-
1.
Follow-Up of Celiac Disease in Adults: "When, What, Who, and Where".
Mulder, CJJ, Elli, L, Lebwohl, B, Makharia, GK, Rostami, K, Rubio-Tapia, A, Schumann, M, Tye-Din, J, Zeitz, J, Al-Toma, A
Nutrients. 2023;(9)
Abstract
For patients with celiac disease (CeD), a lifelong gluten-free diet is not a voluntary lifestyle choice-it is a necessity. The key end points in clinical follow-up are symptom resolution, the normalization of weight, prevention of overweight, seroconversion, and negation or minimization of increased long-term morbidity. For the latter, a surrogate endpoint is mucosal healing, which means the normalization of histology to Marsh 0-1. Ideally, celiac follow-up care includes a multidisciplinary approach, effective referral processes, improved access that leverages technological advances, and following guidelines with the identification of measurable quality indicators, ideally informed by evidence-based research. Face-to-face CeD care and telemedicine are considered the standards for this process, although published data are insufficient. Guidelines and statements on diagnosis are readily available. However, data are lacking on optimal clinic visit intervals and outcomes and quality indicators such as improvement of symptoms, function and quality of life, survival and disease control, and how to most effectively use healthcare resources. The results of future research should provide the basis for general recommendations for evidence-based standards of quality of care in CeD.
-
2.
Prevalence of Clostridioides difficile and Other Gastrointestinal Pathogens in Patients with COVID-19.
Laszkowska, M, Kim, J, Faye, AS, Joelson, AM, Ingram, M, Truong, H, Silver, ER, May, B, Greendyke, WG, Zucker, J, et al
Digestive diseases and sciences. 2021;(12):4398-4405
-
-
Free full text
-
Abstract
BACKGROUND Gastrointestinal symptoms are common in patients with COVID-19, but prevalence of co-infection with enteric pathogens is unknown. AIMS This study assessed the prevalence of enteric infections among hospitalized patients with COVID-19. METHODS We evaluated 4973 hospitalized patients ≥ 18 years of age tested for COVID-19 from March 11 through April 28, 2020, at two academic hospitals. The primary exposure was a positive COVID-19 test. The primary outcome was detection of a gastrointestinal pathogen by PCR stool testing. RESULTS Among 4973 hospitalized individuals, 311 were tested for gastrointestinal infections (204 COVID-19 positive, 107 COVID-19 negative). Patients with COVID-19 were less likely to test positive compared to patients without COVID-19 (10% vs 22%, p < 0.01). This trend was driven by lower rates of non-C.difficile infections (11% vs 22% in COVID-19 positive vs. negative, respectively, p = 0.04), but not C. difficile infection (5.1% vs. 8.2%, p = 0.33). On multivariable analysis, infection with COVID-19 remained significantly associated with lower odds of concurrent GI infection (aOR 0.49, 95% CI 0.24-0.97), again driven by reduced non-C.difficile infection. Testing for both C.difficile and non-C.difficile enteric infection decreased dramatically during the pandemic. CONCLUSIONS Pathogens aside from C.difficile do not appear to be a significant contributor to diarrhea in COVID-19 positive patients.
-
3.
Celiac disease serology and gut microbiome following proton pump inhibitor treatment.
Jang, S, Lebwohl, B, Abrams, JA, Green, PHR, Freedberg, DE, Alaedini, A
Medicine. 2020;(35):e21488
-
-
Free full text
-
Abstract
BACKGROUND Celiac disease is an autoimmune enteropathy characterized by an aberrant immune response to ingested gluten in genetically predisposed individuals. Studies have pointed to a rising prevalence of celiac disease in recent decades. Changes in diet and use of medication that may impact the gut microbiome have been suggested as potential contributors. Exposure to proton pump inhibitors (PPIs) was recently found to be associated with an increased risk for subsequent diagnosis of celiac disease. We aimed to investigate potential mechanisms for this link by examining the relationship between PPI use and gluten-related immune responses in the context of changes in gut microbiome. METHODS We performed a post hoc analysis of blood and fecal samples from a recent randomized trial in order to assess the potential association between PPI use and development of celiac disease serology in conjunction with alterations in gastrointestinal microbial composition. The study included 12 healthy participants who were administered a PPI (Omeprazole; 40 mg twice daily) for 4 or 8 weeks. RESULTS The analysis did not reveal an overall significant change in levels of serologic markers of celiac disease for the study cohort in response to PPI treatment. However, one individual developed a marked increase in the celiac disease-specific autoantibody response to transglutaminase 2 in conjunction with enhanced immune reactivity to gluten during the trial. Genotyping revealed positivity for the celiac disease-associated HLA-DQ2 and -DQ8 alleles. Furthermore, the observed elevation in antibody responses was closely associated with a sharp increase in fecal abundance of bacteria of the order Actinomycetales. CONCLUSIONS The results of this exploratory analysis support further investigation of molecular mechanisms involved in the contribution of PPIs to celiac disease risk through the potential enhancement of gluten immunopathology and changes in gut microbial population.
