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Celiac.com 10/01/2010 - Scleroderma is a chronic, systemic autoimmune disease characterized by tissue fibrosis, or hardening, vascular changes, and autoantibodies. There are two forms of scleroderma. The first is called limited systemic sclerosis/scleroderma cutaneous, and manifests mainly affect the hands, arms and face. This form of scleroderma was earlier known as CREST syndrome, because symptoms included Calcinosis, Raynaud's phenomenon, Esophageal dysfunction, Sclerodactyly, and Telangiectasias. This form of scleroderma triggers pulmonary arterial hypertension in up to one third of patients, which is the most serious problem. The second, less common form of scleroderma is called diffuse systemic sclerosis/scleroderma. This form progresses quickly and affects large areas of skin and one or more internal organs, generally the kidneys, esophagus, heart and lungs. A recent letter by doctors R. Thonhofer M. Trummer, and C. Siegel noted that capillaroscopy shows an active pattern of scleroderma in celiac disease. They are affiliated with the Department of Internal Medicine at the State Hospital Muerzzuschlag, and with the Department of Rheumatology at the Medical University of Graz in Austria. Their letter notes that previous studies have shown celiac disease to be associated with higher rates of Raynaud’s phenomenon, sclerodactyly, arthritis, polymyositis, pericarditis, vasculitis, and scleroderma. The doctors describe the case of a 41-year-old, non-smoking woman, who presented with Raynaud's phenomenon and progressive weight loss. For nearly twenty years, the woman had suffered symptoms of Raynaud's phenomenon, with classical tricolore phenomenon and symmetrical bilateral involvement of hands, with lesser effect on her feet. The woman's weight loss had persisted for two years, accompanied by unspecific abdominal symptoms including meteorism and episodic diarrhea. The attacks of Raynaud's phenomenon seemed to be triggered by exposure to cold or by emotional stress. The doctors ruled out digital ulcers, vibration injury, and ingestion of toxic agents as possible causes. A color Doppler ultrasound examination of the arteries of the upper and lower extremities showed nothing remarkable. Radiographs of the hands, feet, clavicles, cervical, and lumbar spine were also not remarkable. Nailfold capillaroscopy of digits two to five bilaterally showed capillary loss in some areas, mild, focally moderate to severe disorganization of the vascular architecture, frequent giant capillaries, and hemorrhages adjacent to enlarged, nearly normal, and giant capillaries. The patient showed negative test results for anti-nuclear antibodies, complement factors, anti-DNA antibodies, anti-neutrophil cytoplasmic antibodies, anti-cardiolipin antibodies, cryoglobulinaemia, and rheumatoid factor. Erythrocyte sedimentation rate and C-reactive protein were in the normal range. The patient showed positive screens for anti-endomysial antibodies and anti-tissue transglutaminase antibodies. Endoscopy and several biopsies of the large bowel and terminal ileum showed nothing remarkable. Gastroduodenoscopy showed normal mucosa in the upper gastrointestinal tract. Looking at biopsy results from different parts of the duodenum, the team found an increase in intraepithelial lymphocytes, with about 60 to 70 per 100 enterocytes, along with shortening of the epithelial cells, and a reduction of globlet cells. As a result of antibody testing, anamnesis, and histology, the team was able to make a diagnosis of celiac disease. After the patient began treatment with a gluten-free diet, the abdominal symptoms and weight loss subsided, and the Raynaud's phenomenon attacks became less frequent. Clinical and laboratory evaluation over the last four years have not shown any connective tissue disease in the patient. The team used capillaroscopy every 6 months to show that the pattern of damage