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Pyogenic Arthritis Pyoderma Gangrenosum and Acne (PAPA) Syndrome

  • Marilynn G. PunaroEmail author
  • Carol A. Wise
Chapter

Abstract

PAPA is a rare autosomal dominant disorder classically characterized by early onset destructive Pyogenic Arthritis, Pyoderma gangrenosum, and severe nodulocystic Acne (PAPA). It is caused by missense mutations in the PSTPIP1 gene. Proline-Serine-Threonine Phosphatase-Interacting Protein 1 (PSTPIP1) is a multifunctional adaptor protein that is expressed predominantly in hematopoietic cells. Its adaptor function with pyrin originally linked it to the inflammasome and related it to familial Mediterranean fever and other autoinflammatory diseases.

Although medications targeting interleukin (IL)-1 and tumor necrosis factor (TNF) have been effective for certain disease manifestations in some PAPA patients, a consistently effective treatment remains elusive. PSTPIP1 has been linked more recently to Wiskott-Aldrich syndrome protein (WASP)-mediated macrophage podosome function, and to SHIP1/2-mediated osteoclast functions. These pathways are likely involved in invasive skin and bone destruction, respectively, and are attractive candidates for therapeutic targeting. Thus, although PAPA is a “simple” Mendelian disease, its pathogenesis is complicated by the effects of mutations on the diverse roles of the PSTPIP1 adaptor protein. Current outlook suggests that combined therapies targeting each PSTPIP1-mediated pathway may prove the most beneficial to individual PAPA patients.

It is now appreciated that PAPA syndrome represents a single clinical entity within a spectrum of PSTPIP1 associated inflammatory diseases (PAIDs) that have been linked to specific mutations. In addition, reports of PAPA cases negative for PSTPIP1 mutations raise the possibility of additional disease genes. Further research to define molecular mechanisms and to develop specific molecular therapeutics is warranted and will likely provide insights into other related autoinflammatory diseases and disorders marked by invasive tissue destruction.

Keywords

Pyogenic arthritis Pyoderma gangrenosum Acne Pathergy PSTPIP1 Autoinflammatory disease Rare Mendelian Inflammasome Podosome biogenesis 

Abbreviations

CD2BP1

CD2-binding protein 1

CNO

Chronic non-bacterial osteomyelitis

FasL

Fas ligand

F-BAR

Fer-CIP4 homology—Bin/Amphiphysin/Rvs

IL

Interleukin

PAAND

Pyrin-associated autoinflammation with neutrophilic dermatosis syndrome

PAID

PSTPIP1 associated inflammatory diseases

PAMI

PSTPIP1-associated myeloid-related proteinemia inflammatory syndrome

PAPA

Pyogenic arthritis pyoderma gangrenosum acne

PSTPIP1

Proline-Serine-Threonine Phosphatase-Interacting Protein 1

PTP-PESTs

Protein tyrosine phosphatases-rich in proline (P), glutamic acid (E), serine (S), and threonine (T) residues

SAPHO

Synovitis acne palmoplantar pustulosis hyperostosis osteitis

SH3

Src homology 3

SHIP1/2

SH-2 containing inositol 5′ polyphosphatases 1 and 2

TNF

Tumor necrosis factor

WASP

Wiskott-Aldrich Syndrome Protein

Notes

Acknowledgements

We thank the PAPA patients and families who have participated in biomedical research studies.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Texas Scottish Rite HospitalUT Southwestern Medical CenterDallasUSA

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