LIFE-THREATENING ALLERGY (ANAPHYLAXIS) Allergy manifests with hives, itching, swelling, difficulty breathing, and even anaphylaxis, and involves mast cell degranulation and release of histamines and other mediators. The histamine triggers vasodilation in the skin leading to hives and itching and swelling in the airway including the larynx and can shut off breathing. This is a life-threatening situation called anaphylaxis. 

DETAILS ABOUT ANAPHYLAXIS The serology of this kind of inflammation involves IgE production and is known as type 1immune hypersensitivity. IgG-mediated sensitivity is not an allergy. There is no evidence that IgG-mediated hypersensitivity is associated with anaphylaxis. Immunologically, the process begins with Th2 lymphocytes which produce IL4 which triggers B lymphocytes to make IgE antibodies. The IgE antibodies then bind to mast cells and await allergen contact. IgE mediated food allergies can lead to intense intestinal cramps and if the allergens to transport to the lungs, this can cause asthma. 

MISCELLANEOUS The inflammatory response associated with parasites is similar to that of allergies in that they involve parasitic inflammatory responses involving Th2 lymphocytes and eosinophils. A food allergy response leading to abdominal cramps may be due to serotonin production which is associated with gut inflammation. Serotonin is a vasoconstrictor and can lead to abdominal cramps. Histamine is a vasodilator and promotes white blood cell movement towards the intestinal area of concern. IgE antibodies involved in the body’s response to parasites because of the mechanism mentioned above. 

FOOD ALLERGY Food allergies causing IgE reaction should be avoided because of the risk of hives and potentially anaphylaxis. The most common food allergens are milk, eggs, peanuts, tree nuts, fish, shellfish, soy, and wheat; interestingly all of these foods are GMO or extremely processed. Diagnostically, skin prick testing has a high rate of false-positive, so patients may test positive for antibodies but may not actually have a true allergy. The best type of IgE testing is ImmunoCAP Fluorescent Enzyme Immunoassay. IgE blood testing is preferred to provocation testing due to the false positives associated with provocation testing. Gastrointestinal allergies or food allergies should be associated with abdominal symptoms of nausea, vomiting, diarrhea, abdominal pain after eating certain foods. Constitutional symptoms such as brain fog and fatigue may be associated with leaky gut and a microbiome-based imbalance or an inflammatory response to the food not necessarily allergy inflammation. 

MAST CELL ACTIVATION DISORDER Mast cell activation disorder can affect any organ. Symptoms include fatigue, weakness, chills, sweats, constitutional symptoms, difficulty focusing, sinusitis, rhinitis, wheezing, mucous production in the throat causing throat clearing, tachycardia, diarrhea, abdominal pain, any abdominal symptom, bladder pain, cystitis, skin rashes, headaches, depression, neuropsych disorders, and even coagulopathy. Anaphylaxis may even occur without the IgE antibodies triggering event. Foods associated with mastocytosis include anchovy, sardines, potatoes, tomatoes, green peas, spinach, nuts, peanuts, tree nuts, strawberry, banana, oranges, spicy foods, hot beverages, fermented beverages, wine, beer, cheese, sauerkraut. Mast cell proliferation can occur on the skin, connective tissues, mucosa, blood vessels, the lining of the intestine, eyes, respiratory tract, endothelial cells, epithelial cells, and fibroblasts. Mast cells only mature cells in the body with CD117 receptors. When CD117 receptors are activated, cell division is triggered and this can lead to excess cell division of mast cells and this leads to an activation disorder of mast cells. Mast cells can be activated by IgE and by anti-IgE IgG, i.e., IgG that targets IgE which is associated with chronic urticaria. Mast cell IgE activation can also be triggered by dietary lectins and the IgG receptors that can activate mast cells can be up-regulated by Interferon-gamma which is controlled by gut bacteria. Mast activation syndrome is a major underlying cause of interstitial cystitis and irritable bowel syndrome. The diagnostic criteria for mast cell activation disorder are clinical but elevated levels of serum tryptase, serum chromogranin A, heparin, urinary n-methylhistamine, urinary prostaglandin d2, urinary leukotriene e4 are all associated with mast cell activation disorder but often these are all normal. Treatment of mast cell hyperactivation disorder can be done with antihistamines or NSAIDs or naturopathic antihistamines such as lavender and quercetin. Serum histamine levels are also associated inversely with vitamin C levels and so vitamin C levels can decrease histamine levels. Inflammatory cytokines originating from the gut microbiome can also trigger mast cell activation. Bacterial overgrowth is associated with LPS production which increases mast cell activity. Mast cell survival can be decreased by decreasing NF-kB production (nuclear factor kappa beta) and melatonin and curcumin do this. 

