Optimal management of severe symptomatic gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a common disorder, and empirical proton pump inhibitor (PPI) treatment is often the first step of management; however, up to 40% of patients remain symptomatic despite PPI treatment. Refractory reflux refers to continued symptoms despite an adequate trial of PPI, and management remains challenging. The differential diagnosis is important; other oesophageal (e.g. eosinophilic oesophagitis) and gastroduodenal disorders (e.g. functional dyspepsia) should be ruled out, as this changes management. A combination of clinical assessment, endoscopic evaluation and in selected cases oesophageal function testing can help characterize patients with refractory reflux symptoms into oesophageal phenotypes so appropriate therapy can be more optimally targeted. Medical options then may include adding a H2 receptor antagonist, alginates, baclofen or antidepressant therapy, and there is emerging evidence for bile acid sequestrants and diaphragmatic breathing. The demonstration of a temporal association of symptoms with reflux events on pH-impedance testing (reflux hypersensitivity) serves to focus the management on modulating oesophageal perception and reducing the reflux burden, or identifies those with no obvious pathophysiologic abnormalities (functional heartburn). Anti-reflux surgery based on randomized controlled trial evidence has a role in reflux hypersensitivity or continued pathological acid reflux despite PPI in carefully considered, fully worked up cases that have failed medical therapy; approximately two of three cases will respond but there is a small risk of complications. In patients with persistent volume reflux despite medical therapy, given the lack of alternatives, anti-reflux surgery is a consideration. Promising newer approaches include endoscopic techniques. This review aims to summarize current diagnostic approaches and critically evaluates the evidence for the efficacy of available treatments.

A pragmatic comparative study of palliative care clinician's reports of the degree of shadowing visible on plain abdominal radiographs.

The assessment of constipation symptoms is based on history and physical examination. However, the experience is highly subjective perhaps explaining why palliative medicine doctors continue to use plain abdominal radiographs as part of routine assessment of constipation. Previous studies have demonstrated poor agreement between clinicians with this work in palliative care, limited further by disparity of clinicians' experience and training. The aim of this work was to explore whether there was less variation in the assessments of faecal shadowing made by more experienced clinicians compared to their less experienced colleagues. This pragmatic study was conducted across six palliative care services in Sydney (NSW, Australia). Doctors of varying clinical experience were asked to independently report their opinions of the amount of shadowing seen on 10 plain abdominal radiographs all taken from cancer patients who self-identified themselves as constipated. There were 46 doctors of varying clinical experience who participated including qualified specialists, doctors in specialist training and lastly, doctors in their second- and third post-graduate years. Poor agreement was seen between the faecal shadowing scores allocated by doctors of similar experience and training (Fleiss's kappa (FK): RMO 0.05; registrar 0.06; specialist 0.11). Further, when the levels of agreement between groups were considered, no statistically significant differences were observed. Although the doctors did not agree on the appearance of the film, the majority felt they were able to extrapolate patients' experiences from the radiograph's appearance. As it remains challenging in palliative care to objectively assess and diagnose constipation by history and imaging, uniform and objective assessment and diagnostic criteria are required. It is likely that any agreed criteria will include a combination of imaging and history. The results suggest the use of radiographs alone to diagnose and assess constipation in palliative care represents low value care.

Characterisation of the gastrointestinal mucosa-associated microbiota: a novel technique to prevent cross-contamination during endoscopic procedures.

