In this blog post I thought it only right to start at the beginning, the foundation of what food allergy is. I explain the difference between IgE-mediated food allergy, non IgE-mediated food allergy and mixed IgE and non-IgE food allergy and I also discuss the immune mechanism that underlies an allergic reaction and what the methods are to diagnosing food allergy with a specific focus on IgE-mediated food allergy. I also share stories along the way of my personal experiences of IgE-mediated food allergy symptoms.
What is Food allergy?
Food allergy is an adverse immune reaction to food protein antigen also known as an allergen. It occurs when the immune system which is the body's defence against infection mistakenly treats an allergen as a threat causing an allergic reaction (Valenta et al 2016 & David et al 2000 ).
Food allergies are different to intolerances because food allergies involve the immune system whilst intolerances involve the digestive system. Intolerance are often caused by a lack of a digestive enzyme or the inability to digest food (Lomer et al 2015).
Food allergy categories:
Food allergy can be classified into three broad categories such as IgE-mediated food allergy, non-IgE mediated food allergy or a mixed so both IgE dependent and IgE independent food allergy (Valenta et al 2016 ).
1. IgE-mediated food allergy is the most common type of food allergy. It is triggers by Immunoglobulin E (IgE) which is an antibody produced by your body when an allergen is encountered (Yu et al 2016).
Symptoms arise often rapidly with 2 minuets but can take up to 2 hours after encountering the trigger food protein antigen and include an itchy sensation inside the mouth, throat or ears, a raised itchy red rash ("hives"), swelling of the face, around the eyes, lips, tongue and roof of the mouth, nausea, vomiting, diarrhoea. In more severe cases known as anaphylaxis which can be potentially fatal, symptoms can include breathing difficultly, trouble swallowing, feeling dizzy or faint (Yu et al 2016).
When I was in school, my mom decided to make me a sandwich for lunch as she had bought my favourite salami. However, my mom hadn’t checked the ingredients and little did she know that the salami she had bought was a different one to the one I normally eat. This one had pistachios in it. I remember eating it and instantly my tongue started tingling and my lips started swelling. The swelling on my lips was white and getting bigger and bigger very fast. My throat started to feel tight too. I also remember when I was abroad at my cousin’s henna party the night before her wedding and I took a bit out of a sandwich which contained sesame seeds. I remember instantly my lips started swelling and I spat the bite out. The swelling on my lips was slightly different to when I ate pistachio as it did not turn white. I also started to feel sick and started vomiting immediately. These are reactions I have experienced are IgE mediated food allergy reactions.
2. Non-IgE mediated food allergy are mediated by other immune cells not IgE. Allergen-specific T cells are thought to play a role in this group of food allergies. Non-IgE mediated food allergies can affect primarily the gastrointestinal tract, rather than the skin and respiratory tracts (Yu et al 2016). And symptoms include abdominal discomfort, vomiting and diarrhoea. In some cases constipation or colic can be the presenting symptoms. The symptoms often take longer to develop (hours-days) rather than those of IgE mediated food allergies which frequently more rapidly following food ingestion. Non IgE food allergy can include Food protein-induced enteropathy , food protein-induced enterocolitis syndrome (FPIES) and food protein-induced proctocolitis (FPIP), coeliac disease, Allergic proctocolitis (AP), Heiner syndrome, Cow’s milk protein induced iron deficiency anaemia (Connors et al 2018 & Valenta et al 2016).
3. Mixed IgE dependent and IgE independent food allergy which are conditions that are associated with food allergy and involve both IgE- and non-IgE-mediated mechanisms. Some people may experience symptoms from both types. Atopic manifestation of this type of reaction can include delayed food-allergy-associated atopic dermatitis/eczema triggered by T helper 2 (TH2) cells (Roerdink et al 2016 and Connors et al 2018). Although, strictly speaking ezema is generally not though to be an allergic disease, many infants and young children with atopic eczema have IgE-mediated food allergy. Egg allergy is a common food allergy in children with eczema and so appropriate diagnosis of food allergy and elimination of the allergen leads to improvement of eczema. Another example is Allergic Eosinophilic Eesophagitis (EoE) (Connors et al 2018 and Yu et al 2016 and Furesta et al 2015, Roerdink et al 2016).
Figure 2: A flow diagram describing the 3 broad categories of food allergy. Taken from Connors et al 2018.
More about IgE mediated food allergy
IgE-mediated food allergy occurs once a person has been sensitised to a allergen. Essentially what sensitisation means is the ability to produce IgE specific antibodies to an allergen (Boyce et al. 2010).
