First report of paracoccidioidomycosis reactivation as a complication of immunosuppressive therapy for acute severe colitis in a caving enthusiast

Treatment for ulcerative colitis often requires the administration of immunosuppressive therapy. Shortly after rescue therapy with infliximab for acute severe colitis, a patient who was also taking corticosteroids, azathioprine and adalimumab became rapidly unwell with atypical pneumonia, which did not respond to conventional antimicrobials. Re-examining the travel history revealed a prior caving trip to Costa Rica. Dimorphic fungal serology was thus tested and a diagnosis of paracoccidioidomycosis was made. After a lengthy intensive care unit admission, the patient made a recovery after the administration of appropriate antifungal therapy and was discharged home on long-term oral antifungals.

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Endoscopic and Histologic Predictors of Outcomes in Pediatric Ulcerative Colitis—Caveat Emptor

Frontiers in Pediatrics ◽

10.3389/fped.2021.678132 ◽

2021 ◽

Vol 9 ◽

Author(s):

Lorraine Stallard ◽

Séamus Hussey

Keyword(s):

Ulcerative Colitis ◽

Mucosal Healing ◽

Term Treatment ◽

Clinical Settings ◽

Adult Disease ◽

Long Term Treatment ◽

Acute Severe Colitis ◽

The Impact ◽

Severe Colitis

The impact of endoscopic and histological mucosal healing on outcomes in adult settings is impressive. Despite many clinical parallels, pediatric ulcerative colitis (UC) is set apart from adult disease in several respects. Many frequently used indices are not fully validated, especially in pediatric settings, and consensus on precise definitions in clinical settings are lacking. Endoscopic mucosal healing is an acceptable long-term treatment goal in pediatrics, but not histologic normalization. Early prediction of disease course in UC may allow treatment stratification of patients according to risks of relapse, acute severe colitis, and colectomy. Putative endoscopic and histologic predictors of poor clinical outcomes in adults have not held true in pediatric settings, including baseline endoscopic extent, endoscopic severity, and specific histologic characteristics which are less prevalent in pediatrics at diagnosis. In this mini-review we appraise predictive endoscopic and histologic factors in pediatric UC with reference to relapse, severe colitis, and colectomy risks. We recommend that clinicians routinely use endoscopic and histologic sores to improve the quality of clinical and research practice. The review summarizes differences between adult and pediatric prediction data, advises special consideration of those with primary sclerosing cholangitis, and suggests areas for future study in this field.

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Long-term Outcomes of Paediatric Patients Admitted With Acute Severe Colitis— A Multicentre Study From the Paediatric IBD Porto Group of ESPGHAN

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz092 ◽

2019 ◽

Vol 13 (12) ◽

pp. 1518-1526 ◽

Cited By ~ 3

Author(s):

Alex Krauthammer ◽

Christos Tzivinikos ◽

Amit Assa ◽

Erasmo Miele ◽

Caterina Strisciuglio ◽

...

Keyword(s):

Ulcerative Colitis ◽

Activity Index ◽

Age Groups ◽

New Drugs ◽

Therapeutic Drug ◽

Necrosis Factor Alpha ◽

Paediatric Patients ◽

Acute Severe Colitis ◽

Severe Colitis

Abstract Background and Aim Acute severe colitis [ASC] is associated with significant morbidity in paediatric patients with ulcerative colitis [UC]. Most outcome studies in ASC since tumour necrosis factor alpha [TNFα] antagonists became available have focused on the first year after admission. The aim of this study was to characterise the longer-term outcomes of paediatric patients admitted with ASC. Methods This retrospective study was conducted in 25 centres across Europe and North America. Data on patients with UC aged <18 years, admitted with ASC (defined as paediatric ulcerative colitis activity index [PUCAI] score ≥65) between 2009 and 2011, were collected at discharge and 1, 3 and 5 years after admission. The primary outcome was colectomy-free rates at each time point. Results Of the 141 patients admitted with ASC, 137 [97.1%] were treated with intravenous corticosteroids. Thirty-one [22.6%] patients were escalated to second-line therapy, mainly to infliximab. Sixteen patients [11.3%] underwent colectomy before discharge. Long-term follow-up showed colectomy-free rates were 71.3%, 66.4% and 63.6% at 1, 3 and 5 years after initial ASC admission, respectively, and were similar across different age groups. Sub-analysis of colectomy rates in patients with new-onset disease [42.5% of the cohort] yielded similar results. In a multivariate analysis, use of oral steroids in the 3 months before admission, erythrocyte sedimentation rate >70 mm/h, and albumin <2.5 g/dL, were significantly associated with 5-year colectomy risk. Conclusions High colectomy rates were demonstrated in paediatric UC patients admitted with ASC. Additional studies are required to determine whether intensification of anti-TNFα treatment, close therapeutic drug monitoring, and use of new drugs alter this outcome.

