Identification of a homozygous PSTPIP1 mutation in a patient with a PAPA-like syndrome responding to canakinumab treatment

Alexandra Geusau, Nadine Mothes-Luksch, Hesam Nahavandi, Winfried F. Pickl, Carol A. Wise, Zahra Pourpak, Elisabeth Ponweiser, Leopold Eckhart, Raute Sunder-Plassmann

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

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. Observations: 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.

Original languageEnglish (US)
Pages (from-to)209-215
Number of pages7
JournalJAMA Dermatology
Volume149
Issue number2
DOIs
StatePublished - Feb 2013

ASJC Scopus subject areas

  • Dermatology

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