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Celiac.com 09/12/2024 - Celiac disease is an autoimmune disorder where the ingestion of gluten leads to damage in the small intestine. This condition affects roughly one in 133 people worldwide, though it often goes undiagnosed due to its diverse symptoms. Celiac disease can co-occur with other autoimmune diseases, complicating its presentation and management. The disease’s prevalence and diagnosis are influenced by demographic and genetic factors, making it a significant health concern globally. Ophthalmic Manifestations of Celiac Disease Celiac disease is not just a gastrointestinal disorder; it can also have various ophthalmic manifestations. Patients with celiac disease may exhibit a range of eye-related issues that are not typically associated with the condition, such as decreased endothelial cell density, vitamin A deficiency causing dryness, altered corneal nerve density, cataracts, uveitis, changes in choroidal thickness, papilledema, and neurological issues like nystagmus. These manifestations highlight the systemic nature of celiac disease and the importance of comprehensive care. The Need for Thorough Evaluation Before Corneal Refractive Surgery Corneal refractive surgery, which includes procedures like LASIK, is increasingly popular for correcting vision problems. However, for patients with celiac disease, it is crucial to conduct a thorough evaluation before proceeding with such surgeries. The variability in ocular manifestations among celiac patients necessitates individualized assessments to determine surgical candidacy and optimize outcomes. This evaluation should include both subjective and objective assessments. Subjective Assessments A detailed medical history focusing on the patient’s experience with celiac disease is essential. This includes questions about dietary gluten intake, weight loss, joint pain, and cognitive impairments like brain fog. Understanding these aspects can help in identifying potential complications that might affect surgical outcomes. Objective Assessments A comprehensive objective assessment should include several diagnostic tests: Slit-lamp biomicroscopy to examine the eye’s structures. Schirmer test and tear break-up time (TBUT) to assess tear production and dry eye. Optical coherence tomography (OCT) to measure retinal and choroidal thickness. Scheimpflug imaging and fundoscopy to evaluate the anterior and posterior segments of the eye. Specific Considerations for Celiac Disease Patients Given the diverse ocular manifestations associated with celiac disease, several specific considerations should be addressed: Dry Eye Disease: Patients with celiac disease are more prone to dry eye disease. Symptoms like ocular discomfort, irritation, redness, and burning can be managed with artificial tears and punctal plugs before surgery. Endothelial Cell Density (ECD): Celiac disease patients may have lower ECD, which can lead to corneal edema post-surgery. Specular microscopy is recommended to evaluate ECD before proceeding with surgery. Anterior Chamber Depth (ACD): Some celiac disease patients might have shallower ACDs, which can indicate early-onset cataracts. Scheimpflug imaging can help assess ACD. Choroidal and Retinal Health: OCT is crucial to evaluate choroidal thickness and retinal health. Thinner choroids and other posterior segment abnormalities can affect visual outcomes post-surgery. Thyroid-Associated Orbitopathy (TAO): Celiac disease patients may also suffer from TAO, which can impact corneal health and refractive surgery outcomes. Thyroid function tests and orbital ultrasound are necessary for a thorough evaluation. Vitamin A Deficiency: This can lead to dryness and other ocular surface issues. Serum retinol levels should be checked, and vitamin A supplementation should be managed appropriately. Neurological Issues: Conditions like gluten ataxia and nystagmus can complicate surgery due to motor control issues. These conditions need careful assessment and management. Autoimmune Co-morbidities: The presence of other autoimmune conditions, like Type 1 Diabetes Mellitus, can increase the risk of complications like diabetic retinopathy, impacting surgical outcomes. Comprehensive retinal evaluations are necessary in these cases. Conclusion: The Importance of Comprehensive Care This study underscores the need for a thorough and individualized evaluation of celiac disease patients considering corneal refractive surgery. By addressing the various ophthalmic manifestations and related autoimmune conditions, healthcare providers can improve surgical outcomes and patient satisfaction. The recommendations provided in this study serve as preliminary guidelines, highlighting the importance of further research to better understand the impact of celiac disease on corneal refractive surgery outcomes. For celiac patients, these insights are crucial, as they emphasize the need for comprehensive care and tailored management strategies to ensure the best possible surgical results. Read more at: cureus.com

Celiac.com 03/27/2023 - Celiac disease, a chronic inflammatory disorder of the intestines, affects about 1% of the world's population. Celiac disease causes diarrhea, abdominal discomfort, bloating, flatulence, and, in rare cases, constipation in the digestive tract. Since the identification of gluten as the disease-causing antigen, celiac patients have been treated with a gluten-free diet, which usually eliminates symptoms and restores gut health, but which also has limitations for some patients. Celiac disease is also associated with numerous neurological and psychological manifestations. A recent article details findings from the most recent study, but here we try to provide more comprehensive information. Neurological Manifestations of Celiac Disease The neurological manifestations of celiac disease are varied and can include psychiatric and neurological symptoms such as ataxia, peripheral neuropathy, seizures, headaches, cognitive impairment, and myoclonus. The specific mechanisms of celiac disease's neurological effects are still being researched, but they may involve gluten-mediated pathogenesis that can lead to antibody cross-reactions, immune-complex deposition, direct neurotoxicity, or extreme vitamin or food deficiencies. A gluten-free diet can alleviate most celiac disease symptoms, except for cortical myoclonus and dementia, which may require immunosuppressive therapy. However, there is currently no consensus on whether serological or neurophysiological data can accurately predict or monitor celiac disease-related neurological involvement. Treatment for gluten-related neurological symptoms typically involves embarking on a strict gluten-free diet as soon as possible, which can have a positive therapeutic effect for most cases. Symptomatic management may also be required. Immunosuppression is only used in cases where a gluten-free diet alone has not been beneficial or for patients with refractory celiac disease. Peripheral Neuropathy and Gluten Ataxia Peripheral neuropathy and gluten ataxia are common in celiac patients, with up to 39% of patients experiencing gluten neuropathy. Gluten-free diets have been shown to improve neuropathy and ataxia. Gluten ataxia is an uncommon immune-mediated neurological disease that can be difficult to identify. The early signs of ataxia may be subtle, but worsen if left untreated. Patients with gluten ataxia may experience structural alterations in different parts of the brain, including the cerebellum and thalamus, and have larger lateral ventricles. Higher Epilepsy Risk Celiac disease increases the risk of epilepsy, especially in children and adolescents. The presence of villus atrophy on follow-up biopsies may reduce the risk of epilepsy but does not affect