Introduction

Clostridioides difficile infection (CDI) represents the leading cause of nosocomial diarrhea in the Western world. Patients with ulcerative colitis (UC) have a higher risk of developing this infection, which has been associated with an increased risk of flare-ups, need for surgery, and mortality. The aim of the present study was to evaluate the impact of this infection in patients hospitalized for a UC flare-up.

Aims & Methods

Retrospective case-control study including all patients hospitalized for a UC flare-up at Reina Sofía Hospital in Córdoba between January 2000 and January 2023. To avoid potential selection biases, Propensity Matching Score (PMS) adjusted for age, gender, duration, and extent of the disease, with a 1:2 ratio was used. Primary objective was to assess the need for treatment intensification (initiation or dose escalation of biologics/small molecules or immunosuppressant). Secondary endpoints included readmission rate, colectomy, mortality, and CDI risk factors identification.

Results

During the study period, 419 patients were hospitalized for a UC flare-up, of whom 251 (59.9%) were men, with a median age of 41 (IQR 28-55) years and disease duration of 0.89 (0-5.8) years. Of all admissions, 46 (11%) had CDI. After PMS, CDI was associated with increased therapeutic intensification between 3-12 months after discharge (27.5% vs. 11.7%, p = 0.004) and a higher risk of readmission at 12 months (37.5% vs. 13.7%, p = 0.009) but not to risk of colectomy or mortality (Table 1). Infection recurrence was detected in 8 (16.7%) patients.
Classical risk factors for CDI were not found to increase the risk of CDI among UC patients, however antiTNF therapy was associated to CDI in both models: full cohort (OR 3.52, 95%CI 1.46-8.49) and PMS (OR 4.63, 95%CI 1.32-16.31).

Table 1. Hospitalisation characteristics, evolution and complications

Conclusion

CDI in UC was associated with a greater need for therapeutic intensification and a higher readmission rate at one year. There was no evidence of an increased risk of colectomy or mortality in these patients. Classical risk factors for CDI were not identified but patients on antiTNF were at higher risk of CDI.

Disclosure

Beatriz Gros has served as a consultant for Galapagos and Abbvie and as a Speaker for Abbvie, Janssen, Takeda, Pfizer and Galapagos.

Introduction

Patients with ulcerative colitis (UC) are at increased risk of developing colorectal cancer (CRC), and this is assumed to be due to chronic inflammation of the colorectal mucosa.

Aims & Methods

To identify risk factors for the development of dysplasia or CRC in patients with UC. Retrospective observational cohort study. Clinical data and colonoscopy findings were collected from medical records. A 1:2 Propensity Score Matching (PSM) was performed to balance covariates adjusting for disease extension, age, gender, smoking habit and disease duration. An Andersen-Gill model was used to account for multiple colonoscopies per patient and time-varying risk of dysplasia or CRC, allowing for recurrent events and intra-individual correlation.

Results

A total of 571 UC patients were identified, median age at diagnosis was 39.5 (27.3-54.2), and 304 (53.2%) were men. At diagnosis, 147 (25.7%) had proctitis, 203 (35.6%) left side colitis and 191 (33.5%) extensive colitis. During a median follow-up of 7.1 years (IQR 3.7– 13.3), 51 patients (9.8%) developed dysplasia/CRC. This was more frequent in males (72.9% vs. 27.1%, p=0.004) and in older patients [48.1 years (36.7–60.2) vs. 38.5 years (26.5–53.8), p=0.004].
After PSM adjustment, 123 patients were included, 41 of whom had dysplasia/CRC, with a total of 381 colonoscopies over a follow-up period of 14.6 years (IQR 8.0–22.4). Macroscopic inflammatory activity was present in 283 (74.3%) colonoscopies and microscopic involvement in 5 (1.3%). Older age at diagnosis (aHR 1.03, 95% CI 1.04–1.10, p<0.001) and higher degree of macroscopic inflammation (aHR 1.44, 95% CI 1.02–2.03, p=0.041) were associated with an increased risk of dysplasia/CRC development; advance therapy, family history of CRC, disease extension and microscopic inflammation were not associated with an increased risk.

Table 1. Baseline characteristics of the complete cohort and after Propensity Matching Score.

Conclusion

Older age at diagnosis and the presence of macroscopic involvement on successive colonoscopies are associated with an increased risk of developing dysplasia or CRC in patients with UC.

Disclosure

Beatriz Gros has worked as an advisor for Abbvie, Pfizer, Alphasigma and Roche and has served as an speaker for Abbvie, Pfizer, Alphasigma, Roche, Janssen, Takeda and Gilead.

Introduction

Numerous studies have implicated hormonal contraceptive therapy (HCT) as a potential trigger for IBD onset. However, data regarding disease flares in hormonal contraceptive users are limited in ulcerative colitis (UC). This study aims to explore this association.

