A dermatologic perspective on autoinflammatory diseases

Clin Exp Rheumatol. 2018 Jan-Feb;36 Suppl 110(1):32-38. Epub 2018 May 3.

Abstract

Autoinflammatory diseases (AIDs) encompass a heterogeneous group of disorders pathogenetically related to an abnormal activation of the innate immunity and clinically characterised by aseptic inflammation in the affected organs in the absence of high titer of circulating autoantibodies or autoreactive T cells. In classic monogenic AIDs, the skin is frequently involved with a wide range of cutaneous lesions. Monogenic AIDs result from different mutations in a single gene, which regulates the innate immunity. These mutations cause an uncontrolled activation of the inflammasome, leading to an overexpression of interleukin (IL)- 1β. IL-1β is the pivotal cytokine which is responsible for the exaggerated production of cytokines and chemokines that induce the recruitment of neutrophils, key cells in autoinflammation. Paradigmatic autoinflammatory forms are the cryopyrin-associated periodic syndromes (CAPS), whose skin involvement consists of urticarial lesions. Similar IL-1β-mediated autoinflammatory pathomechanisms also occur in deficiency of IL-1 receptor antagonist (DIRA) and deficiency of IL-36 receptor antagonist (DITRA), whose cutaneous appearance is characterised by pustular lesions, as well as in pyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome. Pyoderma gangrenosum, which is the cutaneous hallmark of the PAPA syndrome, is a prototypic neutrophil-mediated skin disease, manifesting as single or multiple ulcers with undermined, raised erythematous to violaceous borders. This review is focused on the CAPS, DIRA/DITRA and PAPA syndromes with emphasis on their cutaneous manifestations, as well as their histology and pathophysiology.

Publication types

  • Review

MeSH terms

  • Acne Vulgaris / complications
  • Acne Vulgaris / immunology
  • Acne Vulgaris / pathology
  • Arthritis, Infectious / complications
  • Arthritis, Infectious / immunology
  • Arthritis, Infectious / pathology
  • Cryopyrin-Associated Periodic Syndromes / complications
  • Cryopyrin-Associated Periodic Syndromes / immunology
  • Cryopyrin-Associated Periodic Syndromes / pathology
  • Cytokines / immunology*
  • Hereditary Autoinflammatory Diseases / complications
  • Hereditary Autoinflammatory Diseases / immunology*
  • Hereditary Autoinflammatory Diseases / pathology
  • Humans
  • Immunity, Innate / immunology*
  • Inflammasomes / immunology*
  • Interleukin 1 Receptor Antagonist Protein / immunology
  • Pyoderma Gangrenosum / complications
  • Pyoderma Gangrenosum / immunology
  • Pyoderma Gangrenosum / pathology
  • Skin Diseases / etiology
  • Skin Diseases / immunology*
  • Skin Diseases / pathology

Substances

  • Cytokines
  • Inflammasomes
  • Interleukin 1 Receptor Antagonist Protein

Supplementary concepts

  • Deficiency of interleukin-1 receptor antagonist
  • Pyogenic arthritis, pyoderma gangrenosum, and acne