hospitalizations for epilepsy emergencies. Unexplained epilepsy should prompt celiac disease screening since early identification and therapy may increase the effectiveness of anti-epileptic drugs. Celiac patients also have a higher prevalence of migraines and tension headaches. The underlying relationship between celiac disease and headache involvement is still unknown, but adherence to a gluten-free diet can alleviate neurological symptoms. Celiac disease can also cause cognitive impairment, including memory loss, clouded thinking, personality shifts, and an inability to calculate. Nutrient deficiencies, systemic inflammation, and low brain serotonin levels have been suggested as possible reasons for this. Celiac disease has also been associated with Alzheimer's and vascular and fronto-temporal dementias. Neuropsychological assessments should be conducted in celiac disease patients to assess cognitive function. Psychiatric Manifestations of Celiac Disease Celiac disease is associated with depression, anxiety, eating disorders, autism spectrum disorder, attention deficit hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, and mood disorders. The relationship between celiac disease and these psychiatric disorders is not well-known or established. Particular biological aspects as well as the effect of a gluten-free diet require additional research. Depression and Anxiety Celiac disease has been associated with various psychiatric disorders such as depression, anxiety, eating disorders, autism spectrum disorder, attention deficit hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, and mood disorders. However, the relationship between these disorders and celiac disease remains unclear and requires further research. Research suggests that gastrointestinal disorders have a link with depression and anxiety due to prolonged pain and inflammation, affecting specific brain targets like the anterior cingulate cortex. Gastrointestinal disorder patients have reduced cognitive and mood status, leading to anxio-depressive phenotypes, even in the absence of clear evidence of threats. Children with celiac disease may experience anxiety and depressive symptoms, and pediatric patients with celiac disease should be frequently assessed for mental health issues, especially anxiety and sadness. Adults with celiac disease have reported experiencing anxiety and depression as well, particularly due to clinical illnesses and symptoms. Following a gluten-free diet may worsen symptoms like anxiety and fatigue, leading to a diminished quality of life. Therefore, clinicians must recognize the importance of promoting both dietary adherence and social and emotional well-being in celiac disease patients. Studies have shown that individuals with celiac disease experience low quality of life, anxiety, and depressive symptoms, and nutrition plays a crucial role in reducing these effects. However, the role of motivation in the quality of life and adherence remains unclear and requires further research. Eating Disorders Eating disorders may be a comorbidity with celiac disease (celiac disease) and the need for further investigation. celiac disease patients may experience disordered eating due to the disease itself or other factors such as food neophobia. It is crucial for gastroenterology clinicians to be aware of potential risks for eating disorders in celiac disease patients. The article notes that while numerous examples of eating disorders have been described in celiac disease patients, few epidemiological studies have investigated this potential link. One study found that patients with celiac disease had higher Eating Attitude Test scores than controls when testing individuals aged 13 and up, but no clear differences were seen between patients with celiac disease and controls when using other screening measures for ED. The article suggests that further investigations with larger samples and prospective designs are needed to corroborate these results. The article also discusses how celiac disease may cause food neophobia, which is linked to sensory aversions or fears of the negative effects of eating particular foods. This fear may be more severe in celiac disease patients than in non-celiac disease patients who choose to follow a gluten-free diet and can be linked to the possibility of having an unfavorable reaction to gluten-contaminated food products. The article emphasizes the importance of gastroenterology clinicians being aware of potential risks for eating disorders in celiac disease patients. It notes that eating disorders are defined by thoughts and actions linked to physical and/or psychological problems and that it is crucial to identify past, current, and potential risks for eating disorders in celiac disease patients. Autism Disorder Autism spectrum disorder is caused by a complex interplay of genetic and environmental factors, affecting individuals in diverse ways. Recent studies suggest that immune system dysfunction could contribute to the development of autism spectrum disorder in some people [55]. While some research suggests a connection between celiac disease, an autoimmune disorder triggered by gluten consumption that mainly affects the small intestine, and autism spectrum disorder, other studies have not found a significant association between the two conditions. Attention Deficit Hyperactivity Disorder (ADHD) Research has suggested a potential link between celiac disease and ADHD, with studies showing that celiac disease is overrepresented in ADHD patients, and a gluten-free diet improved ADHD symptoms in celiac disease patients. However, routine screening for ADHD in people with celiac disease or vice versa is not recommended. Cognitive problems similar to those seen in children with ADHD, such as a lack of focus or trouble paying attention, were linked to gluten-free diet noncompliance in childhood celiac disease, as were psychosomatic symptoms and antisocial behavior. Individuals with untreated celiac disease may be at risk for engaging in ADHD-like behavior, specifically inattention. Out of 23 studies, 13 found a favorable correlation between ADHD and celiac disease. Bipolar Disorder Bipolar Disorders refer to a group of serious and long-term mental health conditions that are characterized by manic and depressive episodes. Research has shown that people with bipolar disorder have higher levels of immunoglobulin G (IgG) antibodies against gliadin than those without a history of psychiatric illness. However, there is still a need for further investigation into the specific antibody response to gluten antigens in bipolar disorder. Close associations have also been observed between celiac disease and major depressive disorder, panic disorder, and bipolar disorder, leading to reduced quality of life. Therefore, early reporting of symptoms and screening for celiac disease is recommended, especially for those with a family history of the disease or essential symptoms. Schizophrenia Schizophrenia is a severe mental illness that increases the risk of premature death 2-4 times compared to the general population. Genetic and environmental factors, including drug abuse, especially involving cannabis, are associated with an increased risk of developing schizophrenia. Research suggests an association between schizophrenia and celiac disease, although a causal link has yet to be established. Although having elevated antibodies against gliadin is a common immunological abnormality between schizophrenia and celiac disease, most patients with schizophrenia who had elevated anti-gliadin antibodies (AGA) did not have celiac disease. However, there is evidence that a gluten-restricted diet may benefit schizophrenia patients with immunological gluten sensitivity. One treatment-resistant schizophrenia patient with