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Gluten Related Disorders

Gluten related disorder is a disease created by reaction of body when cereal gluten proteins, glutenin & gliadin (especially gliadin), are ingested. They are classified as autoimmune, allergic or mal-digestive (non-autoimmune, non-allergic). Even though reactive mechanisms in gluten related disorders are different, symptoms are so similar that they can be easily confused with each other. These symptoms are also common with symptoms of Irritable Bowel Syndrome (IBS). Although it is not a gluten related disorder, some researches indicate that gluten free diet can improve IBS symptoms in around half of people studied. This is important because about 10% to 15% of population suffers IBS, and number of women having IBS is twice of men with IBS.

Very Common Symptoms of Gluten Related Disorders and IBS; Karın ağrısı, şişkinlik, kendini kötü hissetme, yorgunluk

Common Symptoms; of Gluten Related Disorders and IBS: diarrhea, epigastric pain, nausea, aerophagia, gastroesophageal reflux, aphthous stomatitis, alternating bowel habits, constipation, headache, migraine, gluten related peripheral neuropathy, anxiety, foggy mind, numbness, joint or muscle pain, skin rash.

Gluten Related Autoimmune Disorders

Autoimmune disease happens when the body’s natural defense system can’t tell the difference between your own cells and foreign cells, causing the body to mistakenly attack normal cells.

Celiac Disease

In a person with celiac disease, exposure to gluten causes inflammation in the gut. Repeated exposure gradually damages the small intestine, which can lead to problems absorbing minerals and nutrients from food. Inflammation starts after digestion of gluten.  Gluten peptides are deaminated by the tissue-transglutaminase (tTG) enzyme and presented to activated T cells, which then produce interferon-gamma and other cytokines, leading to mucosal damage of the small bowel.

Celiac disease has been known for more than 2,000 years and it was already in the middle of the 20th century that its relationship with gluten intake was established. People with celiac disease constitute about 1% of overall population. The symptoms of celiac disease can range from mild to severe. They can change over time, and they vary from person to person. Some people have no symptoms or only experience them later in life. A person may not know that they have celiac disease until they develop a nutrient deficiency or anemia.

People with celiac disease may develop nutrient deficiencies as damage to the gut gradually limits the absorption of nutrients such as vitamins B12, D, and K. For the same reason, a person may also develop iron deficiency anemia. Beyond malnutrition, celiac disease can also cause damage to the large intestine and more subtle damage to other organs.

Sources

Catalina Ortiz, Romina Valenzuela, Yalda Lucero, Celiac disease, non-celiac gluten sensitivity and wheat allergy: comparison of 3 different diseases triggered by the same food, Revista chilena de pediatría vol.88 no.3 Santiago jun. 2017, doi: http://dx.doi.org/10.4067/S0370-41062017000300017

Celiac disease. https://www.niddk.nih.gov/health-information/digestive-diseases/celiac-disease

Celiac disease and cancer. https://www.beyondceliac.org/celiac-disease/related-conditions/cancer/

Definition & facts for celiac disease. https://www.niddk.nih.gov/health-information/digestive-diseases/celiac-disease/definition-facts

Future therapies for celiac disease. https://celiac.org/about-celiac-disease/future-therapies-for-celiac-disease/

Gluten and food labeling. https://www.fda.gov/food/nutrition-education-resources-materials/gluten-and-food-labeling

Posner, E. B., et al.Celiac disease. https://www.ncbi.nlm.nih.gov/books/NBK441900/

Refractory celiac disease. https://rarediseases.org/rare-diseases/refractory-celiac-disease/

Symptoms of celiac disease. http://www.cureceliacdisease.org/symptoms/

What is celiac disease? https://celiac.org/about-celiac-disease/what-is-celiac-disease/

Dermatitis Herpetiformis (Dühring’s Disease)

Dermatitis herpetiformis (sometimes known as DH, Duhring’s disease, the gluten rash or the celiac rash), is a long-term (chronic) skin condition that causes itchy bumps and blisters. The direct cause of dermatitis herpetiformis is a sensitivity to gluten. Of those diagnosed with celiac disease, 10% to 25% also have dermatitis herpetiformis. But, dermatitis herpetiformis patients usually don’t have the digestive symptoms that go along with celiac disease.

Almost all patients with dermatitis herpetiformis have celiac disease, though the disease is asymptomatic (they have no gastrointestinal symptoms). Dermatitis herpetiformis is sometimes called the skin manifestation of celiac disease.

In the word “dermatitis,” “derm” means “skin” and “itis” means “inflammation.” The word as a whole means “inflammation of the skin.” The word “herpetiformis” is used because the blisters and bumps look like herpes lesions. However dermatitis herpetiformis is not caused by the herpes virus. The only connection it has to the herpes virus is sharing its name and the way it looks.

