Gluten-related disorders
[1][2] The umbrella category has also been referred to as gluten intolerance, though a multi-disciplinary physician-led study, based in part on the 2011 International Coeliac Disease Symposium, concluded that the use of this term should be avoided due to a lack of specificity.
[5] However, a 2020 study by the Leibniz-Institute for Food Systems Biology casts doubt on the idea that modern wheat has higher gluten levels.
[9] The population of people with gluten ataxia and other neurological conditions appears to have a different HLA distribution, in particular more HLA-DQ1, compared to most persons with celiac disease, who have HLA-DQ2 and HLA-DQ8.
[10] Coeliac disease (American English: celiac) (CD) is one of the most common chronic, immune-mediated disorders, triggered by the eating of gluten, a mixture of proteins found in wheat, barley, rye, and derivatives.
[11][12] Evidence has shown that this condition not only has an environmental component but a genetic one as well, due to strong associations of CD with the presence of HLA (Human leukocyte antigen) type II, specifically DQ2 and DQ8 alleles.
Added difficulties for diagnosis are the fact that serological markers (anti-tissue transglutaminase [TG2]) are not always present[15] and many people may have minor mucosal lesions, without atrophy of the intestinal villi.
[16] Diagnosis of CD should be based on a combination of person's familial history, genetics (i.e. presence of HLA DQ2/DQ8) serology and intestinal histology.
[17] CD affects approximately 1–2% of general population all over the world,[18] but most cases remain unrecognized, undiagnosed and untreated, and exposed to the risk of long-term complications.
[20] Untreated CD may result in the lack of absorption of nutrients, reduced quality of life, iron deficiency, osteoporosis, an increased risk of intestinal lymphomas and greater mortality.
[21] CD with "classic symptoms", which include gastrointestinal manifestations such as chronic diarrhea and bloating, malabsorption of certain vitamins and minerals, loss of appetite, impaired growth and even bone pain, is currently the least common presentation form of the disease and affects predominantly to small children generally younger than two years of age.
[14][19][20] CD with "non-classic symptoms" is the most common clinical found type[20] and occurs in older children (over two years old),[20] adolescents and adults.
[20] It is characterized by milder or even absent gastrointestinal symptoms and a wide spectrum of non-intestinal manifestations that can involve any organ of the body such as, cerebellar ataxia, hypertransaminasemia and peripheral neuropathy.
[17][23][24] With continuous mass genetic modification of grain crops, for instance for drought resistance and pest repellence, the occurrence of diagnosed CD had increased by 400% in the past 50 years alone.
[19] Dermatitis herpetiformis (DH), or Duhring-Brocq disease, is a chronic blistering skin autoimmune condition, characterized by the presence of skin lesions that have an extensive and symmetrical distribution, predominating in areas of greater friction, and affecting mainly both elbows, knees, buttocks, ankles, and may also affect the scalp and other parts of the body, and non-symmetrical occasionally.
DH may be confused with many different cutaneous lesions, such as atopic dermatitis, eczema, urticaria, scabies, impetigo, polymorphic erythema and other autoimmune blistering diseases.
[2] With gluten ataxia, damage takes place in the cerebellum, the balance center of the brain that controls coordination and complex movements like walking, speaking and swallowing, with loss of Purkinje cells.
The effectiveness of the treatment depends on the elapsed time from the onset of the ataxia until diagnosis, because the death of neurons in the cerebellum as a result of gluten exposure is irreversible.
[33][36] Extra-intestinal symptoms, which can be the only manifestation of NCGS even in absence of gastrointestinal symptoms, may be any of the following: headache or migraine, "foggy mind", fatigue,[33][36][37] fibromyalgia,[37][38][39] joint and muscle pain,[33][36][37] leg or arm numbness,[33][36][37] tingling of the extremities,[33][36] dermatitis (eczema or skin rash),[33][36] atopic disorders,[33] allergy to one or more inhalants, foods or metals[33][37] (such as mites, graminaceae, parietaria, cat or dog hair, shellfish, or nickel),[37] depression,[33][36][37] anxiety,[37] anemia,[33][36] iron-deficiency anemia, folate deficiency, asthma, rhinitis, eating disorders,[37] or autoimmune diseases.
[33] In a review of May 2015 published in Gastroenterology, Fasano et al. conclude that ATIs may be the inducers of innate immunity in people with coeliac disease or NCGS.
[41][42][33] As occurs in people with coeliac disease, the treatment is a gluten-free diet (GFD) strict and maintained, without making any dietary transgression.
[52] Sensitivity may also present with extraintestinal symptoms, including headache, "brain fog", tingling and/or numbness in hands and feet, fatigue, as well as muscular disturbances and bone or joint pain;[53][54][55] also neuropsychiatric manifestations ("gluten-sensitive idiopathic neuropathies") have been reported on.
There is evidence that not only gliadin (the main cytotoxic antigen of gluten), but also other proteins named ATIs which are present in gluten-containing cereals (wheat, rye, barley, and their derivatives) may have a role in the development of symptoms.
[33][41] FODMAPs, especially fructans, are present in small amounts in gluten-containing grains and have been identified as a possible cause of some gastrointestinal symptoms in persons with NCGS.
[65] Celiac disease (CD) and NCGS are closely linked with human leukocyte antigen (HLA) class II genes, HLA-DQ2 and HLA-DQ8, located on chromosome 6p21.
[2] A literature review of 2014 found that non-coeliac gluten sensitivity diagnosis can be reached only by excluding celiac disease (CD) and wheat allergy.
[70] Knowledge of hidden sources of gluten is important for people with celiac disease as they need to be very strict regarding eating only gluten-free food.
The implementing regulation also clarifies how consumers are to be informed of the difference between foods that are naturally free of gluten and products that are specially formulated for gluten-intolerant persons.
[17][44] In a 2015 double-blind placebo cross-over trial, small amounts of purified wheat gluten triggered gastrointestinal symptoms (such as abdominal bloating and pain) and extra-intestinal manifestations (such as foggy mind, depression and aphthous stomatitis) in self-reported NCGS.
[44] A 2016 review of the recent research advancements in understanding diet's role in attenuating IBS patient's symptoms concluded that gluten was a common trigger.
[41][42] Although the differences between the three interventions was very small, the authors concluded that fructans (the specific type of FODMAP found in wheat) are more likely to be the cause of NCGS gastrointestinal symptoms, rather than gluten.
