Gerarda Mastrogiorgio

The Celiac Iceberg: Characterization of the Disease in Primary Schoolchildren

Objective: Celiac disease (CD) has a prevalence of 0.55% to 1% in Italy. Identifying CD in schoolchildren to characterize CD iceberg and evaluate the effect of diagnosis in screening-detected children. Methods: A total of 7377 5- to 8-year-old children were invited to participate. A total of 5733 salivary samples were collected and tested for anti-transglutaminase antibodies (tTGAb), using a fluid-phase radioimmunoassay. Salivary tTGAb-positive children were analyzed for serum antibodies (anti-endomysium antibodies, radioimmunoassay, and enzyme-linked immunosorbent assay tTGAb). Positive children underwent endoscopy and then started gluten-free diet (GFD) and periodical follow-up. Results: Forty-six subjects were found salivary tTGAb–positive and 16 border-line. Forty-five of 46 and 5 of 15 of them were also serum antibody–positive. Forty-two children showed duodenal villous atrophy and 1 had only type 1 lesions. Three children started GFD without performing endoscopy. CD prevalence (including 23 previously diagnosed children with CD) was 1.2%. Considering all 65 celiacs in our sample, a silent CD was found in 64%, typical in 28%, atypical in 7%, and potential in 1%. All patients showed strict adherence to GFD, weight and stature increase, and well-being improvement. Eighty-five percent and all but 2 screening-detected children with CD had Italian parents. Conclusions: Our sample size, representative of primary schoolchildren of our region, demonstrated that CD prevalence is growing in Italy, with a modified clinical spectrum and iceberg deepness.

Duodenal bulb in celiac adults: The "whether biopsying" dilemma

Background: Celiac disease (CD)-related lesions were described in duodenal bulb of celiac patients. Goal: Our aim was to evaluate the morphology of bulb mucosa in adult celiac patients and in controls to evaluate its usefulness for CD diagnosis. Study: We studied 43 celiac patients (10 male, median age: 35.2 y) at diagnosis and 43 gastroenterological controls (10 male, median age: 37.8 y), submitted to upper endoscopy for gastroenterological complaints. Histologic lesions were assayed by an experienced pathologist according to the Marsh modified classification. Antiendomysium antibodies and antitransglutaminase antibodies-tTGAb (ELISA and/or RIA) have been tested. In selected patients, DNA was typed for DRB1, DQA1, and DQB1 genes by sequence-specific primer polymerase chain reaction. Results: In all celiac patients lesions were present in the bulb mucosa. One female with thyroiditis, who had a CD daughter, showed lesions only in the duodenal bulb. Patchy villous atrophy was found in another patient. All celiacs were antiendomysium and/or tTGAb positive. DQ2 heterodimer was present in 5 CD patients. The gastroenterological controls showed normal mucosa in the duodenum. Conclusions: This study demonstrates that CD-related histologic lesions are present in duodenal bulb of adult patients. Moreover, the normal aspect of this mucosa in gastroenterological controls implies the high negative predictive value of this finding. Therefore, we suggest taking at least 1 biopsy on the bulb area and 1 from the distal duodenum for CD diagnosis, in all the patients submitted to upper endoscopy, to avoid missed or delayed diagnosis.

Celiac disease in a large cohort of children and adolescents with recurrent headache: A retrospective study.

BACKGROUND The clinical picture of celiac disease is changing with the emergence of subclinical forms and growing evidence reporting associated neurological disorders. AIMS To establish the prevalence of celiac disease in children suffering from recurrent headache. METHODS In our retrospective study we collected charts from 1131 children attending our tertiary care Centre for Paediatric Headache over the period 2001-2012. They were screened for celiac disease and positive patients were referred to our Operative Unit for Coeliac disease and confirmed positive children underwent upper endoscopy with multiple duodenal biopsies. Celiac children started a gluten-free diet. RESULTS 883 children (481 females; median age, 9.8 years, range 3-19) performed celiac disease screening, and among them, 11 children (7 females; median age, 8.2 years, range: 4.8-13.9) were diagnosed with celiac disease. Seven children (5 females, median age, 11.9 years, range: 10.3-13.9) had been diagnosed as celiac prior to the neurological evaluation. The prevalence of celiac disease in our sample is 2.04% vs. 1.2% of the general population (p=0.034). CONCLUSIONS Our study demonstrates, on a large series, that celiac disease prevalence is doubled in patients with chronic headache. Screening for celiac disease could be advised as part of the diagnostic work-up in these paediatric patients, particularly among pharmacological non-responders.