Aims & Methods

Female patients who were diagnosed with UC after 1^st January 2014, and born between 1966-2008 were included. The Andersen-Gill extension of the Cox proportional hazards model was used to account for recurrent events within the same subjects. Two models were employed: the first included each patient corresponding to only one cohort, while in the second one those who initiated HCT after diagnosis, were included twice, one from diagnosis to HCT as non-exposed and as exposed thereafter.

Results

Among 2359 patients in our local database, 545 were women with UC, of whom 132 met the inclusion criteria for analysis. The majority had UC proctitis 57 (43.2%) with 24 (18.2%) were smokers. The median age was 32.5 (23.3-42) years.
Of the cohort, 52 (39.1%) women exposed HCT, with a median exposure duration of 1.5 (0.5-5.0) years. Of these, 33 (25%) were exposed to HCT during follow-up.
Over 518 person-years of follow up, 178 flares and 198 courses of steroids were observed with 56 admissions and one colectomy, differences were observed among the incidence rates between groups Table 1. Additionally, there were 24 pregnancies documented.
No differences in time to first flare (log-rank test p=0.83). However, the Cox proportional hazard model showed that HCT was associated with higher cumulative risk of flares in both models (HR 1.53, 95%CI 1.05-2.22, p=0.029) and (HR 1.47, 95%CI 1.019-2.11, p=0.039), Figure 1A and 1B. No adverse events associated to HCT occurred during follow-up.

Conclusion

Our study suggests that HCT is associated with an increased cumulative risk of flares, steroid prescription and hospitalization rates in ulcerative colitis patients. Furthermore, no safety signals were observed with the use of HTC in this cohort.

Disclosure

Beatriz Gros has served as consultant to Galapagos and Abbvie and as speaker for Abbvie, Jansen, Takeda, Pfizer and Galapagos.

Introduction

Severe acute colitis (SAC) <represents a critical complication of inflammatory bowel disease (IBD), requiring prompt and appropriate management. Opportunistic infections, particularly those caused by cytomegalovirus (CMV) and Clostridioides difficile (C. difficile), can significantly influence clinical outcomes and therapeutic responses, especially in immunocompromized individuals. This study aims to evaluate the incidence of these opportunistic infections in patients with SAC complicating IBD and to analyze their impact on clinical progression and treatment efficacy.

Aims & Methods

A retrospective study was conducted involving patients admitted for SAC, diagnosed based on Truelove and Witts criteria and a Lichtiger score exceeding 10. Initial assessments included CMV polymerase chain reaction (PCR) testing on colonic biopsies and/or blood samples, detection of C. difficile toxins A/B in stool specimens, and standard microbiological evaluations. Clinical, biological, and therapeutic response data were systematically collected.

Results

Fifty-five patients over the age of 18 were included, with a mean age of 42.36 years (range: 18–74) and a slight female predominance (55%). In 34% of cases, SAC was the initial manifestation of IBD. All patients met the Truelove and Witts criteria and had a Lichtiger score >10 upon admission. Endoscopic signs of severity were observed in 40% of patients.
Intravenous corticosteroid therapy using hydrocortisone hemisuccinate was administered as the first-line treatment for all patients, yielding a 60% response rate.
CMV co-infection was identified in 4 patients, all of whom were refractory to intravenous corticosteroids and subsequently received ganciclovir. Two patients responded favorably to second-line therapy with cyclosporine, while the remaining two did not respond to infliximab and required subtotal colectomy.
C. difficile co-infection was detected in 6 patients, treated with intravenous metronidazole and oral vancomycin. Among these, 3 patients did not respond to first-line medical therapy; one acheved clinical improvement with cyclosporine, whereas two required emergency subtotal colectomy due to the development of toxic megacolon.
Bivariate analysis revealed a statistically significant association between CMV co-infection and corticosteroid treatment failure (p=0.009). No significant association was found between C. difficile co-infection and first-line treatment failure in SAC.

Conclusion

Opportunistic infections, particularly CMV, are linked to unfavorable therapeutic responses in patients with SAC. Early detection of these co-pathogens is crucial for promptly adjusting treatment strategies, including the consideration of second-line therapies or surgical interventions. These findings underscore the importance of systematic screening for opportunistic infections in SAC patients to optimize management and improve clinical outcomes.