BACKGROUND: The mucosa-associated microbiota appears to be highly relevant to host-microbe interactions in the gastrointestinal (GI) tract. Thus, precise characterisation of the mucosa-associated microbiota may provide important insights for diagnostic and therapeutic development. However, for technical reasons, mucosal biopsies taken during standard endoscopic procedures are potentially contaminated by GI luminal contents. AIM: To develop and validate a biopsy device that minimises contamination during sampling of the mucosa-associated microbiota. METHODS: A new, encased biopsy forceps was developed, the Brisbane Aseptic Biopsy Device (BABD). This comprises sterile forceps encased by a sheath with a plug at the tip, allowing targeted, aseptic sampling of the mucosa. Matched duodenal biopsies were obtained using the BABD, standard biopsy forceps, and a sterile brush, from patients undergoing upper GI endoscopy for iron deficiency (n = 6). Total genomic deoxyribonucleic acid (gDNA) was extracted from samples and bacterial 16S rRNA gene libraries sequenced to investigate the mucosa-associated microbiota. RESULTS: Microbial DNA was recovered from biopsies obtained by the BABD, confirming the presence of a duodenal mucosa-associated microbiota. This microbiota was dominated by the genus Streptococcus, with lower levels of Prevotella, Veillonella and Neisseria. At the individual patient level, substantial differences were observed between matched samples obtained using the different devices. A greater degree of bacterial diversity was observed in samples collected using the standard forceps, indicating the BABD affords collection of samples more representative of the mucosa-associated microbiota, by precluding luminal cross-contamination. CONCLUSIONS: Cross-contamination can occur when mucosal biopsies are taken during standard endoscopic procedures. Utilising the novel Brisbane Aseptic Biopsy Device can reduce cross-contamination, and it offers improved opportunities to more precisely examine host-mucosa-associated microbiota interactions.

Differentiation of functional constipation and constipation predominant irritable bowel syndrome based on Rome III criteria: a population-based study.

BACKGROUND: While the Rome III classification recognises functional constipation (FC) and constipation predominant IBS (IBS-C) as distinct disorders, recent evidence has suggested that these disorders are difficult to separate in clinical practice. AIM: To identify whether clinical and lifestyle factors differentiate Rome III-defined IBS-C from FC based on gastrointestinal symptoms and lifestyle characteristics. METHOD: 3260 people randomly selected from the Australian population returned a postal survey. FC and IBS-C were defined according to Rome III. The first model used logistic regression to differentiate IBS-C from FC based on lifestyle, quality-of-life and psychological characteristics. The second approach was data-driven employing latent class analysis (LCA) to identify naturally occurring clusters in the data considering all symptoms involved in the Rome III criteria for IBS-C and FC. RESULTS: We found n = 206 (6.5%; 95% CI 5.7-7.4%) people met strict Rome III FC whereas n = 109 (3.5%; 95% CI 2.8-4.1%) met strict Rome III IBS-C. The case-control approach indicated that FC patients reported an older age at onset of constipation, were less likely to exercise, had higher mental QoL and less health care seeking than IBS-C. LCA yielded one latent class that was predominantly (75%) FC, while the other class was approximately half IBS-C and half FC. The FC-dominated latent class had clearly lower levels of symptoms used to classify IBS (pain-related symptoms) and was more likely to be male (P = 0.046) but was otherwise similar in distribution of lifestyle factors to the mixed class. CONCLUSION: The latent class analysis approach suggests a differentiation based more on symptom severity rather than the Rome III view.

Oesophageal narrowing is common and frequently under-appreciated at endoscopy in patients with oesophageal eosinophilia.

BACKGROUND: Estimation of the prevalence of oesophageal narrowing and its clinical relevance in patients with oesophageal eosinophilia is probably underestimated by endoscopy. AIMS: To determine the sensitivity and specificity of oesophagogastroduodenoscopy (EGD) for oesophageal narrowing when compared to a structured oesophagram. METHODS: We conducted a retrospective chart review at Mayo Clinic, Rochester of adult patients with eosinophilic oesophageal infiltration of >15 eosinophils/hpf with symptomatic dysphagia, who underwent a structured barium oesophagram. The sensitivity and specificity of EGD were evaluated against the gold standard of oesophagram. Demographic and multiple clinical factors were evaluated as potential predictors of oesophageal narrowing. RESULTS: Of the 58 patients identified, 34 (58.6%) had a narrowed oesophageal diameter (<21 mm). EGD had poor sensitivity (14.7%, 95% CI 5.0-31.1%) for detection of a narrowed oesophagus and only modest specificity (79.2%, 95% CI 57.8-92.9%). Even at a cut-off diameter of EDmax  ≤ 15 mm, EGD had a sensitivity of only 25.0% (95% CI 5.5-57.2%) for narrowed oesophagus. A history of >5 food impaction episodes, endoscopic rings, and female sex were the best predictors of oesophageal narrowing. 86% (6/7) patients with persistent dysphagia despite remission of histological eosinophilia responded to oesophageal dilation all of whom had radiological oesophageal narrowing and 71% of whom had no perceived oesophageal narrowing at EGD. CONCLUSIONS: Symptomatic oesophageal narrowing identified by barium oesophagography is common and under-recognised at endoscopy in patients with oesophageal eosinophilia.