Initial sensitisation occurs the first time your body encounters this allergen and produces IgE. The allergen enters through your cell barrier on either the skin, gastrointestinal and respiratory tract and is picked up by different cells resulting in a cascade of reactions eventually causing the production of IgE antibodies (Yu et al 2017, Wood 2006 & Valenta et al 2016). These antibodies bind to the surface of cells such as mast cells. This is called priming and when for example you mast cells are primed this is when you can get an allergic reaction (Yu et al 2017, Wood 2006 & Valenta et al 2016).
On second exposure and any repeat exposure of the allergen after this activates a secondary immune response where symptoms arise. On second exposure when an allergen is eaten it is encountered by around half a million IgE molecules on mast cells (Yu et al 2016). These IgE antibodies bind to the antigens and this causes mast cells to burst releasing many chemicals like histamine (Yu et al 2016, Wood 2006 & Valenta et al 2016). Histamine can cause vasodilation increasing the permeability in your capillaries your blood vessels. This causes fluid to escape from your capillaries into the tissues, which leads to for example symptoms of an allergic reaction such as a runny nose and watery eyes. Other chemicals are also released from mast cells which result in inflammation too (White 1990) .
Figure 1. Manifestation of Immunoglobulin E (IgE) Food Allergy (IgE-FA). First exposure: the allergen diffuses through the epithelial cell barrier and antigen presenting cells present the allergens antigens to CD4 T-cells. T cells differentiate into T helper 2 cells and secrete cytokines. B cells differentiate into IgE producing plasma cells. IgE bind to FcRs receptors on effector cells and prime them for future allergen encounter. Future exposure: allergen epitopes bind to IgE on effector cells triggering degranulation of effector cells. Mediators are release like histamine, cytokines and interleukins resulting in a symptomatic reaction. Created by Ayah Wafi.
Diagnosis of IgE mediated food allergy
A Double-blind Placebo-controlled Food Challenge (DPCFC) is the only gold standard clinical diagnostic method to diagnose IgE-mediated food allergy. It is a challenge where a subject is given increasing incremental dosages of food within a time frame until a symptomatic reaction occurs (Sicherer 1999). DPCFC is costly and time consuming thus a less common way to diagnose patients as having IgE-mediated food allergy. Historically a combination of sensitisation tests skin prick tests, blood tests called serum IgE test and clinical history have been used to ‘diagnose’ IgE-mediated food allergy (Heinzerling et al. 2013, Boyce et al. 2010 & Sicherer, S.H., 1999).
- A skin prick test is administered by first pricking the subject’s skin, then dispensing a test solution containing the allergen protein antigen. If skin swelling occurs the subject is sensitised (Heinzerling, et al. 2013).
- A serum IgE test is a blood test which measures the level of IgE produced when your serum is mixed with a solution of the allergen (Boyce et al .2010).
These sensitisation tests, test whether your body produces IgE antibodies to a specific food protein. However just because you produced IgE antibodies to this allergen does not mean you will have an allergic reaction (Boyce et al. 2010). Being sensitised doesn’t mean you are allergic but it can be a great indicator of an allergy. Therefore, these tests are often back up by clinical history conversations to diagnose someone as having a food allergy (Heinzerling, et al 2013 and Boyce et al 2010).
This is exactly what happened to me and continues to happen thanks to the NHS. When I was a child I had an amazing allergy nurse who I would routinely see me regarding my allergies. As I grew older and moved out of my home to university I was referred to an adult allergy clinic and was seen my a consultant allergist. Throughout, these visits to the hospital allergy clinics I have routinely had skin prick tests and serum IgE tests. Skin prick tests are extremely itchy if you are sensitised to the allergen. I remember an allergy nurse telling me role up my sleeves and then mentioning I would just feel a small scratch and then pricking my skin and adding a liquid droplet to the pricked skin containing the allergen protein antigens. I would have to wait in the waiting room whist watching my skin swell up and turn red and resisting urge to scratch the itch. I would then get called up and my nurse would measure the size of swelling to predict the severity to allergic reactions to that food. I would then have a discussion would my consultant about my skin prick results and how I am managing or if I have had any reactions. Often we would practice administering a dummy adrenaline autoinjector to remind myself how use one. I would also get blood taken and later that week I would receive a letter telling me my serum IgE test results as well as what was discussed during the consultation.
Overall in this post I discussed, what food allergy is. I explained the difference between IgE-mediated food allergy, non -gE mediated food allergy and mixed IgE and non-IgE food allergy and I also talk about the immune mechanism that underlies an allergic reaction and what the methods are to diagnosing food allergy with a specific focus on IgE-mediated food allergy in this post. If you would like to find out more about what happens during this immune response I have created a YouTube video presentation where I discussed this in more detail, so be sure to check this out!
References
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