EpiPens and anaphylaxis

In the news last week, people with severe allergic reactions to certain things were told that they can use their EpiPens past their expiry date. So why is this? What actually happens in an allergic reaction and what is an EpiPen?

With EpiPen supplies due to run out in a few days the medicines regulator has stated that current EpiPens (some 0.3mg) can be used for up to 4 months past their expiry date. These devices are life saving for those that suffer from severe allergic reactions and should be kept on their person at all times.

There are 4 types of hypersensitivity reaction:

- Type I: immediate

o Examples include anaphylaxis, drug reactions, food allergies

- Type II: cytotoxic

o Examples are acute haemolytic transfusion reaction, autoimmune haemolytic anaemia

o IgM and IgG antibodies bind to antigens on the cells, activating the complement system leading to phagocytosis of cells

- Type III: immune complex

o Examples include poststreptococcal glomerulonephritis, polyarteritis nodose

o Antibodies bind to antigens in circulations which leads to immune complex formation and deposits in particular tissues resulting in inflammation

- Type IV: delayed (cell-mediated)

o Examples, acute and chronic transplant rejection, contact dermatitis

o Antigen presented to T cells within the body’s immune system, usually occurs in lymph nodes. This activates macrophages and inflammatory reaction within tissue

Type 1 hypersensitity reactions are what we are going to concentrate on this week as anaphylaxis is an immediate type 1 reaction.

This type of reaction is mediated by IgE antibodies. Plasma cells are stimulated by T helper cells to produce IgE antibodies to a specific antigen. Usually in an immune response IgA, IgG or IgM are released. During a period of sensitization these IgE antibodies bind to a receptor on the surface of mast cells and blood basophils. These cells coated in IgE are called sensitized. With exposure later, the same allergen attaches to these IgE molecules on the basophils and mast cells forming cross bridges. This bridging of the “sensitized” cells causes anaphylactic degranulation, a process of immediate and explosive release of pharmacologically active pre-formed mediators and inflammatory mediators from granules stored within the cells. These mediators include histamine and prostaglandins which act on proteins in surrounding tissue, resulting in vasodilation and contraction of smooth muscle. In anaphylaxis bronchial smooth muscle contracts and vasodilation is triggered leading to fluid leaking out of the blood vessels and cause myocardium depression.

There are two forms of anaphylaxis

- Systemic anaphylaxis – severe reaction occurring within minutes, leading to symptoms such as acute asthma, laryngeal oedema, diarrhoea, urticaria and shock. Examples include a penicillin allergy and bee sting allergy.

- Local anaphylaxis (atopy) – produces hay fever, hives, asthma etc. Classically from food allergies and pollen.

EpiPens are given to patients that have a severe allergy to a substance, for example peanuts. EpiPens contain adrenaline which should be administered intramuscularly into the mid anterolateral thigh (on the front slightly away from the groin). This injection can be repeated up to every 5minutes if there isn’t a good initial response. Adrenaline increases peripheral vascular resistance and coronary artery perfusion therefore increasing the blood pressure by acting on alpha-adrenergic receptors. It also leads to bronchodilation by activating beta-2-adrenergic receptors and also increase the intracellular cAMP which inhibits further mast cell mediator release.

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