Clinical Case Summary

Discussion: This opportunistic infection affects patients with UC who are receiving immunosuppressants and biological therapy, especially anti-TNF (1). Two-thirds of patients debut with pneumonia, as in the presented case. Its clinical course is subacute or chronic, granulomatous, affecting the lungs and may test positive with Ziehl-Neelsen staining, resembling tuberculosis, which is the main differential diagnosis (3-4). In comparison to other biologics, infliximab carries a higher risk of opportunistic infections. (2-5). The initial treatment is 14 days with an aminoglycoside followed by 6 months with trimethoprim/sulfamethoxazole (1-6). Vedolizumab has a local intestinal effect without systemic effects. It is likely to reduce relapses and new opportunistic infections. However, randomized studies of these scenarios are needed (8). Conclusion: Nocardiosis is an opportunistic infection that requires a high level of suspicion for its diagnosis in patients with UC.

References

1. Ali T, Chakraburtty A, Mahmood S, Bronze MS. Risk of Nocardial Infections With Anti-tumor Necrosis Factor Therapy. Am J Med Sci. agosto de 2013;346(2):166-8.
2.Verma R, Walia R, Sondike SB, Khan R. Pulmonary nocardiosis in an adolescent patient with Crohn’s disease treated with infliximab: a serious complication of TNF-alpha blockers. W V Med J. 2015;111(3):36-9.
3. Alonso-Sierra M, Calvo M, González-Lama Y. Nocardia and Aspergillus Coinfection in a Patient with Ulcerative Colitis during Golimumab Therapy. J Crohns Colitis. septiembre de 2016;10(9):1127-8.
4. Abreu C. Nocardia infections among immunomodulated inflammatory bowel disease patients: A review. World J Gastroenterol. 2015;21(21):6491.
5. Drone E, McCrory A, Lane N, Fiala K. Disseminated nocardiosis in a patient on infliximab and methylprednisolone for treatment-resistant Sweet′s syndrome. Indian Dermatol Online J. 2014;5(3):300.
6. Parra MI, Martinez MC, Remacha MA, et al. Pneumonia due to Nocardia cyriacigeorgica in a patient with Crohn’s disease treated with infliximab. J Crohns Colitis. diciembre de 2008;2(4):331-2
8. Rahier JF, Magro F, Abreu C, Armuzzi A, Ben-Horin S, Chowers Y, et al. Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis. 1 de junio de 2014;8(6):443-68.

Disclosure

We have no conflicts of interest

Introduction

Acute Severe Ulcerative Colitis (ASUC) is a serious, potentially life-threatening condition. Hospital admission and prompt medical therapy with intravenous steroids is crucial, but rescue medical therapy with infliximab is frequently needed. Despite its frequency and relevance, there is no clear evidence about the optimal infliximab (IFX) dosing and timing in this context.

Aims & Methods

In a prospective multicentre, international cohort study, consecutive patients hospitalized for ASUC between 2/2019-1/2020 were included. The primary outcome was surgery during the first 90 days after admission (failure of medical treatment). For this analysis we identified and analyzed all patients receiving IFX as rescue therapy during the index admission. We used descriptive statistics along with non-parametric tests to determine patient characteristics and outcomes between IFX usage patterns.

Results

A total of 823 patients from 123 centers in 32 countries in five continents were included (median age 39 years [IQR, 28-54], 56% male, 64% non-smokers). IFX was started in 159 patients (19%) after a median of 6 days (IQR, 4-8) after starting steroids, with 27% after >7 days. The initial IFX dose was mostly 5 mg/kg (74%), followed by 10 mg/kg (23%). The overall response was considered adequate in 74%, this was numerically superior among those receiving 10 mg/kg (83% vs 74%, p=0.5). In 41 patients a second dose of IFX (26%) was administered during the admission. After a first dose of IFX 5 mg/kg or 10 mg/kg, most patients received a subsequent infusion with the same dosing (92% and 79%, respectively). Colectomy was performed in 35 patients (22%), without statistically significant differences between those with an initial dose of 5 or 10 mg/kg (23% vs 19%, p=0.6).

Conclusion

IFX is a relevant rescue therapy, required in around one in five patients with ASUC. Most patients receive 5 mg/kg, and this is usually followed by the same dosage. Still a proportion of patients receive higher doses with 10 mg/kg, but colectomy risk remains similar between both groups.