immunological gluten sensitivity benefited from a gluten-restricted diet improvement in both mental and physical symptoms, as well as a reduction in the plasma quantitative level of AGA-IgG. Chronic inflammation, which is thought to increase due to gluten intolerance, may worsen the symptoms of schizophrenia and make it harder for patients to respond to treatment and absorb medications. Schizophrenia patients also have a higher rate of digestive and liver problems. While removing gluten from the diet may alleviate some symptoms, it is not recommended for all patients. Gluten intolerance is believed to increase chronic inflammation, exacerbating symptoms and reducing medication absorption. However, the available data on the link between celiac disease, gluten allergies, and schizophrenia are inconsistent, and a gluten-free diet is not recommended for people with psychosis and mood disorders without further research. Other Psychiatric Disorders Previous research has shown that people with celiac disease are more likely to suffer from neuropsychiatric disorders than the general population. So far, more than 60 non-human leukocyte antigen (HLA) genes have been linked to celiac disease by genome-wide association studies; of these, it is believed that 15% have a role in neurological health. Many common neuropsychiatric disorders include celiac disease as a primary predisposing factor. It's possible that the co-occurrence of diseases is in large part due to shared molecular networks and biological processes. To determine what causes these disorders, we need to look at the underlying molecular mechanisms. Celiac disease was associated with an increased risk of psychiatric problems in children, raising their lifetime risk by 1.4 times that of the general population. Celiac disease in children has been linked to an increased likelihood of developing psychosocial difficulties later in life, including depression, anxiety, eating disorders, antisocial behavior, attention deficit hyperactivity disorder, autism spectrum disorder, and intellectual disability. It was also more common to have been diagnosed with a mood, eating, or behavioral condition prior to the celiac disease diagnosis. In contrast, no elevated risk was found for any of the psychological diseases studied in the siblings of people with celiac disease. A cohort study included nearly 20,000 children with biopsy-verified celiac disease, pairing each patient with 5 reference child controls. Approximately 16.5% of celiac children were diagnosed with a psychological condition during a median follow-up of 12.3 years, compared to 14.1% of controls. Celiac disease in childhood increased the risk of psychiatric illness by 19% and this risk increases during maturity, in particular, mood, anxiety, eating, ADHD, and autism spectrum problems. There was no statistically significant increase in psychotic disorders, psychoactive substance use, behavioral disorders, personality disorders, suicide attempts, or suicides. Celiac disease increases the use of psychiatric medication. Psychological issues associated with celiac disease were also more prevalent. As a result, the attending physician should conduct routine surveillance of potential psychiatric symptoms in patients of all ages who have gluten-related diseases, including both children and adults. Conclusions In conclusion, celiac disease has been linked to numerous neurological and psychiatric conditions, including depression, anxiety, eating disorders, autism spectrum disorder, attention deficit hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, and mood disorders. Clinicians should assess mental health factors when making a celiac disease diagnosis. Overall, the relationship between celiac disease and these neurological and psychiatric disorders is not well-known or established. More research is needed to understand the pathophysiology of celiac disease's neurological and psychiatric manifestations. Particular biological aspects as well as the effect of a gluten-free diet require additional research. Read more at Cureus.com

Celiac.com 10/08/2022 - Celiac disease is now recognized as a spectrum of gluten-sensitive illness in which the gut is no longer seen as the sole target. For example, dermatitis herpetiformis is a skin manifestation of gluten sensitivity. Celiac disease is no longer considered just in individuals with classic intestinal damage but in individuals with other signs of immune activation and/or degrees of gut involvement, triggered by the ingestion of gluten. Substantial evidence demonstrates that the nervous system also can be a target organ with or without the presence of gut involvement(1). Neurological Complications in Celiac Disease Approximately ten percent of celiac disease patients develop neurological complications(2) . Based on case studies, the most common neurological disorders associated with celiac disease are cerebellar dysfunction, epilepsy and peripheral neuropathy. From 1964 to 2000, data compiled from case reports of 83 celiac patients with neurological complications revealed that 70% of them were diagnosed with either ataxia or peripheral neuropathy(3) . A retrospective data survey of 620 patients attending the Derby Coeliac Clinic found the following neurological and psychiatric complications: Depression (12%), epilepsy (4%), migraine (3%), carpal tunnel syndrome (2%), stroke (2%), anxiety (2%), self poisoning (2%), myopathy (1%), learning difficulty (1%), sciatica (1%), meningitis (1%), Parkinson’s disease (1%), tension headache (1%), multiple sclerosis (1%) and peripheral neuropathy (1%)2 . However, further study needs to clarify the relationship between celiac disease and these complications. A recent study found 13 (8%) among 160 celiac patients had neurological disorders(4) . Ten of the thirteen patients had central nervous system disorders such as epilepsy, attention/memory impairment, and cerebellar ataxia. The remaining patients had peripheral nervous system disorders. In eleven out of thirteen cases, the celiac disease diagnosis came after the onset of the neurological disorder. Seven celiac patients were diagnosed and treated within six months of the neurological onset. All seven had either substantial or complete resolution of their neurological symptoms. In contrast, four out of five patients who were diagnosed with celiac disease from 10 to 264 months after the appearance of their neurological disorder showed no improvement in their neurological symptoms on the gluten-free diet. This study demonstrated that the crucial timing of treatment with a gluten-free diet in celiac patients who have neurological disorders might affect whether the neurological symptoms are reversible. While the incidence of neurological complications in celiac disease is estimated to be ten percent, the incidence of celiac disease in neurological patients is still unknown. Celiac disease can escape detection in blood antibody screenings(5). Not all gluten-sensitive individuals demonstrate classic biopsy evidence of celiac disease, but exhibit milder intestinal features. Also, not all celiac patients present with gastrointestinal symptoms. Therefore, neurological patients with gluten-sensitivity may be missed if they are evaluated for neurological symptoms alone. To identify gluten-sensitivity in neurological patients, antigliadin antibodies were determined in two groups of neurological patients. In a group with idiopathic neurological illness versus another group with identifiable neurological illness, a marked difference of 57% versus 5%, respectively, were antigliadin antibody positive(2) . Twenty-six (86%) of those in the idiopathic group consented to small bowel biopsy and nine (34%) of them had intestinal features characteristic of celiac disease. However, 12% of the healthy