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Celiac.com 08/14/2024 - Refractory celiac disease type II, commonly referred to as RCDII, is a rare and severe form of celiac disease. Unlike typical celiac disease, RCDII does not respond to a gluten-free diet. This condition is marked by the clonal expansion of abnormal intraepithelial lymphocytes, which can lead to high mortality rates due to the lack of effective treatment options. One promising treatment involves the use of tofacitinib, a small-molecule inhibitor targeting specific enzymes known as JAK1 and JAK3. This study explores the potential of tofacitinib to induce clinical remission in patients with RCDII. Study Overview and Methodology This open-label clinical study involved six patients diagnosed with RCDII, who had not responded to previous treatments, including the drug cladribine. Four patients were treated according to the study protocol in the Netherlands, while two patients in Germany received similar treatment outside the protocol. The patients were given 10 mg of tofacitinib twice daily for 12 weeks. The study aimed to assess both the clinical and immunologic responses to the treatment. Baseline Characteristics of Patients At the beginning of the study, all patients exhibited significant symptoms of malabsorption, such as weight loss, diarrhea, abdominal pain, and low levels of albumin in the blood. Small intestine biopsies showed a high percentage of abnormal intraepithelial lymphocytes, ranging from 70% to 90%. Two patients also had ulcerative jejunitis, a severe condition causing ulcers in the small intestine. Histological examinations revealed varying degrees of villous atrophy, a condition where the finger-like projections in the small intestine are damaged, affecting nutrient absorption. Clinical Response to Tofacitinib Treatment All patients completed the 12-week treatment course with tofacitinib. Within a span of two to fourteen days, patients experienced a noticeable resolution of diarrhea and abdominal pain. Additionally, they showed significant weight gain, with a median increase of over 12% by the end of the 12 weeks. One patient with severe ulcerative jejunitis was even able to discontinue total parenteral nutrition by week nine. However, upon discontinuation of tofacitinib, all patients quickly relapsed, experiencing weight loss and a return of symptoms. When tofacitinib treatment was resumed, patients again showed rapid and complete clinical improvement. Immunologic and Histologic Findings The primary immunologic endpoint was to achieve a reduction of at least 20% in the number of abnormal intraepithelial lymphocytes. This goal was not met by any patient. The median percentage of abnormal cells remained relatively unchanged from baseline to the end of the 12-week treatment period. Despite this, four out of six patients showed significant improvement in the histology of their small intestine, indicating mucosal healing. This improvement was particularly evident in patients with ulcerative jejunitis. Adverse Events and Safety Throughout the study, all patients experienced adverse events. The most common was lymphopenia, a condition characterized by low levels of lymphocytes in the blood. One patient suffered a serious adverse event, developing a pulmonary embolism associated with a line sepsis caused by a bacterial infection. This patient continued to receive tofacitinib at a reduced dose of 5 mg twice daily, with continued clinical improvement. No other serious infections were reported, and there was no progression to enteropathy-associated T-cell lymphoma in any patient. Extended Follow-Up and Long-Term Outcomes During an extended follow-up period of up to two years, the patients continued to show persistent clinical remission while on a reduced dose of tofacitinib. The median weight gain further increased, and duodenal biopsies indicated ongoing histologic improvement. Capsule endoscopy revealed complete or near-complete resolution of intestinal ulcerations in patients with ulcerative jejunitis. These findings suggest that tofacitinib not only provides short-term relief but also contributes to long-term clinical remission in patients with RCDII. Implications for Future Treatment of Celiac Disease This study is significant for several reasons. First, it demonstrates that tofacitinib can induce rapid and sustained clinical remission in patients with refractory celiac disease type II, a condition that has been notoriously difficult to treat. Second, the study's findings suggest that while tofacitinib may not reduce the number of abnormal intraepithelial lymphocytes, it effectively mitigates their harmful activity. This functional impact is crucial for improving patient outcomes. For those with celiac disease, particularly the rare and severe RCDII, this study offers hope for a viable treatment option where none previously existed. It also underscores the importance of continued research and clinical trials to explore and refine new therapies. The potential for tofacitinib to change the treatment landscape for RCDII patients is substantial, offering a path to better management and improved quality of life. Read more at: cghjournal.org
