PAPA, PASH and PAPASH Syndromes: Pathophysiology, Presentation and Treatment

Am J Clin Dermatol. 2017 Aug;18(4):555-562. doi: 10.1007/s40257-017-0265-1.

Abstract

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis usually manifesting as skin ulcers with undermined erythematous-violaceous borders. It may be isolated, associated with systemic conditions or occurring in the context of autoinflammatory syndromes such as PAPA (pyogenic arthritis, PG and acne), PASH (PG, acne and suppurative hidradenitis) or PAPASH (pyogenic arthritis, acne, PG and suppurative hidradenitis). From a physiopathological point of view, all these conditions share common mechanisms consisting of over-activation of the innate immune system leading to increased production of the interleukin (IL)-1 family and 'sterile' neutrophil-rich cutaneous inflammation. From a genetic point of view, a number of mutations affecting the proteins of the inflammasome complex (the molecular platform responsible for triggering autoinflammation) or the proteins that regulate inflammasome function have been described in these disorders. As these debilitating entities are all associated with the over-expression of IL-1 and tumour necrosis factor (TNF)-α, biological drugs specifically targeting these cytokines are currently the most effective treatments but, given the emerging role of IL-17 in the pathogenesis of these syndromes, IL-17 antagonists may represent the future management of these conditions.

Publication types

  • Review

MeSH terms

  • Acne Vulgaris* / diagnosis
  • Acne Vulgaris* / drug therapy
  • Acne Vulgaris* / immunology
  • Acne Vulgaris* / physiopathology
  • Arthritis, Infectious* / diagnosis
  • Arthritis, Infectious* / drug therapy
  • Arthritis, Infectious* / immunology
  • Arthritis, Infectious* / physiopathology
  • Biomarkers / blood
  • Diagnosis, Differential
  • Hidradenitis Suppurativa* / diagnosis
  • Hidradenitis Suppurativa* / drug therapy
  • Hidradenitis Suppurativa* / immunology
  • Hidradenitis Suppurativa* / physiopathology
  • Humans
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / blood*
  • Interleukin-17 / antagonists & inhibitors
  • Interleukin-17 / blood*
  • Pyoderma Gangrenosum* / diagnosis
  • Pyoderma Gangrenosum* / drug therapy
  • Pyoderma Gangrenosum* / immunology
  • Pyoderma Gangrenosum* / physiopathology
  • Syndrome
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / blood*

Substances

  • Biomarkers
  • Interleukin-1
  • Interleukin-17
  • Tumor Necrosis Factor-alpha

Supplementary concepts

  • Pyogenic arthritis, pyoderma gangrenosum, and acne