PROGRAMM JAHRESTAGUNG 2012 30. Nov. – 2. Dez ... - ÖGDV

Freie Vorträge
FV 3
A novel recessive PAPA-like syndrome responsive to Canakinumab
Alexandra Geusau 1
Nadine Mothes-Luksch 1
Hesam Nahavandi 2
Winfried F. Pickl 3
Carol A. Wise 4
Zahra Pourpak 5
Elisabeth Ponweiser 6
Leopold Eckhart 7
Raute Sunder-Plassmann 6
1 Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases
(DIAID), Medical University of Vienna, Austria
2 Medical Department, Hanusch Hospital, Vienna, Austria
3 Institute of Immunology, Medical University of Vienna, Austria
4 Sarah M. and Charles E. Seay Center for Musculoskeletal Research, Texas Scottish Rite
Hospital for Children, Dallas, TX, USA
5 Immunology, Asthma and Allergy Research Institute, Tehran University of Medical
Sciences, Tehran, Iran
6 Department of Laboratory Medicine, Medical University of Vienna, Austria
7 Department of Dermatology, Research Division of Biology and Pathobiology of the
Skin, Medical University of Vienna, Austria
Introduction: Pyogenic arthritis, pyoderma gangrenosum, and acne, i.e. PAPA
syndrome (OMIM 604416), is a rare autosomal dominant inherited autoinflammatory
syndrome, characterized by pyogenic sterile arthritis less frequently accompanied by
pyoderma gangrenosum, and acne. Previously reported cases of PAPA syndrome were
associated with dominant missense mutations in the proline serine threonine
phosphatase-interacting protein 1 (PSTPIP1) gene localized on chromosome 15.
PSTPIP1 has been suggested to be involved, amongst other processes, in the regulation
of interleukin-1 beta processing.
Methods: We diagnosed a patient with features of PAPA syndrome but with emphasis
on cutaneous manifestations including pyoderma gangrenosum and acne fulminans-
The PSTPIP1 gene of the patient and his extended family was sequenced. The patient
was treated with Canakinumab, a human anti-interleukin-1 beta monoclonal antibody.
Results: DNA sequence analysis of the patient revealed a homozygous nucleotide
exchange c.773G>C in the PSTPIP1 gene leading to the substitution of glycine 258 by
alanine (p.Gly258Ala). Heterozygous changes at the same nucleotide were identified
in both of the patient's parents and in seven other family members, each of them
asymptomatic. Treatment with Canakinumab led to rapid remission of the symptoms.
In conclusion, our study provides evidence of a novel PAPA-like syndrome, an
autoinflammatory disorder with a recessive inheritance pattern. PAPA and PAPA-like
syndromes appear to have great variations in the expression of clinical phenotypes.
Importantly, this is the first reported instance worldwide of a patient with PAPA-like
syndrome successfully treated with an anti-IL-1beta monoclonal antibody.
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