Endoscopic and Histological Gastric Lesions in Children With Celiac Disease: Mucosal Involvement Is Not Only Confined to the Duodenum

Objectives: Lymphocytic gastritis (LG) has been reported in patients with celiac disease (CD). The aim of the present study was to evaluate gastric mucosa involvement in celiac children and gastroenterological controls (GC). Methods: In a retrospective study on 226 patients with CD (82 M; median age: 5.7years) at diagnosis and 154 GC (66 M; median age: 7.4 years), the evaluation of gastric and duodenal mucosa was performed. CD was diagnosed according to the North America Society for Pediatric Gastroenterology, Hepatology, and Nutrition criteria. Gastric lesions were classified according to Updated Sydney System. Anti-gastric parietal cell antibodies (GPCA) were assayed by enzyme-linked immunosorbent assay. Results: A total of 21.2% and 7% of patients with CD showed chronic superficial gastritis (CSG) and LG, respectively. Helicobacter pylori (Hp) infection was found in 6 (2.7%) children with CD (66.7% had CSG, 16.7% LG, and 16.7% interstitial gastritis). CSG was present in 21.4% of controls. No control subject showed LG. Hp infection was found in 24 (15.6%) children with GC (91.7% had CSG). Among patients with CSG, Hp infection was more frequent in controls than in celiac children (P < 0.0001). Ten of 90 patients with CD and 1 of 29 controls were positive for GPCA. Conclusions: Gastritis is a common finding in children with CD and adolescents. In celiac subjects, CSG is the most frequently detected. Our data suggest the hypothesis that LG may be related to a longer exposure to gluten. The presence of GPCA may suggest the presence of an underlying autoimmune process.

Anti-transglutaminase immunoreactivity and histological lesions of the duodenum in coeliac patients

Coeliac disease (CD) is characterized by several markers, including anti-transglutaminase auto-antibodies (tTGAb) directed against multiple epitopes of the gliadin protein. We aimed to investigate the correlation among CD duodenal lesions, tTGAb titres and the immunoreactivity against tTG constructs. A total of 345 CD patients (209 females, 136 males, overall median age: 7.3 years) were tested for full-length (fl) tTGAb with a fluid-phase radioimmunoassay. Out of the total, 231 patients were also tested for immunoreactivity against tTG fragments (F1: a.a. 227-687 and F2: a.a. 473-687). Patients were classified according to diffuse (D), patchy (P) or bulb (B) histological lesions. All sera were found fltTGAb positive. Patients with D, P and B lesions had a mean Ab index of 0.84±0.39, 0.57±0.39 and 0.45±0.24, respectively. Mean tTGAb titre varied between D and localized (P+B) patients (0.84±0.39 versus 0.52±0.34, P < 0.0001). Overall, 86.1% of patients were F1 auto-antibody (F1Ab) positive (D: 89%, P: 75%, B: 40%; D versus P+B: P = 0.004) and 49% of patients were F2 auto-antibody (F2Ab) positive (D: 53%, P: 19%, B: 10%; D versus P+B: P = 0.0006). Of the D patients 50.7% showed combined F1Ab-F2Ab (D versus P+B: P = 0.001), whereas 60% of B patients were negative for both F1Ab and F2Ab (B versus D: P < 0.0001). Coeliac-specific tTGAb immunoreactivity correlates with the grading and extension of histological duodenal lesions in CD patients at diagnosis. The immunoreactivity against single and combined tTG fragments is significantly higher in patients with D lesions. This is the first evidence of a distinct coeliac-specific immunoreactivity in patients with different duodenal involvement.

Duodenal bulb for diagnosing adult celiac disease: much more than an optimal biopsy site

monopolar snare polypectomy in both establishing a histologic diagnosis and offering treatment.5 The application of a detachable snare for the induction of polyp ischemia and necrosis may be an attractive option in selected cases with large polyps and high risk for polypectomy. In this case, pathologic analysis is mandatory, and regular follow-up and endoscopic examination are suggested after the procedure.6

Coeliac Disease-Related Antibodies Appearance in a IgA Deficiency Celiac Girl after Starting the Gluten-Free Diet

Celiac disease (CD) is a gluten-dependent autoimmune enteropathy which occurs in genetically predisposed individuals. CD can manifest in a typical form (with gastrointestinal symptoms), with an atypical form (iron-deficiency anemia, headache, recurrent aphthous stomatitis) or be asymptomatic (silent form). Over the last decades CD prevalence increased (1.2%), mainly due to the improvement and diffusion of screening tools such as anti-gliadin, anti-endomysium and anti-tissue transglutaminase antibodies. The authors report a case of a 39 months old IgA deficiency girl with a severe abdominal distention and iron deficiency anemia, negative for CD-related antibodies, who was diagnosed celiac. Surprisingly, after six months of gluten-free diet, the patient showed the appearance of IgG class – CD specific antibodies.

