Intestinal permeability in children with recurrent respiratory and gastrointestinal symptoms.

AIM: Increased intestinal permeability has been reported in asthmatic subjects as well as in patients with gastrointestinal disease, thus suggesting the involvement of all the mucosal immune system. We aimed to assess intestinal permeability according to recurrent respiratory and gastrointestinal symptoms in children with asthma and children with functional gastrointestinal disorders (FGIDs). METHODS: In 108 outpatients aged 3-14 years (45 asthmatic, 63 with FGIDs), we measured the urinary lactulose/mannitol (L/M) ratio, performed allergy skin prick tests and administered questionnaires for recurrent respiratory and gastrointestinal symptoms starting from at least 2 months which persisted over the previous 4 weeks. L/M ratios were compared with previously reported normal values yielded by our chromatographic method (liquid chromatography-mass spectrometry). RESULTS: High L/M ratios (>0.030) were less frequent in asthmatic children than in children with FGIDs (9/45: 20% vs. 41/63: 65%, P < 0.001). High L/M ratios were associated with gastrointestinal symptoms in 8/9 asthmatic (P < 0.05) and 39/41 subjects with FGIDs (P < 0.005). L/M ratios were not associated with respiratory symptoms or atopy. In a regression model, a high L/M was predicted by low height, absence of asthma and presence of gastrointestinal symptoms (r = 0.72, P < 0.001). CONCLUSIONS: Increased intestinal permeability is associated with recurrent gastrointestinal symptoms rather than with recurrent respiratory symptoms in both asthmatic children and those with FGIDs. Our findings do not support the hypothesis of mucosal intestinal damage following an inflammatory stimulus in the respiratory mucosa.

Gastroesophageal reflux disease vs. Panayiotopoulos syndrome: an underestimated misdiagnosis in pediatric age?

Autonomic signs and symptoms could be of epileptic or nonepileptic origin, and the differential diagnosis depends on a number of factors which include the nature of the autonomic manifestations themselves, the occurrence of other nonictal autonomic signs/symptoms, and the age of the patient. Here, we describe twelve children (aged from ten months to six years at the onset of the symptoms) with Panayiotopoulos syndrome misdiagnosed as gastroesophageal reflux disease. Gastroesophageal reflux disease and Panayiotopoulos syndrome may represent an underestimated diagnostic challenge. When the signs/symptoms occur mainly during sleep, a sleep EEG or, if available, a polysomnographic evaluation may be the most useful investigation to make a differential diagnosis between autonomic epileptic and nonepileptic disorders. An early detection can reduce both the high morbidity related to mismanagement and the high costs to the national health service related to the incorrect diagnostic and therapeutic approaches. To decide if antiseizure therapy is required, one should take into account both the frequency and severity of epileptic seizures and the tendency to have potentially lethal autonomic cardiorespiratory involvement. In conclusion, we would emphasize the need to make a differential diagnosis between gastroesophageal reflux disease and Panayiotopoulos syndrome in patients with "an unusual" late-onset picture of GERD and acid therapy-resistant gastroesophageal reflux, especially if associated with other autonomic symptoms and signs.

Nutritional Deficiencies in Children with Celiac Disease Resulting from a Gluten-Free Diet: A Systematic Review.

BACKGROUND: A strictly gluten-free diet (GFD) is the basis for managing celiac disease (CD). Numerous studies have reported nutritional deficiencies/imbalances ascribable to a GFD. The aim of this review is to describe nutritional deficiencies observed in children with celiac disease on a GFD, to discuss the clinical consequences related to these nutritional imbalances, and to identify strategies that may be adopted to treat them. METHODS: We reviewed the MEDLINE and EMBASE databases between January 1998 and January 2019. RESULTS: Children are, regardless of whether they are on a gluten-free diet or not, at risk of consuming too much fat and insufficient fiber, iron, vitamin D, and calcium. These imbalances may be exacerbated when children are on a gluten-free diet. In particular, the intake of folate, magnesium, zinc, and foods with a high glycemic index in children with CD who are on a GFD is significantly altered. CONCLUSIONS: Therapeutic protocols should include nutritional education to help teach subjects affected by disorders such as CD the importance of labels, the choice of foods, and the combination of macro- and micronutrients. Children with CD on a GFD should be encouraged to rotate pseudo-cereals, consume gluten-free commercial products that have been fortified or enriched, and use foods that are local and naturally gluten-free.

