1.
Multifactorial Etiology of Anemia in Celiac Disease and Effect of Gluten-Free Diet: A Comprehensive Review.
Martín-Masot, R, Nestares, MT, Diaz-Castro, J, López-Aliaga, I, Alférez, MJM, Moreno-Fernandez, J, Maldonado, J
Nutrients. 2019;11(11)
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Anaemia is a common clinical expression of Celiac Disease (CD) alongside vitamin B12, iron and folate deficiencies. This review looks at the latest evidence and effects of a gluten free diet, the mainstay of treatment for CD. Typically, symptoms subside whilst adhering to a GF diet however in 20% of people anaemia and nutrient deficiencies can persist. Some of this is attributed to lack of adherence to the diet, oftentimes accidental given the wide range of foods containing gluten. This in turn leads to further damage of the intestine and can be difficult to detect and monitor effectively. Inflammation of the gastrointestinal tract, and malabsorption, are the main reasons for nutrient deficiencies leading to anaemia in CD. Iron is a critical nutrient which can easily be affected by damage to the intestinal villi, common in CD, and over time lead to iron deficiency anaemia as the body is unable to absorb dietary iron and the body’s iron stores are depleted. Likewise, absorption of vitamins B12 and B9 (folate) are also impaired by damaged villi and vitamin B12 is further affected by small intestine injuries including decreased gastric acid production, bacterial overgrowth and reduced intrinsic factor efficiency. Deficiencies of these two nutrients can lead to macrocytic anaemia with low blood cell volumes. Overall a gluten free diet is shown to reduce symptoms of CD in a matter of weeks. The more patients adhere to the diet, the more the risk of nutrient deficiencies and anaemia reduces.
Abstract
Celiac disease (CD) is a multisystemic disorder with different clinical expressions, from malabsorption with diarrhea, anemia, and nutritional compromise to extraintestinal manifestations. Anemia might be the only clinical expression of the disease, and iron deficiency anemia is considered one of the most frequent extraintestinal clinical manifestations of CD. Therefore, CD should be suspected in the presence of anemia without a known etiology. Assessment of tissue anti-transglutaminase and anti-endomysial antibodies are indicated in these cases and, if positive, digestive endoscopy and intestinal biopsy should be performed. Anemia in CD has a multifactorial pathogenesis and, although it is frequently a consequence of iron deficiency, it can be caused by deficiencies of folate or vitamin B12, or by blood loss or by its association with inflammatory bowel disease (IBD) or other associated diseases. The association between CD and IBD should be considered during anemia treatment in patients with IBD, because the similarity of symptoms could delay the diagnosis. Vitamin B12 deficiency is common in CD and may be responsible for anemia and peripheral myeloneuropathy. Folate deficiency is a well-known cause of anemia in adults, but there is little information in children with CD; it is still unknown if anemia is a symptom of the most typical CD in adult patients either by predisposition due to the fact of age or because biochemical and clinical manifestations take longer to appear.
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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)
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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.
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Lack of immunogenicity of hydrolysed wheat flour in patients with coeliac disease after a short-term oral challenge.
Mandile, R, Picascia, S, Parrella, C, Camarca, A, Gobbetti, M, Greco, L, Troncone, R, Gianfrani, C, Auricchio, R
Alimentary pharmacology & therapeutics. 2017;46(4):440-446
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A gluten-free diet is currently the only reliable therapeutic approach for coeliac disease (CD), an immune-mediated condition where eating gluten causes intestinal inflammation. Hydrolysing wheat flour with a sourdough enriched with lactobacilli and fungal proteases has been shown to be effective in reducing the gluten in the bread baked with it to less that 10ppm (which should be safe for CD patients). This randomised prospective study was designed to confirm the lack of an immunological response to the hydrolysed gluten in CD patients, both in vitro and in vivo. 20 CD patients who were in clinical remission and had followed a gluten-free diet (GFD) for at least three years were enrolled into this study and randomised to receive either natural wheat (10g gluten per day) or hydrolysed wheat (10g hydrolysed gluten per day) for three days. In vitro studies using intestinal cells from three of the study participants showed that the hydrolysed gluten did not elicit an immune response, whilst the natural gluten did. In vivo, there were no statistically significant increases in immune reactivity in the hydrolysed gluten patients, and no-one in this group experienced any symptoms. In the natural wheat group significant increases in immune reactivity to gluten were seen although only one person experienced symptoms (abdominal pain). The authors conclude that wheat flour hydrolysed with an enriched sourdough may be an alternative for the CD patient’s diet.
