Combined eosinophilic gastroenteritis and ulcerative colitis successfully treated by vedolizumab: a case report
Article information
Abstract
A 47-year-old man with over 10 years’ duration of ulcerative colitis treated by 5-aminosalicylic acid and intermittent topical steroids complained of acute epigastric pain. Esophagogastroduodenoscopy revealed diffuse mucosal edema with patchy redness, multiple erosions and nodularity of the stomach. Bioptic examination revealed marked eosinophilic infiltration, confirming the diagnosis of eosinophilic gastroenteritis. Systemic steroid therapy was initiated, whereas his ulcerative colitis and eosinophilia recurred when tapering the steroid. Addition of azathioprine was ineffective, and we subsequently started vedolizumab for eosinophilic gastroenteritis and ulcerative colitis. The medication effectively improved his abdominal symptoms and esophagogastroduodenoscopy and ileocolonoscopy 1 year later revealed endoscopic improvement of both diseases with histologically decreased level of eosinophilic infiltration. Considering that eosinophils also express α4β7 integrins, vedolizumab can be a possible therapeutic candidate for eosinophilic gastroenteritis as well as ulcerative colitis.
INTRODUCTION
Eosinophilic gastroenteritis (EGE), initially described by Kaijser in 1937, is a relatively rare disease characterized by dense eosinophilic infiltration of the gastrointestinal (GI) tract, and has been recently classified as eosinophilic gastrointestinal disease (EGID) along with eosinophilic esophagitis (EoE) [1,2]. While its etiology remains uncertain, T helper 2 (Th2) immune response is suggested to play a central role in the dysfunctional eosinophilic inflammation in the GI tract [3]. Corticosteroids are commonly used for the treatment of EGE, however, patients sometimes relapse when tapering the medication, being obliged to continue steroid therapy that increase the risk of various complications. Other treatment options including elimination diets, antiallergic agents, and immunomodulators, have been suggested, whereas more effective treatment options are awaited [4,5].
Vedolizumab is a humanized monoclonal antibody to the α4β7 integrin, preventing binding to its ligand, mucosal addressing cell adhesion molecule-1 (MadCAM-1). Vedolizumab is approved for the treatment of inflammatory bowel diseases and provides anti-inflammatory effect via specific inhibition of GI migration of effector T lymphocytes [6]. Although vedolizumab has been considered as a possible therapeutic candidate for EGE [7], its clinical use has been limited to date [8-10].
We herein described a case of EGE with ulcerative colitis (UC) successfully treated with vedolizumab and discuss the efficacy of vedolizumab for EGE. Informed consent was obtained from the patient for being included in the report.
CASE REPORT
A 47-year-old man with over 10 years’ duration of UC of entire colitis type treated by 5-aminosalicylic acid (5-ASA) and occasional topical steroid therapy complained of acute epigastric pain. He had been eradicated Helicobacter pylori infection at the age of 30 years. The patient had no history of allergic disease. Laboratory data revealed elevated white blood cell count (10,700 μL) with eosinophilia (1,145/μL), thrombocytosis (40.4 × 104/μL) and hypoalbuminemia (3.5 g/dL), whereas other inflammatory biomarkers remained within normal limit (C-reactive protein 0.09 mg/dL, erythrocyte sedimentation rate 5 mm/hr). Esophagogastroduodenoscopy revealed diffuse mucosal edema with patchy redness, multiple erosions and nodularity of the stomach (Fig. 1A-C). No endoscopic abnormalities were found in the esophagus and the duodenum. Histologic examination of the bioptic specimens from the stomach showed marked eosinophilic infiltration (eosinophil counts > 60/high-powered field) (Fig. 1D). We thus made a diagnosis of EGE. Since his abdominal symptoms possibly related to his UC also deteriorated (increased stool frequency ≥ 3–6 times/day), 25 mg/day of oral prednisolone (PSL) was started and tapered down by 5 mg every 2 weeks for a total of 10 weeks. His abdominal pain and stool frequency quickly improved after PSL administration, however abdominal symptoms and eosinophilia recurred when tapering PSL, and additional administration of azathioprine (25 mg/day) was ineffective. Ileocolonoscopy demonstrated reddish friable mucosa with purulent mucus in the left side of the colon (Fig. 2A and B). Histological examination of the colonic bioptic specimens revealed increased eosinophilic infiltration along with chronic inflammatory cells infiltration (eosinophil counts > 20/high-powered field) (Fig. 2C). Considering possible contribution of eosinophilic infiltration to the deterioration of UC and concomitant development of EGE, vedolizumab was selected for the induction of remission of UC because eosinophils also express α4β7 integrin. Expectedly, his upper and lower abdominal symptoms improved and he subsequently maintained clinical remission. Esophagogastroduodenoscopy and ileocolonoscopy with biopsy 1 year after the induction of vedolizumab demonstrated endoscopic improvement of the stomach (Fig. 3A-C) and colon (Fig. 4A and B) with decreased eosinophilic infiltration in both organs (Figs. 3D, 4C).
Endoscopic and histopathological findings of the stomach at diagnosis of eosinophilic gastroenteritis (EGE). (A-C) Esophagogastroduodenoscopy at diagnosis of EGE demonstrates mucosal edema, redness, erosion, and multiple nodules (arrows) in the stomach (A: antrum, B: body, C: cardia). (D) Histological findings of biopsy specimens from the stomach show marked eosinophilic infiltration (hematoxylin and eosin staining, ×400).
Endoscopic and histopathological findings of the colon before vedolizumab therapy. (A, B) Ileocolonoscopy before vedolizumab therapy demonstrates reddish friable mucosa with purulent mucus in the left side colon (A: descending colon, B: rectum). (C) Histological findings of biopsy specimens from the descending colon show increased eosinophilic infiltration (hematoxylin and eosin staining, ×400).
