case study of ulcerative colitis

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• Published: 10 September 2020
• Ulcerative colitis
• Taku Kobayashi 1 ,
• Britta Siegmund 2 ,
• Catherine Le Berre 3 ,
• Shu Chen Wei 4 ,
• Marc Ferrante 5 ,
• Bo Shen 6 ,
• Charles N. Bernstein 7 ,
• Silvio Danese 8 ,
• Laurent Peyrin-Biroulet 3 &
• Toshifumi Hibi 1  

Nature Reviews Disease Primers volume  6 , Article number:  74 ( 2020 ) Cite this article

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• Gastrointestinal diseases

Ulcerative colitis (UC) is a chronic inflammatory bowel disease of unknown aetiology affecting the colon and rectum. Multiple factors, such as genetic background, environmental and luminal factors, and mucosal immune dysregulation, have been suggested to contribute to UC pathogenesis. UC has evolved into a global burden given its high incidence in developed countries and the substantial increase in incidence in developing countries. An improved understanding of the mechanisms underlying UC has led to the emergence of new treatments. Since the early 2000s, anti-tumour necrosis factor (TNF) treatment has significantly improved treatment outcomes. Advances in medical treatments have enabled a paradigm shift in treatment goals from symptomatic relief to endoscopic and histological healing to achieve better long-term outcomes and, consequently, diagnostic modalities have also been improved to monitor disease activity more tightly. Despite these improvements in patient care, a substantial proportion of patients, for example, those who are refractory to medical treatment or those who develop colitis-associated colorectal dysplasia or cancer, still require restorative proctocolectomy. The development of novel drugs and improvement of the treatment strategy by implementing personalized medicine are warranted to achieve optimal disease control. However, delineating the aetiology of UC is necessary to ultimately achieve disease cure.

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Acknowledgements

B.S. acknowledges the DFG (German Research foundation) for funding her research (CRC-TRR 241 and CRC1340).

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Contributions

Introduction (T.H., T.K. and S.D.); Epidemiology (C.N.B.); Mechanisms/pathophysiology (B. Siegmund); Diagnosis, screening and prevention (S.C.W.); Management (M.F. and B. Shen); Quality of life (C.L.B. and L.P.-B.); Outlook (T.K.); Overview of Primer (T.K. L.P.-B and T.H.).

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T.K. receives research support from AbbVie GK, Alfresa Pharma, EA Pharma, Kyorin Pharmaceutical Co., Ltd, Mochida Pharmaceutical, Nippon Kayaku, Otsuka Holdings, Thermo Fisher Scientific and ZERIA; receives advisory fees from AbbVie GK, Activaid, Alfresa Pharma, Bristol-Myers Squibb, Celltrion, CovidienÐ, Eli Lilly, Ferring Pharmaceuticals, Gilead Sciences, Janssen, Kissei, Kyorin Pharmaceutical, Mochida Pharmaceutical, Nippon Kayaku, Pfizer, Takeda Pharmaceutical and Thermo Scientific and receives lecture fees from AbbVie GK, Astellas, Alfresa Pharma, Celltrion, EA Pharma, Gilead Sciences, Janssen, JIMRO, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku, Takeda Pharmaceutical and ZERIA. B. Siegmund received speaker’s fees from Abbvie, CED Service GmbH, Falk, Ferring, Janssen, Novartis, and Takeda (B. Siegmund served as representative of the Charité) and has served as consultant for AbbVie, Boehringer, Celgene, Falk, Janssen, Lilly, Pfizer, Prometheus and Takeda. C.L.B. receives honoraria from AbbVie and Ferring. S.C.W. reports consultancy fees from AbbVie, AbGenomics, Celltrion, Ferring Pharmaceuticals Inc., Gilead, Janssen, Pfizer, Takeda, and Tanabe and receives lecture fees from AbbVie, Celltrion, Eisai, Excelsior Biopharma Inc., Ferring Pharmaceuticals Inc., Janssen, Takeda, Tanabe, Tillotts Pharma, and TSPC (Taiwan Specialty Pharma Corp.). M.F. receives research grants from Amgen, Biogen, Janssen, Pfizer, and Takeda and receives consultancy fees from AbbVie, Boehringer-Ingelheim, Janssen, MSD, Pfizer, Sandoz, and Takeda and receives speaker fees from AbbVie, Amgen, Biogen, Boehringer-Ingelheim, Falk, Ferring, Janssen, Lamepro, MSD, Mylan, Pfizer, and Takeda. B. Shen receives consultant fees for AbbVie, Takeda and Janssen. C.N.B. has received educational grants from AbbVie Canada, Janssen Canada, Pfizer Canada, Shire Canada, and Takeda Canada and a research grant from AbbVie Canada. C.N.B. has performed contract research for AbbVie, Boehringer Ingelheim, Celgene, Janssen, Pfizer and Roche. He is on the advisory boards for AbbVie Canada, Janssen Canada, Pfizer Canada, Takeda Canada, and Shire Canada and consulted to Mylan Pharmaceuticals. S.D. receives consultancy fees from AbbVie, Allergan, Amgen, AstraZeneca, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ely Lilly, Enthera, Ferring Pharmaceuticals Inc., Gilead, Hospira, Janssen, Johnson & Johnson, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB Inc., and Vifor. L.P.-B. receives research grants from AbbVie, MSD, and Takeda and reports personal fees from AbbVie, Allergan, Alma, Amgen, Applied Molecular Transport, Arena, Biogen, Boehringer Ingelheim, BMS, Celltrion, Celgene, Enterome, Enthera, Ferring, Fresenius, Genentech, Gilead, Hikma, Index Pharmaceuticals, Janssen, Lilly, MSD, Mylan, Nestle, Norgine, Oppilan Pharma, OSE Immunotherapeutics, Pfizer, Pharmacosmos, Roche, Samsung Bioepis, Sandoz, Sterna, Sublimity Therapeutics, Takeda, Vifor, and Tillots and stock options from CTMA. T.H. has received research grants from AbbVie, EA Pharma, JIMRO, Otuska Holdings, and Zeria Pharmaceuticals and lecture fees from Aspen Japan KK, AbbVie GK, Ferring, Gilead Sciences, Janssen, JIMRO, Kissei Pharmaceutical, Mitsubishi-Tanabe Pharma, Mochida Pharmaceutical, Nippon Kayaku Pfizer, Takeda Pharmaceutical, and Zeria Pharmaceutical and advisory or consultancy fees from AbbVie, Bristol-Myers Squibb, Celltrion, EA Pharma, Eli Lilly, Gilead Sciences, Janssen, Kyorin, Mitsubishi-Tanabe Pharma, Nichi-Iko Pharmaceutical, Pfizer, Takeda Pharmaceutical, and Zeria Pharmaceuticals.

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An abnormal narrowing of the digestive tract.

An abnormal connection between two organs or spaces.

A medical sign of facial swelling with deposition of fat.

An abnormal feeling of incomplete defecation.

Dilation of the colon without any mechanical obstruction.

A repetitive invagination of colonic surface epithelium.

A collection of neutrophils in an intestinal crypt.

The presence of plasma cells beneath the base of the crypts.

A transformation of one differentiated cell type to another.

A type of colonic epithelial cell that secrete mucus.

An abnormally fragile surface of the intestine due to inflammation.

A surgically created opening of the small intestine in the abdominal wall.

A space or a cavity in a bone.

The process of formation of a kidney stone.

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Kobayashi, T., Siegmund, B., Le Berre, C. et al. Ulcerative colitis. Nat Rev Dis Primers 6 , 74 (2020). https://doi.org/10.1038/s41572-020-0205-x

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Ulcerative Colitis With an Unexpected Cause

— can the immune response to covid-19 trigger inflammatory bowel disease.

by Kate Kneisel , Contributing Writer, MedPage Today March 1, 2022

A 50-year-old male patient presented to an outpatient clinic in the spring of 2020 with fever and dyspnea; he told clinicians that the symptoms had persisted for the past 3 days.

Physical examination findings included a fever of 37.8°C (100°F), respiratory rate of 24 breaths/min, and heart rate of 105 beats/min. There was no organomegaly, and the patient was a non-smoker.

Initial laboratory test findings included:

• White blood cell count: 6.4 × 109/L
• C-reactive protein (CRP): 4.6 mg/L
• Ferritin: 162 ng/mL
• D-dimer: 842 ng/mL

Findings of a polymerase chain reaction (PCR) test for SARS-CoV-2 were negative. However, the patient's wife and two children had positive PCR test results; and the patient's CT chest scan revealed diffuse ground-glass opacities consistent with viral pneumonia. Clinicians diagnosed him with COVID-19, and he was started on a now-debunked 7-day regimen of hydroxychloroquine and azithromycin. Once he was clinically stable, he was released with instructions to return for a follow-up assessment.

He returned several weeks later with bloody diarrhea, which he explained had come on about 2 weeks after he completed COVID-19 treatment. Stool analysis revealed 10 to 12 erythrocytes and five to six leukocytes. However, there was no evidence of amoebas or Clostridium difficile A+B. Complete blood count and CRP were within normal ranges. Clinicians prescribed treatment with ciprofloxacin, metronidazole, and probiotics.

On follow-up assessment 1 week later, the patient reported no improvement in symptoms. His stool calprotectin level was 1800 μg/g (normal range: 0-50 μg/g). Endoscopy revealed a diffuse, micro-ulcerated, granulated appearance that clinicians noted continued uninterrupted from the dentate line to the sigmoid colon, as well as distortion of the submucosal vascularization.

Based on presumed diagnoses of infectious colitis and ulcerative colitis, biopsies were taken. Pathology findings included mucin loss and distortion in the colonic glands, as well as evidence of polymorphonuclear leukocytes (PMNL) and plasma cell infiltration. Clinicians also noted cryptitis and a crypt abscess between the glands; no granulomatous or specific micro-organisms were detected.

The patient was diagnosed with ulcerative colitis, which clinicians believed had been triggered by COVID-19. The patient was prescribed treatment with 5-aminosalicylic acid (5-ASA) therapy, initiated orally and by enema. After 3 days of this drug therapy, his bloody diarrhea and other symptoms resolved.

On testing, the patient's anti-SARS-CoV-2 antibodies were found to be IgG positive and IgM weak positive. A subsequent CT scan revealed significant improvement from the initial findings and evidence of a sequela lesion.

Clinicians presenting this case – which they believe is the second documentation of ulcerative colitis with COVID-19 in the literature – made the report "to show that COVID-19 can appear with other organ pathologies, in addition to upper and lower respiratory tract complaints."

The group noted that initial reports of COVID-19 from China around the time this patient was diagnosed focused only on its respiratory manifestations, so the absence of reports of diarrhea or other gastrointestinal complaints may have "led to under-recognition of these symptoms."

They noted that several studies have since reported the involvement of other organs and diarrhea symptoms. For example, a single-center study of 95 COVID-19 patients admitted to the hospital found GI symptoms in 61% (n=58) of patients overall. Of those symptomatic patients, about 12% were symptomatic on admission, and the remaining 49% developed symptoms (primarily elevated bilirubin and, to a lesser extent, diarrhea) during hospitalization, possibly aggravated by various medications, including antibiotics, researchers reported.

Those researchers found "no statistically significant difference in the general demographics or clinical outcomes between patients with and without GI symptoms." Of the 58 patients with GI manifestations , impaired hepatic function occurred in about 31% during hospitalization, compared with only 1% who were affected on initial presentation.

The next most common symptom, diarrhea (two to 10 loose or watery stools a day) was noted in 24% overall, followed by anorexia and nausea, each affecting 18%. Vomiting affected just 4% of patients.

The researchers noted that antibiotic treatment was associated with development of diarrhea ( P =0.034) and elevated bilirubin levels ( P =0.028) during hospitalization, effects that were not noted with antiviral treatment. Importantly, of the 11 patients with GI symptoms only, 12% had no evidence of COVID-19 pneumonia on imaging, that paper stated.

Authors of the current case report noted that while "COVID-19 RNA can be detected by PCR tests in the stool after respiratory samples become negative in some infected patients," it is not known how long the COVID-19 virus can remain viable in the stool.

They referred to a recent study conducted at China's Wuhan Inflammatory Bowel Disease (IBD) Center which suggested that the prompt measures taken to prevent the spread of the virus may explain why none of the 318 registered IBD patients developed COVID-19. While another case series noted diarrhea in just 3% to 5% of patients, authors of the current case report wrote that "clinicians have begun to question the prevalence of IBD as a symptom of COVID-19," citing another report in which 31% of 84 patients with COVID-19 pneumonia had diarrhea.

Case authors pointed to the other report of COVID-19 and ulcerative colitis in which a 19-year-old female from Italy "presented with fever, vomiting, bloody diarrhea, and loss of taste and smell ... a positive PCR test but no CT evidence of pneumonia, and contrast enhancement in the ileum and colon." She recovered fully, returned a negative PCR test, and was diagnosed with ulcerative colitis following an ultrasound of the small bowel on day 16, with no evidence of COVID-19 in stool samples.

Likewise, case authors noted that their patient also tested negative for COVID-19, despite CT evidence of diffuse ground-glass opacities, "the most common manifestation of COVID-19"; he also developed GI symptoms after finishing treatment for COVID-19, which improved on CT.

While noting that their patient's clinical picture was not compatible with ischemic colitis, case authors advised clinicians to also "consider ischemic colitis in the differential diagnosis of antibiotic-induced colitis." Regarding the latter, the group noted that while "late-onset antibiotic-induced colitis can occur on rare occasions," that did not apply in the current case, given his lack of symptoms for 2 weeks after antibiotic treatment, and the absence of amoeba and C. difficile toxins in stool analyses.

In this case, authors noted that their patient's clinical parameters, the presence of bloody diarrhea in the absence of a toxic condition (such as ischemia or necrosis), endoscopic and pathological findings, plus his "very rapid response to 5-ASA treatment for ulcerative colitis, and the onset of complaints after recovery from COVID-19" suggest his ulcerative colitis may have been due to an immune response triggered by COVID-19.

