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