-
4.
Phenotypic shift of small intestinal intra-epithelial type 1 innate lymphoid cells in celiac disease is associated with enhanced cytotoxic potential.
Uhde, M, Yu, X, Bunin, A, Brauner, C, Lewis, SK, Lebwohl, B, Krishnareddy, S, Alaedini, A, Reizis, B, Ghosh, S, et al
Clinical and experimental immunology. 2020;(2):163-175
-
-
Free full text
-
Abstract
The small intestinal (SI) epithelium harbors a heterogeneous population of lymphocytes that mediate mucosal damage and repair in celiac disease (CD). The composition and roles of human proximal SI intra-epithelial innate lymphoid cells (ILCs), and their alterations in CD, are not well understood. We report that duodenal intra-epithelial ILCs predominantly consist of natural killer (NK)p44+ CD127- cytotoxic ILC1s and NKp44- CD127+ helper ILC1s, while ILC3s only represent a minor population. In patients with newly diagnosed or active CD (ACD) and refractory CD type 1 (RCD I), the frequency of SI NKp44+ ILCs is decreased, with restoration of NKp44+ ILC frequency observed in patients adhering to a gluten-free diet who show evidence of mucosal healing. Moreover, the frequency of SI NKp44- ILCs is increased in ACD and RCD I patients and correlates with the severity of villous atrophy and epithelial damage, as assessed by serum levels of fatty acid binding protein 2 (FABP2). We show that the ILC alterations in CD represent a phenotypic shift of cytotoxic ILC1s rather than an increase in helper ILC1s or transdifferentiation of ILC1s to ILC3s, and activation-induced loss of NKp44 by cytotoxic ILC1s is associated with increased interferon (IFN)-γ expression and release of lytic granules. These findings suggest that intra-epithelial NKp44- CD127- cytotoxic ILC1s may contribute to mucosal damage in CD.
-
5.
Neurological Manifestations of Neuropathy and Ataxia in Celiac Disease: A Systematic Review.
Mearns, ES, Taylor, A, Thomas Craig, KJ, Puglielli, S, Leffler, DA, Sanders, DS, Lebwohl, B, Hadjivassiliou, M
Nutrients. 2019;11(2)
-
-
-
Free full text
Plain language summary
Coeliac disease (CD) is a chronic, immune-mediated enteropathy in which dietary gluten triggers an inflammatory reaction of the small intestine in genetically predisposed individuals. The clinical presentation of the disease varies broadly and may include both intestinal symptoms and extra-intestinal manifestations, including iron-deficiency anaemia, osteoporosis, dermatitis herpetiformis, and neurological disorders, such as peripheral neuropathies and ataxia (a condition that affects co-ordination, balance and speech). Many patients who present with neurological manifestations of CD have no gastrointestinal symptoms, commonly leading to a delay in diagnosis. The aim of this systematic review was to assess the prevalence of peripheral neuropathies and gluten ataxia. Nine studies on gluten ataxia and 13 on gluten neuropathy were included in this review. The prevalence of both, neuropathy and ataxia, in the general population is very low, but this risk is increased in patients with CD. Estimates of the prevalence of neuropathy in CD patients ranged from 0% to 39%, with an increased risk in older and female patients. Prevalence of gluten ataxia varied from 0% to 6%. Symptoms of gluten neuropathy improve when patients with CD follow a gluten free diet (GFD), whilst the benefits of a GFD for ataxia vary between studies, possibly due to differences in study design. The authors note that this review primarily concentrated on patients with CD (i.e. those with evidence of enteropathy). However, neurological manifestations may exist in the presence of anti-gliadin antibodies alone (gluten sensitivity without evidence of enteropathy), and such patients benefit equally from a GFD. The authors conclude that patients with CD have an increased risk of gluten ataxia and gluten neuropathy, and that clinicians should check for gluten sensitivity in patients with ataxia and neuropathy of unknown origin.
Abstract
Celiac disease (CD) is an immune-mediated gastrointestinal disorder driven by innate and adaptive immune responses to gluten. Patients with CD are at an increased risk of several neurological manifestations, frequently peripheral neuropathy and gluten ataxia. A systematic literature review of the most commonly reported neurological manifestations (neuropathy and ataxia) associated with CD was performed. MEDLINE, Embase, the Cochrane Library, and conference proceedings were systematically searched from January 2007 through September 2018. Included studies evaluated patients with CD with at least one neurological manifestation of interest and reported prevalence, and/or incidence, and/or clinical outcomes. Sixteen studies were included describing the risk of gluten neuropathy and/or gluten ataxia in patients with CD. Gluten neuropathy was a neurological manifestation in CD (up to 39%) in 13 studies. Nine studies reported a lower risk and/or prevalence of gluten ataxia with a range of 0%⁻6%. Adherence to a gluten-free diet appeared to improve symptoms of both neuropathy and ataxia. The prevalence of gluten neuropathy and gluten ataxia in patients with CD varied in reported studies, but the increased risk supports the need for physicians to consider CD in patients with ataxia and neurological manifestations of unknown etiology.
