The Ashtown Concordance is an agreement between the Skizziks and Lorcatha families that was signed long ago in the city of Ashtown that enforced a restraining order between them.
What led up to it
The Skizziks and Lorcatha families were "rivals". Per the 'Enter the Trash Witch' podcast, in which Strix was summoned to the Acq Inc airship through a different infernal contract (purchased by Omin to force the greatest member of the Skizziks family to serve the summoner), Omin's research revealed that the Skizziks were originally a human family in Sigil that was nearly wiped out by the Lorcatha, and that "fearing annihilation...[they] forged a pact with the Nine Hells and Asmodeus himself, [and] were transformed into tieflings [which] tainted them...forever." They were also awarded "vassals...of the devilish persuasion" to serve them as bodyguards and assistants, which Omin compared to a "lower planar mafia-type thing".
When trapped in a nightmare inside Dendar the Night Serpent's temple, a vision of the god Ubtao greeted Strix, but told her mixtures of truth and lies, claiming he was only a human who got mazed by the Lady of Pain, and that Strix's encounters with the Crew were just stories she made up when she found their dolls. Interestingly, he also told her that the Skizziks "became" a kazram "at the the end of the wars, after so many died on both sides, and the Accords were reached".
He described the Lorcatha as "another family of humans, with ties to the angelic world, [who] had angels try to help them". Nevertheless, "in the end, it looked like they were going to be destroyed, so some sort of deal was reached...to keep the multiverse in balance". When Strix asked why Mercykillers had been sent to get her, Ubtao guessed, "maybe because you were trying to break the deal...that the two sides would never go to war again, and never bring the multiverse to the precipice of annihilation again, [and that] they never had anything more to do with each other". Although anything this fake Ubtao said could be considered suspect, when Diath insisted that Shemeshka teleport him back to the Crew so he could either stop the force bomb or die alongside them, she scoffed at his feelings and said, "this is exactly [what caused] you mortals to...nearly destroy the multiverse twice already".
Izek also explained to the Crew while in a Zone of Truth that (in Chris's words): "the Skizziks and the Lorcatha are two families that were largely based in a faraway city--he doesn't know what it's called or where it is [at which point Holly laughs and says it's called Sigil.] He tells you that they were spread far and wide and they had a lot of power and influence, but...they hated each other...their blood had been spilled for eons...and there was no reconciliation possible. He also tells you that some of the Skizziks forged a pact with devils and were turned into tielfings, and with their newfound power and their alliance with Asmodeus, they sought to wipe the Lorcatha out, which led to a great multiversal conflict. Fearing that they would be annihilated, they tried to forge an alliance with the devils' ancient enemies--angelic beings from the plane of something-or-other, he doesn't know. This triggered a huge war that killed millions [Anna then wonders aloud why Evelyn has never heard of their holy war]. A peace was forced upon the two families, and all he knows is Asmodeus had a hand in it...a lot of very important 'cutters' had a hand in the crafting of this peace accord, which...he thinks he heard Lady Wachter call...the Ashtown Concordance, because apparently it was signed in a city or settlement that got dragged into hell called Ash Town, or Ashton. And as part of the peace, the Lorcathas had to give up their souls to Asmodeus except for one. All he knows is that Lady Wachter was always very interested in these stories and these two families...and may have a book or two that goes into detail about these conflicts." Referring to Diath, Izek then tells Strix, "If you stay with him, you'll destroy everything. You two can't be together. The Astown Concordance forbids it! No friendship, no alliance, nothing. The Skizziks will destroy you before they let you be friends with him." However, despite the properties of the Zone of Truth spell, Izek's words may still be suspect, as his explanation for how he lost his arm contradicted the fact that the Crew had recently seen him with both arms intact (one possibility is that Izek's memory had been altered, which might also explain why he was now friendly towards Lady Wachter).
What was the price
Both the Ubtao hallucination and Izek said that as a price for peace, all the Lorcatha lost their souls but one. [One fan theory has been that Diath's keys--which were handed to him when he was younger by a hooded stranger that Kerek later noticed in the streets of Sigil had a face that was "half-angelic"--might represent these lost Lorcatha souls. However, Izek revealed that those souls went to Asmodeus, making this theory unlikely]. The one remaining soul is hinted to belong to Diath's ancestor, Dareth Woodrow, who Shemeshka had dealings with. Shemeshka was revealed by the Sewn Sisters to have mediated the Ashtown Concordance, and was awarded a piece of a soul (implied to be Diath's, which could be explained by the soul also having originally belonged to Dareth) as payment for her services, which she keeps in a box. The yuant-ti had told Diath he had "an ancient soul". In Dendar's hallucination, Diath had a vision of himself rising from the snow with a pair of angel wings freshly torn from his bleeding back [although Holly and many fans speculated at the time that Diath might be an Aasimar (an angel-human hybrid) or a Deva (a humanoid with a reincarnating angelic soul), Chris has confirmed through multiple NPCs that the Lorcatha were humans. Diath also took the feat "human determination", although Jared did say that he had to check with Chris that it was ok to do so. However, Shemeshka has commented that Lorcatha are filled with a kind of light. Shemeshka also said that Diath bears "a resemblance" to Dareth, and his father Ashton's dworc companion told Diath that "you look like him". When Magnus Burnsides met Diath, he was struck by how much Diath resembled someone he had traveled with ten years prior, but who had a crescent-shaped scar around the middle of his eyebrow. This is assumed to be Ashton, but Magnus couldn't remember anything else about him.
