TBA (25S170)

Clinical Case: Blindsided by Immunotherapy – A Case of ICI-Associated Colitis and Severe Infectious Complications

Author(s)

Dr Shane Elwood, Dr Shreyashee Sengupta, Prof Valerie Byrnes

Department(s)/Institutions

University Hospital Galway

Introduction

EM is a 71-year-old female with oesophageal melanoma diagnosed in May 2024. She was initiated on immune checkpoint-inhibitor (ICI) therapy, receiving three cycles of ipililumab/nivolilumab from June 2024. In August 2024, EM presented with a one-week history of bloody diarrhoea. A sigmoidoscopy confirmed ICI colitis. She was treated with a single dose of Infliximab (10mg/kg) and discharged with a plan for further Infliximab infusions at weeks two and six. ICIs were discontinued at this time.

Aims/Background

EM represented in October 2024 with 2 weeks of bloody diarrhoea, having received three doses of IFX. Initial management included intravenous methylprednisolone and a single dose of intravenous vedolizumab, which had minimal effect. She was then commenced on Tofacitinib 10mg BD. At this point, EM required TPN due to weight loss and persistent diarrhoea. A partial symptomatic improvement was seen on tofacitinib, however, her symptoms worsened after one week. Given the initial response to JAK inhibition, therapeutic options included increasing the tofacitinib dose to a thrice-daily regimen or switching to upadacitinib (Upa). The decision was made to commence Upa at 45mg daily.

Method

EM had a significant response to Upa, achieving normalisation of her colonic symptoms and successful weaning from TPN within a week. Unfortunately, after eight days of Upa therapy she developed painful bilateral vision loss and was subsequently diagnosed with bilateral aspergillus endophthalmitis and HSV keratitis of the left eye. Anti-fungal therapy was commenced, initially with amphotericin B followed by variconazole, and Upa was discontinued. Her bowel symptoms remained well controlled, and her prednisolone therapy was weaned weekly with a plan to remain at 10mg until gastroenterology outpatient review in January 2025.

Results

Significant derangement of her LFTs in a cholestatic pattern was noted in January 2025, coinciding with steroid tapering. While these abnormalities may be secondary to antifungal therapy, there remains concern for ICI-induced hepatitis. She continues to be monitored in the outpatient setting. Despite multiple vitrectomy procedures and intravitreal antifungal treatment, EM is now irreversibly blind in the left eye.

Conclusions

This case highlights the complexities of managing ICI-associated colitis, the challenges of immunosuppressive therapy, and the risks of opportunistic infections.