Background
The term prurigo has been used for many decades in dermatology without clear definition, and currently used terminology of prurigo is inconsistent and confusing. Especially, itch‐related ...prurigo remains unexplored regarding the epidemiology, clinical profile, natural course, underlying causes, available treatments and economic burden, although burdensome and difficult to treat.
Objective
To address these issues, the multicentre European Prurigo Project (EPP) was designed to increase knowledge on chronic prurigo (CPG). In the first step, European experts of the EADV Task Force Pruritus (TFP) aimed to achieve a consensus on the definition, classification and terminology of CPG. Additionally, procedures of the cross‐sectional EPP were discussed and agreed upon.
Methods
Discussions and surveys between members of the TFP served as basis for a consensus conference. Using the Delphi method, consensus was defined as an agreement ≥75% among the present members.
Results
Twenty‐four members of the TFP participated in the consensus conference. Experts consented that CPG should be used as an umbrella term for the range of clinical manifestations (e.g. papular, nodular, plaque or umbilicated types). CPG is considered a distinct disease defined by the presence of chronic pruritus for ≥6 weeks, history and/or signs of repeated scratching and multiple localized/generalized pruriginous skin lesions (whitish or pink papules, nodules and/or plaques). CPG occurs due to a neuronal sensitization to itch and the development of an itch‐scratch cycle.
Conclusion
This new definition and terminology of CPG should be implemented in dermatology to harmonize communication in the clinical routine, clinical trials and scientific literature. Acute/subacute forms of prurigo are separated entities, which need to be differentiated from CPG and will be discussed in a next step. In the near future, the cross‐sectional EPP will provide relevant clinical data on various aspects of CPG leading to new directions in the scientific investigation of CGP.
Pruritus is a frequent sensation in dermatoses, but its prevalence in patients in dermatological practices has not been fully studied. The aim of this cross-sectional study is to investigate its ...prevalence and characteristics in all patients attending a dermatology practice in Germany over a period of one week (n = 334; 52.7% female; median age 45.0 years). The point prevalence of pruritus in this study population was 36.2% (87.6% of whom had chronic pruritus). It inhibited the everyday life of 73.6% of all patients, with 77.7% reporting a frequently to permanently experienced moderate intensity. (5.2 ± 2.3 on the numerical rating scale). Of the patients, 52.1% had previously consulted their general practitioner, and 62% had visited the dermatologist due to pruritus. This study shows that pruritus is a highly prevalent, clinically and economically relevant symptom in dermatological practices. The majority of patients suffering from chronic pruritus are severely burdened and medically underserved. Dermatologists should be aware that pruritus also occurs frequently in patients who do not primarily present due to their symptoms.
Chronic pruritus (CP) is frequent in general medicine and the most common complaint in general dermatology. The prevalence of CP is expected to rise in the future due to the ageing population. The ...clinical presentation, underlying aetiology and treatment strategy of CP are heterogeneous. Also, individual treatment aims and physical, psychic and economic burdens of patients might vary. Chronic prurigo (CPG) is the most severe disease in the chronic pruritus spectrum, being associated with long-standing scratch-induced skin lesions and a therapy refractory itch-scratch-cycle. It is thus important to raise disease awareness for CP and CPG in the general public and among decision-makers in the health system. Further, there is a need to support a rational clinical framework to optimize both diagnostics and therapeutics. Currently, there is still a shortcoming regarding approved therapies and understanding CP/CPG as severe medical conditions. Therefore, the EADV Task Force Pruritus decided to publish this white paper based on several consensus meetings. The group consented on the following goals: (a) ensure that CP is recognized as a serious condition, (b) increase public awareness and understanding of CP and CPG as chronic and burdensome diseases that can greatly affect a person's quality of life, (c) clarify that in most cases CP and CPG are non-communicable and not caused by a psychiatric disease, (d) improve the support and treatment given to patients with CP to help them manage their disease and (e) publicize existing therapies including current guidelines. We aim to point to necessary improvements in access and quality of care directed to decision-makers in health policy, among payers and administrations as well as in practical care.
Summary
Background
Rare variants in the genes IL36RN, CARD14 and AP1S3 have been identified to cause or contribute to pustular skin diseases, primarily generalized pustular psoriasis (GPP).