Dermatitis herpetiformis is most common in people of northern European heritage. One statistic states that up to 75 per 100,000 people in northern Europe have it. Dermatitis herpetiformis affects 10% to 25% of celiac disease patients.

Dermatitis herpetiformis looks like a cluster of itchy bumps that can be easily confused with acne or eczema. Blisters can also form, and you could be misdiagnosed with herpes. Dermatitis herpetiformis commonly occurs on the: knees, elbows, buttocks, hairline.

Dermatitis herpetiformis looks like a cluster of itchy bumps that can be easily confused with acne or eczema. Blisters can also form, and you could be misdiagnosed with herpes. Dermatitis herpetiformis commonly occurs on the: knees, elbows, buttocks, hairline.

Sources

Celiac Disease Foundation. Dermatitis Herpetiformis. (https://celiac.org/about-celiac-disease/related-conditions/dermatitis-herpetiformis/) Accessed 11/9/2021.

NORD: National Organization for Rare Disorders. Dermatitis Herpetiformis. (https://rarediseases.org/rare-diseases/dermatitis-herpetiformis/) Accessed 11/9/2021.

Beyond Celiac. Dermatitis Herpetiformis. (https://www.beyondceliac.org/celiac-disease/related-conditions/dermatitis-herpetiformis/) Accessed 11/9/2021.

Beyond Celiac. Dermatitis Herpetiformis and Celiac Disease. (https://qa.beyondceliac.org/celiac-disease/related-conditions/dermatitis-herpetiformis/) Accessed 11/9/2021.

NIH: National Institute of Diabetes and Digestive and Kidney Diseases. Dermatitis Herpetiformis. (https://www.niddk.nih.gov/health-information/professionals/clinical-tools-patient-management/digestive-diseases/dermatitis-herpetiformis?dkrd=hisce0127) Accessed 11/9/2021.

DermNet NZ. Dermatitis Herpetiformis. (https://www.dermnetnz.org/topics/dermatitis-herpetiformis/) Accessed 11/9/2021.

Merck Manual. Dermatitis Herpetiformis. (https://www.merckmanuals.com/professional/dermatologic-disorders/bullous-diseases/dermatitis-herpetiformis) Accessed 11/9/2021.

NCBI. Dermatitis Herpetiformis. (https://www.ncbi.nlm.nih.gov/books/NBK493163/) Accessed 11/9/2021.

Imaware. Celiac Disease and Hair Loss. (https://www.imaware.health/blog/celiac-disease-and-hair-loss#toc-can-intestinal-problems-cause-hair-loss-) Accessed 11/9/2021.

Celiac Disease Foundation. Gluten-Free Foods. (https://celiac.org/gluten-free-living/gluten-free-foods/) Accessed 11/9/2021

Gluten Ataxia

Gluten ataxia is a rare neurological condition in which an autoimmune response to the gluten protein can irreversibly damage the part of the brain called the cerebellum. This can potentially cause problems with gait and gross motor skills, resulting in loss of coordination. In some cases of gluten ataxia, this loss resulting may become significant. 

Patients with gluten ataxia, the antibodies their body produce in response to gluten ingestion mistakenly attack their cerebellum, the part of your brain responsible for balance, motor control, and muscle tone.

Gluten ataxia symptoms are indistinguishable from symptoms of other forms of ataxia. For gluten ataxia, the symptoms may start out as mild balance problems. For example, patients may be unsteady on their feet or have trouble moving your legs.  As symptoms progress, some people say they walk or even talk as if they’re drunk. As the autoimmune damage to the cerebellum worsens, the eyes likely will become involved, potentially moving back and forth rapidly and involuntarily.

The resulting problems in balance and motor control eventually are irreversible due to brain damage. Up to 60% of patients with gluten ataxia have evidence of cerebellar atrophy—literally, shrinkage of that part of the brain—when examined with magnetic resonance imaging (MRI) technology. In some people, an MRI also will reveal bright white spots on the brain that indicate damage.

If you’re diagnosed with gluten ataxia, you need to follow a very strict gluten-free diet. The neurological symptoms spurred by gluten ingestion seem to take longer to improve than the gastrointestinal symptoms, and seem to be more sensitive to lower amounts of trace gluten in your diet.