Risk of developing colorectal cancer and benign colorectal neoplasm in patients with chronic constipation.

BACKGROUND: Chronic constipation (CC) is a highly prevalent health problem, potentially associated with increased risk of colorectal cancer (CRCancer). AIM: To investigate the association between CC, its severity, and CRCancer by estimating the relative risk of developing CRCancer and benign colorectal neoplasm (BCN) among severity-stratified patients with and without CC. METHODS: Chronic constipation patients from a large retrospective US claims database were matched 1:3 with CC-free controls by demographic characteristics. CRCancer and BCN prevalence were measured over 1 year. In pre-index CRCancer- and BCN-free patients, incidence rate ratios (IRRs) of new CRCancer and BCN were calculated. Multivariate regression models adjusted for comorbidities and family history. CC patients' disease severity was rated based on CC-related resource use. IRRs for new CRCancer and BCN were estimated for CC severity groups and controls. RESULTS: Chronic constipation (N = 28,854) and CC-free (N = 86,562) patients had mean age 61.9 years; 66.7% were female. One-year CRCancer prevalence was 2.7% and 1.7%, and BCN prevalence was 24.8% and 11.9% for CC and CC-free patients, respectively. Adjusted IRRs between CC and CC-free patients were 1.59 [95% confidence interval (CI): 1.43-1.78] and 2.60 [95% CI: 1.51-2.70] for CRCancer and BCN, respectively. Patients with severe and very severe CC had significantly greater incidence of CRCancer and BCN. At ≥ 2 and ≥ 5 years of observation, CRCancer and BCN incidence remained consistently and significantly higher for CC patients. CONCLUSIONS: Patients with chronic constipation are associated with significantly higher prevalence and incidence of colorectal cancer and benign colorectal neoplasm than matched chronic constipation-free patients. These risks increase with the severity of chronic constipation.

Review article: bacteria and pathogenesis of disease in the upper gastrointestinal tract--beyond the era of Helicobacter pylori.

BACKGROUND: Study of the upper gastrointestinal microbiome has shown that other bacteria besides Helicobacter pylori flourish despite the hostile environment. Whilst H. pylori is the most studied bacteria in this region with a defined role in inflammation and neoplasia, it is apparent that other bacteria may contribute to UGI disease. AIM: To review current knowledge of bacteria inhabiting the oesophagus, stomach and duodenum. METHODS: Published studies on the upper gastrointestinal microbiome (extracted from PubMed during the last 20 years). RESULTS: The stomach is a hostile environment for bacteria; however, recent studies categorising the microbiota have shown surprising results. Helicobacter pylori has been intensively studied since 1984 and recent sequencing analysis of other gastric microbiota shows that H. pylori is not alone. Composition can be influenced by acid suppression, gastritis and abundance of H. pylori. Eradication of H. pylori, whilst decreasing gastric cancer is associated with an increase in asthma, reflux and obesity. A future approach may be to selectively eradicate bacteria which predispose to inflammation and cancer as opposed to a comprehensive knockout policy. In the oesophagus, viridans streptococci are the most common bacteria influenced by both oral and gastric bacteria. Oesophagitis and Barrett's oesophagus are characterised by a significant decrease in Gram-positive bacteria and an increase in Gram-negative bacteria. An inverse association of H. pylori and oesophageal adenocarcinoma is described. The duodenal microbiome has been shown to influence small intestinal bacterial overgrowth, irritable bowel syndrome and coeliac disease. The numbers of bacteria recoverable by culture are variable in the stomach mucosa and gastric juice, typically 10(2) -10(4) colony-forming units (CFU)/g or mL and in the oesophagus, up to 10(4) bacteria per mm(2) mucosal surface. In the small bowel, in health, 10(3) CFU/mL are normal. CONCLUSION: This review highlights current knowledge of upper gastrointestinal bacteria and associations with disease.

Abdominal pain is associated with anxiety and depression scores in a sample of the general adult population with no signs of organic gastrointestinal disease.