...Objectives
To better understand the disease relevance of these genes, we screened our cohorts of patients with pustular skin diseases primarily GPP and palmoplantar pustular psoriasis (PPP) for coding changes in these three genes. Carriers of single heterozygous IL36RN mutations were screened for a second mutation in IL36RN.
Methods
Coding exons of IL36RN, CARD14 and AP1S3 were sequenced in 67 patients – 61 with GPP, two with acute generalized exanthematous pustulosis and four with acrodermatitis continua of Hallopeau. We screened IL36RN and AP1S3 for intragenic copy‐number variants and 258 patients with PPP for coding changes in AP1S3. Eleven heterozygous IL36RN mutations carriers were analysed for a second noncoding IL36RN mutation. Genotype–phenotype correlations in carriers/noncarriers of IL36RN mutations were assessed within the GPP cohort.
Results
The majority of patients (GPP, 64%) did not carry rare variants in any of the three genes. Biallelic and monoallelic IL36RN mutations were identified in 15 and five patients with GPP, respectively. Noncoding rare IL36RN variants were not identified in heterozygous carriers. The only significant genotype–phenotype correlation observed for IL36RN mutation carriers was early age at disease onset. Additional rare CARD14 or AP1S3 variants were identified in 15% of IL36RN mutation carriers.
Conclusions
The identification of IL36RN mutation carriers harbouring additional rare variants in CARD14 or AP1S3 indicates a more complex mode of inheritance of pustular psoriasis. Our results suggest that, in heterozygous IL36RN mutation carriers, there are additional disease‐causing genetic factors outside IL36RN.
What's already known about this topic?
The genes IL36RN, CARD14 and AP1S3 have been implicated in pustular skin disease with IL36RN having a major role.
Most studies have analysed variants in different genes separately.
Significant subsets of patients with a pustular skin disease carry a single heterozygous mutation in IL36RN, leaving unanswered whether and how the variant is disease‐contributing.
What does this study add?
Intragenic copy‐number variants or noncoding mutations in carriers of single IL36RN mutations were not found.
In total, 15% of patients with generalized pustular psoriasis (GPP) with IL36RN mutations carried variants in CARD14 or AP1S3, providing evidence for a complex inheritance.
Lack of causal /disease‐contributing variants in 64% of GPP patients suggests a role for other, not yet identified genes.
Genotype–phenotype correlation did not reveal significant correlations aside from the presence of IL36RN mutations with age at onset.
What is the translational message?
This study of three genes provides evidence that the inheritance of GPP is more complex than previously understood.
The role of known genes in GPP is rather limited, as almost two‐thirds of patients do not carry a variant in any of these genes.
In palmoplantar pustular psoriasis, the percentage of noncarriers is even lower.
Further genetic studies will reveal the diseases’ pathogenesis and provide a basis to use/develop more specific treatments.
Linked Comment: Capon. Br J Dermatol 2018; 178:589–590
Respond to this article
Position Statement: Linear prurigo is a subtype of chronic prurigo Pereira, M.P.; Zeidler, C.; Nau, T. ...
JEADV. Journal of the European Academy of Dermatology and Venereology/Journal of the European Academy of Dermatology and Venereology,
February 2019, Volume:
33, Issue:
2
Journal Article
Peer reviewed
Open access
Background
Chronic prurigo (CPG) is a distinct disease characterized by chronic pruritus, history and/or signs of prolonged scratching and multiple pruriginous lesions. It may present with various ...clinical manifestations, including papules, nodules, plaques or umbilicated lesions. Some patients with chronic pruritus show pruriginous linear and scaring scratch lesions (LSSL) and it is unclear whether these lesions belong to the spectrum of CPG.
Objective
To achieve a consensus on the classification of pruriginous LSSL and establish criteria to differentiate them from similar appearing conditions of different nature.
Methods
Members of the Task Force Pruritus (TFP) of the European Academy of Dermatology and Venereology participated in the consensus conference, discussing representative clinical cases. Using the Delphi method, consensus was reached when ≥75% of members agreed on a statement.
Results
Twenty‐one members of the TFP with voting rights participated in the meeting. It was consented that LSSL occurs due to chronic pruritus and prolonged scratching, and share common pathophysiological mechanisms with CPG. LSSL were thus considered as belonging to the spectrum of CPG and the term ‘linear prurigo’ was chosen to describe this manifestation.