blood donors were also antigliadin antibody positive and no explanation was given. Therefore, it was unclear whether the rate of gluten-sensitive neurological illness could be overstated by 12 percent or that 12 percent of the normal population could have gluten-sensitivity. Gluten Ataxia Gluten ataxia is the most common form of neurological dysfunction to be attributed to gluten sensitivity1 . Up to 41% of sporadic idiopathic ataxia is caused by gluten ataxia, as evidenced by the presence of antigliadin antibodies. Patients with gluten ataxia have difficulty controlling their upper and/or lower limb movements. Hadjivassiliou et al found 79% (54 of 68) of gluten ataxia patients had damage to the part of the brain called the cerebellum which is involved in coordination and steadiness. Not all gluten-sensitive, neurological patients will also have classic intestinal biopsy evidence of celiac disease. Of 51 gluten ataxia patients who underwent duodenal biopsy, 24% of them had biopsy proof of celiac disease and only 13% had gastrointestinal symptoms1 . Yet, treatment with a gluten-free diet can be helpful, irrespective of gut involvement. For example, 26 patients with gluten ataxia were offered a gluten-free diet and were confirmed to be adhering to the gluten-free diet by evidence of negative serology within six months to one year of treatment(6). When compared to the control group of patients with gluten ataxia who did not receive treatment of a gluten-free diet, all 26 patients in the treatment group improved significantly in their ataxia based on a battery of tests. The response observed in the treatment group was irrespective of gut involvement or the duration of the ataxia (mean duration of nine years). These results contrasted with the expectation that the ataxia would remain despite evidence of the loss of cerebellar Purkinje cells which are the target cells in gluten ataxia(3, 6). Malabsorption or Autoimmunity? Two potential mechanisms to explain the neurological dysfunctions of celiac disease are nutrient deficiencies due to malabsorption, and autoimmune disease. Currently, it is unknown which of these, or both, is the underlying cause of neurological disorder in celiac disease. A reference to these potential mechanisms came in 1966 when Cooke and Smith reported a landmark study of 16 adult celiac patients with neurological complications3 . For most of them, symptoms of classic celiac disease pre-existed their neurological symptoms. All 16 were found with extreme weight loss and vitamin deficiencies along with anemia due to severe malabsorption. Subsequently, over half of them died, despite gluten restriction, due to the progression of their neurological complications involving sensory ataxia and/or other features. Post-mortem findings in four patients revealed cerebellar Purkinje cell loss and T-cells (type of white blood cell) infiltrating parts of the brain, brainstem, and spinal cord(7). Deficiencies of folic acid, vitamin B-12, and vitamin E have been implicated as a potential cause of neurological complications(4). However, vitamin deficiencies alone do not explain the absence of neurological deficits in some patients(2). In addition, vitamin deficiencies are rarely found or can be attributed to neurological dysfunction in association with gluten ataxia patients of which the majority don’t have histological evidence of celiac disease(3). Furthermore, in a current study of 13 neurological celiac patients, only 2 had been diagnosed with malabsorption(4). In support of the hypothesis of an autoimmune mechanism of celiac disease neurological complications, Hadjivassiliou et al found that gluten ataxia patients with inflammation located in the white matter of the cerebellum part of the brain was marked by the loss of Purkinje cells. The inflammation in celiac disease, which is thought to be mediated by T-cells, is not confined to the small bowel as gliadin-specific T cells and antigliadin antibodies are found in the blood(8). Antigliadin antibodies also have been found in the cerebrospinal fluid(3) . In gluten ataxia patients, antigliadin antibodies were found to bind to Purkinje cells in the cerebellum that might result in damage to this part of the brain(9). This finding suggests that common binding sites are shared between cerebellar Purkinje cells and gliadin proteins. Patients with gluten ataxia also have anti-Purkinje cell antibodies. How antigliadin antibodies gain access to the cerebellum might be due to possible alterations of the blood-brain barrier. In further support of an autoimmune basis of celiac disease neurological complications, 8 of 13 celiac patients with neurological dysfunction had anti-neuronal antibodies to the central nervous system(4). This was significantly higher when compared with only 1 in 20 celiac patients who had anti-neuronal antibodies but no neurological involvement. Furthermore, 30 non-celiac control patients, who had other autoimmune gastrointestinal diseases or had donated blood, had no detectable anti-neuronal antibodies. After one year of treatment on a gluten-free diet, anti-neuronal antibodies disappeared in 6 of the 8 celiac patients with neurological dysfunction. In 5 of these 6 patients, the neurological symptoms partially or completely resolved. However, anti-neuronal antibodies are not specific for neurological disorders associated with celiac disease since they are also found in other patients with nervous system disorders. Identification of neurological patients with gluten-sensitivity with or without histological evidence of celiac disease is necessary in order to provide them the opportunity for treatment with a gluten-free diet. Identification should be further aided when the exact mechanisms of neurological complications in gluten-sensitive patients are understood. Finally, immediate treatment with a gluten-free diet early in the progression of the disease may be crucial in the prognosis of whether the neurological disorder is reversible. Glossary of Terms: ataxia: impaired muscle coordination Central Nervous System (CNS): the portion of the nervous system involving the brain and spinal cord cerebellum: portion of the brain involved in equilibrium and coordination; cerebellar (adj.) dementia: impaired intellectual function epilepsy: neurologic disease resulting in convulsions or loss of consciousness idiopathic: the disease has an unknown cause neurological: having to do with the nervous system neuron: nerve cell neuropathy: any disease of the nervous system paroxysm: convulsion Peripheral Nervous System (PNS): the portion of the nervous system outside of the brain and spinal cord; peripheral (adj.) Purkinje cell: a type of neuron that is highly branched, mostly found in the cerebellum References: Hadjivassiliou M et al 2003. Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics. Brain 126: 685-91. Tengah D et al 2002. Neurological complications of coeliac disease. Postgrad Med J 78: 393-98. Hadjivassiliou, et al. 2002. Gluten sensitivity as a neurological illness. J Neurol Neurosurg Psychiatry 72: 560-3 Volta U, et al. 2002. Clinical findings and anti-neuronal antibodies in coeliac disease with neurological disorders. Scand J Gastroenterol 37: 1276-81. Tursi A et al 2001. Low prevalence of antigliadin and anti-endomysium antibodies in subclinical/silent celiac disease. Am J Gastroenterol 96: 1507-1510. Hadjivassiliou M, et al. 2003. Dietary treatment of gluten ataxia. J Neurol Neurosurg Psychiatry 74: 1221-24. Will AJ. 2000. The neurology and neuropathy of coeliac disease. Neuropathy and Applied Neurobio 226: 493-96. Cross A, and Golumbek, P. 2003. Neurologic manifestations of celiac disease. Neurology 60: 1566-1568. Hadjivassiliou M, et al. 2002. The humoral response in the pathogenesis of gluten ataxia. Neurology 58: 1221-26.