The group explained that the etiology of ulcerative colitis is unknown -- the disease may be induced by inflammation triggered by any condition. That their patient had no history of GI complaints; developed bloody diarrhea and abdominal pain shortly after the onset of COVID-19 symptoms; and had imaging and pathology findings compatible with ulcerative colitis "might suggest that the disease could be triggered by COVID-19," the group noted.

The high levels of angiotensin-converting enzyme-2 (ACE-2) and transmembrane serine protease required for the COVID-19 virus to enter cells are expressed by human intestines, they noted, citing emerging data suggesting the virus's effect on the GI system and liver may also be associated with hepatic cells' expression of ACE-2, "a major receptor for gastrointestinal epithelial cells and COVID-19."

Case authors observed that, while little is known about COVID-19 and inflammatory bowel disease (IBD), "the International Organization for the Study of Inflammatory Bowel Disease (IOIBD) ... recently recommended reducing corticosteroid therapy and maintaining thiopurines and biologics." In 2021, that group also released consensus recommendations regarding SARS-CoV-2 vaccination for IBD patients.

Given the dynamic course seen in COVID-19 and the increasing range of clinical symptoms being reported, "there is an urgent need to properly determine the clinical features of COVID-19," case authors wrote. They acknowledged that while the lack of PCR investigations in stool or tissue samples was a limitation in this case, there was considerable evidence to suggest that the patient did experience COVID-19.

They concluded by urging further study of the association between COVID-19 and IBD, especially ulcerative colitis, and COVID-19 testing in patients presenting with gastrointestinal complaints.

Kate Kneisel is a freelance medical journalist based in Belleville, Ontario.

Disclosures

The case report authors noted no conflicts of interest.

Primary Source

Turkish Journal of Gastroenterology

Source Reference: Aydın MF, Taşdemir H "Ulcerative colitis in a COVID-19 patient: A case report" Turk J Gastroenterol 2021; DOI: 10.5152/tjg.2021.20851.

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Gastroenterology & Hepatology

October 2023 - volume 19, issue 10, case report: medical management of acute severe ulcerative colitis.

Sudheer Kumar Vuyyuru, DM Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada  Alimentiv, London, Ontario, Canada 

Vipul Jairath, MD, PhD Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada  Alimentiv, London, Ontario, Canada  Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada

Jurij Hanžel, MD, PhD Alimentiv, London, Ontario, Canada  Faculty of Medicine, University of Ljubljana and Department of Gastroenterology, University Medical Center Ljubljana, Ljubljana, Slovenia 

Christopher Ma, MD, MPH Alimentiv, London, Ontario, Canada  Division of Gastroenterology and Hepatology, Departments of Medicine and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada

Brian G. Feagan, MD Division of Gastroenterology, Department of Medicine, Western University, London, Ontario, Canada  Alimentiv, London, Ontario, Canada  Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada

A   29-year-old female patient presented 5 years ago with bloody diarrhea, fecal urgency, and crampy abdominal pain. A colonoscopy was performed, which revealed diffuse loss of vascular pattern and superficial ulcers throughout the colon with a normal terminal ileum. Histopathologic examination of colonic biopsies showed chronic inflammatory changes with cryptitis, crypt abscesses, and architectural distortion of crypts. On this basis, the patient was diagnosed with ulcerative colitis (UC) and began receiving 5-aminosalicylic acid (4.8 g/day). After an initial period of remission, she experienced flare-ups requiring oral corticosteroids, azathioprine (2 mg/kg), and then vedolizumab (Entyvio, Takeda; 300 mg intravenously at weeks 0, 2, and 6, followed by every 8 weeks).  

The patient was in clinical remission for 2 years and then presented to the emergency department with an acute exacerbation of UC, with 20 bloody bowel movements per day. On physical examination, there was tachycardia (120 beats per minute), fever (38.3 °C), and mild tenderness in the left lower quadrant of the abdomen. Laboratory findings revealed a markedly elevated C-reactive protein (CRP; 104 mg/L) and fecal calprotectin (3000 µg/g), anemia (hemoglobin 90 g/L), leukocytosis (14,000 cells/mm 3 ), and hypoalbuminemia (28 g/L). She was hospitalized and received intravenous methylprednisolone (60 mg/day) along with other supportive measures, including thromboprophylaxis.  

Despite 48 hours of intravenous corticosteroids, the patient continued to have bloody stools (15 per day) and her CRP concentration remained elevated (98 mg/L). Flexible sigmoidoscopy showed deep ulcers and spontaneous mucosal bleeding (modified Mayo endoscopic score of 3), and histopathology indicated features of severe colitis. There was no evidence of cytomegalovirus (CMV) inclusion bodies on immunohistochemistry, and stool culture and toxin testing for Clostridioides difficile were negative. Abdominal radiograph did not demonstrate colonic dilatation.  

Infliximab (10 mg/kg) was administered as rescue therapy, and surgical consultation was obtained. Two days after the first dose of infliximab, stool frequency was still 12 times per day with blood and the CRP level was persistently high (98 mg/L). A second infusion of infliximab was administered on day 8 of hospitalization. On day 10, the patient experienced worsening abdominal pain without clinical improvement, and subtotal colectomy with temporary end ileostomy was performed. Following surgery, the patient recovered well and without any postoperative complications, and corticosteroids were rapidly tapered. Subsequently, she underwent surgery for ileal pouch formation and ileostomy closure.

Approximately one-fourth of patients diagnosed with UC will experience an acute exacerbation requiring hospital admission during their lifetime. 1 An episode of acute severe UC (ASUC) can be a life-threatening medical emergency with an overall mortality of 1%. 2 ASUC can lead to serious complications such as toxic megacolon and colonic perforation, and emergency colectomy may be needed in medically refractory cases. 3 Up to 20% of patients admitted with ASUC require a colectomy on their first admission, and this risk increases to 40% after 2 admissions. 1,4

Global hospitalization rates for UC have declined as a result of advanced biologic therapies, optimization of management algorithms, and shifting patterns in UC epidemiology. 5 Although hospitalization rates for UC are decreasing in Western nations, there has been an increase in hospitalizations in newly industrialized countries. 6 This could be attributed to increasing incidence of UC along with limited access to advanced therapies in developing countries. 7 Similarly, in a nationwide registry–based study, a declining trend in emergency colectomy rates was observed from 2000 to 2014 in the United States, while rates of elective ileoanal pouch surgery remained stable. 8 Rates of colectomy in patients with UC from 2007 to 2016 in the United States have decreased as the use of biologic drugs has increased, suggesting a potential association between advanced treatment and the reduction in need for colectomy. 9

Risk Stratification

In 1955, Truelove and Witts conducted a randomized controlled trial (RCT) of cortisone in hospitalized patients with UC in which patients with severe disease experienced worse outcomes than patients with moderate or mild disease. 10 Nearly 70 years later, the criteria that they developed to define severe disease are still commonly used. According to the Truelove and Witts definition, ASUC is characterized by the presence of 6 or more bloody stools per day and at least one of the following signs of systemic toxicity: tachycardia (mean pulse rate >90 beats per minute), fever (>37.8 °C), anemia (hemoglobin <105 g/L), and/or a raised erythrocyte sedimentation rate (>30 mm/hr). These criteria were later modified to include elevated CRP (>30 mg/L) (Table 1). 11  

Initial Management

Patients with ASUC should be admitted urgently and treated according to a standardized management approach to prevent complications. Intravenous corticosteroids remain the gold standard for initial treatment. The pooled response rate following intravenous corticosteroids is reported to be 67% (95% CI, 65-69) with a colectomy rate of 27% (95% CI, 48-76). 12 In patients requiring nutritional support, enteral nutrition is preferred over parenteral nutrition because it is associated with fewer adverse events in ASUC. 13 All patients should receive thromboprophylaxis unless there is a clear contraindication. 14 Importantly, rectal bleeding associated with ASUC is generally not a contraindication to thromboprophylaxis. Stool cultures are essential to rule out C difficile and other bacterial infections. Although C difficile infection in patients with ASUC requires appropriate antibiotic therapy, routine antibiotics are not recommended in all patients. Colonic biopsy with immunohistochemistry should be performed to exclude active CMV infection, especially in patients with a history of corticosteroid dependency. 15 Performing CMV polymerase chain reaction analysis in peripheral blood and tissues is not routinely recommended, as sensitivity and specificity are suboptimal. 16  

Predictors of Response to Corticosteroids

Corticosteroids (methylprednisolone 60 mg or hydrocortisone 300-400 mg intravenously) are generally administered for at least 3 to 5 days before proceeding to salvage therapy, as a longer course of corticosteroids is associated with increased morbidity 17 and higher doses are not superior to standard doses. 12,18 Approximately 40% of patients fail to respond to intravenous corticosteroids and are at an increased risk of complications. 3 Therefore, early identification of these patients and instituting appropriate salvage therapy are crucial.  

A number of prognostic indices comprised of clinical, endoscopic, and biochemical parameters have been developed to predict corticosteroid therapy failure and subsequent colectomy (Table 2). CRP is one of the commonly monitored biomarkers, and a persistently high CRP on day 3 of corticosteroids has been associated with corticosteroid failure. 19 Criteria developed by Travis and colleagues based on a retrospective case series of 48 patients with ASUC demonstrated that elevated stool frequency (>8 per day) or between 3 and 8 stools per day along with a CRP concentration of greater than 45 mg/L on day 3 of admission predicted an 85% likelihood of colectomy. 20 Ho and colleagues formulated a risk score using stool frequency, colonic dilatation, and serum albumin levels on day 3 as predictive variables in which patients with a score of 4 or greater had a corticosteroid failure rate of 85%. 21 Similarly, the Seo index predicted a colectomy rate of 60% and 83% after 1 and 2 weeks of corticosteroids, respectively, in patients with a score of greater than 200. 22 In the index developed by Lindgren and colleagues, CRP and stool frequency were considered predictive factors of corticosteroid response (CRP mg/L × 0.14 + number of bowel movements). 19 A score of greater than 8 on day 3 of intravenous corticosteroids was associated with colectomy in 72% of patients within 30 days.  

Some markers have been shown to be useful in predicting outcomes as early as day 1 of hospitalization. Notably, the number of systemic Truelove and Witts criteria present on admission, in addition to at least 6 bloody stools per day, has been correlated with colectomy (1 criterion: 8.5%; ≥3 criteria: 48%). 1 The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) has been used to identify high-risk patients at the time of admission. A UCEIS score of 7 or greater was shown to be associated with the need for salvage therapy in 79% (n=11/14) of patients with ASUC. 23 In a subsequent study, 100% of patients with a UCEIS score of greater than 6 on admission day and a fecal calprotectin level greater than 1000 µg/g on day 3 did not respond to corticosteroid therapy. 24 Most recently, a predictive model composed of objective parameters (serum albumin, CRP, and UCEIS score) was developed in a patient cohort from Oxford, United Kingdom, and was externally validated in 2 additional cohorts. A score of 3 or greater on the day of admission had a predictive value of 84% for corticosteroid failure. 25  

Medical Salvage Therapy

Patients who fail intravenous corticosteroids require either medical or surgical salvage therapy. Cyclosporine and in­fliximab have been systematically investigated in clinical trials and are recommended as medical salvage therapy in ASUC. In the open-label CYSIF trial, 115 patients with corticosteroid-refractory ASUC were randomized 1:1 to infliximab (5 mg/kg intravenously on days 0, 14, and 42) and cyclosporine (2 mg/kg intravenously per day for 1 week followed by oral cyclosporine). 26 The primary outcome was treatment failure (absence of clinical response at day 7, relapse between day 7 and day 98, absence of corticosteroid-free remission at day 98, a severe adverse event leading to treatment interruption, colectomy, or death). There was no statistically significant difference between infliximab and cyclosporine in treatment failure, adverse events, and colectomy-free survival at 1 year and 5 years. 27 In the subsequent open-label, pragmatic RCT CONSTRUCT, 270 patients were randomly allocated 1:1 to receive infliximab (5 mg/kg intravenously at weeks 0, 2, and 6) or cyclosporine (2 mg/kg intravenously for 7 days, followed by 5.5 mg/kg orally per day for 12 weeks). 28 No significant differences were found between the 2 drugs with respect to the primary endpoint of quality-adjusted survival, or the secondary endpoints of colectomy rates, time to colectomy, serious adverse events, and death. A meta-analysis of RCTs that investigated infliximab and cyclosporine as salvage therapy in corticosteroid-refractory UC also found no significant differences between infliximab and cyclosporine. 29 Although consensus guidelines do not favor either agent, infliximab is generally preferred at regular or accelerated dosing regimens because of ease of administration and concerns of cyclosporine-related nephrotoxicity and neurotoxicity, especially when associated with hypercholesterolemia and hypomagnesemia. Therefore, long-term use of cyclosporine is not recommended, and patients who responded to intravenous cyclosporine should be bridged to an alternative maintenance therapy such as thiopurines. 30 Thus, cyclosporine is not advisable for patients who have previously failed thiopurine therapy. 30 However, recent evidence for the use of biologics as maintenance therapies, including vedolizumab, ustekinumab (Stelara, Janssen), and ozanimod (Zeposia, Bristol Myers Squibb), following cyclosporine rescue therapy has emerged. 31-35 Additionally, there have been reports of sequential rescue therapy after failure of initial salvage therapy, but it is not recommended owing to increased risk of adverse events. 36  

Accelerated Dosing of Infliximab

Increased clearance of infliximab in patients with ASUC, especially in those with high inflammatory burden, led to the hypothesis that higher induction doses of infliximab may be needed in this population. However, the data supporting this hypothesis are conflicting.  

