Sting-associated vasculopathy M35.8

Rare autosomal-dominantly inherited autoinflammatory disease that is classified as a type 1 interferonopathy due to constitutive STING activation (STINGis the acronym for "STimulator of INterferonGenes").

The type 1 interferonopathies represent a group of rare, genetically and phenotypically heterogeneous disease entities caused by a dysfunction of the innate immune system (Crow YJ 2011). With the exception of multifactorial SLE, these are very rare diseases.

Pathogenetically, the type 1 interferonopathies are based on disturbances in the metabolism and in the immunological recognition of intracellular nucleic acids.

STING-associated vasculopathy is based on heterozygous de novo gain-of-function mutations in the TMEM173 gene encoding the cGAS-associated adapter molecule STING, leading to constitutive activation of the IFNB promoter with upregulation of type I interferon production (Günther C et al. 2016).

STING-associated vasculopathy manifests in early infancy with systemic vasculitis leading to severe necrotizing skin lesions of the face and acras, accompanied by episodes of fever and interstitial lung involvement (Liu Y et al. 2014).

The skin lesions resemble lupus vasculitis. Numerous mutations in the STING1 gene (syn: TMEM173 gene) with different phenotypes have now been described . A dominantly inherited TMEM173 mutation in a family with STING-associated vasculopathy and SLE symptoms caused symptoms such as arthritis, fever, butterfly erythema and antinuclear antibodies (Jeremiah N et al 2014).

In addition to the clinical symptoms (fever, vasculitic changes with nasal septal perforation, skin necrosis and lung involvement in the sense of tachypnoea and, in the course, pulmonary fibrosis), patients show increased inflammatory parameters in the blood.

In addition to ANAs, anti-phospholipid antibodies and occasionally c-ANCA can be detected.

In addition to symptom-oriented diagnostics (capillary microscopy, lung function, HR-CT), an infectious cause of the symptoms should be excluded.

Genetic diagnostics to detect the existing mutation in TMEM173 (coding for STING) should be initiated.

Due to the activation of the type I interferon system, therapeutic approaches consist in the inhibition of Janus kinase(JAK inhibition).

Baricitinib as a JAK1/2 inhibitor was able to show an improvement of the symptoms as well as the inflammatory parameters in the blood (including the interferon signature).

1. Crow YJ (2011) Type I interferonopathies: a novel set of inborn errors of immunity. Ann N Y Acad Sci 1238:91-98
2. Crow YJ et al (2015) Aicardi-Goutieres syndrome and the type I interferonopathies. Nat Rev Immunol 15:429-440
3. Guenther C et al (2016) Type I interferonopathies. Z Rheumatol 75: 134-140
4. Jeremiah N et al (2014) Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations. J Clin Invest 124:5516-5520
5. Liu Y et al (2014) Activated STING in a vascular and pulmonary syndrome. N Engl J Med 371:507-518