BACKGROUND: Abdominal pain is common in the community, but only a subset meet diagnostic criteria for irritable bowel syndrome (IBS). Although anxiety and depression have been linked to IBS, the role of mood disturbances in the remainder with symptoms remains unclear. We aimed to study the associations between abdominal pain, anxiety, depression, and quality of life in the general population who were free of organic colonic disease by colonoscopy. METHODS: Two hundred and seventy-two randomly selected subjects from the general population, mean age 54 years (27-71), were clinically evaluated, had a colonoscopy and laboratory investigations to exclude organic gastrointestinal (GI) disease. All subjects completed GI symptom diaries for 1 week, the Rome II modular questionnaire, the Hospital Anxiety and Depression Scale, and Short Form 36. KEY RESULTS: Twenty-two subjects were excluded due to organic disease; 1532 daily symptom records were available for analysis in the remainder. Thirty-four percent (n = 83) recorded at least one episode of abdominal pain on the diary. Twelve percent fulfilled Rome II criteria for IBS. Both anxiety and depression scores were higher in subjects who reported abdominal pain vs those who did not (P < 0.0005 and P < 0.0005). Anxiety and depression scores independently from IBS diagnosis (Rome II) predicted pain reporting and also correlated positively with pain burden. Quality of life scores were generally lower in subjects with abdominal pain. CONCLUSIONS & INFERENCES: Anxiety and depression are linked to functional abdominal pain, not only in subjects with IBS but also in otherwise healthy people with milder, subtle GI symptoms.

Cyclic vomiting syndrome and functional vomiting in adults: association with cannabinoid use in males.

BACKGROUND: Cyclic vomiting syndrome (CVS) is characterized by stereotypical episodes of vomiting separated by symptom-free intervals. However, the difficulty encountered in the management of patients with CVS may be a reflection of a deficiency in our understanding of the disorder. We aimed to evaluate whether clinical or gastric emptying (GE) data discriminate patients labeled as having CVS from functional vomiting (FV) or irritable bowel syndrome (IBS). METHODS: The medical records of patients diagnosed with any vomiting (including CVS, FV) over a 13-year period (1993-2006) at our institution were carefully reviewed. Disease controls were age and gender matched subjects with IBS. Gastric emptying was performed by scintigraphy (99mTc-egg meal). The associations of clinical factors and GE data with patient status (CVS vs FV or IBS) were analyzed. KEY RESULTS: A total of 82 patients with CVS and 62 FV patients were identified. Younger age [per 10 years, OR = 0.7 (0.5, 0.9)], male gender [OR = 0.4 (0.2, 0.9)], and cannabinoid use [OR = 2.9 (1.2, 7.2)] were significantly associated with CVS compared with FV. However, there were no significant associations between patient status (CVS vs FV) and age, BMI, smoking, alcohol use, gastrointestinal symptoms, or GE. The proportion of cannabinoid users was significantly higher in patients with CVS compared with patients with IBS, whereas proportions for headaches and psychiatric disease were higher in subjects with IBS. CONCLUSIONS & INFERENCES: Cyclic vomiting syndrome (vs FV) was not associated with clinical factors, but was associated with younger age, male gender and cannabinoid use. A larger proportion of CVS (vs IBS) patients had used cannabinoids.

Oesophageal eosinophilic infiltration in patients with noncardiac chest pain.

BACKGROUND: Eosinophilic oesophagitis clinically presents with recurrent episodes of dysphagia and food impaction. Recently, we observed patients with noncardiac chest pain and eosinophilic oesophagitis. AIMS: To estimate the prevalence of abnormal eosinophilic infiltration in noncardiac chest pain patients and examine diagnostic utility of demographic, clinical and endoscopic variables to predict eosinophilic oesophagitis. METHODS: Retrospective study of 171 consecutive patients referred for EGD evaluation of noncardiac chest pain. Endoscopic signs consistent with eosinophilic oesophagitis were recorded. The histological findings were grouped as normal: 0-5 eosinophils/high power field (e/hpf), indeterminate: 6-20 e/hpf, and eosinophilic oesophagitis: ≥21 e/hpf. Abnormal eosinophilic infiltration was defined as ≥6 e/hpf. RESULTS: Abnormal eosinophilic infiltrate was noted in 24 patients (14%). Thirteen (8%) had indeterminate counts, while 11 (6%) had eosinophilic oesophagitis. Compared with normal, those with abnormal oesophageal eosinophilic infiltration were more likely to be male (71% vs. 34%, P=0.001), have allergies (29% vs. 12%, P=0.050), have current GER symptoms (42% vs. 18%, P=0.013), rings (54% vs. 22%, P=0.002), furrows (21% vs. 1%, P<0.001) and abnormal eosinophilic oesophagitis findings on endoscopy (67% vs. 32%, P=0.001). Of the 24 abnormal patients, 23 (96%) were either male or had rings, furrows, or white specks. Conversely, 68 of 69 patients (99%) who were female did not have rings, furrows, or white specks, and endoscopy was normal. Eight patients (33%) with abnormal eosinophilic infiltration had a normal endoscopy. CONCLUSIONS: Eosinophilic oesophagitis should be considered in the evaluation of noncardiac chest pain. Our findings suggest that oesophageal biopsies should be obtained particularly in males with recurrent unexplained chest pain, whether endoscopy is normal or abnormal.