remained unchanged, and was not improved by the gluten-free diet within the first year. After 18 months, the vascular architecture showed some improvement, with no further bleeding or enlarged capillaries. Repeated examinations after that point showed similar, near-normal findings. There have been previous reports of several rheumatological disorders, including Raynaud's phenomenon in people with celiac disease, but this seems to be the first report of extensive microvascular damage, similar to capillary changes in scelroderma, documented by nailfold capillaroscopy in a patient with celiac disease. Because they excluded any underlying connective tissue disease or other secondary causes of Raynaud's phenomenon, the team's findings support a causal relationship between celiac disease and Raynaud's phenomenon, especially in regards to the described capillary pattern. Normalization of the patient's vascular architecture after a year and a half on a gluten-free diet further bolster their findings. The team admits the possibility of evolving scelroderma in the patient, but points out that the negative laboratory testing, organ screening, and inconspicuous clinical examination would seem to make that scenario highly unlikely. It will be interesting to see what doctors can learn through additional nailfold capillaroscopy investigations into the special capillary pattern in celiac disease patients. Source: Scand J Rheumatol.Vol. 1, No. 1, Jul 2010. DOI: 10.3109/03009742.2010.489230

Celiac.com 09/09/2015 - Some researchers and clinicians suspect a connection between eosinophilic esophagitis (EoE) and celiac disease, but prior studies have shown conflicting results A team of researchers recently set out to determine the relationship between EoE and celiac disease among patients with concomitant esophageal and duodenal biopsies. The research team included Elizabeth T. Jensena, Swathi Eluria, Benjamin Lebwohl, Robert M. Gentab, and Evan S. Dellon. For their cross-sectional study, they team used data covering the period from January 2009 through June 2012 from a U.S. national pathology database. They defined esophageal eosinophilia as the presence of ≥15 eosinophils per high-power field. The crude and age and sex adjusted odds of esophageal eosinophilia for patients with active celiac disease were compared with those without celiac disease. Sensitivity analyses were performed by using more stringent case definitions and by estimating the associations between celiac disease and reflux esophagitis and celiac disease and Barrett’s esophagus. Out of 292,621 patients in the source population, the team looked at data from 88,517 patients with both esophageal and duodenal biopsies. Four thousand one hundred one (4.6%) met criteria for EoE, and 1203 (1.4%) met criteria for celiac disease. Patients with celiac disease had 26% higher odds of EoE than patients without celiac disease (adjusted odds ratio, 1.26; 95% confidence interval [CI], 0.98–1.60). The strength of the connection varied according to EoE case definition, but all definitions showed a weak positive association between the two conditions. Interestingly, this study showed no connection between celiac disease and reflux esophagitis (adjusted odds ratio 0.95; 95% CI, 0.85–1.07) or between celiac disease and Barrett’s esophagus (adjusted odds ratio 0.89; 95% CI, 0.69–1.14). Overall, this study showed only a weak increase in EoE in patients with celiac disease. The connection strengthened in direct relation to the strength of definitions of EoE, and was not seen with other esophageal conditions. Doctors should consider concomitant EoE in patients with celiac disease where clinical indications support it. Disclosures: Dellon reports receiving research funds from Meritage Pharma, consulting for Aptalis, Novartis, Receptos and Regeneron, and receiving an educational grant from Diagnovus. Source: Clinical Gastroenterology and Hepatology. doi:10.1016/j.cgh.2015.02.018.

