Diagn Interv Radiol 2012; 18:183–188 GASTROINTESTINAL IMAGING © Turkish Society of Radiology 2012 CASE REPORT

Eosinophilic disorders of the : imaging features

Chandramohan Anuradha, Rohin Mittal, Myla Yacob, M. T. Manipadam, Susy Kurian, Anu Eapen

ABSTRACT osinophilic disorders of the gastrointestinal (GI) tract are a group Eosinophilic disorders of the gastrointestinal tract are increas- of rare inflammatory conditions characterized by focal or diffuse ingly rare but remain an important cause of long-standing gastrointestinal symptoms. Diagnosis is usually delayed be- E eosinophilic infiltration of the bowel wall (1). These disorders cause the disease mimics other inflammatory disorders and is can involve any segment of the GI tract from the pharynx to the rec- often not suspected initially. We report a series of four cases to highlight the various imaging appearances of this condi- tum. The location and depth of the involved bowel wall determine the tion. Two patients presented with upper gastrointestinal in- clinical presentation. These disorders should be considered in the dif- volvement, one patient presented with small and large bowel ferential diagnosis for longstanding non-resolving GI symptoms, such involvement, and one patient presented with diffuse involve- ment of the entire gastrointestinal tract. as dysphagia, food impaction, weight loss, , and (1, 2). Although histopathology is the gold standard for diagnosis, recognition Key words: • gastrointestinal tract • diagnostic imaging • eosinophilia of imaging features of this rare disorder aids in early diagnosis and ther- apy. Literature on the imaging features of the disease is sparse. We report four cases with varied presentations to highlight the imaging features of this disease.

Case reports Case 1 A 28-year-old male presented with progressive dysphagia, vomiting, and weight loss for two months. He was receiving treatment for allergic rhinitis. Clinical examination was unremarkable. Initial laboratory tests were unremarkable with no peripheral eosinophilia. An initial contrast swallow revealed a contained mid-esophageal per- foration with a right esophagobronchial fistula. Mucosal irregularity, ulceration and diverticulae of the mid and lower thoracic , the gastroesophageal junction, and the lesser curve of the were noted. The stomach was non-distensible, and gastric rugae were markedly thickened (Fig. 1a–1c). In addition, computed tomography (CT) of the thorax revealed a short segment of circumferential smooth wall thickening in the upper thoracic esophagus, multiple subcentim- eter mediastinal, and lesser omental nodes without central necrosis (Fig. 1d and 1e). Upper GI revealed an esophagobronchial fistula at 30 cm with edematous and friable mucosa covered with thick inflammatory exudates along the entire length of esophagus and stom- ach. Multiple endoscopic biopsies of the esophagus and stomach were non-diagnostic. The patient underwent laparotomy with a full thickness gastric wall biopsy and a feeding jejunostomy. Gastric biopsy was consistent with eosinophilic . Oral steroids were administered, and the patient From the Departments of Radiology (C.A.  responded well to this treatment. The patient was scheduled for elective [email protected], A.E.), Surgery (R.M., M.Y.), and Pathology (M.T.M., S.K.), Christian Medical College, Vellore, surgical repair of the esophagobronchial fistula. Tamil Nadu, India. Case 2 Received 15 April 2011; revision requested 10 May 2011; revision received 28 June 2011; accepted 2 July 2011. A 38-year-old female presented with non-progressive dysphagia that had persisted for one year. The patient had a history of melena and Published online 27 September 2011 DOI 10.4261/1305-3825.DIR.4490-11.1 one episode of . She had undergone a tracheostomy for

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Figure 1. a–e. Contrast swallow (a–c) shows mucosal irregularity, ulceration and diverticulae (a, arrows) in the mid and lower thoracic esophagus, mid-esophageal perforation and right esophagobronchial fistula (b, asterisk), poor gastric distension with thickened gastric rugae and gastric wall thickening (c, asterisk). Contrast-enhanced CT of the thorax and abdomen reveals diffuse esophageal thickening (d) and gastric wall thickening (e, asterisk). Note the preserved mucosal lining (e, arrows) of the stomach wall.

