Pediatric and adult eosinophilic esophagitis: similarities and differences

Early in the 1990s, several case series described adults suffering from dysphagia and children with refractory reflux symptoms, both accompanied by an eosinophil-predominant infiltration, thereby conclusively distinguishing it from gastroesophageal reflux disease. Eosinophilic esophagitis (EoE) was recognized as its own entity in the adult and in the pediatric literature. In the last decade, evidence has accumulated that EoE represents a T-helper (Th)2-type inflammatory disease. Remodeling of the esophagus is a hallmark of EoE, leading to esophageal dysfunction and bolus impaction. Familial occurrence and disease association with single-nucleotide polymorphisms underscore the influence of genetics in this disease. Eosinophilic esophagitis may affect individuals at any age, although the clinical presentation is highly age dependent. There is a significant allergic bias in the EoE population, with the majority of patients having concurrent allergic rhinitis, asthma, eczema, and/or a history of atopy. One noteworthy difference is that in children, EoE seems to be primarily a food antigen-driven disease, whereas in adults, mainly aeroallergen sensitization has been observed. Treatment modalities for EoE include the 3Ds: drugs, diet, and dilation. The crucial question of whether adult and pediatric EoE are different phenotypes of one single entity or whether we are confronted with two different diseases is still open. Here, we review similarities and differences between EoE in adults and children.

Quantification of dental erosions in patients with GERD using optical coherence tomography before and after double-blind, randomized treatment with esomeprazole or placebo

OBJECTIVES: Dental erosion, the chemical dissolution of enamel without bacterial involvement, is a rarely reported manifestation of gastroesophageal reflux disease (GERD), as well as of recurrent vomiting and dietary habits. It leads to loss of tooth substance, hypersensitivity, functional impairment, and even tooth fracture. To date, dental erosions have been assessed using only very basic visual methods, and no evidence-based guidelines or studies exist regarding the prevention or treatment of GERD-related dental erosions. METHODS: In this randomized, double-blind study, we used optical coherence tomography (OCT) to quantify dental tissue demineralization and enamel loss before and after 3 weeks of acid-suppressive treatment with esomeprazole 20 mg b.i.d. or placebo in 30 patients presenting to the Berne University Dental Clinic with advanced dental erosions and abnormal acid exposure by 24-h esophageal pH manometry (defined as >4% of the 24-h period with pH<4). Enamel thickness, reflectivity, and absorbance as measures of demineralization were quantified by OCT before and after therapy at identical localizations on teeth with most severe visible erosions as well as several other predefined changes in teeth. RESULTS: The mean+/-s.e.m. decrease of enamel thickness of all teeth before and after treatment at the site of maximum exposure was 7.2+/-0.16 black trianglem with esomeprazole and 15.25+/-0.17black trianglem with placebo (P=0.013), representing a loss of 0.3% and 0.8% of the total enamel thickness, respectively. The change in optical reflectivity to a depth of 25 black trianglem after treatment was-1.122 +/-0.769 dB with esomeprazole and +2.059+/-0.534 dB with placebo (P 0.012), with increased reflectivity signifying demineralization. CONCLUSIONS: OCT non-invasively detected and quantified significantly diminished progression of dental tissue demineralization and enamel loss after only 3 weeks of treatment with esomeprazole 20 mg b.i.d. vs. placebo. This suggests that esomeprazole may be useful in counteracting progression of GERD-related dental erosions. Further validation of preventative treatment regimens using this sensitive detection method is required, including longer follow-up and correlation with quantitative reflux measures.

