Acral Cutaneous Thrombotic Vasculopathy and Covid-19 Infection: Search for Acquired Thrombophilia and Interferon-alpha Signature

Spectrum of skin lesions may arise during Covid-19 virus infection. It includes non-specific urticaria, aphtoids lesions, but also acrosyndromes, in particular suggestive of chilblains. Pathological findings showed thrombocytic lymphocytic vasculitis. Chilblains are sometimes associated with Raynaud's phenomenon or acrocyanosis. Dermatological features may present pathophysiological similarities with the inflammatory and respiratory vascular disturbances, which makes all the gravity of this disease, or even with other organs. Indeed, genetic conditions such as familial lupus chilblains, linked to a mutation of TREX1 gene, and SAVI (Sting associated vasculopathy with onset on infancy) have similar clinical presentations. In particular, SAVI associates both acral skin and lung damage, and auto-antibodies. They have recently been identified as type I interferonopathies. Hallmark is interferon signature, i.e. hyperexpression of type I interferon in the blood.

The investigators hypothesize Covid-19 may lead to similar skin involvement as in type I interferonopathies. The interferon pathway is involved in anti-viral defense. Covid-19 could cause excessive activation of this pathway. In addition, hyperactivation of the type I interferon pathway leads to modulation of the adaptive immune response. Production of autoantibodies, in particular antiphospholipid antibodies, have thrombogenic properties. Searching for acquired hemostasis disorders and high level of interferon secondary Covid-19 virus infection, could explain this new and misunderstood skin disorder. Then, targeted therapies, both treating and preventing, could be considered.