Skip to main content
SpringerLink
Log in
Book cover

Acneiform Eruptions in Dermatology pp 137–148Cite as

PAPA Syndrome

  • Chapter
  • First Online:

  • 1721 Accesses

Abstract

The pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome was first recognized in 1997 when ten family members in three generations manifested with variable expression of juvenile-onset arthritis and subsequent presentation of pyoderma gangrenosum and cystic acne in adolescence and adulthood [1]. This inherited disorder stems from dysregulation of the innate immune system, presenting with symptoms of seemingly unprovoked episodes of synovial tissue and skin inflammation [1]. Recurrent inflammation seen in PAPA syndrome typifies that classically seen in autoinflammatory disorders. Autoinflammatory disorders, though lacking clear diagnostic criteria, are marked by chronic and intermittent episodes of fever, cytokine dysregulation, and organ inflammation; skin and joint involvement is a prominent feature [2, 3]. Unlike autoimmune diseases, autoinflammatory disorders lack high-titer autoantibodies and autoreactive T lymphocytes [2]. Genes associated with inherited syndromes of autoinflammation encode for protein mediators of apoptosis, inflammation, and cytokine processing (Table 20.1) [3].

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

ASC:

Apoptosis-associated speck-like protein with a caspase recruitment domain

C3:

Complement component 3

CAPS:

Cryopyrin-associated periodic syndromes

CD2BP1:

CD2-binding protein 1

DMARDs:

Disease-modifying antirheumatic drugs

FMA:

Familial Mediterranean fever

IgM:

Immunoglobulin M

IL:

Interleukin

IL-1β:

Interleukin-1-beta

kD:

Kilodalton

NLRP3:

Nucleotide oligomerization domain-like receptor family pyrin domain containing 3

NSAIDs:

Nonsteroidal anti-inflammatory drugs

PAPA:

Pyogenic sterile arthritis, pyoderma gangrenosum, and acne

PSTPIP1:

Proline-serine-threonine phosphatase interacting protein 1

PTP-PEST:

Proline-glutamic acid-serine-threonine-rich family of protein tyrosine phosphatases

TNFα:

Tumor necrosis factor alpha

References

  1. Lindor NM, Arsenault TM, Solomon H, Seidman CE, McEvoy MT. A new autosomal dominant disorder of pyogenic sterile arthritis, pyoderma gangrenosum, and acne: PAPA syndrome. Mayo Clin Proc. 1997;72(7):611–5.

    PubMed  CAS  Google Scholar 

  2. Wise CA, Gillum JD, Seidman CE, Lindor NM, Veile R, Bashiardes S, Lovett M. Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an autoinflammatory disorder. Hum Mol Genet. 2002;11(8):961–9.

    Article  PubMed  CAS  Google Scholar 

  3. Hull KM, Shoham N, Chae JJ, Aksentijevich I, Kastner DL. The expanding spectrum of systemic autoinflammatory disorders and their rheumatic manifestations. Curr Opin Rheumatol. 2003;15(1):61–9.

    Article  PubMed  CAS  Google Scholar 

  4. Smith EJ, Allantaz F, Bennett L, Zhang D, Gao X, Wood G, Kastner DL, Punaro M, Aksentijevich I, Pascual V, Wise CA. Clinical, molecular, and genetic characteristics of PAPA syndrome: a review. Curr Genomics. 2010;11(7):519–27.

    Article  PubMed  CAS  Google Scholar 

  5. McDermott MF. A common pathway in periodic fever syndromes. Trends Immunol. 2004; 25(9):457–60.

    Article  PubMed  CAS  Google Scholar 

  6. Veillette A, Rhee I, Souza CM, Davidson D. PEST family phosphatases in immunity, autoimmunity, and autoinflammatory disorders. Immunol Rev. 2009;228(1):312–24.

    Article  PubMed  CAS  Google Scholar 

  7. Goldfinger S. The inherited autoinflammatory syndrome: a decade of discovery. Trans Am Clin Climatol Assoc. 2009;120:413–8.