Conclusion
Considering linear prurigo as belonging to the spectrum of CPG has important clinical implications, since both the diagnostic and therapeutic approach of these patients should be performed as recommended for CPG. Importantly, linear prurigo should be differentiated from self‐inflicted skin lesions as factitious disorders or skin picking syndromes. In the latter, artificial manipulation rather than pruritus itself leads to the development of cutaneous lesions, which can show clinical similarities to linear prurigo.
Summary
Background The topical calcineurin inhibitors pimecrolimus and tacrolimus have been demonstrated to be an effective new anti‐inflammatory therapy. The only clinically relevant side‐effect ...reported is transient application site burning and stinging itch at the beginning of topical therapy.
Objectives In order to understand the underlying mechanism of this effect, we examined whether or not the compounds are able to stimulate neuropeptide release in normal murine skin as well as in a mouse model of experimentally induced irritant contact dermatitis.
Methods Balb/c mice were treated with 1% pimecrolimus cream or 0·1% tacrolimus ointment. Untreated and corresponding vehicle‐treated mice served as controls. Skin specimens were investigated by light, immunofluorescence and electron microscopy as well as enzyme‐linked immunosorbent assay and polymerase chain reaction.
Results Topical application of pimecrolimus and tacrolimus was followed by an initial release of substance P and calcitonin gene‐related peptide from primary afferent nerve fibres in murine skin during the early inflammatory response. The release of the neuropeptides and their binding to mast cells (MCs) led to MC degranulation. Mediators of MCs such as histamine and tryptase may induce pruritus and burning by binding to the corresponding receptors (histamine receptor 1, proteinase‐activated receptor 2) on sensory nerve fibres, which explains the initial side‐effects during therapy with calcineurin inhibitors.
Conclusions It may be speculated that calcineurin inhibitors directly stimulate intracellular signalling pathways or bind to ion channels such as transient receptor potential vanilloid 1 or receptors involved in nociception.
Chronic Prurigo of Nodular Type: A Review Zeidler, Claudia; Tsianakas, Athanasios; Pereira, Manuel ...
Acta dermato-venereologica,
2018-Feb-07, Volume:
98, Issue:
2
Journal Article
Peer reviewed
Open access
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-of-the-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.
Background
Chronic nodular prurigo (CNPG) is a condition characterized by chronic itch, a prolonged scratching behaviour and the presence of pruriginous nodules. A comprehensive understanding of this ...condition, especially regarding its clinical characteristics and impact on quality of life is still lacking.
Objectives
Aim of this pan‐European multicentre cross‐sectional study was to establish the clinical profile of CNPG, including its associated burden.
Methods
Fifteen centres from 12 European countries recruited CNPG patients presenting at the centre or using the centres' own databases. Patients were asked to complete a questionnaire in paper or electronic format. Demography, current co‐morbidities, underlying disease, itch intensity, additional sensory symptoms, quality of life, highest burden and emotional experience of itch were assessed.
Results
A total of 509 patients (210 male, median age: 64 years 52; 72) were enrolled. Of these, 406 reported itch and CNPG lesions in the previous 7 days and qualified to complete the whole questionnaire. We recorded moderate to severe worst itch intensity scores in the previous 24 h. Scores were higher in patients with lower educational levels and those coming from Eastern or Southern Europe. Most patients experience itch often or always (71%) and report that their everyday life is negatively affected (53%). Itch intensity was considered to be the most burdensome aspect of the disease by 49% of the patients, followed by the visibility of skin lesions (21%) and bleeding of lesions (21%). The majority of patients was unaware of an underlying condition contributing to CNPG (64%), while psychiatric diseases were the conditions most often mentioned in association with CNPG (19%).
Conclusions
This multicentre cross‐sectional study shows that itch is the dominant symptom in CNPG and reveals that the profile of the disease is similar throughout Europe.
Induction of tolerance by subsequent UV exposures is the most effective therapy for solar urticaria; however, it is time-consuming and takes a long time until protection is achieved. Three patients ...with solar urticaria were exposed to multiple UVA irradiations at 1-hour intervals per day. With this rush hardening regimen, protection was achieved within 3 days.
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