Celiac.com 04/28/2021 - Dermatitis herpetiformis is an external skin manifestation of gluten sensitivity. In people with dermatitis herpetiformis, an autoimmune response targets transglutaminase 3 (TG3) in the skin. Transglutaminase 2 (TG2) is a celiac disease autoantigen marked by the presence of enteropathy, while TG6 is the autoantigen that plays a role in neurological manifestations of gluten sensitivity. Researchers don't fully understand the interplay between B cell responses to these three transglutaminases in developing the clinical spectrum of disease manifestations. They also do not fully understand the individual or combined diagnostic and predictive value of the respective autoantibodies. To get a better idea of those values, a team of researchers recently assessed rates of TG6 antibodies in a group of patients with dermatitis herpetiformis. The research team included Marios Hadjivassiliou, Timo Reunala, Kaisa Hervonen, Pascale Aeschlimann, and Daniel Aeschlimann. They are variously affiliated with the Academic Department of Neurosciences, Sheffield Teaching Hospitals NHS Trust and University of Sheffield in Sheffield, UK; the Department of Dermatology, Tampere University Hospital in Tampere, Finland; the Celiac Disease Research Center, Tampere University and Faculty of Medicine and Health Technology in Tampere, Finland; and the Matrix Biology and Tissue Repair Research Unit, College of Biomedical and Life Sciences, School of Dentistry, Cardiff University in Cardiff, UK. The team looked at rates of TG6 antibodies in a group of 33 patients with dermatitis herpetiformis. Thirteen of the 33 patients (39%) were positive for TG6, 11 for IgA, three for IgG, and one for both. This was substantially higher than the 14% rate seen classic celiac disease cases in a Finnish population. Sixty percent of dermatitis herpetiformis patients with no enteropathy, ten patients in all, were TG6 positive, compared with 17% percent of those showing overt enteropathy, twelve in all (Marsh IIIB). Gluten-Free Diet Improves TG6 Antibody Levels After one year on a gluten-free diet, repeat testing showed that seven patients were TG6 negative, while 85% (11 of 13) showed reduced titers for TG6 antibodies. Four patients seroconverted and tested positive for TG6 antibodies at one year, due to the ongoing exposure to gluten. The team reports another patient who presented with encephalopathy leading to the diagnosis of celiac disease, who was intermittently adhering to a gluten-free diet. At baseline serological testing, the patient was positive for antibodies to all 3 transglutaminases. Eleven years later, he developed dermatitis herpetiformis, and eventually developed ataxia and peripheral neuropathy. Even though TG3 and TG6 autoantibodies are associated to certain disease expressions, TG2, TG3, and TG6 autoantibodies can be present across the spectrum of GRD patients, and may develop years before extra-intestinal symptoms appear. This supports the idea that gluten-dependent adaptive immunity is a necessary, but not sufficient condition for the development of organ-specific damage. TG6 antibodies seem to develop more frequently in patients with gluten intolerance, but, either there was no development of the molecular state driving the tissue damage in the gut, or more likely perhaps, a greater resistance to developing the phenotype in the first place. Read the full report in Nutrients 2020, 12(9), 2884

Celiac.com 06/12/2020 - What happens in Gluten Ataxia? Well, first, we want every celiac person to know what Gluten Ataxia is to ensure we are on the same "wave length". Gluten Ataxia is an autoimmune disorder in which the antibodies that are released in sensitive individuals when digesting gluten attack part of the brain by mistake. Since Gluten is a protein found in wheat, rye and barley, one would think that gluten exposure would have nothing to do with the brain, but since most people have no trouble with digesting this protein, others have a gluten sensitivity or celiac disease. In some cases the body's reaction to gluten can become quite severe. In these cases, the body starts to attack the central nervous system which may cause gluten ataxia. People who have issues digesting gluten may also develop digestive problems that cause damage to the small intestine. Gluten Ataxia usually starts off with mild symptoms, and gradually become worse over time. When left untreated the condition could lead to permanent damage. There is also evidence that people who suffer from gluten ataxia will show signs of cerebellar atrophy. Cerebellum atrophy is the shrinkage of the cerebellum. The cerebellum if the part of the brain located in the back of the head above the neck. The cerebellum is responsible for movement and has a direct impact on activities such as balance, speech, posture, walking and running. Gluten Ataxia is a relatively new discovery and thus not yet widely known to doctors and other medical professionals. This can make a diagnosis and proper treatment difficult to obtain. However, there are groups of researchers dedicated to spreading information abut this rare condition. As mentioned, it is a progressive condition, which means that symptoms may start off mild and almost unnoticed, and gradually progress to being debilitating. The symptoms of gluten ataxia are similar to symptoms of other ataxia conditions, which can make it tricky to get an accurate diagnosis. The symptoms appear in basic movements, such as walking or arm control, unsteady gait, difficulty walking, and loss of precise movement skills such as the ability to write or button a shirt. Parents should be on the lookout for ataxia symptoms in their kids. Children with celiac disease, specifically those in their early teens, would likely benefit from mental health evaluation. Strict adherence to the gluten-free diet does not mean you will never get gluten ataxia, especially for those who are not strict enough with their gluten-free diets. Some researchers have estimated that potentially up to 41 percent of all people with ataxia of unknown origin may have gluten ataxia. Other studies have indicated much lower numbers. A review of mental health studies indicated a prevalence of roughly 23 percent in patients with unexplained ataxia. In the last eight years or so the celiac community has finally been made aware of "gluten sensitivity" as a legitimate diagnosis. Twenty-five years ago you would not have heard of it, but now it has been given a rightful place along side of celiac disease and dermatitis herpetiformis. The same is true for gluten ataxia, its recent discovery will allow those who have it to say: "Finally, finally, someone is finally listening to me!" Read more at medicalnewstoday.com

Celiac.com 12/29/2018 - Imbalance and clumsiness may not be the most common symptom of the nervous system related to gluten intolerance but one of the most researched areas. Physicians use the term “ataxia” to describe poor coordination and balance. It can affect your walking and your ability to stand. While many systems contribute to your balance your cerebellum in the brain is the location that organizes all of the information and navigates your movements precisely. Some doctors claim that ataxia is one of the most common disorders produced by gluten in relationship to our nervous system. Poor coordination and clumsiness does occur with gluten intolerance and affects children as well as adults. Evidence suggests that this is all due to the immune system’s reaction to gluten itself. In people who are genetically at-risk for gluten sensitivity, gluten induces an immune attack against the protein gliadin and this antibody not only attacks gliadin in the gut but also attacks tissues far away from the intestines. In this case, through the bloodstream, these antibodies travel to the cerebellum and attack the Purkinje cells. As these cells become inflamed from the immune attack, the ability to integrate all the “balance information” is impaired, and coordination suffers. Symptoms like poor balance and coordination can result. A study in Britain examined 224 people with ataxia disorders. Some had an inherited disorder of ataxia, some had ataxia combined with other neurologic symptoms, and some simply had ataxia without known cause. Of those that were without known cause, 41 percent were found to have anti-gliadin antibodies supporting gluten sensitivity as a cause. In another study, ten patients with headaches and/or clumsiness were placed on a gluten-free diet. Over time, nine of the ten showed a beneficial response in all symptoms. The evidence is overwhelming. The presence of gluten antibodies, shrinkage of the cerebellum and the dramatic response to dietary change all support gluten as the cause.

