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. 2024 Apr 7:16:97-102.
doi: 10.1016/j.jdin.2024.03.022. eCollection 2024 Sep.

Immune stimulus exposure as a trigger for the development of chronic pruritus and circulating blood type 2 inflammation

Jaya Manjunath  1   2   3 , Viviane Liao  1   2   3 , Anusha Kambala  1   2 , Aaron Bao  1   2   3 , Alexander L Kollhoff  1   2   3 , Emily Z Ma  1   2   3 , Brenda Umenita Imo  1   2 , Hannah Cornman  1   2 , Sriya V Reddy  4 , Kevin K Lee  1   2   3 , Weiying Lu  4 , Selina M Yossef  4 , Madan M Kwatra  4 , Shawn G Kwatra  1   2
Affiliations

Immune stimulus exposure as a trigger for the development of chronic pruritus and circulating blood type 2 inflammation

Jaya Manjunath et al. JAAD Int. .

Abstract

Background: Chronic pruritus (CP) is a poorly characterized condition associated with intense pruritus without a primary skin eruption. This condition tends to emerge more commonly in older adults, and there is limited research on triggering factors.

Objective: To explore the clinical characteristics and pathophysiology of CP following exposure to an immune stimulus.

Methods: Clinical characteristics and plasma samples were collected from 15 patients who developed CP following an immune stimulus such as checkpoint inhibitors or vaccination. A multiplex panel was used to analyze plasma cytokine concentrations within these patients.

Results: Most immunotherapy-treated patients experienced CP during treatment or after 21 to 60 days of receiving treatment, while vaccine-stimulated patients developed pruritus within a week of vaccination. Plasma cytokine analysis revealed elevated levels of 12 cytokines in patients with immune-stimulated CP compared to healthy controls. Notably, T helper 2 (Th2) related cytokines interleukin (IL)-5 (fold change 2.65; q < 0.25) and thymic stromal lymphopoietin (fold change 1.61 q < 0.25) were upregulated.

Limitations: Limitations of this study include limited sample size, particularly in the plasma cytokine assay.

Conclusions and relevance: This study reveals triggers of CP development and describes alterations in blood Th2 markers in patients with CP, including IgE, increased blood eosinophils, and cytokines IL-5 and thymic stromal lymphopoietin.

Keywords: cytokines; dermatology; pruritus; type 2 inflammation.

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Conflict of interest statement

Dr Shawn Kwatra is an advisory board member or consultant for AbbVie, Celldex Therapeutics, Incyte Corporation, Galderma, Pfizer Inc, Regeneron Pharmaceuticals, and Menlo Therapeutics; and is a recipient of a Dermatology Foundation Medical Dermatology Career Development Award.

Figures

Fig 1
Fig 1
A and B, Chronic pruritus developed in a 79-year-old male shortly after starting treatment with nivolumab for metastatic melanoma. The patient experienced intense pruritus without a primary skin eruption.
Fig 2
Fig 2
Heatmap of Th2 cytokines in chronic pruritus (CPUO) and matched healthy control (HC) patients. The color intensity scale represents the log-transformed cytokine concentrations, with red corresponding to the greatest concentration. TSLP, Thymic stromal lymphopoietin. IL, Interleukin; MCP, monocyte chemoattractant protein; MDC, macrophage-derived chemokine; TARC, thymus and activation regulated chemokine.
See this image and copyright information in PMC

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