Introduction

Rescue treatment is administered to patients with acute severe ulcerative colitis (ASUC) who do not respond sufficiently to the initial treatment with intravenous (iv) corticosteroids. Gastrointestinal ultrasound (GIUS) can be used to detect the degree of inflammation in ulcerative colitis and show response in the treatment of ASUC^1,2, but can it be used to detect treatment response of rescue treatment?

Aims & Methods

Can GIUS be used for early prediction of treatment response in patients receiving rescue treatment for ulcerative colitis?
Patients with ulcerative colitis were included from June 2020 to Nov 2024 at two hospitals in Bergen, Norway and treated with iv corticosteroids. At day 3 to 5 patients with insufficient clinical response were treated with infliximab (10mg/kg) as rescue. The patients were examined with GIUS before rescue treatment (baseline), at the day of the 2nd infusion (after 1-2 weeks) and after 3 months. Bowel wall thickness (BWT), bowel wall vessel density with colour Doppler, loss of haustration and fatty tissue reaction was registered for every segment of the colon as well as an activity score (UC-score) based on these parameters³. The two main outcomes of the study based on the partial MAYO score (pMAYO) at 3 months. Clinical response was defined as a change in pMAYO ≥ 3 points and ≥ 30% and with an absolute reduction in the rectal bleeding score ≥ 1 or with the score for rectal bleeding ≤ 1. Clinical remission was defined as pMAYO ≤2.

Results

68 patients with colitis were recruited and of these 37 failed the initial treatment with iv corticosteroids and were given rescue treatment. At baseline 8 had left-sided colitis while 29 had subtotal or total colitis. After 3 months 3 patients had received surgery, 28/34 had treatment response compared to baseline and 24/34 were in remission. There were significantly more patients with left-sided colitis in remission (p=0.034). At the 2^nd infusion there were no significant differences between responders and non-responders for the GIUS parameters, but patients in remission at 3 months had significantly lower BWT in the ascending colon (1.3 ±0.5 vs 2.9 ±2.2 mm, p=0.002) and the transverse colon (1.7 ±0.9 vs 2.8 ±0.9 mm, p<0.001), lower sum of BWT (9.1 ±3.0 vs 13.1 ±5.0 mm, p=0.005) and UC-score (8.0 ±4.7 vs 12.9 ±7.2, p=0.018). At 3 months there was a significant difference in BWT for all segments, the sum of BWT (7.0 ±2.6 vs 14.0 ±4.5, p<0.001) and the UC-score (3.9 ±4.6 vs 16.3 ±5.6, p<0.001) for responders. For patients in remission similar results were found except for the rectum. The sum of BWT (6.8 ±2.6 vs 11.9 ±4.6 mm, p<0.001) as well as the UC-score (3.8 ±4.6 vs 11.7 ±7.8, p<0.001) was significantly lower.

Conclusion

The significant differences in BWT of the ascending and transverse colon at the 2^nd infusion could reflect prognostic differences between left-sided and total colitis. At 3 months the BWT of all colon segments was lower except for the rectum for patients in remission.

References

1) Ilvemark J, Wilkens R, Thielsen P, et al. Early Intestinal Ultrasound Predicts Intravenous Corticosteroid Response in Hospitalised Patients With Severe Ulcerative Colitis. J Crohns Colitis. Nov 23 2022;16(11):1725-1734. doi:10.1093/ecco-jcc/jjac083
2) Nylund, K., et al. ⟪ Sonorescue⟫-treatment response in acute severe Ulcerative Colitis measured with ultrasound. In: J Crohns Colitis. Great Clarendon St, Oxford OX2 6DP, England: Oxford Univ press, 2025. p. i239-i239.
3) Bots S, Nylund K, Lowenberg M, Gecse K, D'Haens G. Intestinal Ultrasound to Assess Disease Activity in Ulcerative Colitis: Development of a novel UC-Ultrasound Index. J Crohns Colitis. Aug 2 2021;15(8):1264-1271. doi:10.1093/ecco-jcc/jjab002

Disclosure

Odd Helge Gilja has received speaker’s honoraria from AbbVie, Bracco, Allmirall, GE healthcare, Takeda AS, Ferring AS, Allergan and Janssen-Cilag and has served as a consultant for Bracco, GE Healthcare, Takeda and Samsung. ​The other authors have nothing to dislose.

Introduction

Inflammatory Bowel Diseases (IBD) can lead to various complications, with Acute Severe Colitis (ASC) being among the most critical. ASC is a medical and surgical emergency that poses a significant risk to life, necessitating prompt and effective diagnosis and management. The first-line treatment typically involves intravenous corticosteroids. However, some cases are resistant to corticosteroids and require second-line medical therapy or immediate surgical intervention.

