Type 1 Hypersensitivity

Core

Allergies and Allergens

Type 1 hypersensitivity reactions are immune reactions that are caused by an environmental, non-infectious allergen. It is colloquially known as allergy, which can result in a localised reaction or a widespread systemic reaction, also known as anaphylaxis. The reaction is immediate and manifests within 30 minutes of exposure to the trigger (allergen). Exposure to the allergen can come in many forms, such as inhalation, ingestion, injection or physical contact.

Allergens can be divided into several categories:

• Seasonal environmental exposure - e.g. tree and grass pollens
• Perennial (year-long) environmental exposure - e.g. house dust mites, animal dander, fungal spores
• Accidental exposure, which can include:
  
  • Food - peanuts, eggs
  • Iatrogenic - penicillin, latex
  • Other - venom from insect stings

Pathophysiology

When the immune system is first exposed to the allergen, the immune system activates T Helper II Cells. These T Helper Cells stimulate B cells to produce IgE antibodies, which then bind to mast cells and basophils. This results in the release of leukotrienes, histamines and cytokines.

Leukotrienes cause bronchoconstriction whereas histamines and cytokines cause vasodilation and increased vascular permeability. Together, these trigger inflammation as blood flow is increased. If the contact with the allergen is localised, the response will result in a mild, localised irritation but if systemic, this can cause anaphylactic shock and can be life-threatening. This means that reactions to allergens can be very dangerous; an inhaled allergen causing even localised inflammation in the lungs can be life-threatening, and allergens injected into the bloodstream can cause massive widespread effects.

It is important to note that type 1 hypersensitivity reactions involve a sensitisation phase. On first exposure, allergen-specific IgE is generated and binds to mast cells. Clinical reactions typically occur on subsequent exposure when cross-linking of bound IgE triggers mast cell degranulation.

Hygiene Hypothesis

Type 1 hypersensitivity reactions are generally more common in developed countries and this is believed to be due to the Western lifestyle which is often associated with a low infectious exposure. The Hygiene Hypothesis was first described by David P. Strachan in 1989 as he observed that children who were exposed to animals and microbes in the early postnatal period seemed to have a lower incidence of certain allergic conditions (such as hay fever and eczema).

Indeed, the Western lifestyle is associated with a lower microbial diversity: it has been shown to induce alterations to the microbiome that exists inside the body. This reduces diversity, and disrupts the symbiotic relationships on the mucosal surfaces of the human body (mainly the gut), a phenomenon scientifically known as dysbiosis. This loss of microbiota diversity has recently become a focus in research and links have been suggested between dysbiosis and a variety of other immune diseases such as Crohn’s Disease, ulcerative colitis, type one diabetes mellitus, coeliac disease or multiple sclerosis.

Symptoms

The most common manifestations of allergic reactions happen on the skin as all type 1 hypersensitivity reactions involve mast cell degranulation, and mast cells are abundant within the dermis of the skin. This appears as urticaria rash (hives). Prolonged and chronic exposure to an allergen can also cause atopic dermatitis or eczema.

On the face, allergic reactions present with angioedema caused by mast cell degranulation within the deeper layer of the dermis and mediated primarily by histamine released from mast cells. It can cause swelling of the lips, eyes, tongue and constriction of the upper respiratory airway.

Finally, systemic activation of mast cells can result in anaphylaxis, common in cases of systemic absorption of the allergen (e.g. drug ingestion or infusion). This causes hypotension and cardiovascular collapse, as well as angioedema and bronchial constriction and is a life-threatening emergency known as anaphylactic shock.

Treatment

Adrenaline

Treatment of anaphylaxis requires immediate intramuscular injection of adrenaline; this is usually done using an autoinjector pen, with brands such as EpiPen^® being very common.

Adrenaline is an effective initial treatment for anaphylaxis as it reverses lots of the symptoms:

• Peripheral vasoconstriction counteracts the vasodilation caused by histamine and cytokine release, acting to raise blood pressure.
• Prevents ongoing fluid loss to the extravascular space by reducing vascular permeability.
• Reverses bronchoconstriction to help airways remain functional.
• Inhibits further mast cell degranulation to try to prevent further symptoms and deterioration.

Treatment should be given as soon as possible, so people with known allergies will usually carry an adrenaline autoinjector such as an EpiPen® with them and will have been trained on how to use it. When possible, basic observations should be monitored, e.g. pulse, blood pressure, oxygen saturation, temperature, respiratory rate and ECG.

While adrenaline is the most important and life-saving treatment of anaphylaxis, it is important to remember that adrenaline alone will not remove the allergen. Given the very short half-life of adrenaline once injected, multiple doses may be required to keep symptoms at bay until the other treatments listed below can be put into place or the allergen can be removed. A biphasic allergic reaction may occur, where there is a period of resolving symptoms followed by deterioration with no new exposure to the allergen, even after appropriate initial treatment.

Other Treatments in the Acute Phase

Over the years there have been many medications and strategies suggested to aid adrenaline use in the acute phase of an allergic reaction. Some of these are listed below:

• Steroids - intravenous hydrocortisone may be used in some settings, but there is limited evidence that it prevents biphasic reactions and it is not life-saving in the acute phase
• Antihistamines - act to inhibit histamine and can help with skin symptoms, but they do not treat airway or circulatory compromise
• Intravenous Fluids - support the circulatory system by increasing the intravascular volume, helping to counteract the negative consequences of vasodilation
• Bronchodilators - help to reverse bronchoconstriction

Long-Term Management of Allergies

Life-threatening allergies can be massively debilitating to live with, so there are a number of therapies that have been developed to try to reduce their severity.

Pharmacological treatments can include Anti-IgE monoclonal antibody therapy, antihistamines, leukotriene receptor antagonists, or corticosteroids.

One of the most common non-pharmacological management strategies for allergies is allergen desensitisation therapy, which refers to the progressive administration of increasing doses of allergen extracts over time. It is generally considered most effective for allergens such as bee and wasp sting venom, but can also be used for food allergies. It is carried out in a controlled environment where the patient can be monitored for signs of anaphylaxis and treated promptly to reduce the risks. If the patient was able to be repeatedly exposed to their allergen with no reaction, their exposure would increase and the process would start again.

Edited by: Dr. Maddie Swannack

Reviewed by: Dr. Thomas Burnell

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