Toxic Epidermal Necrolysis in response to drug reaction - What's the mechanism?

Factual Questions
1

I was reading this article that referenced a child’s death from Toxic Epidermal Necrolysis and in searching found the pic below

Toxic Epidermal Necrolysis (warning very medically graphic)

What is the specific mechanism that makes the skin do this in response to drug reaction?

2

Toxic epidermal necrolysis (TEN) is thought to be a cell-mediated immunologic reaction to drug metabolites. Specifically, drug metabolites may accumulate because of abnormal metabolism of the drug, and this results in the presence and then persistence of immunogenic substances (i.e. the metabolites).

Indeed, there is a reported association of TEN with the HLA-B12 haplotype; an association which suggests a role for abnormal immunity in the development of the syndrome (i.e. since HLA genes are involved in the immune response).

Further support for an immunologic cause is found in the fact that the skin necrosis occurring in TEN appears to be mediated by CD8+ T cells by way of Fas-mediated apoptosis. Note that CD8+ T cells are prime immunologic players. As well, treatment of TEN with intravenous gamma globulin (a non specific but effective way of “neutralizing” pathogenetic antibodies) is an effective therapy for TEN. This, again, suggests an immune cause of the syndrome.

So, to say the same thing in fewer words, TEN results from 1) abnormal metabolism of a drug leading to 2) the accumulation of drug metabolites which elicit an (auto)immune response which causes 3) an immune reaction.

3

Wow, I’m glad I’m taking immunology right now. It’s cool when something from the real world pops up in your classwork.

Anyway, Dr. Gauss, what’s the prognosis from acute TEN like in this photo onward? I presume that infection is a relatively major risk. Also, what will the skin eventually return to?

4

Sorry, one more question. What’s your specialty?

Thanks,
threemae

5

Thank you KarlGauss! Far more in depth response than I was able to find anywhere else. .

6

I can answer that question with some reservation. It would be treated the same as a burn. It appears to be equivilant to second and third degree burns. Picture examples: scroll down the page, the first picture is a second degree thremal burn the second is a full thickness or third degree. If you’re squeamish, don’t continue from there. The remaining pictures are graphic.
Treatment for second degree burns is supportive. Preventing infection is very important. Keeping the area from drying out helps prevent contractures of the skin from scarring. Keeping the patient hydrated is very important, since extensive second degree burns can cause hypovolemic shock. Nutrition is necessary for healing, so tube feedings, for severely injured patients are started immediately.
Also, untreated second degree injury can progress to full thickness (third degree) as tissue death continues.
Full thickness injury must be treated with skin grafting. Infection control is even more important, since grafts will fail if they become infected. Autografting is most common (taking skin from an uneffected part of the patient’s own body) Skin culturing* is done when possible, especially for patients with burns so extensive, they don’t have enough donor area.
Allografts (Donor skin) and porcine graft (pig skin) can be used as a stop gap, but very rarely “take.” They are used to prevent infection and fluid loss until the patient is stable enough for autografting.

  • I couldn’t find the research article done in San Diego I was involved with. It may not be on-line. It was in The New England Journal of Medicine. I think the year was 1991, but I can’t remember for sure.
7

There is an additional problem that I don’t think the previous posters mentioned:

In many burn injuries the burn is limited in area, so there is some healthy skin to work with. Also problems like dehydration are less severe with less area burned.

With TEN, it takes very quick recognition of the problem and immediate treatment to keep it from removing every last square inch of skin from the body - only two people are known to have survived that, ever.

One article I found said that the death rate from TEN can be as high as 75%, depending on the setting (was the patient immediately rushed to an urban level-I trauma center, or was she deep in the wilderness, 5 hours from the nearest hospital, for example.)

8

That’s why I mentioned skin culturing.
The first patient in our study was 99% full thickness. Only the bottoms of his feet were available. The team was able to culture enough skin to cover all but the fingers of one hand. He was even given new eye lids.
TEN is very similar to skin graft vs host disease in bone marrow transplantation, but it progresses faster.

9

Wow. Horrifying.

Thanks, picunurse.