Clinical Case Summary

We report the case of a 47 year old female patient diagnosed with ulcerative colitis 8 years ago with an overall stable clinical course. Strikingly, the patient presented with bilateral upper and lower limb ischemia with gangrenous patches at the fingers and toes. In addition, she had multiple erythema nodosum and pyoderma gangrenosum at both lower limbs, upper limbs and at the back with reported acute onset over the past 5 days. (Images present) Additionally, she reported severe joint pains with overlying joint effusions over the wrists and knees. In terms of the gastrointestinal symptoms she reported 4 bowel motions per day with occasional blood. Her labs showed a fecal Calprotectin level of 581, a CRP of 63 and normal hemoglobin level at 13.8. A Doppler study of both upper and lower limbs was normal. Steroids were administered intravenously for 3 days with inadequate response. Thus, the patient was shifted to Infliximab accelerated regimen such that the three induction doses were given each one week apart. A significant improvement of the arthralgia and the dermatological manifestation was seen after the second dose with gradual improvement of the ischemic fingers and toes. Complete healing of the ischemic toes and fingers were seen at three months of medical treatment with residual nail dystrophy (Images present). The acute synchronous onset of a variety of extraintestinal manifestations (EIM) including dermatological (Eythema nodosum and pyoderma gangrenosum), rheumatological (Arthritis with joint effusion) and vascular (perihpheral gangrene) as opposed to the usual single EIM and her relatively milder colonic manifestations remains peculiar to our case. In light of the severity of this presentation, a rapid escalation of therapy was mandatory. Worth highlighting is the fact that anti-TNF and specifically Infliximab remains a most valuable and effective drug not only in acute severe ulcerative colitis but also, as in our case, in morbid extraintestinal disease.

Clinical Case Summary

A 39-year-old woman was admitted on June 20, 2024, with a right middle cerebral artery stroke, nine weeks after starting Upadacitinib for ulcerative colitis. She presented with dysarthria, dysphagia, and severe left-sided weakness. CT imaging revealed a wedge-shaped infarction without intracranial hemorrhage (CT head/ Brain MRI).
She was diagnosed with ulcerative colitis in November 2023, she initially responded to Mezavent and steroids but was hospitalized on March 31, 2024 for moderate UC flare, requiring infliximab rescue therapy. The patient presented with four bloody bowel movements and elevated inflammatory markers (CRP>100), confirmed by a Mayo score of 2 on flexible sigmoidoscopy and cytomegalovirus (CMV) infection was excluded. Clostridium difficile tests were negative twice and a CT scan revealed pancolitis. Despite minimal response to rescue therapy, she opted for medical treatment over colectomy.
On April 23, 2024, she began an eight-week induction of Upadacitinib 45 mg, which she tolerated well. However, on June 20, she developed sudden stroke symptoms while eating dinner, including difficulty swallowing, choking, left-sided weakness, and numbness. She had no vascular risk factors or family history of premature cardiovascular conditions. Lupus, and vasculitis work up were unremarkable and extensive thrombophilia screenings were all negative.
Discussion: Thrombosis in IBD patients can result from various potential causes. First of all, Inflammation and hypercoagulability, driven by elevated cytokines like TNF, interleukins, and CRP, activate the coagulation cascade, increasing thrombosis risk.
Conclusion: IBD is a known risk of thromboembolic disease, this risk increased during flare up will raise future research questions regarding extended anticoagulation prophylaxis during flare and uses of Jak stats inhibitor.

References

1. Ferro JM,Oliveira Santos M. Neurology of inflammatory bowel disease. J Neurol Sci. 2021 May 15;424:117426. doi: 10.1016/j.jns.2021.117426. Epub 2021 Mar 27.

2. Solitano V.Thrombosis in IBD in the Era of JAK Inhibition. Curr Drug Targets. 2021;22(1):126-136. doi: 10.2174/1389450121666200902164240.

3. Guiu A,a new opportunistic pathogen associated with cystic fibrosis?]Enferm Infecc Microbiol Clin. 2014 Oct;32(8):497-501. Spanish.DOI: 10.1016/j.eimc.2013.08.003

4. Tan JT, Ng DP.Genetic variation in KCNQ1 associates with fasting glucose and beta-cell function: a study of 3,734 subjects comprising three ethnicities living in Singapore.Diabetes. 2009 Jun;58(6):1445-9.DOI: 10.2337/db08-1138

5. Reddy VB.The burden of diverticular disease on patients and healthcare systems.Gastroenterol Hepatol (N Y). 2013 Jan;9(1):21-7.