Functional dyspepsia impairs quality of life in the adult population.

BACKGROUND: Data on the impact of functional dyspepsia on health-related quality of life in the general adult population are scarce. AIM: To explore the impact of functional dyspepsia applying the Rome III definition on health-related quality of life in the general population. METHOD: A random sample of an adult Swedish population (n=1001, The Kalixanda study) was invited to undergo an oesophagogastroduodenoscopy. An extended abdominal symptom questionnaire and Short Form-36 (SF-36) questionnaire, which includes eight domains measuring physical, mental and social aspects of quality of life, were completed at the clinic visit just before oesophagogastroduodenoscopy. RESULTS: Two hundred and two (20%) individuals reported uninvestigated dyspepsia (UID), 157 (16%) functional dyspepsia (FD), 52 (5%) epigastric pain syndrome (EPS) and 122 (12%) postprandial distress syndrome (PDS). UID, FD and PDS had a clinically meaningful (a ≥ 5 point) and statistically significant impact (P<0.05) on health-related quality of life in all SF-36 domains except for Role Emotional. EPS had a significant impact on Bodily Pain and Vitality. Overlap of FD with irritable bowel syndrome (IBS) had a significant impact on Bodily Pain (P=0.002) and General Health (P=0.02) while FD overlap with gastro-oesophageal reflux symptoms (GERS) had a significant impact on Bodily Pain (P=0.02) compared with FD without any overlap with IBS or GERS. CONCLUSION: Functional dyspepsia impacts all main domains describing physical, mental and social aspects of health-related quality of life in the general population. Overlap of functional dyspepsia with irritable bowel syndrome or gastro-oesophageal reflux symptoms impacts the domain related to bodily pain.

Implications of eosinophilia in the normal duodenal biopsy - an association with allergy and functional dyspepsia.

BACKGROUND: Allergy and functional gastrointestinal disorders have been associated with eosinophilia in duodenal mucosa. AIM: To assess the prevalence of eosinophilia in duodenal biopsies of patients attending for oesophogastroduodenoscopy and delineate associated clinical conditions. METHODS: A total of 155 patients (mean age 55 years, 59% women) with normal duodenal biopsies were randomly selected for audit from histopathology files. Eosinophil counts in five high power fields (HPFs) were assessed. Records were analysed for symptoms, diagnosis and medications; patients were divided into five groups based on upper gastrointestinal (UGI) symptom profiles, including a control group of those without predominant UGI symptoms. The prevalence of duodenal eosinophilia (defined as >22/5HPFs a priori) was calculated. RESULTS: In the control group, the mean duodenal eosinophil count was 15/5HPFs; prevalence of duodenal eosinophilia was 22.5%. In postprandial distress syndrome (PDS), both mean eosinophil counts (20.2/5HPF, P < 0.04) and prevalence of duodenal eosinophilia (47.3%, P < 0.04) were significantly higher. Duodenal eosinophilia was significantly associated with allergy (OR 5.04, 95% CI 2.12-11.95, P < 0.001). There was no association with irritable bowel syndrome or medications. CONCLUSIONS: Subtle duodenal eosinophilia is relatively common in routine oesophogastroduodenoscopy and previously overlooked; it is associated with allergy and may indicate a hypersensitivity mechanism in some patients with PDS including early satiety.