Abstract
BACKGROUND A gluten-free diet is currently the only reliable therapeutic strategy that is approved for coeliac disease (CD). For many patients, however, compliance remains inadequate. AIM: To investigate the immunogenicity of wheat flour that was pre-treated with selected lactobacilli and fungal proteases (hydrolysed wheat gluten) in coeliac patients. METHODS The immunogenicity of hydrolysed wheat gluten was evaluated both in vitro in intestinal T cell lines (TCLs) and in vivo in treated CD patients after a short-term gluten challenge. Twenty treated CD patients were enrolled and equally randomised into two groups. The patients ate bread that was prepared with hydrolysed wheat flour or natural wheat flour (10 g of gluten/d for 3 days). The interferon (INF)-γ responses to natural gliadin and a 33-mer peptide were assessed by the enzyme-linked immunospot (ELISPOT) assay on peripheral blood mononuclear cells (PBMCs) both before and 6 days after the start of the challenge. RESULTS Hydrolysed wheat was not able to activate the TCLs from the coeliac intestinal mucosa. Consistent with the in vitro results, no significant increase in INF-γ secretion was observed in patients who consumed hydrolysed wheat flour. Conversely, the consumption of natural wheat gluten mobilised INF-γ secreting cells in the blood (P<.05). CONCLUSIONS We confirm that fermentation of wheat flour with sourdough lactobacilli and fungal proteases is capable of abolishing the T cell immunogenicity of gluten in coeliac patients. Our data also validate the short-term oral challenge as a useful tool for testing the efficacy of novel therapeutic approaches.
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Serum cytokine pattern in young children with screening detected coeliac disease.
Björck, S, Lindehammer, SR, Fex, M, Agardh, D
Clinical and experimental immunology. 2015;179(2):230-5
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Coeliac disease (CD) is an autoimmune disorder characterised by inflammation in the small bowel after ingesting gluten. Many patients may be asymptomatic and clinically silent, prolonging their diagnosis and treatment. This may put them at risk for long-term complications due to chronic systemic inflammation. Circulating cytokines indicate inflammatory activity in the body and have been shown to be elevated in patients with CD. The aim of this study was to measure the levels of serum cytokines in 26 3-year-old children with CD, both at the time of diagnosis and after starting a gluten-free diet. The findings of this study showed that young children with CD demonstrated elevated levels of serum cytokines at the time of diagnosis. After maintaining a gluten-free diet, many cytokine levels decreased. Based on this study, the authors’ conclude that systemic inflammation due to undiagnosed disease in young children may contribute to long-term complications associated with chronic inflammation, and should be accounted for when screening for the disease.
Abstract
Coeliac disease is an autoimmune disease characterized by inflammation localized to the small bowel, but less is known about systemic signs of inflammation. The aim was to measure cytokines of the T helper 1 (Th1) and T helper 2 (Th2) cell patterns in children with screening-detected coeliac disease before and after treatment with a gluten-free diet. Serum samples selected before and after the start of a gluten-free diet from 26 3-year-old children diagnosed with biopsy-proven coeliac disease and from 52 matched controls were assayed in an multiplex enzyme-linked immunosorbent assay (ELISA) for the 10 cytokines: interferon (IFN)-γ, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, IL-13 and tumour necrosis factor (TNF)-α. Among Th1 cytokines, IFN-γ and IL-12p70 were elevated significantly in children with coeliac disease compared to controls (P < 0.001 and P = 0.001, respectively). Similar findings were demonstrated for the Th2 cytokines IL-5 (P < 0.001), IL-10 (P = 0.001) and IL-13 (P = 0.002). No difference in cytokine levels between the two groups was found for TNF-α, IL-1β, IL-2, IL-4 and IL-8. After gluten-free diet, levels of IL-5, IL-12 and IL-10 decreased significantly (P < 0.001, P = 0.002 and P = 0.007) and IFN-γ levels were reduced (P = 0.059). Young children with coeliac disease detected by screening demonstrate elevated levels of serum cytokines at time of diagnosis. A prolonged systemic inflammation may, in turn, contribute to long-term complications known to be associated with untreated coeliac disease.