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

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.

Generalized pustular psoriasis that developed in a patient with an NFKB2 variant

“…Many MPO variants have been reported to be associated with the development, although the variant in our case has never been reported as pathogenic. 13 This is the first case of GPP associated with the novel NFKB2 variant and the novel MPO variant. Further investigation of the variants is necessary to elucidate the pathogenesis of GPP.…”

Increased neutrophil‐derived IL‐17A identified in generalized pustular psoriasis

“…Myeloperoxidase in neutrophils encoded by MPO is involved in the hyperactivation of innate immunity. An incomplete hypomorphic loss‐of‐function variant in MPO has been proved to be associated with the mild phenotype of GPP 7 . Whereas CARD14 and AP1S3 variants mediate GPP pathogenesis primarily by increasing IL‐36, IL‐1, IL‐8, CXCL1, CXCL2 and CXCL8 through activation of the NF‐κB signal pathway in keratinocytes 8 …”

“…An incomplete hypomorphic loss-of-function variant in MPO has been proved to be associated with the mild phenotype of GPP. 7 Whereas CARD14 and AP1S3 variants mediate GPP pathogenesis primarily by increasing IL-36, IL-1, IL-8, CXCL1, CXCL2 and CXCL8 through activation of the NF-κB signal pathway in keratinocytes. 8 In present study, we performed a comparative transcription analysis of skin samples from GPP and PV to identify the difference in pathogenesis between GPP and PV.…”