Drug Eruptions and Types of Hypersensitivity in Patients with Darker Skin: Introduction

00:01 Welcome to our lecture on drug eruptions.

00:05 So what are drug eruptions? These are acute or subacute adverse cutaneous reactions to a drug or medicine.

00:12 There are many types of drug eruptions.

00:15 They can range from clinically mild and unnoticed rash to a severe cutaneous adverse reaction, which may be life threatening and result in death.

00:26 It is estimated that 1 in 1000 hospitalized patients have a serious cutaneous drug eruption. Now let's talk about the types of hypersensitivity reactions.

00:38 There are four types of hypersensitivity reactions.

00:41 The type I: IgE-mediated hypersensitivity, type II: cytotoxic hypersensitivity, type III: immune complex-mediated hypersensitivity, and IV: T cell-mediated hypersensitivity.

00:58 Let's focus on type I hypersensitivity.

01:01 This is mediated by IgE antibodies, which are specific for non-microbial environmental agents or allergens.

01:10 Type I hypersensitivity starts with the first contact with an antigen or allergen, e.g., pollen. The antigen or allergen is presented to antigen-specific B cells in predisposed patients. These B cells activate and start producing IgE that are specific for that particular allergen.

01:31 So once in the bloodstream, these IgE antibodies bind to the FC receptors of the muscles and basophils.

01:40 Even an individual gets re-exposed to the same allergen again, it binds directly to the IgE which is on the mast cells and basophils.

01:51 This causes the activation of basophils and mast cells, resulting in the release of different inflammatory mediators or cytokines.

02:01 So what do these mediators do? They induce different changes, but most prominently, vasodilatation and increased permeability of vascular epithelium.

02:14 The extent of mast cell and basophil activation dictates the variety of clinical manifestations observed in type I hypersensitivity reactions.

02:25 Now let's move on and talk about the examples that we've seen in type one hypersensitivity.

02:32 Patients may present with weals or what we call Urticaria .

02:35 And these may be quite extensive.

02:38 Patients may also present with angioedema.

02:40 Sometimes this can be so fatal.

02:42 I do remember once a patient came in with a swelling of the lips, the eyes and the nose, and the patient had to be quickly intubated to avoid complications of death.

02:53 So this could be a dermatological emergency.

02:58 Anaphylaxis is another important example of this type of hypersensitivity, and it is a dermatological emergency.

03:07 Now let's move on and look at the type II hypersensitivity reactions.

03:12 This type of hypersensitivity reaction causes the destruction of the host cell, hence the name Cytotoxic hypersensitivity.

03:22 So what happens here? IgG and less commonly, IgM antibodies attached to either extrinsic antigens or intrinsic antigens on the surface of the cell.

03:34 Then this antigen antibody complex activates the complement system that eventually causes the destruction of the host cell.

03:41 So there are four different mechanisms involved.

03:44 The first one, there's direct destruction of the host cell by complement system.

03:49 In short, proteins of complement system are involved in the cascade activation which results in formation of membrane attack complex, what we call the MAC complex that then penetrates the cell wall.

04:02 The second mechanism is indirect activation of the neutrophils to the complement system.

04:08 This then causes the release of enzymes that destroy the host cell.

04:13 Thirdly, the complement system opsonize the cell which the macrophages recognize and phagocytosis. The fourth mechanism is activation of the natural killer cells by the FC regions of the IgG or IgM antibodies.

04:30 This results in release of toxic granules that destroy the host cell.

04:38 So let's talk about the examples of type II hypersensitivity.

04:42 Patients with bullous pemphigoid, which is a blistering disease, and pemphigus vulgaris.

04:47 This is a typical examples of this type of hypersensitivity.

04:54 What about type III hypersensitivity? This one is mediated by IgG and IgM antibodies, which are specific for soluble antigens in the blood.

05:04 The antigen-specific IgG or IgM binds to the soluble antigens in the blood, causing the formation of the antigen antibody immune complexes.

05:16 Because these complexes are small, they are less immunogenic and fly under the radar of the immune cells, which means that they stay longer into the blood system. Eventually, these complexes start to deposit in different tissues, for example, the blood vessels, the glomeruli, skin, joints, etc., causing the complement activation and immune response.

05:42 Let's look at the examples of type III hypersensitivity.

05:46 The small vessel vasculitis and as well as systemic lupus erythematosus.

05:51 As you can see this clinical picture.

05:55 Lastly, let's take a look at type IV hypersensitivity.

06:00 We spoke about type I, type II, type III and type IV hypersensitivity reactions mediated by the T cells, hence the name T cell-mediated hypersensitivity.

06:11 So that's what this group entails.

06:16 The antigen gets presented to the CD4 T helper cell by an antigen-presenting cell.

06:22 This is then followed by activation of CD8 killer T-cells within about 48 to 72 hours.

06:30 The inflammatory reaction cascade is triggered.

06:34 So what are some of examples of type Y for sensitivity.

06:38 Allergic contact dermatitis is a typical example of this hypersensitivity.

06:42 For example, some people who have nickel allergic contact dermatitis.

06:47 Nickel we find in buttons, earrings, and if one is allergic to nickel, you then get a reaction could be around your ear where your earrings are, buckle of your belt or your jean starts.

07:05 A morbilliform drug eruption as well is an example of this type of reaction.

07:11 Erythema multiforme, where you see targetoid lesions, is also another example of type IV hypersensitivity.

07:19 Stevens-Johnson syndrome or toxic epidermal necrolysis is another example of type four hypersensitivity, where this whole immune inflammatory cascade is directed towards a particular drug. We spoke about this, and we know that drugs like antibiotics, sometimes anti-epileptics, can give you this type of reaction.