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Optimising Early Management of Acute Severe Ulcerative Colitis in the Biologics Era: Admission Model for Intensification of Therapy in Acute Severe Colitis (ADMIT-ASC)

10.1101/2021.07.14.21260477 ◽

2021 ◽

Author(s):

Alex Adams ◽

Vipin Gupta ◽

Waled Mohsen ◽

Thomas P Chapman ◽

Deloshaan Subhaharan ◽

...

Keyword(s):

Ulcerative Colitis ◽

Medical Therapy ◽

Rescue Therapy ◽

University Hospital ◽

New Delhi ◽

Early Management ◽

Improved Outcomes ◽

Hospitalised Patients ◽

Acute Severe Colitis ◽

Severe Colitis

Background & aims: We aimed to determine whether changes in ulcerative colitis management have translated to improved outcomes, in order to develop a simple model to predict steroid non-response on admission. Methods: Outcomes of 131 adult ASC admissions (117 patients) in Oxford, UK between 2015-19 were compared with prospectively collected data from 1992-3. All patients received standard treatment with intravenous corticosteroids and endoscopic disease activity scoring (UCEIS). Steroid non-response was defined as receiving rescue medical therapy or surgery. A predictive model created in the Oxford cohort was validated in Australia and India (110 hospitalised patients Gold Coast University Hospital 2015-20; 62 hospitalised patients AIIMS, New Delhi 2018-20). Results: In the 2015-19 Oxford cohort, 71 (54%) patients received medical rescue therapy (27% ciclosporin, 27% anti-TNF), compared to 27% ciclosporin in 1992-3, p=0.0015. Only 15% required colectomy during admission vs 29% in 1992-3 (p=0.033). Admission CRP, albumin, and UCEIS scores predicted steroid non-response (FDR p=0.00066, 0.0066 and 0.015). A four-point model was developed involving CRP ≥ 100mg/L (1 point), albumin ≤ 25g/L (1 point), UCEIS ≥ 4 (1 point) or ≥ 7 (2 points). Scoring 0 or 4 was 100% predictive of steroid response and non-response, respectively, in all three cohorts. Patients scoring 3-4 had 83% risk of steroid non-response in Oxford and 84% (0.70-0.98) in the validation cohorts -- OR 11.9 (10.8-13). Conclusion: Colectomy rates for ASC have halved in 25 years, while use of rescue medical therapy has doubled. Patients who are highly unlikely to respond to parenteral steroid treatment alone may be readily identified on admission, to be prioritised for early intensification of therapy.

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Tofacitinib: An Option for Acute Severe Ulcerative Colitis?

GE Portuguese Journal of Gastroenterology ◽

10.1159/000514781 ◽

2021 ◽

pp. 1-3

Author(s):

Sara Santos ◽

Verónica Gamelas ◽

Rita Saraiva ◽

Guilherme Simões ◽

Joana Saiote ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Improvement ◽

Rescue Therapy ◽

New Drugs ◽

Multiple Drug ◽

Disease Course ◽

Efficacy And Safety ◽

Severe Ulcerative Colitis ◽

Rapid Absorption

Tofacitinib has emerged as a new option for ulcerative colitis. Its rapid absorption, metabolism, and clinical improvement make it an interesting option for rescue therapy in acute severe ulcerative colitis (ASUC), a situation with limited therapeutic options in patients with a long-term disease course and multiple drug failure. The management of ASUC in this setting becomes challenging, underlying the need for new drugs and data on their efficacy and safety. We describe 2 cases of acute episodes in which tofacitinib was used as a rescue therapy.