Several observational studies have assessed different accelerated induction regimens, including higher doses (10 mg/kg) and increased frequency of dosing than the standard dosing schedule (5 mg/kg intravenously at weeks 0, 2, and 6, followed by every 8 weeks). In a retrospective study by Kohn and colleagues, a statistically higher proportion of patients receiving a single infusion of infliximab underwent colectomy compared with patients who received more than 1 infusion (35% vs 5%; P =.001). 37 Gibson and colleagues significantly decreased colectomy rates with intensified infliximab dosing in patients with corticosteroid-refractory ASUC compared with historical controls (6.7% vs 40%; P =.039) during the induction period; however, longer-term colectomy rates were similar between standard and accelerated dosing regimens. 38 Conversely, a systematic review by Sebastian and colleagues that included 10 observational studies assessing a pooled population of 705 patients found no difference between accelerated and standard induction regimens associated with either short-term (17% vs 14.5%) or long-term (25% vs 30.7%) colectomy rates, and no significant difference in complication rates. 39 Although clinicians often use accelerated regimens as off-label therapy, the evidence supporting this practice is limited. RCTs exploring optimal dosing strategy for infliximab in ASUC (NCT02770040, 40 NCT03937609 41 ) are underway.  

Factors Influencing Response to Salvage Therapy

Despite improved management protocols and availability of biologics, short- and long-term colectomy rates with medical salvage therapy remain high (26%-47% and 36%-58% for cyclosporine, and 0%-50% and 35%-50% for infliximab, respectively). 42 To date, no validated scores exist to predict medical salvage therapy response. Age over 40 years, high CRP and low serum albumin at the time of infliximab initiation, and severe endoscopic lesions have been shown to be predictive of salvage therapy failure. 42 These factors indirectly suggest that high inflammatory burden is associated with poor response, especially for infliximab, and could be a result of increased clearance of infliximab by several mechanisms. High mucosal and systemic levels of tumor necrosis factor (TNF), which is associated with severe disease, neutralize anti-TNF antibodies, acting as an “antigen sink.” 43 Intestinal losses owing to increased gut permeability secondary to mucosal ulceration also contribute to lower drug exposure. Last, observational studies have suggested that fecal loss of anti-TNF is associated with severe disease and lower serum drug concentrations. 44 These clearance mechanisms can result in subtherapeutic infliximab levels and may contribute to poor response. 45

Tofacitinib Salvage Therapy

Tofacitinib (Xeljanz, Pfizer) is a Janus kinase (JAK) inhibitor that blocks predominantly JAK1 and JAK3 at therapeutic doses. Phase 3 pivotal studies from the OCTAVE clinical program demonstrated the efficacy and safety of tofacitinib in moderate to severe UC, leading to approval by the US Food and Drug Administration (FDA) in 2018. 46 However, concerns were raised regarding an increased risk of major adverse cardiac events and thrombotic events in patients with rheumatoid arthritis exposed to tofacitinib. 47 Consequently, the FDA issued a black box warning for all currently approved JAK inhibitors, and guidelines now recommend tofacitinib as a second-line agent after failure of anti-TNF therapy in the United States.

Case reports and series have described off-label use of tofacitinib in patients with ASUC who did not respond to corticosteroid therapy. 48,49 Conceptually, several characteristics make tofacitinib an attractive candidate for inpatient induction therapy. First, the drug is readily absorbed and symptomatic improvement can be seen as early as day 3 in moderate to severe UC. 50  Second, as a small molecule, tofacitinib is less susceptible to intestinal loss than infliximab. Third, tofacitinib has been shown to be effective in patients with moderate to severe UC who have failed anti-TNF therapy. 51 Broad-spectrum immunosuppressive effects are important limitations among patients who are at substantial risk of life-threatening infections and thromboembolic disease.  

A retrospective cohort study of tofacitinib in hospitalized pediatric patients with UC who had failed corticosteroids and infliximab demonstrated that 8 out of 11 (73%) patients were free of colectomy at 90 days and 6 (54%) were free of colectomy at 6 months. 52 In a case-control study, patients hospitalized with ASUC who received tofacitinib (n=40) were matched to controls with ASUC according to sex and date of admission (n=113). 53 The 90-day colectomy rate was significantly lower in patients managed with tofacitinib induction therapy in addition to intravenous corticosteroids (hazard ratio, 0.28; 95% CI, 0.10-0.81;  P =.018) compared with patients in the control group when adjusted for disease severity covariables. Subgroup analyses showed that this benefit was statistically significant with tofacitinib doses of 10 mg 3 times daily, but not with twice-daily dosing. Although these data are interesting, they are largely limited to retrospective case series and should not be used to inform routine clinical practice. The efficacy and safety of tofacitinib for ASUC should be assessed rigorously in an RCT.

Patients who are refractory to medical therapy should be offered surgery. Subtotal colectomy is the surgery of choice in the emergent setting. Subsequently, ileal pouch–anal anastomosis performed in a staged manner is generally the preferred approach, although some patients choose completion proctectomy with permanent end ileostomy. Emergency colectomy is associated with higher morbidity and mortality rates than semi-elective procedures, 54 so controlling inflammation promptly with timely initiation of medical therapy is important. 55 Age, longer hospital stay, superimposed infections, prior admission owing to inflammatory bowel disease, and male sex are some of the factors associated with increased mortality after emergency colectomy. 56 However, delaying the decision for surgery can be associated with increased postoperative morbidity and mortality, especially in patients exposed to intravenous corticosteroids for longer than 7 days. 57 This underscores the importance of predicting response to medical therapy early in the course of ASUC and early decision-making.  

ASUC is a potentially life-threatening condition that requires hospitalization and intensive medical and supportive management to prevent complications. Early identification of patients at a high risk for corticosteroid failure and timely initiation of salvage therapy are critical. The choice of therapy depends on several factors, including clinical, endoscopic, and laboratory parameters and prior treatment history, and should be a collective decision made by the patient and a multidisciplinary team of health care professionals comprised of the treating physician, gastroenterologists, and surgeons. Although a number of models have been developed to predict corticosteroid response in patients with ASUC, validated tools to predict the failure of medical salvage therapy are lacking.

Infliximab and cyclosporine are the only agents currently approved for medical salvage therapy, and off-label use of tofacitinib has been reported in case series. Although available data supporting use of tofacitinib in patients with ASUC are insufficient to make any recommendations, future clinical trials might shed light. Surgical decision-making should not be delayed while cycling through different agents; therefore, early prediction of response to medical therapy failure is crucial.  

Disclosures

Dr Vuyyuru has no relevant conflicts of interest to disclose. Dr Jairath has received consulting/advisory board fees from AbbVie, Alimentiv, Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris, AstraZeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Metacrine, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma, Roche, Sandoz, Second Genome, Sorriso Pharmaceuticals, Takeda, Teva, TopiVert, Ventyx, and Vividion; and speaker’s fees from AbbVie, Ferring, Bristol Myers Squibb, Galapagos, Janssen, Pfizer, Shire, Takeda, and Fresenius Kabi. Dr Hanžel has received speaker’s fees from AbbVie, Janssen, and Takeda; and consulting fees from Alimentiv. Dr Ma has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma, BioJAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Pendopharm, Pfizer, Prometheus Biosciences, Roche, Sanofi, Takeda, and Tillotts Pharma; speaker’s fees from AbbVie, Amgen, AVIR Pharma, Alimentiv, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Organon, Pendopharm, Pfizer, and Takeda; royalties from Springer Publishing; and research support from Ferring and Pfizer. Dr Feagan has received grant/research support from AbbVie, Amgen, AstraZeneca/MedImmune, Atlantic Pharmaceuticals, Boehringer Ingelheim, Celgene, Celltech, Genentech/Hoffmann-La Roche, Gilead Sciences, GlaxoSmithKline, Janssen Research & Development, Pfizer, Receptos/Celgene International, Sanofi, Santarus, Takeda Development Center Americas, Tillotts Pharma, and UCB; consulting fees from Abbott/AbbVie, Akebia Therapeutics, Allergan, Amgen, Applied Molecular Transport, Aptevo Therapeutics, AstraZeneca, Atlantic Pharmaceuticals, AVIR Pharma, Biogen, BiomX, Boehringer Ingelheim, Bristol Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring, Roche/Genentech, Galapagos, gIcare Pharma, Gilead Sciences, Gossamer Pharma, GlaxoSmithKline, Inception IBD, Johnson & Johnson/Janssen, Kyowa Kirin, Lexicon, Lilly, Lycera, Merck, Mesoblast Pharma, Millennium, Nestlé, Nextbiotix, Novo Nordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Progenity, Protagonist, Receptos, Salix Pharmaceuticals, Shire, Sienna Biologics, Sigmoid Pharma, Sterna Biologicals, Synergy Pharma, Takeda, Teva, TiGenix, Tillotts Pharma, UCB, Vertex Pharmaceuticals, Vivelix Pharmaceuticals, VHsquared, and Zyngenia; speakers bureau fees from Abbott/AbbVie, Johnson & Johnson/Janssen, Lilly, Takeda, Tillotts Pharma, and UCB; is a scientific advisory board member for Abbott/AbbVie, Allergan, Amgen, AstraZeneca, Atlantic Pharmaceuticals, Avaxia Biologics, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Centocor, Elan/Biogen, Galapagos, Genentech/Roche, Johnson & Johnson/Janssen, Merck, Nestlé, Novartis, Novo Nordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharmaceuticals, Sterna Biologicals, Takeda, Teva, TiGenix, Tillotts Pharma, and UCB; and is the Senior Scientific Officer of Alimentiv.

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22. Seo M, Okada M, Yao T, Matake H, Maeda K. Evaluation of the clinical course of acute attacks in patients with ulcerative colitis through the use of an activity index.  J Gastroenterol . 2002;37(1):29-34.

23. Corte C, Fernandopulle N, Catuneanu AM, et al. Association between the ulcerative colitis endoscopic index of severity (UCEIS) and outcomes in acute severe ulcerative colitis.  J Crohns Colitis . 2015;9(5):376-381.

24. Jain S, Kedia S, Bopanna S, et al. Faecal calprotectin and UCEIS predict short-term outcomes in acute severe colitis: prospective cohort study.  J Crohns Colitis . 2017;11(11):1309-1316.

25. Adams A, Gupta V, Mohsen W, et al. Early management of acute severe UC in the biologics era: development and international validation of a prognostic clinical index to predict steroid response.  Gut . 2023;72(3):433-442.

26. Laharie D, Bourreille A, Branche J, et al; Groupe d’Etudes Thérapeutiques des Affections Inflammatoires Digestives. Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial.  Lancet . 2012;380(9857):1909-1915.

27. Laharie D, Bourreille A, Branche J, et al; Groupe d’Etudes Thérapeutiques des Affections Inflammatoires Digestives. Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab.  Gut . 2018;67(2):237-243.

28. Williams JG, Alam MF, Alrubaiy L, et al. Infliximab versus ciclosporin for steroid-resistant acute severe ulcerative colitis (CONSTRUCT): a mixed methods, open-label, pragmatic randomised trial.  Lancet Gastroenterol Hepatol . 2016;1(1):15-24.

29. Narula N, Marshall JK, Colombel JF, et al. Systematic review and meta-analy­sis: infliximab or cyclosporine as rescue therapy in patients with severe ulcerative colitis refractory to steroids.  Am J Gastroenterol . 2016;111(4):477-491.

30. Lamb CA, Kennedy NA, Raine T, et al; IBD guidelines eDelphi consensus group. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults.  Gut . 2019;68(suppl 3):s1-s106.

31. Tarabar D, El Jurdi K, Traboulsi C, et al. A prospective trial with long term follow-up of patients with severe, steroid-resistant ulcerative colitis who received induction therapy with cyclosporine and were maintained with vedo­lizumab.  Inflamm Bowel Dis . 2022;28(10):1549-1554.

32. Shaffer SR, Traboulsi C, Krugliak Cleveland N, Rubin DT. Combining cyclosporine with ustekinumab in acute severe ulcerative colitis.  ACG Case Rep J . 2021;8(5):e00604.

33. Cohen NA, Dalal SR, Choi D, Rubin DT. Ozanimod maintenance therapy after cyclosporine induction in acute severe ulcerative colitis.  ACG Case Rep J . 2022;9(7):e00832.

34. Pellet G, Stefanescu C, Carbonnel F, et al; Groupe d’Etude Thérapeutique des Affections Inflammatoires du tube Digestif. Efficacy and safety of induction therapy with calcineurin inhibitors in combination with vedolizumab in patients with refractory ulcerative colitis.  Clin Gastroenterol Hepatol . 2019;17(3):494-501.

35. Ollech JE, Dwadasi S, Rai V, et al. Efficacy and safety of induction therapy with calcineurin inhibitors followed by vedolizumab maintenance in 71 patients with severe steroid-refractory ulcerative colitis.  Aliment Pharmacol Ther . 2020;51(6):637-643.

36. Narula N, Fine M, Colombel J-F, Marshall JK, Reinisch W. Systematic review: sequential rescue therapy in severe ulcerative colitis: do the benefits outweigh the risks?  Inflamm Bowel Dis . 2015;21(7):1683-1694.

37. Kohn A, Daperno M, Armuzzi A, et al. Infliximab in severe ulcerative colitis: short-term results of different infusion regimens and long-term follow-up.  Aliment Pharmacol Ther . 2007;26(5):747-756.

38. Gibson DJ, Heetun ZS, Redmond CE, et al. An accelerated infliximab induction regimen reduces the need for early colectomy in patients with acute severe ulcerative colitis.  Clin Gastroenterol Hepatol . 2015;13(2):330-335.e1.

39. Sebastian S, Myers S, Nadir S, Subramanian S. Systematic review: efficacy and safety of accelerated induction regimes in infliximab rescue therapy for hospitalized patients with acute severe colitis.  Dig Dis Sci . 2019;64(5):1119-1128.

40. ClinicalTrials.gov. Optimising infliximab induction therapy for acute severe ulcerative colitis (PREDICT UC). https://classic.clinicaltrials.gov/show/NCT02770040. Identifier: NCT02770040. Accessed September 9, 2023.

41. ClinicalTrials.gov. TITRATE (inducTIon for acuTe ulceRATivE Colitis). https://classic.clinicaltrials.gov/show/NCT03937609. Identifier: NCT03937609. Accessed September 9, 2023.

42. Seah D, De Cruz P. Review article: the practical management of acute severe ulcerative colitis.  Aliment Pharmacol Ther . 2016;43(4):482-513.

43. Yarur AJ, Jain A, Sussman DA, et al. The association of tissue anti-TNF drug levels with serological and endoscopic disease activity in inflammatory bowel disease: the ATLAS study.  Gut . 2016;65(2):249-255.

