Plasma Steroids and Endocannabinoids Used as Biomarkers to Assess the Pruritus Severity of Patients With Prurigo Nodularis. / [Artículo traducido] Esteroides y endocannabinoides plasmáticos utilizados como biomarcadores para evaluar la gravedad del prurito de los pacientes con prúrigo nodular.

BACKGROUND: Prurigo nodularis (PN) as an extremely pruritic and hyperplastic chronic dermatosis induces psychologically and physiologically stressful responses. PN-induced responses in the hypothalamic-pituitary-adrenal, hypothalamic-pituitary-gonadal axes and endocannabinoid system are abnormal. Extant studies on the PN's pathogenesis mostly focused on the PN's psychological responses. To date, the PN's physiological responses remain not been fully uncovered yet. OBJECTIVES: To investigate the PN-induced physiological responses via the levels of 5steroids and 2endocannabinoids combined with their ratios in plasma and examine the association between the psychological and physiological responses. MATERIALS AND METHODS: Thirty-six patients with PN, 36 age- and gender-matched healthy controls were recruited. The PN's psychological symptoms including pruritus severity, pain and life quality were measured with the visual analogue scale, the prurigo score index, numerical rating scale, verbal rating scale and dermatology life quality index. Their concentrations of steroids and endocannabinoids were determined with liquid chromatography-tandem mass spectrometry. RESULTS: Compared to controls, the PN patients showed lower plasma levels in cortisol, cortisone, N-arachidonoyl-ethanolamine, and the ratio of DHEA to 1-arachydonoyl glycerol (1-AG), which negatively moderately and over correlated with PN's symptoms, especially with the pruritus severity. Additionally, the PN patients exhibited higher levels in the ratios of testosterone and 1-AG to cortisol, which positively moderately and over correlated with pruritus severity. Thus, the 7biomarkers would be sensitive and reliable biomarkers for assessing the pruritus severity of PN because they met the screening criteria that the biomarkers show intergroup differences and showed moderate or over correlation with the pruritus severity of PN. CONCLUSIONS: To the best of our knowledge, this is the first study exploring PN-induced physiological responses. The findigs suggest that alterations in these 3endocrine systems may lead to new insights to psychological mechanisms and responses to PN.

Plasma Steroids and Endocannabinoids Used as Biomarkers to Assess the Pruritus Severity of Patients With Prurigo Nodularis.

BACKGROUND: Prurigo nodularis (PN) as an extremely pruritic and hyperplastic chronic dermatosis induces psychologically and physiologically stressful responses. PN-induced responses in the hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonadal (HPG) axes and endocannabinoid system (ECS) are abnormal. Extant studies on the PN's pathogenesis mostly focused on the PN's psychological responses. To date, the PN's physiological responses remain not been fully uncovered yet. OBJECTIVES: To investigate the PN-induced physiological responses via the levels of five steroids and two endocannabinoids combined with their ratios in plasma and examine the association between the psychological and physiological responses. MATERIALS AND METHODS: Thirty-six patients with PN, 36 age- and gender-matched healthy controls were recruited. The PN's psychological symptoms including pruritus severity, pain and life quality were measured with the visual analog scale, the prurigo score index, numerical rating scale, verbal rating scale and dermatology life quality index. Their concentrations of steroids and endocannabinoids were determined with liquid chromatography-tandem mass spectrometry. RESULTS: Compared to controls, the PN patients showed lower plasma levels in cortisol, cortisone, N-arachidonoyl-ethanolamine (AEA), and the ratio of DHEA to 1-arachydonoyl glycerol (1-AG), which negatively moderately and over correlated with PN's symptoms, especially with the pruritus severity. Additionally, the PN patients exhibited higher levels in the ratios of testosterone and 1-AG to cortisol, which positively moderately and over correlated with pruritus severity. Thus, the seven biomarkers would be sensitive and reliable biomarkers for assessing the pruritus severity of PN because they met the screening criteria that the biomarkers show intergroup differences and showed moderate or over correlation with the pruritus severity of PN. CONCLUSIONS: To the best of our knowledge, this is the first study exploring PN-induced physiological responses. The findings suggest that alterations in these three endocrine systems may lead to new insights to psychological mechanisms and responses to prurigo nodularis.