    PubMed  Google Scholar 

  8. Waite AL, Schaner P, Richards N, Balci-Peynircioglu B, Masters SL, Brydges SD, Fox M, Hong A, Yilmaz E, Kastner DL, Reinherz EL, Gumucio DL. Pyrin modulates the intracellular distribution of PSTPIP1. PLoS One. 2009;4(7):e6147.

    Article  PubMed  Google Scholar 

  9. Yu JW, Fernandes-Alnemri T, Datta P, Wu J, Juliana C, Solorzano L, McCormick M, Zhang Z, Alnemri ES. Pyrin activates the ASC pyroptosome in response to engagement by autoinflammatory PSTPIP1 mutants. Mol Cell. 2007;28(2):214–27.

    Article  PubMed  CAS  Google Scholar 

  10. Shinkai K, McCalmont TH, Leslie KS. Cryopyrin-associated periodic syndromes and autoinflammation. Clin Exp Dermatol. 2008;33(1):1–9.

    PubMed  CAS  Google Scholar 

  11. Wise CA, Bennett LB, Pascual V, Gillum JD, Bowcock AM. Localization of a gene for familial recurrent arthritis. Arthritis Rheum. 2000;43(19):2041–5.

    Article  PubMed  CAS  Google Scholar 

  12. Cortis E, De Benedetti F, Insalaco A, Cioschi S, Muratori F, D’Urbano LE, Ugazio AG. Abnormal production of tumor necrosis factor (TNF) alpha and clinical efficacy of the TNF inhibitor etanercept in a patient with PAPA syndrome. J Pediatr. 2004;145(6):851–5.

    Article  PubMed  Google Scholar 

  13. Dierselhuis MP, Frenkel J, Wulffraat NM, Boelens JJ. Anakinra for flares of pyogenic arthritis in PAPA syndrome. Rheumatology. 2005;44(3):406–8.

    Article  PubMed  CAS  Google Scholar 

  14. Tallon B, Corkill M. Peculiarities of PAPA syndrome. Rheumatology. 2006;45(9):1140–3.

    Article  PubMed  CAS  Google Scholar 

  15. Brenner M, Ruzicka T, Plewig G, Thomas P, Herzer P. Targeted treatment of pyoderma gangrenosum in PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome with the recombinant human interleukin-1 receptor antagonist anakinra. Br J Dermatol. 2009;161(5):1199–201.

    Article  PubMed  CAS  Google Scholar 

  16. Hong JB, Su YN, Chiu HC. Pyogenic arthritis, pyoderma gangrenosum, and acne syndrome (PAPA syndrome): report of a sporadic case without an identifiable mutation in the CD2BP1 gene. J Am Acad Dermatol. 2009;61(3):533–5.

    Article  PubMed  Google Scholar 

  17. Schellevis MA, Stoffels M, Hoppenreijs EP, Bodar E, Simon A, van der Meer JW. Variable expression and treatment of PAPA syndrome. Ann Rheum Dis. 2011;70(6):1168–70.

    Article  PubMed  Google Scholar 

  18. Lolis MS, Bowe WP, Shalita AR. Acne and systemic diseases. Med Clin North Am. 2009; 93(6):1161–81.

    Article  PubMed  CAS  Google Scholar 

  19. Stichweh DS, Punaro M, Pascual V. Dramatic improvement of pyoderma gangrenosum with infliximab in a patient with PAPA syndrome. Pediatr Dermatol. 2005;22(3):262–5.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, University of California, San Francisco, 1701 Divisadero Street, 3rd Floor, San Francisco, CA, 94115, USA

    Fan Liu B.A., M.D. & Kanade Shinkai M.D., Ph.D.

Authors
  1. Fan Liu B.A., M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kanade Shinkai M.D., Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kanade Shinkai M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Mount Sinai Medical Center, New York, USA

    Joshua Zeichner

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Liu, F., Shinkai, K. (2014). PAPA Syndrome. In: Zeichner, J. (eds) Acneiform Eruptions in Dermatology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8344-1_20

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-8344-1_20

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-8343-4

  • Online ISBN: 978-1-4614-8344-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation