Refractory Ulcerative Colitis in a Young Child; VEO IBD
Ravi Shankar B1*, Akhil K1; Srikant Darisetty2; Ramesh Darisetty2; Vamsi Krishna Reddy Boddireddy1; Naga Sarika V3
¹Department of Medical Gastroenterology, Yashoda Hospital, Secunderbad, India
²Department of Pediatrics, Yashoda Hospital, Secunderbad, India
³Department of Pathology, Yashoda Hospital, Secunderbad, India
*Corresponding author
B Ravi Shankar, Department of Medical Gastroenterology, Yashoda Hospital, Secunderbad, India
DOI: 10.55920/JCRMHS.2025.11.001493
Abstract
Ulcerative colitis (UC) is a chronic idiopathic inflammatory disorder diagnosed based on clinical presentation and endoscopic evidence of inflammation in the colon and/ or rectum. factors contributing to the complexity.In case of pediatric IBD, genetic differences and inexperience with newer therapies are two
We present the case of a six year old male child with a medical history of refractory Ulcerative colitis. He was treated initially with 5- ASA and wysolone followed by budesonide, tacrolimus, tofacitinib, adalimumab and infliximab. Due to non response, Ustekinumab was initiated and yielded a significant response.
Severe IBD in pediatric subjects might be difficult to treat and may require genetic studies for better diagnosis and treatment. However in this case, there were no genetic studies performed, but an attempt to use ustekinumab yielded a good result.
Keywords: Early onset Ulcerative Colitis; Very early onset - inflammatory bowel disease; Ustekinumab; steroids; Pediatric ulcerative colitis activity index.
Introduction
Ulcerative colitis (UC) is a chronic idiopathic inflammatory disorder that involves rectum and extends to a variable distance in the colon presenting with symptoms of bloody diarrhea, abdominal pain, and rectal urgency1. Clinical presentation of disease usually dictates the choice of pharmacologic therapy, where the goal is to first induce remission and then maintain corticosteroid-free remission. UC is diagnosed based on clinical presentation and endoscopic evidence of inflammation in colon or rectum. Treatment depends on severity, localization and course of the disease. For proctitis, topical therapy with 5-aminosalicylic acid (5-ASA) is used. More extensive or severe disease is treated with oral and local 5-ASA compounds and corticosteroids to induce remission. Intravenous steroids, calcineurin inhibitors (cyclosporine, tacrolimus), tumor necrosis factor-α antibodies (infliximab, adalimumab) , vedolizumab, ustekinumab or immunomodulators (azathioprine, 6-mercaptopurine) are utilized for severe cases. Indications for emergency surgery include refractory toxic megacolon, perforation, and severe colorectal bleeding. Pediatric IBD has its complexity in being genetically different as well as the lack of experience with newer therapeutic agents in this age group.
Case Report
A six year old boy presented to the hospital with history of loose stools, intermittent bloody diarrhea, occasional rectal bleed, intermittent fever of 8 months duration. He was diagnosed as ulcerative colitis earlier elsewhere and treated with multiple agents. Present physical examination revealed pallor, pulse rate 76/minute, blood pressure 100/70 mmHg, temperature 98°F and had mild abdominal tenderness. BMI was 12.9 kg/cm2; weight, height was 3rd and 50th percentile respectively. Lab investigation revealed hemoglobin 8.3 g %, white cells 13,000/µL, neutrophils 60 %, platelets 8.28 L/cumm, ESR 120 mm/hr, CRP 31.05 mg/dL. Colonoscopy revealed inflammed, friable mucosa extending from rectum to caecum (pancolitis). Total Mayo score was 8, suggestive of severe disease. Truelove and Witts criteria (modified) was suggestive of moderate to severe disease. The PUCAI (Pediatric ulcerative colitis activity index) score was 55 suggestive of moderate to severe disease. Histopathology revealed ulceration, cryptitis, crypt abscesses, crypt distortion, crypt shortening and diffuse plasmacytic infiltration (Fig 1 & 2).