Clinical characteristics and disease burden in prurigo nodularis.

BACKGROUND: Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intense pruritus, but information on patient experience and impact on quality of life (QoL) remains understudied. AIM: To characterize disease characteristics and QoL in a global sample of patients with PN. METHODS: An anonymous survey was distributed via patient support groups for PN. RESULTS: In total, 231 members responded to the survey. The majority of respondents reported itch localized both to nodules and to intervening skin (67.0%). Associated symptoms included prickling, pain, stinging and burning. The extensor lower legs (69% right, 67.3% left) and flexor forearms (66.1% right, 62% left) were the most common sites of itch. Participants reported frequent healthcare utilization, with 36.3% visiting a doctor ≥ 10 times in the past year. Physician-diagnosed anxiety (45.4%), depression (16.4%) and the atopic triad (18.7%) were commonly reported. Patients with PN had mean scores of 16.4, 11.6 and 16.8 on the Dermatology Life Quality Index, Pittsburgh Sleep Quality Index and 5-Dimensions Itch, respectively. CONCLUSIONS: Severe pruritus with accompanying pain, stinging and burning is characteristic of PN, with the majority of patients experiencing itch in both nodular and interlesional skin. Patients further report decreased QoL scores and impaired sleep. Patient experiences should guide future management of PN.

The impact of prurigo nodularis on quality of life: a systematic review and meta-analysis.

Prurigo nodularis (PN) is a chronic, pruritic, debilitating disease. Previous studies found that chronic pruritus in general negatively affects patients' quality of life (QoL). However, results about the impact of PN on QoL are conflicting. Our objective was to assess the QoL burden of PN. A systematic review was conducted of all published studies that assessed QoL measures in PN. OVID MEDLINE, EMBASE, SCOPUS, and Web of Science were searched. Pooled meta-analysis (means) was performed using random-effects weighting. Overall, 13 studies met inclusion criteria. All studies identified QoL reductions in patients suffering from PN compared to control groups. The most common QoL instrument used was the Dermatology Life Quality Index [n = 9 studies; pooled mean (95% confidence interval): 13.8 (10.6-16.9), denoting a very large effect]. In particular, PN was associated with substantial impact on multiple domains of QoL. No publication bias was detected. In conclusion, QoL is negatively impacted in PN. Future studies are necessary to determine the best instruments of measuring QoL in PN patients, better understand this association, and assess the impact in males and females separately. PROSPERO CRD42019136193.

Prurigo nodularis: Epidemiology and clinical features.

Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by intensely pruritic, hyperkeratotic nodules that favor the extensor surfaces of the extremities and the trunk. In addition to its significant impact on quality of life, many patients with PN are recalcitrant to therapy because there are currently no therapies approved by the US Food and Drug Administration. In the first article of this 2-part continuing medical education series, we describe the broader epidemiology, patient demographics, physical examination findings, and symptoms to aid in the timely recognition and diagnosis of PN. Furthermore, we quantify the burden of comorbidities in PN by discussing the broad spectrum of systemic diseases and mental health conditions that have been associated with this condition. The second article of this 2-part series focuses on the pathogenesis of PN and provides detailed algorithms for comprehensive work-up and management.

Prurigo nodularis: Pathogenesis and management.

Prurigo nodularis is a chronic skin condition characterized by severely pruritic nodules that cause a profound negative impact on quality of life. The second article in this 2-part continuing medical education series focuses on reviewing the pathogenesis of prurigo nodularis and exploring management algorithms for this condition. In addition, we discuss some emerging and novel therapies for treating prurigo nodularis. The first article in this 2-part series describes the broader epidemiology, patient demographics, physical examination findings, and symptoms to aid in the timely recognition and diagnosis of prurigo nodularis.

Association of prurigo nodularis and lichen simplex chronicus with hospitalization for mental health disorders in US adults.