Natural course of pontocerebellar hypoplasia type 2A

INTRODUCTION Pontocerebellar hypoplasia Type 2 (PCH2) is a rare autosomal recessive condition, defined on MRI by a small cerebellum and ventral pons. Clinical features are severe developmental delay, microcephaly and dyskinesia.Ninety percent carry a p.A307S mutation in the TSEN54-gene. Our aim was to describe the natural course including neurological and developmental features and other aspects of care in a homogeneous group of PCH2 patients all carrying the p.A307S mutation. PATIENTS AND METHODS Patients were recruited via the German patients' organizations. Inclusion criteria were imaging findings of PCH2 and a p.A307S mutation. Data were collected using medical reports and patient questionnaires discussed in a standardized telephone interview. RESULTS Thirty-three patients were included. When considering survival until age 11 years, 53% of children had died Weight, length and head circumference, mostly in the normal range at birth, became abnormal, especially head circumference (-5.58 SD at age 5 yrs). Neurologic symptoms: Choreathetosis was present in 88% (62% with pyramidal signs), 12% had pure spasticity. Epileptic seizures were manifest in 82%, status epilepticus in 39%. Non-epileptic dystonic attacks occurred in 33%. General symptoms: feeding difficulties were recorded in 100%, sleep disorder in 96%, apneas in 67% and recurrent infections in 52%; gastroesophageal reflux disease was diagnosed in 73%, 67% got percutaneous endoscopic gastrostomy and 36% a Nissen-fundoplication. Neurodevelopmental data: All children made progress, but on a low level: such as fixing and following with the eyes was seen in 76%, attempting to grasp objects (76%), moderate head control (73%), social smile (70%), rolling from prone to supine (58%), and sitting without support (9%). Ten percent lost achieved abilities on follow-up. The presence of prenatal symptoms did not correlate with outcome. CONCLUSION Phenotype of this genetically homogeneous group of PCH2 children was severe with reduced survival, but compatible with some developmental progress. Our data support the hypothesis of an early onset degeneration which thereafter stabilizes.

Mechanisms of airway obliteration after lung transplantation

Post-transplant bronchiolitis obliterans, also called bronchiolitis obliterans syndrome, affects up to 50-60% of patients who survive 5 yr after surgery according to its clinical definition, which is based on the degree of obstructive airway disease. Alloimmune-independent and -dependent mechanisms produce injuries and inflammation of epithelial cells and subepithelial structures, leading to aberrant tissue repair. The triggering of innate immunity by various infections or chemical injuries after, for example, gastroesophageal reflux, may lead to the release of danger signals that are able to activate dendritic cells, a crucial link with adaptive immunity. Inflammation can also increase the expression and display of major histocompatibility alloantigens and thus favor the initiation of rejection episodes. These phenomena may be limited in time and location or may be protracted. Reducing the risk of alloimmune-independent factors may be as important as treating acute episodes of lung rejection. Excessive immunosuppression may be deleterious by increasing the risk of infection, thereby triggering innate and adaptive immunity. New potential therapeutic targets are emerging from the research performed on leukotriene receptors, chemokine receptors, and growth factors. Neutralizing these molecules reduces the initial mononuclear and polynuclear infiltrates or the subsequent fibroproliferative process and the neovascular changes, feeding this process.

Reflux monitoring: pH-metry, Bilitec and oesophageal impedance measurements

Gastro-oesophageal reflux disease (GERD) is a highly prevalent condition in Western countries leading to millions of outpatient visits per year. GERD symptoms including heartburn, regurgitation and chest pain are caused by reflux of gastric content in the oesophagus even in the absence of endoscopically visible mucosal lesions. Several procedures are used to identify gastro-oesophageal reflux, the clinically widely used are: conventional (catheter-based) pH monitoring, wireless oesophageal pH monitoring (Bravo), bilirubin monitoring (Bilitec), and combined multichannel intraluminal impedance-pH monitoring (MII-pH). Each technique has strengths and limitations of which clinicians and investigators should be aware when deciding which to choose in a particular patient. Important is the ability to quantify gastro-oesophageal reflux and evaluate the relationship between symptoms and reflux episodes. The present review summarises the technical aspects in performing and interpreting esophageal reflux monitoring procedures.

