[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Lymphoid aggregates are normally found throughout the small and large intestine. Known as lymphoid nodular hyperplasia (LNH), these aggregates are observed especially in young children and are not associated with clinical symptoms being considered 'physiological'. In children presenting with gastrointestinal symptoms the number and size of the lymphoid follicles are increased. Patients suffering from gastrointestinal symptoms (i.e. recurrent abdominal pain) should systematically undergo gastroduodenoscopy and colonoscopy. With these indications LNH, especially of the upper but also of the lower gastrointestinal tract has been diagnosed, and in some children it may reflect a food hypersensitivity (FH) condition. AIM: To review the literature about the relationship between LNH and FH, particularly focusing on the diagnostic work-up for LNH related to FH. METHODS: We reviewed literature using Pubmed and Medline, with the search terms 'lymphoid nodular hyperplasia', 'food hypersensitivity', 'food allergy' and 'food intolerance'. We overall examined 10 studies in detail, selecting articles about the prevalence of LNH in FH patients and of FH in LNH patients. RESULTS: Collected data showed a median of 49% (range 32-67%) LNH in FH patients and a median of 66% (range 42-90%) FH in LNH patients. Literature review pointed out that the most important symptom connected with LNH and/or FH was recurrent abdominal pain, followed by diarrhoea and growth retardation. Both LNH and FH are associated with an increase in lamina propria γ/δ+ T cells, but the mechanisms by which enhanced local immune responses causing gastrointestinal symptoms still remain obscure. CONCLUSIONS: When assessing FH, we rely on clinical evaluation, including elimination diet and challenge tests, and endoscopic and immunohistochemical findings. Considering the possible co-existence of duodenal and ileo-colonic LNH, upper endoscopy can be recommended in children with suspected FH, especially in those presenting with additional upper abdominal symptoms (i.e. vomiting). Likewise, lower endoscopy might be additionally performed in patients with suspected FH and LNH of the duodenal bulb, also presenting with lower abdominal symptoms (i.e. recurrent abdominal pain).
[Show abstract][Hide abstract] ABSTRACT: To evaluate the usefulness of abdominal ultrasound examination (US) for the diagnostic workup of cases of suspected CD involving negative serum antibodies and difficult diagnosis.
524 consecutive patients with symptoms of suspected CD underwent an extensive diagnostic workup. 76 (14 %) were excluded since they were positive for serum anti-tTG and/or EmA antibodies. 377 were excluded since they were diagnosed with something other than CD or did not have the alleles encoding for HLA DQ 2 or DQ 8. A diagnosis of CD with negative serum antibodies was probable in 71 patients who underwent abdominal US and duodenal biopsy for histology evaluation.
Intestinal histology and subsequent clinical and histological follow-up confirmed the CD diagnosis in 12 patients (GROUP 1) and excluded it in 59 subjects (GROUP 2). Abdominal US showed that the presence of dilated bowel loops and a thickened small bowel wall had a sensitivity of 83 % and a negative predictive value (NPV) of 95 % in CD diagnosis. Furthermore, in 11 of the 12 CD seronegative patients there was at least one of these two abdominal US signs. Therefore, considering the presence of one of these two signs, abdominal US sensitivity increased to 92 % and NPV to 98 %.
Abdominal US is useful in the diagnostic workup of patients with a high clinical suspicion of CD but with negative serology.
Ultraschall in der Medizin 03/2010; 32 Suppl 1:S53-61. · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the relationship between ferritin and steatosis in patients with chronically abnormal liver function tests (LFTs) and high ferritin level.
One hundred and twenty-four consecutive patients with hyperferritinemia (male > 300 ng/mL, female > 200 ng/mL) were evaluated; clinical, biochemical and serological data, iron status parameters, HFE gene mutations and homeostasis model assessment score were obtained. Steatosis was graded by ultrasound as absent or present. Histology was available in 53 patients only.
