The classic form of the disease manifested by CORRELATION OF ENDOSCOPIC AND HISTOLOGICAL FEATURES IN ADULTS WITH SUSPECTED CELIAC DISEASE IN A REFERRAL CENTER OF MINAS GERAIS , BRAZIL

Context Clinical presentation of celiac disease is extremely variable and the diagnosis relies on serologic tests, mucosal intestinal biopsy and clinic and serologic response to a gluten-free diet. Objectives To correlate the endoscopic and histological aspects of adult patients with suspicion of celiac disease and to evaluate the interobserver histological agreement. Method Endoscopic aspects of 80 adult patients were evaluated and correlated with the histological features according the Marsh-Oberhuber classification system. The interobserver histological agreement was based on kappa values. Results The symptoms of the patients varied largely, with prominence for chronic diarrhea, present in 48 (60%) patients. The endoscopic aspects related with the duodenal villous atrophy had been observed in 32 (40%) patients. There were confirmed 46 cases of celiac disease, with prevalence of 57.5%. The sensitivity, specificity, positive predictive value and negative predictive value of the endoscopic markers for celiac disease diagnosis were of 60.9%, 88.2%, 87.5% and 62.5%. There was moderate interobserver histological agreement (kappa = 0.46). Conclusions The endoscopic markers of villous atrophy, although not diagnostic, had assisted in the suspicion and indication of the duodenal biopsies for diagnosis proposal. Histology is sometimes contradictory and new biopsies or opinion of another professional can provide greater diagnostic agreement. HEADINGS Celiac disease, diagnosis. Endoscopy. Histology. Declared conflict of interest of all authors: none 1 Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Universidade Federal de Minas Gerais UFMG, Belo Horizonte, MG; 2 Departamento de Medicina Interna da Faculdade de Medicina, UFMG. 3 Departamento de Anatomia Patológica e Medicina Legal, UFMG; 4 Escola de Medicina da Universidade Federal de Ouro Preto, Ouro Preto. MG. Brasil. Correspondence: Rodrigo Macedo Rosa. Rua Dr. Lucídio Avelar, 171/801, Bairro Buritis. CEP:30.455-790, Belo Horizonte, MG, Brasil. E-mail: rodrigogastro@yahoo.com. br chronic diarrhea and weight loss affects only a small portion of patients and most of them have atypical gastrointestinal manifestations, extraintestinal symptoms or even complete absence of symptoms. Despite the high prevalence (0.7% 2% of the general population)(5, 12, 18, 20, 22, 30, 31) and the availability of modern methods of investigation, the definitive diagnosis of CD remains challenging. For each new confirmed case of the disease, three to seven patients remain underdiagnosed(15, 16, 26, 28). With the goal to contribute to the diagnosis of the disease, this study aimed to: (a) correlate the endoscopic aspects and histological findings accordind the Marsh-Oberhuber classification(23) in an adult population with clinical and/or laboratory suspicion of CD; (b) evaluate the interobserver histological agreement among the three pathologists; and (c) describe the clinical and endoscopic characteristics of patients with confirmed diagnosis of CD. Rosa RM, Ferrari MLA, Pedrosa MS, Ribeiro GM, Brasileiro-Filho G, Cunha AS. Correlation of endoscopic and histological features in adults with suspected celiac disease in a referral center of Minas Gerais, Brazil v. 51 no. 4 out. /dez. 2014 Arq Gastroenterol 291 METHODS This study was conducted between March 2009 and December 2010 at the Digestive Endoscopy Unit of the Clinics Hospital of the Federal University of Minas Gerais, Belo Horizonte, Brazil. Adult patients with serological positive tests for CD or with symptoms of chronic diarrhea for more than 30 days, anemia by iron deficiency, weight loss of more than 5% of the body weight in 6 months and dermatitis herpetiformis were included in the study. Besides the evaluation of clinical signs and symptoms of all patients, 51 of them underwent serological tests for CD by means of antigliadin (AGA), antiendomysium (EmA) and tissue transglutaminase (tTG) antibodies. All patients underwent esophagogastroduodenoscopy (EGD) through endoscope with magnification (Fujinon EG-450 ZW) and single working channel of 2.8 mm. In all patients, EGD was performed by the same researcher. A detailed study of the duodenum analyzing possible endoscopic changes with the aid of the water-immersion technique and magnification was conducted. The endoscopic findings potentially indicative of duodenal villous atrophy were: (a) reduction or absence of duodenal folds, (b) scalloping of folds, (c) visible submucosal vessels, (d) mosaic pattern, i.e., micronodular appearance of the mucosa, and (e) mucosal fissures, crevices, or grooves(4, 8). The final endoscopic diagnosis included three categories: (a) normal mucosa with preserved villous and no atrophy endoscopic markers; (b) partial villous atrophy with signs of mucosal atrophy and villous flattening; and (c) total mucosal atrophy with no villous present. Biopsies were obtained by forceps with the diameter of 7.3 mm (FB 55K1, Olympus). Four specimens of the distal duodenum (second and third duodenal portions) and one of the proximal duodenum (duodenal bulb) from each patient were obtained. The fragments were placed on filter paper with the cut surface down, and the free surface up. The correct orientation of the fragments was confirmed with the aid of a magnifying glass. The specimens were fixed in 10% formalin solution. The samples were routinely processed for paraffin embedding. Histological sections 5 μm thick were stained with hematoxylin and eosin (HE). All slides were examined by three pathologists with good experience in the analysis of intestinal biopsies. In all cases, biopsies were considered adequate for analysis because they contained the entire thickness of the mucosa, including the muscularis mucosa and at least four continuous villi. Each pathologist issued his diagnosis according the Marsh-Oberhuber(23) classification based on a 6-stage grading, namely: (1) type 1 infiltrative lesions, characterized by normal mucosal architecture with an increased number of intraepithelial lymphocytes (IEL), namely 40 or more lymphocytes per 100 enterocytes; (2) type 2 hyperplastic lesions, characterized by an increase in crypt depth without villous flattening and an increased number of IEL; (3) type 3a, 3b, and 3c destructive lesion, characterized by mild, marked, and complete villous flattening, respectively and an increased number of IEL; and (4) type 4 hypoplastic lesions, characterized by villous atrophy and normal crypt height and IEL count. Statistical analysis was performed using R software, version 2.7. 1, and Epi Info version 6.04. Initially, a descriptive analysis was made of the evaluated variables determining the frequencies and percentages for each objective variable and central tendency measures for the quantitative variables. The agreement rates among the pathologists were evaluated based on multiple kappa coefficient. To assess the level of agreement among the three pathologists, kappa measure was determined, based on the number of agreeing responses. From the sample values, multiple kappa was estimated, as well as its respective 95% confidence interval (CI), and calculated the P-value. Since there was disagreement on the CD diagnosis among the three pathologies in the initial evaluation, the three pathologists jointly examined each case to reach a consensus diagnosis. For endoscopic findings and their relation to the histological diagnosis of CD, sensitivity, specificity, positive predictive value and negative predictive value were calculated. The likelihood ratio for a positive test and a negative test was also determined. This study was approved by the Research Ethics Committee of the Federal University of Minas Gerais (ETIC 193/09). All patients provided written, informed consent prior to initiation of the study.