Aims & Methods

The objective was to identify factors associated with the failure of first-line medical treatment in patients with ASC. A retrospective descriptive and analytical study was conducted over ten years (January 2014 to March 2024) in the gastroenterology department of Charles Nicolle Hospital. The study included patients with IBD complicated by ASC, defined by the Truelove and Witts criteria and a Lichtiger score greater than 10.Patients with bacterial superinfection were not included.

Results

Forty-five patients over 18 years old were included, with a mean age of 37.87 years (range: 18–74 years). There was a slight female predominance (53%), with a male-to-female ratio of 0.87. In 31% of cases, ASC was the initial presentation of the disease. Endoscopic signs of severity at admission were observed in 49% of patients. All patients received intravenous corticosteroid therapy with hydrocortisone hemisuccinate as the first-line treatment. The response rate to first-line treatment was 64.5%. Second-line medical therapy was administered to 24.4% of patients, consisting of cyclosporine in 11.1% and infliximab in 13.3%. Five patients (11.1%) underwent subtotal colectomy due to corticosteroid failure.
In univariate analysis, factors associated with corticosteroid failure included male gender (p=0.011), absence of extraintestinal manifestations (p=0.017), higher average number of stools on the first day (p=0.013), Lichtiger score >10 on the third (p=0.011) and fifth day (p<0.001), hemoglobin levels >11 g/dL on the first day (p<0.001), >10 g/dL on the third day (p=0.009), >9 g/dL on the seventh day (p=0.013), white blood cell count >10,000/mm³ on the first day (p=0.008), >12,000/mm³ on the third (p=0.001) and seventh day (p=0.004), C-reactive protein (CRP) level >30 mg/L on the seventh day (p=0.005), and persistent endoscopic signs of severity after three to five days of corticosteroid therapy (p=0.001).
Multivariate Analysis showed that only the presence of severe endoscopic signs on follow-up endoscopy after three to five days of corticosteroid therapy was predictive of corticosteroid failure (Odds Ratio = 42.2; p=0.028).

Conclusion

Acute Severe Colitis is a potentially life-threatening complication. The presence of severe endoscopic signs after five days of corticosteroid therapy should prompt the initiation of second-line therapy. Understanding the predictive factors for corticosteroid failure is essential for individualized management to improve both immediate and long-term outcomes.

Disclosure

The authors declare no conflicts of interest.

Clinical Case Summary

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

Introduction

Abdominal pain is a common but often overlooked symptom in patients with ulcerative colitis (UC). The causes of pain during deep remission remain incompletely known, although factors in the brain-gut axis may play a role.

Aims & Methods

The aim of this study was to determine factors associated with abdominal pain in UC patients. Three existing study cohorts of adults with UC were used. Cohort I included 133 patients (49 active), cohort II 287 patients (155 active) and cohort III 92 patients (20 active). The abdominal pain domain of the Gastrointestinal Symptom Rating Scale was used to assess the severity of pain, identifying subjects with at least mild severity of abdominal pain. The Hospital Anxiety and Depression Scale was used to identify subjects with anxiety and or depression (scores ≥8) Patients also completed questionnaires to assess severity of fatigue (Fatigue Impact Scale (FIS, cohort I)), and quality of life (QoL, the IBD questionnaire (IBDQ, cohort II)).

Results

In the three cohorts 39%, 24% and 20% of the patients with active disease and 20%, 7% and 15% of the patients in remission reported at least mild severity of abdominal pain. A higher proportion of UC patients with at least mild abdominal pain had anxiety (83%, 44%, and 40% vs 42%, 18% and 7%; p<0.01) and depression (40%, 33% and 40% vs 13%, 9% and 13% p<0.05). Disease-specific QoL was lower in patients with at least mild abdominal pain, both in patients with active disease (median [IQR] IBDQ score 182 [150-198] vs 144 [115-160], p<0.001) and in remission (IBDQ score 203 [190-213] vs 171 [141-181], p<0.001). In UC patients in remission, having at least mild abdominal pain was associated with more severe impact of fatigue on daily life, (FIS 81 [67-100] versus 29 [14-58], p<0.001).

Conclusion

Abdominal pain is relatively common in patients with UC with active disease as well as in remission. This is associated with anxiety, depression and more severe fatigue and a lower QoL. Hence, paying attention to abdominal pain and associated factors seems important to optimize clinical management of these patients.