Mean level of ferritin was 881 +/- 77 ng/mL in men and 549 +/- 82 ng/mL in women. The diagnosis was chronic hepatitis C in 53 (42.7%), non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in 57 (45.9%), and cryptogenic liver damage in 14 (11.3%). None was diagnosed as hereditary hemochromatosis (HH). Hepatic siderosis on liver biopsy was present in 17 of 54 (32%) patients; grade 1 in eight and grade 2 in nine. Overall, 92 patients (74.2%) had steatosis. By logistic regression, ferritin and gamma-glutamyltransferase were independent predictors of steatosis. Ferritin levels were significantly related to low platelet count, steatosis and hepatitis C virus infection.
In a non-obese cohort of non-alcoholic patients with chronically abnormal LFTs without HH, high serum ferritin level is a risk factor for steatosis.
World Journal of Gastroenterology 05/2009; 15(17):2132-8. · 2.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The jejunal mucosa is the major site involved in celiac disease, but modifications have also been found in the gastric, rectal and esophageal mucosa. Few studies have focused on the histomorphological features of the oral mucosa in celiac disease patients. Our objectives were: (i) to assess the presence, quality and intensity of lymphocytic infiltrate in clinically healthy oral mucosa and its relation to celiac disease severity (villous height to crypt depth ratio); and (ii) to detect any other histological features connected to celiac disease.
Twenty-one untreated celiac disease patients (age range 13-68 years) with clinically healthy oral mucosa were enrolled and compared with 14 controls. Intestinal and oral biopsies were carried out and specimens were evaluated after staining with hematoxylin and eosin.
Intra-epithelial lymphocyte B and T infiltrates of the oral mucosa were found to be similar in both groups; likewise, intensity of the lymphocytic infiltrate in the lamina propria was similar in both groups and was not related to intestinal damage; important signs of spongiosis were found to be more significantly present in celiac disease patients compared with controls (P = 0.0002).
Our study showed that the healthy oral mucosa of untreated patients does not reflect the intestinal damage by celiac disease, but it is unexpectedly affected by spongiosis, as being detected for the first time in the literature. This latter feature could be related to gliadin ingestion and could contribute to explain the higher susceptibility of celiac disease patients to suffering from oral mucosa lesions.
Journal of Oral Pathology and Medicine 08/2008; 38(1):34-41. · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Oral mucosal lesions may be markers of chronic gastrointestinal disorders, such as those causing malabsorption. Our objectives were to assess the prevalence of recurrent oral aphthous-like ulcers in coeliac disease patients living in the Mediterranean area, and to evaluate the impact of a gluten-free diet.
A test group of 269 patients (age range 3-17 years) with coeliac disease confirmed both serologically and histologically was compared with a control group of 575 otherwise clinically healthy subjects for the presence, or a positive history of aphthous-like ulcers. Coeliac disease patients with aphthous-like ulcers were re-evaluated 1-year after starting a gluten-free diet.
Aphthous-like ulcers were found significantly more frequently in coeliac disease, in 22.7% (61/269) of patients with coeliac disease versus 7.1% (41/575) of controls (p=<0.0001; chi-square=41.687; odds ratio=4.3123; 95% confidence interval=2.7664:6.722). Most coeliac disease patients with aphthous-like ulcers and adhering strictly to gluten-free diet (71.7%; 33/46) reported significant improvement on gluten-free diet, with no or reduced episodes of aphthous-like ulcers (p=0.0003; chi-square=13.101; odds ratio=24.67; 95% confidence interval=2.63:231.441).
The epidemiological association found between coeliac disease and aphthous-like ulcers suggests that recurrent aphthous-like ulcers should be considered a risk indicator for coeliac disease, and that gluten-free diet leads to ulcer amelioration.
Digestive and Liver Disease 02/2008; 40(2):104-7. · 3.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Many coeliac disease patients with atypical symptoms remain undiagnosed.
To examine the frequency of oral lesions in coeliac disease patients and to assess their usefulness in making coeliac disease diagnosis.