44. Brandse JF, van den Brink GR, Wildenberg ME, et al. Loss of infliximab into feces is associated with lack of response to therapy in patients with severe ulcerative colitis.  Gastroenterology . 2015;149(2):350-355.e2.

45. Seow CH, Newman A, Irwin SP, Steinhart AH, Silverberg MS, Greenberg GR. Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis.  Gut . 2010;59(1):49-54.

46. Sandborn WJ, Su C, Sands BE, et al; OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain Investigators. Tofacitinib as induction and maintenance therapy for ulcerative colitis.  N Engl J Med . 2017;376(18):1723-1736.

47. Ytterberg SR, Bhatt DL, Mikuls TR, et al; ORAL Surveillance Investigators. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis.  N Engl J Med . 2022;386(4):316-326.

48. Sedano R, Jairath V. High-dose rescue tofacitinib prevented inpatient colectomy in acute severe ulcerative colitis refractory to anti-TNF.  Inflamm Bowel Dis . 2021;27(5):e59-e60.

49. Gilmore R, Hilley P, Srinivasan A, Choy M, De Cruz P. Sequential use of high-dose tofacitinib after infliximab salvage therapy in acute severe ulcerative colitis.  J Crohns Colitis . 2022;16(1):166-168.

50. Hanauer S, Panaccione R, Danese S, et al. Tofacitinib induction therapy reduces symptoms within 3 days for patients with ulcerative colitis.  Clin Gastroenterol Hepatol . 2019;17(1):139-147.

51. Sandborn WJ, Peyrin-Biroulet L, Sharara AI, et al. Efficacy and safety of tofacitinib in ulcerative colitis based on prior tumor necrosis factor inhibitor failure status.  Clin Gastroenterol Hepatol . 2022;20(3):591-601.e8.

52. Constant BD, Baldassano R, Kirsch J, Mitchel EB, Stein R, Albenberg L. Tofacitinib salvage therapy for children hospitalized for corticosteroid- and biologic-refractory ulcerative colitis.  J Pediatr Gastroenterol Nutr . 2022;75(6):724-730.

53. Berinstein JA, Sheehan JL, Dias M, et al. Tofacitinib for biologic-experienced hospitalized patients with acute severe ulcerative colitis: a retrospective case-control study.  Clin Gastroenterol Hepatol . 2021;19(10):2112-2120.e1.

54. Nicholls RJ, Clark DN, Kelso L, et al. Nationwide linkage analysis in Scotland implicates age as the critical overall determinant of mortality in ulcerative colitis.  Aliment Pharmacol Ther . 2010;31(12):1310-1321.

55. Singh S, Al-Darmaki A, Frolkis AD, et al. Postoperative mortality among patients with inflammatory bowel diseases: a systematic review and meta-analysis of population-based studies.  Gastroenterology . 2015;149(4):928-937.

56. Bernstein CN, Ng SC, Lakatos PL, Moum B, Loftus EV Jr; Epidemiology and Natural History Task Force of the International Organization of the Study of Inflammatory Bowel Disease. A review of mortality and surgery in ulcerative colitis: milestones of the seriousness of the disease.  Inflamm Bowel Dis . 2013;19(9):2001-2010.

57. Saha SK, Panwar R, Kumar A, et al. Early colectomy in steroid-refractory acute severe ulcerative colitis improves operative outcome.  Int J Colorectal Dis . 2018;33(1):79-82.

58. Grant RK, Jones G-R, Plevris N, et al. The ACE (albumin, CRP and endoscopy) index in acute colitis: a simple clinical index on admission that predicts outcome in patients with acute ulcerative colitis.  Inflamm Bowel Dis . 2021;27(4):451-457.

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• What is ulcerative colitis? A Mayo Clinic expert explains

Listen to gastroenterologist William Faubion, M.D., walk through ulcerative colitis basics.

[Music playing]

William A. Faubion, Jr., M.D., Gastroenterology, Mayo Clinic I'm Dr. Bill Faubion, a gastroenterologist at Mayo Clinic. In this video, we'll cover the basics of ulcerative colitis. What is it? Who gets it? The symptoms, diagnosis, and treatment. Whether you're looking for answers for yourself or someone you love, we're here to give you the best information available.

Ulcerative colitis is an inflammatory bowel disease that causes chronic inflammation and ulcers in the superficial lining of the large intestine, also called the colon. And that includes the rectum. It's estimated that about a million Americans are living with ulcerative colitis, making it the most common form of inflammatory bowel disease. It can be painful and debilitating, occasionally leading to severe complications. It can also be emotionally stressful. And while there is no cure, once you've been diagnosed, treatment can help you get back to a much more normal and comfortable life.

Who gets it?

The exact cause of ulcerative colitis is unknown, but there are things that appear to trigger or aggravate it. It may involve an abnormal immune response against some microorganism in which your tissues are also attacked. Genetics might also play a role. You are at higher risk if a first-degree relative has it. There's also a correlation with age. Although it can show up at any stage of life, most people are diagnosed before the age of 30. And ethnicity is a risk factor. Whites have the highest risk, especially among people of Ashkenazi Jewish descent. While diet and stress don't cause ulcerative colitis, they are known to exacerbate symptoms.

What are the symptoms?

Most people have mild to moderate cases of ulcerative colitis. Although it can be more severe, you may also experience periods of remission when you have no issues at all. A person's symptoms depend on the severity of the case in the area of the colon that's involved. They usually develop over time, and they can include diarrhea, often with blood or pus, fever, fatigue, anemia, loss of appetite and weight loss, abdominal pain and cramping, rectal pain and bleeding, the need for a bowel movement, yet the inability to do so despite the urgency. And in children, delayed growth and development. Over time, ulcerative colitis can lead to other complications, such as severe dehydration, a perforated colon, bone loss, inflammation of your skin, joints and eyes. It can also increase your risk for blood clots and colon cancer. These symptoms don't automatically mean that you have ulcerative colitis. But if you're experiencing anything that concerns you, it's a good idea to make an appointment with your doctor.

How is it diagnosed?

The only way to definitively diagnose ulcerative colitis is with a biopsy after taking a tissue sample through an endoscopic procedure. But first, less invasive things can be done to rule out other causes. First, your doctor will consider your medical history. They may want to run a variety of tests or procedures. And at some point, your general practitioner may refer you to a specialist called a gastroenterologist like myself. A blood test can check for anemia and check for signs of infection. A stool study can test for white blood cells and other specific proteins that point to ulcerative colitis, as well as rule out certain pathogens. A colonoscopy may be needed. This allows your doctor to view the entirety of the large intestine using an endoscope, a small camera mounted on a thin flexible tube. They can take tissue samples for a biopsy at the same time. Or if your colon is extremely inflamed, they may do a flexible sigmoidoscopy, which only goes as far as the rectum and lower or sigmoid colon. If your symptoms are more severe, your doctor may want some imaging done. An abdominal x-ray can rule out serious complications, like a perforated colon. An MRI or CT scan can also be performed for a more detailed view of the bowel, as well as to reveal the extent of the inflammation.

How is it treated?

Although there is no cure for ulcerative colitis there are widely effective treatments, usually involving either drug therapy or surgery. Your doctor can work with you to find things that alleviate your symptoms and in some cases, even bring about long-term remission. Treatments may include anti-inflammatory drugs like corticosteroids and immune system suppressants. Certain targeted therapies directed against the immune system called biologics can help. Antidiarrheals, pain relievers, antispasmodics and iron supplements can help counter other symptoms. And surgery may be required to remove the damaged tissue. In extreme cases, the whole colon may be removed. Which sounds drastic, but this can sometimes be the best option for eliminating the pain and struggle of ulcerative colitis once and for all. Some of these therapies may have side effects themselves. So be sure to review the risks and benefits with your doctor.

Ulcerative colitis can be physically and emotionally challenging, but there are things that can help. Although there's no firm evidence that any foods cause ulcerative colitis, certain things seem to aggravate flare-ups. So a food diary can help you identify personal triggers. Beyond that, limit dairy products, eat small meals, stay hydrated, try to avoid caffeine and alcohol and carbonation. If you're concerned about weight loss or if your diet has become too limited, talk to a registered dietitian. It's important to take care of your mental health, too. Find ways to manage stress, like exercise, breathing and relaxation techniques or biofeedback. Some symptoms like abdominal pain, gas, and diarrhea can cause anxiety and frustration. That can make it difficult to be out in public for any amount of time. It can feel limiting and isolating and lead to depression. So learn as much as you can about ulcerative colitis. Staying informed can help a lot in feeling like you're in control of your condition. Talk to a therapist, especially one familiar with inflammatory bowel disease. Your doctor should be able to give you some recommendations. And you might want to find a support group for people going through the same thing that you are. Ulcerative colitis is a complex disease, but having expert medical care and developing a treatment strategy can make it more manageable and even help patients get back to the freedom of a normal life. Meanwhile, significant advances continue to be made in understanding and treating the disease and getting us closer to curing it or preventing it entirely. If you'd like to learn even more about ulcerative colitis, watch our other related videos or visit mayoclinic.org. We wish you well.

Colon and rectum

The colon is a long tube-like organ in the abdomen. It's the largest part of the large intestine. The colon carries waste to be expelled from the body. The rectum makes up the last several inches of the colon.

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Ulcerative colitis (UL-sur-uh-tiv koe-LIE-tis) is an inflammatory bowel disease (IBD) that causes inflammation and ulcers (sores) in your digestive tract. Ulcerative colitis affects the innermost lining of your large intestine, also called the colon, and rectum. In most people, symptoms usually develop over time, rather than suddenly.

Ulcerative colitis can be draining and can sometimes lead to life-threatening complications. While it has no known cure, there are several new treatments that can greatly reduce signs and symptoms of the disease and bring about long-term remission.

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Ulcerative colitis symptoms can vary, depending on the severity of inflammation and where it occurs. Signs and symptoms may include:

• Diarrhea, often with blood or pus
• Rectal bleeding — passing small amount of blood with stool
• Abdominal pain and cramping
• Rectal pain
• Urgency to defecate
• Inability to defecate despite urgency
• Weight loss
• In children, failure to grow

Most people with ulcerative colitis have mild to moderate symptoms. The course of ulcerative colitis may vary, with some people having long periods when it goes away. This is called remission.

Health care providers often classify ulcerative colitis according to its location. Symptoms of each type often overlap. Types of ulcerative colitis include:

• Ulcerative proctitis. Inflammation is confined to the area closest to the anus, also called the rectum. Rectal bleeding may be the only sign of the disease.
• Proctosigmoiditis. Inflammation involves the rectum and sigmoid colon — the lower end of the colon. Symptoms include bloody diarrhea, abdominal cramps and pain, and an inability to move the bowels despite the urge to do so. This is called tenesmus.
• Left-sided colitis. Inflammation extends from the rectum up through the sigmoid and descending portions of the colon. Symptoms include bloody diarrhea, abdominal cramping and pain on the left side, and urgency to defecate.
• Pancolitis. This type often affects the entire colon and causes bouts of bloody diarrhea that may be severe, abdominal cramps and pain, fatigue, and significant weight loss.

When to see a doctor

See your health care provider if you experience a persistent change in your bowel habits or if you have signs and symptoms such as:

• Abdominal pain
• Blood in your stool
• Ongoing diarrhea that doesn't respond to nonprescription medications
• Diarrhea that awakens you from sleep
• An unexplained fever lasting more than a day or two

Although ulcerative colitis usually isn't fatal, it's a serious disease. In some cases, ulcerative colitis may cause life-threatening complications.

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The exact cause of ulcerative colitis remains unknown. Previously, diet and stress were suspected. However, researchers now know that these factors may aggravate but don't cause ulcerative colitis.

One possible cause is an immune system malfunction. When your immune system tries to fight off an invading virus or bacterium, an irregular immune response causes the immune system to attack the cells in the digestive tract, too.

Heredity also seems to play a role in that ulcerative colitis is more common in people who have family members with the disease. However, most people with ulcerative colitis don't have this family history.

Risk factors

Ulcerative colitis affects about the same number of women and men. Risk factors may include:

• Age. Ulcerative colitis usually begins before the age of 30, but it can occur at any age. Some people may not develop the disease until after age 60.
• Race or ethnicity. Although white people have the highest risk of the disease, it can occur in any race. If you're of Ashkenazi Jewish descent, your risk is even higher.
• Family history. You're at higher risk if you have a close relative, such as a parent, sibling or child, with the disease.

