Pathophysiology, diagnosis, and management of opioid-induced constipation.

Opioids are potent analgesics used for the treatment of acute and chronic pain. Side-effects are common and among the most bothersome are those associated with opioid-induced bowel dysfunction, which includes opioid-induced constipation. In this Review, we provide a summary of the pathophysiology, diagnosis, and management of opioid-induced constipation, which can be defined as a change in baseline bowel habit or defecatory patterns following initiation, alteration, or increase of opioid therapy. Opioid-induced constipation is a consequence of the action of opioids on their receptors in the gastrointestinal tract. A comprehensive clinical assessment is beneficial, including evaluation of the patient's understanding of their constipation and underlying condition for which opioids are used. Clinical assessment should also aim to differentiate opioid-induced constipation from pre-existing constipation exacerbated by the opioids. Preventive strategies need to be considered when patients start treatment with opioids, such as lifestyle changes. First-line management includes simple over-the-counter laxatives. The bowel function index can be useful to objectively identify patients who are refractory to these initial measures. In this context, alternative over-the-counter laxatives (or combinations of laxatives), secretogogues, or peripherally acting µ-opioid receptor antagonists might also be considered. Educational strategies need to be developed to improve the knowledge base of health-care providers on the identification and management of opioid-induced constipation.

Seronegative celiac disease: Shedding light on an obscure clinical entity.

BACKGROUND: Although serological tests are useful for identifying celiac disease, it is well established that a minority of celiacs are seronegative. AIM: To define the prevalence and features of seronegative compared to seropositive celiac disease, and to establish whether celiac disease is a common cause of seronegative villous atrophy. METHODS: Starting from 810 celiac disease diagnoses, seronegative patients were retrospectively characterized for clinical, histological and laboratory findings. RESULTS: Of the 810 patients, fourteen fulfilled the diagnostic criteria for seronegative celiac disease based on antibody negativity, villous atrophy, HLA-DQ2/-DQ8 positivity and clinical/histological improvement after gluten free diet. Compared to seropositive, seronegative celiac disease showed a significantly higher median age at diagnosis and a higher prevalence of classical phenotype (i.e., malabsorption), autoimmune disorders and severe villous atrophy. The most frequent diagnosis in the 31 cases with seronegative flat mucosa was celiac disease (45%), whereas other diagnoses were Giardiasis (20%), common variable immunodeficiency (16%) and autoimmune enteropathy (10%). CONCLUSIONS: Although rare seronegative celiac disease can be regarded as the most frequent cause of seronegative villous atrophy being characterized by a high median age at diagnosis; a close association with malabsorption and flat mucosa; and a high prevalence of autoimmune disorders.

Features and Progression of Potential Celiac Disease in Adults.

BACKGROUND & AIMS: Individuals with potential celiac disease have serologic and genetic markers of the disease with little or no damage to the small intestinal mucosa. We performed a prospective study to learn more about disease progression in these people. METHODS: We collected data from 77 adults (59 female; median age, 33 years) diagnosed with potential celiac disease (on the basis of serology and HLA type) at Bologna University in Italy from 2004 through 2013. The subjects had normal or slight inflammation of the small intestinal mucosa. Clinical, laboratory, and histologic parameters were evaluated at diagnosis and during a 3-year follow-up period. RESULTS: Sixty-one patients (46 female; median age, 36 years) showed intestinal and extraintestinal symptoms, whereas the remaining 16 (13 female; median age, 21 years) were completely asymptomatic at diagnosis. All subjects tested positive for immunoglobulin A endomysial antibody and tissue transglutaminase antibody, except for 1 patient with immunoglobulin A deficiency; 95% of patients were carriers of HLA-DQ2. Duodenal biopsies from 26% patients had a Marsh score of 0, and 74% had a Marsh score of 1. A higher proportion of symptomatic patients had autoimmune disorders (36%) and antinuclear antibodies (41%) than asymptomatic patients (5% and 12.5%, respectively), and symptomatic patients were of older age at diagnosis (P < .05). Gluten withdrawal led to significant clinical improvement in all 61 symptomatic patients. The 16 asymptomatic patients continued on gluten-containing diets, and only 1 developed mucosal flattening; levels of anti-endomysial and tissue transglutaminase antibodies fluctuated in 5 of these patients or became undetectable. CONCLUSIONS: In a 3-year study of adults with potential celiac disease, we found most to have symptoms, but these improved on gluten withdrawal. Conversely, we do not recommend a gluten-free diet for asymptomatic adults with potential celiac disease because they do not tend to develop villous atrophy.

Chronic constipation in the elderly: a primer for the gastroenterologist.

Constipation is a frequently reported bowel symptom in the elderly with considerable impact on quality of life and health expenses. Disease-related morbidity and even mortality have been reported in the affected frail elderly. Although constipation is not a physiologic consequence of normal aging, decreased mobility, medications, underlying diseases, and rectal sensory-motor dysfunction may all contribute to its increased prevalence in older adults. In the elderly there is usually more than one etiologic mechanism, requiring a multifactorial treatment approach. The majority of patients would respond to diet and lifestyle modifications reinforced by bowel training measures. In those not responding to conservative treatment, the approach needs to be tailored addressing all comorbid conditions. In the adult population, the management of constipation continues to evolve as well as the understanding of its complex etiology. However, the constipated elderly have been left behind while gastroenterology consultations for this common conditions are at a rise for the worldwide age increment. Aim of this review is to provide an update on epidemiology, quality of life burden, etiology, diagnosis, current approaches and limitations in the management of constipation in the older ones to ease the gastroenterologists' clinic workload.

