Circulating blood eosinophils as a biomarker for variable clinical presentation and therapeutic response in patients with chronic pruritus of unknown origin

Roh, Youkyung S.; Patel, Sagar P.; Gopinath, Shilpa; Williams, Kyle; Khanna, Raveena; Pritchard, Thomas; Sutaria, Nishadh; Choi, Justin; Alphonse, Martin P.; Kwatra, Madan M.; Kwatra, Shawn G.

doi:10.1016/j.jaip.2021.01.034

Cited by 12 publications

(9 citation statements)

References 7 publications

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“…This supports clinical observations of heterogeneity in response to type 2 inflammatory-modulating therapies in PN patients ( 6 ). Additional evidence of varying degrees of type 2 inflammatory dysregulation clinically includes highly variable levels of blood eosinophils and IgE, which serve as predictors of response to immunomodulatory therapy in other chronic pruritic conditions such as chronic pruritus of unknown origin ( 26 , 27 ).…”

Section: Discussionmentioning

confidence: 99%

Circulating plasma IL-13 and periostin are dysregulated type 2 inflammatory biomarkers in prurigo nodularis: A cluster analysis

et al. 2022

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ImportancePrurigo nodularis (PN) is a chronic heterogeneous inflammatory skin disease.ObjectiveTo elucidate which components of type 2 inflammation are dysregulated systemically in PN.DesignWhole blood was obtained from PN patients with uncontrolled disease and control patients without pruritus. Plasma was assayed for IL-4, IL-5, IL-13, IgE, and periostin. ANOVA was utilized to compare PN and control patients and multiple-hypothesis adjusted p-value was calculated with the significance threshold at 0.05. Clustering was performed using K-means clustering.ParticipantsPN patients (n = 29) and controls (n = 18) from Johns Hopkins Dermatology had similar age sex, and race distributions.ResultsSingle-plex assays of the biomarkers demonstrated elevated circulating plasma IL-13 (0.13 vs. 0.006 pg/mL, p = 0.0008) and periostin (80.3 vs. 60.2 ng/mL, p = 0.012) in PN compared to controls. IL-4 (0.11 vs. 0.02 pg/mL, p = 0.30) and IL-5 (0.75 vs. 0.40 pg/mL, p = 0.10) were not significantly elevated, while IgE approached significance (1202.0 vs. 432.7 ng/mL, p = 0.08). Clustering of PN and control patients together revealed two clusters. Cluster 1 (n = 36) consisted of 18 PN patients and 18 controls. Cluster 2 (n = 11) consisted entirely of PN patients (p < 0.01). Cluster 2 had higher levels of IL-13 (0.33 vs. 0.008 pg/mL, p = 0.0001) and IL-5 (1.22 vs. 0.43 pg/mL, p = 0.03) compared to cluster 1.Conclusion and relevanceThis study demonstrates elevation of IL-13 and periostin in the blood of PN patients, with distinct clusters with varying degrees of type 2 inflammation. Given this heterogeneity, future precision medicine approaches should be explored in the management of PN.

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Section: Discussionmentioning

confidence: 99%

Circulating plasma IL-13 and periostin are dysregulated type 2 inflammatory biomarkers in prurigo nodularis: A cluster analysis

et al. 2022

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“…Recent findings on the pathophysiology of chronic pruritus have broadened our understanding of itch, suggesting that the type 2 interleukins, interleukin 4 and interleukin 13, and downstream JAK signaling modulate sensory nerves and can be responsible for chronic pruritus, at least in some patients. 4 , 5 , 6 Based on a recent analysis of 40 patients with CPUO, Roh et al 7 concluded that patients with CPUO without increased circulating blood eosinophils are more likely to respond to treatment with gabapentin and less likely to respond to immunomodulators, including dupilumab. Our patient had no elevated eosinophil levels in the blood but failed to show a sustained improvement from treatment with either gabapentin or sertraline.…”

Section: Discussionmentioning

confidence: 99%

Baricitinib rapidly and sustainably relieves a patient from chronic pruritus of unknown origin refractory to dupilumab

2021

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“…Elderly patients are at an increased risk of CP due to the cumulative effects of aging on the skin barrier and neurotrophic function. Patients with CPUO frequently present clinical features of a 'mild' or 'atopic-like', type 2-inflammatory phenotype, including eosinophilia, weakly elevated IgE levels, and subclinical skin inflammation [114,115]. Aging-related immunosenescence might drive a Th2-immune imbalance, further aggravating the itch sensation in elderly patients.…”

Section: Chronic Pruritus Of Unknown Origin and Of The Elderlymentioning

confidence: 99%

Pruritus as a Distinctive Feature of Type 2 Inflammation

et al. 2021

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Pruritus is a common symptom of several skin diseases, both inflammatory and neoplastic. Pruritus might have a tremendous impact on patients’ quality of life and strongly interfere with sleep, social, and work activities. We review the role of type-2 inflammation and immunity in the pathogenesis of chronic pruritic conditions of the skin. Type 2 cytokines, including IL-4, IL-13, thymic stromal lymphopoietin, periostin, IL-31, IL-25, and IL-33 are released by mast cells, innate lymphoid cells 2, keratinocytes, and type 2 T lymphocytes, and are master regulators of chronic itch. These cytokines might act as direct pruritogen on primary sensory neurons (pruriceptors) or alter the sensitivity to other itch mediators Type 2 inflammation- and immunity-dominated skin diseases, including atopic dermatitis, prurigo nodularis, bullous pemphigoid, scabies, parasitic diseases, urticaria, and Sézary syndrome are indeed conditions associated with most severe pruritus. In contrast, in other skin diseases, such as scleroderma, lupus erythematosus, hidradenitis suppurativa, and acne, type 2 inflammation is less represented, and pruritus is milder or variable. Th2 inflammation and immunity evolved to protect against parasites, and thus, the scratching response evoked by pruritus might have developed to alert about the presence and to remove parasites from the skin surface.

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Circulating blood eosinophils as a biomarker for variable clinical presentation and therapeutic response in patients with chronic pruritus of unknown origin

Cited by 12 publications

References 7 publications

Circulating plasma IL-13 and periostin are dysregulated type 2 inflammatory biomarkers in prurigo nodularis: A cluster analysis

Circulating plasma IL-13 and periostin are dysregulated type 2 inflammatory biomarkers in prurigo nodularis: A cluster analysis

Baricitinib rapidly and sustainably relieves a patient from chronic pruritus of unknown origin refractory to dupilumab

Pruritus as a Distinctive Feature of Type 2 Inflammation

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