Transcriptomic, Epigenomic, and Neuroanatomic Signatures Differ in Chronic Prurigo, Atopic Dermatitis, and Brachioradial Pruritus

Modulation of Neuroimmune and Epithelial Dysregulation in Patients With Moderate to Severe Prurigo Nodularis Treated With Nemolizumab

“…With respect to neural pathways, synaptogenesis signaling and neuritogenesis were significantly downregulated after treatment with nemolizumab. The pathogenesis of PN involves intraepidermal nerve fiber hypoplasia with increased branching of nerve fibers and increased dermal levels of neuropeptide signaling, via factors such as substance P and nerve growth factor . Interleukin 31 can activate transient receptor potential vanilloid 1–positive nociceptive neurons of the peripheral nervous system, which leads to transmission of pruritus sensation and enhances inflammation .…”

“…Immunophenotyping studies of PN show increased T lymphocytes, mast cells, and eosinophils associated with PN, as well as increased inflammatory cytokines including interleukin 4 (IL-4), IL-13, IL-31, IL-17, IL-22, and IL-31. Prurigo nodularis is also associated with disturbed neuronal architecture (increased epidermal neuronal branching and dermal neuronal hyperplasia) and dysregulation of neuropeptides that may contribute to inflammation . Epidermal dysregulation is seen as a result of these processes, characterized by epidermal hyperplasia and hyperkeratosis, as well as proinflammatory vascularization processes in the dermis through activation of vascular endothelial growth factor (VEGF) …”

“…Prurigo nodularis is also associated with disturbed neuronal architecture (increased epidermal neuronal branching and dermal neuronal hyperplasia) and dysregulation of neuropeptides that may contribute to inflammation. [13][14][15][16] Epidermal dysregulation is seen as a result of these processes, characterized by epidermal hyperplasia and hyperkeratosis, as well as proinflammatory vascularization processes in the dermis through activation of vascular endothelial growth factor (VEGF). [17][18][19] Targeting the IL-31 receptor α (IL-31RA) in PN with subcutaneous injection of nemolizumab, 0.5 mg/kg every 4 weeks, improved clinical responses in adults with moderate to severe PN in a randomized, double-blind phase 2 clinical trial.…”

Lingual innervation in male and female marmosets

“…We used GFAP as a pan-nerve filament marker as it is known to stain myelinating and non-myelinating Schwann cells ( Bianchini et al, 1992 , McKenzie et al, 2006 , Yang and Wang, 2015 ). However, PGP9.5 which is a widely used pan-neuronal marker ( Boyd et al 2021 ; Lindquist et al 2021 ; Brady et al 2004 ; Chou et al 2001 ; Atherton et al 2023 ; Agelopoulos et al 2023 ), also stained well and can also be used as an alternate, for marmoset tongue tissues ( Fig S4 ). We did not find any evidence of pan-nerve fiber staining of human tongue tissues, although we speculate that both GFAP and PGP9.5 can potentially be used as pan-nerve markers in human tongue as well.…”

State of the Art on the Role of Staphylococcus aureus Extracellular Vesicles in the Pathogenesis of Atopic Dermatitis

“…It shows worldwide occurrence, affecting both children and adults, whose prevalence is approximately 15–20% and 1–5%, respectively [ 1 , 2 , 3 ]. Although a common disease, the pathogenesis of AD is a complex network of skin barrier defects, imbalance in adaptive and innate immunity, and chronic skin colonization by Staphylococcus aureus ( S. aureus ) [ 4 , 5 , 6 ], all of which drive an inflammatory vicious cycle culminating in the main symptom: pruritus [ 7 , 8 , 9 , 10 ]. But among the variables associated with AD development, the interaction between the host defense system and the microbial virulence factors involved in S. aureus skin colonization, infection and the perpetuation of inflammation are gathering increased attention [ 11 ], mostly due to clinical evidence that, in AD flares, decreased bacterial diversity associated with increased S. aureus abundance has been described and related to disease severity [ 11 , 12 , 13 , 14 ].…”