Celiac.com 11/28/2018 - Patients with gluten ataxia without enteropathy have lower levels of antigliadin antibodies (AGA) compared to patients with celiac disease. Magnetic Resonance Spectroscopy (NAA/Cr area ratio) of the cerebellum improves in patients with gluten ataxia following a strict gluten-free diet, and is associated with an improvement in symptoms. A team of researchers recently set out to present their experience of the effect of a gluten-free diet in patients with ataxia and low levels of AGA antibodies measured by a commercial assay. The research team included Marios Hadjivassiliou, Richard A Grünewald, David S Sanders, Panagiotis Zis, Iain Croall, Priya D Shanmugarajah, Ptolemaios G Sarrigiannis, Nick Trott, Graeme Wild, and Nigel Hoggard. They are variously affiliated with the Academic Departments of Neurosciences and Neuroradiology; the Departments of Gastroenterology, the Departments of Dietetics; the Departments of Immunology, Sheffield Teaching Hospitals NHS Trust, in Sheffield, UK. The team conducted MR spectroscopy on 21 consecutive patients with ataxia and serum AGA levels below the positive cut-off for celiac disease, but above a re-defined cut-off in the context of gluten ataxia, at baseline and after a gluten-free diet. Of the 21 included patients with gluten ataxia, the team found that ten were on a strict gluten-free diet with elimination of AGA, 5 were on a gluten-free diet, but continued to have AGA, while 6 patients did not follow a gluten-free diet. The NAA/Cr area ratio from the cerebellar vermis increased in all patients on a strict gluten-free diet, increased in only 1 out of 5 patients on a gluten-free diet with persisting circulating AGA, and decreased in all patients who did not follow a gluten-free diet. From these results, the team concludes that patients with ataxia and low levels of AGA benefit from a strict gluten-free diet. The results suggest an urgent need to redefine the serological cut-off for circulating AGA in the diagnosis of gluten ataxia. Read more in Nutrients 2018, 10(10), 1444; doi:10.3390/nu10101444

Celiac.com 08/29/2018 - Up to one in twelve patients with gluten sensitivity develops neurological symptoms such as ataxia, dementia, seizures or peripheral neuropathy, though the reasons for this are still poorly understood. As a means of better understanding the immunological mechanisms behind this reality, a team of researchers recently reported the case of a 68‐year‐old male patient suffering from progressive ataxia and dementia associated with chronic diarrhea, and both elevated IgG and IgA antigliadin‐antibodies. The research team included Michel Mittelbronn, Jens Schittenhelm, Gellert Bakos, Rob A. De Vos, Manfred Wehrmann, Richard Meyermann, and Katrin Bürk. They are variously affiliated with the Institute of Brain Research at the University of Tübingen, and the Institute for Cell Biology, Department of Immunology at the University of Tübingen, Tübingen, Germany, the Neurological Institute/Edinger Institute, Goethe University Medical School, Frankfurt, the Department of Pathology, St. Georg Hospital, Leipzig, Germany, and with the Laboratory for Pathology, Enschede, the Netherlands. Autopsy indicated that frequent argyrophilic glial and neuronal inclusions within the basal nucleus of Meynert were the structural markers of the cognitive decline. The patient showed substantial neuronal loss in the cerebellar cortex and the inferior olives, along with infiltrating CD8+/perforin+/granzyme B+ cells, and reactive astrogliosis and microglial activation. In patients with gluten sensitivity and neurological disease, it is likely that CD8+ cytotoxic T and NK cells function as effector cells that trigger neuronal cell death, and thus might play some role in triggering cerebellar symptoms in gluten ataxia cases. The team concludes by noting that an absence of B‐ or plasma cells, along with multiple CD8+, granzyme B and perforin expressing cells in ataxia‐associated brain areas, indicates pronounced cytotoxic effects in neuro-pathogenesis of gluten sensitivity. This is one of the first reports to indicate that CD8+, perforin+, and granzyme B+ effector cells infiltrate the cerebellum and inferior olives in cases of gluten ataxia. Read more in: Neuropathology

Celiac.com 05/03/2018 - Time to spring into action and take control of your celiac disease and dermatitis herpetiformis! This means I have to "Scare you Silly" about not fully conforming to the gluten-free diet. Anemia, tiredness, and vitamin deficiency will continue to dog you if your gluten-free diet is non-compliant. You know those "just can't resist" items in your diet, the ones where the ingredient list does not actually say it is gluten-free, which may leave you open to cross-contamination that is common in the food industry? There is an estimated three million Americans with celiac disease, yet the vast majority still remain undiagnosed. The prevalence of celiac disease in Canada and the United States is growing, not diminishing! The high prevalence of celiac disease is also found in individuals with other disorders such as Type 1 diabetes, autoimmune thyroid disease and Down Syndrome. The prevalence of celiac disease in Type 1 diabetes around the world is 3 – 16%. According to Shelley Case, Author of Gluten-Free Diet: A Comprehensive Resource Guide: "Studies by Columbia University in New York and the Canadian Celiac Association revealed that adults suffer from the disease for an average of 10 - 12 years before being correctly diagnosed." The rare, but wise, physician who has diagnosed celiac disease correctly also sends the patient to be checked for diabetes and thyroid disease. Do you know what Gluten Ataxia is? Ataxia is a symptom in many conditions that affect the nervous system. Ataxia causes clumsiness or loss of balance and coordination that is not due to muscle weakness. Ataxia symptoms can be worrisome, and more so if you have been cheating on your celiac diet. Symptoms may vary but can include: Trouble using fingers, hands, arms and/or/legs Trouble speaking Trouble moving eyes Poor coordination and/or balance Tingling in extremities Gait problems Damage to the cerebellum (the part of the brain that controls coordination). Gluten ataxia is a rare immune-mediated disease in which the body's immune system attacks the nervous system as a reaction to the ingestion of gluten. It is a rare condition, but it can be related to celiac disease as well as non-celiac gluten sensitivity. Those with gluten ataxia often do not always have digestive issues or other symptoms. A strict gluten-free diet usually improves symptoms for those with gluten ataxia. Early diagnosis and treatment through the gluten-free diet can help stop progression and further cerebellum damage. People who have dermatitis herpetiformis know only too well what that gluten-containing doughnut or tart can do to their bodies. The DH sores are so itchy, and well, just sore, that prior to my first