PSEUDOALLERGY FROM BIOACTIVE AMINE TOXICITY Pseudoallergy associated with biogenic amines can provoke a similar array of reactions but there are no triggering antigens, antibodies, or degranulation of mast cells or basophils. Pseudoallergy is not an immune response but it is a toxic reaction from histamine and other biogenic amines in the food itself. Dietary biogenic amines are present in aged cheese, fine red wine, and rich chocolate, all of which are common triggers for migraine. We also have gut bacteria that make toxic biogenic amines such as trimethylamine which is produced in bacterial fermentation of the protein in meat that can trigger pseudoallergy. Furthermore, histidine can be converted by intestinal bacteria into histamine and histidines present in high amounts present in chicken. Tyrosine can be converted into tyramine, lysine can be converted into cadaverine, and cysteine can be converted by bacteria in the gut such as Desulfovibrio pyrogen into hydrogen sulfide. Any amino acids can be converted into ammonia. Histamine is not necessarily associated with tinnitus. DAO, also known as AOC1 which is amine oxidase copper containing 1, the remainder of this was referred as DAO, is present on epithelial cells in the intestine and this enzyme clears biogenic amines from blood plasma and destroys bioamines in food preventing absorption. However, loss of DAO can occur leading to a buildup of histamine in the intestine. Alcohol can suppress DAO activity or inadequate S-Adenosyl methionine levels (SAM-e) and can also impair MAF/DAO levels and in the setting of intestinal increased permeability from leaky gut, there could be increased absorption of bioamines in the intestine. The foods that are high in bioamines content are pickle foods, smoked and fermented foods, meats, seafood, alcohol, fermented beverages, fermented dairy, fermented soy products, chocolate, fermented vegetables, legumes, peanuts, fruits including avocado, banana, red plums, pineapple, raspberry, Brazil nuts, cactuses, vanilla, eggplant, all the ripe fruits and vegetables that have been fermented, yeast and yeast extracts including bread. The content of the fermented food depends on the culture used. Serotonin syndrome or even in mild levels of serotonin toxicity is now associated with gut inflammation and can lead to manic symptoms, tachycardia, sweating, headaches, agitation, restlessness, flushing, diarrhea, and can be triggered in the right setting by certain foods especially butternuts, black walnuts, English walnuts, pecans, and plantains. It needs to be emphasized that vitamin C is essential to maintain DAO activity. Foods containing sulfide that can promote direct mast cell activation include baked goods, soup mixes, jams, frozen canned vegetables or foods, pickle foods, grays, dried fruits, potato chips, molasses, shellfish and wine, and nutrients that can decrease sulfide induced mast cell degranulation include B vitamin, selenium, vitamin D, copper, niacin, zinc, SAM-e, taurine, alpha-lipoic acid, melatonin. There is sulfide containing food additives such as potassium bisulfite, potassium metabisulphite, sulfur dioxide, sodium bisulfite, sodium metabisulphite, and sodium sulfite. 

LEUKOTRIENE INDUCED MAST CELL ACTIVATION AND SALICYLATES There are leukotriene associated hypersensitivities as well that can trigger mast cell activity such as salicylates. A study published in 1985 by Swain analyzed the salicylate content of multiple foods and this became the primary source of knowledge of how to avoid salicylate sensitivity. Salicylates are not common in food but they are common in wine and alcohol. The main herb to avoid salicylate toxicity or sensitivity is Willow bark, aspirin products, and wintergreen. There are salicylate type antioxidants that are beneficial found in coconuts, strawberries, and carrots, however, there are preservatives such as sodium benzoate which can trigger salicylate sensitivity. Leukotriene induced mast cell activation or salicylate toxicity or sensitivity can be addressed by consuming leukotriene inhibiting phenol compounds such as elderberry, Loganberry, capers, black olives, turmeric, cloves, clove oil, soy products, chocolate, peppermint, oregano oil, and cumin caraway

. PSEUDOALLERGY FROM BIOACTIVE AMINE TOXICITY Food allergy IgE mediated inflammation in response to food can cause responses within few minutes up to a few hours can cause, rashes, wheezing, edema, and anaphylaxis and can cause itching, anxiety, bronchoconstriction wheezing and nausea. IgG-mediated inflammation can cause irritability, abdominal pain, and fatigue which is associated with mast cell activation and could be tested with IgG or IgG core antibody testing. The most common allergens include milk, wheat, baker’s yeast and beer, also soybean. There are four subclasses of IgG antibody: IgG1 is an early response, IgG4 is the most common associated with food immunogenicity and it is similar to secretory IgA. IgG4 can cause immune complexes to be performed and activate the complement cascade which can cause mast cell degranulation and this process can trigger Th17 induced inflammation which can lead to autoimmune disease. 

SUMMARY: Plan of action is thus following: 1. IgG testing can indicate which foods are causing mast cell symptoms. 2. Improving digestion by decreasing stomach pH and digestive enzymes can help with decreasing the immunogenicity of large proteins such as biogenic amines and common allergens of dairy and wheat should be avoided. The most common dietary lectin that causes damage to the intestine is wheat and gluten and potatoes should be avoided too temporarily since there are antitrypsin proteins that are mostly denatured by cooking but sometimes potatoes can lead to excess antitrypsin enzymes and prevent enzymatic degradation of proteins in food. Also, the resolution of bacterial dysbiosis should be done. Mast cell activation is associated with bacterial overgrowth syndrome so antimicrobials may be useful. Rotation of foods can be helpful as well and easing anti-inflammatory efforts such as vitamin C, melatonin, acetylcysteine, glutathione, alpha-lipoic acid, magnesium, fish oil may be beneficial. Foods that are removed can be reintroduced after three months.