Prurido Crónico: Fisiopatologia, Classificação Clínica, Diagnóstico e Tratamento

Pruritus persisting for six weeks or longer is considered chronic. It may arise from dermatological, systemic, neurological, psychosomatic or psychiatric conditions or result from a combination of several factors. Due to chronicity processes, such as peripheral and central sensitization, pruritus may persist even after treatment of the underlying cause. Additionally chronic pruritus constitutes often a high burden for the affected patients, who frequently develop associated conditions, such as anxiety, depression or sleep disorders. Owing to the multiple dimensions of chronic pruritus, it presents a diagnostic and therapeutic challenge to the attending physician. The categorization of the condition according to the clinical presentation helps directing the diagnostic and treatment efforts. Therapeutically a step-wise approach should be undertaken. First basic measures, such as the use of emollients for dry skin, topical steroids for inflamed or excoriated skin and antihistamines should be initiated. If the origin underlying the chronic pruritus is found, a causal therapy should be attempted. If no cause is found or a causal treatment is not possible, a symptomatic multimodal therapy with topical and systemic agents is often necessary. With increasing knowledge of the pathophysiological mechanisms underlying chronic pruritus, novel drugs with promising effects are being developed.Prurido com seis ou mais semanas de duração é considerado crónico (PC). Pode ter como origem causas dermatológicas, sistémicas, neurológicas, psicossomáticas ou psiquiátricas ou advir de uma combinação de vários factores. Devido a processos de cronificação, nomeadamente sensibilização neuronal periférica e central, o prurido pode persistir apresar do tratamento da causa subjacente. Além disso, PC leva frequentemente a doenças reativas, como depressão, ansiedade ou distúrbios de sono, tendo como consequência um substancial decréscimo da qualidade de vida. Devido à multidimensionalidade do PC, esta condição representa um desafio importante para o médico assistente. A classificação do doente com PC de acordo com a apresentação clínica facilita a orientação dos procedimentos de diagnóstico necessários bem como ajuda a estabelecer uma estratégia terapêutica. A nível terapêutico uma abordagem por etapas é recomendada. Primeiramente devem-se iniciar medidas básicas como a aplicação de emolientes para a xerose cutânea, corticoesteróides tópicos para pele inflamada ou com escoriações bem como o uso de medicamentos anti-histamínicos. Caso a origem do PC seja conhecida, deve-se proceder, se possível, ao tratamento da causa subjacente. Se a causa permanecer desconhecida ou não for passível de tratamento, uma terapia sintomática multimodal com agentes tópicos e sistémicos é frequentemente necessária. Com o aumento do conhecimento dos mecanismos patofisiológicos subjacentes ao PC, novos fármacos tem sido desenvolvidos mostrando resultados promissores

Geschlechtsspezifische Unterschiede bei chronischem Pruritus

"Chronischer Juckreiz ist mit einer Lebenszeitprävalenz von ca. 23 % ein sehr häufiges Symptom, das durch zahlreiche dermatologische, internistische, neurologische und auch psychische Erkrankungen ausgelöst werden kann. Während bei jüngeren Patientinnen und Patienten eher der entstellende Aspekt der durch Kratzen beschädigten Haut eine Rolle spielt, leiden ältere Patientinnen und Patienten oftmals unter einem schwer zu behandelbaren Juckreiz unterschiedlichster Ursache. Obwohl der chronische Pruritus als Volkssymptom angesehen werden kann, liegen bisher nur sehr wenige Studien zu geschlechtsspezifischen Unterschieden vor. Diese zeigen, dass Frauen und Männer eine unterschiedliche Pruritus- Wahrnehmung haben - Frauen nehmen das Symptom intensiver wahr. Dies führt bei Frauen nicht nur zu einer höheren psychischen Belastung, sondern auch zu einem unterschiedlichen Verhalten - Frauen kratzen vermehrt. Aber auch die Qualitäten des Symptoms sind unterschiedlich, Frauen empfinden beispielsweise vermehrt einen brennenden Juckreiz, was u. a. auf die Aktivierung von schmerzleitenden Nervenfasern (neuropathische Komponente) hindeutet. Dies deutet auf eine unterschiedliche Verarbeitung von Pruritus im Gehirn hin. Die geschlechtsspezifischen Unterschiede hinsichtlich der Juckempfindung sollten dringend weiter untersucht werden, um eine geschlechtsadaptierte Diagnostik und möglicherweise auch Therapie anbieten zu können und somit zur verbesserten Behandlung der Betroffenen beitragen zu können." (Autorenreferat)"Chronicitch is a common symptom with a life-time prevalence of around 23% which is provoked by numerous dermatological, internal, neurological and mental disorders. While the disfiguring resulting from skin being damaged by scratching plays an important role in younger patients, older patients often suffer from a difficult-to-treat pruritus of various causes. Although chronic pruritus can be considered as a widespread disease, there are only a few studies which have examined sex-/ gender-specific differences. These studies have indicated that females and males have a different pruritus perception: females experience the symptom more intensively. This not only leads to a greater psychological burden in females, but results in a different behaviour, because females scratch more. Women also experience different symptoms, for example more women experience a burning itch, which indicates a stronger involvement of nerve fibres (neuropathic component). Women not only experience greater itch intensity, they are also more distracted by the itching than men are. This indicates a different cerebral perception and modulation. Sex-/genderspecific differences in regard to itching need further investigation in order to be able to offer sex-/gender-specific diagnostics and tailor therapy to improve the clinical situation of the affected patients." (Autorenreferat

