Abbreviations: TP: Total Protein; Alb: Albumin; AST: Aspartate Aminotransferase; ALT: Alanine Aminotransferase; LDH: Lactate Dehydrogenase; BUN: Blood Urea Nitrogen; Cre: Creatinine; UIBC: Unsaturated Iron Binding Capacity; WBC: White Blood Cell; RBC: Red Blood Cell; Hb: Hemoglobin; Hct: Hematocrit: RET; Reticulocyte; Plt: Platelet

Introduction

In Japan, Obscure Gastrointestinal Bleeding (OGIB) is defined as persistent or recurrent bleeding with no apparent source on Esophagogastroduodenoscopy (EGD) and Colonoscopy (CS) [1]. OGIB accounts for approximately 5–10% of all cases of gastrointestinal bleeding, and 75% of these cases involve the small bowel [1-3]. Pyogenic Granulomas (PGs) are inflammatory vascular tumors commonly occurring on the oral mucosa or skin and characterized by a propensity to bleed [4]. PGs rarely occur in the gastrointestinal tract, especially in the small intestine, and are a rare cause of gastrointestinal bleeding. In this report, we describe a case of as OGIB diagnosed as PG by Capsule Endoscopy (CE) and Double Balloon Endoscopy (DBE).

Case Presentation

The patient was an 84-year-old woman. She was receiving treatment for arteriosclerosis obliterans and diabetes and was taking two antithrombotic medications. She underwent Esophagogastroduodenoscopy (EGD) and Colonoscopy (CS) two months before, due to abdominal pain and diarrhea. No abnormalities were detected in the examinations at that time, and the patient was under observation. However, the progression of anemia was observed during the course of the follow-up, and the patient visited the department of gastroenterology for a second examination. She was not aware of melena. EGD and CS were performed; however, no obvious source of bleeding was found. Laboratory data at the time of admission to our hospital are shown in (Table 1).

Table 1: Descriptive lab data at the initial visit.

Contrast-enhanced Computed Tomography (CT) did not reveal an obvious source. We suspected OGIB and performed CE, revealing a polyp-like finding in the jejunum with adherent blood (Figure 1). This was thought to be the cause of the anemia and the source of the bleeding; therefore, an oral DBE was performed for close examination. A submucosal raised tumor-like lesion with a blood clot was found in the upper jejunum, though not large in size (approximately 10 mm in diameter) (Figure 2). The lesion was judged to be difficult to resect endoscopically; it was marked with ink dots and surgical resection was planned. A partial resection of the small intestine was performed (Figure 3) and the patient was discharged after 15 days without major complications. Histological examination revealed a single layer of proliferating capillaries covered with endothelial cells, inflammatory cells in the interstitium, and pathologically diagnosed PG (Figure 4). The postoperative course was uneventful, and there was no subsequent relapse of symptoms.

Figure 1: A lesion (5 mm mass) was discovered using capsule endoscopy; its head was erythematous and some parts were hemorrhaging.

Figure 2: Double-balloon endoscopy findings. There was no bleeding; however, the entire mass was erythematous and submucosal tumor-like in morphology.

Figure 3: A partial small bowel resection surgery was performed.

Figure 4: Microscopic appearance of the hematoxylin and eosin (H&E)-stained PG. Histologically, tumors have large and small vascular hyperplasia, and many inflammatory cells infiltrating the stroma.

Discussion

PG, also called granuloma telangiectatic or lobular capillary hemangioma, was first described in 1897 [5]. PG lesions are generally seen as polypoid masses with prominent erythematous lesions that hemorrhage easily. They are thought to originate exclusively from the mucosal or submucosal layer and are caused by a local injury or irritant. However, a hormonal mechanism may exist, as the incidence increases during pregnancy. In general, PG affects both sexes equally and occurs in all age groups [6]. PG occurring in the gastrointestinal tract is reported to be more common in older adults, although there is no significant difference with respect to sex [7]. The characteristic histopathologic features of PG include capillary proliferation and lobular arrangement with inflammation and edematous stroma and endothelial cell swelling. PG is generally treated by local resection [8].

Gastrointestinal PG is extremely rare and a very rare cause of gastrointestinal bleeding. When limited to the small intestine from the duodenal jejunal bend to the ileum, a search of PubMed revealed only 31 cases [5,7-29]. The demographic characteristics of cases reported to date were as follows: 15 men (48.4%), 16 women (51.6%); mean age: 60.8 (26–86) years. Anemia was the most common complaint (n = 18), followed by melena (n = 8). Three patients were asymptomatic. The most common site was the ileum [n = 20 (64.5%)], followed by the jejunum [n = 11 (35.5%)].　Surgery was performed in 17 patients (54.8%) and endoscopic mucosal resection in 13 (41.9%); only one patient underwent laser ablation.

