USMLE® Step 1 style questions USMLE
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A 26-year-old man comes to the clinic because of a burning rash, fever, productive cough and headache. The rash began on his face three days ago and spread to his upper torso. On examination, you note lesions of two colors that have a target-like appearance. The oral mucosa is involved. Which of the following findings can most likely distinguish the condition seen in this patient from the self-limited condition known as erythema multiforme?
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Tanner Marshall, MS, Sam Gillespie, BSc, Alex Aranda, Stefan Stoisavljevic, Samantha McBundy, MFA, CMI
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.
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.
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