Celiac.com 03/13/2013 - To determine if the probiotic Bifidobacterium natren life start (NLS) strain might affect the treatment and clinical features of patients with untreated celiac disease, a team of researchers recently conducted an exploratory, randomized, double-blind, placebo-controlled study on the effects of Bifidobacterium infantis natren life start super strain in active celiac disease. The research team included E. Smecuol, H.J. Hwang, E. Sugai, L. Corso, A.C. Cherñavsky, F.P. Bellavite, A. González, F. Vodánovich, M.L. Moreno, H. Vázquez, G. Lozano, S.Niveloni, R. Mazure, J. Meddings, E. Mauriño, and J.C. Bai. They are variously affiliated with the Small Intestinal Section of the Department of Medicine in the Department of Alimentation at the Hospital de Gastroenterología "Dr. C. Bonorino Udaondo," the Department of Immunogenetics of the Hospital de Clínicas "José de San Martín" at the Universidad de Buenos Aires, the Consejo de Investigación en Salud, Ministerio de Salud in Ciudad de Buenos Aires, the Department of Gastroenterology at the Universidad del Salvador in Buenos Aires, Argentina, and the Gastrointestinal Research Group at the University of Calgary in Calgary, Alberta, Canada. For their study, the team enrolled 22 adult patients with two positive celiac disease-specific tests. Over a three week period, patients randomly received two capsules of either Bifidobacterium infantis natren life start strain super strain (Lifestart 2) (2×10 colony-forming units per capsule). All patients consumed at least 12 g of gluten per day for the duration of the test. In all, twelve patients received the bifidobacterium, while ten received the placebo. At the end of the trial, the team used biopsy to confirm celiac disease in all patients. The primary factor being measured was changes to intestinal permeability. The secondary factor was changes in symptoms and the Gastrointestinal Symptom Rating Scale, and in immunologic indicators of inflammation. Neither treatment caused significant changes in abnormal baseline intestinal permeability. In contrast to patients receiving the placebo, patients who received B. infantis experienced significant improvements as measured by the Gastrointestinal Symptom Rating Scale (P=0.0035 for indigestion; P=0.0483 for constipation; P=0.0586 for reflux). The administration of B. infantis was completely safe. Patients who received B. infantis showed lower ratios of IgA tTG and IgA DGP antibody (P=0.055 for IgA tTG and P=0.181 for IgA DGP). Patients who received B. infantis also had significantly higher levels of serum macrophage inflammatory protein-1β (P<0.04). The results indicate that B. infantis may alleviate symptoms in untreated celiac disease. The probiotic produced some immunologic changes, but did not change abnormal intestinal permeability. The researchers call for further study to confirm and/or expand these results. Source: J Clin Gastroenterol. 2013 Feb;47(2):139-47. doi: 10.1097/MCG.0b013e31827759ac.

Celiac.com 04/20/2016 - People with celiac disease very often have reflux symptoms. A team of researchers recently set out to evaluate mucosal integrity and motility of the lower esophagus as possible contributors to reflux symptoms in patients with celiac disease. The research team included María Inés Pinto-Sánchez, Fabio D. Nachman, Claudia Fuxman, Guido Iantorno, Hui Jer Hwang, Andrés Ditaranto, Florencia Costa, Gabriela Longarini, Xuan Yu Wang, Xianxi Huang, Horacio Vázquez, María L. Moreno, Sonia Niveloni, Premysl Bercik, Edgardo Smecuol, Roberto Mazure, Claudio Bilder, Eduardo C. Mauriño, Elena F. Verdu, and Julio C. Bai. They are variously affiliated with the Farncombe Family Digestive Health Research Institute at McMaster University, in Hamilton, Ontario, Canada, the Department of Medicine, "Dr. Carlos Bonorino Udaondo" Gastroenterology Hospital in Buenos Aires, Argentina, Favaloro University Hospital in Buenos Aires, Argentina, Consejo de Investigación en Salud, MSAL, Gobierno de la Ciudad Autónoma de Buenos Aires, Argentina, and with the Gastroenterology Chair, Universidad del Salvador in Buenos Aires, Argentina. For their study, they enrolled newly diagnosed celiac disease patients with and without reflux symptoms, non-celiac patients with classical reflux disease (GERD), and control subjects, who had no reflux symptoms. Using both light microscopy and electron microscopy, they assessed endoscopic biopsies from the distal esophagus for dilated intercellular space (DIS). They used qRT-PC to determine tight junction (TJ) mRNA proteins expression for zonula occludens-1 (ZO-1) and claudin-2 and claudin-3 (CLDN-2; CLDN-3). Overall, patients with active celiac disease showed higher DIS scores than controls, and similar to GERD patients. They found altered DIS even in celiac disease patients without reflux symptoms, who had normalized after one year of a gluten-free diet. Celiac disease patients with and without reflux symptoms had lower expression of ZO-1 than controls. Celiac disease and GERD patients showed similar expression of CLDN-2 and CLDN-3. This study shows that patients with active celiac disease have altered esophageal mucosal integrity, independent of any reflux symptoms. Loss of TJ integrity in the esophageal mucosa may result from altered expression of ZO-1, which may contribute to the development of reflux symptoms. Source: Open Original Shared Link