Shemeshka had forged the magical sword Gutter for Dareth, which was eventually passed down to Ashton, and finally to Diath. Gutter's relation to the Lorcatha is unknown, but the dworc did say that the sword "wants to be with the Woodrows". Since Dareth was a woman, it's possible her maiden name was Lorcatha and she married into the Woodrow line. Or 'Lorcatha' might be the name of a large clan or organization of smaller families, one of which was the Woodrows. Gutter's purpose appears to be tied to the keys, since it has a keyhole in its hilt that fits them, but will only allow any individual key to turn inside it once. Turning the key will also summon Shemeshka and bind her to answer any three questions that are properly phrased and relate to knowledge she actually possesses, but in exchange, she keeps the key. This is implied to follow an arrangement Shemeshka had previously made with Dareth, however Shemeshka is open to making additional deals, such as teleporting the Crew and allies to Chult in exchange for a specific favor enforced by a geas spell, and later teleporting Diath to the force bomb in exchange for an open favor. Gutter is also sentient and can mind-control its user to some extent, forcing the dworc to find Diath and carry it to him. Although Chris initially said that hearing its voice required attunement, Paultin was able to hear it ask "who are you?" the moment he picked it up. Gutter has also hinted that it enjoys being bloodied, and doesn't like being separated from Diath. Whether it has any additional motivations or purpose is unknown. Chris explained at PAX West that he had wanted one of the Crew to inherit a sentient weapon with a disturbing history tied to their past, and realized it had to be Diath. When Holly pointed out it was also connected to Sigil, Chris elaborated, "then somehow it has to be tied to Strix. And so how can I use this sword to bring Diath and Strix together, or pull them apart? What can I do as the DM to test the strength of that friendship?"
Per the Ubtao hallucination, the Skizziks "became" a kazram after the Accords, however we do not know what that word means. A Mercykiller told Strix that "the Skizziks kazram is after you". The infernal contract that Omin used to summon Strix may have been forced upon the family as an additional term of the Accords, but its origin is unknown other than the fact that Omin purchased it for a cheap price (10 gold) along with a pile of other documents in a sale, and that the contract is enforced by Asmodeus. While Diath may be the only remaining Lorcatha, it is implied that the Skizziks have thrived over the "eons" since the wars. At least two tieflings that were likely Skizziks members were seen in Sigil when the Crew fought the Mercykiller. In addition, during Diath's hallucination inside Dendar's nightmare, he was taunted by a swarm of cranium rats impersonating Strix who said, "we are many, you are one"  (however, this may also be in reference to the cranium rat hive-mind creature called 'The Us').
Diath and Strix were ignorant of their family history, but still managed to travel together for a time without triggering any reaction from the Accord that was supposed to forbid their families from interacting. Izek, despite being a Skizziks, was actually able to hang Diath in Barovia without any immediate consequences (Diath's soul was unable to pass on due being trapped in the Barovian mists both times he died, however the one time Izek killed him, a skull shape did appear in the clouds and ravens began attacking anyone nearby, which could be considered an unusual portent. It is also possible that Izek did not actually escape punishment, as he was later seen missing his demonic arm, despite him giving an excuse for it that didn't match the facts). However, it was not until after van Richten performed the Vistani soul-bonding ceremony that alarms were sounded and more serious steps had to be taken.
Consequences for breaking the treaty
Immediately after the ceremony, the dworc carrying Gutter appeared to Diath, and Shemeshka was summoned. She took note of Strix, commenting that years ago, she had tried to buy her from Baba Yaga, who had been taking care of her at the time. Shemeshka left a bad impression on Diath, who tried to resist summoning her again but was forced to when Strix later disappeared. Despite Shemeshka pointing out that Xandala was also a sorcerer and possibly a better replacement, she noted Diath's refusal, and how much he seemed to care for Strix. At that point, Shemeshka began to drop the name "Lorcatha", which Izek had also called Diath when they had been briefly pulled back into Barovia. She also warned Diath that "the Skizziks are coming for you".
The Skizziks did not come themselves, but hired a Mercykiller to bring Strix back to Sigil. Although Diath had not been the original target, the Mercykiller was aware enough of who he was that he knew he could still get something of value in exchange for him. Despite defeating the Mercykiller with Kerrek's help, Strix worried that her family would not stop sending people after them, and tried to turn herself in. Kerrek convinced her to stay, and despite spending many days looking over her shoulder afterwards, no one else immediately came after them.
although the treaty was signed in Ashtown, it is likely that a more official version was brought to the Hall of Concordance in Sigil. The typical procedure is that for a fee, contracts there can become magically enforced, with any breach causing the release of a near-indestructible construct called a Marut, which hunts down the offending parties and drags them back to the Hall to face punishment. Chris confirmed that "there is [a Marut] stomping its way towards Waterdeep right now". The signal for its release may in fact have been a pulse of energy that emanated from Strix and Diath after Diath gave her one of his keys for safekeeping, which Chris described as a "breach of protocol warning" or a "planar shockwave".
