PAPA Syndrome

Abstract

PAPA syndrome is a hereditary autosomal auto-inflammatory disorder characterised by the presence of pyogenic arthritis, pyoderma gangrenosum and acne. The onset of the disease usually occurs in childhood with osteoarticular symptoms followed by the development of skin manifestations in puberty. Similarly to other auto-inflammatory disorders, the pathogenesis of PAPA syndrome is linked to a dysregulation of innate immune system with elevated levels of interleukin-1β and, consequently of TNFα and metalloproteinases responsible for inflammation and tissue destruction. PAPA syndrome usually begins in childhood (average 8 years) showing recurrent episodes of sterile non-axial arthritis. In most cases, skin manifestations occur at puberty or early before puberty with acne followed by episodes of pyoderma gangrenosum that may persist into adulthood. Topical treatments are used in some cases of pyoderma gangrenosum and acne. In most cases, they are not sufficient, and intralesional or systemic therapies are required. First-line systemic treatments of PAPA syndrome consist of glucocorticoids that are generally effective on skin and articular symptoms. In non-responding patients, treatments with disease-modifying anti-rheumatic drugs or biologic therapies are reported with good results.