6. Kim WJ.Major constituents and antimicrobial activity of Korean herb Acorus calamus.Nat Prod Res. 2011 Aug;25(13):1278-81.DOI: 10.1080/14786419.2010.513333

7. Lou JS, Effect of expectancy and personality on cortical excitability in Parkinson's disease.Mov Disord. 2013 Aug;28(9):1257-62.DOI: 10.1002/mds.25471PMID: 23630185

8. Parra-Izquierdo I,Janus kinase inhibitors ruxolitinib and baricitinib impair glycoprotein-VI mediated platelet function.Platelets. 2022 Apr 3;33(3):404-415.DOI: 10.1080/09537104.2021.1934665Epub 2021 Jun 7.

9. Kwak SH, Incidentally found resectable lung cancer with the usage of artificial intelligence on chest radiographs.PLoS One. 2023 Mar 10;18(3):e0281690.DOI: 10.1371/journal.pone.0281690PMID: 36897865;

10. Nguyen GC, et al. Consensus Statements on the Risk, Prevention, and Treatment of Venous Thromboembolism in Inflammatory Bowel Disease: Canadian Association of Gastroenterology. Gastroenterology. 2014;146(3):835–848. doi:10.1053/j.gastro.2014.01.042

Clinical Case Summary

Clinical history: Patient S., a 26-year-old female born in 1995, presented with general weakness, altered bowel habits, and the presence of blood and mucus in her stool, which first appeared after a period of psycho-emotional stress in late 2018. She had a history of UC with total large intestine involvement, confirmed by morphological examination, and had previously been diagnosed with IBS and erosive sigmoiditis.
Investigations and differential diagnoses: The patient underwent outpatient and inpatient examinations at various hospitals between August 2020 and September 2021. Laboratory findings showed elevated creatinine levels (247 mmol/l), proteinuria (0.5 g/s – 0.2 g/s), and high ESR (80-89-57 mm/h). A nephrobiopsy was performed, revealing granulomatous interstitial nephritis. Differential diagnoses may include drug-induced interstitial nephritis, sarcoidosis, and other autoimmune disorders.
Difficult aspects: The case presents a rare extraintestinal manifestation of UC, granulomatous interstitial nephritis, which may be attributed to the toxic effects of 5-ASA medications. The association between kidney damage and UC is supported by the improvement in both intestinal and renal involvement following immunosuppressive therapy.
Final diagnosis: Granulomatous interstitial nephritis as a rare extraintestinal manifestation of ulcerative colitis.
Therapeutic approach: The patient underwent pulse therapy with methylprednisolone (1000mg) three times and received mesavant (3 t/day), resulting in improved clinical and laboratory parameters.
Points to be discussed: The role of 5-ASA medication toxicity in the progression of renal failure in UC patients.
The importance of regular monitoring of renal function in UC patients, especially those on long-term 5-ASA therapy.
The efficacy of immunosuppressive therapy, including pulse therapy sessions, in managing granulomatous interstitial nephritis associated with UC.

References

Laboratory analysis data
Nephrobiopsy results

Introduction

Acute severe ulcerative colitis (ASUC) is a medical emergency requiring hospitalisation. Overtime, there has been an increasing number of biologic and non-biologic treatment options available to induce and maintain disease remission. A previous study found no significant difference in length of stay or colectomy rates for those on biologic or small molecule therapy prior to admission compared to those who were not on advanced ulcerative colitis (UC) therapies, but found they had higher rates of surgical consultation and 90-day readmission rates.¹ We aimed to evaluate the preadmission medications patients were receiving at time of ASUC presentation, and to determine whether maintenance biologic and small molecule therapy had an effect on patient outcomes, including need for rescue therapy, colectomy, total parental nutrition (TPN), length of stay (LOS), readmission rates and mortality.

Aims & Methods

A retrospective review was conducted on all ASUC presentations to a quaternary Sydney hospital over a 10-year period. A modified Truelove and Witts’ criteria was used to define ASUC.Data was collected on preadmission UC medications, including aminosalicylates, thiopurines, steroids and advanced UC therapies, including biologics and small molecule inhibitors. Outcomes assessed included need for biologic rescue therapy, colectomy, TPN, length of stay, 30- and 90-day readmission rates, and 30- and 90-day mortality rate.

