Brief report: genotype, phenotype, and clinical course in five patients with PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne).

To describe the genotypes, phenotypes, immunophenotypes, and treatments of PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne), a rare autoinflammatory disease, in 5 patients.
Clinical information was gathered from medical records and through interviews with 5 patients from 4 kindreds. PSTPIP1 (CD2BP1) exon 10 and exon 11 sequencing was performed in each patient. Neutrophil granule content and cytokine levels were determined in plasma and stimulated peripheral blood mononuclear cells (PBMCs) from patients and controls.
We identified 2 previously described PAPA syndrome-associated PSTPIP1 mutations, A230T and E250Q, and a novel change, E250K. Disease penetrance was incomplete, with variable expressivity. The cutaneous manifestations included pathergy, cystic acne, and pyoderma gangrenosum. Interleukin-1β (IL-1β) and circulating neutrophil granule enzyme levels were markedly elevated in patients compared to those in controls. PBMC stimulation studies demonstrated impaired production of IL-10 and enhanced production of granulocyte-macrophage colony-stimulating factor. Good resolution of pyoderma gangrenosum was achieved in 3 patients with tumor necrosis factor α (TNFα) blockade treatment.
This analysis of 5 patients demonstrates that mutations in PSTPIP1 are incompletely penetrant and variably expressed in the PAPA syndrome. Neutrophil granule proteins are markedly elevated ex vivo and in the plasma, and elevated levels might be compatible with a diagnosis of PAPA syndrome. TNFα blockade appears to be effective in treating the cutaneous manifestations of PAPA syndrome.
AuthorsAndrew P Demidowich, Alexandra F Freeman, Douglas B Kuhns, Ivona Aksentijevich, John I Gallin, Maria L Turner, Daniel L Kastner, Steven M Holland
JournalArthritis and rheumatism (Arthritis Rheum) Vol. 64 Issue 6 Pg. 2022-7 (Jun 2012) ISSN: 1529-0131 [Electronic] United States
PMID22161697 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
CopyrightCopyright © 2012 by the American College of Rheumatology.
Chemical References
  • Adaptor Proteins, Signal Transducing
  • Antirheumatic Agents
  • Cytoskeletal Proteins
  • Interleukin 1 Receptor Antagonist Protein
  • PSTPIP1 protein, human
  • Acne Vulgaris (diagnosis, drug therapy, genetics)
  • Adaptor Proteins, Signal Transducing (genetics)
  • Adolescent
  • Antirheumatic Agents (therapeutic use)
  • Arthritis, Infectious (diagnosis, drug therapy, genetics)
  • Child
  • Cytoskeletal Proteins (genetics)
  • Disease Progression
  • Female
  • Genotype
  • Humans
  • Infant, Newborn
  • Interleukin 1 Receptor Antagonist Protein (therapeutic use)
  • Male
  • Middle Aged
  • Mutation
  • Phenotype
  • Pyoderma Gangrenosum (diagnosis, drug therapy, genetics)
  • Syndrome
  • Treatment Outcome
  • Young Adult

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