title: Identification of a homozygous PSTPIP1 mutation in a patient with a PAPA-like syndrome responding to canakinumab treatment.
abstract: BACKGROUND
  Pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome (OMIM 604416) is a rare autosomal dominant inherited autoinflammatory syndrome characterized by pyogenic sterile arthritis and less frequently accompanied by pyoderma gangrenosum and acne. It is associated with dominant missense mutations in the proline-serine-threonine phosphatase-interacting protein 1 gene (PSTPIP1) located on chromosome 15. The patient was diagnosed as having features of a PAPA-like syndrome in which cutaneous manifestations, such as pyoderma gangrenosum and acne fulminans, predominated.
  
  
  METHODS
  Sequencing of the PSTPIP1 gene was performed in the patient and his extended family. The patient's DNA analysis revealed a homozygous nucleotide exchange c.773G>C in the PSTPIP1 gene, leading to the substitution of glycine 258 by alanine (p.Gly258Ala), a previously reported heterozygous polymorphism. Heterozygous changes were identified in both of the patient's parents and in 7 other family members, all of whom were asymptomatic. The patient was treated with canakinumab, a human anti-interleukin 1β monoclonal antibody, which led to rapid remission of the symptoms.
  
  
  CONCLUSIONS
  To our knowledge, this is the first reported case of the resolution of dermatological symptoms associated with a PAPA-like syndrome using canakinumab treatment. Further study of the p.Gly258Ala variant is warranted to determine whether this mutation has a role in causing an apparently recessive cutaneous syndrome resembling PAPA syndrome.
authors: Division of Immunology, Allergy, and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. alexandra.geusau@meduniwien.ac.at
authors: Alexandra
authors: A
authors: Geusau
authors: Nadine
authors: N
authors: Mothes-Luksch
authors: Hesam
authors: H
authors: Nahavandi
authors: Winfried F
authors: WF
authors: Pickl
authors: Carol A
authors: CA
authors: Wise
authors: Zahra
authors: Z
authors: Pourpak
authors: Elisabeth
authors: E
authors: Ponweiser
authors: Leopold
authors: L
authors: Eckhart
authors: Raute
authors: R
authors: Sunder-Plassmann
mesh_terms: D000152:Acne Vulgaris / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D019943:Amino Acid Substitution; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001170:Arthritis, Infectious / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics*; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors*; D008297:Male; D009154:Mutation; D017511:Pyoderma Gangrenosum / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D012074:Remission Induction / Q000379:methods; D017422:Sequence Analysis, DNA; D013577:Syndrome; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003598:Cytoskeletal Proteins; D053583:Interleukin-1beta; C486382:PSTPIP1 protein, human; C541220:canakinumab