Evaluation of Serum Biomarkers and Itch Severity in Prurigo Nodularis

Among patients with prurigo nodularis, no correlation was identified between serum biomarkers and itch severity — including interleukin 13 (IL-13) and caspase-8 — although significant elevations in IL-13 were reported in single-plex cytokine analysis and in levels of caspase-8 in the Olink panel, according to study findings presented at the 2023 Annual Meeting of the American Academy of Dermatology (AAD), held from March 17 to 21, 2023 in New Orleans, Louisiana.

Prurigo nodularis, an inflammatory skin condition distinguished by severely pruritic, hyperkeratotic nodules distributed symmetrically across the trunk and extremities, has an incidence rate of about 37 to 44 per 100,000 population. Researchers aimed to describe the systemic inflammatory signature of the condition and correlate the proteomic signature with patient itch severity scores.

Investigators recruited 33 patients with prurigo nodularis from the Miami Itch Center and 20 sex- and age-matched healthy control individuals. They collected serum samples and clinical data, including itch duration and self-reported intensity, from all participants. Single-plex immunoassay was used to analyze all serum samples for IL-4, IL-5, IL-13, IL-17A, IL-22, periostin, and immunoglobulin E (IgE). The comprehensive Olink Target 96 Inflammation panel was also used to test samples. Patients with concomitant atopic diagnosis were excluded from participation in the study.

Patients had Investigator Global Assessment scores of at least 3, average 24-hour numeric rating scale (NRS) score was 7.67±0.4 standard error of the mean (range, 0.0-10.0), and average itch duration was 10.3±1.5 (1.0-30.0) years.

Researchers identified significant elevation in IL-13 (4.39-fold changes [FC]; P =.0004) in patients with prurigo nodularis vs those in the healthy control group in single-plex cytokine analysis. No correlation between NRS itch severity scores and IL-13 was reported. Biomarkers IL-4, IL-5, IL-17A, IL-22, periostin, and IgE failed to yield significant results. There was no evaluation of IL-31, a common pruritogen found in lesional skin of patients with prurigo nodularis, due to limitations in reliability and sensitivity of the available immunoassays.

Caspase-8 (1.56-FC; P =9.35E-5 [.0000935]) was significantly elevated in the Olink panel, and IL-17C was significantly decreased (-2.61-FC; P =1.38E-9). IL-17C, mainly expressed by epithelial cells rather than immune cells, is upregulated in lesional pruritus nodularis and downregulated in the serum.

Researchers concluded there was no correlation between serum biomarkers and itch severity among patients with prurigo nodularis. However, they commented, “Serum proteomic signature of [prurigo nodularis] showed significant elevation of IL-13, a key Th2 cytokine, providing further support that it has a significant role in [prurigo nodularis].” They further wrote “Although [caspase]-8 has been generally regarded to have anti-inflammatory properties, there are findings that suggest [caspase]-8 may also be proinflammatory by inducing cytokine and chemokine expression depending on cell type and context.” They added “As [caspase]-8 was upregulated in this study, it may play a more proinflammatory role in [prurigo nodularis] pathogenesis.”

Disclosure: This research was supported by Eli Lilly and Company. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.