PAPA syndrome is a rare autosomal dominant disorder characterized by the triad of pyogenic sterile arthritis, pyoderma gangrenosum (PG), and acne.

Arthritis typically presents in childhood and is often how the disorder initially manifests. Joint involvement is monoarticular, aseptic, and characterized by a prominent neutrophilic infiltrate. The arthritis is recurrent and often induced by a traumatic event, but episodes can occur spontaneously. As the disease progresses, joint erosion can ensue, eventually leading to articular destruction.

Cutaneous involvement varies. Nodulocystic acne and PG typically develop in puberty and persist into adulthood. However, pathergy is frequently observed, so minimal trauma may induce ulcers earlier in life. In PAPA syndrome, PG is typically similar to its classical presentation and the inflammatory components of acne typically predominate.

Various mutations in the PSTPIP1 gene on chromosome 15q have been identified in PAPA syndrome. These mutations impair the interaction between PSTPIP1 and PTP-PEST phosphatases, causing the hyperphosphorylation of PSTPIP1. It is suggested that this leads to the activation of the inflammasome, overproduction of IL-1ß, and thus neutrophil-mediated inflammation.