Symptoms with acid and nonacid reflux may be produced by different mechanisms

Twenty-four-hour multichannel intraluminal impedance and pH (MII-pH) esophageal monitoring detects both acid and nonacid gastroesophageal reflux episodes. The MII-pH catheter contains six impedance segments placed 3, 5, 7, 9, 15, and 17 cm above the lower esophageal sphincter (LES). A pH electrode at 5 cm above the LES identifies the type of reflux, i.e. acid or nonacid. Patients with acid and nonacid reflux exhibit typical and atypical symptoms often within 5 min following a reflux episode. The aim of this study is to compare the timing of symptoms after reflux episodes in patients with acid and nonacid reflux. Methods include a review of 70 MII-pH tracings (42 females, mean age 40, range 18-85 years) either on (50 points) or off (20 points) acid suppression therapy. Typical (heartburn, regurgitation) and atypical (cough) symptoms with acid or nonacid reflux episodes detected by impedance were analyzed. Symptoms were considered positive with acid reflux if there was a pH drop to <4, plus an MII detected a reflux episode and with nonacid reflux if pH remained >4 and MII detected a reflux episode. The timing of the symptom after each reflux episode was recorded. Symptom perception occurred significantly sooner after acid versus nonacid reflux (P < 0.05). Acid reflux episodes are more likely to be perceived in the first 2 min following the reflux episode. Patients with acid reflux are likely to perceive symptoms earlier, and symptoms with acid and nonacid reflux may be produced by different mechanisms.

Nonacid reflux episodes reaching the pharynx are important factors associated with cough

BACKGROUND: Gastroesophageal reflux is implicated in the pathogenesis of asthma and chronic cough. To date most studies have focused on acid reflux measured by pH below the upper esophageal sphincter (UES). The aim of this study was to assess the relationship between cough and reflux through the UES into the pharynx. METHODS: Thirty-seven patients with asthma (19) and chronic cough (18) were recruited from the respiratory clinic. Reflux was monitored using a combined multichannel intraluminal impedance and pH probe by detecting (1) bolus reflux episodes within the esophagus and in the pharynx and (2) acidic reflux episodes within the esophagus and in the pharynx. All acid suppressive therapy was stopped for at least 7 days before the study. Demonstration of cough being linked to reflux was achieved using the symptom association probability (SAP). This was calculated using a 2-minute association window between symptoms and bolus entry into the esophagus. SAP was considered positive if >95%. RESULTS: A positive SAP for cough was noted in 7/26 patients reporting symptoms on the day of monitoring. Compared with SAP-negative patients, SAP-positive patients had both a greater number [median (interquartile range), 5(2 to 8) vs. 2(0 to 4), P<0.05] and a higher proportion of reflux episodes crossing the UES into the pharynx [25%(14% to 28%) vs. 7% (2% to 14%), P<0.02]. There was no difference in the number of reflux episodes or acid exposure time in the distal esophagus between SAP-positive and SAP-negative patients. Only 1% to 2% of episodes were detected by the pharyngeal pH sensor. CONCLUSIONS: Impedance detected pharyngeal reflux episodes are important factors in symptom production in cough patients.

Reflux nach bariatrischen Operationen

Obesity and gastro-esophageal reflux disease (GERD) are two of the major health problems of the industrialized world. Both condition have increased prevalence, pathophysiological and endoscopic studies identified obesity a major risk factor in the development of GERD. Conversely, successful weight reduction improves GERD symptoms and diminishes the use of acid suppressive medication. Bariatric interventions are not all equal when it comes to controlling GERD symptoms, lesions and use of medication. Gastric banding has a variable influence on GERD, while most patients report improved reflux symptoms, up to 20% of patient can develop "de novo" reflux symptoms following gastric banding. Gastric sleeve resection increases reflux symptoms, in particular in patients with an ideal, tubular gastroplasty and those with proximal (fundic) pouch. Roux-en-Y gastric bypass has a positive effect of GERD, reducing symptoms and use of acid suppressive medications. From an esophageal perspective, gastric bypass is the preferred bariatric procedure to treat and prevent GERD in morbidly obese patients.

