A Clinicopathologic Study of Small Intestinal Perforations in Patients With Eosinophilic Granulomatosis With Polyangiitis: A Series of 3 Patients

Eosinophilic granulomatosis with polyangiitis (EGPA), or Churg-Strauss syndrome, first described by Churg and Strauss in 1951, is characterized by disseminated necrotizing vasculitis with extravascular granulomas occurring exclusively in patients with asthma and tissue eosinophilia.¹ There is no significant sex difference, with a mean age at onset of 38 to 54 years.^2,3 Characteristic histopathologic features include necrotizing vasculitis in arteries or veins with an infiltrate consisting mainly of eosinophils in vessels and surrounding tissues.⁴

Gastrointestinal manifestations are frequent in patients with EGPA (20% to 50%)⁵ with a variety of symptoms including abdominal pain, diarrhea, nausea, and vomiting to more severe symptoms such as bleeding, pancreatitis, bowel perforation, ischemia, and cholecystitis.^6–8 However, severe gastrointestinal involvement is rare.⁹ Corticosteroids remain the cornerstone of the initial treatment of EGPA.¹⁰ Corticosteroids impair tissue repair and induce fibrotic changes in the vascular intima, resulting in intestinal perforation due to vascular occlusion and ischemia.¹¹ We report 3 patients with EGPA who developed small intestinal perforations due to angiitis while undergoing corticosteroid treatment.

Case Presentation

From January 1, 2001 to December 31, 2014, 71 patients underwent surgery for small bowel perforations at Jichi Medical University Hospital. Of these, 3 patients were diagnosed with EGPA. These 3 patients required hospitalization due to comorbidities of progressive neuropathy. One patient underwent 2 operations for recurrent perforations. Clinical, surgical, pathologic, and outcome data were collected retrospectively.

All 3 patients with EGPA in this series were men, with a mean age of 56 years. The length of resected intestine ranged from 10 to 60 cm. Histopathologic examination revealed ulcers and perforations of the small intestine associated with vasculitis, compatible with EGPA. Only 1 of the 3 patients with EGPA was positive for myeloperoxidase-antineutrophil cytoplasmic antibody. All patients had an uneventful postoperative course, although the first patient had a recurrent intestinal perforation. All 3 patients were undergoing corticosteroid therapy at the time of presentation. A summary of the clinical features of these patients is shown in Table 1.

Table 1 Summary of 3 patients with EGPA

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Table 1 Extended

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Figure 1 shows the preoperative clinical course of these patients. Laboratory data obtained preoperatively, including white blood cell count, C-reactive protein level, and percent of eosinophils did not suggest the presence of peritonitis (Fig. 1). All patients had severe abdominal pain and fever, which suggested intestinal perforation.

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The first patient underwent resection of 55 cm of small intestine repaired with a primary anastomosis. An 8-mm perforation with a 2.5-cm ulcer (Fig. 2A) and multiple small ulcers were found in the resected ileum macroscopically. Histopathologic examination revealed active angiitis with granuloma, surrounded by slight eosinophilic infiltration in the mesenteric fat (Fig. 2B). A tear in the internal elastic membrane of a small artery was detected by Elastica van Giesen stain (Fig. 2C). The pathologic findings of the resected intestine from the second operation were similar to the findings from the first resection.

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Patient 2 was explored laparoscopically, and a 5-mm perforation in the ileum with purulent exudate was identified. This area of the ileum was resected (Fig. 2D). Histopathologic examination showed necrotizing vasculitis of small vessels, with luminal obstruction (Fig. 2E), as well as destruction of the internal elastic membrane (Fig. 2F).

Patient 3 had several perforations 8 to 10 mm in size with multiple ulcers in the resected ileum measuring 58 cm in length (Fig. 2G). Histopathologic examination showed fibrinoid necrosis of small arteries surrounded by a pronounced inflammatory infiltrate consisting of eosinophils in the mesentery (Fig. 2H) and destruction of the internal elastic membrane (Fig. 2I).

Discussion

EGPA is a rare vasculitis that affects small- to medium-sized vessels and is associated with asthma and eosinophilia.³ The etiology of EGPA is unclear, but outcomes are generally good.¹² Factors such as renal disease, gastrointestinal involvement, cardiomyopathy, and central nervous system involvement predict a poor prognosis in patients with EGPA.¹³ Gastrointestinal perforations are responsible for approximately 10% of deaths associated with systemic necrotizing vasculitis.¹⁴

Gastrointestinal involvement occurs in up to 50% of patients with EGPA, and the small intestine is the most common site.¹⁵ In contrast, colonic perforations are relatively uncommon.¹⁵ Corticosteroids are used for the initial management of patients with EGPA.¹⁰ However, corticosteroids enhance fibrotic changes in the vascular intima, which can lead to vascular occlusion, ischemia, and perforation.¹⁶ Even if treatment with corticosteroids is stopped, fibrosis and organized thrombus formation persist once these changes occur.¹¹ As is well-known among surgeons, the anti-inflammatory properties of corticosteroids may mask symptoms of gastroduodenal ulcers or other intra-abdominal conditions, and this may lead to a delay in diagnosis.¹⁷

The first patient in this series underwent reoperation due to a second small bowel perforation. Corticosteroids may increase the risk of postoperative complications, such as anastomotic leak.¹¹ We did not perform an anastomosis in patient 3 because this patient was receiving high-dose corticosteroids at that time (Table 1). A previous report suggested changing the therapy to immunosuppressive agents. This may be considered when gastrointestinal involvement is suspected based on symptoms and may reduce the incidence of perforation.¹⁶

Performing an anastomosis is associated with an increased risk of anastomotic leaks in patients receiving high-dose corticosteroid therapy.¹⁸ Patients must be carefully evaluated for the development of such complications in the postoperative period, with appropriate workup as indicated.

Investigating the entire length of the small intestine can be difficult. Recently, the use of double balloon endoscopy¹⁹ and capsule endoscopy²⁰ have been reported in patients with EGPA. These techniques allow the identification of multiple ulcers in the small intestine that could lead to perforation. In patients with abdominal symptoms and no definite evidence of perforation, these techniques may be useful to evaluate the entire length of the small intestine, although the risks associated with these evaluations must also be considered.

Patients with EGPA who present with abdominal symptoms must be evaluated carefully, considering the possibility of intestinal perforation, especially in patients undergoing treatment with corticosteroids.