Although there are no guidelines for the endoscopic resection of small intestinal polyps, pedunculated and sub-pedunculated small intestinal polyps are considered to have a relatively low risk of perforation and are eligible for endoscopic treatment [29]. However, PGs that have invaded the submucosal layer through the muscularis have been reported [30], and preoperative endoscopic ultrasonography may be considered to avoid incomplete endoscopic resection or perforation associated with endoscopic treatment. There is no established treatment for PG; however, appropriate and safe treatment should be selected for each individual case. This case showed a submucosal tumor-like morphology, and the risk of perforation was considered high if endoscopic treatment was chosen. Surgical treatment was chosen for safety, and the patient has not exhibited the recurrence of symptoms. Arakawa et al. [31] reported that the rate of diagnosis of OGIB by CE was 54%, which is not significantly different from that of DBE, indicating the effectiveness of CE. If a tumor lesion is detected at CE, detailed observation should be performed by DBE to determine the treatment strategy.

Conclusions

In summary, PG in the small intestine is a rare cause of OGIB and should be considered in the differential diagnoses. It is useful to perform CE for the detection of OGIB after eliminating other sources of bleeding. With surgical resection, PG is a disease with no recurrence and a good prognosis.

Disclosure

Acknowledgments: We would like to extend our heartfelt thanks to Gifu University School of Medicine Graduate School of Medicine for their invaluable support and contributions, which significantly enriched our research and made its success possible.

Funding: This research received no external funding.

Informed Consent Statement: Informed consent was obtained from the patient involved in this study. Written informed consent has been obtained from the patient to publish this paper.

Data Availability Statement: Data supporting the study results can be provided followed by request sent to the corresponding author’s e-mail.

Conflicts of Interest: None.