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Ciclosporin or Infliximab as Rescue Therapy in Acute Glucorticosteroid-Refractory Ulcerative Colitis: Systematic Review and Network Meta-Analysis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjaa226 ◽

2020 ◽

Author(s):

Brigida Barberio ◽

Christopher J Black ◽

Edoardo V Savarino ◽

Alexander C Ford

Keyword(s):

Ulcerative Colitis ◽

Rescue Therapy ◽

Meta Analysis ◽

Previous Treatment ◽

Response To Therapy ◽

Cochrane Central Register ◽

Serious Adverse Events ◽

Central Register ◽

Meta Analyses

Abstract Background Despite randomized controlled trials [RCTs] and trial-based meta-analyses, the optimal rescue therapy for patients with acute glucorticosteroid-refractory ulcerative colitis [UC], to avoid colectomy and improve long-term outcomes, remains unclear. We conducted a network meta-analysis examining this issue. Methods We searched MEDLINE, EMBASE, EMBASE Classic and the Cochrane central register up to June 2020. We included RCTs comparing ciclosporin and infliximab, either with each other or with placebo, in patients with glucorticosteroid-refractory UC. Results We identified seven RCTs containing 534 patients [415 in head-to-head trials of ciclosporin vs infliximab]. Risk of colectomy at ≤ 1 month was reduced significantly with both treatments, compared with placebo (relative risk [RR] of colectomy with infliximab vs placebo = 0.37; 95% confidence interval [CI] 0.21–0.65, RR with ciclosporin vs placebo = 0.40; 95% CI 0.21–0.77). In terms of colectomy between > 1 month and < 1 year, both drugs ranked equally [P-score 0.75]. Neither treatment was more effective than placebo in reducing the risk of colectomy at ≥ 1 year. Both ciclosporin and infliximab were significantly more efficacious than placebo in achieving a response. Neither treatment was more effective than placebo in inducing remission, nor more likely to cause serious adverse events than placebo. Conclusions Both ciclosporin and infliximab were superior to placebo in terms of response to therapy and avoiding colectomy up to 1 year, with no significant differences in efficacy or safety between the two. Ciclosporin remains a valid option to treat refractory UC patients, especially those who do not respond to previous treatment with infliximab, or as a bridge to other biological therapies.

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Long-term outcomes of acute severe ulcerative colitis in the rescue therapy era: A multicentre cohort study

United European Gastroenterology Journal ◽

10.1177/2050640620977405 ◽

2020 ◽

pp. 205064062097740

Author(s):

Stefano Festa ◽

Maria L Scribano ◽

Daniela Pugliese ◽

Cristina Bezzio ◽

Mariabeatrice Principi ◽

...

Keyword(s):

