Anaphylaxis

Definitions & Key takeaways

Anaphylaxis is an acute, generalized, multi-systemic allergic reaction to an antigen such as a bee sting. Its symptoms can range from mild pruritus and skin flushing to severe respiratory distress and cardiovascular collapse. Anaphylaxis can lead to rapid deterioration, and without treatment, it can lead to respiratory failure and cardiovascular collapse, and then death.

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Introduction0:00–0:26

Anaphylaxis comes from the greek word “ana-“ which roughly means against and “phylaxis” which means protection, implying that someone’s immune system has reacted to something in such a way that ends up damaging them, instead of protecting them.
It’s basically a severe type of allergic reaction that affects multiple organ systems and it’s potentially life-threatening.
Normally, the immune system recognizes and acts against pathogens that can cause disease. These pathogens have specific molecules on their surface, called antigens, and they help trigger an immune response.

Physiology0:26–1:11

In some individuals, though, the immune system overreacts and starts targeting harmless molecules that don’t cause any problems for most people.
These includes molecules found in foods like peanuts and shellfish, medications like antibiotics, and in the venom of insect bites.
In most cases, there might be a mild to moderate allergy, but sometimes things get really serious, involving two or more organ systems, and at that point it’s called anaphylaxis.

Pathophysiology1:11–5:44

Anaphylaxis, just like any allergic response, happens in two steps, a first exposure, or sensitization, and then a subsequent exposure, which is when it actually gets a lot worse.
So, let’s say a person is stung by a bee from a nearby beehive, for the first time in their life. When the bee pierces the skin with its stinger, its venom gets into the skin.
Part of that venom molecule can get picked up by a dendritic cell, which is a type of immune cell. The dendritic cell gobbles up the foreign particle and presents it to a nearby lymphocyte, called a T cell.
If the T cell is activated, it starts to produce cytokines, which stimulate B cells, another group of lymphocytes, which produce IgE antibodies.
These IgE antibodies get released into the bloodstream and bind to the surface of mast cells and basophils, which are immune cells that are full of granules that contain proinflammatory molecules.
Okay now, let’s say that that same person is stung by a bee again, maybe a few months later, then it’s probably time for this person to move away from this beehive, because they’re obviously lousy neighbors.
Nevertheless, with this second exposure, the mast cells and basophils which already have IgE antibodies on their surface, bind to the antigen and release their proinflammatory molecules.
In a simple allergic reaction, these molecules would cause some localized damage, like swelling around the sting site. In anaphylaxis, these molecules leak into the bloodstream and reach multiple organ systems.
Now, one of the important molecules is histamine, which causes the smooth muscle that lines the bronchi and gastrointestinal tract to contract, making those passageways narrow and tougher for air and food to get through.
At the same time, histamine causes blood vessel dilation and increased permeability, meaning that while blood vessel diameter and blood flow to the affected area increase, fluid is also allowed to more easily leak out the blood vessel wall and get into the interstitium, the space between cells.
That causes the pressure in the vessels to fall, and causes swelling or edema, as well as urticaria or hives. In addition to histamine, tryptase is also released by mast cells.
Tryptase is a type of protease that breaks down proteins, causing tissue injury. In some cases, mast cells and basophils also start synthesizing small proteins, called cytokines, such as interleukin- 4 (IL-4) and interleukin-13 (IL-13) that signal the B-cells to make more IgE antibodies, and tumor necrosis factor-α (TNF-α), but also leukotrienes, which are smaller molecules made out of fatty acids, like leukotriene B4 (LTB4) and leukotriene C4 (LTC4), which can attract immune cells - like neutrophils, mast cells, and eosinophils to their location even after the allergen is long-gone.
Since all these signalling molecules take a while to be formed, though, their effects don’t get seen until hours later. Now although most anaphylactic reactions involve IgE, sometimes anaphylactic reactions don’t.
For example, blood products, including intravenous IgG antibodies, used to treat a number of autoimmune and infectious diseases, can sometimes bind to various circulating antigens of the host and form immune complexes.
These immune complexes can activate complement proteins which are called anaphylatoxins - specifically complement 3 (C3a), complement 4 (C4a) and complement 5 (C5a) - and these can then trigger mast cell and basophil degranulation.
Both the IgE- and non-IgE mediated mechanisms are considered immunologic causes of anaphylaxis, and they’re responsible for the vast majority of anaphylactic reactions.
But in rare cases, certain agents, like contrast medium and opioids, can cause direct non-immunologic degranulation of mast cells and basophils, meaning without involvement of IgE, other antibodies, or immune complexes.
And the mechanism of how that happens isn’t well understood. Anaphylaxis causes symptoms in multiple body systems.

Symptoms5:44–7:02

For example, tissues all over the body might start to swell up, called angioedema, and there might also be respiratory symptoms like shortness of breath, coughing, or wheezing.
Anaphylaxis can also cause gastrointestinal symptoms like abdominal cramps, vomiting, or diarrhea. In more extreme cases, there can be widespread vasodilation causing the blood pressure to dramatically drop.
If blood pressure gets so low that the body can’t supply vital organs, like the brain, with enough oxygen, it’s called anaphylactic shock.
Reduced blood supply to the heart muscle could cause myocardial infarction, or heart attack, especially in individuals who already had an underlying heart disease, and reduced blood supply to the brain can cause loss of consciousness.
Most commonly, symptoms of anaphylaxis peak within 30 minutes, but sometimes symptoms can go away, and then recur hours later without additional exposure to the allergen.
These are called biphasic anaphylactic reactions. Even less commonly, anaphylactic reactions can last for days, in which case they’re called protracted reactions.

Diagnosis7:02–7:21

Diagnosis of anaphylaxis is usually based on identifying a likely trigger and seeing that multiple body systems are affected.
Specific lab tests can help like histamine, tryptase, and IgE levels, all of which are usually elevated. One way to identify an allergic trigger is through skin prick tests, which is where small drops of allergens are pricked into the skin with a tool, to see if there’s evidence of an allergy, like raised, itchy red bumps or weals.

Treatment7:21–8:19

Unfortunately, these tests can be wrong sometimes. For example, a person might have have a normal skin test, but still have symptoms with an allergen, or might have an abnormal skin test, but not have any symptoms with an allergen.
Treatment for anaphylaxis starts with epinephrine, most often given intramuscularly. First off, epinephrine causes blood vessel constriction, which decreases swelling and increases blood pressure.
Second, epinephrine boosts the heart’s contractility and heart rate, which can help prevent cardiovascular collapse, and third, it relaxes the smooth muscles that line the bronchi, helping the airways to open up.
Antihistamines can also be used to reverse the actions of histamine. Anaphylaxis and especially anaphylactic shock are medical emergencies because if there’s airway swelling it can close off the airway.
That’s why they have to be treated right away - sometimes that means airway management, supplemental oxygen, and large amounts of intravenous fluids.
Close monitoring for at least a day after symptoms resolve are important, in case there’s a biphasic reactions and another wave of symptoms.

Review8:19–8:44

All right, as a quick recap, anaphylaxis is an acute, potentially deadly, allergic reaction caused by the release of chemical mediators by mast cells and basophils and affecting typically two or more organ systems, most often the skin and the respiratory system.
Immediate treatment with intramuscular epinephrine and close monitoring of the airway are both extremely important.