Pathophysiology of Prurigo Nodularis: Neuroimmune Dysregulation and the Role of Type 2 Inflammation

Shawn G Kwatra; Sonja Ständer; Gil Yosipovitch; Brian S Kim; Noah A Levit; John T O'Malley

doi:10.1016/j.jid.2024.06.1276

Pathophysiology of Prurigo Nodularis: Neuroimmune Dysregulation and the Role of Type 2 Inflammation

J Invest Dermatol. 2024 Aug 29:S0022-202X(24)01875-X. doi: 10.1016/j.jid.2024.06.1276. Online ahead of print.

Authors

Shawn G Kwatra¹, Sonja Ständer², Gil Yosipovitch³, Brian S Kim⁴, Noah A Levit⁵, John T O'Malley⁶

Affiliations

¹ Department of Dermatology, University of Maryland School of Medicine, Baltimore, Maryland, USA; Maryland Itch Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.
² Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Münster, Germany.
³ Miami Itch Center, Dr. Philip Frost Department of Dermatology & Cutaneous Surgery, University of Miami, Miami, Florida, USA.
⁴ Mark Lebwohl Center for Neuroinflammation and Sensation, Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁵ Dermatology Physicians of Connecticut, Fairfield, Connecticut, USA.
⁶ Sanofi, Cambridge, Massachusetts, USA. Electronic address: john.o'[email protected].

PMID: 39217537
DOI: 10.1016/j.jid.2024.06.1276

Abstract

Prurigo nodularis (PN) is a chronic, inflammatory skin condition characterized by multiple, intensely pruritic, distinctive nodular lesions. Subsequent scratching can further intensify the pruritus, culminating in a self-reinforcing itch-scratch cycle, which drives lesion development. The latest data indicate dysregulation of the neuroimmune axis in PN pathogenesis, including the involvement of sensory neurons, key effector immune cells, proinflammatory cytokines, dermal fibroblasts, and pruritogens. In this review, we highlight evidence supporting the role of type 2 immune axis dysregulation in driving the clinical presentation of PN and discuss how related signaling pathways may offer effective therapeutic targets to control PN signs and symptoms.

Keywords: Neuroimmune axis; Pathophysiology; Prurigo nodularis; Type 2 immunity.

Publication types

Review