Irritable bowel syndrome: novel views on the epidemiology and potential risk factors.

Symptoms consistent with the irritable bowel syndrome are remarkably frequent around the world. Irritable bowel syndrome prevalence ranges from 2.1% to 22%, depending on criteria used. Women are more frequently affected than men, but the reasons remain obscure; irritable bowel syndrome occurs in all age groups but there appears to be a modest decline in prevalence with advancing age again for unknown reasons. The incidence of irritable bowel syndrome per year has been estimated at approximately 1.5% in community subjects; annually only 0.2% of population will be diagnosed with irritable bowel syndrome. The natural history of irritable bowel syndrome is characterized by symptomatic flare ups and by a high rate of transition to other functional gastrointestinal diseases over the long term. Well recognized risk factors for irritable bowel syndrome include psychological distress and gastroenteritis. However, the association of psychological distress in some cases may reflect confounding factors and might be explained at least in part by cytokine production. Familial aggregation of irritable bowel syndrome occurs, and while the environment is key, twin studies generally support a genetic component in irritable bowel syndrome explaining up to 20% of the variability. Prior surgery may increase risk of irritable bowel syndrome. Early childhood trauma may be important; a low birth weight, nasogastric suction at birth, childhood abuse, and low socioeconomic status may carry an increased risk of suffering with irritable bowel syndrome as an adult. The role of diet remains uncertain but under-studied.

Risk factors for chronic diarrhoea in the community in the absence of irritable bowel syndrome.

In contrast to irritable bowel syndrome (IBS), the prevalence and risk factors for diarrhoea in the absence of IBS in the community are unknown. We aimed to evaluate potential risk factors for chronic diarrhoea (non-IBS). A valid questionnaire that recorded gastrointestinal symptoms required for a diagnosis of chronic diarrhoea, self-reported measures of potential risk factors, and a somatic symptom checklist was mailed to an age- and gender-stratified random sample of Olmsted County, Minnesota residents (30-64 year). Chronic diarrhoea was defined as reporting one or more of the following symptoms more than 25% of the time in the past 3 months: > or =3 bowel movements a day, loose or watery stools, or faecal urgency. Subjects with IBS (Rome III) were excluded. Of 892 eligible subjects, 653 (73%) responded. Among 523 respondents not reporting IBS, chronic diarrhoea was reported by 148 (28%); 90 (61%) had chronic painless diarrhoea. Chronic diarrhoea was significantly associated with self-reported food sensitivity (OR = 2.05 [1.31-3.20]) and stress (OR = 1.99 [1.03-3.85]). Both remained significant in the adjusted variable models that excluded subjects with any abdominal pain. Female gender (OR = 0.67 [0.45-0.98]) and higher education level (OR = 0.60 [0.39-0.92]) had smaller odds for chronic diarrhoea. No association was detected for age, marital status, body mass index, cigarette or alcohol use, coffee, analgesics, emotional support, pets or water source. Chronic diarrhoea in the absence of IBS is common; self-reported food sensitivity, male gender and a lower level of education are risk factors.

Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia.

BACKGROUND: Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common functional disorders without defined pathology. Mast cells and eosinophils interact with T lymphocytes and may alter enteric nerve and smooth muscle function. AIM: To examine mast cell, eosinophil and intraepithelial lymphocyte populations in duodenal biopsies of subjects with IBS and FD. METHODS: A random sample of an adult Swedish population (n = 1001; mean age 54 years; 51% female) underwent upper endoscopy and biopsy; 51 cases with FD and 41 cases with IBS were compared with 48 randomly selected controls. Eosinophils were identified by light microscopy; mast cells by immunocytochemistry (CD117). Intraepithelial lymphocytes were counted per 100 enterocytes. Cell counts were quantified by counting the number per high power field (HPF) in 5HPFs in the bulb (D1) and second part of duodenum (D2), summed over 5HPFs at each site. RESULTS: Cases and controls showed similar demographics. Compared to controls, IELs in IBS-constipation were significantly increased (P = 0.005). Mast cells were significantly increased in IBS in D2 (P < 0.001), while eosinophils were significantly increased in FD in D1 and D2 (P < 0.001). CONCLUSION: Duodenal mast cell hyperplasia is linked to IBS and eosinophilia to FD, and duodenal biopsy may identify subsets of these disorders.