Targeted dual biologic therapy for erythroderma of unknown etiology guided by high-parameter peripheral blood immunophenotyping

Hannah L. Cornman, Department of Dermatology, University of Maryland School of Medicine, 419 West Redwood Street, Suite 235, Baltimore, MD, 21201, USA.
Martin P. Alphonse, Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Arbor Dykema, Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Alexander L. Kollhoff, Department of Dermatology, University of Maryland School of Medicine, 419 West Redwood Street, Suite 235, Baltimore, MD, 21201, USA.
Kevin K. Lee, Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jaya Manjunath, Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Emily Z. Ma, Department of Dermatology, University of Maryland School of Medicine, 419 West Redwood Street, Suite 235, Baltimore, MD, 21201, USA.
Varsha Parthasarathy, Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Junwen Deng, Department of Dermatology, University of Maryland School of Medicine, 419 West Redwood Street, Suite 235, Baltimore, MD, 21201, USA.
Thomas Pritchard, Department of Dermatology, University of Maryland School of Medicine, 419 West Redwood Street, Suite 235, Baltimore, MD, 21201, USA.
Anusha Kambala, Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Melika Marani, Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Kayla A. Parr, Duke Cancer Institute Flow Cytometry Core, Department of Immunology, Duke University School of Medicine, Durham, NC, USA.
Javid P. Mohammed, Duke Cancer Institute Flow Cytometry Core, Department of Immunology, Duke University School of Medicine, Durham, NC, USA.
Madan M. Kwatra, Department of Anesthesiology, Duke University School of Medicine, Durham, NC, USA.
Jay H. Bream, Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Won Jin Ho, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Shawn G. Kwatra, Department of Dermatology, University of Maryland School of Medicine, 419 West Redwood Street, Suite 235, Baltimore, MD, 21201, USA. skwatra@som.umaryland.edu.

Document Type

Journal Article

Publication Date

1-14-2025

Journal

Scientific reports

Volume

15

Issue

1

DOI

10.1038/s41598-024-81060-3

Abstract

Erythroderma is a severe and heterogeneous inflammatory skin condition with little guidance on the approach to management in cases of unknown etiology. To guide therapeutic selection, we sought to create an immunophenotyping platform able to identify aberrant cell populations and cytokines in subtypes of erythroderma. We performed high-parameter flow cytometry on peripheral blood mononuclear cells (PBMCs) and whole blood of a patient with refractory idiopathic erythroderma, erythrodermic patients with Sézary syndrome and pityriasis rubra pilaris, and healthy controls. We found that the index patient had a novel form of erythroderma characterized by increased interleukin (IL)-13- and IL-17-producing γVδ2 T cells, basophils, and activated platelets. Whole-genome sequencing of PBMCs and immunofluorescence staining of skin biopsies revealed increased expression of Th2- (IL-13, IL-4Rα) and Th17-associated markers (IL-17, IL-17Rα) and non-functional mutations associated with Th2 and Th17 signaling, demonstrating that PBMCs can reflect cutaneous disease pathology. Targeted intervention via dual dupilumab and secukinumab therapy resulted in complete disease control and reduction of immunopathogenic cell populations and cytokines. This study highlights a novel form of erythroderma with concomitant Th2 and Th17 dysregulation and introduces a minimally invasive peripheral blood-based immunophenotyping platform that offers a personalized medicine approach to the management of systemic inflammatory diseases.

Department

Dermatology

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