Pyoderma gangrenosum, acne and ulcerative colitis in a patient with a novel mutation in the PSTPIP 1 gene

Summary Background Pyogenic sterile arthritis, pyoderma gangrenosum and acne ( PAPA ) syndrome is a rare hereditary, autosomal dominant, auto‐inflammatory disease caused by mutations in the PSTPIP 1 gene, which encodes proline–serine–threonine phosphatase interacting protein 1. The fact that PSTPIP 1 is involved in immune regulation provides a rationale for treatment of this rare disease with interleukin ( IL )‐1 signalling blocking agents. Aim We investigated a 33‐year‐old man with a long‐standing history of ulcerative colitis, severe acne and recurrent skin ulcerations, and a 3‐year history of a recalcitrant pustular rash. Methods We used direct sequencing to search for mutations in the PSTPIP 1 gene. Results Examination of biopsies obtained from pustules and skin ulcers revealed folliculitis and ulceration with a diffuse neutrophilic dermal infiltrate, consistent with a diagnosis of pyoderma gangrenosum. Because of the known association of acne and pyoderma gangrenosum in PAPA syndrome, we determined the entire coding sequence of the PSTPIP 1 gene, and identified a hitherto unreported heterozygous mutation predicted to alter a highly conserved residue (p. G 403 R ) and to be damaging to the protein function. Based on this finding, we initiated treatment with a human IL ‐1 receptor antagonist, anakinra, which led to a dramatic improvement in the patient's condition. Conclusions We describe a novel mutation in PSTPIP 1 resulting in pyoderma gangrenosum, acne and ulcerative colitis. This novel constellation of clinical manifestations, which we term ‘ PAC syndrome’, suggests the need to regroup all PSTPIP 1 ‐associated phenotypes under one aetiological group.