Results

A total of 172 ASUC presentations were identified. Of these, 143 presentations (83%) were patients with existing diagnosis of UC. Pre-admission medications in these patients included aminosalicylates (62%, n=89), thiopurines (25%, n=36), steroids (61%, n=87), biologics (17%, n=25), and small molecule inhibitors (2%, n=3). Patients taking aminosalicylates as maintenance therapy had significantly lower rates of need for rescue therapy (32% vs 51%, p=0.015). Patients on aminosalicylates-only had lower rates of 90-day readmission compared to those on both aminosalicylates and additional advanced UC therapies (0% vs 31%, p=0.007). There was no significant difference in need for rescue therapy for those on other maintenance therapies. Patients who presented on prednisolone <20 mg/d had a significantly higher rate of 90-day readmission compared to those on a dose ≥20mg (47% vs 13%, p=0.004). Those on biologic maintenance therapy had significantly higher rates of TPN use, colectomy, 90-day readmission, 30-and 90-day mortality and mean length of stay (Table 1). Patients on small molecule inhibitors had a shorter length of stay (7±1 vs 11±9.2 days, p=0.001), but no difference in other treatment outcomes.

Conclusion

Patients with pre-existing diagnosis of UC on maintenance biologic therapy who presented with ASUC were more likely to require TPN, colectomy, 90-day readmission, 30-and 90-day mortality and longer length of stay. Patients on aminosalicylates-only had lower rates of 90-day readmission. Our study findings may reflect that patients on advanced outpatient UC therapies have a more severe phenotype translating to a more severe ASUC admission course. More research is needed to predict such markers of severity.

References

1. Sabrie, N., Jogendran, M., Jogendran, R. & Targownik, L.E. Outcomes of patients admitted with acute, severe ulcerative colitis on biologic therapy: a retrospective analysis from a tertiary referral hospital. Journal of the Canadian Association of Gastroenterology 7, 306-311 (2024).

Introduction

20-25% of ulcerative colitis (UC) patients will experience at least one episode of acute severe colitis (ASUC). Up to 20% of non-responders to medical treatment will require surgery during the index episode. For approximately one third of the patients, ASUC is the first manifestation of the disease, presenting unique challenges.

Aims & Methods

A single-center, retrospective, cohort study. We included adult patients hospitalized in our gastroenterology department with ASUC. We aim to compare the clinical outcomes between patients with new-onset and established UC.

Results

62 (33.5%) patients had new-onset UC, while 123 (66.5%) had established UC. No significant differences were found in demographic and baseline clinical characteristics of the two groups. Patients with new-onset UC experienced longer hospitalizations (19 ± 22 vs. 12 ± 11 days, P = 0.002), longer delay until receiving rescue therapy [11 days (IQR 6) vs. 6 days (IQR 8), (P = 0.014)] and more severe bacterial infections (16% vs. 4%, P = 0.005) compared with patients with established UC. Histological features of chronicity, including architectural distortion, were more frequently observed in patients with established disease. We found no significant differences in steroid response (P = 0.719), need for rescue therapy (P = 0.522), response to rescue therapy (P = 0.234), colectomy (P = 0.655), mortality (P = 0.516) and hospital readmission (P = 0.929) between groups. After one year, colectomy or death occurred in 13.5% of patients. Independent predictors of adverse outcomes included active smoking, extensive colitis, the need for rescue therapy, and severe bacterial infections — but not new-onset disease.

Conclusion

Major clinical outcomes were similar between patients with new onset and established ASUC. These findings support the efficacy of standardized, protocol-driven management in mitigating risks across both groups.

References

Ordás I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ. Ulcerative colitis. Lancet. 2012;380(9853):1606-1619. doi:10.1016/S0140-6736(12)60150-0
Hindryckx P, Jairath V, D’Haens G. Acute severe ulcerative colitis: from pathophysiology to clinical management. Nat Rev Gastroenterol Hepatol. 2016;13(11):654–664. doi: 10.1038/nrgastro.2016.116
Dhaliwal J, Tertigas D, Carman N, et al. Outcomes Following Acute Severe Colitis at Initial Presentation: A Multi-centre, Prospective, Paediatric Cohort Study. J Crohns Colitis. 2024;18(2):233-245. doi:10.1093/ecco-jcc/jjad143
Spinelli A, Bonovas S, Burisch J, et al. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Surgical Treatment. J Crohns Colitis. 2022;16(2):179-189. doi:10.1093/ecco-jcc/jjab177