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Celiac.com 07/25/2023 - Non-celiac gluten sensitivity is a gluten-related disorder that results from immune-mediated reactions in predisposed people. Non-celiac gluten sensitivity usually manifests with gastrointestinal symptoms. However, in rare cases, it might present with psychiatric symptoms that could be severe enough to impair functioning. We've done a number of articles on the psychological and psychiatric manifestations of celiac disease, which can include, anxiety, depression, and eating disorders. There are also studies linked celiac disease to neurological manifestations, along with schizophrenia. Every so often, we cover a case study that may be relevant to celiac disease, in general. Our latest case involves a 15-year-old Sudanese girl, with no prior psychiatric history, who visited the emergency department due to anxiety, behavioral changes, and hallucinations of her deceased father. Girl Treated for Psychosis and Delusions After witnessing her father's burial, she started experiencing flashbacks and intrusive images of him, along with anxiety about death and paranoia towards others. The patient was agitated and psychotic, requiring rapid tranquilization. She was later diagnosed with hyperthyroidism due to Grave's disease. A team of clinicians, including Olfa Selmi, Banan Khalid, and Saleem Al-Nuaimi, present the girl's case report. They are variously affiliated with the Department of Psychiatry and the Mental Health Service at Hamad Medical Corporation and Hospital in Doha, Qatar. Despite receiving appropriate thyroid medication, her psychiatric symptoms did not improve, leading to further investigations. Blood tests revealed positive anti-transglutaminase IgA antibodies, suggesting possible celiac disease. Psychosis Improves on a Gluten-Free Diet A gastroscopy showed mild duodenal changes, and she began a gluten-free diet. Within weeks of starting the gluten-free diet, the patient's psychotic symptoms improved significantly. Whenever she consumed gluten in large quantities, her delusions resurged, and they subsided again with a return to the gluten-free diet. The case suggests a potential link between gluten and psychosis, although the exact mechanism remains uncertain. Prior case reports also show improvements in psychotic symptoms after adopting a gluten-free diet in patients with gluten allergies or sensitivities. As a gluten-free diet is safe and low-cost, it may be considered as part of the treatment plan for reducing psychotic symptoms in patients with gluten-related disorders or autoimmune diseases. This case adds to the growing literature exploring the role of gluten in atypical psychotic presentations and the potential benefits of a gluten-free diet in such cases. It also highlights the importance of considering nonconventional treatments when standard therapeutic interventions do not yield satisfactory results, as aggressive treatments may carry higher risks. The significant improvement of the girl's psychosis upon starting on a strict gluten-free diet suggests a potential connection between gluten ingestion and psychiatric disorders. However, further research is needed to better understand the relationship between gluten and psychiatric symptoms, and to guide the use of a gluten-free diet in appropriate cases. Read more at Cureus 15(7): e41807.
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Celiac.com 05/24/2017 - Refractory celiac disease (RCD) is a rare manifestation of celiac disease that is difficult to treat, and often results in death from enteropathy-associated T-cell lymphoma. Doctors looking to treat RCD have found very limited success with a number of immunosuppressive medications (IMs), including azathioprine, systemic corticosteroids, or regular budesonide. A team of researchers at the Mayo Clinic recently set out to assess open-capsule budesonide (OB) treatment on RCD patients, including those who saw no improvement with previous IM treatments. The research team included Saurabh S Mukewar, Ayush Sharma, Alberto Rubio-Tapia, Tsung-Teh Wu, Bana Jabri and Joseph A Murray. The team first looked for RCD patients treated with OB at Mayo Clinic, Rochester, Minnesota from 2003 to 2015. They then reviewed demographic, serologic, and clinical variables in these patients. The team found a total of 57 patients who received OB as treatment for suspected RCD. Based on clonal T-cell receptor gamma gene rearrangement or aberrant phenotype of intraepithelial lymphocytes (IELs), the team classified 13 patients (23%) as having RCD-2 and 43 (75%) as RCD-1. The team was unable to determine TCR gene rearrangement status for one patient (2%). Most patients were women (69%), with an average age of 60.5 (+/- 3.5) years, while average body mass index was 28.4 kg/m2. Nearly 75% of patients suffered from diarrhea, with an average of 6 bowel movements per day (range, 4–25). Nearly half of these patients failed to improve with IM treatment. Twenty-four patients (42%) were anemic, while 12 patients (21%) had hypoalbuminemia. Biopsies showed Marsh 3 lesions in all patients, broken down as follows: 19% were Marsh 3a, 46% were Marsh 3b, and 35% were Marsh 3c. After OB therapy, 92% showed clinical improvement, while 89% showed histologic improvement. Subsequent biopsies showed that 7 out of 13 patients with RCD-2 (53%) displayed an absence of the previously observed clonal TCR gamma gene rearrangement/aberrant IEL phenotype. During the follow-up period, two patients died of enteropathy-associated T-cell lymphoma. Most RCD patients show clinical and histopathologic improvement with OB treatment, including those who previously failed to respond to other IMs. These results show that treatment with open-capsule budesonide is a promising option for patients looking to manage RCD. Source: The American Journal of Gastroenterology, (21 March 2017). doi:10.1038/ajg.2017.71
