Anemia Etiology and the Response to a Gluten-Free Diet in Untreated Patients With Celiac Disease: A 2-Year Follow-Up.

INTRODUCTION: Anemia and micronutrient deficiencies are common in newly diagnosed patients with celiac disease (CeD). We aim to determine the prevalence and etiology of anemia in a cohort of patients with CeD in the United States and examine the effect of a gluten-free diet (GFD) on the laboratory parameters related to anemia in CeD. METHODS: We analyzed a prospectively collected cohort of adults with biopsy-proven CeD followed in a specialized CeD center between January 2000 and June 2016. We used the level of hemoglobin (Hb) and micronutrients suggested by the World Health Organization to establish the diagnosis of anemia or deficiencies. Demographic data and laboratory parameters related to anemia and micronutrients were recorded at the time of diagnosis and on a GFD. A celiac expert nutritionist or gastroenterologist evaluated all patients. RESULTS: In 572 patients with laboratory evaluation before starting a GFD, approximately 25% presented with anemia at the time of diagnosis of CeD. Iron deficiency was present in 50.8% of the cohort and in 78.8% of the patients with anemia. Within the anemic population, 84.4% of female patients as compared with 58.3% of male patients ( P = 0.02) showed iron deficiency. Folate deficiency (23.2%), vitamin B12 deficiency (11%), and anemia of chronic diseases (7.8%) were also part of both sexes' anemia etiology. Of the initially anemic patients, 81% and 89% normalized their Hb levels within 1 year and 2 years of beginning a GFD, respectively. All patients received appropriate supplementation when needed. DISCUSSION: Approximately 25% of individuals have anemia at CeD diagnosis. The anemia etiology included iron deficiency, vitamin deficiencies, and anemia of chronic diseases. Most of the patients will normalize their Hb levels and the anemia laboratory parameters 1 year after starting a strict GFD.

The present and the future in the diagnosis and management of celiac disease.

Celiac disease is an autoimmune enteropathy caused by gluten in genetically predisposed individuals. In celiac disease, adaptive and innate immune activation results in intestinal damage and a wide range of clinical manifestations. In the past, celiac disease was thought to result in signs and symptoms solely related to the gastrointestinal tract. Now, more than half of the adult population presents with extra-intestinal manifestations that can also be expected to improve on a gluten-free diet. For this reason, it is recommended that physicians have a low threshold of suspicion for celiac disease. Current knowledge of the immune pathogenesis of this autoimmune disease has served as a catalyst for the development of novel diagnostic tools and therapeutics. Over the years, highly sensitive and specific serological assays, in addition to genetic markers, have been found to target specific steps in the cascade pathway of celiac disease. Also the advent of the gluten challenge has enabled experts to design diagnostic algorithms and monitor clinical responses in clinical trials. The gluten challenge has provided substantial benefit in the advance of novel therapeutics as an adjuvant treatment to the gluten free diet. Generally, a strict gluten-free diet is highly burdensome to patients and can be limited in its efficacy. Alternative therapies-including gluten modification, modulation of intestinal permeability and immune response-could be central to the future treatment of celiac disease.

Risk of topical anesthetic-induced methemoglobinemia: a 10-year retrospective case-control study.

IMPORTANCE: Methemoglobinemia is a rare but serious disorder, defined as an increase in oxidized hemoglobin resulting in a reduction of oxygen-carrying capacity. Although methemoglobinemia is a known complication of topical anesthetic use, few data exist on the incidence of and risk factors for this potentially life-threatening disorder. OBJECTIVE: To examine the incidence of and risk factors for procedure-related methemoglobinemia to identify patient populations at high risk for this complication. DESIGN AND SETTING: Retrospective study in an academic research setting. PARTICIPANTS: Medical records for all patients diagnosed as having methemoglobinemia during a 10-year period were reviewed. EXPOSURES: All cases of methemoglobinemia that occurred after the following procedures were included in the analysis: bronchoscopy, nasogastric tube placement, esophagogastroduodenoscopy, transesophageal echocardiography, and endoscopic retrograde cholangiopancreatography. MAIN OUTCOMES AND MEASURES: Comorbidities, demographics, concurrent laboratory values, and specific topical anesthetic used were recorded for all cases. Each case was compared with matched inpatient and outpatient cases. RESULTS: In total, 33 cases of methemoglobinemia were identified during the 10-year period among 94,694 total procedures. The mean (SD) methemoglobin concentration was 32.0% (12.4%). The methemoglobinemia prevalence rates were 0.160% for bronchoscopy, 0.005% for esophagogastroduodenoscopy, 0.250% for transesophageal echocardiogram, and 0.030% for endoscopic retrograde cholangiopancreatography. Hospitalization at the time of the procedure was a major risk factor for the development of methemoglobinemia (0.14 cases per 10,000 outpatient procedures vs 13.7 cases per 10,000 inpatient procedures, P < .001). CONCLUSIONS AND RELEVANCE: The overall prevalence of methemoglobinemia is low at 0.035%; however, an increased risk was seen in hospitalized patients and with benzocaine-based anesthetics. Given the potential severity of methemoglobinemia, the risks and benefits of the use of topical anesthetics should be carefully considered in inpatient populations.

A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge.

OBJECTIVES: In patients with celiac disease, enteropathy is caused by the entry of gluten peptides into the lamina propria of the intestine, in which their immunogenicity is potentiated by tissue transglutaminase (tTG) and T-helper type 1-mediated immune responses are triggered. Tight junction disassembly and paracellular permeability are believed to have an important role in the transport of gluten peptides to the lamina propria. Larazotide acetate is a tight-junction regulator peptide that, in vitro, prevents the opening of intestinal epithelial tight junctions. The aim of this study was to evaluate the efficacy and tolerability of larazotide acetate in protecting against gluten-induced intestinal permeability and gastrointestinal symptom severity in patients with celiac disease. METHODS: In this dose-ranging, placebo-controlled study, 86 patients with celiac disease controlled through diet were randomly assigned to larazotide acetate (0.25, 1, 4, or 8 mg) or placebo three times per day with or without gluten challenge (2.4 g/day) for 14 days. The primary efficacy outcome was the urinary lactulose/mannitol (LAMA) fractional excretion ratio. Secondary endpoints included gastrointestinal symptom severity, quality-of-life measures, and antibodies to tTG. RESULTS: LAMA measurements were highly variable in the outpatient setting. The increase in LAMA ratio associated with the gluten challenge was not statistically significantly greater than the increase in the gluten-free control. Among patients receiving the gluten challenge, the difference in the LAMA ratios for the larazotide acetate and placebo groups was not statistically significant. However, larazotide acetate appeared to limit gluten-induced worsening of gastrointestinal symptom severity as measured by the Gastrointestinal Symptom Rating Scale at some lower doses but not at the higher dose. Symptoms worsened significantly in the gluten challenge-placebo arm compared with the placebo-placebo arm, suggesting that 2.4 g of gluten per day is sufficient to induce reproducible gluten toxicity. Larazotide acetate was generally well tolerated. No serious adverse events were observed. The most common adverse events were headache and urinary tract infection. CONCLUSIONS: LAMA variability in the outpatient setting precluded accurate assessment of the effect of larazotide acetate on intestinal permeability. However, some lower doses of larazotide acetate appeared to prevent the increase in gastrointestinal symptom severity induced by gluten challenge.