Prurigo nodularis (PN) and lichen simplex chronicus (LSC) are debilitating chronic pruritic diseases that can lead to and be exacerbated by psychosocial distress. However, little is known about the mental health (MH) comorbidities of PN/LSC. We sought to evaluate the likelihood and cost-burden of MH comorbidities and emergencies associated with PN/LSC. Data were examined from the 2002-2012 Nationwide Inpatient Sample, including a representative ~ 20% sample of US hospitalizations (n = 87,053,155 admissions). Inpatients with vs. without PN/LSC had higher odds of MH disorders overall (39.4% vs. 20.0%; adjusted odds ratio [95% confidence interval, CI] 2.26 [2.13-2.41]) and in all 15 individual MH disorders examined. Inpatients with vs. without PN/LSC were more likely to be admitted with a primary diagnosis of a MH disorder (4.5% vs. 2.2%; 2.16 [1.91-2.45]), particularly developmental, psychotic, and mood disorders, history of MH disorders or substance abuse, and cognitive disorders. PN/LSC were associated with prolonged inpatient length of stay, and an excess $0.69 million in inpatient costs of care indirectly related to hospitalization for MH disorders. In conclusion, inpatients with PN/LSC had increased likelihood of comorbid MH disorders and emergencies requiring hospitalization. Optimized approaches are needed for screening and managing MH comorbidities in PN/LSC.

The self-assessed psychological comorbidities of prurigo in European patients: a multicentre study in 13 countries.

BACKGROUND: Prurigo is defined by the presence of chronic pruritus and multiple localized or generalized pruriginous lesions. OBJECTIVE: The aim of this study was to assess the psychological burden of prurigo in patients of European countries. METHODS: In this multicentre European study, 3635 general dermatology outpatients and 1359 controls were included. Socio-demographic data and answers to questionnaires (regarding quality of life, general health, anxiety and depression and suicidal ideation) were collected. RESULTS: There were 27 patients with prurigo; of these, 63% were men, and the mean age was 58.6 years. Among patients with prurigo, 10 of 27 (37%) suffered from anxiety and 8 of 27 (29%) from depression. Suicidal ideation was reported in 5 of 27 (19%) patients, and for four of these five patients, suicidal ideation was related to their skin disease. These frequencies were higher in the 10 commonest dermatological diseases (including psoriasis, atopic dermatitis and leg ulcers). The impact on quality of life was severe, with a mean Dermatologic Life Quality Index (DLQI) of 12.4, with an extreme impact on quality of life for 23% of patients and a very large impact for 27% of patients. CONCLUSION: The psychological comorbidities of prurigo are common, greater than those of other skin diseases, and their impact on quality of life is significant. Thus, it is important to study this condition and to find new treatments.

Serotonin and interleukin-6: Association with pruritus severity, sleep quality and depression severity in Prurigo Nodularis.

Prurigo Nodularis (PN) is a chronic skin condition of unknown etiology. It is said to be associated with psychological factors. However, studies to identify the same are few. Hence, we undertook to assess the association between quality of sleep, depression, pruritus severity in cases of PN and to assess association of serum serotonin, interleukin (IL)-6 with sleep, depression and pruritus severity. This cross-sectional study involves 39 patients with PN and 39 age and gender matched healthy controls. Subjective quality of sleep, depressive symptom severity and pruritus severity were collected through clinician based interview. Serum serotonin and serum IL-6 were estimated by ELISA. Spearman correlation was used to assess the strength of association between biochemical parameters and clinical parameters. Cases had significantly higher percentage of depression, a higher score of depression severity, higher serum IL-6 level and lower serum serotonin levels. Serum serotonin and serum IL-6 showed significant correlation with the severity of pruritus (r=-0.66, p<0.01 and r=0.60, p<0.01). However, both these parameters showed a significantly negative correlation between them (r=-0.92, p<0.01). Though cause and effect cannot be established in this type of study, there is a disturbance of the inflammatory-neuroendocrine axis (interleukins-serotonin). PN is characterized by higher IL-6 and lower serotonin and greater depression severity than healthy controls. Findings of this study may have an influence on the treatment of PN.

Prurigo nodularis: Picking the right treatment.

Most patients with localized nodules should receive topical treatment first. But disappointing results or specific findings described here could necessitate additional or alternative options.

[Psychosomatic aspects of prurigo nodularis]. / Psychosomatische Aspekte der Prurigo nodularis.