One hundred and ninety-seven coeliac disease patients and 413 controls were recruited and the oral examination was performed.
Forty-six out of 197 coeliac disease patients (23%) were found to have enamel defects vs. 9% in controls (P < 0.0001). Clinical delayed eruption was observed in 26% of the pediatric coeliac disease patients vs. 7% of the controls (P < 0.0001). The prevalence of oral soft tissues lesions was 42% in the coeliac disease patients and 2% in controls (P < 0.0001). Recurrent aphthous stomatitis disappeared in 89% of the patients after 1 year of gluten-free diet. Multi-logistic analysis selected the following variables as the most meaningful in coeliac disease patients: dental enamel defects (OR = 2.652 CI = 1.427-4.926) and soft tissue lesions (OR = 41.667, CI = 18.868-90.909). Artificial Neural Networks methodology showed that oral soft tissue lesions have sensitivity = 42%, specificity = 98% and test accuracy = 83% in coeliac disease diagnosis.
The overall prevalence of oral soft tissue lesions was higher in coeliac disease patients (42%) than in controls. However, the positive-predictive value of these lesions for coeliac disease diagnosis was low.
[Show abstract][Hide abstract] ABSTRACT: Previous studies have demonstrated that serum anti-actin antibodies are a reliable marker of intestinal damage severity in coeliac disease.
To validate in a multicentre study the clinical usefulness of serum IgA anti-actin antibody ELISA and its possible use in monitoring intestinal mucosa lesions during gluten-free diet.
Four centres recruited 205 newly diagnosed coeliac disease patients with villous atrophy, 80 healthy controls and 81 "disease" controls. Twelve coeliac disease patients on gluten-free diet but with persistent symptoms underwent serum IgA anti-actin antibody assay and intestinal histology evaluation. IgA anti-actin antibody ELISA was performed with a commercial kit. All coeliac disease patients underwent intestinal histology study.
IgA anti-actin antibodies showed a sensitivity of 80% and a specificity of 85% in the diagnosis of coeliac disease patients with villous atrophy. The area under the receiving operator curve for anti-actin antibodies was 0.873 [95% C.I. 0.805-0.899]. Serum anti-actin antibodies values were significantly higher in coeliac disease patients than in healthy or "disease" controls (P<0.0001). Serum anti-actin antibodies were positive in 41 of the 60 coeliac disease patients with mild intestinal histology lesions (69%) and in 123 of the 145 with severe lesions (85.3%) (P<0.05). There was a significant inverse correlation between anti-actin antibody values and the villi/crypts ratio (r=-0.423; P<0.0001). In the 12 coeliac disease patients on gluten-free diet who underwent re-evaluation as they were persistently symptomatic, intestinal histology showed three cases with persistent villous atrophy: all of these were positive for serum anti-actin antibodies ELISA, whereas both serum anti-tTG and EmAs were negative. The other nine patients showed normal intestinal villi and were negative for serum anti-actin antibodies.
Anti-actin antibodies are a reliable marker of severe intestinal mucosa damage in coeliac disease patients and a simple ELISA technique offers an accurate method for their determination. These antibodies seem to be a very reliable marker of persistent intestinal damage in coeliac disease patients.
Digestive and Liver Disease 10/2007; 39(9):818-23. · 3.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Antiendomysial (EmA) and antitransglutaminase (anti-tTG) antibodies are the most specific indirect marker of coeliac disease (CD). It is not known whether the oral mucosa of patients with CD is able to produce these antibodies or not.
To evaluate the ability of the oral mucosa of patients with CD to produce antibodies in an in vitro culture system.
Twenty-eight patients with new diagnosis of CD (15 adults and 13 children) and 14 adult subjects with other diseases (controls) were studied. All underwent oral mucosa biopsy and subsequent EmA and anti-tTG assays on the mucosa culture medium.
