved with glucocorticoid treatment. Discussion: CMV reactivation is common in patients with moderate to severe UC. Symptoms of diarrhea, bloody stool, abdominal pain and complications such as megacolon, fulminant colitis and perforation often overlap in both CMV and UC. Endoscopic evaluation can provide a more definitive means of differentiating CMV colitis from an acute exacerbation of UC, however, may not be able to be quickly performed before complications arise. There has been much debate on the role of CMV in UC and whether it is an active pathogen contributing to the inflammatory state or simply a surrogate marker for disease severity. Multiple studies have demonstrated an association of CMV antigenemia with endoscopically significant severe UC. In such patients, after detection of CMV in the colon with biopsy, treatment with antiviral therapy and withdrawal of immunosuppressive agents would be expected to induce clinical response. Continuation of immunosuppressive therapies was associated with adverse events such as fulminant colitis and colectomy. (Figure) Differentiating an active CMV infection versus a UC flare can be challenging given the wide overlap of symptoms. Colonoscopic evaluation is important in supplementing a diagnosis with histopathological confirmation of CMV and can help guide treatment.Figure 1.: Inflammation characterized by friability, loss of vascularity, mucous, pseudopolyps and deep ulcerations was found in a continuous and circumferential pattern in the terminal ileum (1,2), hepatic flexure (3), transverse colon (4,5,6), descending colon (7,8), sigmoid colon (9,10,11), and rectum (12,13,14). This was graded as Mayo Score 3 (severe, with spontaneous bleeding, ulcerations).

S2489 Differentiating CMV Colitis From GVHD in Post-Transplant Patients: A Case Study

Introduction: Cytomegalovirus (CMV) infection can complicate the clinical course of immunocompromised patients including allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients, where the infection can be serious. CMV can involve different organs including lungs, brain, eyes, and the GI tract. Signs and symptoms of CMV infection may overlap with other conditions including graft-versus-host disease (GVHD), a multisystem disorder commonly seen in allo-HSCT recipients. Case Description/Methods: A 57-year-old female presented with abdominal pain and diarrhea. Past medical history included relapsed acute myeloid leukemia, treated with azacitidine and venetoclax followed by allo-HSCT. She was recently hospitalized for suspected GVHD with skin, liver, and gastrointestinal involvement. She was also found to have a CMV viral load of 920 IU/mL. Endoscopy showed diffuse inflammation across the GI tract, with biopsies revealing apoptotic bodies consistent with acute GVHD. She was treated with ruxolitinib and prednisone for GVHD, and valganciclovir prophylactically for CMV viremia. At this presentation, labs were notable for lymphocytes of 39 x103/uL and platelets of 22 x 103/uL, and CMV viral load of 1,822,242 IU/mL. CT imaging revealed thickened distal small bowel loops, cecum, and right colon, and edematous gastric walls with submucosal enhancement. Infectious work-up, including stool culture, ova/parasite, and clostridium, was negative. She underwent endoscopic evaluation; EGD showed white discoloration that washed off in the esophagus and diffuse erythematous mucosa in the stomach (Figure). Biopsies from gastric mucosa and right colon mucosa revealed focal nuclear changes. Immunohistochemical stains were positive for CMV. She was diagnosed with refractory CMV colitis and treated with maribavir with improvement of symptoms and reduction of viral load, and prior course of steroids was tapered. Discussion: Immunosuppression for GVHD has been identified as an important risk factor for CMV reactivation. Differentiating CMV colitis and GI-GVHD poses a diagnostic challenge, and endoscopic evaluation is needed to address this. Endoscopy can identify cecal ulcers, a reliable finding for CMV colitis in patients with GVHD after allo-HSCT.1 It is important to timely identify CMV colitis to prevent post-transplant morbidity and mortality. This case also demonstrates effectiveness of maribavir, a novel antiviral, for refractory post-transplant CMV colitis.Figure 1.: EGD images showing white discoloration in the entire esophagus and diffuse erythematous mucosa in the entire examined stomach.

