Update on the aetiology and mechanisms of generalized pustular psoriasis

Eur J Dermatol. 2021 Oct 1;31(5):602-608. doi: 10.1684/ejd.2021.4047.


Generalized pustular psoriasis (GPP) is a chronic disease characterized by non-bacterial pustules. Variants in several genes, such as IL36RN, AP1S3, and CARD14, are involved in the pathogenesis of GPP. The prevalence of different gene variants varies among ethnicities, and some variants are related to concurrent psoriasis vulgaris or age at onset. Flares can be triggered by medications (most commonly corticosteroids), infections (possibly due to Toll-like receptor [TLR] and antimicrobial peptides), pregnancy (the onset of GPP has been attributed to endocrine abnormalities such as hypoparathyroidism and hypocalcaemia), hypocalcaemia (presumably due to low levels of calcium and vitamin D regulating the proliferation and differentiation of keratinocytes), and other factors including stress and sun exposure. The mechanisms of pustule formation involve: 1) the LL37/TLR pathway, in which LL37 acts as an alarmin, interacting with TLR and activating the NF-κB and MAPK pathways; 2) the balance between calcium and 1,25(OH)2D levels, and 3) neutrophils and the complement system.

Keywords: aetiology; antimicrobial peptide; pustular psoriasis; toll-like receptor; vitamin D.

Publication types

  • Review

MeSH terms

  • Cathelicidins / immunology
  • Female
  • Genetic Variation
  • Glucocorticoids / adverse effects
  • Humans
  • Hypocalcemia / complications
  • Pregnancy
  • Pregnancy Complications
  • Psoriasis / etiology*
  • Psoriasis / genetics
  • Psoriasis / immunology
  • Respiratory Tract Infections / complications
  • Toll-Like Receptors / immunology
  • Vitamin D Deficiency / complications
  • Withholding Treatment


  • CAMP protein, human
  • Cathelicidins
  • Glucocorticoids
  • Toll-Like Receptors