Sensitivity and specificity of EmA and anti-tTG assayed in the oral mucosa culture medium for CD diagnosis were 54% and 100% and 57% and 100%, respectively. The CD clinical presentation, such as the presence of oral mucosa lesions, did not influence the results of the EmA and anti-tTG assays in the oral mucosa culture medium. There was an association between positivity of antibodies and greater severity of the oral mucosa lymphocyte infiltration.
This study demonstrates that the oral mucosa contributes to EmA and anti-tTG production in untreated patients with CD.
[Show abstract][Hide abstract] ABSTRACT: Coeliac disease, daily more frequently diagnosed in our population, involves many organs also in oligosymptomatic patients and with an adequate nutritional regime. Possible endocrine implications include failure to thrive, pubertal delay and reproduction diseases due to deregulation of GH, FSH and LH secretion. Leptin, an adipose tissue hormone, can be decreased as well and its deficiency could be related to growth and puberty anomalies. We studied 14 asymptomatic coeliac patients in peripubertal age (7.5-13.8 years) and tested their leptin levels in order to correlate them with endocrine and anthropometric data. Before the diet was started leptinaemia (M+/-DS) was: 4.94+/-5.53 ng/ml. In 10/14 patients (71%) leptinaemia was<or=2 DS for gender and age. In all the patients, after a period of 6-12 months of gluten-free diet, Leptin levels appreciably raised to 10.8+/-7.9 ng/ml, with a significant correlation to the time of the diet. Leptinaemia was actually lower in patients with a severe mucosal atrophy, and in these patients it increased more significantly after the diet was started. The removal of gluten itself may reduce immunological hit to adipose tissue and the 'malnutrition' of adipocytes: leptin can hence increase despite no significant increase of body mass index occurs. This study could partially explain the correlation between body mass index, Coeliac disease and the deregulation of puberty and fertility, mainly in patients who started the diet late. It could also explain the reversibility of this alteration if the cause is removed.
Hormone Research 01/2007; 67(2):100-4. · 2.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic constipation is common in the general population. Some studies have shown that in children cow's milk protein hypersensitivity can cause chronic constipation unresponsive to laxative treatment.
To review the literature and summarize the data that point to a relationship between refractory chronic constipation and food hypersensitivity, and to discuss the hypothesis that the pathogenesis of constipation due to food hypersensitivity.
A search in the U.S. National Library of Medicine was performed, matching the key words 'chronic constipation, food intolerance and allergy'.
Thirty-three papers were found but only 19 of them were related to the topic of this review. Most of the data indicated a relationship between constipation and food allergy in a subgroup of paediatric patients with 'idiopathic' constipation unresponsive to laxative treatment. There was only one study in adults that demonstrated the resolution of chronic constipation on hypoallergenic diet in four patients.
An increasing number of reports suggest a relationship between refractory chronic constipation and food allergy in children. Similar data in adults are scarce and need to be confirmed. Further studies should be performed to obtain firmer evidence for the role of allergy in constipation and clarify the pathogenetic mechanisms involved.
[Show abstract][Hide abstract] ABSTRACT: During the first months of life, infants can suffer from many 'minor' gastroenterological disturbances. However, little is known about the frequency of these problems and the factors which predispose or facilitate their onset.
(a) To ascertain the frequency of the most common gastrointestinal symptoms in infants during the first 6 months after birth; (b) to evaluate the influence of some variables on the onset of the symptoms.
Each of the 150 paediatricians distributed throughout Italy followed 20 consecutive infants from birth to 6 months. 2879 infants (1422 f, 1457 m) concluded the study. The presence of the following symptoms was evaluated: constipation, diarrhoea, vomiting, regurgitation, failure to thrive and prolonged crying fits (colic). Symptoms were recorded whenever the parents requested a clinical check-up or during a set monthly examination.
