Pruritus and prurigo: a significant advancement on diagnosis, classification, pathogenesis and treatment

Abstract

Pruritus or itch is defined as an unpleasant sensation, which causes a desire to scratch. This definition has been already elaborated by Samuel Haffenreffer in 1660; however, for decades or even centuries our knowledge about pruritus and ability to control, it was rather negligible. Still, in the 1980s and early 1990s, pruritus was considered as a subtype of pain. It was not until the late 1990s that C-type nerve fibres conducting pruritic stimuli were identified, and then, the presence of neurons in the central nervous system was demonstrated, which were part of the itch-specific conduction pathway. Over the last two decades, we may observe a further significant progress in our understanding of pruritus pathogenesis, which next might be translated into better classification, diagnosis and treatment of this unwanted symptom. The first major step in accelerating the studies on itch was the formation of the International Forum for the Study of Itch (IFSI) in 2005 in Heidelberg, Germany, initially being affiliated with Acta Dermato-Venereologica, but since 2016 having its own journal Itch. Collaborating experts have already been holding regular meetings since 2001, but only the establishing of the society has tightened ties and enabled closer cooperation between interdisciplinary researchers leading to ground-breaking novel findings regarding pathophysiology and therapy target identification. Subsequently, the European Academy of Dermatology and Venerology (EADV) established in 2016, the Task Force Pruritus, being a pruritus expert network based in Europe. With the support of the EADV, this group already ran several successful projects such as the European harmonization of Assessment of Severity of Pruritus (PruNet) or the European Prurigo Project, assessing for the first time comprehensive clinical data in this disease. One of the first and most important papers published by the IFSI experts was the new terminology and classification of chronic pruritus. The proposed classification focused on clinical signs and in the first step divides patients suffering from itch into three subgroups: those suffering from pruritus on diseased (inflamed) skin (group I), from pruritus on non-diseased (noninflamed) skin (group II) and those having chronic secondary scratch lesions (group III). Next, all patients have been allocated to different categories: dermatological diseases, systemic diseases including diseases of pregnancy and drug-induced pruritus, neurological and/or psychiatric diseases. If more than one cause might account for pruritus, ‘mixed’ category is indicated, while those subjects without identifiable cause of pruritus are allocated to ‘others’ category. Establishing the new pruritus classification has harmonized studies on pruritus and enabled better planning of subsequent trials on uniform patient populations. Also, out of date terms such as senile pruritus or pruritus sine materia have been deleted using the new terminology. To improve the care of patients’ suffering from chronic pruritus, in 2012, EADV and IFSI experts also published the European guidelines on chronic pruritus, giving clues on diagnostic procedures, treatment and follow up of patients with itch, which has been updated in 2019. Of note, these guidelines were the first international guidelines focusing specifically on pruritus. Special interest groups of IFSI, led by EADV members, published also guidelines on pruritus assessment in clinical trials, on questionnaires to assess chronic itch, and on paraneoplastic pruritus. Strikingly, over the last twenty years, the Journal of the European Academy of Dermatology and Venereology (JEADV) has significantly contributed to the development of ‘itch field’ and many important papers dealing with pruritus have been published in JEADV. Many studies provided for the first time patient-reported outcome data and uncovered the burden of patients suffering from itch, which have been neglected and underestimated for years. Interestingly, it was clearly demonstrated, that e.g. moderate-to-severe pruritus causes more quality of life impairments, depression and anxiety symptoms and dysmorphic concerns compared to patients with psoriasis. Patients with pruritus feel more stigmatized, suffer from sleep disorders and other mental symptoms, and more often may demonstrate suicidal ideations. In 2018, the group of EADV experts established the definition of chronic prurigo (CPG) being a distinct disease defined by the presence of chronic pruritus, history and/or signs of repeated scratching, and multiple localized or generalized pruriginous lesions. Similar to chronic pruritus, CPG can be of dermatological, systemic, neurologic, psychiatric, multifactorial or undetermined origin and occurs due to a neuronal sensitization to itch and the development of an itch-scratch cycle. In the past, the term prurigo was used in dermatology without clear definition, but the terminology of prurigo was inconsistent and confusing. According to the consensus, CPG should be used as an umbrella term for the range of clinical manifestations, such as papular, nodular, plaque and umbilicated type as well as recently established linear subtype of CPG.