Endoscopic and histopathological findings of the stomach after vedolizumab therapy. (A-C) Esophagogastroduodenoscopy 1 year after the initiation of vedolizumab demonstrates improvement of gastric mucosal abnormalities (A: antrum, B: body, C: cardia). (D) Histological findings of biopsy specimens from the stomach demonstrate decreased level of eosinophilic infiltration (hematoxylin and eosin staining, × 400).
Endoscopic and histopathological findings of the colon after vedolizumab therapy. (A, B) Ileocolonoscopy after vedolizumab therapy demonstrates endoscopic remission of UC (A: descending colon, B: rectum). (C) Histological findings of biopsy specimens from the descending colon show reduced eosinophil infiltration (hematoxylin and eosin staining, ×400).
DISCUSSION
The diagnosis of EGE is based on the combination of medical history, physical examinations, laboratory tests, GI endoscopic findings with histopathological examination of biopsy specimens [1,2,11]. In the present case, while concomitant allergic disease did not exist, peripheral eosinophilia occurred when developing acute epigastric pain and gastric abnormalities under endoscopy were compatible with morphologic characteristics of EGE reported previously [12]. Furthermore, histologic examination demonstrated dense eosinophilic infiltration into the gastric mucosa. Although the upper GI involvement of the present case could conceivably a rare complication of UC, endoscopic and histologic findings of the stomach were inconsistent with those of UC [13]. We thus diagnosed the patient developed concurrent EGE during the clinical course of UC.
EGID can be caused by the allergic reaction to certain foods or medications, the latter of which include clopidogrel, aspirin and ticlopidine, nonsteroidal anti-inflammatory drugs, estroprogestinic agents, rifampicin, carbamazepine, gold, and tacrolimus [5]. In this sense, since 5-ASA can cause acute intolerance syndrome or a variety of adverse reactions, suggesting possible association with EGID. However, there could be found only 1 case report of UC treated with 5-ASA developing eosinophilic corpus gastritis [14]. In addition, acute 5-ASA intolerance syndrome characterized by fever, diarrhea, abdominal pain and elevated C-reactive protein concentration usually occurs within 1–3 weeks after starting 5-ASA [15]. Rare adverse events, such as renal, pulmonary, pericardial, pleuro-pulmonary and hematological toxicity, develops within the first year of treatment [16]. In our case, 5-ASA was started when the diagnosis of UC was made, and had been continued more than 10 years without obvious peripheral eosinophilia. It thus seems unlikely that 5-ASA was associated with the development of EGE in our case
Although there is no established protocol for the treatment of EGE, systemic glucocorticoid administration is widely used [4,5]. However, EGE sometimes recurs when tapering the steroid, being obliged to continue steroid therapy that relates with certain side effects. Other therapeutic candidates, such as elimination diets, leukotriene inhibitors, azathioprine, anti-histamines, and mast cell stabilizers, have been proposed, whereas their therapeutic effects remain inconclusive. From this viewpoint, biologics are considered as new therapeutic targets and vedolizumab is one of the candidates [7].
While the pathogenesis of EGE is not fully understood, the condition is considered to be a chronic Th2 allergic disease caused by food or environmental allergens. Secreted cytokines by Th2 cells, namely interleukin (IL)-5 and IL-13, cause the differentiation, recruitment, and activation of eosinophils [17]. Then, activated eosinophils that express α4β7 integrins on their cell surface bind to their ligand, MadCAM-1, leading the migration into the intestinal mucosa [18].
Vedolizumab has been approved for the treatment of moderately to severely active inflammatory bowel diseases [19]. Its anti-inflammatory effect is caused by blocking the interaction of α4β7 integrin expressed on the surface of effector T cells with MadCAM-1 [6]. In the present case, we selected vedolizumab for the treatment of both UC and EGE considering the inhibitory mechanisms of cellular migration of effector T cells and eosinophils by vedolizumab, while the medication is off label use for EGE in the clinical practice. Consequently, however, we could confirm the therapeutic efficacy of vedolizumab for EGE by endoscopy in our case, and more obvious decreased level of eosinophilic infiltration into the gastric mucosa than the colonic mucosa might further indicate its therapeutic efficacy for EGE.
To the best of our knowledge, 10 cases with EGIDs (including a case with EoE) treated by vedolizumab have been reported so far [8-10]. Most of the cases had refractory EGIDs including anti-tumor necrosis factor treatment failure patients, whereas 60% of cases demonstrated clinical and histological improvement, thereby being able to decrease or wean off systemic steroids as has been demonstrated in our case. The IL-4 receptor α antagonist, dupilumab that has been recently approved for EoE in the United States [5], could be also effective for EGE, however, vedolizumab could be another promising therapeutic candidate for EGIDs when considering its safety profile based on the gut selective action.
Notes
Funding Source
The authors received no financial support for the research, authorship, and/or publication of this article.
Conflict of Interest
No potential conflict of interest relevant to this article was reported.
Data Availability Statement
Not applicable.
Author Contributions
Conceptualization: Takedomi H, Esaki M. Data curation: Takedomi H, Fukuda K, Inoue S, Tsuruoka N, Sakata Y, Esaki M. Acquisition of endoscopic images: Takedomi H, Fukuda K, Inoue S, Tsuruoka N, Sakata Y, Esaki M. Evaluation of histological examination: Aoki S. Writing - original draft: Takedomi H, Esaki M. Writing - review & editing: Takedomi H, Fukuda K, Inoue S, Tsuruoka N, Sakata Y, Aoki S, Esaki M. Approval of final manuscript: all authors.