idiopathic laryngeal stenosis 12 years adenopathy and luminal narrowing at Clinical examination was unremarkable. ago. The patient was receiving treat- the level of pharynx were present. Hematological investigations revealed ment for rheumatoid arthritis and Mucosal biopsy of the pharynx and peripheral eosinophilia (39%–43%). hypothyroidism. Clinical examina- GE junction was diagnostic of eosi- CT revealed diffuse wall thicken- tion of the neck and abdomen was nophilic pharyngitis and esophagi- ing of the entire GI tract from the es- unremarkable except for the trache- tis with 20–100 eosinophil cells/high ophagus to the with a sparing ostomy. Hematological investigations power field (Fig. 2f). Oral steroids were of small segments of the distal . revealed a peripheral eosinophilia administered, and a marked improve- A “halo sign” due to a layering of the (34%). ment was observed. A follow-up CT of bowel wall and an “araneid-limb-like” An upper GI endoscopy revealed the thorax after six months revealed sign due to diffuse mucosal fold thick- an ulcerated polypoidal growth at marked improvement (Fig. 2g–2i). The ening were present (Fig. 3). The trans- the gastroesophageal (GE) junction. patient was symptom-free with a nor- verse colon and the ascending colon CT revealed an asymmetrical homog- mal peripheral eosinophil cell count were predominantly involved with enous circumferential wall thickening and erythrocyte sedimentation rate at marked surrounding fat stranding. of the oropharynx, the entire esopha- a one-year follow-up. There was minimal ascites and no lym- gus and GE junction with an upper phadenopathy. Upper GI endoscopy thoracic esophageal diverticula and a Case 3 and colonoscopy revealed no mucosal large polypoidal mass that projected A 35-year-old male presented with abnormalities. A full thickness open bi- into the stomach lumen at the fundus colicky abdominal pain, vomiting, opsy of the small bowel was consistent (Fig. 2a–2e). Significant mediastinal and diarrhea of one-month duration. with eosinophilic . A tapering

184 • March-April 2012 • Diagnostic and Interventional Radiology Anuradha et al. a b Figure 2. a–i. Contrast- enhanced CT of the thorax at presentation (a–e) revealed circumferential soft tissue thickening (a, asterisk) in the oropharynx and larynx with severe airway narrowing (a, arrow), upper thoracic esophageal diverticulae (b, asterisk), diffuse circumferential thickening (c, asterisk) of the lower thoracic esophagus, thickening of the gastroesophageal junction with a polypoidal mass that projects into the cardia of the stomach (d, e, asterisks). High-power view c d of esophageal mucosa (f) with dense infiltration by eosinophils of the lamina propria (hematoxylin and eosin, ×400). Post-treatment CT of the thorax in the same patient at the six-month follow-up exam (g–i) showing an improvement of airway narrowing, esophageal thickening and the GE junction mass.

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Volume 18 • Issue 2 Eosinophilic disorders of the gastrointestinal tract • 185 a b

Figure 3. a, b. Contrast-enhanced CT of the abdomen reveals diffuse circumferential mural thickening of the small bowel loops and the colon. Ascending and transverse colon shows an “araneid-limb-like” sign (a, arrows) due to mucosal fold thickening and contrast trapped between the thickened folds and a layering of the bowel wall (b, target sign, arrows).

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Figure 4. a, b. Contrast-enhanced CT of the abdomen showing a diffuse thickening of ileal loops with a positive halo sign (a, arrows) and moderate ascites (b, asterisk).

dose of steroids was administered with and transverse colostomy with a pro- improved. She was scheduled for elec- a dramatic improvement of symptoms. visional diagnosis of inflammatory tive ileostomy closure at a later date. A complete resolution of symptoms bowel disease. Final histopathology and peripheral eosinophilia were ob- revealed eosinophilic enteritis pre- Discussion served at a one-year follow-up exam. dominantly in the muscular and sero- Kaijser first described eosinophilic sal layers and mild eosinophilia in the disorders of the GI tract in 1937. These Case 4 regional nodes. disorders are classified as primary A 33-year-old female presented with High-dose corticosteroids were ad- when no apparent inciting cause can abdominal pain, vomiting and loose ministered, and the patient developed be demonstrated and secondary when stools that had persisted for six months. uncontrolled blood sugar that was sta- the disorder appears in response to The patient also had bilateral symmet- bilized with oral hypoglycemic agents various infections, allergies or connec- ric polyarthralgia for six years. Clinical and insulin. Six weeks after the index tive tissue disorders (1), as observed in examination and basic hematological operation, dense adhesions were ob- three of our patients. In 50% to 70% of reports were normal. served during surgery to reverse the these patients, a personal or a family Upper and lower GI stoma that necessitated small bowel history of food allergies or atopic disor- were unremarkable. CT of the abdo- resection and ileocolonic anastomo- der can be elicited (3). men revealed a diffuse thickening of sis. The patient developed an anasto- Clinical features depend on the seg- the terminal ileum and the motic leak that required relaparotomy, ment of bowel and the layers of bowel with a positive “halo sign” and moder- the dismantling of ileocolonic anasto- wall that are involved. Talley et al. ate ascites (Fig. 4). Ascitic fluid was not mosis and end ileostomy, which pro- (2) and Klein et al. (4) have classified analyzed. No significant lymphaden- longed hospitalization. The patient eosinophilic GI disorders as mucosal, opathy was observed. The patient un- was discharged on a tapering dose muscular or serosal disease according derwent a limited right hemicolectomy of corticosteroids and she gradually to the predominant layer of the bowel