diagnosis I thought I had head lice and self-treated myself it on three separate occasions! Though DH is a miserable disorder to have, and the sores appear in the same places time and time again leaving scars, it at least leads to a faster diagnosis once a dermatologist sees the itchy sores, which often appear in bunches on your scalp, upper arms, shoulders and shins. While other people are watching television you are itching at sores in your head, picking off scabs, and in general feeling very miserable until the DH sores eventually heal. A biopsy of one of the lesions by that dermatologist can show dermatitis herpetiformis, but sometimes only after two or even three biopsies. The IgA deposits remain under the skin and that is why the DH sores keep coming back to the same place in your body. They are still there, and just come to the surface when you ingest gluten. Some with DH have to remain on dapsone for the rest of their lives. I have been on dapsone for over 30 years, even though I attempted on several occasions to stop taking it. To me it is a wonder drug, but one that I have to be careful not to abuse, because dapsone can cause anemia, and something similar to anorexia because when you ingest it regularly you do not feel hungry, and thus lose weight. To heavy people this may seem like the perfect weight loss program. Believe me, it isn't. It can also cause Methemaglobinemia which, when ingesting will prevent your arteries from functioning as an oxygen carrier and can seriously affect your body so that oxygenated blood does not reach your starved blood cells. You either carry a SAT Machine to measure the oxygen levels in your blood, or go to the Emergency Department where they can check your saturation levels. If below 90 they will admit you, run a battery of tests, and you may be put into a side room somewhere to get an infusion of Methane Blue to flush out your blood system, and you may need to have a blood transfusion. If you are away on holidays this can be a very serious condition where you are unaware you have Methemaglobinemia, except for a feeling of being out of breath, and NEED to get to hospital as soon as possible so your SAT levels can be monitored. Scaring you straight means not cheating day after day and then hoping a few dapsone will improve the condition. It won't—if you have passed the safe guideline of one pill daily. It is not simply a matter of taking dapsone in a 5 - 4- 3 - 2 - 1 as I was advised to do by an internist when I was first diagnosed with dermatitis herpetiformis. Ingestion over five days will no longer help you, and to my chagrin, can cause the condition to worsen. It is a serious condition; you can actually die from lack of oxygen in your blood! These few descriptions do not cover the fall out (of your hair) and the scarring of the sores on your legs and upper arms the Prednisone that they want to give you can cause a "roid rage" similar to what weight lifters have when they purposely ingest Prednisone to build up their muscles and become extremely irritable because of the Prednisone. ONE helpful clear lotion that I have to buy across the border in the U.S.A. is Scalpacin or Renewal, the latter being the generic name for Salicylic Acid (3%) which lessens the intense itching when applied directly to the sores (not to be ingested!). It says only 3% Salicylic Acid and I will confess that when I first "latched" onto this amazing "scalp itch and Dandruff relief liquid" I often applied twice daily to all the sores in my scalp and on my body. Did you know that approximately 3% of the general population in the U.S.A., according to Dr. Peter Green, have celiac disease? Once a patient develops one autoimmune condition the odds of developing another are greatly increased. Autoimmune disorders run in families, and different diseases may affect different parts of the body. A friend of our grandson was diagnosed as having celiac disease simply because she went to her doctor with complaints of a stomach ache. The doctor could have easily asked her if she had exams coming up, sent her for a blood test to rule out an appendicitis and left it at that, but he was a wise doctor who asked more questions and ordered the celiac blood tests. When that cameback positive he actually followed it up with a biopsy of the jejunum. She, as a teenager, was positive for celiac disease, but that doctor could have easily not ventured past the stomach ache at that first visit and gone no further with his investigations. Fortunately, vigilance paid off this time. He was thorough enough to refer her to a dietitian, but you know, she still cheats! I believe the reason she cheats is because she does not suffer from any of the symptoms of celiac disease right now, and does not have dermatitis herpetiformis. Amazing how vigilant you become with your diet when you break out in painful sores over 25% of your body, and experience diarrhea, stomach aches, nausea and vomiting! We never got into the other diseases she could possibly get from cheating on the gluten-free diet. Sjogren's Disease, Turner Syndrome, Type 1 diabetes, Williams Syndrome, Juvenile idiopathic arthritis, lactose intolerance, migraines, peripheral neuropathy, liver disease, are but a few of the disorders that can be connected to celiac disease. Have you ever looked up the symptomatology of these autoimmune diseases? Time you did! Did you know that there is a Celiac Disease Center at Columbia University which is one of the leading authorities for unexplained infertility issues, and that the prevalence of celiac disease in women with unexplained fertility is higher than the general population? Celiac disease may also be asymptomatic, meaning you show no symptoms at all. This is one of the reasons why it may be difficult for some people and their doctors to connect the dots between celiac disease and unexplained fertility. I worked with obstetrician/gynecologists for years and never found one that, when doing the laboratory testing, included a test for celiac disease, yet it is common knowledge now that a celiac disease screening should definitely be part of the work-up that is done for infertility issues. People of reproductive age spend an enormous amount of money, time and energy trying to become pregnant and carrying the baby to term. There are more women depressed because they cannot conceive or those that cannot bring a baby to term. Several studies over the past ten years have found a link between celiac disease, infertility and spontaneous abortion. It is not known yet whether the nutritional issues (malabsorption) that occurs with untreated celiac disease is the cause of the reproductive issues, or if the immune system may be to blame. Many doctors define infertility as the inability to get pregnant after one year of unprotected sex. In women, fertility difficulties often result from a problem with ovulation, while in men, infertility usually occurs because the man does not produce enough sperm