"EEG abnormalities" may represent a confounding factor in celiac disease: A 4-year follow-up family report.

OBJECTIVE: The occurrence of celiac disease (CD), electroencephalographic (EEG) abnormalities (with "subtle" seizures or even without any clinical seizures), and neurological disorders has been reported since the 1980s, though there has been no definitive consensus about the possible causal relationship. This topic is further complicated by the occurrence in infancy of 'clinical-EEG pictures' called 'benign epilepsy of infancy'. METHODS AND RESULTS: Here, we report a 4-year follow-up on two siblings with newly diagnosed biopsy-proven celiac disease showing EEG abnormalities not responsive to a gluten-free diet. CONCLUSIONS: This family report indicates that in patients with neurologically asymptomatic CD and EEG abnormalities, it is advisable to make a differential diagnosis between EEG abnormalities associated with CD and an incidental association with cortical hyperexcitability, with "subtle" seizures or even without any clinical seizures. PRACTICE IMPLICATIONS: A long follow-up may sometimes be required, as it was in the family described here, to clarify the etiopathogenetic and therapeutic relationships between clinical and EEG features in CD.

Intestinal permeability is increased in children with non-alcoholic fatty liver disease, and correlates with liver disease severity.

BACKGROUND: Increased intestinal permeability seems to play a major role in non-alcoholic liver disease development and progression. AIM: To investigate the prevalence of altered intestinal permeability in children with non-alcoholic fatty liver disease, and to study its potential association with the stage of liver disease. METHODS: We performed a case-control study examining intestinal permeability in children using the lactulose-mannitol bowel permeability test. RESULTS: Overall, 39 consecutive patients (30 males, median age 12 years) and 21 controls (14 males, median age 11.8 years) were included. The lactulose/mannitol ratio resulted impaired in 12/39 patients (31%) and none of the controls. Intestinal permeability was higher in children with non-alcoholic fatty liver disease (lactulose/mannitol ratios: 0.038±0.037 vs. 0.008±0.007, p<0.05). Within the non-alcoholic fatty liver disease group, intestinal permeability was increased in children with steatohepatitis compared to those with steatosis only (0.05±0.04 vs. 0.03 vs. 0.03, p<0.05). Pathological lactulose/mannitol ratio correlated with portal inflammation (p=0.02), fibrosis (p=0.0002), and ballooning of hepatocytes (p=0.003). Blood lipopolysaccharides levels were higher in children with steatohepatitis (2.27±0.68 vs. 2.80±0.35, p<0.05). CONCLUSIONS: Intestinal permeability is increased in children with non-alcoholic fatty liver disease, and correlates with the severity of the disease.

A liquid chromatography/mass spectrometry method for the evaluation of intestinal permeability.

OBJECTIVES: Lactulose to mannitol ratio (L/M) in urine is used as a non invasive assay to measure intestinal permeability. We describe here a rapid, specific and sensitive LC-MS/MS method for the measurement of these compounds in urine of children affected by abdominal recurrent pain (ARP). DESIGN AND METHODS: The study has been performed on 50 children from the Pediatric Unit. The chromatographic separation was accomplished by using an NH(2)-column, the detection with a Q-Trap 2000 system. RESULTS: Multiple calibration curve exhibited consistent linearity and reproducibility. Linear responses were observed in the concentration range 0-400 microg/mL for both mannitol and lactulose. Limits of detection were 12.5 mg/L for lactulose and 1.25 mg/L for mannitol with a signal-to-noise ratio of 10. CONCLUSIONS: The comparison of L/M values of healthy children with those found in children affected by idiopathic ARP demonstrates that in the latter subjects an alteration of intestinal permeability occurs. The method can represent a useful tool to monitor the intestinal functionality in children with ARP conditions and help for an accurate patient discrimination for diet restrictions.