Disclosure

The authors report no conflicts of interest

Clinical Case Summary

Background: Nocardiosis is an opportunistic bacterial infection usually occurring in immunocompromised patients. Patients with Ulcerative Colitis (UC) receiving immunosuppressants drugs can be predisposed to uncommon opportunistic infections.
Results: A 72-year old man with UC history since 1990, after a severe clinical and endoscopic exacerbation (pancolitis MAYO 3), was treated in another clinic for three months with Infliximab 5 mg/kg, Prednisone 25 mg, Budesonide 9 mg/day and Azathioprine 100 mg/day. In November 2020 he was admitted to our ward for diarrhea, low grade fever (37.5°C), severe asthenia and hyperglycaemia. During hospitalization we diagnosed with adrenocortical insufficiency, treated with fludrocortisone. Furthermore, microbiological blood tests were performed and a cytomegalovirus (CMV) systemic infection (treated with Gancyclovir) and blood cultures were positive for Nocardia farcinica. Subsequently, computed tomography (CT) abdominal imaging revealed splenic, hepatic and pulmonary lesions, suggestive of systemic involvement of the nocardiosis. Sudden seizures onset led to performing head CT, showing encephalic lesions by Nocardia. Therefore immunosuppressant therapy was stopped (except for Methylprednisolone 10 mg/day) and to start antibiotic therapy with Imipenem, Amikacin and Trimethoprim/sulphamethoxazole (TMP/SMX) and anticonvulsant treatment with Levetiracetam. As a result, the patient achieved clinical remission and progressive improvement of radiological findings within six months from discharge.
Conclusions: Unappropriated simultaneous administration of immunosuppressant drugs can increase the risk of opportunistic infections that may lead to life threatening systemic conditions, requiring complex therapies. Moreover, the onset of infections, contraindicates the administration of many medications used in UC, hindering the possibility to appropriately treat the patient.

Introduction

Ulcerative colitis (UC) is often complicated by Cytomegalovirus (CMV) colitis. The importance of CMV infection for the outcome of UC is still ill-defined. Common practice consists of obtaining colonic biopsies to search for CMV in patients with UC flares and treat infections with ganciclovir.

Aims & Methods

The aim of the present study is to describe the characteristics and management of patients with UC and concomitant CMV infection. For this purpose, we conducted a retrospective data collection from 2 Greek hospitals for the years 2017-2023. The primary endpoint was defined as the need for colectomy in the first year after CMV infection diagnosis. The statistical program SPSS-23 was used for the analysis.

Results

In total, 47 cases of CMV infection in 37 patients with UC were reported as 7 patients experienced CMV recurrence. Most cases were observed in men (68%) with mean age of 47.5 years (SD 18.2), median UC duration 3 years (IQR 1-8) and Montreal classification E2 in 31.9% and E3 68.1% occasions. The diagnosis was established by PCR in colonic biopsies in 46.8% cases, by immunohistochemistry in another 46.8% and solely by detection of inclusion bodies in 6.4%. At the time of diagnosis of CMV infection 7 (14.9%) cases were receiving combination therapy with a biologic agent and an immunomodulator, 20 (42.6%) monotherapy with a biologic agent, and 1 (2.1%) monotherapy with an immunomodulator. Nine-teen patients (40.4%) were not on immunomodulatory therapy. Most patients (22, 46.8%) received ganciclovir and concomitant corticosteroids, while 4 (8.5%) received infliximab, corticosteroids and ganciclovir and 2 (4.3%) ustekinumab, corticosteroids and ganciclovir. One case required treatment with Foscarnet due to CMV resistance to ganciclovir, and 18 received monotherapy with ganciclovir. Regarding maintenance treatment in patients who did not require immediate colectomy, 18 (38.3%) received anti-TNF, 6 (12.7%) ustekinumab, 4 (8.5%) vedolizumab, 3 (6.4%) tofacitinib and 1 (2.1%) risankizumab. Colectomy rate in the first year after CMV infection was 21.3% with 4 patients undergoing surgery during initial hospitalization. In univariate logistic regression age >54 years (P=0.025), disease duration >6.5 years (P=0.035), serum albumin <3.8 mg/dl (P=0.026), UC PRO bowel movement >2 (P=0.016) and vedolizumab (P=0.035) as treatment at diagnosis were associated with a higher probability of colectomy in the first year. Accordingly, in multivariate logistic regression UC PRO bowel movement >2 (P=0.041) remained a statistically significant factor for colectomy while a tendency remained for albumin <3.8mg/dl (P=0.082).

Conclusion

CMV infection is more common in patients with ulcerative pancolitis under immunomodulatory treatment and should be diagnosed via a combination of immunohistochemistry and PCR in biopsies. Patients with prominent diarrhea [UC PRO bowel movement >2] may be particularly prone to colectomy.

Disclosure

GB: Advisor/lecturer for Janssen, Pfizer, Takeda, Abbvie, MSD, Mylan, Genesis Pharma, Adacyte Therapeutics, Amgen, Ferring, Cooper; Funding (Grants/Honoraria): Pfizer, Takeda, Abbvie, Aenorasis; Research/Clinical Trials: Abbvie, Takeda
EZ: Advisor/lecturer for Pfizer, Takeda, Abbvie, Amgen, Genesis Pharma, Aenorasis, Janssen
SM: Advisory/Lecturer for Pfizer, Takeda, Abbvie, Ferring, MSD, Janssen