Prurigo Nodularis and Its Management

Chronic pruritus has multiple etiologies, ranging from inflammatory to metabolic and neuropathic processes. However, recent advances in itch biology have shed light on potential mechanisms that explain the molecular and cellular basis of these pathologies. Furthermore, new understanding of neuroimmune itch circuits necessitates clarification of terminologies such as “neuropathic” and “neurogenic.” This review provides an overview of ways new concepts may better explain the pathophysiology of a variety of chronic pruritic disorders and the rationale for directing emerging novel therapeutic strategies toward them.

Chronic pruritus (CP) (ie, itch that persists for more than 6 weeks) poses significant challenges to patients’ health and quality of life. It is a common reason for visits to dermatologists and general practitioners and can be caused by a range of conditions, including systemic diseases such as chronic kidney disease or liver diseases, malignancies, neuropathic conditions, and dermatoses such as atopic dermatitis. CP often does not develop in parallel with the course of the disease and can become an entity of its own, which must be treated with antipruritic drugs, even if the underlying cause is already under therapy. Depending on the etiology of CP, different pathways in the pathogenesis have been analyzed recently, following which new treatments have been developed and tested in randomized controlled trials. This article discusses the recent results of these studies and highlights how best to manage health care for patients with CP.

Prurigo nodularis (PN) is a chronic skin disorder of unknown origin which has the features of small nodules and papules along with intolerable itch leading to ulcers, bleeding and sensory neural loss in affected area. PN has quite resemblance with Alasaka in Ayurveda, which is a vata-kapha pradhan kshudra kushtha.

A 50 years old male patient suffering from PN was being treated on the line of Ayurveda just before the beginning of COVID pandemic. Due to sudden surge of first wave of corona virus pandemic and lockdown in India, the planed virechana (purgation) therapy was interrupted. We shifted our plan to mild type of virechana and conservative therapy after a short break of 10 days at patients’ home. However, the case was responded very well and significant clinical improvement was observed in Dynamic Pruritus Score (DPS), Numerical Rating Scale (NRS), Visual Analogue Scale (VAS), Verbal Rating Scale (VRS), Pruritus Severity Scale (PSS), Hamilton Depression Rating Scale (HDRS) and Dermatology Life Quality Index (DLQI).

El prurigo crónico es una entidad con una apariencia clínica común pero que puede ser secundaria a un gran número de patologías. Históricamente ha sido una enfermedad no bien definida y con escasas terapias disponibles, por lo que su manejo es muy complejo. Clínicamente se caracteriza por lesiones escoriadas e hiperqueratósicas en el contexto de un paciente con prurito crónico. Ante la sospecha de un prurigo crónico, es fundamental realizar un buen diagnóstico diferencial e identificar todas sus posibles causas. En los últimos años se han producido importantes avances con la aparición de nuevos criterios diagnósticos y con el desarrollo de nuevos fármacos. Un mayor conocimiento de esta patología redundará en el beneficio de unos pacientes que hasta el momento carecen de un tratamiento claramente efectivo.

Chronic prurigo is itself a common condition, but it can also occur secondary to a large number of diseases. Management is challenging as historically chronic prurigo has been poorly defined and very few treatments are available. Clinically, it presents as excoriated, hyperkeratotic lesions. When chronic prurigo is suspected, a comprehensive differential diagnosis is essential. New diagnostic criteria have appeared in recent years and new drugs have been developed. Although no truly effective treatment is yet available, patients will benefit from a greater understanding of this condition.

Chronic prurigo (CPG) is characterized by intensive itch and interactions among nerves, neuropeptides, and mast cells (MCs). The role of some neuropeptides such as cortistatin (CST) and its receptor, Mas-related G protein–coupled receptor X2 (MRGPRX2), in CPG remains poorly investigated.

We evaluated first whether CST activates human skin MCs, and second whether CST and MRGPRX2 are expressed in the skin of CPG patients, and by which cells.

Skin prick tests and microdialysis with CST were performed in 6 and 1 healthy volunteers, respectively. Degranulation of human skin MCs was assessed using β-hexosaminidase and histamine release assays. Skin samples from 10 patients with CPG and 10 control subjects were stained for CST, MCs, and MRGPRX2 (protein and mRNA) using immunohistochemistry, immunofluorescence, and/or in situ hybridization. Flow cytometry was used to assess CST in human skin MCs. MRGPRX2 levels were measured in serum by ELISA.

CST induced concentration-dependent degranulation of human skin MCs in vivo and ex vivo. Skin lesions of CPG patients exhibited markedly higher numbers of CST-expressing cells, CST-expressing MCs, MRGPRX2-expressing cells, and MRGPRX2 mRNA-expressing cells than nonlesional skin. MCs were the main MRGPRX2 mRNA-expressing cells in the lesions of most CPG patients (70%). Stimulation of human skin MCs with anti-IgE led to a release of CST. The number of MRGPRX2-expressing cells correlated with disease severity (r = 0.649, P = .04). MRGPRX2 serum levels in CPG patients correlated with disease severity (r = 0.704, P = .023) and quality-of-life impairment (r = 0.687, P = .028).

CST and MRGPRX2 may contribute to the pathogenesis of CPG and should be evaluated in further studies as potential biomarkers and novel therapeutic targets.