SAVI, the new autoinflammatory kid on the block

Doctors are discovering new autoinflammatory diseases almost every month.  The latest autoinflammatory disease is called STING-associated vasculopathy with onset in infancy, or SAVI.  As the name implies, the disease becomes noticeable shortly after birth: infants develop a rash, nodules, fever, lung abnormalities, and ulcers or gangrene in their fingertips.  Blood testing shows elevation in markers of inflammation, as are normally seen in autoinflammatory diseases.

However, unlike other autoinflammatory diseases, treatment with steroids and with biologic medications was not effective in these children.   As a result, doctors thought that this constellation of symptoms may be due to a new disease.  They were right–genetic testing in affected children showed a new mutation in a gene that makes a protein called STING.  This mutation causes uncontrolled production of type I interferons.  Interferons are molecules that your body produces to fight viral infections; in a sense, they are your body’s antiviral medication.  Usually, these molecules are very tightly regulated–they are activated when you get the flu, and they go away when you recover.

In patients with STING mutations, however, interferon is active all the time.  Your body makes antiviral molecules as if it were  infected with a virus, but there is no virus to be found.  It seems that these molecules, no longer tightly regulated, cause the signs and symptoms of SAVI.  Fortunately, doctors found that a new type of medication (called JAK inhibitors) can block the effect of the antiviral molecules, and may be useful in children with SAVI.

Children with SAVI do not have significant elevations in IL-1 and IL-6, the main drivers of inflammation in most autoinflammatory diseases.  Instead, the vehicle for inflammation in patients with SAVI is interferon.  Despite essential differences in fuel, the end result–systemic inflammation, fever, rash–is characteristic of an autoinflammatory disease.  Further proof that all roads lead to Rome, even those within our own bodies.