S2946 Chronic Graft versus Host Disease Masquerading CMV Colitis After Liver Transplantation: A Clinical Challenge

Introduction: Graft versus host disease (GVHD) after solid organ transplantation is a rare but serious complication with high mortality that typically occurs 1-8 weeks post liver transplantation (LT). Steroids are first line treatment and data on second line treatment are less widely available. Case Description/Methods: 54-years-old woman with history of alcohol-related cirrhosis went under LT with a positive cytomegalovirus (CMV) and HCV male donor. She was discharged home without any major complications. Immune suppression included tacrolimus, mycophenolate mofetil, (MMF) and prednisone taper. She was admitted to hospital 3 months later with diarrhea and acute kidney injury. C. difficile PCR was negative, CMV PCR was positive, and biopsies obtained during colonoscopy revealed severe CMV colitis. She was started on ganciclovir. Tacrolimus was reduced and MMF was discontinued. Fever and diarrhea were continued despite CMV treatment and later she developed a diffuse skin rash. This initially thought to be due to ganciclovir, but skin biopsy was concerning for GVHD. Gastric and colon biopsies and peripheral blood chimerism (donor T cell 81.3%; normal < 1%) confirmed GVHD. She was started on steroid therapy with minimal improvement in diarrhea as well as minimal improvement after the addition of topical budesonide and octreotide. Her course was complicated by posterior reversible encephalopathy syndrome and status epilepticus and was intubated. Tacrolimus was stopped. She then developed pancytopenia with severe neutropenia despite discontinuation of ganciclovir. Bone marrow biopsy showed 10.7% donor alleles. Infliximab was initiated. Stool output decreased and neutropenia resolved after 1 week. Seizures were controlled and she was extubated. Chimerism analysis of peripheral blood after 11 days showed significant reduction of donor T cells (58.5%). However, after 2 weeks, diarrhea worsened and donor T cells increased to 70.9% in blood. Ruxolitinib and cyclosporin were started in addition to infliximab but she developed septic shock and expired (Figure). Discussion: Persistent diarrhea and skin rash after liver transplantation may be signs of GVHD but these symptoms can also be seen in more common conditions such as C. difficile infection, drug reaction, and CMV colitis. Biopsy and chimerism analysis might both be needed for diagnosis of GVHD in patients with low pretest probability. Post LT GVHD that is refractory to steroid therapy may respond to infliximab. Sepsis is the most common cause of mortality in LT GVHD.Figure 1.: Sample micrographs from short tandem repeat (STR) testing (chimerism analysis) on isolated T cells from peripheral blood.

S2127 Recurrent or Concurrent Colitis: Immune Checkpoint Inhibitor-Induced Colitis vs CMV Colitis

S2127 Recurrent or Concurrent Colitis: Immune Checkpoint Inhibitor-Induced Colitis vs CMV Colitis

S932 Active Tuberculosis and Opportunistic Infections: Pooled Safety Analysis of Ustekinumab Through up to 5 Years Across All Approved Indications

