The Situation here is a scenario where poison joke flowers somehow manage to take root in the Human world and because they're an invasive species and because they still retain the magic of the Everfree forest, spread across the planet and begins mutating every living creature that touches it.

While the mutations in the show are played down due to the cartoon style. In a more realistic style and if a Human came into contact with them, let's just say that it would be straight up Body Horror.

I have the feeling that some of the afflictions and illnesses seen in the show and other parts of G4 aren't so harmful to the ponies but is apocalyptic and species-threatening in scale to the humans as the cure can only be found and accessed to in Equestria.

This idea reminds me of that cursed grove in one of the fablehaven books where the characters had to go through a giant forest of fruit trees that were cursed to be extremely tempting to the point of madness but when eaten had extremely horrific and sometimes fatal effects

....But poison jokes only exist in equestria dude.......if they were here, why won't the cure too?.

Wait. Body Horror? Like the forest?

...id panic at first
Inagine walking into one not realizing it and suddenly? Your most ironic joke comes to life
I'd probably lose my imagination!

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I’m thinking more of a simple body horror then full on horror.

Stuff like.

My friend’s hair is long now.

Dude who once was tall is now very short.

My friend can’t speak due to a new lisp developed, oddly sounds like a horse.

These trees are hunting me… fuck you nature.

Solution:

I actually like this idea a lot. But, can we make it apocalyptic? I don’t think so. Let’s try to rationalize it. Poison Joke is the magical spinoff of poison oak. Maybe we can have it work through the same principles.

Poison oak contains a toxin called Urushiol. This induces a delayed type IV immune reaction in the form of contact dermatitis. This is nerd for: the body takes a few days to figure out what’s happening and it sends immune cells to freak the fuck out and make a rash. Upon first exposure, there’s no reaction. The body hasn’t “learned” yet (this could take up to 14 days for learning to complete). Upon second exposure, a powerful reaction occurs as CD8 cytotoxic T cells (the big guns) come to trounce on the perceived threat. This will only take 1 to 3 days before a rash.

So, how can we work this into poison joke? You said you wanted body horror, which I love you for that. Body horror is the best kind. In the show, poison joke is ironic. Fluttershy has a deep voice, rainbow is uncoordinated, Rarity’s appearance is what she would probably call “uncouth.” In your scenario, the poison joke might make abominations out of its victims that reflects their character flaws. For example, a prideful man might turn into a warped monster with several eyestalks that bend inward and are constantly trained on his own body. If he hears anyone come near by, the monster’s eyes might swivel off of its body and then it will become enraged for having its narcissistic daydream interrupted.

A Korean comic by the title of “HOME” does this concept extremely well but it isn’t limited by the nature of the spread of our poison joke as they never definitively say what caused the monster apocalypse IIRC. In our situation, the sessile nature of these plants makes it hard to do anything greater than a simple point source outbreak.

But don’t fear because point source outbreaks can be extremely serious. Maybe write a story where a group of hikers in a small town goes through a nearby trail, and they unwittingly come across the poison. Let’s say that they’re trying to get to the top of the mountain and they want to check out the trail first before actually completing the summit. We can say that the poison doesn’t have the very long 14 day sensitization delay that typical poison oak does. So the following day, they go back on the trail and pass through the same patch of poison joke. They complete the summit and then they come back to the town and go to bed. Suddenly, the following morning, there’s an outbreak of maybe 5 to 10 monsters inside the town. You could write some sort of drama or mystery where a governmental institution is trying to figure out what happened while also causing a cover-up in order to keep panic from spreading at the obvious supernatural disease.

That’s my two cents let me know if that helps.