The Red Madness is an epidemic that started affecting Enderal after the death of the Light-Born. Those affected by the Red Madness seem to go insane, attacking everything and everyone in their path, yelling about the need for the world to be purified, with their eyes glowing red (and thus the name "Red Madness"). Grandmaster Tealor Arantheal believes that the Red Madness is a symptom of the approaching of The Cleansing.
The only visual symptom of the Red Madness is the iconic red glow that emanates from the eyes of the afflicted, from which the name "Red Madness" comes from. Other symptoms come in a change in behavior: The afflicted starts attacking everyone in sight, with no regards to even their own safety. This is usually accompanied by a mad ranting about "Purifying the corrupted world" and "freeing" those being attacked.
It could be possible that the Red Madness simply slowly degrades one's psyche, and that the more extreme symptoms are a mere consequence of that loss of sanity. This theory is further confirmed by Yero's Diary, whose last letter shows Yero Sunwind slowly abandoning his past ideals and developing a more crazy-like mentality, right before his infamous incident.
The method of transmission of the Red Madness is unknown, but it seems to be magical or spiritual in nature. The Holy Order initially thought that a Shard of the Sigil Stone was able to protect its wearer from the Red Madness, but this was later proven to be wrong.
The most likely explanation for the Red Madness is that the afflicted are being possessed by the High Ones, as the red glow shown in the afflicted's eyes is the same glow that appears on the eyes of objects or around dream figures manipulated by the High Ones. Since the Red Madness contributes to the Emperor's suspicion that leads to their discovery of The Cycle and eventual triggering of The Cleansing itself, the epidemic seems to simply be another "nudge" of the High Ones. As such, it is possible that the High Ones can possess and affect whomever they choose, at any time during a civilization's development. However, as with many others of their actions, they seem to have perfected whom to affect and when to affect them, in order to ensure that The Pattern is repeated as closely as possible.