User:Puffysphere/Non-classical food allergies

A food allergy is defined as an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food. Food allergy may be IgE or non-IgE mediated. This article is about food allergies that have only recently been scientifically established. These include:


 * Food protein-induced enterocolitis syndrome (FPIES)
 * Food protein induced proctocolitis syndrome
 * Food protein induced enteropathy syndrome, etc.
 * Non-celiac gluten sensitivity (NCGS) syndrome

Symptoms
NCGS symptoms include both gastrointestinal and non-intestinal symptoms, occurring within a few hours or days of gluten ingestion. Gastrointestinal symptoms include abdominal pain and bloating, diarrhea, constipation. Non-intestinal symptoms include mental confusion or a ‘foggy mind’, fatigue, skin rash, headache, joint and muscle pain, leg or arm numbness, depression and anxiety, and anemia.

Gluten sensitivity may also have neurological and psychiatric symptoms. Gluten can cause ataxia, likely because antibodies to gluten attack the Purkinje cells in the cerebellum. Gluten ataxia may slowly improve with a gluten-free diet.

Epidemiology
The prevalence of non-IgE mediated food allergy is unknown. However, non-IgE mediated food allergy is thought to be more common than IgE mediated food allergy. The prevalence of non-celiac gluten sensitivity is also unknown, but it may be estimated at 6%, since about 20% of people in Northern Europe have irritable bowel syndrome, and in studies, about 30% of people with irritable bowel syndrome have have non-celiac gluten sensitivity.

Diagnosis
There are no definitive lab tests for non-classical food allergies. The gold standard for diagnosis is:
 * First, rule out classical IgE-mediated allergies by skin or blood allergy testing;
 * Rule out celiac disease with blood tests or small intestinal biopsy, if gluten sensitivity is suspected;
 * Stop eating the food(s) in question for at least two weeks;
 * Do [//files.sld.cu/alergenos/files/2012/12/dbpc-oral-food-challenge-practall-consensus2.pdf double-blind placebo-controlled (DBPC) challenges] with the food(s).

Diagnosis of non-celiac gluten sensitivity (NCGS) is similar. In a study of wheat sensitivity, patients were put on an elimination diet that excluded wheat, cow’s milk, eggs, tomato, chocolate and any other food they felt they were hypersensitive to, for 4 weeks. Then they underwent DBPC food challenges. The challenges were performed with the reintroduction of a single food at a time.

The lymphocyte stimulation test, which is a common method to estimate cellular immunity, may be an effective diagnostic test for cow's milk allergy, when a blood test for IgE antibodies to cow's milk is negative.

Mechanisms
The mechanism for FPIES is unknown. It has been postulated to be a T-cell-mediated disorder, with a major role of tumor necrosis factor alpha (TNF-α). However, the food reaction develops in most cases within 3 hours after the food challenge. This response time is extremely short for a cell-mediated allergic reaction, which is known to require a time period longer than 24 hours, and indistinguishable from IgE-mediated immediate allergic reactions. One study found that atopy patch tests with the specific allergen were positive in FPIES patients, and this supports a role for T cells. Humoral immunity may also be involved in FPIES, since blood levels of specific IgA antibodies to the culprit food tend to be elevated, and blood levels of specific IgG4 antibodies tend to be lower in FPIES patients. IgG4 may protect against food allergy, so a lack of IgG4 may be part of the cause of FPIES.

Blood tests for specific IgE are usually negative in FPIES. However, IgE-mediated allergic reactions can occur in mucous membranes, even when skin and blood tests for IgE-mediated allergy are negative, and some studies suggest that some non-classical food allergies, including FPIES, may be IgE-mediated allergies that are localized in the GI tract. One study was on adults who had food allergy-related gastrointestinal symptoms such as diarrhea that were confirmed by double-blind placebo-controlled food challenges. Biopsy samples were taken from their small intestines, both while they were having food allergy symptoms and while they were symptom-free. The biopsy samples suggested that a localized IgE-mediated response caused their gastrointestinal symptoms. The biopsy results were similar between the patients had positive skin-prick tests/blood allergy tests for the food, and the patients who did not have positive SPT or blood allergy tests. The results were also similar between patients who had symptoms within an hour of ingesting the food, and patients whose food reactions were delayed for more than an hour.

Antigen-specific T-cell responses in patients with non–IgE-mediated gastrointestinal food allergy are predominantly skewed to TH2. It remains unclear why antigen-specific IgE antibodies are not detected.

The innate immune system plays an important role in non-celiac gluten sensitivity. Other components of wheat besides gluten may be involved in NCGS. Amylase/trypsin inhibitors, which are non-gluten proteins in wheat, are strong activators of innate immune responses. Wheat also has FODMAPS (fermentable, poorly absorbed, short-chain carbohydrates), and a study found that people with IBS who had improved on a gluten-free diet, also improved on a low-FODMAPS diet, and worsened when either gluten or whey protein was added to their diet. However, gluten itself also seems to be important in NCGS.