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The Plague Fiend is an abomination made up of toxins and the like. It seems to be the source of all the toxins that pollute the Sky Dominion.
Despite the fact that this boss is rather early to face, this ugly blob is tough. Only a few bosses in the game are harder to beat. You should attack it at no less than Level 45 and with the Javelin of Blinding.
The difficulty of this boss has more to do with the tiny arena you face it in. There is little room to maneuver, so consider purchasing ample amounts of Invulnerability power-ups before heading into this one. 3-Way Shots, Rapid Fires, Super Shots, and Fire Amulets also help out immensely.