Ağustos 2012

40-43

Arzu ENSARİ(1), Yasemin YUYUCU KARABULUT(2)

Ankara Üniversitesi Tıp Fakültesi,(1)Patoloji Bilim Dalı, Ankara Çankırı Devlet Hastanesi,(2) Patoloji Bölümü, Çankırı

Giriş ve Amaç:Eozinofilik özofajit çocuklarda yeni tanımlanmış, özofagusun allerjik hastalığıdır. Diğer özofajit tiplerinde de izlenmekle birlikte özofageal eozinofili, eozinofilik özofajit tanısında temel histopatolojik bulgudur. Çalış-mamızda çocuk yaş gurubunda eozinofilik özofajit tanısında histopatolojik kriterlerin tanımlayıcılığı değerlendirilmiştir. Gereç ve Yöntem: Çalışmamız-da 2007-2011 yılları arasında Ankara Üniversitesi Tıp Fakültesi hastanesine gastrointestinal sistem şikayetleri ile başvuran 145 çocuk olgunun özofageal biyopsi materyalleri retrospektif olarak değerlendirilmiş ve klinik konfirmas-yonu da sağlanan 7 eozinofilik özofajit olgusu çalışmaya dahil edilmiştir. His-topatolojik olarak papiller elongasyon, bazal hücre hiperplazisi ve dilate in-tersellüler boşluklar, büyük büyütme alanında saptanan intraepitelyal eozino-fil, nötrofil ve lenfosit sayıları ile birlikte değerlendirilmiştir. Nekroz/erozyon varlığı, subepitelyal fibrozis ve inşamasyon bulguları da ayrıca değerlendiril-miştir. Hastaların demografik verileri, başvuru şikayetleri, endoskopi öncesi tedavi alıp almadıkları ve endoskopik bulguları hasta kayıtlarından edinilmiş-tir. Bulgular: Hastaların yaş ortalaması 10.57±3.42 (6-17 yaş) olarak saptan-mıştır. Hastaların 3?ü erkek, 4?ü kız olup, olguların sadece 3?ünde özofagusta oluk şeklinde çizgilenme ve beyaz exudasyon olmak üzere anormal endosko-pik bulgular saptanmıştır. Üç olguda bazal hücre hiperplazisi saptanırken, 3 olguda hafif, 3 olguda ise şiddetli olmak üzere toplam 6 olguda papiller elon-gasyon izlenmiştir. Ayrıca ikisi hafif ve ikisi şiddetli olmak üzere toplam 4 ol-guda dilate intersellüler boşluklar saptanmıştır. Olguların tümünde eozinofi-lik mikroabseler görülmüş ve ortanca eozinofil değeri 25 (min:12; max:78), ortanca lenfosit değeri ise 9 (min:2; max:33) olarak bulunmuştur. ?ntraepitel-yal nötrofil görülmemiştir. Sonuç: Çocukluk çağında eozinofilik özofajit ta-nısına epitelyal eozinofili (>15 /hpf), eozinofilik mikroabseler ve yüzeyel eo-zinofilik dansite artışı gibi major histopatolojik parametrelerin klinik bulgu-larla birlikte değerlendirilmesiyle ulaşılabilir, papiller elongasyon, bazal hüc-re hiperplazisi ve dilate intersellüler boşluklar gibi minör histopathologic pa-rametrelerin yol göstericiliği sınırlıdır

Eozinofilik özofajit, histopatolojik kriterler, eozinofil sayısı

Eosinophilic esophagitis (EoE) is a chronic inflammatory di-sease of the esophagus characterized by dense tissue eosinop-hilia (1). In EoE, biopsies show marked eosinophilic infiltra-tes at different levels of the esophagus. However, the presen-ce of an increased number of eosinophils in the esophageal squamous epithelium is a nonspecific finding that may be se-en in several disorders, including reflux esophagitis (RO), in-fections, drugs and Crohn?s disease (2, 3). In order to distin-guish EoE from other causes of mucosal eosinophilia, major and minor histologic criteria for the diagnosis of EoE have be-en described (4). Major features include epithelial eosinophi-lia of more than 15 eosinophils/high power field (hpf), and ?microabscesses? described as clustering of 4 or more eosi-nophils and superficial layering of eosinophils. Minor criteri-a include basal cell hyperplasia (BCH), papiller elongation (PE), spongiosis (intercellular edema) which is currently known as dilated intercellular spaces (DIS), and inflammatory cell infiltration (4, 5). Both major and minor criteria, though helpful, are not pathognomonic for EoE as they may be seen in various types of esophagitis (2) We, therefore, decided to evaluate the discriminatory value of the currently available histologic criteria in the diagnosis of EoE in children.