Introduction: Ustekinumab (UST) is an approved treatment for adults with inflammatory bowel disease (IBD: Crohn’s disease [CD] and ulcerative colitis [UC]), psoriasis (PsO), and psoriatic arthritis (PsA). Here, we present pooled safety analyses in these approved indications of patients (pts) with active tuberculosis (TB) and opportunistic infections (OIs) through 5 years (yrs) of UST treatment. Methods: Pooled data included 13 Phase 2/3 UST studies through 5 yrs of CD and PsO, 2 yrs of UC, and 1 yr of PsA. OIs were identified by clinician review. Herpes zoster (HZ) was evaluated separately. Event rates per 100 pt yrs (PYs) are presented. Concomitant immunomodulators/corticosteroids were permitted in IBD and PsA pts. All pts who received ≥1 UST dose were included. In IBD, placebo (PBO) pts included data up to the first UST dose for pts initially treated with PBO, or >16 weeks after the last UST dose for UST pts who switched to PBO. Results: Across all approved indications, 19 OIs including TB were reported, with rates in PBO of 0.40 and UST of 0.10 through 5 yrs in 13807 PYs of follow-up (Table); rates of HZ were 1.21 and 0.63, respectively. Of 19 OIs, 18 were in IBD pts and 1 in a PsO pt. Overall, 14/16 pts (12/13 UST) with OIs excluding TB were also receiving confounding concomitant medications. A total of 3 active TB cases (2 pts with CD and 1 pt with UC) were reported in PBO (n=2; 1 in a CD pt 10 months after receiving UST 130 mg IV) and UST pts (n=1) (Table). One active TB case was reported in an asymptomatic South African CD pt treated with UST who had a positive QuantiFERON®-TB Gold test on routine screening and bronchial brushings positive for M. tuberculosis. Both CD pts completed TB treatment with disease resolution. The most common OIs were esophageal candidiasis (UST n=3; PBO n=2) and cytomegalovirus colitis (UST n=3; PBO n=1). Conclusion: Rates of OIs, including active TB, in UST-treated pts were low across approved indications through up to 5 years with 13807 PYs of follow-up and not higher in UST pts vs PBO, suggesting no increased risk of OI with long-term UST treatment. Table 1. - Opportunistic infections (OIs) and active tuberculosis (TB) in Inflammatory Bowel Disease (CD, UC) and Psoriatic studies (PsO, PsA) through up to 5 yrs; numbers of events per 100 patient-years (PYs) of follow-up Inflammatory Bowel Disease Indications a Psoriatic Indications a All Approved Indications Pooled Placebo b (n=1389) Ustekinumab c (n=2575) Placebo d (n=1112) Ustekinumab e (n=4135) Placebo b,d (n=2501) Ustekinumab c.e (n=6710) Total PYs of follow-up 916 3960 327 9847 1244 13807 Average duration of follow-up (weeks) 34.31 79.97 15.30 123.83 25.86 107.00 All OIs, event rates per 100 PYs [n] 0.55 [5] 0.33 [13] 0.00 [0] 0.01[1] 0.40 [5] 0.10 [14] OIs excluding TB 0.33 [3] 0.30 [12] 0.00 [0] 0.01 [1] 0.24 [3] 0.09 [13] TB 0.22 [2] 0.03 [1] 0.00 [0] 0.00 [0] 0.16 [2] 0.01 [1] aPsoriatic (PsO and PsA) trials evaluated subcutaneous ustekinumab (UST) 45/90 mg or placebo (PBO), generally at week 0 and 4, then every 12 weeks (q12w). IBD (CD and UC) trials generally evaluated a single intravenous UST dose (130 mg or weight range-based dosing of ∼6 mg/kg) or PBO induction dose at week 0, followed by subcutaneous UST 90 mg at week 8, then q8w or q12w.bCD and UC: includes data up to the first UST dose for patients who were initially treated with PBO; includes data at or after 16 weeks from the first UST dose onward, up to the dose adjustment if patients had a dose adjustment, for patients who crossed-over or re-randomized to PBO maintenancecCD and UC: includes data up to 16 weeks from the first UST dose for patients who crossed-over or re-randomized to PBO maintenance, and from the dose adjustment onward if patients had a dose adjustment from subcutaneous PBO to subcutaneous UST 90 mg q8wdPsoriatic diseases: includes data up to the time of early escape or crossoverePsoriatic diseases: includes data from the first UST dose onward for patients who early escaped or crossed-over from PBO

Amphotericin B-Resistant Disseminated Cryptococcal Infection with Concurrent Cytomegalovirus Colitis in a Renal Transplant Recipient - A Case Report

Post renal transplant opportunistic infections always pose a challenge to the clinician due to the varied nonspecific clinical manifestations and prove fatal if not diagnosed and treated early. Here, we present a case report of a patient who was 22 years post renal transplantation with amphotericin-resistant disseminated cryptococcal infection concurrent with cytomegalovirus colitis treated successfully with oral fluconazole and ganciclovir. The clinician should always take into account the antibiotic susceptibility and culture sensitivity of cryptococcosis to diagnose this rare yet emerging phenomenon of azole resistance. Furthermore, to the best of our knowledge, this is the first reported case of amphotericin-resistant cryptococcosis in posttransplant setting.