Gastro-oesophageal reflux is common in oligosymptomatic patients with dental erosion: A pH-impedance and endoscopic study.

Background: Dental erosion is a complication of gastro-oesophageal reflux disease (GORD) according to the Montreal consensus statement. However, GORD has not been comprehensively characterized in patients with dental erosions and pH-impedance measures have not been reported. Objectives: Characterize GORD in patients with dental erosions using 24-h multichannel intraluminal pH-impedance measurements (pH-MII) and endoscopy. Methods: This single-centre study investigated reflux in successive patients presenting to dentists with dental erosion using pH-MII and endoscopy. Results: Of the 374 patients, 298 (80%) reported GORD symptoms <2 per week, 72 (19%) had oesophagitis and 59 (16%) had a hiatal hernia. In the 349 with pH-MII the mean percentage time with a pH <4 (95% CI) was 11.0 (9.3–12.7), and 34.4% (31.9–36.9) for a pH <5.5, a critical threshold for dental tissue. The mean numbers of total, acidic and weakly acidic reflux episodes were 71 (63–79), 43 (38–49) and 31 (26–35), respectively. Of the reflux episodes, 19% (17–21) reached the proximal oesophagus. In 241 (69%) patients reflux was abnormal using published normal values for acid exposure time and reflux episodes. No significant associations between the severity of dental erosions and any reflux variables were found. The presence of GORD symptoms and of oesophagitis or a hiatal hernia was associated with greater reflux, but not with increased dental erosion scores. Conclusions: Significant oligosymptomatic gastro-oesophageal reflux occurs in the majority of patients with dental erosion. The degree of dental erosion did not correlate with any of the accepted quantitative reflux indicators. Definition of clinically relevant reflux parameters by pH-MII for dental erosion and of treatment guidelines are outstanding. Gastroenterologists and dentists need to be aware of the widely prevalent association between dental erosion and atypical GORD.

Erosive esophageal reflux vs. non erosive esophageal reflux: oral findings in 71 patients.

BACKGROUND The purpose of this clinical study was to assess the prevalence of acidic oral mucosal lesions and periodontal conditions in patients suffering from erosive esophageal reflux disease (ERD) compared with non erosive esophageal reflux disease (NERD) patients, both treated with long term proton pump inhibitors (PPI). METHODS Seventy-one patients with diagnosed GERD were studied: i.e. 29 ERD and 42 NERD patients. Thorough visual examination of the oral mucosa and a periodontal evaluation was performed. The primary outcome was defined as a statistically significant difference, between the two groups, in the presence of acidic lesions of the oral mucosa and specific periodontal parameters. RESULTS This study failed to demonstrate statistically significant differences between ERD and NERD patients with respect to the prevalence of oral mucosal lesions. However, significantly more ERD patients suffered from severe periodontitis (CAL ≥ 5 mm) as compared to NERD patients. Accordingly, it may be assumed that PPI-use had no adverse effects on the prevalence of acidic oral mucosal lesions and on periodontal destruction. CONCLUSIONS Within the limitations of this study it may be concluded that ERD and NERD patients need separate evaluation with respect to periodontal destruction. Moreover, long term PPI medication had no adverse clinical impact on acidic oral mucosal lesions and periodontal destruction. Further studies are necessary to elucidate the role of reflux in the periodontal destruction of ERD individuals.

Manually calculated oesophageal bolus clearance time increases in parallel with reflux severity at impedance-pH monitoring.