Complications

Possible complications of ulcerative colitis include:

• Severe bleeding
• Severe dehydration
• A rapidly swelling colon, also called a toxic megacolon
• A hole in the colon, also called a perforated colon
• Increased risk of blood clots in veins and arteries
• Inflammation of the skin, joints and eyes
• An increased risk of colon cancer
• Bone loss, also called osteoporosis

Ulcerative colitis care at Mayo Clinic

• Feldman M, et al, eds. Epidemiology, pathogenesis, and diagnosis of inflammatory bowel diseases. In: Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management. 11th ed. Elsevier; 2021. https://www.clinicalkey.com. Accessed July 22, 2020.
• Goldman L, et al., eds. Inflammatory bowel disease. In: Goldman-Cecil Medicine. 26th ed. Elsevier; 2020. https://www.clinicalkey.com. Accessed July 22, 2020.
• The facts about inflammatory bowel diseases. Crohn's and Colitis Foundation. https://www.crohnscolitisfoundation.org/. Accessed Sept. 6, 2022.
• Ulcerative colitis. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/digestive-diseases/ulcerative-colitis. Accessed Sept. 6, 2022.
• What is ulcerative colitis? Crohn's and Colitis Foundation. https://www.crohnscolitisfoundation.org/what-is-ulcerative-colitis. Accessed Sept. 6, 2022.
• Kliegman RM, et al. Inflammatory bowel diseases. In: Nelson Textbook of Pediatrics. 21st ed. Elsevier; 2020. https://www.clinicalkey.com. Accessed July 22, 2020.
• AskMayoExpert. Chronic ulcerative colitis. Mayo Clinic; 2019.
• Abraham B, et al. Antibiotics and probiotics in inflammatory bowel disease: When to use them? Frontline Gastroenterology. 2020; doi:10.1136/flgastro-2018-101057.
• What should I eat? Crohn's and Colitis Foundation. https://www.crohnscolitisfoundation.org/diet-and-nutrition/what-should-i-eat. Accessed Sept. 6, 2022.
• Mind-body therapies. Crohn's and Colitis Foundation. https://www.crohnscolitisfoundation.org/complementary-medicine/mind-body-therapies. Accessed Sept. 6, 2022.
• Nguyen H. Allscripts EPSi. Mayo Clinic. April 1, 2022.
• Special IBD diets. Crohn's and Colitis Foundation. https://www.crohnscolitisfoundation.org/diet-and-nutrition/special-ibd-diets. Accessed Sept. 6, 2022.
• Shergill A, et al. Surveillance and management of dysplasia in patients with inflammatory bowel disease. https://www.uptodate.com/contents/search. Accessed Sept. 6, 2022.
• Kashyap PC (expert opinion). Mayo Clinic. Aug. 13, 2020.
• Kane SV (expert opinion). Mayo Clinic. Sept. 12, 2020.
• Xeljanz, Xeljanz XR (tofacitinib): Drug safety communication — Initial safety trial results find increased risk of serious heart-related problems and cancer with arthritis and ulcerative colitis medicine. U.S. Food and Drug Administration. https://www.fda.gov/safety/medical-product-safety-information/xeljanz-xeljanz-xr-tofacitinib-drug-safety-communication-initial-safety-trial-results-find-increased?utm_medium=email&utm_source=govdelivery. Accessed Sept. 6, 2022.
• Khanna S (expert opinion). Mayo Clinic. Aug. 20, 2022.
• Cohen RD, et al. Management of moderate to severe ulcerative colitis in adults. https://www.uptodate.com/contents/search. Accessed Aug. 1, 2022.
• Ulcerative colitis flare-ups: 5 tips to manage them

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Differences in Management and Outcomes of Older and Younger Adults with Acute Severe Ulcerative Colitis

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Taylor Boyd, Elizabeth Bonareri Araka, Bharati Kochar, Ashwin N Ananthakrishnan, Differences in Management and Outcomes of Older and Younger Adults with Acute Severe Ulcerative Colitis, Journal of Crohn's and Colitis , Volume 18, Issue 4, April 2024, Pages 570–577, https://doi.org/10.1093/ecco-jcc/jjad183

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Older adults with ulcerative colitis [UC] have greater morbidity than younger adults. The goal of this study was to investigate differences in the management and outcomes of older and younger patients hospitalised with severe UC.

We conducted a retrospective cohort study of patients hospitalised for acute severe ulcerative colitis requiring intravenous steroids. We compared outcomes of adults aged ≥65 years with outcomes of younger patients. Primary study outcomes included frequency and timing of medical and surgical rescue therapy during the hospitalisation, postoperative complications, frailty, and mortality outcomes up to 1 year following the hospitalisation.

Our cohort included 63 older adults [≥65 years] and 137 younger adults [14–64 years]. Despite similar disease severity at hospitalisation, older adults were half as likely to receive medical rescue therapy (odds ratio 0.45, 95% confidence interval [CI] 0.22–0.91). This difference was more striking among the frailest older adults. Older patients were similarly likely to undergo surgery but were more likely to undergo urgent or emergent procedures [50%] compared with younger patients [13%] [ p  <0.004]. The fraction of older adults at high risk for frailty increased from 33% pre-hospitalisation to 42% post-hospitalisation. Nearly one-third [27.8%] of older adults died within 1 year of hospitalisation, with half the deaths among older adults being attributable to UC or complications of UC.

In comparison with younger patients, older adults had lower frequency use of medical rescue therapy, higher rates of emergency surgery, and increased mortality within 1 year. Further research is needed to optimise care pathways in this population.

• inflammatory bowel disease
• ulcerative colitis
• surgical procedures, operative
• older adult
• emergency surgical procedure
• severity of illness

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Ulcerative colitis.

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• Continuing Education Activity

Ulcerative colitis is an idiopathic inflammatory condition of the colon that results in diffuse friability and superficial erosions on the colonic wall and associated bleeding. It is the most common form of inflammatory bowel disease worldwide. Characteristically, it involves inflammation restricted to the mucosa and submucosa of the colon. Typically, the disease starts in the rectum and extends proximally in a continuous manner. In the United States, the disease accounts for a quarter-million provider visits annually. This activity reviews the evaluation and management of ulcerative colitis and highlights the role of the interprofessional team in evaluating and improving care for patients with this condition.

• Explain the history and physical examination of patients with ulcerative colitis.
• Outline evaluation of patients with ulcerative colitis.
• Describe treatment considerations for patients with ulcerative colitis.
• Identify interprofessional team strategies for improving care coordination and outcomes in patients with ulcerative colitis.
• Introduction

Ulcerative colitis is an idiopathic inflammatory condition of the colon that results in diffuse friability and superficial erosions on the colonic wall associated with bleeding. It is the most common form of inflammatory bowel disease worldwide. It characteristically involves inflammation restricted to the mucosa and submucosa of the colon. Typically, the disease starts in the rectum and extends proximally in a continuous manner. In the United States, the disease accounts for a quarter-million provider visits annually, and medical costs directly related to the disease are estimated to exceed four billion dollars annually. [1] [2] [3]  Ulcerative has no cure and is a lifelong disorder with a significant impact on both physical and mental health.

The specific cause of inflammatory bowel disease is not known. There seems to be a primary genetic component since the most important independent risk factor is a family history of the disease (8% to 14% of patients). A first-degree relative of a patient with ulcerative colitis has a four times higher risk of developing the disease. Additionally, ulcerative colitis has a higher incidence in Jewish populations than other ethnicities.

Although there is little evidence to support this, it has been postulated that alterations in the composition of the gut microbiota and defects in mucosal immunity could lead to ulcerative colitis. Autoimmunity may also play an important role in the etiology of ulcerative colitis. [4] [5]

Some evidence suggests that smoking may be protective, but so far, no one has been able to confirm a direct relationship between the two.

• Epidemiology

Worldwide, the highest incidence and prevalence of inflammatory bowel diseases are seen in Northern Europe and North America. Inflammatory bowel disease is closely linked to a Westernized environment and lifestyle. Ulcerative colitis has an incidence of 9 to 20 cases per 100,000 persons per year. Its prevalence is 156 to 291 cases per 100,000 persons per year. Compared to Crohn disease, ulcerative colitis has a greater prevalence in adults. When considering the pediatric population, however, ulcerative colitis is less prevalent than Crohn disease.

Ulcerative colitis has a bimodal pattern of incidence. The main onset peaks between the age of 15 and 30 years. A second, and the smaller peak of incidence occurs between the age of 50 and 70 years. Though some studies show a slight predilection for men, most studies note no preference regarding sex. There is an increased prevalence of ulcerative colitis in nonsmokers or those who recently quit smoking. Additionally, smokers diagnosed with ulcerative colitis tend to have milder disease, fewer hospitalizations and need for less medication. There is evidence, though weak, that non-steroidal anti-inflammatory drug use is associated with the onset or relapse of ulcerative colitis.

There is also an association of inflammatory bowel disease with the removal of an inflamed appendix. Appendectomy before the age of twenty is associated with a decreased incidence of ulcerative colitis, whereas the opposite is true for Crohn disease. In fact, appendectomy has been shown to reduce the risk of developing ulcerative colitis by 69%. [6] [7]

• Pathophysiology

The pathophysiology of ulcerative colitis involves defects in the epithelial barrier, immune response, leukocyte recruitment, and microflora of the colon. [8] [9]

The epithelial barrier has a defect in colonic mucin and possibly tight junctions, leading to increased uptake of luminal antigens. The lamina propria of the mucosa also has an increased number of activated and mature dendritic cells, which include a large number of toll-like receptors (TLR), specifically TLR2 and TLR4. There also seems to be an atypical T-helper (Th) cell response in patients with ulcerative colitis, specifically Th2, which exerts a cytotoxic response against epithelial cells. Other immune-related factors that play a role in the pathophysiology of ulcerative colitis include tumor necrosis factor-alpha (TNF-alpha), interleukin 13, and natural killer T-cells. Levels of IgM, IgA, and IgG are elevated in inflammatory bowel disease; however, a disproportionate increase in IgG1 antibodies is found in patients diagnosed with ulcerative colitis.

Leukocyte recruitment is affected on two fronts. There is an upregulated release of the chemoattractant CXCL8 in ulcerative colitis so that leukocytes are recruited to the mucosa from systemic circulation. Additionally, there is an upregulation of mucosal cellular adhesion molecule-1 (Mad-CAM1) on the endothelium of mucosal blood vessels, which promotes leukocyte adhesion and extravasation into mucosal tissue.

Studies have shown that enteric microflora is important in the pathogenesis and severity of inflammation and disease phenotype. Ulcerative colitis seems also to result, in part, from a homeostatic imbalance between enteric microflora and the host's mucosal immunity. This results in an aberrant response to non-pathogenic bacteria.

• Histopathology

Histologically, the mucosal layer of the colon in a patient with ulcerative colitis includes infiltrates of varying density and composition, depending on the stage of the disease. These infiltrates primarily consist of lymphocytes, plasma cells, and granulocytes, with the latter being more prominent during acute flares of the disease. Additionally, goblet cell depletion, ulcerations, and alterations in mucosal crypts are sometimes apparent. These findings might also be present on histological evaluation of the distal ileum, even though ulcerative colitis is a disease confined to the colon. This is backwash ileitis.

• History and Physical

The main symptom of ulcerative colitis is bloody diarrhea, with or without mucus. Associated symptoms also include urgency or tenesmus, abdominal pain, malaise, weight loss, and fever, depending on the extent and severity of the disease. The onset of the disease is typically gradual, and patients will likely experience periods of spontaneous remission and subsequent relapses. Factors that typically exacerbate ulcerative colitis include smoking cessation and nonsteroidal anti-inflammatory drug use.

There are some extraintestinal manifestations (EIMs) that are also present in 10% to 30% of patients with ulcerative colitis. Extraintestinal manifestations associated with disease activity include episcleritis, scleritis, uveitis, peripheral arthropathies, erythema nodosum, and pyoderma gangrenosum. Extraintestinal manifestations independent of colitis activity include axial arthropathies, sacroiliitis, and ankylosing spondylitis. A significant hepatic extraintestinal manifestation of ulcerative colitis includes primary sclerosing cholangitis and is associated with a greater risk of colorectal cancer.

Diagnosis of ulcerative colitis is made clinically with supportive findings on endoscopy, biopsy, and by negative stool examination for infectious causes. Because colonic infection can produce clinical findings indistinguishable from idiopathic ulcerative colitis, microbiologic studies for bacterial infection and parasitic infestation should be included in the initial evaluation. [10] [11]

Radiologic examinations are not critical for the diagnosis but may be useful. Patients with longstanding ulcerative colitis may show a "stove-pipe" sign on double-contrast barium enema (DCBE).

Colonoscopy or proctosigmoidoscopy might reveal loss of typical vascular pattern, granularity, friability, and ulceration, which involve the distal rectum and proceed proximally in a symmetric, continuous, and circumferential pattern. The disease can range from isolated to the rectum and sigmoid colon (proctitis) to disease of the entire colon (pancolitis). Population-based studies show that, upon presentation, proctitis is found in 30% to 60% of patients, left-sided colitis is found in 16% to 45%, and pancolitis is found in 14% to 35%.

Laboratory evaluation will usually reveal an increase in inflammatory factors (ESR, CRP, leukocytosis), especially during an acute flare. Regardless of disease stage, 60% to 70% of ulcerative colitis patients are positive for perinuclear antineutrophil cytoplasmic antibodies (P-ANCA). P-ANCA is also found in a small number of patients with Crohn disease. In addition to P-ANCA, anti-saccharomyces cerevisiae antibodies (ASCA) are found in both Crohn disease and ulcerative colitis but are more prevalent in Crohn disease; therefore, testing for both P-ANCA and ASCA has some utility in distinguishing types. Testing for carcinoembryonic antigen (CEA) can also be helpful in ulcerative colitis, as higher levels can indicate a flare.

Testing for fecal calprotectin also has some utility in the diagnosis of ulcerative colitis, though it is nonspecific. Fecal calprotectin correlates with increased neutrophils in the intestine and, therefore, can be helpful in ruling out inflammatory bowel disease. Studies show that less than 1% of patients with low fecal calprotectin are likely to suffer from inflammatory bowel disease.

An endoscopy (colonoscopy) must be done at some point which will reveal:

• Fragile mucosa
• Granular mucosa
• Loss of vascular pattern
• Presence of erosions and pseudopolyposis

Multiple biopsies should be obtained to confirm the diagnosis.

When a diagnosis of ulcerative colitis is made, the most common classification system used to determine the extent and severity of the disease is the Montreal classification system. Extent (E) is determined by endoscopic evaluation and includes E1 (Proctitis), E2 (left-sided or distal colitis), and E3 (pancolitis). Symptoms and systemic findings determine severity (S). It ranges from S0 (remission) to S3 (severe).

• Treatment / Management

Treatment choice for patients with ulcerative colitis is based on both the extent of the disease and the severity. The prognosis during the first decade after diagnosis is often generally good, and most patients go into remission. Rectal application of medical therapy, via suppository or enema, is usually appropriate for isolated distal disease (proctitis); however, a rectal application is usually used in combination with systemic therapy to help target the distal colon and, therefore, decrease tenesmus.  [6] [12] [13]

First-line treatment is sulfasalazine and 5-aminosalicylates, given orally or rectally, which have a remission rate of about 50%. Glucocorticoids, orally or rectally, can be added for those who fail to achieve remission within two weeks. Except for glucocorticoids, all of these medications can be used in the maintenance of remission. Additionally, there is some evidence that probiotics are helpful in attaining remission. Fecal microbiota transplantation also shows promise in the treatment of ulcerative colitis to help establish healthy gut microbiota.