Geschlechtsspezifische Unterschiede bei chronischem Pruritus

Chronischer Juckreiz ist mit einer Lebenszeitprävalenz von ca. 23 % ein sehr häufiges Symptom, das durch zahlreiche dermatologische, internistische, neurologische und auch psychische Erkrankungen ausgelöst werden kann. Während bei jüngeren Patientinnen und Patienten eher der entstellende Aspekt der durch Kratzen beschädigten Haut eine Rolle spielt, leiden ältere Patientinnen und Patienten oftmals unter einem schwer zu behandelbaren Juckreiz unterschiedlichster Ursache. Obwohl der chronische Pruritus als Volkssymptom angesehen werden kann, liegen bisher nur sehr wenige Studien zu geschlechtsspezifischen Unterschieden vor. Diese zeigen, dass Frauen und Männer eine unterschiedliche Pruritus- Wahrnehmung haben – Frauen nehmen das Symptom intensiver wahr. Dies führt bei Frauen nicht nur zu einer höheren psychischen Belastung, sondern auch zu einem unterschiedlichen Verhalten – Frauen kratzen vermehrt. Aber auch die Qualitäten des Symptoms sind unterschiedlich, Frauen empfinden beispielsweise vermehrt einen brennenden Juckreiz, was u. a. auf die Aktivierung von schmerzleitenden Nervenfasern (neuropathische Komponente) hindeutet. Dies deutet auf eine unterschiedliche Verarbeitung von Pruritus im Gehirn hin. Die geschlechtsspezifischen Unterschiede hinsichtlich der Juckempfindung sollten dringend weiter untersucht werden, um eine geschlechtsadaptierte Diagnostik und möglicherweise auch Therapie anbieten zu können und somit zur verbesserten Behandlung der Betroffenen beitragen zu können

S2k guideline: Diagnosis and treatment of chronic pruritus

Pruritus is a cross-disciplinary leading symptom of numerous diseases and represents an interdisciplinary diagnostic and therapeutic challenge. In contrast to acute pruritus, chronic pruritus (CP) is a symptom of various diseases that is usually difficult to treat. Scratching and the development of scratch-associated skin lesions can alter the original skin status. In the presence of an itch-scratch-cycle, even secondary diseases such as chronic prurigo can develop. Chronic pruritus leads to considerable subjective suffering of those affected, which can result in restrictions on the health-related quality of life such as sleep disturbances, anxiety, depressiveness, experience of stigmatization and/or social withdrawal up to clinically relevant psychic comorbidities. Medical care of patients should therefore include (a) interdisciplinary diagnosis and therapy of the triggering underlying disease, (b) therapy of the secondary symptoms of pruritus (dermatological therapy, sleep promotion, in the case of an accompanying or underlying psychological or psychosomatic disease an appropriate psychological-psychotherapeutic treatment) and (c) symptomatic antipruritic therapy. The aim of this interdisciplinary guideline is to define and standardize the therapeutic procedure as well as the interdisciplinary diagnosis of CP. This is the short version of the updated S2k-guideline for chronic pruritus. The long version can be found at www.awmf.org

Sex Differences in Itch Perception and Modulation by Distraction – an fMRI Pilot Study in Healthy Volunteers