Earlier, elsewhere (during 3 years, prior to presentation) he had undergone treatment with 5-ASA and wysolone 20 mg which resulted in remission. During tapering there was flare of disease with recurrence of bloody diarrhea, PUCAI score was 45 suggestive of moderate to severe disease. In view of steroid dependency, he was initiated on azathioprine after TPMT testing. One month later, he presented with acute abdominal pain and elevated lipase 1340 units/mL suggestive of acute pancreatitis. Azathioprine was withdrawn. Oral budesonide (3 mg) was started with tapering of wysolone. Colonoscopy performed 3 months later revealed moderate activity. He was initiated on Tacrolimus 0.25 mg twice daily and continued for 4 months. Inadequate response with decreased appetite and weight loss prompted change of medication. Tofacitinib 5 mg once daily was administered and continued for one year with partial response and later relapsed with 4 - 6 bowel movements per day. Adalimumab was initiated with 40 mg followed by 20 mg every 2 weeks. There was no response. Infliximab 75 mg was administered intravenously followed by another 3 doses. Initial clinical response did not last long with recurrence of fever and loose stools. Sigmoidoscopy at this stage showed moderate disease activity UCEIS 4/8. CRP was 5.6 mg/L, tissue CMV Quantitative PCR was negative, Quantiferon gold was negative.(Table no 2)
He presented to us at 6 years of age with history of exposure and refractoriness to steroids, budesonide, tacrolimus, tofacitinib, adalimumab and infliximab. The options were limited i.e. ustekinumab and vedolizumab (availability in India). Ustekinumab was administered to him at a dose of 130 mg intravenously followed by 90 mg subcutaneously every 2 months (Further reduced to 45 mg after availability). During the follow up of 10 months, there was clinical remission with increased appetite and PUCAI suggested remission. Long term follow up is awaited. Ustekinumab has been approved in India for use in pediatric age groups in June 2024. The experience with ustekinumab in EOIBD is limited and the age group for which it is approved is > 6 years.
Table 1 : Classification of Pediatric UC based on age
Table 2 : List of different drugs used for remission in our patient
Discussion
Multiple studies have shown that 25% of all IBD have their onset in less than 18 years of age2. However, the incidence of the disease is on the rise. A systematic review of international trends in paediatric IBD revealed a statistically significant increase in the period 1950-2009. The SPIRIT registry from Spain collected data in 2100 paediatric patients with IBD (1996-2009), which has shown a collective increase in incidence of IBD from 0.97 to 2.8/100,000 inhabitants during the study period. The median age at diagnosis was 12 years and the increase in CD was more than UC cases, with males being predominantly affected.3
Data from India is limited. The first case series on CD was published from Southern India in 2005, detailing 10 children (5-15 years) with Crohn’s disease4. There was female preponderance (9 out of 10), and interestingly, 50% of the children had received antitubercular therapy prior to diagnosis. Another tertiary referral center from Southern India reported 34 children with IBD (23 with CD and 11 with UC). These cases accounted for 7% of total IBD subjects presenting to that centre. The proportion of IBD was 0.03% of all paediatric cases presented to the outpatient department, and the median delay in diagnosis was 15 months5. A recent questionnaire-based survey from seven centers across India in 221 children and adolescents with IBD showed that children with IBD in India have features similar to adult-onset IBD. UC was present in 42%, CD in 55% and the rest IBD - unclassified. These children shared similarities with adult-onset IBD in terms of distribution of the disease. However, as in other reports on IBD in children, growth failure and more severe form of the disease was observed. The UC subjects had complications like toxic megacolon and bleeding in 12%, while 27% of CD cases had fistulae, strictures or perforation. Biologic agents were used in less than 1% of UC cases and in 12% of CD cases6.
Pediatric UC has been classified based on age of presentation7. (Table no 1)
(*VEO-IBD: Very Early Onset Inflammatory Bowel Disease, EO-IBD: Early Onset Inflammatory Bowel Disease, LO-IBD: Late Onset Inflammatory Bowel Disease)
The present case is reported in view of refractoriness to various therapeutic agents including JAK inhibitors and biologic agents in an young child. Usage of ustekinumab in India for ulcerative colitis has been approved in 2024 and the subject benefited by this IL 12/23 inhibitor. The experience of using ustekinumab in younger age group is limited.
The positive response obtained in this patient with ustekinumab needs to be observed for its efficacy in the long run. Drugs with continued suppression of disease are needed in circumstances of severe pediatric IBD.
(*VEOUC: Very Early onset Ulcerative Colitis, 5ASA: 5- Aminosalicylic Acid)
Conclusion
Severe IBD in the pediatric age group could be difficult to manage and may have significant morbidity. The aetiopathogenesis may be related to a monogenic disorder, unlike the adult onset counterpart (Table no 3). Genetic studies may have to be carried out in these age groups, especially if disease does not respond to medication5. In our patient, genetic studies were not carried out but an attempt at usage of ustekinumab yielded good result.
(*ILRa: Interleukin Receptor subunit alpha , ILR b : Interleukin Receptor subunit beta, FOX P3: forkhead box protein P3, IPEX: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked, XIAP: X-linked inhibitor of apoptosis protein, CTLA-4: Cytotoxic T-lymphocyte antigen 4, VEOIBD : Very Early onset Ulcerative Colitis)
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