Clinical and immunological relevance of anti-neuronal antibodies in celiac disease with neurological manifestations.

AIM: To assess anti-neuronal antibodies (NA) prevalence and their correlation with neurological disorders and bowel habits in celiac disease (CD) patients. BACKGROUND: Neurological manifestations are estimated to occur in about 10% of celiac disease patients and NA to central nervous system (CNS) and enteric nervous system (ENS) are found in a significant proportion of them. Little is known about the clinical and immunological features in CD patients with neurological manifestations. PATIENTS AND METHODS: NA to CNS and ENS were investigated in 106 CD patients and in 60 controls with autoimmune disorders by indirect immunofluorescence on rat / primate cerebellar cortex and intestinal (small and large bowel) sections. RESULTS: IgG NA to CNS (titer 1:50 - 1:400) were positive in 23 celiacs (21%), being more frequently detected in those with neurological disorders that in those without neurological dysfunction (49% vs. 8%, P< 0.0001). Of the 26 celiacs (24%) with IgG NA to ENS, 11 out of 12 with an antibody titer > 1:200 had severe constipation. Only one patient with cerebellar ataxia and intestinal sub-occlusion was positive for NA to CNS and ENS. NA to CNS and ENS were found in 7% and 5% of controls, respectively. CONCLUSION: In CD the positivity of NA to CNS can be regarded as a marker of neurological manifestations. High titer NA to ENS are associated with severe constipation. The demonstration of NA to CNS and ENS suggests an immune-mediated pathogenesis leading to central neural impairment as well as gut dysfunction (hence constipation), respectively.

Fulminant type 1 autoimmune hepatitis in a recently diagnosed celiac disease patient.

Celiac disease (CD) is a small intestine immune-mediated disorder triggered by gluten ingestion in genetically predisposed patients. This condition can also affect many extraintestinal tissues, including the liver. We report a patient presenting with a marked increase of transaminases at diagnosis of CD. The immune markers for autoimmune hepatitis (AIH) were negative. Following a few months of a strict gluten-free diet (GFD), aminotransferase levels decreased significantly (< 2.5x U/L). The response to GFD suggested that the liver damage was due to a gluten-dependent celiac hepatitis, the most common liver abnormality in CD. Despite the fact that the patient never stopped the GFD, yet, in a few months, the aminotransferase levels raise again to high values (> 50x U/L). At this time, the liver autoantibodies turned to be positive thus confirming the development of a type 1 AIH. The hepatic damage progressed to a late onset liver failure requiring liver transplantation.

Enteroendocrine profile of α-transducin immunoreactive cells in the gastrointestinal tract of the European sea bass (Dicentrarchus labrax).

In vertebrates, chemosensitivity of nutrients occurs through the activation of taste receptors coupled with G-protein subunits, including α-transducin (G(αtran)) and α-gustducin (G(αgust)). This study was aimed at characterising the cells expressing G(αtran) immunoreactivity throughout the mucosa of the sea bass gastrointestinal tract. G(αtran) immunoreactive cells were mainly found in the stomach, and a lower number of immunopositive cells were detected in the intestine. Some G(αtran) immunoreactive cells in the stomach contained G(αgust) immunoreactivity. Gastric G(αtran) immunoreactive cells co-expressed ghrelin, obestatin and 5-hydroxytryptamine immunoreactivity. In contrast, G(αtran) immunopositive cells did not contain somatostatin, gastrin/cholecystokinin, glucagon-like peptide-1, substance P or calcitonin gene-related peptide immunoreactivity in any investigated segments of the sea bass gastrointestinal tract. Specificity of G(αtran) and G(αgust) antisera was determined by Western blot analysis, which identified two bands at the theoretical molecular weight of ~45 and ~40 kDa, respectively, in sea bass gut tissue as well as in positive tissue, and by immunoblocking with the respective peptide, which prevented immunostaining. The results of the present study provide a molecular and morphological basis for a role of taste-related molecules in chemosensing in the sea bass gastrointestinal tract.

Audit of digestive complaints and psychopathological traits in patients with eating disorders: a prospective study.

BACKGROUND: Esophago-gastrointestinal symptoms are frequently reported by patients with eating disorders. Scanty data exist on the relationship between psychopathological traits and digestive complaints. AIMS: To prospectively analyze (i) prevalence of digestive symptoms; (ii) psychopathological traits; (iii) relationship between symptom scores and psychopathological profiles. METHODS: Psychopathological and digestive symptom questionnaires were completed at baseline, at discharge, at 1 and 6 months' follow-up in 48 consecutive patients (85.4% female, median age, 15 years) hospitalized for eating disorders. RESULTS: The most frequently reported symptoms were postprandial fullness (96%) and abdominal distention (90%). Pooled esophageal (4; IQR 0-14) and gastrointestinal (34; IQR 19-53) symptoms significantly decreased at 6 months' follow-up (1; IQR 0-3 and 10; IQR 4-34; p<0.0001 and p<0.005, respectively). Pooled gastrointestinal symptoms significantly correlated with hypochondriasis (r=0.42, p<0.01). Both esophageal and gastrointestinal symptoms improved in patients with normal values of hypochondriasis and hysteria scales (p<0.05 and p<0.005, respectively) compared to those with pathological traits. CONCLUSIONS: Digestive symptoms are frequently reported by patients with eating disorders with their expression and outcome being influenced by psychopathological profiles. Hypochondriasis and hysteria traits are predictive factors for symptomatic improvement.