Background: Even though itch is a common syndrome of many diseases there is only little knowledge about sex and gender differences in pruritus, especially in central itch perception and modulation. To our knowledge, this is the first fMRI study examining sex differences in perception and its modulation by distraction. Methods: Experimental itch was induced by application of histamine (0.1 mM) via microdialysis fibers twice at the left forearm and twice at the left lower leg in 33 healthy volunteers (17 females, 16 males). The brain activation patterns were assessed by fMRI during itch without and with distraction (Stroop task). Between the various conditions, subjects were asked to rate itch intensity, desire to scratch and pain intensity. In a second experiment in 10 of the 33 volunteers histamine was replaced by saline solution to serve as control for the ‘Stroop’ condition. Results: Women generally presented higher itch intensities compared to men during itch over the course of the experiment. A more specific analysis revealed higher itch intensities and desire to scratch in women during experimental induced itch that can be reduced by distraction at the lower legs when itch is followed by ‘Stroop’. In contrast, men depicted significant reduction of ‘itch’ by ‘Stroop’ at the forearms. Women depicted higher brain activation of structures responsible for integration of sensory, affective information and motor integration/planning during ‘itch’ and ‘Stroop’ condition when compared to men. No sex differences were seen in the saline control condition. Conclusion: Women and men exhibited localisation dependent differences in their itch perception with women presenting higher itch intensities and desire to scratch. Our findings parallel clinical observations of women reporting higher itch intensities depending on itch localisation and suffering more from itch as compared to men

Targeting the Neurokinin Receptor 1 with Aprepitant: A Novel Antipruritic Strategy

Chronic pruritus is a global clinical problem with a high impact on the quality of life and lack of specific therapies. It is an excruciating and frequent symptom of e.g. uncurable renal, liver and skin diseases which often does not respond to conventional treatment with e.g. antihistamines. Therefore antipruritic therapies which target physiological mechanisms of pruritus need to be developed. Substance P (SP) is a major mediator of pruritus. As it binds to the neurokinin receptor 1 (NKR1), we evaluated if the application of a NKR1 antagonist would significantly decrease chronic pruritus.Twenty hitherto untreatable patients with chronic pruritus (12 female, 8 male; mean age, 66.7 years) were treated with the NKR1 antagonist aprepitant 80 mg for one week. 16 of 20 patients (80%) experienced a considerable reduction of itch intensity, as assessed by the visual analog scale (VAS, range 0 to 10). Considering all patients, the mean value of pruritus intensity was significantly reduced from 8.4 VAS points (SD +/-1.7) before treatment to 4.9 VAS points (SD +/-3.2) (p<0.001, CI 1.913-5.187). Patients with dermatological diseases (e.g. atopic diathesis, prurigo nodularis) had the best profit from the treatment. Side-effects were mild (nausea, vertigo, and drowsiness) and only occurred in three patients.The high response rate in patients with therapy refractory pruritus suggests that the NKR1 antagonist aprepitant may indeed exhibit antipruritic effects and may present a novel, effective treatment strategy based on pathophysiology of chronic pruritus. The results are promising enough to warrant confirming the efficacy of NKR1 antagonists in a randomized, controlled clinical trial

Scratching increases epidermal neuronal branching and alters psychophysical testing responses in atopic dermatitis and brachioradial pruritus

BackgroundChronic scratching imposes a major stress on the skin and can lead to itch intensity worsening, and consequently, patients may enter an itch–scratch cycle. This repetitive mechanical stress can result in lichenification, worsening of epidermal barrier function, and enhanced cutaneous inflammation. Furthermore, a reduction of intraepidermal nerve fibers was previously described in lichenification.AimThe aim of this study was to investigate the influence of chronic scratching on the epidermal neuroanatomy and on sensory changes, in particular the prevalence of hyperknesis and alloknesis in patients after mechanical, chemical, and electrical stimuli.MethodsAnalyses were performed on pruritic lichenified (chronically scratched), pruritic non-lichenified (not chronically scratched), and non-pruritic non-lesional (unaffected) skin areas of patients with inflammatory pruritus, i.e., atopic dermatitis (n = 35), and neuropathic pruritus, i.e., brachioradial pruritus (n = 34) vs. healthy matched controls (n = 64). Our fine-grained spatial skin characterization enabled specifically studying the differential effects of chronic scratching in inflammatory and neuropathic itch.ResultsAnalysis of intraepidermal nerve fiber density showed rarefaction of fibers in all three skin areas of patients compared with healthy controls in both diagnoses. Even more, the two pruritic areas had significantly less nerve fibers than the unaffected skin, whereas electrically induced itch was massively increased. Epidermal branching of the remaining nerve fibers in lichenified/chronically scratched skin was increased, particularly in patients with brachioradial pruritus, which may contribute to the pronounced local neuronal sensitivity. Hyperknesis and alloknesis were found to increase independently of lichenification.ConclusionOur results indicate that chronic scratching may not affect intraepidermal nerve fiber density but leads to a stronger branching pattern of intraepidermal nerve fibers, which may contribute to local hypersensitivity. The increased sensitivity in the pruritic areas suggests mechanisms of peripheral sensitization, whereas the increased sensation of electrically and chemically induced itch in unaffected skin indicates central sensitization for itch