Celiac Disease and Helicobacter Pylori Infection: an Ups and Downs Correlation

Background: Several studies showed an involvement of the gastric mucosa in celiac disease (CD). Helicobacter pylori (Hp) is the major agent of gastric damage. The aim of this article was to present a literature review of a possible correlation between the two conditions. Methods: A literature search was conducted in Medline, Scopus and Directory of Open Access Journal (DOAJ) using appropriate keywords. We included only articles written in English over the period July 1996 - May 2014. Results: The search for Medline, Scopus and DOAJ provided a total of 530 citation. Twenty five studies met the inclusion criteria and were included in quantitative analysis. The prevalence of Hp infection in celiac children and adults from different geographical areas has been reported. The possible correlation between Hp infection and the increase of intraepithelial lymphocytes (IEL) has also been reported. Conclusion: Several studies showed a wide heterogeneity. This is probably due to differences in Hp prevalence, small series of patients, lack of histological confirmation of Hp and lack of adjustment for sociodemographic characteristics. More studies to clarify the possible correlation between these two conditions are necessary.

Occam’s razor reveals a hidden Churg-Strauss syndrome

A 28 year-old caucasian lady, with nine years of uncontrolled bronchial asthma, rhinosinusitis and mild upper limb paresthesia, came to our attention to be followed for coeliac disease (CD). She had a biopsy performed elsewhere which proved the diagnosis five years before. Since there was no clinical improvement on a strict gluten-free diet, we re-evaluated the slides of her duodenal biopsies and we found an overestimation of the duodenal lesions due to the wrong orientation of the specimens. Moreover, she had never had positive CD-related antibodies and she was negative for DQ2/DQ8 MHC Class II heterodimers. Months later, she referred she was suffering from diffuse joint pain, epistaxis and a substantial weight loss. A few days later she was hospitalized because of a sudden onset of dyspnea, peripheral edema and pleural effusion. Her echocardiogram showed global left ventricular hypokenesia with an ejection fraction of 24%. The patient was discharged with a diagnosis of dilated cardiomyopathy and NYHA Class II. After a large spectrum of haematological exams, the diagnosis of Churg Strauss Syndrome (CSS), a rare multisystemic small-vessel necrotizing vasculitis, was confirmed by the presence of four/five out of six diagnostic American College of Rheumatology classification criteria (Asthma, Eosinophilia >10%, Neuropathy, Non-fixed pulmonary infiltrates, Paranasal sinus abnormality and Biopsy containing a blood vessel with extravascular eosinophils). Our patient had been under-diagnosed by pulmonologist and by gastroenterologists although she presented the criteria required for CSS diagnosis. Our case report emphasizes that often seemingly unrelated symptoms can be caused by a single rare clinical complex.

PA36 PSYCHOLOGICAL IMPACT OF COELIAC DIAGNOSIS AND GLUTEN-FREE DIET IN SILENT SALIVARY SCREENING-DETECTED SCHOOL CHILDREN

Objectives: Lymphocytic gastritis (LG) has been described in coeliac disease (CD) patients and in patients with Helicobacter pylori (Hp) infection but the pathogenetic mechanism remains unknown. Aims: The aim of our study was to evaluate the characteristics of the gastric mucosa and the prevalence of lymphocytic gastritis in a large series of CD children and adolescents. Methods: 167 CD children at the diagnosis (F 108; range 11 months–18 years), consecutive performing the upper-intestinal endoscopy at our Department over the period Jan 2008-Dec 2009, were enrolled. Duodenal (2 bulb and 4 distal duodenum samples) together with gastric antral biopsies, were performed. CD diagnosis was performed according to the NASPGHAN criteria. Hp infection was diagnosed by histology and the rapid urease test. Gastric lesions and duodenal biopsies were classified according to the modified Updated Sydney System and to the modified Marsh classification, respectively. Anthropometric and clinical data of each patient were registered at the diagnosis. Moreover, gastric parietal cells antibodies (APCA) were determined with an ELISA. Results: Gastric alterations was found in 38/167 CD children (23%). Particularly, lymphocytic gastritis was found in 13 CD patients (7.8%); superficial chronic gastritis (SCG) was detected in 24 celiacs (14.4%); and one child (0.6%) showed severe interstitial chronic gastritis (ICG). 3/38 children (one with LG, one with SCG and one with ICG) presented Hp infection. Ten patients with LG were symptomatic (7 typical and 3 atypical) while four were silent. Among patients with SCG, 16 children were typical, 5 atypical and 3 silent, and the prevalent symptoms were diarrhoea, abdominal pain and low weight growth. In the table are shown histological grading of the gastric mucosa in LG and SCG patients. The most frequent duodenal lesion, total villous atrophy (Marsh 3C), was detected in 100% and 92% of LG and SCG CD patients. Among CD children, no APCA were found in patients without gastritis, while 3/22 with gastric lesions were positive for APCA (one with mild LG and the other two with mild SCG).