Stevens-Johnson syndrome

Stevens-Johnson Syndrome is named for the physicians who first reported an acute, immune-mediated condition that affects the skin and mucous membranes such as the mouth and genitals.

Stevens-Johnson syndrome and toxic epidermal necrolysis are considered to be the same condition, but are along a spectrum where toxic epidermal necrolysis is the more severe form.

Both can be fatal if not treated, and the risk of fatality increases with severity.

The skin plays an important role in protecting underlying muscles, bones, ligaments, and internal organs by forming a barrier to infectious pathogens; and preventing water loss from the body.

The outermost layer of the skin is the epidermis and, itself, is made of several layers of cells.

The deepest layer is called the stratum basale, or the base layer.

And cells here are anchored to a basement membrane, a thin layer of delicate tissue containing proteins like collagen and laminins, which attach the epidermis to the underlying skin layer called the dermis.

Similar to how the skin lines the outside of the body, mucous membranes, or mucosa, line the inner body surfaces like the mouth, tongue, respiratory tract, conjunctiva of the eyes, genitals, and anus.

Mucosa is made up of one or more layers of epithelial cells, which, again, are attached to a basement membrane that sits on top of a layer called the lamina propria.

Now, 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, also called a CD8+ T cells.

If the cell is healthy, the cytotoxic T cell doesn’t recognize the peptides as foreign, and nothing happens.

But if a cell is infected, say with a virus, the cytotoxic T cell can recognize the peptides as foreign and trigger an immune response.

Once all infected cells have been destroyed, the immune response resolves.

Stevens-Johnson Syndrome and toxic epidermal necrolysis are both type IV hypersensitivity reactions.

They’re also called T-cell-mediated hypersensitivity reactions because cytotoxic T cells directly and aggressively attack the epithelial cells in the mucosa and epidermis, and release a payload of perforin and granzymes to kill them.

Perforin lyses the targeted epithelial cell, forming pores which allow granzymes to enter and induce cell death, or necrosis.

Also, as part of the attack, the cytotoxic T cells release proinflammatory cytokines, like interferon gamma and tumor necrosis factor alpha, which attract other immune cells to the area that cause even more damage.

This leads to a loss of the skin barrier protection, and erosion of the affected skin and mucosa from cellular death and detachment at the basement membrane.

With the skin and mucosa compromised; the body can dehydrate, and pathogens from outside the body can invade and cause an infection which can lead to another strong immunologic response, called sepsis, that can cause large-scale tissue and organ injury and dysfunction.