PReS-FINAL-2324: PAPA syndrome clinical spectrum and IL-1Β release

Introduction Pyogenic sterile Arthritis Pyoderma gangrenosum and Acne (PAPA) syndrome is a rare autosomal dominant inherited autoinflammatory disease caused by mutations of Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1). In childhood, the syndrome is featured by recurrent sterile, erosive arthritis, potentially leading to joint destruction. By puberty, cutaneous symptoms become predominant, with recurrent onset of pathergy, abscesses, severe cystic acne, and pyoderma gangrenosum. Typically, both articular and cutaneous outcomes occur following a minor trauma. PSTPIP1 may interact with ASC and caspase-1 but a clear involvement of interleukin (IL)-1b and the role of NLRP3 is still controversial. While anti-IL1 treatment seems to be effective on joint manifestations, IL inhibition does not display the same effectiveness in the management of skin lesions.