1582/2879 (54.9%) infants suffered from one of the gastrointestinal symptoms. Regurgitation was the most common disturbance (present in 23.1% of infants), followed by colic (20.5%), constipation (17.6%), failure to thrive (15.2%), vomiting (6%) and diarrhoea (4.1%). Low birth weight was the factor most frequently associated with the onset of gastrointestinal symptoms, followed by low gestational age. Feeding habits did not influence the onset of symptoms, with the exception of constipation, which was linked to a low frequency of breast-feeding. Ninety-three infants (3.2%) were hospitalised for one or more of the gastrointestinal symptoms which were considered. During the whole study period the type of formula-milk was changed in 60% of the infants with one or more gastrointestinal symptoms, and in 15.5% of the infants who did not suffer from any gastrointestinal troubles.
Gastrointestinal symptoms are very common in infants during the first 6 months after birth. These symptoms required hospitalisation only in a small percentage of cases, but led to the prescription of a 'dietary' milk formula in approximately 60% of the cases. Low birth weight and low gestational age were the main factors influencing the onset of the symptoms.
Digestive and Liver Disease 07/2005; 37(6):432-8. · 3.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 29.12.2003; accettato per la pubblicazione l'8.1.2004. Indirizzo per la richiesta di estratti: Dott. Scopo. Proporre l' impiego di un sistema di cineradiografia digitale nel-la valutazione della deglutizione dei bambini con gravi alterazioni neu-rologiche o gravi ritardi psicomotori, al fine di identificare correttamente tali condizioni ed approntare soluzioni terapeutiche che, risolvendo il disturbo dell'alimentazione, consentano un miglioramento dello stato di nutrizione del paziente riducendo nel contempo il rischio di infezioni. Materiale e metodi. Nel periodo tra marzo 2001 e luglio 2003 sono sta-ti esaminati con cineradiografia digitale 12 bambini (8 maschi e 4 fem-mine) di età compresa tra i 9 mesi e i 13 anni (media 6,2 anni), con defi-cit neurologico ed alterazioni dello sviluppo psico-motorio. L'esame cineradiografico è stato richiesto per infezioni respiratorie ricorrenti e/o disfagia con calo ponderale. Tutti gli esami sono stati eseguiti median-te apparecchio telecomandato con arco a C digitale. Risultati. Con la tecnica sopra riportata in tutti i 12 bambini è stato pos-sibile differenziare i pazienti con alterazioni della fase orale e/o faringea della deglutizione (9/12) dai pazienti con deglutizione normale (3/12). In 9/9 pazienti erano apprezzabili fenomeni di passaggio del mdc nella via aerea durante gli atti deglutitori: di questi in 2/9 il passaggio di mdc era limitato al vestibolo laringeo (penetrazione subepiglottica) mentre in 7/9 era osservabile l'aspirazione del mdc in trachea (5/9) o nel bronco destro (1/9) o in entrambi i bronchi (1/9). In un paziente l'aspirazione di mdc si riduceva nelle sequenze acquisite con il capo in iperflessione. In 3/9 pazienti era apprezzabile passaggio di mdc in rinofaringe duran-te gli atti deglutitori da deficit di chiusura dell'istmo palato-faringeo da parte del palato molle. In 3/9 pazienti si rilevava incompleto clearing del faringe con ristagno di mdc nelle vallecule glosso-epiglottiche e nei seni piriformi; solamente in un caso il ristagno provocava — comunque — aspirazione post-deglutitoria. In 5/9 pazienti era presente più di una delle alterazioni descritte, mentre in 4/9 ne era presente una sola. Conclusioni. In base ai dati preliminari ottenuti si può concludere che l'esame dinamico della deglutizione con tecnica digitale permette una precisa valutazione del processo deglutitorio con il minimo disagio per il piccolo paziente che tuttavia viene esposto a radiazioni ionizzanti. Ciononostante nei pazienti neurolesi, in rapporto alle importanti rica-dute cliniche e quoad vitam, è nostra opinione, in accordo con la lette-ratura, che le informazioni ottenute siano probabilmente più importanti dei rischi connessi alle radiazioni. PAROLE CHIAVE: Bambini neurolesi -Cineradiografia digitale -Infezioni respi-ratorie.