The reasoning for why a war between human families might put the multiverse in danger remains unclear, however, there is in fact a concern that an imbalance between the forces of good and evil could cause its collapse. Per Chris, Mordenkainen is one of the few who have foreseen this danger and put himself in charge of watching over this balance. Although the side of evil may hold an advantage in terms of sheer numbers, with seemingly countless chaotic evil demons swarming out of the Abyss, the lawful evil devils currently have their hands full keeping them in check and maintaining their control over the hells (a conflict referred to as the Blood War, in which fiends such as Shemeshka have been known to play both sides). If either the demons or devils were to win and turn their focused attention on the other realms, a multiverse-ending cataclysm could ensue. Although prior to Episode 100, neither the Blood War nor the conflict between celestials and fiends had been directly alluded to in the show, in the Amber Temple there was a fresco on a vaulted ceiling that Chris described as "angels being set ablaze in a hell", that when examined by Strix with a religion check, he further described it as "depict[ing] what appears to be an angelic incursion into the Nine Hells; good attacking evil, and evil retaliating. All the angels are fighting through flames and being charred to some extent in their descent. You think that symbolically it represents good fighting against evil and being forced to sacrifice themselves for the battle".
Diath and Strix could argue that they were unaware of the implications of the Vistani ceremony, which van Richten had only explained to them as a way for Evelyn to transfer Saint Markovia's blessing from her own soul into two rings which they wore, in order to protect them from the Death Curse. However, the rings proved to be important not only because they represented a bond between Diath and Strix that was not permitted to exist, but because of the underlying nature and magic of the ritual. Per Chris, the ceremony had originally been used by the Vistani as a form of marriage, binding two peoples' souls together. K'thriss, who had been given one of the rings by Omin--who was originally going to use them to help bring Evelyn back to life--was able to use his father's notes on magical ceremonies to discover that the energy in the rings could even affect the cosmic balance, potentially helping to bring dead gods back to life. K'thriss did not reveal to Diath that the rings actually represented a spiritual bond between him and Strix; however, Diath did allow K'thriss to keep borrowing the rings to try and free the C-team's gods, which he thought Evelyn would approve of. Rosie and K'thriss later visited Strix and Diath in Waterdeep, just as Evelyn and Paultin visited Walnut and Donaar in Red Larch. Both groups were confronted by Mercykillers who were after Strix, however the encounters were cut short when the spirits of an evil pair of married Vistani dark powers, newly awakened by the presence of Evelyn's rings, pulled them to their own domain of dread. They needed the rings to stay tethered to the material plane, again highlighting the importance of the magic inside them. van Richten also made an appearance in order to warn the Crew of the danger they were in due to the ceremony he had performed.
Ultimately, however, the biggest danger proved to be the spilling over of the Blood War into the city of Nightstone, which the Crew were next pulled into. Both devils and Skizziks kazram enforcers again tried to convince Strix to come with them, and again she refused. Finally they faced a pit fiend general and its powerful subordinate, and when the Crew and C-Team managed to hold them off, Asmodeus himself was finally forced to intervene. He was prepared to physically separate Strix and Diath, sending them each to different planes, until Rosie proposed adopting Strix into her Beestinger family so that the Accords no longer applied to her. Satisfied with that arrangement, Asmodeus warned them that he had limited influence in Sigil, and they might still have to face repercussions from the enemies they had made there. According to Chris, Omin has warned Diath (although this was never shown onscreen) that a Marut was coming for them. Whether that is still the case is unknown.
 Acquisitions Inc: Enter the Trashwitch. Penny Arcade Podcast (10:35-15:00)
 DCA Episode 78 (1:28:15-1:30:45)(1:48:52-1:49:17)(1:10:07-1:16:40)
 DCA Episode 80 (1:05:28-1:05:36)
 DCA Episode 85 (40:15-46:25)(48:46-51:01)
 Did Chris make a retcon or is Izek lying? DCA subreddit.
 DCA Episode 69 (2:31:25-2:34:15)(2:21:29-2:26:32)
 DCA Episode 53 (53:28-1:04:13)(1:20:20-1:39:24)
 DCA Episode 89
 DCA Episode 86 (45:35-45:40)
 DCA Episode 81 (4:50-5:46)
 DCA Episode 61
 DCA Episode 96
 DCA Episode 98 (1:42:05-1:43:05)
 DCA Episode 62
 DCA Episode 79 (42:39-43:00)
 Ask the Wafflecrew Anything Panel at PAX West. Twitch.com. (38:46-39:57)
 DCA Episode 8 (27:03-28:37, 39:26-47:13) and DCA Episode 9 (4:04-8:52)
 DCA Episode 52
 DCA Episode 60
 DCA AMA Session.
 DCA Episode 20 (1:02:17-1:05:25)
 Acquisitions Inc: C Team: S2 E19 and Table Talk Discussion. Penny Arcade Website.
 WafflesInc Crossover Episode 100. YouTube.