3-year-old (male) with reaction to peanuts

00:02 A 3 year old male is rushed to the emergency department after consuming a peanut butter sandwich at daycare.

00:09 The patient is in acute distress.

00:12 His blood pressure is 60/40 and heart rate is 110 beats per minute.

00:17 There is an audible inspiratory stridor and the respiratory rate is 27 breaths per minute.

00:24 Upon examination of the patient's chest, we find that it is covered in a maculopapular rash.

00:30 Intubation is attempted and fails due to extensive laryngeal edema.

00:36 The decision for cricothyroidotomy is made.

00:39 Which of the following is a most likely the mechanism of this pathology? Answer choice (A) - c5a production Answer choice (B) - release of interleukin-4 Answer choice (C) - deposition of antigen-antibody complexes Answer choice (D) - interleukin-2 secretion and answer choice (E) - c3b interaction Now take a moment to determine the answer choice for yourself before we go through it together.

01:14 Okay, let's work through this question together.

01:17 The first thing to do is determine what are the question characteristics? Well this is an immunology question.

01:23 We have a patient who has consumed some type of allergen and is producing a systemic response.

01:30 And the answer choices all concern immunology.

01:33 And this is a 2-step question.

01:35 First thing we need to do is determine the diagnosis of what's going on with the child.

01:39 And second, the actual underlying mechanism of the pathology.

01:43 And of course, the stem is required in this case because again it's a very complex question with lots of critical information.

01:50 So let's walk through this question together.

01:52 Now step 1, we need to determine the child's diagnosis.

01:56 Now the history that is provided in the clinical vignette supports the diagnosis of the patient having a severe allergy to peanuts.

02:05 Now the rapid onset of hypotension, respiratory distress and laryngeal edema and rash is suggestive of what's called ANAPHYLAXIS or an anaphylatic reaction.

02:18 Now this is what's called a type 1 hypersensitivity.

02:22 So the patient has a type 1 hypersensitivity reaction to peanuts.

02:27 Now, now that we know that, we need to determine the actual underlying mechanism of this process.

02:33 So type 1 hypersensitivity reactions arise due to the recognition of peanut allergens as being considered a foreign antigen.

02:43 Now let's refer to our image, which is an image that describes the four types of hypersensitivity reactions.

02:50 Type 1 being on the upper left, Type 2 being on the upper right, Type 3 being on the lower left and Type 4 being on the lower right So let's just start with Type 1 hypersensitivity which is the answer to what the diagnosis is with the child.

03:06 Now as we can see by looking at the image, we have an antigen which is going to be the allergen in this case which is going to be that little green dot.

03:16 Imagine it's part of a peanut and that peanut component is a foreign antigen to this child.

03:23 And what we see is that the peanut antigen is actually binding to the immunoglobulin E or IgE and then that's actually activating the Fc receptor at the immunoglobulin E.

03:38 And what happens is we have these type of receptors on both mast cells and basophils.

03:44 So when it's happening, is we have peanut allergen bind to Ige on mast cells or basophils, we get a very classic reaction which is degranulation of the mast cells and basophils and release of vasoactive inflammatory mediators such as histamine.

04:00 Now, interleukin-4, very high-yield, plays a critical role in allergic disorders including food hypersensitivity and is released.. and is involved actually in antibody production.

04:12 So in this case, this is the answer to our clinical vignette, as the release of interleukin-4 is occuring in a type 1 hypersensitivity reaction to the food allergy.

04:24 Now, a very important to know and extremely high-yield is the mechanism of type1 hypersensitivty.

04:30 This is something you just have to memorize.

04:32 Now, the first exposure to an antigen does NOT provoke a reaction but it does cause what is called 'sensitization'.

04:42 So in this case, the first time the child may have a peanut sandwich, he did not get this gross reaction, he just had sensitization to the process.

04:51 Now, during sensitization, IgE antibodies specific to the antigen are produced and bind to the IgE receptors on mast cells.

05:01 Now that happens during the sensitization process.

05:05 Upon second exposure, which may have been what happened here to this child, the antigen binds to the IgE antibodies that are now produced and this causes massive degranulation of both mast cells and basophils which release histamine.

05:22 And interleukin-4 plays a key role in the initial antibody production which is involved in the process of differentiating the B-cells into plasma cells to actually produce the IgE antibodies.

05:35 Now let's go back to our image.

05:37 We thoroughly went through the Type 1 hypersensitivity.

05:40 Now let's go to some high-yield facts to discuss the Type 2, Type 3 and Type 4 hypersensitivity reactions.

05:47 So, Type 2 hypersensitivity is 'cytotoxic hypersensitivity' which is generally mediated by IgG or IgM which is going to react to surface antigens and activate the complement system.

06:02 A typical example here which is extremely high-yield is when you have ABO blood incompatibility.

06:10 So you have a person, say who's A positive and they're given type B blood, they will have a Type 2 hypersensitivty reaction which will activate the complement system.

06:20 Extremely high-yield, take the example of the blood incompatibility and understand that you have complement activation in Type 2 hypersensitivity.

06:30 Looking at our image, we definitely see that.

06:32 We see the actual surface antigen, a cytotoxic cell coming through with an Fc receptor and it actually will activate the complement system to produce a cytotoxic hypersensitivity reaction.

06:45 Now let's look at Type 3 hypersensitivity.

06:48 What occurs here is actually deposition of circulating immune complexes in tissue.

06:54 A very classic and high-yield example here is in rheumatoid arthritis.

06:59 Now if you look at the image, we have immune complexes floating around.

07:03 And neutrophils in this case will again cause complement activation along with the immune complexes to cause the Type 3 hypersensitivity reaction.

07:13 So both Type 2 and Type 3 have complement activation - extremely high-yield.

07:19 Now looking at Type 4 hypersensitivity, this is a unique one, very important to recall.

07:25 This is a delayed recation, it can actually take several days to occur.

07:29 And this is the only hypersensitivity reaction that is NOT, and I repeat NOT mediated by antibodies but instead is mediated by T-cells.

07:39 So if you look at our Type 4 hypersensitivity, we see an antigen coming in to our sensitized T-helper1 cell which will then release cytokines and cause the activation of macrophages.