1.
Celiac disease or non-celiac gluten sensitivity? An approach to clinical differential diagnosis.
Kabbani, TA, Vanga, RR, Leffler, DA, Villafuerte-Galvez, J, Pallav, K, Hansen, J, Mukherjee, R, Dennis, M, Kelly, CP
The American journal of gastroenterology. 2014;109(5):741-6; quiz 747
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Plain language summary
Differentiating between celiac disease (CD) and non-celiac gluten sensitivity (NCGS) is challenging, as both conditions respond to a gluten-free diet but present different clinically. At present, an effective diagnostic protocol specific to NCGS is not available. The aim of this review is to develop a diagnostic algorithm to differentiate CD from NCGS. Records of 238 subjects who presented with gluten-responsive symptoms were reviewed. This study resulted in a clinical model for efficient differential diagnosis of CD and NCGS. On the basis of this model, unnecessary endoscopies could have been avoided in over 60% of subjects. This model offers clinicians a stepwise algorithm for diagnosis and management of patients who present with symptoms responsive to gluten exclusion.
Abstract
OBJECTIVES Differentiating between celiac disease (CD) and non-celiac gluten sensitivity (NCGS) is important for appropriate management but is often challenging. METHODS We retrospectively reviewed records from 238 patients who presented for the evaluation of symptoms responsive to gluten restriction without prior diagnosis or exclusion of CD. Demographics, presenting symptoms, serologic, genetic, and histologic data, nutrient deficiencies, personal history of autoimmune diseases, and family history of CD were recorded. NCGS was defined as symptoms responsive to a gluten-free diet (GFD) in the setting of negative celiac serology and duodenal biopsies while on a gluten-containing diet or negative human leukocyte antigen (HLA) DQ2/DQ8 testing. RESULTS Of the 238 study subjects, 101 had CD, 125 had NCGS, 9 had non-celiac enteropathy, and 3 had indeterminate diagnosis. CD subjects presented with symptoms of malabsorption 67.3% of the time compared with 24.8% of the NCGS subjects (P<0.0001). In addition, CD subjects were significantly more likely to have a family history of CD (P=0.004), personal history of autoimmune diseases (P=0.002), or nutrient deficiencies (P<0.0001). The positive likelihood ratio for diagnosis of CD of a >2× upper limit of normal IgA trans-glutaminase antibody (tTG) or IgA/IgG deaminated gliadan peptide antibody (DGP) with clinical response to GFD was 130 (confidence interval (CI): 18.5-918.3). The positive likelihood ratio of the combination of gluten-responsive symptoms and negative IgA tTG or IgA/IgG DGP on a regular diet for NCGS was 9.6 (CI: 5.5-16.9). When individuals with negative IgA tTG or IgA/IgG DGP also lacked symptoms of malabsorption (weight loss, diarrhea, and nutrient deficiencies) and CD risk factors (personal history of autoimmune diseases and family history of CD), the positive likelihood ratio for NCGS increased to 80.9. CONCLUSIONS On the basis of our findings, we have developed a diagnostic algorithm to differentiate CD from NCGS. Subjects with negative celiac serologies (IgA tTG or IgA/IgG DGP) on a regular diet are unlikely to have CD. Those with negative serology who also lack clinical evidence of malabsorption and CD risk factors are highly likely to have NCGS and may not require further testing. Those with equivocal serology should undergo HLA typing to determine the need for biopsy.
2.
Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study.
Kelly, CP, Green, PH, Murray, JA, Dimarino, A, Colatrella, A, Leffler, DA, Alexander, T, Arsenescu, R, Leon, F, Jiang, JG, et al
Alimentary pharmacology & therapeutics. 2013;37(2):252-62
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Free full text
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Plain language summary
Coeliac disease (CD) is an autoimmune disorder triggered by ingestion of gluten in genetically susceptible individuals. CD can cause inflammation and histological changes including villous atrophy and increased intestinal permeability. Larazotide acetate is a peptide that has been shown to block the gluten-induced increase in intestinal permeability, therefore improving gastrointestinal symptoms in CD patients. The aim of this study was to evaluate the efficacy and tolerability of larazotide acetate during a gluten challenge in patients with CD. The study included 184 adults diagnosed with CD, adhering to a gluten-free diet for at least six months. For six weeks, participants received 2.7 grams of gluten daily and were randomised to receive larazotide acetate three times daily. The findings of this study showed that larazotide acetate reduced gluten-induced immune activation, alleviated gastrointestinal symptoms and was well tolerated. While there was a reduction in the biomarker for intestinal permeability, there was no significant difference found compared with placebo. The authors conclude that the design and results of this study can be used for future pharmacological studies for CD.
Abstract
BACKGROUND Coeliac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten-free diet (GFD), which is difficult for many patients. Larazotide acetate is a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae. AIM: To evaluate the efficacy and tolerability of larazotide acetate during gluten challenge. METHODS This exploratory, double-blind, randomised, placebo-controlled study included 184 patients maintaining a GFD before and during the study. After a GFD run-in, patients were randomised to larazotide acetate (1, 4, or 8 mg three times daily) or placebo and received 2.7 grams of gluten daily for 6 weeks. Outcomes included an experimental biomarker of intestinal permeability, the lactulose-to-mannitol (LAMA) ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels. RESULTS No significant differences in LAMA ratios were observed between larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (P = 0.002 vs. placebo). Mean ratio of anti-tissue transglutaminase IgA levels over baseline was 19.0 in the placebo group compared with 5.78 (P = 0.010), 3.88 (P = 0.005) and 7.72 (P = 0.025) in the larazotide acetate 1-, 4-, and 8-mg groups, respectively. Adverse event rates were similar between larazotide acetate and placebo groups. CONCLUSIONS Larazotide acetate reduced gluten-induced immune reactivity and symptoms in patients with coeliac disease undergoing gluten challenge and was generally well tolerated; however, no significant difference in LAMA ratios between larazotide acetate and placebo was observed. Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with coeliac disease.