If patients are refractory to glucocorticoids, thiopurines or biological drugs can be added to therapy. Thiopurines are immunosuppressants such as azathioprine or 6-mercaptopurine. Biological drugs include anti-TNF-alpha drugs, such as infliximab, adalimumab, and golimumab. Infliximab is the most widely used for ulcerative colitis and can be used in severe cases during hospital admissions. The newest class of biological drugs are anti-adhesion molecule inhibitors, such as vedolizumab, which blocks alpha-4-beta-7 integrin.

Since patients with ulcerative colitis have reduced expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in their colonocytes, future treatment may include (PPAR-gamma) agonistic activity. PPAR-gamma is a negative regulator of NF-KB-dependent inflammation. Novel 5-aminosalicylic acid (5-ASA) analogs are being developed that have greater PPAR-gamma activity. Cardiotoxicity and metabolic toxicity restrict the use of existing PPAR-gamma agonists.

Colectomy is curative in patients with ulcerative colitis since the disease is restricted to the colon. Indications for surgery are a failure of medical therapy, intractable fulminant colitis, toxic megacolon, perforation, uncontrollable bleeding, intolerable side effects of medications, strictures, unresectable high-grade or multifocal dysplasia, cancer, or growth retardation in children. The procedure of choice is proctocolectomy with ileal pouch-anal anastomosis (IPAA); however, in patients who are ineligible for IPAA, proctocolectomy with ileostomy is a viable alternative.

Because of the risk of colon cancer, colonoscopy is recommended at regular intervals.

All patients need maintenance therapy to prevent relapse. Oral aminosalicylates are the drugs of choice, but others may respond to azathioprine and 6-mercaptopurine.

There is no specific diet for patients with ulcerative colitis, but many develop lactose intolerance. Unlike Crohn disease, there is no role for elemental or parenteral nutrition.

• Differential Diagnosis

In patients presenting with lower abdominal pain and bloody diarrhea, the following differentials should be considered:

• Crohn disease
• Parasitic colitis
• Tuberculosis
• Radiation colitis
• Colon cancer
• Toxic megacolon
• Bacterial/viral gastroenteritis

The severity of ulcerative colitis is graded from mild to severe depending upon rectal bleeding:

• Mild: Fewer than four rectal bleeding episodes per day
• Moderate: More than four rectal bleeding episodes per day
• Severe: More than four rectal bleeding episodes  per day, and the patient has systemic features of an illness combined with hypoalbuminemia

Ulcerative colitis is a lifelong illness, but the overall mortality is not greater than in the general population. However, mortality is increased in patients who develop shock and surgical complications. When the muscularis propria is involved, it may damage the nerves resulting in dilatation, aperistalsis, and ischemia (toxic megacolon). Today, toxic megacolon is the most common cause of death in ulcerative colitis. At least 5% of patients develop colon cancer, and this risk increases with the duration of the disease. Unlike Crohn disease, stricture formation is rare.

• Complications

Ulcerative colitis is a lifelong disease with periods of remission and relapse. Following complications can occur in patients suffering from ulcerative colitis:

• Leak from anastomosis
• Pelvic abscess
• Enterocutaneous fistulas
• Pouch prolapse,
• Pouchitis, acute is less than 4 weeks, chronic is more than 4 weeks
• Incontinence
• Sexual dysfunction
• Toxic  megacolon
• Colon/rectal cancer
• Deterrence and Patient Education

American College of Gastroenterology has made guidelines on preventive care in patients with ulcerative colitis. These recommendations include:

• Screening for skin malignancies, irrespective of the use of biological agents
• Assessing bone mineral density
• Be vaccinated against Herpes zoster
• Vaccinated against Pneumococcus, H. influenzae , and the flu virus
• Should not travel to areas of yellow fever without first consulting with an infectious disease expert
• Be screened for depression and anxiety
• Women with ulcerative colitis should get annual cervical cancer screening
• Pearls and Other Issues

There is an increased risk of colorectal cancer in patients with ulcerative colitis. The risk is cumulative, with a 2% chance of colorectal cancer after ten years of diagnosis, 8% after 20 years, and 20% to 30% after 30 years. Two factors associated with increased risk of colorectal cancer are the duration and extent of the disease.

• Enhancing Healthcare Team Outcomes

Ulcerative colitis is a systemic disorder with no cure. The disorder has numerous extraintestinal involvement in addition to the colon. Thus, it is best managed by an interprofessional team. All patients with the disorder need lifelong monitoring. Because of the risk of colorectal cancer, surveillance colonoscopy should occur every 1-2 years. Further, since patients are often treated with biological agents, they need to undergo screening for melanoma and nonmelanoma skin cancer.

The pharmacists should assist the team by educating the patient on the importance of medication compliance to avoid relapse. The nurse should encourage regular vaccinations, hand washing, and cancer screening. A dietary consult should be obtained to educate the patient on foods to eat and what not to eat, especially if they have a stoma. In addition, a stoma nurse should be involved in the teaching of stoma care.

An infectious disease nurse should monitor the patient in the outpatient setting to ensure that they are not immunocompromised. Social workers should be involved to ensure that the patient has ample support and finances so that the treatments are not missed. Patients with risk factors for osteoporosis need screening for bone mineral density periodically. Patients should be encouraged to undergo annual vaccination against influenza and pneumococcus. Finally, many patients with ulcerative colitis develop depression and anxiety and should be referred to a mental health counselor. [14] [15]

Ulcerative colitis has no cure, and despite treatment, many continue to have increased bouts of stool frequency. An increase in mortality is usually seen in older patients, those with complications like infection, shock, and anemia, and those who require repeated surgical interventions. Data show that when the disease involves the muscularis propria, it can lead to bowel dysmotility, necrosis, and gangrene. A certain number of patients also develop toxic megacolon with poor outcomes. It is estimated that about 5% of patients will develop colorectal cancer over time. The risk of colon cancer is higher in patients with pancolitis and in patients whose disease started before the age of 15. Overall, the quality of life in patients with ulcerative colitis is poor. [16] [17]  [Level 5]

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Disclosure: Whitney Lynch declares no relevant financial relationships with ineligible companies.

Disclosure: Ronald Hsu declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

• Cite this Page Lynch WD, Hsu R. Ulcerative Colitis. [Updated 2023 Jun 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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Patient presentation

Differential diagnosis, examination, investigations, special investigations, final outcome.

Patient is a 22 year old female who presented to the surgery department of a tertiary level hospital having been referred from a private clinic, with a two month history of severe abdominal cramps, persistent bloody and mucoid diarrhoea, weight loss and tiredness.

Acknowledgement This case study was kindly provided by Dr Monica Mercer from Immunopaedia

2 months ago: Symptoms began with abdominal cramps and an intense urge to pass stool after every meal. Her symptoms rapidly worsened with passage of stool becoming more frequent. Within two days she was passing persistently watery diarrhoea mixed with fresh blood and mucous. She was seen by her general practitioner who treated her for gastritis.

One week later she collapsed at home and was admitted to hospital for investigations. She was discharged two days later without a diagnosis.

1 month ago: Symptoms persisted and she experienced diarrhoea and vomiting after eating or drinking, which lasted for 10 days. She was admitted to hospital for rehydration and further investigations. No conclusive diagnosis was made.

Currently: Patient is passing 10-20 liquid stools per day. Diarrhoea is mucoid and bloody. Occurs day and night. Patient complains of malaise, lethargy and anorexia. She has lost 8 kg in the past 2 months.

No past surgical history No significant medical history

Family history: Mother – type 2 Diabetes Mellitus No other family members with chronic disease

No known allergies

•     Cryptosporidium,
•     Shigella,
•     salmonella,
•     E.coli,
•     Campylobacter,
•     Clostridium difficile
•     If HIV positive consider- MAC, Isospera beli, cryptosporidium, TB
• Functional bowel syndromes e.g. irritable bowel syndrome (IBS)
• Malabsorbtion
• Coeliac disease
• Inflammatory bowel disease (IBD)

Thin ill looking young woman, conscious and alert, in obvious discomfort.

Vitals : Heart rate:             80bpm Respiratory rate:     18 bpm Blood pressure:       120/70 Temperature:          37˚C

Pale mucous membranes

Abdominal examination: Guarding and tenderness noted in the left iliac fossa and hypogastrium.

No results available from previous admissions.  All results are from current admission.

Abdominal X-ray: No toxic megacolon

Gastroscopy Report: Oesophagus and gastro- oesopahageal junction were normal. Stomach mucosa was intact and normal. No gastritis, ulceration or blood was noted. Cardia was normal. Pylorus and duodenum normal.

Colonoscopy report: Very friable mucosa. Extensive ulceration with pseudopolyps, involving the rectum, entire sigmoid and left colon up to the transverse colon. Multiple biopsies of the colonic tissue were taken for histological analysis.

Histological Findings: Pathology is limited to the mucosa and submucosa. Intense infiltration of the mucosa and submucosa with neutrophils and crypt abscesses, lamina propria with lymphoid aggregates, plasma cells, mast cells and eosinophils, and shortening and branching of the crypts.

What is the Diagnosis?

Ulcerative Colitis, which is a chronic disease associated with diffuse mucosal inflammation of the colon, giving rise to significant morbidity and recurrent symptoms of intermittent bloody diarrhea, rectal urgency and tenesmus. Patients also present with fever, anemia, fatigue, weight loss, loss of appetite, loss of body fluids and nutrients, skin lesions, joint pain, and failure to grow. The latter is specifically seen in children. About half of the people diagnosed with ulcerative colitis have mild symptoms (Ulcerative colitis, no date). Onset of symptoms typically occurs between 15 and 40 years of age, with a second peak in incidence between 50 and 80 years of age.

Ulcerative colitis is closely related to another inflammatory intestinal condition called Crohn’s disease, which can lead to chronic inflammation in any part of the gastrointestinal tract. Together, these two conditions are collectively referred to as inflammatory bowel disease, or IBD. (Ulcerative colitis, no date).

Men and women are equally likely to develop ulcerative colitis. Extraintestinal manifestations may occur in up to 25% of patients. These include osteoporosis in 15%, oral ulcerations in 10%, arthritis in 5% to 10%, primary sclerosing cholangitis in 3%, uveitis in 0.5% to 3%, pyoderma gangrenosum in 0.5% to 2.0%, deep venous thrombosis in 0.3% and pulmonary embolism in 0.2%. Current cigarette smoking is associated with a reduction in the risk for ulcerative colitis, but former smokers have a higher risk of developing ulcerative colitis vs never smokers. Although the exact cause of ulcerative colitis is still unknown, there is strong evidence that primary dysregulation of the mucosal immune system causes an excessive immunologic response to normal microflora. Other contributing factors to ulcerative colitis are taken to be both genetic and environmental in nature (Richards, 2019).

What is the pathogenesis of ulcerative colitis?

What gene associations occur in ulcerative colitis?

The array of genetic polymorphisms associated with UC would point to the likelihood of abnormalities in the epithelial barrier contributing to the onset of this condition, one hypothesis supporting the presence of an epithelial cell defect that initiates the disease under pressure from the colonic microbiome (figure 4) (Fuss and Strober, 2015).

Figure 4:” Proposed mechanism of immune-mediated inflammation in UC. Inflammation in UC is initiated by release of glycolipid antigen(s) arising from genetically impaired epithelial cells under stress from exposure to components of the gut microbiome. These antigens are presented to and stimulate NK T cells in the context of CD1 on the surface of epithelial cells or on lamina propria dendritic cells. The NK T cells so stimulated cause epithelial cell damage by direct cytotoxic activity via interaction with CD1d loaded with glycolipid on the epithelial cell surface. Alternatively, the NK T cells cause epithelial apoptosis by release of IL-13 that then causes epithelial damage. Interleukin-13 also enhances inflammation by interacting with IL-13Rα2 on NK T cells, thereby inducing further NK T cell cytotoxic activity. Finally, epithelial ulceration resulting from these processes allows entry of bacterial components into the lamina propria that stimulates secondary inflammatory reactions.” Source: (Fuss and Strober, 2015)

What are Peyer’s patches?

Peyer’s patches are aggregations of lymphoid tissue, made up of lymphoid follicles located in the lamina propria of the mucosa. In adults, B lymphocytes are seen to predominate in the follicles’ germinal centers. T lymphocytes are found in the zones between follicles. With the lumen exposed to to the external environment, there are large numbers of potentially pathogenic microorganisms present. Peyer’s patches therefore carry out immune surveillance containing macrophages, dendritic cells, B-lymphocytes, and T-lymphocytes. The lymphoid tissue is covered by a special epithelium that contains specialized cells called M cells which sample antigen directly from the lumen and deliver it to antigen-presenting cells. These cells then pass to the mesenteric lymph nodes where the immune response is amplified.

How do you grade the severity of the disease?

Ulcerative Colits disease severity (based on Truelove and Witt classification):

• Symptoms Mild Severe Fulminant
• Stools per day 6 >10
• Hematochaezia Intermittent Frequent Continuous
• Temperature Normal >37.5 C
• Pulse Normal >90
• Haemoglobin Normal <75% of normal Transfusion
• ESR 30mm/hr

Download images for case

Ulcerative colitis.

Treatment and management: On admission patient was rehydrated and given Solucortef 100 mg IMI tds.  She continued to pass 10 stools the following day.

Day 3: Patient continued to experience diarrhoea and unable to tolerate food or water. Transfused with 2 units of packed cells Prescribed: Asacol 1.2g po, tds ( mesalazine ) Asacol suppository PR bds Morphine 15mg IMI PRN Flagyl 500mg tds

Day 6: Patient has continued to experience diarrhoea of watery, bloody stools. Abdominal pain has decreased and abdomen is soft and undistended. It was decided to continue medical management for a further 7 days, with the addition of: Cyclosporine 80mg IVI, infused over 2hrs Losec 20 mg po daily ( omeprazol ) Slow K rider IVI bds Slow Magnesium IVI daily Clexane 40 mg S/C daily ( enoxaparin )

Day 13: It was decided that medical management had failed as no relief of symptoms was achieved. Surgical management was therefore required.

A laparoscopic total colectomy and ileostomy was performed. Three months post surgery the patient is scheduled to return for ileal-anal pouch surgery, to eliminate the need to wear a bag.