Sources

Hadjivassiliou M, Davies-jones GA, Sanders DS, Grünewald RA. Dietary treatment of gluten ataxia. J Neurol Neurosurg Psychiatry. 2003;74(9):1221-4. doi:10.1136/jnnp.74.9.1221

Hadjivassiliou M, Grünewald R, Sharrack B, et al. Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics. Brain. 2003;126(Pt 3):685-91. doi:10.1093/brain/awg050

Hadjivassiliou M, Sanders DS, Woodroofe N, Williamson C, Grünewald RA. Gluten ataxia. Cerebellum. 2008;7(3):494-8. doi: 10.1007/s12311-008-0052-x

Hadjivassiliou M, Sanders DD, Aeschlimann DP. Gluten-related disorders: gluten ataxia. Dig Dis. 2015;33(2):264-8. doi:10.1159/000369509

Khwaja GA, Bohra V, Duggal A, Ghuge VV, Chaudhary N. Gluten sensitivity – a potentially reversible cause of progressive cerebellar ataxia and myoclonus – a case report. J Clin Diagn Res. 2015;9(11):OD07-OD8. doi:10.7860/JCDR/2015/13299.6743

Freeman HJ. Neurological disorders in adult celiac disease. Can J Gastroenterol. 2008;22(11):909–911. doi:10.1155/2008/824631

Mal-Digestive (Non-Autoimmune, Non-Allergic) Gluten Related Disorders

Non Celiac Gluten Sensitivity (NCGS)

Non-coeliac gluten sensitivity (NCGS) is a condition where intestinal and extra-intestinal symptoms are triggered by gluten ingestion in the absence of coeliac disease and wheat allergy, as defined by discussions held at three different international consensus conferences. The symptoms occur soon after gluten ingestion, improving or disappearing within hours or a few days after gluten withdrawal and then relapsing following its reintroduction. Even though pathogenic mechanisms in NCGS are still not known, it is probably caused by the disturbances in the innate immune response to gluten.

Although NCGS has been suggested to be the most common gluten-related disorder, its prevalence remains unknown because of a lack of diagnostic markers. According to self-reported data, the prevalence rate of NCGS ranges between 0.5% and 13% in the general population, and prevalence is higher in women, teenagers, and patients in the third to fourth decade of life.

Symptoms of NCGS are abdominal pains (68%), diarrhea (33%), cutaneous (40%), headache (35%), bone and joint pain (11%), muscle contractions (34%), numbness of hands and feet (20%), chronic tiredness (33%), anemia (20%), depression (22%).

Since symptoms of NCGS overlap with symptoms of celiac disease, wheat allergy and even irritable bowel syndrome (IBS), diagnosis of NCGS is difficult. First of all, patients should be diagnosed as not having celiac disease, wheat allergy and even irritable bowel syndrome (IBS). After exclusion of other possibilities, several criteria should be checked for probable diagnosis such as types of antibodies in serum and situation of duodenal villi. Half of NCGS patients have Immunoglobulin G Antigliadin Antibodies (IgG-AGA) and none of patients has atrophy of duodenal villi (typical in celiac disease).

Half of NCGS patients have Immunoglobulin G Antigliadin Antibodies (IgG-AGA) and none of patients has atrophy of duodenal villi (typical in celiac disease).

Sources

Grazyna Czaja-Bulsa, Non coeliac gluten sensitivity – A new disease with gluten intolerance, Clinical Nutrition 34 (2015) 189e194, doi: https://doi.org/10.1016/j.clnu.2014.08.012

Anna Roszkowska, Marta Pawlicka, Anna Mroczek, Kamil Bałabuszek and Barbara Nieradko-Iwanicka, Non-Celiac Gluten Sensitivity: A Review, Medicina 2019, 55(6), 222; https://doi.org/10.3390/medicina55060222

Catalina Ortiz, Romina Valenzuela, Yalda Lucero, Celiac disease, non-celiac gluten sensitivity and wheat allergy: comparison of 3 different diseases triggered by the same food, Revista chilena de pediatría vol.88 no.3 Santiago jun. 2017, doi: http://dx.doi.org/10.4067/S0370-41062017000300017

Gluten Related Allergic Disorders

Allergic disorders are classified into 2 subgroups: Non-IgE (Immunoglobulin E) -mediated Wheat Allergies and IgE (Immunoglobulin E)-mediated Wheat Allergies. 

Immunoglobulin E (IgE) is a type of antibody that has been found only in mammals. IgE is synthesized by plasma cells. IgE is thought to be an important part of the immune response against infection by certain parasitic worms. IgE is also utilized during immune defense against certain protozoan parasites IgE may have evolved as a defense to protect against venoms.

Non-IgE (Immunoglobulin E) -Mediated Wheat Allergies

Non-IgE mediated food allergies are caused by a reaction involving other components of the immune system apart from IgE antibodies. The reactions do not appear immediately after the ingestion of the food and usually relate to reactions in the gastrointestinal tract such as vomiting, bloating and diarrhea.

