Case Report
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 28, 2021; 27(20): 2657-2663
Published online May 28, 2021. doi: 10.3748/wjg.v27.i20.2657
Cyclophosphamide-associated enteritis presenting with severe protein-losing enteropathy in granulomatosis with polyangiitis: A case report
Hiroko Sato, Tsuyoshi Shirai, Hiroshi Fujii, Tomonori Ishii, Hideo Harigae
Hiroko Sato, Tsuyoshi Shirai, Hiroshi Fujii, Tomonori Ishii, Hideo Harigae, Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai 9808574, Japan
Author contributions: Sato H and Shirai T performed the literature review, and wrote the manuscript; Shirai T, Fujii H, Ishii T, and Harigae H were involved in the clinical management.
Supported by Funding for Scientific Research (Funding for Academic Research), No. 18K16136.
Informed consent statement: Written informed consent for the publication of this case report was obtained from the patient.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Tsuyoshi Shirai, MD, PhD, Assistant Professor, Doctor, Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 9808574, Japan.
Received: January 25, 2021
Peer-review started: January 25, 2021
First decision: February 27, 2021
Revised: March 9, 2021
Accepted: May 7, 2021
Article in press: May 7, 2021
Published online: May 28, 2021

Although cyclophosphamide (CPA) is the key drug for the treatment of autoimmune diseases including vasculitides, it has some well-known adverse effects, such as myelosuppression, hemorrhagic cystitis, infertility, and infection. However, CPA-associated severe enteritis is a rare adverse effect, and only one case with a lethal clinical course has been reported. Therefore, the appropriate management of patients with CPA-associated severe enteritis is unclear.


We present the case of a 61-year-old woman diagnosed with granulomatosis with polyangiitis based on the presence of symptoms in ear, lung, and, kidney with positive myeloperoxidase-antineutrophil cytoplasmic antibody. She received pulsed methylprednisolone followed by prednisolone 55 mg/d and intravenous CPA at a dose of 500 mg/mo. Ten days after the second course of intravenous CPA, she developed nausea, vomiting, and diarrhea, and was admitted to the hospital. Laboratory testing revealed hypoalbuminemia, suggesting protein-losing enteropathy. Computed tomography revealed wall thickening of the stomach, small intestine, and colon with contrast enhancement on the lumen side. Antibiotics and immunosuppressive therapy were not effective, and the patient’s enteritis did not improve for > 4 mo. Because her condition became seriously exhausted, corticosteroids were tapered and supportive therapies including intravenous hyperalimentation, replenishment of albumin and gamma globulin, plasma exchange, and infection control were continued. These supportive therapies improved her condition, and her enteritis gradually regressed. She was finally discharged 7 mo later.


Immediate discontinuation of CPA and intensive supportive therapy are crucial for the survival of patients with CPA-associated severe enteritis.

Keywords: Antineutrophil cytoplasmic antibody, Cyclophosphamide, Enteritis, Granulomatosis with polyangiitis, Plasma exchange, Vasculitis, Case report

Core Tip: Cyclophosphamide-associated enteritis is rare, but a fatal complication of the treatment for the vasculitides. This is the first successful report of the treatment for the severe cyclophosphamide-associated enteritis, and indicates the importance of immediate discontinuation of cyclophosphamide and intensive supportive therapy.