186 • March-April 2012 • Diagnostic and Interventional Radiology Anuradha et al. wall that is involved. Mucosal disease not continuous rings; feline esopha- of HIV (16). Most incidences of the is the most common (25%–100%) and gus, which may be mistaken for ringed esophageal tuberculosis are secondary presents with , vomiting, ab- esophagus but is a transient phenom- and are associated with mediastinal dominal pain, diarrhea, weight loss enon; and congenital esophageal ste- lymphadenopathy, which is necrotic and GI bleeding. Muscular disease is nosis (8, 9). with peripheral rim enhancement the next most common (13%–70%) Smooth segmental strictures are ob- and abnormal lung densities. Primary and presents with symptoms of ob- served in 70% of patients predomi- esophageal tuberculosis is extremely struction or its related complica- nantly in the mid and distal portions rare. Moreover, esophagobronchial fis- tions. Serosal disease is less common of the esophagus. tula in tuberculosis occurs where large (12%–40%) and is characterized by with irregular ulcerated lumen is not mediastinal necrotic nodes indent and intense peripheral eosinophilia and commonly observed (10%); granu- erode into the esophagus and bron- eosinophilic ascites (1). Serosal disease lar mucosa, which is suggestive of es- chus (16, 17). promptly responds to steroid therapy ophagitis, is observed in approximate- Lymphoma of the esophagus is an (1–3, 5). Rare associations with pleural ly 30% of patients (8, 10). Other signs, uncommon condition, but primary effusion, pericardial effusion, urinary such as “small caliber esophagus”, have esophageal lymphoma without extra- bladder and gall bladder thickening, been described in which the esophagus esophageal manifestation has been and focal lesions in the appears essentially normal on barium reported in fewer than 10 cases in spleen and liver have been described esophagogram except for small lumen the literature (18). Imaging features (1, 5). size, but this reduction in size does not include mucosal thickening, submu- Although any segment of the GI qualify as a stricture (11). Hiatal cosal nodules, ulcers and erosions, tract can be affected by eosinophilic and reflux are commonly the relative preservation of the lumen GI disorder, the stomach is most com- associated with eosinophilic esophagi- despite a large mass, achalasia-cardia- monly involved (43%) followed by a tis in 77% and 69% of patients, re- like appearance, spontaneous perfora- combined involvement of the stom- spectively (8). Diffuse esophageal wall tion and esophagobronchial fistula. ach, and proximal small thickening is observed on CT (9, 10). Inflammatory bowel diseases, such as bowel and esophageal involvement. Our first patient had unusual imag- Crohn’s disease, have multifocal areas Large bowel involvement is less com- ing findings, such as severe diffuse of involvement. mon, and eosinophilic pharyngitis mucosal irregularity and ulcerations, Imaging features of eosinophilic gas- is extremely rare (1, 2, 6). Peripheral spontaneous esophageal perforation troenteritis include bowel wall thick- eosinophilia has been reported in up and esophagobronchial fistula. To our ening, layering of the bowel wall, to 80% of cases with a higher absolute knowledge, an esophagobronchial diffuse mucosal fold thickening and eosinophil count in serosal disease (1, fistula secondary to eosinophilic es- luminal narrowing with or without 2, 5, 6). Peripheral eosinophilia was ophagitis has not been reported pre- intestinal obstruction. Signs such as observed in two of our patients; one viously in the literature. Spontaneous the “halo sign” and the “araneid limb- patient had mucosal disease, and the has been described like” sign have been described previ- other patient had serosal disease. previously, but it is extremely rare, es- ously (19) and were observed in our is more pecially in adults (12). Most perfora- cases. The halo sign is observed due common in children than adults. tions in eosinophilic esophagitis are to submucosal edema, which causes a Adults with eosinophilic esophagitis iatrogenic and occurred after endosco- layering of the bowel wall. When dif- are usually 30 to 50 years old, and the py and esophageal stricture dilatation fuse mucosal thickening is present, disease has a mild male predominance (13). Our patient also had severe mu- contrast within the mucosal sinuses in (1). Imaging features of eosinophilic cosal irregularity and ulcerations. This the longitudinal section of the bowel esophagitis depend on the degree of degree of mucosal abnormality has not on CT produces an “araneid-limb-like” inflammation and the layer of esopha- been described in previous reports. sign. Both of these signs are only ob- geal wall that is involved. In a study of The involvement of the pharynx and served in inflammatory pathologies, idiopathic eosinophilic esophagitis in larynx in eosinophilic esophagitis is which aids in the differentiation of adults, Zimmerman et al. (7) demon- extremely rare in adults (14). Airway eosinophilic from neo- strated that 71% of patients with eosi- involvement is reported more com- plastic conditions, such as lymphoma nophilic esophagitis had esophageal monly in children with eosinophilic and carcinoma. strictures, and 50% of these patients esophagitis, and 15% of children with In tuberculosis, is had a “ringed esophagus”. A ringed eosinophilic esophagitis have airway due to ulcerohypertrophic disease and esophagus is multiple, fixed tracheal and extra-intestinal symptoms (15). fibrotic strictures of the bowel, which rings that appear as closely packed in- Pharyngeal and laryngeal stenosis was predominantly occur in the duodenum dentations on the esophageal lumen. observed in one of our patients. and the ileum. The ileocecal junction Although this sign is observed in only Conditions such as esophageal tu- is involved in 80%–90% of gastroin- 50% of patients, it is highly sugges- berculosis, lymphoma, malignancy testinal tuberculosis. Peritoneal and tive of the diagnosis of eosinophilic and Crohn’s disease share similar im- omental thickening are commonly as- esophagitis when present. The differ- aging findings. Although tuberculo- sociated (20). However, eosinophilic ential diagnosis for ringed esophagus sis is a very common infection in our gastroenteritis is a predominantly mus- includes peptic strictures, which are country, esophageal tuberculosis is un- cular disease that shows features of ob- fixed transverse fold indentions in the common. However, esophageal tuber- struction, and unlike tuberculosis, it is lumen that appear as a step ladder but culosis is more common in the setting not associated with ascites, peritoneal