Wheat can cause a non-IgE mediated allergic disorder by inducing a Th2 lymphocytic response largely independent from IgE-specific antibodies to wheat (non-IgE mediated inflammation). The vast majority of these responses are characterized by an eosinophilic infiltration in the gastrointestinal (GI) tract, and are called eosinophilic gastrointestinal diseases (EGIDs). Eosinophils are leukocyte in which their cytoplasm granules can be stained as red color with eosin dye. In normal individuals, eosinophils make up about 1–3% of white blood cells. Number of eosinophils increases in two situations: parasitic disorders and Type I hypersensitivity reactions (allergy). Increase in number of blood eosinophils is called eosinophilic 

The types of eosinophilic gastrointestinal diseases that are mainly triggered by wheat are Eosinophilic Esophagitis (EoE) and  Eosinophilic Gastritis (EG). EoE is the most common type of EGID, with an incidence rate estimated to be similar to Crohn’s disease. EoE is a food allergy driven atopic disease characterized by Th2 inflammation and limited to the esophagus. Esophageal epithelial cell dysfunction is likely to start the inflammatory process in genetically predisposed individuals.

EG is a rare disease that is associated with severe symptoms which needs prompt treatment with oral steroids followed by an elimination diet in an attempt to maintain such remission. EG is a different disease than EoE being more systemic and is associated with high levels of blood/GI eosinophilia and Th2 immunity.

Source

Antonella Cianferoni, Wheat allergy: diagnosis and management, Journal of Asthma and Allergy (2016), doi: https://doi.org/10.2147/JAA.S81550

IgE (Immunoglobulin E)-Mediated Wheat Allergies

These are the allergies that Immunoglobulin E (IgE) antibodies have significant role as immune response to wheat proteins (gluten). IgE mediated allergies can be divided into 3 subgroups according to part of body affected: Wheat Dependent Exercise Induced Anaphylaxis (WDEIA), Baker’s Asthma and Contact Dermatitis.

Wheat Dependent Exercise Induced Anaphylaxis (WDEIA)

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a rare but potentially severe food allergy characterized by anaphylactic reactions that range from urticaria to respiratory, gastrointestinal or cardiovascular symptoms that occur 1 to 4 hours after the ingestion of wheat, followed by physical exercise. Wheat allergens (especially omega-5 gliadin) play an important role in the elicitation of WDEIA. Cofactors such as aspirin, alcohol intake, infections, stress can substitute for or synergize with exercise to instigate the immediate-type hypersensitivity reaction after the ingestion of wheat.

Source

Zhu Rongfei, Li Wenjing, Huang Nan, Liu Guanghui, Wheat – Dependent Exercise-Induced Anaphylaxis Occurred With a Delayed Onset of 10 to 24 hours After Wheat Ingestion:A Case Report, Allergy Asthma Immunol Res. 2014 July;6(4):370-372, doi: http://dx.doi.org/10.4168/aair.2014.6.4.370

Baker’s Asthma and Rhinitis

Baker’s Asthma and Rhinitis are respiratory allergies in which they are allergic responses secondary to inhalation of wheat and cereal flours. Baker’s Asthma is one of the most prevalent occupational allergies in many countries.

Respiratory IgE mediated allergies to wheat are represented by baker’s asthma or rhinitis, and are often associated as occupational diseases. Baker’s Asthma is one of the most prevalent occupational allergies in many countries. The incidence of bakers’ asthma range from 1%–10% of bakers, and the incidence of rhinitis range from 18%–29%. Respiratory IgE mediated allergies tend to be more frequent in atopic subjects who are exposed to high levels of wheat allergens for several hours per day. The majority of affected individuals did not suffer from asthma before developing the occupational disease.

The classic clinical picture occurs minutes after antigenic exposure, when mast cells and basophils bound to IgE recognize the antigen and are activated, releasing powerful vasoactive compounds such as histamine, which account for the symptomatology characteristic of type 1 hypersensitivity responses (immediate reaction).

Source

Zana L. Lummus, PhD, Adam V. Wisnewski, PhD, and David I. Bernstein, MD, Pathogenesis and Disease Mechanisms of Occupational Asthma, Immunol Allergy Clin North Am. 2011 November ; 31(4): 699–vi. doi:10.1016/j.iac.2011.07.008

Antonella Cianferoni, Wheat allergy: diagnosis and management, Journal of Asthma and Allergy (2016), doi: https://doi.org/10.2147/JAA.S81550

Contact Dermatitis

Contact dermatitis is a type of eczema triggered by contact with a particular substance. Eczema is the name for a group of conditions that cause skin to become dry and irritated. Contact dermatitis usually improves or clears up completely if the substance causing the problem is identified and avoided. Treatments are also available to help ease the symptoms.

Contact dermatitis causes the skin to become itchy, blistered, dry and cracked. Lighter skin can become red, and darker skin can become dark brown, purple or grey. This reaction usually occurs within a few hours or days of exposure to an irritant or allergen. Symptoms can affect any part of the body but most commonly the hands and face

Source

Contact dermatitis, NHS, https://www.nhs.uk/conditions/contact-dermatitis/

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