REVIEW ARTICLE
173 Advances in dermatology and venereology ActaDV Acta Dermato-Venereologica ActaDV
Chronic Prurigo of Nodular Type : A Review
Claudia ZEIDLER 1 , Athanasios TSIANAKAS 1 , 2 , Manuel PEREIRA 1 , Hartmut STÄNDER 3 , 4 , Gil YOSIPOVITCH 5 and Sonja STÄNDER 1
1
Center for Chronic Pruritus , Department of Dermatology , University Hospital Münster , Münster , 2 Department of Dermatology , Fachklinik Bad Bentheim , 3 Dermatological Practice , Bad Bentheim , 4 Department of Dermatology , Klinikum Dortmund GmbH , Dortmund , Germany , and
5
Itch Center Department of Dermatology and Cutaneous Surgery , University of Miami Hospital , Miami , FL , USA
Prurigo nodularis ( PN ) is a subtype of chronic prurigo presenting single to multiple symmetrically distributed , hyperkeratotic and intensively itching papules and nodules . PN evolves along with chronic pruritus in the context of diverse dermatological , systemic , neurological or psychiatric conditions . Permanent scratching is possibly a major trigger of PN , although its exact pathophysiology remains unclear . Current state-ofthe-art therapy for PN consists of topical steroids , capsaicin , calcineurin inhibitors , ultraviolet ( UV ) therapy , systemic administration of gabapentinoids , μ-opioid receptor antagonists , antidepressants or immunosuppressants . Novel treatment concepts , such as inhibitors of neurokinin-1 , opioid and interleukin-31 receptors , have been developed and are currently being clinically tested .
Key words : itch ; pruritus ; chronic scratch lesions ; prurigo nodularis ; Hyde ’ s prurigo ; interleukin-31 ; neurokinin-1 .
Accepted Aug 23 , 2017 ; Epub ahead of print Aug 23 , 2017 Acta Derm Venereol 2018 ; 98 : 173 – 179 .
Corr : Claudia Zeidler , Center for Chronic Pruritus , University Hospital Münster , Von-Esmarch-Str . 58 , DE-48149 Münster , Germany . E-mail : claudia . zeidler @ ukmuenster . de
Prurigo nodularis ( PN ) is a highly pruritic , chronic disease clinically defined by the existence of many , usually symmetrically distributed , hyperkeratotic and erosive papules and nodules ( 1 ). PN evolves along with consistent scratching in patients with chronic pruritus , and is a subtype of chronic prurigo ( CPG ), which was defined recently by members of the European Academy of Dermatology and Venereology ( EADV ) Task Force Pruritus group , as a skin disease due to neuronal sensitization to itch and development of an itch – scratch cycle ( 2 ). The debate on the nature of CPG was initiated over 100 years ago after the first description of PN by Hyde ( 3 ), and is ongoing , as relevant aspects of the pathogenesis of CPG remain unclear ( 4 ). Part of the confusion is the use of the term “ prurigo ” for other not-primarily itch-related skin diseases ( e . g . actinic prurigo ), but also for scratching-related dermatoses . An attempt has been made recently to classify subtypes of CPG based on clinical criteria , differentiating between several types , such as papular , nodular , plaque or umbilicated prurigo , signifying the generally increased acceptance of this terminology ( 1 ). An important aspect of this terminology is the acceptance that the presence of CPG should initiate proper treatment and diagnosis of potential underlying diseases that might trigger scratching ( 5 ). The itch – scratch cycle in CPG appears to be linked to pruritus induced by various disorders , with 50 % of PN patients showing an atopic predisposition ( 6 ). Other dermatoses , as well as various systemic diseases , infections , neurological and psychiatric disorders , are also known to cause PN ( 5 ). Most patients then develop the vicious itch – scratch cycle that is difficult to treat with existing therapies . Itch intensity in PN is thought to be the highest among the different types of chronic itch ( 5 , 7 ), resulting in reduced quality of life , including sleep disturbances and psychiatric comorbidities ( 8 ).
This review summarizes current knowledge and recent findings on the clinical presentation and therapeutic management of PN , discusses ongoing research and indicates areas of future research needs .
EPIDEMIOLOGY
Epidemiological data regarding the incidence and prevalence of PN are lacking . Based on observations from case series , all age groups , including children ( 9 ) can be affected by PN , but elderly people are the most frequently affected ( 5 ). Furthermore , African Americans with atopic eczema appear to have more PN lesions than other racial groups ( 10 ). No conclusion can be drawn on differences between the sexes , as these results have not been reported consistently ( 5 ).
PATHOPHYSIOLOGY
Cutaneous inflammation and neuronal plasticity appear to play an important role in PN , but the exact pathogenesis of the condition remains unclear ( 11 ).
In 1934 , Pautrier ( 12 ) observed the presence of neural dermal hyperplasia ( Pautrier ’ s neuroma ) in PN . Thirtyfive years earlier Johnston described hypertophy of dermal nerve fibres in a papular dermatitis ( 13 ).
Histopathological studies revealed increased dermal nerve fibre density and changes in many types of skin cells , including mast cells , collagen fibres , Merkel cells , epidermal keratinocytes , dendritic cells and endothelial cells ( 14 – 16 ). The aforementioned cells cause inflammation and pruritus through the release of tryptase , interleukin-31 ( IL-31 ), prostaglandins , eosinophil cationic protein , histamine , and neuropeptides , such as substance P , calcitonin gene-related peptide ( CGRP ) and nerve growth factor ( NGF ) ( 16 – 19 ). In fact , PN skin
This is an open access article under the CC BY-NC license . www . medicaljournals . se / acta Journal Compilation © 2018 Acta Dermato-Venereologica . doi : 10.2340 / 00015555-2774 Acta Derm Venereol 2018 ; 98 : 173 – 179