Gluten-related disorders (GRDs) are characterized by abnormal immunological responsiveness to ingested gluten in genetically susceptible individuals. Gluten proteins are present in wheat, barley, and rye. GRDs are heterogeneous, reflecting their autoimmune, allergic, and non-autoimmune-allergic etiology.
The most common general symptoms of GRDs include bloating, abdominal pain, constipation, diarrhea, headache, tingling and numbness in hands and feet, fatigue and joint pain.
Celiac disease (CD), dermatitis herpetiformis (DH), gluten ataxia (GA), wheat allergy (WA), and non-celiac gluten sensitivity (NCGS) are the five major GRDs that present with a wide range of clinical manifestations.
Celiac disease
Celiac disease (CD) is the most prominent autoimmune gluten-related disorder. The ingestion of gluten in genetically predisposed individuals carrying HLA type Ⅱ DQ2/DQ8 alleles can arouse a T-cell mediated immune reaction against tissue transglutaminase, an enzyme of the extracellular matrix, leading to mucosal damage and eventually to intestinal villous atrophy.
When celiac disease patients follow a gluten-free diet, the normal architecture of the intestinal villi is restored and the skin lesions heal.
Dermatitis herpetiformis
Dermatitis herpetiformis (DH), also known as Duhring disease, is the cutaneous counterpart of CD (“skin CD”).
Dermatitis Herpetiformis (DH) is a chronic, autoimmune, and recurrent cutaneous-intestinal disorder identified in genetically susceptible individuals, which is often associated with celiac disease. Anti tTG (anti-tissue transglutaminase) antibodies that are produced in response to gluten exposure can also recognize epidermal transglutaminase (ETG).
Gluten ataxia
Gluten ataxia (GA) is a form of cerebellar ataxia, affecting mainly Purkinje cells, and is caused by antibodies released when digesting gluten that mistakenly attacks part of the brain in individuals that are sensitive and genetically susceptible.
Wheat allergy
An IgE and non-IgE mediated immune response characterize wheat allergy (WA), resulting in an allergic reaction in some individuals upon contact, inhalation, or uptake of foods containing wheat but not necessarily other grains as barley or rye.
Wheat allergy is classified into occupational asthma (baker’s asthma) and rhinitis; food allergy (FA), affecting the skin, the gastrointestinal tract or the respiratory tract; wheatdependent exercise-induced anaphylaxis (WDEIA) and contact urticaria. Ingested wheat can cause IgEmediated wheat allergies in both children and adults.
Non-celiac gluten sensitivity
Non-celiac wheat/gluten sensitivity (NCWGS) makes people experience symptoms similar to CD and WA. However, patients with NCWGS do not have specific IgE against wheat proteins or IgA anti-TG2 autoantibodies.
Gluten related disorders