or produces abnormal sperm. Note that undiagnosed or untreated celiac disease can lead to a host of seemingly unrelated problems, including osteoporosis, depression, and anemia. Medical researchers “along with some observant obstetrician/gynecologists are realizing that undiagnosed celiac disease may also be a cause of otherwise unexplained infertility in both men and women." A study undertaken in England, which has one of the world's largest celiac populations, indicates that fertility often returns after you start the gluten-free diet. There are many causes for infertility, but up to 30 percent of couples who are infertile will be told that no specific reason for their infertility can be found. When this happens a diagnosis of unexplained infertility is given. In recent years, awareness of celiac disease has increased. You may not be able to quote "Celiac Disease is a chronic autoimmune disorder", but it is a good sentence to spread around to those who ask you, "Do you follow the gluten-free diet because it is trendy or you want to lose weight"? As awareness for celiac disease has increased, some researchers have started looking at a possible like between celiac disease and unexplained infertility. Some of the known causes are: Low sperm count, - sperm with mobility or motility issues Enlarged veins in the scrotum called varicocele. Klinefelter syndrome, a genetic disorder. Although Klinefelter syndrome carries with it the risk testicular cancer, autoimmune diseases have been associated with this disorder, which is a chromosomal disorder. KS might increase the risk of some autoimmune diseases. It has been suggested that some autoimmune diseases may be more common in people with Klinefelter syndrome than in others, but the evidence so far is sparse. A research paper out of Oxford, England entitled "Associations between Klinefelter's Syndrome and Autoimmune Diseases” came to the conclusion that those with Klinefelter syndrome have increased risk of some autoimmune diseases. If you have the test for celiac disease, at least the blood test, and if your partner has the ultrasound done for it you can go into the obstetricians office with a list of questions, including family history, research you have undertaken yourself. I have seen so much heartache while nursing, watching a couple lose their baby prior to delivery, and those than cannot conceive but cannot afford invitro- fertilization. The damage that undiagnosed or untreated celiac disease can result in ongoing gastrointestinal symptoms such as vomiting, chronic diarrhea, stomach pain, and cramps. A number of these symptoms may also affect the reproductive system of women, for example: Delayed onset of menstruation Irregular periods No periods at all, known as amenorrhea Chronic pelvic pain And yes, endometriosis (where part or parts of the uterine lining attaches itself to the uterus and begins to grow) needs to be mentioned here. Many women who have this painful disease have been told that their only way of ridding themselves of this very painful disorder is to get a total hysterectomy. This is not always the case. There are now medications to help rid the uterus of endometriosis. Many obstetricians will perform a laparoscopy to determine the extent of the endometriosis, endeavour to lyse the adhesions from the wall of the uterus. Often this is all that is needed to ensure an introduction from the egg to the sperm and conception takes place. Other, more difficult cases can be referred to an infertility specialist, but be prepared for large costs. Many infertility specialists will tell you that if you can obtain a pregnancy while still struggling with endometriosis it often alleviates the problem. Did you know that men with celiac disease may have gonadal dysfunction, which could complicate fertility issues? (That was a big learning surprise for me!) This ultrasound test can be ordered by your family physician, a gonadal ultrasound to rule out a cystocele. Finding out that your husband has a cystocele is not Earth shattering—it involves a small corrective surgery. Did you know that Semen issues (specifically sperm morphology) found in men with celiac disease improved after following a gluten-free diet? Few studies have been conducted on celiac disease and male infertility. There is also a lack of scientific information and research studies on the potential link between non-celiac gluten sensitivity (NCGS), also commonly referred to as "gluten intolerance" and infertility. While research needs to be done, those with non-celiac gluten sensitivity are thought to possibly be at an increased risk of reproductive issues. However, the connection between NCGS and infertility is not yet known or proven. One case review did suggest that a strict gluten-free diet may improve fertility for those with NCGS. According to Healthline experts do not fully understand the effects of celiac disease on the reproductive system. The effects may be caused by malabsorption of nutrients, the impact it has on the immune system, or another currently unexplained reason. Some studies have noticed a link in untreated celiac disease in the mother and recurrent miscarriage, pre-term birth, and low birth weight. In a meta analysis that looked at studies on infertility and celiac disease, researchers noted that women with infertility were over three times more likely to have celiac disease than the control group. You have to admit that is a large number, and what upsets me is the fact that numerous obstetrician/gynecologists do not automatically send this part of the women's population for celiac disease screening. Yet women with unexplained infertility, were six times more likely to have celiac disease than women in the control group. Despite these studies, not all experts in the field are convinced about the connection. They state that more research is needed. BUT wouldn't you want to know that there is strong evidence that infertility and celiac disease are connected, and at least make your own decision with regards to getting tested? The tests undertaken by people with infertility are difficult to endure, are not only embarrassing but invasive. If celiac disease or gluten sensitivity runs in your family, or you suspect you have celiac disease, make a list of your symptoms. You'll want to discuss your concerns with your doctor and ask to be screened for celiac disease. A Reproductive Endocrinologist is who you would be referred to here in Canada, but you may have another title in the United States. If you are vigilante about eliminating gluten from your diet, you will stop the damage celiac disease is doing to your body. This may include lessening or eliminating the impact it may be having on your reproductive system. Sources: Celiac Disease A Hidden Epidemic, Dr. Peter H.R. Green American College of Obstetricians and Gynecologists (ACOG) Resource Center: http://www.acog.org American Society for Reproductive Medicine: http://www.asrm.org Healthline