• Ulcerative colitis (no date) MedicineNet. Available at: https://www.medicinenet.com/ulcerative_colitis/article.htm (Accessed: November 14, 2022).
• Richards, M. (2019) Immunopathogenesis of Ulcerative Colitis. USA: Maureen Richards Immunology & Microbiology: YouTube channel. Available at: https://www.youtube.com/watch?v=FnahtfSmP60 .
• Fuss, I. J. and Strober, W. (2015) “Ulcerative Colitis,” in Mucosal Immunology. Elsevier, pp. 1573–1612.

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• Case Study: Severe Ulcerative Colitis

Final diagnosis: Ulcerative Colitis

Patient: Female, 27-year-old

Ulcerative colitis signs and Symptoms: bloody diarrhoea, abdominal tenderness and crampy abdominal pain, and weight loss

Speciality: Gastroenterology and hepatology

Causes, symptoms, and treatment of severe ulcerative colitis

Ulcerative colitis is a chronic inflammatory disease of the colon and rectum. Going by the severe ulcerative colitis definition, it does not affect the upper gastrointestinal tract. It causes inflammation and ulcers in the digestive tract. It affects the inner lining of the large intestine and rectum. The symptoms of the disease develop over time; they do not appear suddenly. Although the disease can occur at any age, it is less common in children. ulcerative colitis symptoms in females

Case Review

In this case study on ulcerative colitis, a twenty seven-year-old girl was brought to the clinic with a history of prolonged diarrhoea that had lasted ten weeks and was progressive. The patient presented frequent passage of stool with small amounts of blood, abdominal pain and noticeable weight loss. She also reported bowel movements about ten times per day. On reviewing the patient, it was observed that there was fever, vomiting, jaundice, joint pains or mouth ulcers. She was suffering from crampy abdominal pain, which was neither relieved nor aggravated by any known factor. The symptoms were associated with noticeable weight loss despite a good appetite and sufficient diet. No other urinary or respiratory symptoms were reported.  On physical examination, she was pale, weighed 19 kgs and was neither irritable nor dehydrated. The rectum appeared to be narrowed, and the examination finger had stains of blood. These findings suggested the presence of ulcerative colitis.

Case Discussion

Ulcerative colitis affects adults and children globally. Currently, there is an ulcerative colitis cure for the disease. The goal of the treatment is to control the symptoms with the least possible side effects of the medicines prescribed and enable the patient to function normally. A comprehensive approach is suggested for effective treatment and management of ulcerative colitis. She should be treated and followed up by a team consisting of a gastroenterologist, paediatrician and hepatologist. The line of treatment for severe ulcerative colitis treatment depends on the severity of the infection. The signs of abdominal cramps, bloody diarrhoea, the urgency to defecate but an inability to do so, weight loss, and abdominal tenderness were indicative of mild ulcerative colitis. Medicines were prescribed to reduce inflammation and patient-reported reduction of symptoms after a continual treatment. In some instances of acute colitis ulcerative colitis complications, the patient may require surgery. However, it is complementary to the medical procedures and is advised only for preventing complications.

Clinical Symptoms

Ulcerative colitis, an inflammatory bowel disease, causes inflammation and sores in the digestive tract. The symptoms can vary depending on the location of the inflammation and its severity. The symptoms do not happen overnight but usually develop over time. The inflammation damages the inner lining of the large intestine (colon) and rectum. Some common symptoms include diarrhoea often accompanied with pus or blood, pain in the abdomen, pain in the rectum area, rectal bleeding, or blood with stool, having a feeling to defecate but not being able to despite the urgency. In severe cases, the patient may experience fatigue, weight loss and fever.

The patient had mild to moderate symptoms with bleeding, pain, and problems in passing stool.

The type of treatment depends on the reasons behind ulcerative colitis. In most cases, the treatment option includes symptomatic care, medicines to regulate bowel movement. In some cases, patients who have acute colitis may need IV fluid to restore fluid balance. Blood tests and stool tests were advised to confirm the diagnosis of ulcerative colitis. Primarily, the treatment involves medications that reduce inflammation. The medicines that work on some people may not work for another person usually, as it takes some time to identify medicines that help relieve the symptoms. As drugs have side effects, the risks and benefits were weighed before prescribing the medicines and supporting disease management. When medicines do not seem to be effective, then surgery is an option. The process involves the removal of the rectum and colon. Though disease management is a challenge, making lifestyle and diet changes can help control the symptoms. Though there is no evidence that what you eat causes ulcerative colitis, certain foods are known to aggravate the symptoms and flare-ups. Here are some general suggestions for a severe ulcerative colitis diet:

• Restrict dairy products intake: Often, problems like diarrhoea, gas, and abdominal pain can improve by limiting or eliminating the dairy products.
• Eat small meals: The symptoms often abate by consuming five to six smaller meals than two to three larger ones.
• Keep hydrated: It is best to drink as much water as possible. Consuming drinks that contain caffeine can worsen the symptoms.

In this case, the patient was put on medicines as it was a mild case of ulcerative colitis. After a few months of therapy, the patient reported relief in the symptoms. She was advised to make lifestyle changes as complementary to medicine.

With routine check-ups and adequate treatment, ulcerative colitis can be cured.  If you or someone you know is experiencing any of the symptoms above, consult the gastro & liver clinic Patna Bihar. It is best to consult gastroenterologists online free or online gastroenterologist doctors. Excellent medical assistance is available in several cities, including best physician in Jammu city, max hospital liver specialist, nor gastro liver clinic Gurgaon, the best doctor in Patna for stomach, best female gynaecologist in Jhansi, liver cirrhosis specialist doctor in India, and gastro surgeon in Delhi

1. Is the colon the same as the large intestine?

Yes, ulcerative colitis is the inflammation of the large intestine or the colon.

2. What is the most primary symptom of ulcerative colitis?

Rectal bleeding is a significant symptom. However, other symptoms presented with the disease are diarrhoea and cramping abdominal pain.

3. Can antibiotics help in curing ulcerative colitis?

Antibiotics cannot help in the cure of ulcerative antibiotics. They only help in the management of the disease.

Privacy Preference Center

Privacy preferences, nutrition counselling.

Nutrition counseling is the assessment of an individual’s dietary intake after which, they are helped set achievable goals and taught various ways of maintaining these goals. The nutrition counselor provides information, educational materials, support and follow-up care to help an individual make and maintain the needed dietary changes for problems like obesity.

Obesity/ Food allergy

I assist people dealing with weight-related health problems by evaluating the health risks and help in obesity management. I also help patients manage various food allergies.

As a hepatologist, I specialize in the treatment of liver disorders, pancreas, gallbladder, hepatitis C, jaundice and the biliary tree. I also see patients suffering from pancreatitis, liver cancers alcoholic cirrhosis and drug induced liver disease(DILI), which has affected the liver.

Gastroenterology

As a gastroenterologist, my primary focus is the overall health of the digestive system. I treat everything from acid reflux to ulcers, IBS, IBD: Crohns disease and ulcerative colitis, and colon cancer.

Endoscopy is a nonsurgical procedure to examine a person’s digestive tract. It is carried out with an endoscope, a flexible tube with a light and camera attached to it so that the doctor can see pictures of the digestive tract on a color TV monitor.

Medical Gastroenterology

Gastroenterology is a specialty that evaluates the entire alimentary tract from the mouth to anus and involves studying the diseases of the pancreas.

Liver Transplant Services

A liver transplant is a surgical procedure that removes a patient’s non-functioning liver and replaces it with a healthy liver from a deceased donor or a portion of healthy liver from a living donor. It is reserved as a treatment option for people who have significant complications due to end-stage chronic liver disease or in case of sudden failure of a previously healthy liver.

Exploring the Role of GDF-15 in Inflammatory Bowel Disease: A Case-Controlled Study Comparing Crohn's Disease and Ulcerative Colitis with Non-Inflammatory Controls

Affiliations.

• 1 Department of Medicine, First Faculty of Medicine, Charles University and Military University Hospital Prague, 169 02 Prague, Czech Republic.
• 2 Department of Military Internal Medicine and Military Hygiene, Military Faculty of Medicine, University of Defence, 500 02 Hradec Kralove, Czech Republic.
• 3 Department of Clinical Biochemistry, Military University Hospital, 169 02 Prague, Czech Republic.
• 4 Department of Food Chemistry and Analysis, University of Chemistry and Technology, 160 00 Prague, Czech Republic.
• PMID: 38668313
• PMCID: PMC11051727
• DOI: 10.3390/metabo14040185

Inflammatory bowel disease, encompassing Crohn's disease and ulcerative colitis, is a persistent immune-mediated inflammatory gastrointestinal disease. This study investigates the role of growth differentiation factor 15 in severe IBD cases, aiming to identify a reliable parameter to assess disease severity and monitor activity. We analyzed plasma samples from 100 patients undergoing biologic therapy for severe IBD and 50 control subjects. Our analysis included evaluations of GDF-15 levels, inflammatory markers, and clinical features. We employed statistical methods such as the Mann-Whitney U test, ANOVA, and Spearman's correlation for an in-depth analysis. Our results demonstrated consistently higher GDF-15 levels in patients with both Crohn's disease and ulcerative colitis compared to the control group, irrespective of the biologic treatment received. The correlation analysis indicated significant relationships between GDF-15 levels, patient age, fibrinogen, and IL-6 levels. This study positions GDF-15 as a promising biomarker for severe IBD, with notable correlations with age and inflammatory markers. These findings underscore GDF-15's potential in enhancing disease monitoring and management strategies in an IBD context and encourage further research to clarify GDF-15's role in the IBD pathophysiology.

Keywords: Crohn’s disease; GDF-15; Inflammatory Bowel Disease; ulcerative colitis.

Grants and funding

• Specific research SV/FVZ202201/Ministry of Education, Youth and Sports of the Czech Republic
• projects MO 1012 (Military University Hospital Prague, Czech Republic) and MO 1011 - Clinical Fields II (Military Faculty of Medicine, University of Defence, Hradec Kralove, Czech Republic)/Ministry of Defence of the Czech Republic

Is There a Link Between IBD and MS?

Prevalence of MS and IBD

“We don’t know how to predict who with IBD is going to get MS or vice versa, but it’s something doctors need to think about when we’re prescribing medications or treatments,” says Gil Melmed, MD , director of inflammatory bowel disease clinical research at Cedars-Sinai Medical Center in Los Angeles.

“While it’s not common to have both MS and IBD, having one of these conditions is a risk factor for having the other,” adds Brian Barry, MD , attending neurologist at MedStar Washington Hospital Center in Washington, DC. Dr. Barry notes that he has seen several patients with both conditions.

What Is IBD?

IBD is often referred to as an autoimmune disease, but Dr. Melmed prefers the term immune-mediated. “In IBD, the body is not attacking itself per se, but the immune system is being triggered by bacteria commonly found in the gut and going into overdrive,” he explains.

What Is MS?

In MS on the other hand, it’s generally thought that the immune system attacks the protective sheath, or myelin, around nerve fibers, which causes communication problems between your brain and the rest of your body. Over time, it can cause permanent damage to the nerve fibers.

IBD and MS: Some Overlapping Symptoms

How are ibd and ms connected.

Researchers don’t yet fully understand the exact connection between IBD and MS. “The gut plays a large role in the nervous system and the immune system, but we are not totally certain how that directly interacts with MS,” says Barry.

“Research has shown that the immune system is shaped by events in the gut and that immune cells in the gut can actually travel all the way to the central nervous system,” notes Carlos Camara-Lemarroy, MD , assistant professor at the University of Calgary’s Hotchkiss Brain Institute in Canada. “This is why the gut-brain axis may be important for development of MS and other inflammatory conditions.”

Whatever the exact nature of the connection between IBD and MS, there seems to be an elevated risk in people with one of the conditions to have the other as well.

The reason that’s important, Barry adds, is that anti-TNF therapy, also known as  biologics  — one of the most common classes of medication that’s prescribed for IBD —  is associated with the potential worsening of MS, as well as other demyelinating neurological conditions like transverse myelitis and optic neuritis. “It’s not entirely clear, but that’s definitely a conversation that I as a neurologist would want to have with a patient’s gastroenterologist,” he says.

On the other hand, there are also classes of drugs that are effective in both IBD and MS. “For example, there’s a drug called natalizumab that’s approved for both MS and CD, and a newer drug called ozanimod that’s approved for MS and UC,” Melmed says. “So in instances where the two conditions overlap, those might be drugs to consider.”

“There would be an opportunity there to potentially treat the patient with one of these medications, as long as the gastroenterologist is in agreement as well,” adds Barry.

Melmed is quick to add that people who have IBD or MS shouldn’t necessarily rush to be tested for the other condition unless their symptoms clearly indicate that they might have both. “It’s not an easy, clear-cut diagnosis in someone who isn’t symptomatic, so it isn’t feasible to do MRI scans for MS in everyone with IBD.”

However, given the increased prevalence of MS in people who have IBD, Barry recommends that people with IBD get a referral to a neurologist if they experience weakness, tingling or numbness, or trouble walking.

Risk Factors and Prevention

• Higher socioeconomic status
• Vitamin D deficiency
• Cold climate

Other common risk factors include:

Editorial Sources and Fact-Checking

Everyday Health follows strict sourcing guidelines to ensure the accuracy of its content, outlined in our editorial policy . We use only trustworthy sources, including peer-reviewed studies, board-certified medical experts, patients with lived experience, and information from top institutions.