-
6.
Benefits From and Barriers to Portable Detection of Gluten, Based on a Randomized Pilot Trial of Patients With Celiac Disease.
Wolf, RL, Green, PHR, Lee, AR, Reilly, NR, Zybert, P, Lebwohl, B
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2019;(12):2605-2607
-
-
Free full text
-
Abstract
Research links diminished quality of life (QOL) to the challenges of a strict gluten-free diet (GFD), the only treatment for celiac disease (CD).1-4 This pilot study assessed the acceptability and feasibility of a portable gluten sensor device (Nima) to promote GFD adherence and QOL.
-
7.
Prevalence of Celiac Disease in Patients With Iron Deficiency Anemia-A Systematic Review With Meta-analysis.
Mahadev, S, Laszkowska, M, Sundström, J, Björkholm, M, Lebwohl, B, Green, PHR, Ludvigsson, JF
Gastroenterology. 2018;(2):374-382.e1
-
-
Free full text
-
Abstract
BACKGROUND & AIMS Anemia is common in patients with celiac disease (CD) and a frequent mode of presentation. Guidelines recommend screening patients with iron-deficiency anemia (IDA) for CD. However, the reported prevalence of CD in patients with IDA varies. We performed a systematic review to determine the prevalence of biopsy-verified CD in patients with IDA. METHODS We performed a systematic review of articles published in PubMed Medline or EMBASE through July 2017 for the term "celiac disease" combined with "anemia" or "iron deficiency." We used fixed-effects inverse variance-weighted models to measure the pooled prevalence of CD. Meta-regression was used to assess subgroup heterogeneity. RESULTS We identified 18 studies composed of 2998 patients with IDA for inclusion in our analysis. Studies originated from the United Kingdom, United States, Italy, Turkey, Iran, and Israel. The crude unweighted prevalence of CD was 4.8% (n = 143). Using a weighted pooled analysis, we found a prevalence of biopsy-confirmed CD of 3.2% (95% confidence interval = 2.6-3.9) in patients with IDA. However, heterogeneity was high (I2 = 67.7%). The prevalence of CD was not significantly higher in studies with a mean participant age older or younger than 18 years or in studies with a mixed-sex vs female-predominant (≥60%) population. On meta-regression, year of publication, female proportion, age at CD testing, and prevalence in the general population were not associated with the prevalence of CD in patients with IDA. In the 8 studies fulfilling all our quality criteria, the pooled prevalence of CD was 5.5% (95% confidence interval = 4.1-6.9). CONCLUSIONS In a systematic review and meta-analysis, we found that approximately 1 in 31 patients with IDA have histologic evidence of CD. This prevalence value justifies the practice of testing patients with IDA for CD.
-
8.
Nonceliac Gluten Sensitivity.
Krigel, A, Lebwohl, B
Advances in nutrition (Bethesda, Md.). 2016;(6):1105-1110
-
-
Free full text
-
Abstract
Nonceliac gluten sensitivity (NCGS) refers to a clinical phenotype in which patients experience intestinal and extraintestinal symptoms related to ingesting a gluten-containing diet after a diagnosis of celiac disease (CD) or wheat allergy has been excluded. CD, an autoimmune disease characterized by villous atrophy triggered by the ingestion of gluten, has increased in prevalence in recent decades, although the majority of patients remain undiagnosed. There is now an increasing public awareness of NCGS and growing interest in the health effects of gluten among health professionals and the lay public. Several randomized controlled trials have explored NCGS but have left many questions unanswered surrounding the pathophysiology, biomarkers, and established diagnostic approach to patients with this condition. Future studies are necessary to establish biomarkers and to elucidate the pathophysiology of this condition because at present, NCGS likely comprises a heterogeneous patient population. In this review, we outline the clinical trials of NCGS as well as the approach to patients with possible NCGS as recommended by an international expert panel. Because maintaining a gluten-free diet has important health, social, and economic consequences, it is necessary for medical professionals to provide practical and evidence-based advice to patients with this condition.
-
9.
Celiac disease and non-celiac gluten sensitivity.
Lebwohl, B, Ludvigsson, JF, Green, PH
BMJ (Clinical research ed.). 2015;:h4347
-
-
Free full text
-
Abstract
Celiac disease is a multisystem immune based disorder that is triggered by the ingestion of gluten in genetically susceptible individuals. The prevalence of celiac disease has risen in recent decades and is currently about 1% in most Western populations. The reason for this rise is unknown, although environmental factors related to the hygiene hypothesis are suspected. The pathophysiology of celiac disease involves both the innate and adaptive immune response to dietary gluten. Clinical features are diverse and include gastrointestinal symptoms, metabolic bone disease, infertility, and many other manifestations. Although a gluten-free diet is effective in most patients, this diet can be burdensome and can limit quality of life; consequently, non-dietary therapies are at various stages of development. This review also covers non-celiac gluten sensitivity. The pathophysiology of this clinical phenotype is poorly understood, but it is a cause of increasing interest in gluten-free diets in the general population.