Ulcerative Colitis ◽

Tumour Necrosis ◽

Rescue Therapy ◽

Tumour Necrosis Factor Alpha ◽

Necrosis Factor Alpha ◽

Severe Ulcerative Colitis ◽

Factor Alpha ◽

Necrosis Factor

Background The long-term course of ulcerative colitis after a severe attack is poorly understood. Second-line rescue therapy with cyclosporine or infliximab is effective for reducing short-term colectomy but the impact in the long-term is controversial. Objective The purpose of this study was to evaluate the long-term course of acute severe ulcerative colitis patients who avoid early colectomy either because of response to steroids or rescue therapy. Methods This was a multicentre retrospective cohort study of adult patients with acute severe ulcerative colitis admitted to Italian inflammatory bowel disease referral centres from 2005–2017. All patients received intravenous steroids, and those who did not respond received either rescue therapy or colectomy. For patients who avoided early colectomy (within three months from the index attack), we recorded the date of colectomy, last follow-up visit or death. The primary end-point was long-term colectomy rate in patients avoiding early colectomy. Results From the included 372 patients with acute severe ulcerative colitis, 337 (90.6%) avoided early colectomy. From those, 60.5% were responsive to steroids and 39.5% to the rescue therapy. Median follow-up was 44 months (interquartile range, 21–85). Colectomy-free survival probability was 93.5%, 81.5% and 79.4% at one, three and five years, respectively. Colectomy risk was higher among rescue therapy users than in steroid-responders (log-rank test, p = 0.02). At multivariate analysis response to steroids was independently associated with a lower risk of long-term colectomy (adjusted odds ratio = 0.5; 95% confidence interval, 0.2–0.8), while previous exposure to anti-tumour necrosis factor alpha agents was associated with an increased risk (adjusted odds ratio = 3.0; 95% confidence interval, 1.5–5.7). Approximately 50% of patients required additional therapy or new hospitalization within five years due to a recurrent flare. Death occurred in three patients (0.9%). Conclusions Patients with acute severe ulcerative colitis avoiding early colectomy are at risk of long-term colectomy, especially if previously exposed to anti-tumour necrosis factor alpha agents or if rescue therapy during the acute attack was required because of steroid refractoriness.

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P057 Gut microbiome diversity in acute severe colitis is distinct from mild-to-moderate ulcerative colitis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjy222.181 ◽

2019 ◽

Vol 13 (Supplement_1) ◽

pp. S114-S115

Author(s):

S Kedia ◽

T S Ghosh ◽

B Das ◽

S Jain ◽

S Bopanna ◽

...

Keyword(s):

Ulcerative Colitis ◽

Gut Microbiome ◽

Microbiome Diversity ◽

Acute Severe Colitis ◽

Severe Colitis

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Ciclosporin Therapy After Infliximab Failure in Hospitalized Patients With Acute Severe Colitis is Effective and Safe

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz032 ◽

2019 ◽

Vol 13 (9) ◽

pp. 1105-1110 ◽

Cited By ~ 7

Author(s):

Roni Weisshof ◽

Jacob E Ollech ◽

Katia El Jurdi ◽

Olivia V Yvellez ◽

Russell D Cohen ◽

...

Keyword(s):

Adverse Events ◽

Rescue Therapy ◽

Drug Discontinuation ◽

Second Line ◽

Steroid Resistant ◽

Tertiary Centre ◽

Acute Severe Colitis ◽

To Receive ◽

Severe Colitis ◽

Steroid Refractory

Abstract Background and Aims Options for medical management of patients with acute severe colitis [ASC] failing intravenous (i.v.) steroids are limited and include rescue therapy with either infliximab or ciclosporin. In patients failing infliximab, second-line rescue therapy with ciclosporin is an alternative. The aim of this study was to investigate the efficacy and safety of ciclosporin in patients with steroid-refractory ASC failing first-line rescue therapy with infliximab. Methods This is a retrospective, tertiary centre study undertaken from 2010 to 2017. Included were patients hospitalized for ASC and treated with i.v. ciclosporin after failing i.v. steroids and infliximab within the previous 2 months. Time to colectomy, clinical response, and occurrence of adverse events were analysed. Results Forty patients with steroid-resistant ASC were included. Patients were followed for a median of 13 months (interquartile range [IQR] 5–32 months). Colectomy-free survival was 65%, 59.4%, and 41.8% at 1 month, 3 months and 1 year, respectively. Sixty percent of patients [24/40] achieved clinical remission at a median of 2 weeks [IQR 1–3 weeks]. Infliximab levels before ciclosporin infusion were available for 26 patients [median level 17.5 mg/mL, IQR 8–34 mg/mL] and were not associated with adverse events. Sixteen patients [40%] experienced adverse events after ciclosporin treatment, but none resulted in drug discontinuation. Conclusions In patients with i.v. steroid–refractory ASC who failed infliximab therapy, second-line rescue therapy with ciclosporin was shown to be effective and safe. This is the largest patient cohort to receive ciclosporin as second-line rescue therapy for ASC. We believe that ciclosporin may be offered to selected patients prior to referral for colectomy.

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