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Itachi's mysterious sickness

Back in August, I started seriously asking myself the question - what disease does Itachi
have? When the internet couldn't give me anything better than 'advance-the-plot-itis,' I
decided to take matters into my own hands.

After months of intense research, I think it's finally time to give Itachi Uchiha a REAL
diagnosis... microscopic polyangiitis.

In short, MPA is a rare form of systemic vasculitis. It is an auto-immune disorder,

characterized by antineutrophil cytoplasmic antibodies attacking the small vessels, causing
them to bleed as they become damaged and inflamed. It can have far-reaching consequences
throughout different organ systems that, when compared to Itachi's mysterious sickness, is
nothing short of startling.

The most visible symptom of Itachi's illness is hemoptysis.

The hemoptysis is, more likely than not, a result of diffuse alveolar hemorrhage. This is a
classic symptom of MPA when it presents with pulmonary manifestations. There is also
shortness of breath, and coughing.
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Unlike many other forms of vasculitis, such as wegener granulomatosis for example, the
upper respiratory tract is usually spared. All the damage is deeper in the lungs. Itachi's case is
consistent with this.

Other symptoms along the same vein can be seen during his final battle with Sasuke when
Itachi grabs his shirt, reacting to what appears to be a heart attack.

Chest pain, myocardial infarction and other signs of cardiac failure are not uncommon effects
of this disease, especially considering how it presented.

It is also no secret that by the time of his death, Itachi was nearly blind. This, we know, to be
a direct result of the mangyeko sharingan. When the mangyeko is used, it clearly puts a
tremendous amount of strain on the eye, and the nerves and blood vessels that surround it.
Needless to say, it's inflammatory in and of itself. But it is hasty to assume that Itachi's eye
problems are caused by the mangyeko alone.

Ocular involvement in MPA is uncommon, but can exist - usually in the form of retinal
hemorrhage and scleritis. The bloodshot eyes Itachi sports in his final battle with Sasuke show
these symptoms clearly.
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And given this, it's no stretch to assume that MPA played a large role in accelerating the
damage the mangyeko did to his eyes, hastening his vision loss.

Those are the only clues to Itachi's symptoms given outright in canon. But we can extrapolate
others from the way he conducts himself.

His low stamina as reported by the databook suggest constitutional symptoms of malaise and
fatigue. The peculiar way he rests one hand in his cloak could be an attempt to alleviate
painful sensations attributed to peripheral nervous system involvement manifesting as
mononeuritis multiplex or myalgia, or simply to support a weakened limb. One could
probably even argue his thin stature is evidence of weight loss.

There are, of course, come classic manifestations of MPA that cannot be observed in Itachi.
This, however, dos not mean that they can't be rectified.

One of the most common ways MPA manifests itself is with renal involvement. We have no
evidence that Itachi's kidneys have been damaged by disease. However, it is possible the
damage is there, and simply did not produce outward, observable symptoms. At least half the
cases of MPA also report skin involvement. This can range from small blisters to necrosis and
gangrene. There are reports, however, of MPA only causing splinter hemorrhages, or small
areas of bleeding under the nails. As the Akatsuki always wear nail polish, this would be
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completely unobservable.

Long story short, the symptoms fit. In fact, they're pretty much textbook.

Next, we consider what we know about how the disease was managed. Madara describes
Itachi's disease to Sasuke in one panel.

There, he reveals that Itachi took a variety of different medicines to keep himself alive. He
could easily be describing the treatment of MPA, which requires a combination of different
steroids and immunosuppressive agents. Because treating the disease requires suppressing his
immune system, Itachi likely needed other drugs as well, including specific types of
antibiotics and vitamins. Considering the high mortality rate of untreated microscopic
polyanglitis, (a five-year survival rate of under 25%) this really did have the purpose of
prolonging his life. Madara did not lie.

Lastly, we consider the prognosis.

The average age of onset is usually in the fifth decade of life, but cases around Itachi's age
have been reported in medical literature. The cause of the disease is currently unknown. It is
seen as an auto-immune disorder, but because it doesn't have a tendency to run in families, it's
not viewed as genetic. (Sasuke, after all, is still healthy.) However, it is theorized that there
needs to be a trigger event, such as a disease or a major bout of inflammation that sets the
production of antibodies into overdrive. This trigger could easily be the initial, or repeated,
activation of the mangyeko sharingan, which as stated before, is clearly inflammatory in and
of itself.

The natural course of the disease fits cleanly into the time line of canon events as well. It is
conceivable that, in the period of time following the chunin exam arc, he fell victim to the
disease in full force. His whereabouts are unknown during the time-skip, where he likely
managed to control it through medication, go into remission and then relapse again. That
relapse would be the deciding factor in seeking out his final battle with Sasuke. The time
between induced remission and relapse is usually around 2 years if it occurs, again fitting
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nicely with the chronology of the canon universe. And his death at Sasuke's feet is thus, easily
explained.