Volume 18 • Issue 2 Eosinophilic disorders of the gastrointestinal tract • 187 and omental thickening. In lympho- the gross radiological abnormalities, 7. Zimmerman SL, Levine MS, Rubesin SE, et ma, there is a homogenous circum- and full thickness open biopsy was re- al. Idiopathic eosinophilic esophagitis in ferential thickening of the bowel wall quired. Approximately 90% of patients adults: the ringed esophagus. Radiology 2005; 236:159–165. with no bowel wall layering or features with eosinophilic GI disorders respond 8. Vitellas KM, Bennett WF, Bova JG, of bowel obstruction, which may be well to treatment with systemic ster- Johnston JC, Caldwell JH, Mayle JE. associated with an “aneurysmal dilata- oids. Patients may have a relapsing and Idiopathic eosinophilic esophagitis. tion” of bowel. These features should remitting disease course, but many pa- Radiology 1993; 186:789–793. 9. Cantu P, Velio P, Prada A, Penagini R. aid in the differentiation of these two tients have long periods of remission. Ringed oesophagus and idiopathic eosi- conditions. Patients with eosinophilic esophagitis nophilic oesophagitis in adults: an asso- Eosinophil-rich ascites have a well have chronic disease due to strictures ciation in two cases. Dig Liver Dis 2005; described association with serosal pre- (1, 2, 5). All four patients in our series 37:129–134. dominant disease (19). Serosal disease is responded well to corticosteroid treat- 10. White SB, Levine MS, Rubesin SE, Spencer GS, Katzka DA, Laufer I. The small-caliber non-obstructive in nature (19). Two of ment. One patient with serosal disease esophagus: radiographic sign of idiopathic our patients with serosal predominant had multiple surgeries and a morbid eosinophilic esophagitis. Radiology 2010; disease showed some ascites. However, postoperative period. 256:127–134. ascitic fluid was not analyzed due to the In conclusion, radiology plays an 11. Vasilopoulos S, Murphy P, Auerbach A, et important role in the management of al. The small-caliber esophagus: an unap- small amounts of ascites. Eosinophilic preciated cause of dysphagia for solids in mesenteric lymphadenopathy is asso- patients with eosinophilic disorders of patients with eosinophilic esophagitis. ciated with serosal disease. However, the GI tract by the accurate identifi- Gastrointest Endosc 2002; 55:99–106. the imaging features of these nodes are cation of the site of the abnormality, 12. Robles-Medranda C, Villard F, Bouvier R, limited to a few case reports in which which allows for the targeting of biop- Dumortier J, Lachaux A. Spontaneous es- ophageal perforation in eosinophilic es- nodes with central necrosis have been sies to the correct site. In the appropri- ophagitis in children. Endoscopy 2008; described (19). Mesenteric nodes with ate clinical setting, imaging features aid 40:171. peripheral enhancement and central in the diagnosis of suspect eosinophilic 13. Prasad GA, Arora AS. Spontaneous per- necrosis are classically observed in tu- gastrointestinal disorders. Imaging also foration in the ringed esophagus. Dis helps in the identification of compli- Esophagus 2005; 18:406–409. berculosis, and 80% of disseminated 14. Watanabe M, Matsui N, Hamada S, et al. tuberculosis and 52% of non-dissemi- cations and in the follow-up examina- A rare case of idiopathic hypereosinophilic nated tuberculosis are associated with tion of these patients. syndrome involving the oral cavity associ- abdominal lymphadenopathy (21). ated with the esophagus and gastrointesti- Although abdominal lymphadenopa- Conflicts of interest disclosure nal tract. Intern Med 2004; 43:336–339. 