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1.
A fight between two or more people on twitter. Most commonly with one side suffering a severe mental issue causing said twuffle in the first place.

Consisting of, but not limited to; fight, battle, tussle, scuffle, war.
I'm in a twuffle with Audi's marketing team over Twitter best practices. It's terribly one-sided.
by TwuffleMaster April 26, 2011
 
2.
a person who is everything nothing and something all at the same time.
you are a twuffle.
by ellamendez October 29, 2014