A Tough Pill to Swallow: A Case of Rituximab-associated Esophageal Ulcers

Abstract

Idiopathic giant esophageal ulcers were initially reported in patients with acquired immunodeficiency syndrome (AIDS), and later in other immunocompromised patients such as transplant recipients. However, there are no reported cases of esophageal ulcers associated with rituximab in lymphoma patients to our knowledge. A 44-year old male with history of Stage IV B-cell Lymphoma diagnosed 2 years ago, initially treated with Rituximab-Bendamustine, currently on rituximab maintenance therapy presented to the clinic for 2-week history of odynophagia and dysphagia. Physical exam was unremarkable. Labs showed WBC count of 2900 cells/uL with mild neutropenia of 1500 cells/uL and lymphopenia of 400 cells/uL (normal 0.7-4 k cells/uL). Esophagogastroduodenoscopy (EGD) showed multiple large ulcers in the mid-esophagus measuring 5-6 cm. Biopsies demonstrated reactive squamous epithelial changes and granulation tissue with no evidence of viral infection or malignancy. Testing for CMV, HSV, AFB, bacterial and fungal cultures, were negative. The patient was initially given a trial of PPI and empiric antiviral therapy with Valganciclovir for a week with no subjective improvement in symptoms. Repeat EGD showed mid-esophageal ulcers, unchanged from prior exam with negative biopsies. Repeat labs showed normal white count with Lymphopenia of 400 cells/uL. At this juncture, the patient was thought to have esophageal ulcers secondary to immunosuppression and rituximab was stopped. He was started on prednisone 20mg twice a day. He reported symptomatic relief within a week. EGD after 4 weeks showed healing ulcers. The patient is currently being tapered off the steroids. Idiopathic giant esophageal ulcers are rare and occur in the distal half of esophagus. Pathogenesis of these ulcers is unclear. Literature review shows few cases of idiopathic ulcers in AIDS and transplant patients that respond to steroid therapy with endoscopically documented healing. Alterations in the immune system leading to leukopenia may be the underlying mechanism for these ulcers. Even though our patient did not have a significant leukopenia, he did have lymphopenia. Rituximab may have induced an imbalance between various lymphocyte subpopulations and played a role in the pathogenesis of these ulcers. Steroid therapy and discontinuation of rituximab may have restored the immune balance. In conclusion, rituximab was the likely cause of multiple esophageal ulcers in our patient, and they responded to steroids.