Mild generalised pustular psoriasis patient with a heterozygous hypomorphic MPO variant successfully treated with granulocyte and monocyte adsorption apheresis

Exp Dermatol. 2023 Sep;32(9):1557-1562. doi: 10.1111/exd.14846. Epub 2023 Jun 1.

Abstract

Pathogenic variants in MPO, which encodes the myeloperoxidase, were reported as causative genetic defects in several cases of generalised pustular psoriasis (GPP) in addition to patients with myeloperoxidase deficiency in 2020. However, which clinical subtypes of GPP patients have pathogenic variants in MPO remains largely undetermined, and elucidating this is clinically important. The present report outlines a mild case of GPP with a rare missense heterozygous variant, c.1810C>T p.(Arg604Cys), in MPO. Our structural analysis and functional assays to measure myeloperoxidase activity suggest that the present MPO substitution is a hypomorphic variant in MPO. Thus, the mild phenotype of the present GPP patient might be associated with an incomplete hypomorphic loss-of-function variant in MPO. Additionally, the severe intractable edematous pustules and erythema improved dramatically after five rounds of granulocyte and monocyte adsorption apheresis (GMA) therapy. This is the first report of GMA treatment for GPP associated with a pathogenic variant in MPO, as far as we know. Our findings suggest that GMA might be a useful and powerful tool for controlling GPP in patients with myeloperoxidase deficiency.

Keywords: autoinflammation; autoinflammatory keratinization diseases; myeloperoxidase; myeloperoxidase deficiency.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adsorption
  • Blood Component Removal*
  • Chronic Disease
  • Granulocytes / pathology
  • Humans
  • Interleukins / genetics
  • Monocytes
  • Peroxidase / genetics
  • Psoriasis* / genetics
  • Psoriasis* / pathology
  • Psoriasis* / therapy
  • Skin Diseases, Vesiculobullous* / therapy

Substances

  • Interleukins
  • Peroxidase

Supplementary concepts

  • Myeloperoxidase Deficiency