title: Pyoderma gangrenosum, acne and ulcerative colitis in a patient with a novel mutation in the PSTPIP1 gene.
abstract: BACKGROUND
  Pyogenic sterile arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is a rare hereditary, autosomal dominant, auto-inflammatory disease caused by mutations in the PSTPIP1 gene, which encodes proline-serine-threonine phosphatase interacting protein 1. The fact that PSTPIP1 is involved in immune regulation provides a rationale for treatment of this rare disease with interleukin (IL)-1 signalling blocking agents.
  
  
  OBJECTIVE
  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 PSTPIP1 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 PSTPIP1 gene, and identified a hitherto unreported heterozygous mutation predicted to alter a highly conserved residue (p.G403R) 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 PSTPIP1 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 PSTPIP1-associated phenotypes under one aetiological group.
authors: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors: T
authors: T
authors: Zeeli
authors: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors: G
authors: G
authors: Padalon-Brauch
authors: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors: E
authors: E
authors: Ellenbogen
authors: Department of Institute of Pathology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors: A
authors: A
authors: Gat
authors: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors: O
authors: O
authors: Sarig
authors: Department of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors: E
authors: E
authors: Sprecher
mesh_terms: D000152:Acne Vulgaris / Q000235:genetics*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D001170:Arthritis, Infectious / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D017511:Pyoderma Gangrenosum / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C486382:PSTPIP1 protein, human