La radiologia medica 04/2004; 107(4):286-292. · 1.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although anti-endomysial antibodies (EmA) have been found in the supernatants of cultured intestinal mucosa from patients with coeliac disease (CD), in no study has the clinical reliability of this new diagnostic tool been investigated. Our aims were to evaluate the clinical usefulness of the in vitro production of EmA in CD diagnosis in consecutive patients with suspected CD, and to evaluate the reliability of the in vitro challenge in CD patients on a gluten-free diet (GFD).
For the former aim, consecutive patients who were due to undergo intestinal biopsy for suspected diagnosis of CD were enrolled: according to the final diagnosis, these patients were divided into two groups: Group 1 comprised 91 newly diagnosed CD patients (40 males; age range 7 months to 84 years), Group 2 included 100 subjects with diseases other than CD (44 males; age range 9 months to 76 years). For the latter aim, we also studied 21 CD patients on a gluten-free diet after 16-123 months (8 males; age range 3-51 years), with normal intestinal architecture (Group 3) and 22 patients who served as controls (12 males; age range 4-60 years) with gastroesophageal reflux disease-like symptoms (Group 4). All patients underwent determination of serum anti-gliadin (AGA) and EmA antibodies, histology evaluation of the intestinal biopsies and EmA assay in the supernatants of in vitro gliadin-challenged duodenal mucosa.
EmA assay in the supernatants showed a sensitivity and specificity of 96% and 100%, respectively; these were not significantly different from those observed for serum EmA (88% and 99%, respectively). However, EmA assay in the supernatants was useful in CD patients with mild intestinal histology lesions (infiltrative/hyperplastic type): in this subgroup it was positive in 9/12 of cases, but serum EmA was positive in only 2/12. As regards the reliability of the in vitro gliadin challenge, EmA production in supernatants was recorded only in 10/21 CD patients on a gluten-free diet. The patients with a positive in vitro challenge had a higher number of intra-epithelial lymphocytes than patients with a negative challenge.
1) EmA assay in the medium of cultured intestinal biopsy can detect gluten-sensitive enteropathy, characterized by an infiltrative/hyperplastic histological pattern, which is often associated with negative serum EmA. 2) The in vitro challenge in CD patients on a gluten-free diet detects EmA production in the culture medium only in half of the cases and other studies must be performed to evaluate whether EmA production after in vitro challenge can be considered a reliable test for confirming CD diagnosis.
Scandinavian Journal of Gastroenterology 02/2002; 37(1):32-8. · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In patients with coeliac disease, a regression of intestinal damage without a gluten-free diet is a very rare event. We describe a young child with diarrhoea, intestinal mucosa atrophy and positive serum anti-endomysial and anti-tissue transglutaminase (anti-tTG) antibodies during intestinal giardiasis infection. He showed normal intestinal mucosa architecture and negative anti-endomysial and anti-tTG antibodies after his giardiasis was cured, although he continued to assume a normal diet. Re-evaluations on a 6-monthly basis showed that he was symptom free, and all haemato-chemical parameters were within normal limits. Three years after the initial diagnosis, a third intestinal biopsy showed: normal mucosa architecture; an increase in the intra-epithelial CD3+ and gamma/delta+ lymphocyte counts; and immunoglobulin-A anti-endomysial antibody detection in the supernatant of the intestinal mucosa culture incubated with gliadin. An active coeliac disease status, with intestinal mucosa atrophy, may regress to a latent coeliac disease status with normal intestinal mucosa histology after removal of the environmental factors that have presumably precipitated mucosa damage. Serum anti-endomysial and anti-tTG antibody behaviour is not a permanent, life-long feature and this must recommend the repetition of anti-endomysial or anti-tTG antibody assays in the same patient whenever coeliac disease diagnosis is again suspected, irrespective of previous negativity.
European Journal of Gastroenterology & Hepatology 10/2001; 13(9):1101-5. · 1.92 Impact Factor