There are very few studies on EoE in children, including a few case series from Turkey. Here, we described the demograp-hic, endoscopic and histopathologic features of 7 children with EoE. The exact etiopathogenesis of EoE is not well understood (2, 6, 7), though a history of atopy is commonly present in pati-ents with EoE. Upper endoscopy is the first diagnostic step in the evaluation of an individual with suspected EoE. Longitu-dinal furrowing, white exudates, esophageal trachealization, esophageal narrowing and strictures, Schatzki?s ring, and fri-ability described as ?crepe paper? mucosa, though not pat-hognomonic, are endoscopic signs of EoE (1). However, Potter et al. (8) commented that when a patient had both esop-hageal narrowing and trachealization, a physicians-should strongly suspect a diagnosis of EoE. On the other hand, nor-mal endoscopy may be observed in 26 to 32% of children with EoE (9, 10). In our series, 42.8% patients had abnormal endoscopic findings including white exudates and furrowing while the rest had normal endoscopy. The number of intraepithelial eosinophils in esophageal bi-opsy specimens is the main diagnostic criterion for EoE. The American Gastrointestinal Association (AGA) first released a consensus statement on the diagnosis and management of EoE in 2007 and updated it recently in 2011. They recom-mended a threshold of >15 eosinophils in one high power fi-eld as a diagnostic criterion for EoE (1). A recent review also described major and minor histologic features associated with EoE, which may distinguish it from other entities, especially, gastroesophageal reflux disesase. In that review, epithelial eo-sinophilia (>15/hpf), eosinophilic microabscesses and super-ficial eosinophilic density are described as major, while PE, BCH, intercellular edema, and an increase in inflammatory cells were introduced as minor histopathologic features (4). Due to the patchy distribution of the eosinophilic infiltration, the biopsies should be taken from several locations to maxi-mize diagnostic yield (1). One previous report demonstrated that five biopsies increased the sensitivity of the diagnosis of EoE to 100% (11). In our EoE cases, a minimum of 2 and a maximum of 3 esophageal biopsies had been taken. While all our cases presented with all major histologic featu-res, minor histologic features were observed with varying in-cidences. This is in accordance with the current literature (1, 4, 7) which suggests that the minor criteria such as BCH, PE and DIS represent reactive changes of the squamous epitheli-um to injury, and thus, are nonspecific. In conclusion, multiple biopsies and good orientation are criti-cal for correct interpretation of features such as BCH, and PE while inflammatory cells, and in particular eosinophils, should be counted in areas where they are most numerous. Furthermore, presence of, eosinophilic ?microabscesses? in the superficial squamous epithelium should be searched as they are present in almost all cases of EoE. Particularly in cases whe-re the histopathology is less discriminatory, the diagnosis will rely upon a good clinicopathologic correlation, hence, the awa-reness of the physician and pathologist of EoE is mandatory for a correct diagnosis in children.

We retrospectively evaluated the esophageal biopsies of 145 children who underwent upper gastrointestinal endoscopy for various gastrointestinal symptoms in Ankara University Medical School hospital between 2007 and 2011, and retrie-ved 7 cases of clinically confirmed EoE. Esophageal biopsies were taken from the middle and distal esophagus using standard biopsy forceps and were oriented with the luminal side upwards, embedded in paraffin and cut in 4 micrometer-thick sections and stained with hematoxylin and eosin (H&E). Histological assessment was performed by two pathologists together in a blinded manner, and the pre-sence of PE (>50% of epithelial thickness) (Figure 1), DIS (Figure 2), and BCH (Figure 3) was noted in terms of severity graded as mild, moderate and marked, together with the number of intraepithelial eosinophils (Figure 4), eutrophils and lymphocytes (Figure 5) per hpf. Presence of necrosis/ero-sions, subepithelial inflammation and fibrosis, vascular con-gestion, and intestinal metaplasia was also recorded. When lesions were not homogenously distributed in a given samp-le, the area with the most severe change was evaluated. We analyzed the patients? medical records for data regarding de-mographic information, clinical presentation, laboratory data, endoscopic findings and the response to treatment given be-fore upper gastrointestinal endoscopy

Among 145 children who underwent upper gastrointestinal endoscopy for various gasrointestinal complaints, there were 7 cases consistent with a diagnosis of EoE. The age of the pa-tients ranged from 6-17 years. There were 3 boys and 4 girls with a mean age of 10.57±3.42 years. Four patients were di-agnosed as GERD refractory to adequate proton pump inhibi-tor (PPI) therapy before upper GI endoscopy. Among the 7 cases, 3 had GERD ? like symptoms, 1 had abdominal pain, 1 had dysphagia, 2 of the patients were consultation cases with no clinical information. A total of 3 patients had conco-mitant allergic disease, which consisted of asthma in 1, and food allergy in 2 patients. Distribution of demographic featu-res and clinical information are summarized in Table 1. In 3 patients with endoscopic abnormalities, 2 had white exu-dates and 1 had furrowing, while 4 cases presented with nor-mal endoscopy. Subepithelial inflammation was seen only in 1 case, whereas submucosal fibrosis was absent. BCH was found in 3 cases and PE in 6 cases, 3 of which were mild and 3 were severe. DIS was observed in 4 cases, 2 of which were mild and 2 severe. The distribution of endoscopic and histologic findings are summarized in Table 2. Eosinophilic microabscesses were found in all cases with a eo-sinophil count of 25 (min:12; max:78). Four of our patients had >15/hpf intraepithelial eosinophils in their esophageal bi-opsies while the remaining three had 12 /hpf intraepithelial eosinophils. The mean lymphocyte count was 9 (min:2; max:33) while no neutrophils were determined in any of the cases