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Celiac.com 12/24/2019 - Celiac disease is a common autoimmune disease triggered by dietary gluten that can lead to severe gastrointestinal symptoms. The only current treatment is a lifelong gluten‐free diet, but many patients continue to have chronic symptoms. Could enzyme therapy help these people? A team of researchers recently set out to assess the effectiveness of the oral enzyme latiglutenase, for improving multiple gluten‐induced symptoms and patient quality of life (QOL) due to accidental gluten consumption by celiac patients on a gluten‐free diet. The researcher team included Jack A. Syage, Peter H.R. Green, Chaitan Khosla, Daniel C. Adelman, Jennifer A. Sealey‐Voyksner, and Joseph A. Murray. They are variously affiliated with ImmunogenX, Newport Beach, CA, USA; Celiac Disease Center, Columbia University, New York, NY, USA; Stanford University, Stanford, CA, USA; Aimmune Therapeutics, Brisbane, CA, USA; and the Division of Gastroenterology and Hepatology, Mayo Clinic For the study, 398 symptomatic celiac patients received doses of either latiglutenase or placebo for 90 days, and responded to a daily symptom diary, along with multiple QOL questionnaires at weeks 0, 6 and 12 of the treatment periods as secondary endpoints. The results were organized according to patient antibody levels. The reults showed a statistically significant and dose‐dependent improvement in seropositive, but not seronegative, celiac patients. In subjects receiving 900 mg latiglutenase, improvements (P‐values) in the severity of these symptoms for week 12 were 58% (0.038), 44% (0.023), 21% (0.164) and 104% (0.049) respectively, compared with those receiving a placebo. Overall, the greater the symptoms, the greater the relief seen in symptomatic patients. Similar results were seen in QOL reports. Although the results do not show a clear benefit of latiglutenase in seropositive celiac patients across the board, they do seem to show an improvement in the severity and frequency of symptoms, including abdominal pain, bloating, tiredness and constipation, and in QOL for such patients taking latiglutenase with meals. Targeted enzymes, such as latiglutenase could play a role in improving symptoms and quality of life in celiac patients with ongoing sensitivity and symptoms, even while following a gluten-free diet. Going forward, look for more study, and more investigation into the value of targeted enzymes in treating celiac disease. Read more at the International Journal of Gastroenterology and Hepatology Funding disclosures for the study: Clinical trial NCT01917630 was sponsored by Alvine Pharmaceuticals; all data from this trial is presently owned by ImmunogenX. The data analysis reported here was supported in part by a grant from the National Institutes of Health (R01 DK063158 to CK).
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Symptoms ongoing
nataliet24 posted a topic in Post Diagnosis, Recovery & Treatment of Celiac Disease
Is it worrying that I still don’t feel any better after being gluten free for nearly 7 months. Still have constant belly pain everyday and brain fog. Worrying I will have refractory coeliac I’m only 22 and had total villous atrophy -
Athletic Improvement Through the Gluten-Free Diet
Tracy Grabowski posted an article in Autumn 2014 Issue
Celiac.com 08/09/2016 - Is athletic improvement, after beginning a gluten-free diet, a sign that the athlete had gluten intolerance or celiac disease? Or, could it simply be a benefit of following a gluten-free diet? The real cause of the gluten-free athlete's improved athletic performance may be harder to uncover than you think. Could the serious athlete's diet, free from gliadin and glutenin (the two protein groups found in wheat, barley, rye and triticale which create what we collectively label as "gluten"), cause improved physical output? Or, is it possible that these high-performing machines we call athletes may have had an undiscovered intolerance to the gluten substance before they ever discovered the diet? The "cause and effect" here may be hard to define; or, quite possibly, impossible. Most data now supports that as many as 10% of people may have negative reactions, or an intolerance to, the gluten found in wheat, barley and rye products and by-products(1). However, most people may not even realize they have symptoms, and like many of us, chalk them up to numerous other issues: I worked out too much. I have a sensitive stomach. I ate something bad. It's too hot out to digest properly… and, of course, the list goes on. If a marathon runner, soccer player, football player, Olympic athlete, or anyone else who trains recreationally, semi-professionally, or professionally, were to have some level of intolerance