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Pyoderma gangrenosum, acne and ulcerative colitis in a patient with a novel mutation in the PSTPIP 1 gene
Author(s) -
Zeeli T.,
PadalonBrauch G.,
Ellenbogen E.,
Gat A.,
Sarig O.,
Sprecher E.
Publication year - 2015
Publication title -
clinical and experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.587
H-Index - 78
eISSN - 1365-2230
pISSN - 0307-6938
DOI - 10.1111/ced.12585
Subject(s) - pyoderma gangrenosum , medicine , ulcerative colitis , acne , dermatology , inflammatory bowel disease , generalized pustular psoriasis , missense mutation , gene mutation , immunology , mutation , pathology , disease , gene , psoriasis , biology , genetics
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.