BACKGROUND Oesophageal clearance has been scarcely studied. AIMS Oesophageal clearance in endoscopy-negative heartburn was assessed to detect differences in bolus clearance time among patients sub-grouped according to impedance-pH findings. METHODS In 118 consecutive endoscopy-negative heartburn patients impedance-pH monitoring was performed off-therapy. Acid exposure time, number of refluxes, baseline impedance, post-reflux swallow-induced peristaltic wave index and both automated and manual bolus clearance time were calculated. Patients were sub-grouped into pH/impedance positive (abnormal acid exposure and/or number of refluxes) and pH/impedance negative (normal acid exposure and number of refluxes), the former further subdivided on the basis of abnormal/normal acid exposure time (pH+/-) and abnormal/normal number of refluxes (impedance+/-). RESULTS Poor correlation (r=0.35) between automated and manual bolus clearance time was found. Manual bolus clearance time progressively decreased from pH+/impedance+ (42.6s), pH+/impedance- (27.1s), pH-/impedance+ (17.8s) to pH-/impedance- (10.8s). There was an inverse correlation between manual bolus clearance time and both baseline impedance and post-reflux swallow-induced peristaltic wave index, and a direct correlation between manual bolus clearance and acid exposure time. A manual bolus clearance time value of 14.8s had an accuracy of 93% to differentiate pH/impedance positive from pH/impedance negative patients. CONCLUSIONS When manually measured, bolus clearance time reflects reflux severity, confirming the pathophysiological relevance of oesophageal clearance in reflux disease.

Adverse effects of drugs on the esophagus

Given the function of the esophagus to transport orally ingested solids and liquids into the stomach there are several medications with adverse effect on esophageal structures and function. Various pharmacologic agents can induce esophageal injury, promote gastroesophageal reflux by decreasing lower esophageal sphincter tone or affect esophageal perception and motility. The risks of bisphosphonates, doxycycline, ferrous sulfate, ascorbic acid, aspirin/NSAIDs and chemotherapeutic agents to induce esophageal lesions have been documented in case reports and short series. In addition to direct mucosal injury, many commonly used medications including nitroglycerins, anticholinergics, beta-adrenergic agonists, aminophyllines, and benzodiazepines promote/facilitate gastroesophageal reflux by reducing lower esophageal sphincter pressure. Additional evidence accumulates on the adverse effects of various medications on esophageal motility and perception. The treatment of medication-induced esophageal lesions includes (1) identifying and discontinuing the causative medication, (2) promoting healing of esophageal injury by decreasing esophageal acid exposure or coating already existing esophageal lesions, (3) eventual use of protective compounds.

Severe systemic adverse reaction to proton pump inhibitors in an infant

Episodes of respiratory distress with chest retraction and wheezing, sometimes associated with facial edema, were noted after administering the proton pump inhibitors omeprazole and esomeprazole in an infant with gastroesophageal reflux. The disturbances relieved dramatically after withdrawing the proton pump inhibitor.

Erosive tooth wear in children.

Erosive tooth wear in children is a common condition. Besides the anatomical differences between deciduous and permanent teeth, additional histological differences may influence their susceptibility to dissolution. Considering laboratory studies alone, it is not clear whether deciduous teeth are more liable to erosive wear than permanent teeth. However, results from epidemiological studies imply that the primary dentition is less wear resistant than permanent teeth, possibly due to the overlapping of erosion with mechanical forces (like attrition or abrasion). Although low severity of tooth wear in children does not cause a significant impact on their quality of life, early erosive damage to their permanent teeth may compromise their dentition for their entire lifetime and require extensive restorative procedures. Therefore, early diagnosis of erosive wear and adequate preventive measures are important. Knowledge on the aetiological factors of erosive wear is a prerequisite for preventive strategies. Like in adults, extrinsic and intrinsic factors, or a combination of them, are possible reasons for erosive tooth wear in children and adolescents. Several factors directly related to erosive tooth wear in children are presently discussed, such as socio-economic aspects, gastroesophageal reflux or vomiting, and intake of some medicaments, as well as behavioural factors such as unusual eating and drinking habits. Additionally, frequent and excessive consumption of erosive foodstuffs and drinks are of importance.