There are very few studies on EoE in children, including a few case series from Turkey. Here, we described the demograp-hic, endoscopic and histopathologic features of 7 children with EoE. The exact etiopathogenesis of EoE is not well understood (2, 6, 7), though a history of atopy is commonly present in pati-ents with EoE. Upper endoscopy is the first diagnostic step in the evaluation of an individual with suspected EoE. Longitu-dinal furrowing, white exudates, esophageal trachealization, esophageal narrowing and strictures, Schatzki?s ring, and fri-ability described as ?crepe paper? mucosa, though not pat-hognomonic, are endoscopic signs of EoE (1). However, Potter et al. (8) commented that when a patient had both esop-hageal narrowing and trachealization, a physicians-should strongly suspect a diagnosis of EoE. On the other hand, nor-mal endoscopy may be observed in 26 to 32% of children with EoE (9, 10). In our series, 42.8% patients had abnormal endoscopic findings including white exudates and furrowing while the rest had normal endoscopy. The number of intraepithelial eosinophils in esophageal bi-opsy specimens is the main diagnostic criterion for EoE. The American Gastrointestinal Association (AGA) first released a consensus statement on the diagnosis and management of EoE in 2007 and updated it recently in 2011. They recom-mended a threshold of >15 eosinophils in one high power fi-eld as a diagnostic criterion for EoE (1). A recent review also described major and minor histologic features associated with EoE, which may distinguish it from other entities, especially, gastroesophageal reflux disesase. In that review, epithelial eo-sinophilia (>15/hpf), eosinophilic microabscesses and super-ficial eosinophilic density are described as major, while PE, BCH, intercellular edema, and an increase in inflammatory cells were introduced as minor histopathologic features (4). Due to the patchy distribution of the eosinophilic infiltration, the biopsies should be taken from several locations to maxi-mize diagnostic yield (1). One previous report demonstrated that five biopsies increased the sensitivity of the diagnosis of EoE to 100% (11). In our EoE cases, a minimum of 2 and a maximum of 3 esophageal biopsies had been taken. While all our cases presented with all major histologic featu-res, minor histologic features were observed with varying in-cidences. This is in accordance with the current literature (1, 4, 7) which suggests that the minor criteria such as BCH, PE and DIS represent reactive changes of the squamous epitheli-um to injury, and thus, are nonspecific. In conclusion, multiple biopsies and good orientation are criti-cal for correct interpretation of features such as BCH, and PE while inflammatory cells, and in particular eosinophils, should be counted in areas where they are most numerous. Furthermore, presence of, eosinophilic ?microabscesses? in the superficial squamous epithelium should be searched as they are present in almost all cases of EoE. Particularly in cases whe-re the histopathology is less discriminatory, the diagnosis will rely upon a good clinicopathologic correlation, hence, the awa-reness of the physician and pathologist of EoE is mandatory for a correct diagnosis in children.

1. Liacouras CA, Furuta GT, Hirano I, et al. Eosinophilic esophagitis: up-dated consensus recommendations for children and adults. J Allergy Clin Immunol 2011; 128: 3-20. 2. Moawad FJ, Veerappan GR, Wong RK. Eosinophilic esophagitis. Dig Dis Sci 2009; 54: 1818-28. 3. Yan BM, Shaffer EA. Primary eosinophilic disorders of the gastrointesti-nal tract. Gut 2009; 58: 721-32. 4. Odze RD. Pathology of eosinophilic esophagitis: what the clinician needs to know. Am J Gastroenterol 2009; 104: 485-90. 5. Mueller S, Aigner T, Neureiter D, Stolte M. Eosinophile infiltration and degranulation in oesophageal mucosa from adult patients with eosinop-hilic oesophagitis: a retrospective and comparative study on pathologi-cal biopsy. J Clin Pathol 2006; 59: 1175-80. 6. Rothenberg ME. Biology and treatment of eosinophilic esophagitis. Gat-roenterology 2009; 137: 1238-49. 7. Schoepfer AM, Simon D, Straumann A. Eosinophilic oesophagitis: latest intelligence. Clin Exp Allergy 2011; 41: 630-9. 8. Potter JW, Saeian K, Staff D, et al. Eosinophilic esophagitis in adults: an emerging problem with unique esophageal features. Gastrointest Endosc 2004; 59: 355-61. 9. Liacouras CA, Spergel JM, Ruchelli E, et al. Eosinophilic esophagitis: a 10-year experience in 381 children. Clin Gastroenterol Hepatol 2005; 3: 1198-206. 10. Chehade M, Sampson HA, Morotti RA, Magid MS. Esophageal subepit-helial fibrosis in children with eosinophilic esophagitis. J Pediatr Gastro-enterol Nutr 2007; 45: 319-28. 11. Gonsalves N, Policarpio-Nicolas M, Zhang Q, et al. Histopathologic va-riability and endoscopic correlates in adults with eosinophilic esophagi-tis. Gastrointest Endosc 2006; 64: 313-9.