Original article
Pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH)–a new autoinflammatory syndrome distinct from PAPA syndrome

https://doi.org/10.1016/j.jaad.2010.12.025Get rights and content

Background

PAPA syndrome is a recently identified hereditary autoinflammatory syndrome clinically characterized by pyogenic arthritis, severe acne, and pyoderma gangrenosum. It is caused by mutations in the PSTPIP1 gene and may be closely linked to the aseptic abscesses syndrome, which has been shown to be associated with CCTG repeat amplification in the promoter region of PSTPIP1.

Objective

We describe two unrelated patients with a clinical presentation quite similar to, yet distinct from, PAPA syndrome.

Results

Both patients had pyoderma gangrenosum and acute or remittent acne conglobata, but, in contrast to PAPA syndrome, lacked any episodes of pyogenic arthritis. Instead, they had suppurative hidradenitis. Mutations in PSTPIP1 exons 1 to 15 were excluded. In the promoter region, an increased repetition of the CCTG microsatellite motif was present on one allele in both patients. Alterations of the most commonly affected exons of the MEFV, NLRP3, and TNFRSF1A genes also were not detectable. One patient was treated with the interleukin (IL)-1 receptor antagonist anakinra and responded well, although without complete remission. This implies that IL-1ß may be of pathogenetic importance.

Limitations

Small number of patients, no gene mutation identified, and unclear efficacy of therapy are limitations.

Conclusions

The clinical triad of pyoderma gangrenosum, acne, and suppurative hidradenitis represents a new disease entity within the spectrum of autoinflammatory syndromes, similar to PAPA and aseptic abscesses syndrome. For this disease, we propose the acronym “PASH” syndrome. PASH syndrome may respond to IL-1ß blockade.

Section snippets

Case 1

A 34-year-old man (172 cm; 92 kg) of Russian descent had severe cystic acne lesions on his face and back since adolescence, and from clusters of chronic and repeatedly draining sinuses and abscesses in both axillae for 7 years (Fig 1, A to D). During the last 6 months, slowly expanding and painful ulcerations developed on his arms and lower legs. His medical history was otherwise unremarkable in particular for any kind of arthritis, inflammatory bowel disease, or hematologic malignancy; his

Discussion

PAPA syndrome is clinically characterized by pyogenic sterile arthritis, PG, and acne, and has been defined as an autosomal dominant autoinflammatory syndrome caused by mutations in the PSTPIP1 gene. Herein, we present two unrelated patients with a symptom complex very close to, but clearly distinct from, PAPA syndrome. They share the dermatologic signs of PG and acne with PAPA syndrome, but in distinction to PAPA lack the intensive joint inflammation and instead experience severe SH at large

References (26)

  • M.P. Dierselhuis et al.

    Anakinra for flares of pyogenic arthritis in PAPA syndrome

    Rheumatology (Oxford)

    (2005)
  • B. Tallon et al.

    Peculiarities of PAPA syndrome

    Rheumatology (Oxford)

    (2006)
  • C.N. Renn et al.

    Pyogenic arthritis, pyoderma gangrenosum and acne syndrome (PAPA syndrome)

    Hautarzt

    (2007)
  • Cited by (251)

    • The genetics behind inflammasome regulation

      2022, Molecular Immunology
      Citation Excerpt :

      However, in the last years, the spectrum of PSTPIP1-associated inflammatory diseases (PAID) has expanded encompassing PSTPIP1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome and the anecdotal description of other clinical phenotypes. Causative mutations operate in a dominant inheritance pattern and include both missense mutations and potentially promotor microsatellite expansions (Braun-Falco et al., 2012; Demidowich et al., 2012) (Table 3). Several PSTPIP1 mutations have been shown to increase binding to pyrin, and activate both the pyrin and NLRP3-inflammasomes.

    • Genetics and Epigenetics of Hidradenitis Suppurativa

      2022, A Comprehensive Guide to Hidradenitis Suppurativa
    View all citing articles on Scopus

    Funding sources: None.

    Conflicts of interest: None declared.

    View full text