Chronic Angelus Crystallus Inofficium (永続天使性無機結晶症?, "Persistent Angel Inorganic Crystal Disease"), initially referred to as Angel Toxicosis, is a sickness in Tales of Symphonia that affects one-in-a-million users of Cruxis Crystals. The only known people to have had this disease are Martel Yggdrasill and Colette Brunel.
The primary symptom of the sickness is the Cruxis Crystal causes the victim's skin to crystallize, eventually leading to death when their internal organs freeze. At the time of her sickness, Colette believes she is going to become "one big Exsphere". Another symptom may involve mana drain, as Colette often collapses in pain after being brought back from her soulless state. Although the specific reason for Colette's rejection of her Cruxis Crystal is unknown, she may have contracted the sickness because of the lack of a Key Crest, which Lloyd Irving eventually gives her. Another possibility is directed toward her mana signature being the same as Martel's, the only other known individual to contract the sickness.
In order to cure the sickness, a "Rune Crest", another version of the Key Crest, is needed. To create a Rune Crest, a "Mana Fragment", a "Mana Leaf Herb", and "Zircon" are required, in addition to the power of the "Unicorn Horn". To collect these necessary ingredients, Lloyd and his companions travel to various locations, including Heimdall and Derris-Kharlan. Afterward, the group gives the items to Altessa, who makes the Rune Crest, which cures Colette.