Erythema multiforme

A 14-year-old boy living in the Southwest United States is brought to the office by his parent because of a nonpruritic rash on his hands for the past two days. He has also had mild shortness of breath, dry cough, and malaise since last week. He has no prior medical conditions and does not take any medication. Vaccinations are up-to-date, and he has not traveled recently. Temperature is 37.7°C (99.9°F), pulse is 92/min, respirations are 22/min, and blood pressure is 115/80 mmHg. Examination of the hands reveals the following:

^{Reproduced from Flickr}Lung auscultation reveals bilateral coarse crackles. Chest x-ray shows patchy, non-segmental bilateral opacities. Which of the following is the most likely cause of this patient’s skin lesions?

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Herpes simplex virus (HSV-1/HSV-2)

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Macules p. 485

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Mycoplasma pneumoniae p. , 148

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Phenytoin

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Skin lesions

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Sulfa drugs p. 251

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Vesicles (skin) p. 483

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Erythema multiforme is an acute, immune-mediated condition that affects skin and mucous membranes such as the mouth and genitals.

The skin is the largest organ in our body, and it’s divided into three layers - the epidermis, dermis, and hypodermis.

The epidermis forms the thin outermost layer of skin.

Underneath, is the thicker dermis layer.

And finally, there’s the hypodermis, the deepest layer.

The epidermis itself is made of multiple layers of developing keratinocytes - which are flat pancake-shaped cells that are named for the keratin protein that they make.

Keratinocytes start their life at the lowest layer of the epidermis called the stratum basale, or basal layer, which is made of a single layer of stem cells called basal cells that continually divide and produce new keratinocytes.

These new keratinocytes then migrate upwards to form the other layers of the epidermis, such as the spinous and granular cell layers.

Below the epidermis is the basement membrane which is a thin layer of delicate tissue containing collagen, laminins, and other proteins.

Basal cells are attached to the basement membrane, and help form the dermoepidermal junction.

Similar to how the skin lines the outside of the body, mucosa lines the inside of the body. And it’s named for the surface it covers.

So there’s oral mucosa, nasal mucosa, bronchial mucosa, gastric mucosa, and so forth.

Mucosa is made up of one or more layers of epithelial cells that sits on top of a layer of connective tissue called lamina propria.

Just like with the skin, there is a basement membrane that sits between and attaches the epithelial layer and the lamina propria.

Now, basal epithelial cells, as well as most cells in the body, have a protein called major histocompatibility complex or MHC class I molecule on the surface of their membrane. This protein presents peptides from within the cell to immune cells called cytotoxic T cells.

If a cytotoxic T cell recognises the peptides as foreign, for example like in a virally infected cell, then the cytotoxic T cell will kill the presenting cell.

Otherwise, if the cell is healthy and the cytotoxic T cell doesn’t recognize the peptide as foreign, nothing happens.

Erythema multiforme is a type IV hypersensitivity reaction, meaning that the damage is caused when cytotoxic T cells inappropriately attack the basal epithelial cells.

As part of the attack, the cytotoxic T cells release proinflammatory cytokines like interferon gamma and tumor necrosis factor alpha which attracts other immune cells to the area, causing more damage.

And the result of all of this damage is the formation of vesicles and erosions in the skin and mucosa.

As the name suggests, erythema multiforme can appear in a variety of shapes and sizes.

There can be macules, which are flat red, or pink patches.

There can be vesicles which are small, raised, fluid-filled lesions or bullae which are large, raised, fluid-filled lesions.

There can also be papules which are solid elevations containing no fluid.

However, the most characteristic of all erythema multiforme lesions are targetoid lesions which are between 2mm and 2 cm, and have central necrosis of the epidermis, surrounded by concentric rings of erythema, making them look like a bull’s eye or target.

Histologically, early on, there are a few lymphocytes near the dermoepidermal junction.

Summary

Erythema multiforme is an immune-mediated skin condition that typically causes red, itchy patches on the skin. It can also affect the mucous membranes of the mouth and genitals; in some cases, the patches can blister and form lesions. Erythema multiforme is commonly triggered by a Mycoplasma or Herpes simplex virus infection. Some drugs can also cause it, such as penicillins, ciprofloxacin, and anticonvulsants such as carbamazepine.

Sources

"Robbins Basic Pathology" Elsevier (2017)

"Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)

"Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)

"CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)

"From HSV infection to erythema multiforme through autoimmune crossreactivity" Autoimmunity Reviews (2018)

"Erythema multiforme: a review and contrast from Stevens-Johnson syndrome/toxic epidermal necrolysis" Dental Clinics of North America (2005)

Erythema multiforme

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