References

1. Yamamoto H, Ogata H, Matsumoto T, Ohmiya N, Ohtsuka K, et al. (2017) Clinical practice guideline for enteroscopy. Dig. Endosc. 29: 519–546.
2. Gerson LB, Fidler JL, Cave DR, Leighton JA (2015) ACG clinical guideline: diagnosis and management of small bowel bleeding. Am. J. Gastroenterol 110: 1265–1287.
3. Pennazio M, Spada C, Eliakim R, Keuchel M, May A, et al. (2015) Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline. Endoscopy 47: 352–376.
4. Hamid J, Majid S, Nooshin M 2006) Oral pyogenic granuloma: a review. J. Oral Sci 48: 167–175.
5. Misawa S, Sakamoto H, Kurogochi A, Kirii Y, Nakamura S, et al. (2015) Rare cause of severe anemia due to pyogenic granuloma in the jejunum. BMC Gastroenterol 15: 126.
6. Rosai J. (1995) Ackerman’s Surgical Pathology. 8th ed. Mosby Company, St Louis.
7. van Eeden S, Offerhaus GJ, Morsink FH, van Rees BP, Busch OR, et al. (2004) Pyogenic granuloma: an unrecognized cause of gastrointestinal bleeding. Virchows Arch 444: 590–593.
8. Nagoya H, Tanaka S, Tatsuguchi A, Mitsui K, Ehara A, et al. (2010) Rare cause of obscure gastrointestinal bleeding due to pyogenic granuloma in the ileum detected by capsule endoscopy and treated with double balloon endoscopy. Dig. Endosc 22: 71–73.
9. Payson BA, Karpas CM, Exelby P (1967) Intussusception due to pyogenic granuloma of ileum. N Y State J. Med 67: 2135–2138.
10. Meuwissen SG, Willig AP, Hausman R, Starink TM, Mathus-Vliegen EM (1986) Multiple angiomatous proliferations of ileal stoma following Campylobacter enteritis. Effect of laser photocoagulation. Dig. Dis. Sci 31: 327–332.
11. Iwakubo A, Tsuda T, Kubota M, Wakabayashi J, Kobayashi K, et al. (1989) Diagnostic 99mTc-labeled red blood cells scintigraphy in gastrointestinal tract bleeding from an intestinal pyogenic granuloma. Kaku Igaku 26: 1439–1443.
12. Hizawa K, Iida M, Matsumoto T, Kohrogi N, Yao T, et al. (1993) Neoplastic transformation arising in Peutz-Jeghers polyposis. Dis. Colon Rectum 36: 953–957.
13. Yao T, Nagai E, Utsunomiya T, Tsuneyoshi M (1995) An intestinal counterpart of pyogenic granuloma of the skin. A newly proposed entity. Am. J. Surg. Pathol 19: 1054–1060.
14. Motohashi Y, Hisamatsu T, Ikezawa T, Matsuoka K, Ogawa S, et al. (1999) A case of pyogenic granuloma in the small intestine. Nihon Shokakibyo Gakkai Zasshi 96: 1396–1400.
15. Shirakawa K, Nakamura T, Endo M, Suzuki K, Fujimori T, et al. (2007) Pyogenic granuloma of the small intestine. Gastrointest. Endosc 66: 827–828.
16. Chou JW, Lai HC, Lin YC (2009) Image of the month. Pyogenic granuloma of the small bowel diagnosed by capsule endoscopy and double-balloon enteroscopy. Clin. Gastroenterol. Hepatol 7: A26.
17. Moffatt DC, Warwryko P, Singh H (2009) Pyogenic granuloma: an unusual cause of massive gastrointestinal bleeding from the small bowel. Can. J. Gastroenterol 23: 261–264.
18. Kuga R, Furuya CK, Jr, Fylyk SN, Sakai P (2009) Solitary pyogenic granuloma of the small bowel as the cause of obscure gastrointestinal bleeding. Endoscopy 41: E76–77.
19. Yamashita K, Arimura Y, Saito M, Iida T, Suzuki R, et al. (2013) Pyogenic granuloma of the small bowel. Endoscopy 45: E9–10.
20. Katsurahara M, Kitade T, Tano S, Hamada Y, Inoue H, et al. (2015) Pyogenic granuloma in the small intestine: a rare cause of obscure gastrointestinal bleeding. Endoscopy 47: E133–134.
21. Kikuchi A, Sujino T, Yamaoka M, Yoneno K, Ohgo H, et al. (2014) Pyogenic granuloma of the ileum diagnosed by double-balloon enteroscopy. Intern. Med 53: 2057–2059.
22. De María J, Curvale C, Guidi M, Hwang H, Matanó R (2017) Pyogenic granuloma of the jejunum; diagnosis and treatment with double-balloon enteroscopy: A case report. Rev. Gastroenterol. Mex 82: 94–96.
23. Romero Mascarell C, García Pagán JC, Araujo IK, Llach J, González-Suárez B (2017) Pyogenic granuloma in the jejunum successfully removed by single-balloon enteroscopy. Rev. Esp. Enferm. Dig 109: 152–154.
24. Zhang D, Glover SC, Liu W, Liu X, Lai J (2019) Small bowel pyogenic granuloma with cytomegalovirus infection in a patient with Crohn's disease (report of a case and review of the literature). In Vivo 33: 251–254.
25. Castela J, Mao de Ferro S, Ferreira S, Cabrera R, Dias Pereira A (2018) Pyogenic granuloma of the jejunum: an unusual cause of anemia. J. Gastrointest. Surg 22: 1795–1796.
26. Mizutani Y, Hirooka Y, Watanabe O, Nakamura M, Yamamura T, et al. (2015) Pyogenic granuloma of the small bowel treated by double-balloon enteroscopy. Gastrointest. Endosc 81: 1023–1024.
27. Iravani A, Law A, Millward M, Warner M, Sparrow S (2015) Bleeding small intestine pyogenic granuloma on 18F-FDG PET/CT. Clin. Nucl. Med 40: 869–870.
28. Hirata K, Hosoe N, Imaeda H, Naganuma M, Murata H, et al. (2014) Obscure gastrointestinal bleeding: resection of a pyogenic granuloma of the ileum via double-balloon enteroscopy. Clin. J. Gastroenterol 7: 397–401.
29. Hayashi Y, Hosoe N, Takabayashi K, Kamiya KJL, Mutaguchi M, et al. (2020) Clinical and endoscopic characteristics of pyogenic granuloma in the small intestine: a case series with literature review. Intern. Med 59: 501–505.
30. Motohashi Y, Hisamatsu T, Ikezawa T, Matsuoka K, Ogawa S, et al. (1999) A case of pyogenic granuloma in the small intestine. Nihon Shokakibyo Gakkai Zasshi 96: 1396–1400.
31. Arakawa D, Ohmiya N, Nakamura M, Honda W, Shirai O, et al. (2009) Outcome after enteroscopy for patients with obscure GI bleeding: diagnostic comparison between double-balloon endoscopy and videocapsule endoscopy. Gastrointest. Endosc 69: 866–874.