P041 An Interesting Case of Refractory Immune-Mediated Esophageal Stricture Following Immunotherapy With Nivolumab Treated With Esophageal Dilation
Authors: Jayoushe Majdoline , Gupta Nancy , Bellaguarda Emanuelle 
Published: December 2019

INTRODUCTION:
Immune checkpoint-inhibitors (ICIs) are a type of immunotherapy that targets proteins expressed by T-lymphocytes which stimulate the immune system to attack cancer cells. ICIs have gained popularity due to their effective action against several metastatic malignancies. There have been a few well-described immune-related adverse events (irAEs) which include dermatitis, uveitis, hepatitis, and colitis. The incidence of immune-mediated stomatitis and mucositis has been reported in 5–9% of patients treated with Nivolumab or Pembrolizumab therapy. Furthermore, gastroesophagitis remains an under recognized irAE which is associated with stricturing of the esophageal mucosa. Here we describe an interesting case of steroid-refractory immune-mediated ulcerative esophagitis complicated by an esophageal stricture, following immunotherapy with Nivolumab.

CASE DESCRIPTION:
A 68 year-old female with stage IIIA melanoma of the right foot, underwent wide excision followed by adjuvant Nivolumab therapy. She later presented with a three month duration of significant odynophagia and dysphagia to both solids and liquids, associated with regurgitation of undigested food particles. Initial upper esophagogastroduodenoscopy (EGD) demonstrated circumferential ulceration 35 cm from the incisors. Pathology revealed inflamed granulation tissue with ulceration and fibrinopurulent exudate, negative for herpes simplex virus, cytomegalovirus and fungal stains. There was no evidence of Helicobacter Pylori infection. Nivolumab was discontinued and the patient was started on an empiric trial of proton-pump inhibitor (PPI) and Carafate with no symptomatic improvement. A follow-up EGD eight months later, was notable for scattered islands of salmon-colored mucosa with no active inflammation and a moderately severe stenosis 25 cm from the incisors, which could not be traversed with an adult upper endoscope. A biopsy of the esophageal stricture exhibited evidence of granulation tissue, marked ulceration, and both acute and chronic inflammation. Due to recurrence of her symptoms with steroid tapering, she was given three induction doses of Infliximab. A follow-up EGD four weeks later was remarkable for post-esophagitis scarring and a decreased vascular pattern, with persistent ulceration in the esophagus despite treatment with steroids and Infliximab. There was a benign-appearing severe esophageal stenosis 15 cm from the incisors, measuring 25 cm in length with an 8-mm inner diameter. The stricture was effectively dilated to 12 mm with a favorable clinical response thereafter.

CONCLUSION:
There is a wide spectrum of irAEs which clinicians need to be aware of as ICI therapy becomes more prevalent. Close surveillance is warranted in patients suspected of developing irAEs. Ulcerative esophagitis is a rare side effect of immunotherapy that can quickly progress to stricturing disease. It is important to highlight that management of immune-mediated ulcerative esophagitis includes cessation of immunotherapy, followed by a trial of PPI and corticosteroid therapy. For refractory cases complicated by an esophageal stricture, endoscopic dilation is often the treatment of choice. Our case is unique in that the patient demonstrated a favorable clinical response following esophageal dilation. To date, there has only been one case reported in the literature of a radiation-induced esophageal stricture which was successfully treated with serial esophageal dilation.