Doctors are discovering new autoinflammatory diseases almost every month. The latest autoinflammatory disease is 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 biologic medications was ineffective in these children. As a result, doctors thought 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 your body produces to fight viral infections; in a sense, they are your body’s antiviral medication. Usually, these molecules are tightly regulated–they are activated when you get the flu and go away when you recover.
In patients with STING mutations, however, interferon is always active. Your body makes antiviral molecules as if it were infected with a virus, but no virus can be found. These molecules, no longer tightly regulated, seem to cause the signs and symptoms of SAVI. Fortunately, doctors found that a new type of medication (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 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.