Clinical Case Summary

We present a case of a 37-year-old woman with ulcerative pancolitis (diagnosis in 2004), under therapy with salicylates until 2016. At that time, the patient had a flare up with need of corticosteroid therapy and started infliximab and azhatioprine. In 2018, she was in deep remission, so azathioprine was stopped. In may 2022, the patient developed intermittent fever and palpable purpura on lower limbs. It was evaluated by Dermatology who, after extensive negative ethiological study and partial response to corticosteroids, decided to perform a skin biopsy - leukocytoclastic vasculitis. Subsequently, she started intermittent episodes of hematuria, fatigue and arthralgias. Laboratory tests showed an increase in creatinine twice above the patient's baseline value, large amounts of red blood cells in the urinary sediment and moderate (subnephrotic) proteinuria. From the additional study, only an immunoglobulin A (IgA) elevation of 538 (LSN < 400) is reported. At this time, due to suspicion of IgA nephropathy, a renal biopsy was performed, which confirmed the presence of IgA deposits in the glomerular mesangium. After ruling out infectious, autoimmune and neoplastic causes, Henoch-Schönlein purpura (non-thrombocytopenic purpura and IgA nephropathy) secondary to anti-TNFα was assumed. In an IBD meeting, it was decided to stop anti-TNF and start azathioprine. Due to gastrointestinal intolerance and herpetic infection, vedolizumab was proposed, with a favorable response so far.
The approach of the adverse effects of IBD therapy can be challenging and not very consensual, requiring a multidisciplinary discussion. Henoch-Schönlein purpura is a rare adverse effect of anti-TNFα, particularly in adulthood, which in the present case appeared several years after the start of therapy. We intend to emphasize the need for a high degree of suspicion in this condition, as an early diagnosis has an impact on discontinuation of therapy and can radically change the prognosis.

Introduction

Older adults with ulcerative colitis (UC) have greater morbidity than younger adults, yet there is paucity of data on the management and outcomes of those who present with acute severe ulcerative colitis (ASUC) in this patient population. This study aims to investigate differences in the management and outcomes between older and younger patients hospitalised with ASUC.

Aims & Methods

We conducted a retrospective study on all ASUC presentations to a Quaternary Sydney hospital over a 10-year period. A modified True-love Witts’ Criteria was used to identify ASUC as ≥6 bloody bowel motions daily and presence of at least one systemic feature, including heart rate >90 bpm, temperature >37.8°C, haemoglobin <105 g/L, and C-reactive protein (CRP) ≥30 mg/L. Older patients who presented with ASUC was defined as those ≥65 years old at time of presentation. Data collected on management included rates of rescue therapy, colectomy and TPN requirement. Data collected on outcomes included hospital length of stay and rates of ICU admission, 30- and 90-day readmission, and 30- and 90-day mortality.

Results

A total of 172 presentations met criteria for ASUC. Of these presentations, 148 patients (86.1%) were <65 years old and 24 patients (13.9%) were ≥65 years old. Median age at presentation in older adults was 73.6 years old and in younger adults was 32.0 years old. Older adults had similar rates of need for rescue therapy (37.5% vs 35.1%, p=0.08), colectomy (12.5% vs 9.5%, p=0,64) and TPN (12.5% vs 10.1%, p=0.73), as their younger counterparts. Older adults (n=6, 25.0%) had significantly higher rates of ICU admission (p<0.01) compared to those <65 years old (n=3, 2.0%). Older adults also had significantly higher 30- and 90-day mortality rates (n=3, p<0.01). There was no mortality observed in adults <65 years old. There was no significant difference in 30- and 90-day readmission rates between older adults and those <65 years old at time of ASUC presentation. Table 1 compares management and outcomes in adults <65 years old and ≥65 years old who presented with ASUC.

Table 1. Comparison of management and outcomes in adults <65 years old and ≥65 years old who presented with ASUC

Conclusion

Despite similar rates of need for rescue therapy and colectomy, older patients who present with ASUC are more likely to have poorer outcomes, with increased requirement of ICU admission and higher mortality rates compared to patients <65 years old. The higher morbidity and mortality observed in our study in older adults who present with ASUC highlights the need for further research to optimise care pathways and improve outcomes in this patient population.