and remove gluten from their diet, it is very likely they would see a marked improvement in their performance. This boost in athleticism could be credited to a number of factors including increased and improved absorption of vital nutrients such as iron, calcium, and vitamin D as well as secondary nutrients such as B12, copper, folate, magnesium, niacin, riboflavin and zinc. Athletic improvement can also be attributed to better overall awareness and tracking of what is being consumed. (This better management and awareness generally leads most athletes to eat cleaner, less refined and less processed foods as a result.) On the flip side, the reverse is also true: Athletes might be seeing better performance results… even if they are not intolerant to gluten or have celiac disease. The improved performance may, in fact, be a product of increased protein intake (which tends to happen when processed carbohydrates are removed from the diet), better overall decision-making (like choosing whole foods or "clean" foods in order to avoid gluten), as well as higher natural fiber intake (from beans, vegetables, and whole grains such as quinoa, rice, and even amaranth) which aid the body's systems and digestion. The foods that performance and endurance athletes eat on a strict gluten-free diet are less likely to have been processed, and therefore low in salt, low in chemicals, and anti-inflammatory. (Thus, making it easier to train harder, faster, and longer.) As you can see, it's a real "what came first.. chicken or the egg" dilemma. Both groups, both gluten intolerant and non-intolerant athletes could be showing improvement on a gluten-free diet. So how do you know if the athlete has an intolerance that led to the improvement? In a landmark study, conducted by the University of Chicago Celiac Disease Center(2), it was estimated that 60% of children and 41% of adults who were diagnosed with celiac disease were asymptomatic when they received their diagnosis. Yes, asymptomatic. That means they didn't have any clue that they were negatively, medically, affected by gluten. One can only imagine in highly-maintained, otherwise "fit" populations, such as athletes who are striving for peak health, aimed at peak performance, these sample numbers might be even higher. These numbers seem to imply that it is very likely that athletes who see an increase in athletic performance may, indeed, be suffering from either celiac disease or non-celiac gluten intolerance symptoms…that they didn't even know they had. However, that being said, it might be next to impossible to render a celiac diagnosis without subjecting the athlete to a rash of testing which will include the request that they, once again, consume gluten. (Try telling an athlete who is performing better than ever to change their ways. It's not likely to happen, especially during peak season.) Adding to the difficulty in diagnosis of gluten sensitivity is the lack of a verified blood or stool marker. The closest factor that can be studied to determine gluten sensitivity is the AGA-IgG antibodies. (Antibodies the body from exposure to "foreign" substances. AGA stands for antigliadin antibodies, which are antibodies produced by the body in response to contact with gliadin, a part of the gluten molecule. IgG stands for immunoglobulin G, which are generalized antibody molecules(3)) While it is true that about 40% of people with proven gluten sensitivity have elevated AGA-IgG, it is also true that about 15-25% of healthy individuals also have elevated AGA-IgG. Therefore, about 60% of gluten sensitive people do not have elevated AGA-IgG (making the test not sensitive enough); and about 20% of "normal", or non-gluten sensitive people have elevated AGA-IgG for no apparent reason (making the test not specific enough(4)). In either case, many high-level athletes are finding comfort and elevated performance in a gluten-free diet. In The Gluten-Free Edge: A Nutrition and Training Guide for Peak Athletic Performance and an Active Gluten-Free Life (Bronsky, McLean Jory, Yoder Begley, Published by The Experiment, December 2012) there are several real-life gluten-free athletes who are discussed. They also provide insight into the "fuel" these athletes use instead of typical carbohydrates found in wheat-based pastas and products. There are also several websites dedicated to the insights, training methods, and nutrition of athletes that also promote the gluten-free diet to promote enhanced performance, better recovery, and increased stamina as a result of stabilized blood sugars (reducing the hypoglycemic effect of intense exercise) as well as decreased inflammation, and leaner muscle. Sources: National Institutes of Health, Univ. of Chicago Celiac Disease Center, May 7, 2013. A multi-center study on the sero-prevalence of celiac disease in the United States among both at risk and not at risk groups. Fasano et. al., Archives of Internal Medicine. February 2003. Celiac Disease Center at Columbia University. http://www.cumc.columbia.edu February 14, 2011. Detection of secretory IgA antibodies against gliadin and human tissue transglutaminase in stool to screen for coeliac disease in children: validation study (Published 26 January 2006) BMJ 2006;332:213
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