An Investigation of the Pathogenesis of Paradoxical Eczema in Psoriasis Patients Treated with Biologics

  • Ali Al-Janabi

Student thesis: Phd

Abstract

Aim: This thesis aimed to investigate the pathogenesis of paradoxical eczema (PE), an atopic eczema phenotype, occurring in psoriasis patients treated with biologics. Methods: Following systematic review of published PE cases, a prospective cohort study was undertaken using data from the British Association of Dermatologists Biologic Interventions Register (BADBIR) to explore PE risk factors. Next, a genome-wide association study (GWAS) was completed using data from BADBIR and the allied Biomarkers and Stratification to Optimise outcomes in Psoriasis (BSTOP) study. The systemic inflammatory signature of paradoxical eczema was explored using proximity extension assays on serum, single cell RNA-seq (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) and cytometry by time of flight (CyTOF) on PBMCs. Results: The systematic review revealed that "eczema" was reported as an adverse event in up to 12.1% (ixekizumab) of biologics clinical trials. The cohort study, which included 24,997 biologic exposures in 13,699 psoriasis participants, found increased PE risk with age, prior atopic eczema, prior hay fever and lower risk in males. Relative to TNF inhibitors (TNFi), there was a reduced risk with interleukin (IL)-23i exposure. A GWAS of 88 PE cases and 3212 psoriasis control identified two genome-wide significant (P =
Date of Award1 Aug 2024
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorStephen Eyre (Supervisor), Christopher Griffiths (Supervisor), Paul Martin (Supervisor), Richard Warren (Supervisor) & Amy Foulkes (Supervisor)

Keywords

  • Proteomics
  • Transcriptomics
  • Paradoxical eczema
  • Genomics
  • Therapeutics
  • Psoriasis
  • Atopic dermatitis

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