study of myasthenics revealed that 1 in 23 had high levels of anti-transglutaminase. peripheral neuropathies peripheral neuropathies are greatly increased in people who have gse. in clinical cd there is an obvious reason; avitaminosis and the inability to adsorb essential fatty acids and vitamins can lead to nervous system problems, including sensitivity of the peripheral nervous system. in addition to these problems there are a number or rare autoimmune conditions, secondary autoimmunities, such as fibromyalgia that are more frequent in gse than in the normal population. gulliane-barre syndrome is associated with peripheral neuropathies, and it has been found that anti-ganglioside autoantibodies take part in the binding to axons and schwann cells. antibodies to these gangliosides have been found elevated in coeliac disease ataxia a sizable fraction of individuals who have gluten ataxia have signs of gse (either cd or elevated intraepitheal lymphocytes) and ataxia is a common symptom in gse. studies of clinically undefinable ataxia generally had higher proportion of late onset gait ataxia, mild upper limb symptoms, and evidence of peripheral neuropathy, questions were raised about the specificity of testing and false positives. patients with ataxia and cd have antibodies that react with purkinje fibers but is restricted to the anti-gliadin iga/igg. a recent swedish study of 14,000 registered coeliacs showed no association of gse with ataxia. dementia and epilepsy epilepsy has been noticed in a sampling of coeliac disease patients. one prime example is calcium channel obstruction in the brain and dementia. there is a growing body of evidence suggesting that subclinical cases in older adults will typically progress toward dementia, a large number of studies in italy and spain have documented earlier onset cases, though the autoimmune condition is not known, folic acid malabsorption may be the cause. visual and auditory disturbances according to recent studies, calcifications of channels seen in dementia can also occur in specific brain areas such as the visual complex in the occipital lobe. such calcium channel blockages can cause visual problems or partial field hallucinations (paroxysmal visual manifestations). other papers show a link between migraine, visual aura and cerebral calcifications. disturbances may be followed by convulsions and associated with gastrointestinal phenomena. white matter lesions ten (of 75) young patients had neurologic findings such as febrile seizures, single generalized seizures, mild ataxia, and muscular hypotonia with retarded motor development, but magnetic resonance imaging detected unilateral and bilateral t2-hyperintensive white-matter lesions in 15 patients (20%) depression depression in gse has several causes; in the more severe cd, depression can be the result of lower vitamin adsorption and essential fatty acid adsorption (see section on autism). depression and anger may also be the result of lower quality of life issues as a result of gluten-free diet. depression appears to persist on gluten free diet in a sizable fraction of gse. elevated anger has been noted also with gse. anxiety anxiety is a common feature of gse; treatment on a gluten-free diet is effective at reducing anxiety, some aspect of which may be due to malabsorption phenomena and cytokine activity (i.e. constant stress). fibromyalgia fibromyalgia was found in 9% of adult patients relative to 0.03% in the general population with a link common to ibd. concurrent ibs is found in 30% to 70%. small intestinal bacterial overgrowth is associated is common with a transient response to antimicrobial therapy. chronic fatigue chronic fatigue associated with gse is a systemic disorder, however there are neurological components that are especially manifest in blood deficiencies like avitaminosis, amineralosis and anemia. reduced iron and the lack of vitamins folate, b6, b12 and malabsorption of essential fatty acids can cause depression and chronic fatigue. anti-gliadin antibodies correlate with higher risk for chronic-fatique when no clinical finding of cd is present. while fatigue is reduced on gluten-free diet, bouts of depression can become worse. connective tissue disorders arthritis some instance of arthritis with small bowel villous atrophy have been found to resolve on gluten free diet, and anti-connective tissue antibodies have been found in increased levels in coeliac disease. anti-rheumatoid factor antibodies are also increased. in addition, cross-reactive anti-beef-collagen antibodies (igg) may explain some rheumatoid arthritis (ra) incidences. although the presence of anti-beef collagen antibodies does not necessarily lead to ra, the ra association with triticeae consumption is secondary to gse and involves drb1*0401/4 linkages to dq8 and is debatable. in one instance rheumatoid arthritis was tied directly to refractory disease. still's disease still's disease (aosd) is a rheumatic disorder of unknown etiology characterized by a triad of fever, polyarthritis and evanescent rash. an idiopathic case has been reported with coeliac disease. myositis some myopathies may be the indirect result of malabsorption of fat soluble vitamins such as vitamin e. dermatomyositis dermatomyositis is associated with cd in children and more recently established in adults. gsea nephritis coeliac disease is associated with immune complex glomerulonephritis. anti-gliadin iga antibodies are found also more commonly in patients with iga nephropathy. the paper finds a link between gse and iga nephropathy, but not between cd and nephropathy. calcium oxalate correlates with severity of fat malabsorption in coeliac disease. precancerous states cd is associated with two grades of disease linked precancerous states. this condition is known as refractory coeliac disease (rcd), defined as malabsorption due to gluten-related enteropathy (villous atrophy or elevated intraepitheal lymphocytes) after initial or subsequent failure of a strict gluten-free diet (usually 1 year) and after exclusion of any disorder mimicking coeliac disease. rcd 1 involves precancerous tissues in which transformed t-cells continue to produce a response even though gluten is no longer present. some rcd1 patients have been treated successfully with immunosuppressants (azathioprine, prednisone) when caught early. elemental diet (proteins digested to amino acids) seems to be an effective alternative diet, indicating other proteins are stimulating the iel. 5 year viability is high when treated. dq representation is similar to non-rcd coeliacs. rcd 2 involves neoplastic tissues that the lack of surface expression of usual t-cell markers. increased expression of: intracytoplasmic cd3e, surface cd103 decreased expression of: cd8, cd4, tcr-alpha/beta clonal t-cell expansion in rcd2 is not manageable with steroids (see: rcd 1) and sometimes manageable with chemotherapeutic drugs, however, more aggressive therapies seem more affective. a high percentage of rcd 2 patients spontaneously develop lymphoma (eatl), the 5 year survival rate is markedly lower than rcd1 but higher than lymphoma. dq2.5/dq2 individuals are more frequently found. causes of rcd. coeliac disease age at cd/gse diagnosis – most people are over the age of 50 when first diagnosed at rcd dietary noncompliance – some eatl appears years after diagnosis with non-gf diets. length of latency – the length of time, often unknown in which the person is gse+. severity – the severity of the microscopic destruction appears to be a factor, and genetics appears now to play a role. genetics – for rcd 2 and eatl, genetics plays large role dq2.5/dq2+ individuals are over-represented in the patient set cancers gse, particularly coeliac disease, increases the risk of cancers of specific types. there are two predominant cancers associated with coeliac disease, cancer of the esophagus and lymphoproliferative diseases such as gluten-sensitive enteropathy-associated t-cell lymphoma (eatl). for non-eatl cancers it is thought the mineralemias such as zinc and selenium may play a role in increasing risk. gse associated cancers are invariably associated with advanced coeliac disease, however, in de-novo eatl, the cancer is frequently detected in advance of the coeliac diagnosis, also eatl is the most common neoplasm. esophageal cancer squamous carcinoma of the esophagus is more prevalent in coeliac disease. the increased prevalence may be secondary to gerd that results from chronic delayed gastric emptying. other studies implicate the malabsorption of vitamin a and zinc as a result of multi-vitamin and mineral deficiencies seen in coeliac disease. adenocarcinoma adenocarcinoma of the bowel has been associated with coeliac disease.