15. Dauer EH, Ponikau JU, Smyrk TC, Murray thy is observed in lymphoma, these The authors declared no conflicts of interest. JA, Thompson DM. Airway manifestations nodes are homogenous in nature and of pediatric eosinophilic esophagitis: a become necrotic only after treatment References clinical and histopathologic report of an (20). None of our patients showed sig- 1. Yan BM, Shaffer EA. Primary eosinophilic emerging association. Ann Otol Rhinol disorders of the gastrointestinal tract. Gut Laryngol 2006; 115:507–517. nificant lymphadenopathy. 16. Nagi B, Lal A, Kochhar R, et al. Imaging Therefore, protean clinical and im- 2009; 58:721–732. 2. Talley NJ, Shorter RG, Phillips SF, of esophageal tuberculosis: a review of 23 aging appearances of eosinophilic GI Zinsmeister AR. Eosinophilic gastroenteri- cases. Acta Radiol 2003; 44:329–333. disorders closely mimic other diseases, tis: a clinicopathological study of patients 17. Mokoena T, Shama DM, Ngakane H, Bryer such as tuberculosis, Crohn’s disease, with disease of the mucosa, muscle layer, JV. Oesophageal tuberculosis: a review of eleven cases. Postgrad Med J 1992; 68:110– lymphoma and malignancy. The di- and subserosal tissues. Gut 1990; 31:54–58. 3. Yun MY, Cho YU, Park IS, et al. Eosinophilic 115. agnosis of eosinophilic GI disorders is gastroenteritis presenting as small bowel 18. Oguzkurt L, Karabulut N, Cakmakci E, not often considered at initial presen- obstruction: a case report and review of Besim A. Primary non-Hodgkin’s lym- tation. The diagnosis is confirmed by the literature. World J Gastroenterol 2007; phoma of the esophagus. Abdom Imaging 13:1758–1760. 1997; 22:8–10. a histopathological examination of the 19. Zheng X, Cheng J, Pan K, Yang K, Wang H, tissue that is obtained by endoscopy 4. Klein NC, Hargrove RL, Sleisenger MH, Jeffries GH. Eosinophilic gastroenteritis. Wu E. Eosinophilic enteritis: CT features. or open biopsy. Multiple biopsies are Medicine (Baltimore) 1970; 49:299–319. Abdom Imaging 2008; 33:191–195. often required to prove the diagno- 5. Sheikh RA, Prindiville TP, Pecha RE, 20. Gulati MS, Sarma D, Paul SB. CT appear- sis because eosinophilic infiltration is Ruebner BH. Unusual presentations of ances in abdominal tuberculosis. A picto- rial essay. Clin Imaging 1999; 23:51–59. patchy (2). Therefore, the final diagno- eosinophilic gastroenteritis: case series and review of literature. World J Gastroenterol 21. Yang ZG, Min PQ, Sone S, et al. Tuberculosis sis and treatment are delayed (1). This 2009; 15:2156–2161. versus lymphomas in the abdominal delay was observed in our first patient 6. Naylor AR. Eosinophilic gastroenteritis. lymph nodes: evaluation with contrast- in whom multiple endoscopic biopsies Scott Med J 1990; 35:163–165. enhanced CT. AJR Am J Roentgenol 1999; 172:619–623. did not reveal the diagnosis despite

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