Can I ask your thoughts, pertinent to the nature of Itachi's illness? Like, would you say that it has a connection with Kimimaro's mysterious illness? Or, alternatively, that it stemmed from utilizing The Mangekyō Sharingan, and The Susano'o?
Also, Welcome Back To Naruto Base ! X'D < 3 !
Thank you! My honest thoughts are that they're probably two unrelated illnesses that Kishimoto used to weaken both characters before their fights to advance the plot. I'll try to come up with something just for the sake of it, though since I don't think it's too absurd to say that they may be connected.
Regarding Kimimaro's illness, this is the most popular theory:
The Kaguya clan's kekkei genkai allowing them to strengthen, grow, and repair their bones through osteoblast and osteoclast cell manipulation. However, Shizune warns us about cell manipulation and overusing cell division with the consequences of Tsunade's ability a few arcs prior.
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One could assume that the Kaguya clan's kekkei genkai falls under the same rule and that the more it's used, the more it lessens the user's lifespan. This could result in something such as a much weaker immune system or a very specific illness that stems specifically from the constant use of osteoclast cells in the regeneration and maintenance of the users bones.
The biggest issue with this would be this line that Kabuto drops in a flashback. This is where I drop the previous theory.
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As far as medical knowledge goes, I don't think there's too significant of a gap between Kabuto and Shizune. I think Kabuto would come to the same conclusion as Shizune if "too much cell division" was the case. It also seems like the most simple answer. So, you have to look at what information both Kabuto and Orochimaru are missing in regards to the Kaguya clan.
Well, the fact that the Kaguya clan are descendants of Kaguya Otsutsuki.
You can view Kimimaro's illness as a consequence of using the Shikotsumyaku to the point of passing the limits of his body - as a descendant of the Kaguya clan so many generations removed from the Otsutsuki. He would still have the capability of using the technique but not the same mastery or frequency as a clan member from an earlier generation, who would have a less "diluted" version of the technique and their body would be closer Kaguya's.
Itachi's illness would be the Uchiha variant of it, as the Uchiha are also descendants of the Otsutsuki and the Sharingan come from Hagoromo. Apply the same line of thinking from the Kaguya clan to the Uchiha and now you have a different reason for why they cannot use the Mangekyo Sharingan as much. The blindness and constant cell damage would come from their bodies not being built to withstand it as a result of their bloodline distancing themselves too much from the Otsutsuki. It would also only stack further and further with each generation. Perhaps this is why someone like Madara never encountered the same illness, also helps that he obtained the EMS early.
Otsutsuki descendants suffer from these genetic illnesses and they probably also compound with incest related health issues as the clans try to retain enough genetic purity to guarantee their offspring obtain the kekkei genkai. The Kaguya clan is probably the most guilty of that last point, since they were a ferocious blood-thirsty clan made for combat. It's not unreasonable to assume they would have kids at a young age and die relatively young as well, so most probably did not get to see the consequences of overusing the kekkei genkai like Kimimaro did. They would also never find out what their equivalent of the Mangekyo Sharingan is; At least the Uchiha figured out a loophole and could negate the negative effects of overusing their powerful kekkei genkai.
That's all I have. I haven't read the novels but apparently Hagoromo and Naruto had some similar disease? Someone with more knowledge than me could fill in those blanks. I don't buy into this theory too much, I just thought it would be fun to come up with something.