• Kadowaki A et al. The Gut-CNS Axis in Multiple Sclerosis. Trends in Neurosciences . August 2020.
• Alkhawajah M et al. Multiple Sclerosis and Inflammatory Bowel Diseases: What We Know and What We Would Need to Know! Multiple Sclerosis Journal . October 2012.
• Wang X et al. Multiple Sclerosis and Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. Annals of Clinical and Translational Neurology . February 2022.
• Inflammatory Bowel Disease (Overview). Cleveland Clinic. May 3, 2021.
• Symptoms & Causes of Multiple Sclerosis. Mayo Clinic. December 24, 2022.
• Bourre B et al. Multiple Sclerosis and Bowel Symptoms: Frequency and Barriers to Their Management. Multiple Sclerosis and Related Disorders . October 2023.
• Bowel. MS Society UK.
• Morís G. Inflammatory Bowel Disease: An Increased Risk Factor for Neurologic Complications. World Journal of Gastroenterology . February 2014.
• Yang Y et al. Acute Transverse Myelitis in an Adult-Patient With Underlying Ulcerative Colitis: A Case Report. BMC Gastroenterology . April 2022.
• Transverse Myelitis. National Institute of Neurological Disorders and Stroke. February 22, 2024.
• Keogh C et al. Myelin as a Regulator of Development of the Microbiota-Gut-Brain Axis. Brain, Behavior, and Immunity . January 2021.
• Inflammatory Bowel Disease (IBD). Mayo Clinic. September 3, 2022.

Related Topics

• Ulcerative Colitis vs. Crohn's
• Omeprazole Side Effects

• Case report
• Open access
• Published: 01 May 2024

Mycophenolate-induced colitis in a patient with lupus nephritis: a case report and review of the literature

• Ziyad Alakkas 1 ,
• Abdulaziz M. Gari 2 ,
• Sara Makhdoum 3 &
• Eman A. AlSindi 2  

Journal of Medical Case Reports volume  18 , Article number:  229 ( 2024 ) Cite this article

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Mycophenolate mofetil (MMF) is an immunosuppressive drug that is frequently prescribed to patients with rheumatological diseases. MMF’s side effects include abdominal discomfort, nausea, vomiting, and other gastro-intestinal side effects, which typically appear in the first few months of treatment. However, late-onset diarrhea does not rule out the presence of MMF-induced colitis, which can be misdiagnosed since it is linked to a broad range of histopathological characteristics, including alterations that resemble inflammatory bowel disease, graft-versus-host disease, and ischemia. The differences in treatment response may be explained by the complexity of the histopathologic characteristics.

Case presentation

Here we present a case of a 29-year-old Arabian female with lupus nephritis who started on MMF as induction therapy. In two months, the patient was presented to the Emergency Department with diarrhea and manifestations of severe dehydration. Infectious diseases and adverse drug events were suspected, so the patient was admitted for further workup, and MMF was stopped. The patient was diagnosed with MMF-induced colitis based on colonoscopy and histological findings. Fourteen days after stopping MMF, she was within her baseline.

The purpose of this paper is to report a case of early-onset MMF-induced colitis in a patient with lupus nephritis who had started MMF as induction therapy. A review of the available literature on this uncommon immunosuppressive effect is also presented.

Peer Review reports

Introduction

Mycophenolate mofetil (MMF) is widely used as an immunosuppressive agent for various inflammatory and/rheumatic conditions, including lupus nephritis and organ transplantation. Mycophenolic acid is an active metabolite of MMF that reversibly inhibits inosine monophosphate (IMP) dehydrogenase, preventing purine synthesis in T and B cells [ 1 , 2 ]. Dose modification or even discontinuation of MMF is quite common due to adverse effects, especially gastro-intestinal side effects, which occur in nearly 45% of cases [ 2 ]. Enterocytes are particularly susceptible to the antimetabolic effects of MMF due to their reliance on the de novo process of purine synthesis. This prevents the growth and reproduction of small bowel epithelial cells, which disrupts fluid absorption and causes diarrhea [ 3 , 4 ]. However, MMF is a well-tolerated therapy in general.

One of the major adverse effects of MMF is colitis, which can lead to serious complications that include perforation, bleeding, and hospitalization. In recent years, several studies have investigated the factors associated with MMF-induced colitis. One study evaluated the incidence of gastro-intestinal complications following kidney transplant and showed that MMF-induced colitis was the most common type of colitis, occurring in 6–9% of patients, and the most common symptom was diarrhea [ 5 , 6 ]. MMF is one of the common immunosuppression medications for rheumatological disease and has been used for the last two decades with very good outcomes in terms of different aspects and system involvement.

There are only a few reports of patients who developed MMF-related colitis (Table  1 ). A small retrospective study evaluated 11 patients with rheumatologic disease who had been treated with MMF and found that only one patient had medication-related colitis [ 7 ]. We report a case of a young female who had systemic lupus erythematosus and lupus nephritis and presented with abdominal pain and diarrhea. We also discuss the challenges in the diagnosis of MMF-induced colitis.

Written consent was obtained from the patient, and ethical approval was provided by the Institutional Review Board (IRB) of the Study and Research Department of King Fahad Hospital, Jeddah.

The patient was a 29-year-old Arabian woman with a known case of systemic lupus erythematosus, which had been diagnosed 5 years prior based on the criteria of the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR). She was started on hydroxychloroquine at 200 mg orally once per day, and she had no comorbidities except for hypothyroidism.

The patient had not been followed up due to the COVID-19 pandemic, but in January 2023, she presented to the clinic with an incidental lab result showing a creatinine level of 4.3 mg/dL. Thus, a renal biopsy was planned, and she was diagnosed with class IV lupus nephritis. She received pulse methylprednisolone therapy at 500 mg intravenously for 3 days, which was then switched to a tapering dose of prednisolone. Induction therapy using MMF was initiated at 500 mg orally twice daily then titrated up weekly until she was discharged to home on 1.5 g orally twice per day, which is the maximum recommended dose of induction phase for lupus nephritis.

After 2 months, the patient presented to the emergency department with complaints of nausea, vomiting, and left-sided abdominal pain associated with diarrhea 5–6 times per day, which was watery but contained no blood or mucus. Her symptoms started at just 2 weeks after starting MMF therapy and had progressed over the last month. She denied having fever, weight loss, or night sweats. Upon physical examination, she was alert and oriented but in pain. The abdomen was tender, but there were no signs of peritonitis. The rest of the physical examination was unremarkable apart from Cushingoid face. She was afebrile, and her blood pressure, heart rate, respiratory rate, and oxygen saturation were within normal ranges. Her weight was 90 kg.

Upon admission, MMF was promptly discontinued due to the possibility that it might have led to an infection. The immediate care involved the delivery of intravenous fluids, a low-residue diet, analgesic medications like intravenous acetaminophen, and antispastic treatments. Routine blood tests performed at admission indicated leukopenia 3.800 × 10 6 /L normal range (4–11 × 10 6 /L), elevated creatinine 6.3 mg/dL normal range (07–1.3 mg/dL) while her baseline of creatinine was 2 mg/dL and GFR 60 ml/min, and noticeably increased inflammatory markers (C-reactive protein 32 mg/dL normal range < 5 mg/dL, erythrocyte sedimentation rate 40 mm/hour normal range < 20 mm/hour). The C3 and C4 complement levels were 0.6 g/L (0.8–1.6 g/L) and C4 0.18 g/L (0.20–0.65 g/L), respectively. Stool analysis indicated + 2 pus cells and a negative culture. Urine analysis indicated a protein level of + 1 with no red blood cell crystals or casts. An abdominal ultrasound was performed, but the result was unremarkable.

Later, computed tomography scan was performed, which did not reveal any other abnormalities and confirmed the ultrasound results. A colonoscopy showed erythematous patches with few erosions and rectal-sparing colitis. Multiple biopsies been taken (Fig.  1 ). Infectious colitis, drug-induced colitis, newly diagnosed inflammatory bowel disease (IBD), gastro-intestinal involvement associated with systemic lupus erythematosus, and mesenteric ischemia were all considered in the differential diagnosis. Cytomegalovirus (CMV) infection is the main concern among infectious causes of colitis in patients with impaired immune systems, and its possible endoscopic findings include diffuse erythema, ischemia, erosions, and ulcers.

Colonoscopy shows hyperemic mucosa with some superficial ulcers from sigmoid up to the cecum, while the terminal ileum shows superficial ulceration with some area of inflammatory patches

The endoscopic appearance of drug-induced colitis can resemble that of ulcerative colitis, infectious colitis, and ischemic colitis. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common cause of drug-induced colitis, but MMF was probably involved in the present case. Rectal sparing almost always occurs in MMF-induced colitis. Microscopically, the colonic mucosa displayed a mild architectural distortion, with ruptures of few dilated glands. Mild cryptitis is observed. However, no obvious apoptosis seen as been previously described in few cases of MMF induced colitis. There were no evidence of viral cytopathic changes, granuloma, dysplasia or malignancy (Fig.  2 A–D),

Mycophenolate Mofetil induced colitis. A Colonic biopsy with mild architectural distortion, crypt hyperplasia and lamina propria inflammation (HEx 4 ×). B Higher magnification (HE 20 ×) show dilated colonic glands. C Destructed ruptured colonic glands with mucin spillage (HE × 20 ×). D Acute inflammation within the glands (cryptitis), at high power magnification (HE x 40 ×)

Following the cessation of MMF, the gastro-intestinal symptoms and the biomarkers for systemic inflammation gradually subsided and returned to base line levels after 14 days without further therapy, thus supporting the suspicion of drug-induced colitis. The patient was discharged 24 days after admission, MMF was discontinued, and the Euro-Lupus protocol was started with cyclophosphamide as induction therapy for lupus nephritis. The patient has been followed up closely and has shown improvement of active and chronic issues with 6 doses of cyclophosphamide completed. Azathioprine with a low dose of steroid was initiated. There have been no other gastro-intestinal manifestations.

MMF is an immunosuppressive medication that was first used to decrease the risk of organ rejection after transplantation, but now, it is also being used to treat patients with autoimmune systemic disorders, including systemic lupus erythematosus. The target dose of MMF for the treatment of Lupus Nephritis is 2–3 g per day in combination with glucocorticoids especially for those high-risk patients for kidney failure including reduced GFR. Dosage may need to be adjusted according to adverse events, toxicity, efficacy and MPA blood level [according to 2019 European Leage Against Rheumatism and European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendation for the management of Lupus Nephritis]. General recommendation to not exceed 2 g in patients with chronic renal failure with GFR less than 25 mL/min.

As far as we are aware, there have been only a few documented cases of colitis caused by MMF in a patient with a rheumatological condition. The onset of MMF-induced colitis in a patient with lupus nephritis, sclerosis, mixed connective tissue disease (MCTD), and polymyositis has previously been documented by other authors (Table  1 ). In transplant recipients, however, MMF is a well-known trigger of drug-induced colitis [ 6 ].

Mycophenolate targets tissues with fast cell division and reliance on purine synthesis. Lymphocytes and gut cells are the two main organs in which regeneration is dependent on this system. Immunosuppression results from lymphocytes (B and T cells) being more dependent on this route (by 90%) [ 8 ]. The blood level of mycophenolic acid is directly inversely correlated with mycophenolate’s adverse effects [ 9 ]. Since 50% of enterocytes rely on the mycophenolate-targeting mechanisms, it is believed to explain why 45% of patients experience gastro-intestinal side effects, including simple diarrhea, esophagitis, gastroesophageal reflux disease, enteritis, and colitis, as in our patient [ 2 ]. The most typical gastro-intestinal mucosal pattern associated with MMF is mucosa that seems normal [ 10 ]. The histological changes in patients receiving MMF have mostly been classified in many studies as normal or near normal in around one-third of cases, followed by changes resembling IBD, graft-versus-host disease (GVHD), self-limited colitis, and ischemia [ 11 , 12 , 13 ]. Another study reported histological results that were in line with an acute colitis-like pattern in half of cases as being the most common, followed by IBD-like pathologic findings in 36% of cases, ischemia-like characteristics in 5.6% of cases, and GVHD-like abnormalities in 8.3% of cases [ 6 ]. Examples of specific histological characteristics of MMF-related colitis include crypt architectural disarray, increased lamina propria inflammation, dilated damaged crypts, increased crypt epithelial apoptosis, and GVHD-like alterations [ 14 ].

The wide morphological spectrum documented in MMF-induced colitis includes features that can lead to misdiagnosis and delayed intervention. Therefore, it is essential to discuss the clinical history of MMF therapy with pathologists and to take this diagnosis into consideration, regardless of the length of therapy, given the variations in the therapeutic management and prognosis of these disorders. The most frequent indication for a colonoscopy referral for patients on MMF medication is diarrhea. Nearly half of such patients have normal colonoscopy results. Other endoscopic findings include erythema (33%) and erosions/ulcers (19%), which indicate a need for routine biopsies to help with confirmation of the diagnosis [ 6 ].

Treatment options range from stopping MMF use to using specialized immunosuppressive medications to correct the histological pattern replicated by MMF-induced colitis. There are no recommendations available to help clinicians treat colitis induced by MMF. Case reports have frequently shown that after stopping MMF, diarrhea symptoms improve within a week. In another study, after unsuccessful attempts with MMF cessation, a patient was given 50 mg of intravenous steroids daily for two weeks and a single infusion of 5 mg/kg of infliximab, which led to decreased stool frequency within three days after infusion [ 28 ].

It is well known that MMF causes drug induced colitis with a variety of patterns and clinical manifestations. When caring for people with autoimmune systemic disorders, colitis should be recognized as a rare side effect of MMF therapy. It is necessary for physicians to be aware that discontinuing the medicine is typically effective without the need for extra treatments.

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Abbreviations

• Mycophenolate mofetil

Mycophenolate sodium

Inosine monophosphate

Gastro-intestinal

Inflammatory bowel disease

Cytomegalovirus

Polyendocrinopathy-candidiasis-ectodermal dystrophy

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Alakkas, Z., Gari, A.M., Makhdoum, S. et al. Mycophenolate-induced colitis in a patient with lupus nephritis: a case report and review of the literature. J Med Case Reports 18 , 229 (2024). https://doi.org/10.1186/s13256-024-04539-7

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DOI : https://doi.org/10.1186/s13256-024-04539-7

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Food & Function

6-gingerol ameliorates ulcerative colitis by inhibiting ferroptosis based on the integrative analysis of plasma metabolomics and network pharmacology.

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W. Li, Y. Zhang, Q. Wang, Y. Wang, Y. Fan, E. Shang, S. Jiang and J. Duan, Food Funct. , 2024, Accepted Manuscript , DOI: 10.1039/D4FO00952E

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