Increased sensitivity to touch‐evoked itch (punctate hyperknesis) in prurigo nodularis and type 2 inflammation: A cross‐sectional pilot study

Abstract

Dear Editor, Mechanical stimuli can provoke an itch sensation, known as 'mechanical itch' or 'touch-evoked itch'. 1 An increase in sensitivity to touch-evoked itch (STTI) by pinprick stimuli is referred to as punctate hyperknesis. 2,3 Punctate hyperknesis can be found in patients with chronic itch conditions and is as debilitating as the itch itself. Its pathogenesis is reported to involve IL-4/13 and IL-31 signalling. 2,4 Prurigo nodularis (PN), a neuroimmune skin disease with multiple pruritic nodules, features chronic itch. 5 However, it is unclear whether PN patients show punctate hyperknesis. Therefore, we examined STTI in patients with PN and investigated the dermal expression of IL-4, IL-13 and IL-31 through immunohistochemical analysis in this cross-sectional pilot study. We enrolled 11 Japanese patients with PN (eight males and three females; age, 12-81 years old; three patients had atopic dermatitis [AD]) and nine healthy individuals without AD (eight males and one female; age, 18-43 years old). STTI was assessed as the mean value of itch intensity resulting from stimulation with preoptimized von Frey filaments (1.0, 1.4 and 2.0 g; Danmic Global, USA), rated on a numerical rating scale (NRS) from zero (no itch) to 10 (the worst imaginable itch). 2,6 STTI was probed on the slope (not the center) of the nodules located on the extremities (five patients) or on the trunk (six patients), and

Prurigo Nodularis: Pathogenesis and the Horizon of Potential Therapeutics

“…Similarly, there was an observed increase in the expression of genes associated with axonal growth, like NGF, in PN patients [66]. The altered neuroanatomy of the epidermis is linked to changes in nerve fiber function and neuronal hypersensitivity [66,[69][70][71]. In chronic prurigo of diverse origins, hyperkinesis resulting from electrical stimulation has been detected, indicating common mechanisms of central neuronal sensitization [72].…”

“…Another sign of neuronal sensitization is the heightened responsiveness to itching triggered by pinprick stimuli (punctate hyperkinesis), which is notably more pronounced at the location of itchy lesions compared to unaffected skin in PN patients. As Hashimoto et al suggested, this could result from changes in the neural structures within the epidermis and the influence of immune processes [69]. Interestingly, pain-transmitting mechanisms remain unchanged in PN [72].…”

Chronische Prurigo

“…Es wurde eine erhöhte Expression des Nervenwachstumsfaktors (NGF), von Matrixmetalloproteinasen, dem Chemokin CXCL2 und insulin-like growth factor 1 (IGF-1) beobachtet, was auf komplexe Mechanismen und Interaktionen zwischen verschiedenen Hautzelltypen hindeutet. 17 18,19 Die dominierenden Zellen, die IL-31RA exprimieren, sind Mastzellen und Makrophagen. 20 Die Intensität des Pruritus wurde mit der Expression von Proteinen und Rezeptoren in Verbindung gebracht, die am IL-31-Signalweg beteiligt sind.…”

“…[23][24][25][26] Bei CNPG wurde eine verringerte intraepidermale Nervenfaserdichte nachgewiesen, und die veränderte Neuroanatomie steht in Zusammenhang mit einer veränderten Nervenfaserfunktion und neuronaler Überempfindlichkeit. 15,18,27 Genetische Studien haben spezifische Varianten identifiziert, die mit CNPG assoziiert sind, unter anderem in der Nähe der Gene PLCB4 (Phospholipase C-β4) und TXNRD1 (Thioredoxin-Reduktase 1). 28 Diese Ergebnisse deuten auf ein komplexes Zusammenspiel zwischen dem Immunsystem und dem peripheren Nervensystem bei der Pathophysiologie der CNPG hin.…”

Chronic Prurigo

“…Interleukin-31 is found in T lymphocytes and CD11c + dermal myeloid dendritic cells that are abundant in lesional skin of CNPG patients. 18,19 Mast cells and macrophages are the dominant cell types expressing IL-31RA. 20 The intensity of pruritus has been associated with the expression of proteins and receptors involved in the IL-31 signaling pathway.…”