MPN-166 Myeloproliferative Neoplasm (MPN) Post-Renal Transplant (RT)-A Single-Center Review.

MPN post-RT is a rare disease. There is little data on the clinicopathological features and outcomes of patients with post-RT MPN. The main objective of this study was to analyze the clinical outcome of MPN post-RT. This was a single-center retrospective study Settings: Patients who had post-RT MPN at Memorial Herman Hospital, Texas Medical Center. We reviewed 1998 patients who underwent RT between January 1, 1999, and December 31, 2019. Three cases of post-RT MPN were identified. None Main Outcome Measures: We analyzed the incidence, the interval between RT and MPN diagnosis, MPN treatment, and clinical outcome of patients with post-RT MPN. Among 1998 RT recipients, 3 cases (0.1%) of MPN were identified. All occurred in women with a mean age of 53 years. Races were African American (n=2) and white (n=1). Causes of end-stage renal disease were diabetes, hypertensive, and IgA nephropathy. Two patients received RT, and one patient simultaneous kidney and pancreas transplant. All three patients were on tacrolimus, mycophenolate, and prednisone for post-transplant immunosuppression. Two patients developed chronic myeloid leukemia (CML), and one had polycythemia vera (PV). The mean interval between RT and diagnosis of MPN was 9 years. Cytogenetics demonstrated JAK-2 mutation in the patient with PV and BCR-ABL translocation in the two CML patients. The CML patients received BCR-ABL tyrosine kinase inhibitors (TKIs; imatinib/dasatinib) and continue to have a major molecular response. The patient with PV remains on hydroxyurea (HU) and aspirin with excellent hematocrit control. Mycophenolate was discontinued in all three patients after the diagnosis of MPN. TKI and HU were well tolerated. No thrombotic events or leukemic transformation were reported. One CML patient developed cytomegalovirus colitis. No other infectious complications were noted. She also developed immune-related hemolytic anemia and thrombocytopenia that were successfully treated with glucocorticoids. All three patients still have preserved allograft function and are alive at a median follow-up of 42 months. MPN post-RT is rare. Standard-of-care therapies for MPN are well tolerated. Further studies are required to explore the pathophysiology and outcomes of MPN in RT recipients.

Evaluation of colonoscopy results in HIV infected cases

Objective: GI system plays an important role in the clinical symptoms and pathogenesis of HIV infection. Significant progress has been made towards understanding the role of the GI system in both the early and late stages of HIV infection. In this study, our aim is to evaluate the results of colonoscopy in HIV-infected patients followed up in our clinic. Material and Methods: HIV (+) cases followed in our clinic were included in our study. The computer records of the cases were retrospectively examined and the findings of the patients who underwent colonoscopy were recorded. Age, gender, CD4 values and colonoscopy results of these patients were recorded simultaneously. Results: A total of 27 HIV-infected patients who underwent colonoscopy were included in our study. The mean age of the cases was 41.2, and the rate of males was 92.6% (25/27). It was observed that the mean age of patients with colonoscopy findings was 41.8, and the mean age of those without colonoscopy findings was 41.1. It was determined that 44.4% (12/27) of our cases in total had colonoscopic findings. While normal colonoscopic findings were reported in 15 (55.6%) of patients, benign anorectal diseases (fissure, hemorrhoids) were found in 7 (25.9%) and polyps were found in 3 of them (11.1%). CMV colitis was diagnosed in 2 (7.4%) patients with pathological diagnosis. Conclusion: As a result, although the number of our cases is small, it is observed that approximately 55% of patients have normal colonoscopy findings, but those with perianal disease and polyps have a higher CD4 count than those with normal colonoscopy. It has been revealed that patients with CMV infection also have a CD4 count of <200. Studies with more patients in HIV-infected patients will contribute to the diagnosis, follow-up, and treatment preferences of the patients.

CMV Colitis Masquerading as MALT Lymphoma in an Immunocompetent Patient.

CMV Colitis Masquerading as MALT Lymphoma in an Immunocompetent Patient.