Disclosure

Tom van Gils: None
Hans Törnblom: Consultant/Advisory Board member: Cinclus Pharma, Dr Falk Pharma Gmbh, VIPUN Medical.
Speakers’ bureau: Tillotts, Takeda, Galapagos
Börje Jonefjäll: Consultant/advisory board member: Tillots. Speaker for MSD, AbbVie, Tillotts, MEDA, and Takeda.
Hans Strid: Consultant/Advisory Board member: Tillotts, Takeda, Abbvie, Pharmacosmos, BMS
Magnus Simrén: Unrestricted research grants: Glycom/DSM, Genetic Analysis AS
Consultant/Advisory Board member: Danone Nutricia Research, Ironwood, Biocodex, Genetic Analysis AS, Tillotts, Takeda, Arena, Kyowa Kirin, Abbvie, BioGaia, Cinclus Pharma and Pharmanovia.
Speakers’ bureau: Tillotts, Kyowa Kirin, Takeda, Biocodex, Sanofi, Janssen Immunology, Pfizer, Ferrer, BioGaia and Falk Foundation.

Introduction

For decades, corticosteroids have been the first-line therapy in patients with severe ulcerative colitis (UC), however 30-40% of patients fail to respond and require second-line rescue therapy with cyclosporine (CsA) or infliximab to avoid colectomy.

Aims & Methods

We conducted a single-center, retrospective study including all patients with active severe, steroid-refractory UC and with at least one year follow-up, to assess the short- and long-term effectiveness and safety of CsA therapy. Disease severity was defined according to Mayo disease activity index. Patients with a pMayo score of ≥7 and an eMayo score of ≥2 were enrolled, and received 4 mg/kg/day CsA IV for 5-7 days for second-or third-line rescue therapy between 2001 and 2023. IV CsA therapy was followed by oral CsA in case of clinical response. Colectomy-free survival was assessed using Kaplan-Meier analysis. Multivariable logistic regression analyses were performed to identify the predictive value of various factors for therapeutic response to CsA and colectomy during or after CsA treatment.

Results

Ninety-two steroid-refractory UC patients (54.4% male, mean age: 40.0 ± 14.0 years, median disease duration: 4.0 years) were included with the median follow-up time of 14.0 years (IQR:7-18). Clinical response was achieved in 59/92 (64.1%) patients, and clinical remission was observed in 22/92 (23.9%) patients after the IV phase. During oral CsA therapy (10.4 ± 11.7 months) relapse rate was 42.0%, whereas 33 (40.7%) patients achieved or maintained remission until treatment discontinuation. Remission with oral CsA therapy was significantly higher among those who received concomitant immunomodulator treatment (p=0.004, OR:6.98, 95% CI:1.9-26.4). 20/92 (21.7%) patients underwent colectomy during CsA therapy, while a total of 45 (48.9%) patients required surgery at the end of follow-up. Non-response to IV CsA was the only predictor of colectomy during CsA therapy (p=0.04. OR: 0.17, 95% CI:0.03-0.94). No predictors for the effectiveness of the IV CsA could be found. Neither the need for colectomy during CsA therapy (p=0.33), nor the rate of remission with oral CsA (p=0.49) was influenced by the prior use of biologics. Remission with oral CsA was found to be the only predictor of colectomy within 3 years after CsA discontinuation. The probability of colectomy-free survival was 74.7%, 62.6%, 57.1% and 45.6% at 1, 3, 5 and 14 years. In 52 patients (64.1%), biological therapy was needed after an average of 7.2 (± 6.74) months from the start of CsA. Immunomodulators were used in 50 out of 89 patients following CsA discontinuation, as maintenance therapy or as part of combination therapy. Adverse events (AEs) occurred in 53.3% of patients, 57.2% of them required a dose reduction or treatment discontinuation. AEs were mainly reversible, but 1 patient died of opportunistic infections (acute tuberculous pneumonia). The occurrence of AEs was not associated with the use of concomitant immunomodulators (p=0.92). Malignancy was observed in 5 patients during follow-up, mainly melanoma and non-melanoma skin cancer.

Conclusion

CsA is an effective therapeutic option for avoiding colectomy in patients with active severe UC, even in the era of biologicals. Moreover, its effectiveness can be enhanced by concomitant immunomodulator therapy without compromising safety. CsA can be used as a "bridge" until the therapeutic effect of immunomodulators or biological therapy is fully developed. However, due to the high occurrence of AEs, tight patient monitoring during CsA therapy is needed.