BACKGROUND/OBJECTIVES: This article gives an overview of the theoretical background and the empirical research concerning psychosomatic aspects of prurigo nodularis (PN). MATERIALS AND METHODS: Literature research in PubMed with the search terms "prurigo nodularis", "nodular prurigo", "psych*"; clinical experience and research of the authors. RESULTS: Although reviews on PN frequently mention psychosomatic aspects, there is little empirical research concerning the subject. Psychosomatic aspects of PN may play a role in (1) the etiology of the chronic pruritus; (2) scratching, which leads to the typical nodules of PN; (3) the consequences of the chronic pruritus, the scratching and the skin lesions; (4) comorbidity. There is evidence for higher psychic comorbidity and higher psychopathology (anxiety, depression) in PN patients than in healthy controls, but PN patients were comparable to patients with other pruritic dermatoses. DISCUSSION: Increased levels of psychopathological problems and comorbidities also have been found in other dermatoses; they are not specific for PN. Because all of the research on this topic is cross-sectional, we cannot be sure whether these aspects are etiological factors or consequences of PN or independent comorbidities. Nevertheless, psychosomatic aspects should be considered in diagnosis and treatment of PN patients.

Psychological factors involved in prurigo nodularis: A pilot study.

Emotional stresses and psychological disorders seem to be concurrent factors in some cases of prurigo nodularis (PN), a chronic skin condition with a difficult therapeutic approach. In order to improve the therapeutic strategies, we performed a psychometric study on 20 patients affected by generalized and histological proven PN. Specific questionnaires were employed to examine the hypotheses (General Health Questionnaire, State Trait Anxiety Inventory - form Y, Beck Depression Inventory-II, and Eysenck Personality Questionnaire). The results show that symptoms of anxiety and depression associated with PN are more severe than in the control group and that some specific traits of personality are more frequently represented in such subjects. The results of our study represent a first attempt to analyze the psychological problems and the personality dimensions which seem to characterize PN patients. Such evidence supports the importance of a psychological approach in the clinical management of PN, which should always include psychological assessment and treatment together with the other therapeutic options.

Prurigo nodularis and lichen simplex chronicus.

Emotional tensions in predisposed subjects may play a key role in inducing a pruritic sensation, leading to a scratching that, becoming a self-perpetuating pathomechanism, may represent the main feature of two distinct cutaneous clinical entities: prurigo nodularis and lichen simplex chronicus. Psychogenic factors play a relevant role in both conditions, and they are often associated with depression and dissociative experiences. Hence, the importance of the evaluation of these patients from the point of view of psychodermatology, which may analyze the relationship between skin disease and psychological factors. Patients with real or perceived imperfections in particular areas of the body (face, scalp, hands, and genital area) are more prone to psychologic distress, whereas cutaneous diseases may lead to experience a heightened level of distress. As psychosomatic factors have been estimated to be present in at least one-third of dermatologic patients, effective management of skin conditions involves consideration of the associated emotional factors.

Psychological factors in prurigo nodularis in comparison with psoriasis vulgaris: results of a case-control study.

BACKGROUND: It has been suggested that psychological factors such as repressing anger and altruistic interpersonal behaviour may play a role in the aetiology of chronic itching in prurigo nodularis (PN). Whether these issues are specific for PN or are also common in other chronic skin diseases, e.g. psoriasis, has not been investigated until now. OBJECTIVES: To investigate psychosomatic problem areas and psychiatric comorbidity in patients with PN in comparison with patients with psoriasis. METHODS: Ninety-four patients with PN and 91 patients with psoriasis were administered the Hospital Anxiety and Depression Scale, Toronto Alexithymia Scale, State-Trait Anger Expression Inventory, Inventory of Interpersonal Problems, Screening for Somatoform Disorders and the Whiteley Index for hypochondriasis. RESULTS: After Bonferroni post hoc adjustment, the metrical scales demonstrated no significant differences between patients with PN and those with psoriasis. There was only a tendency to less 'anger-out' and to less autocratic/dominant and more insecure/submissive behaviour in the patients with PN. Patients with PN were, in general, comparable with those with psoriasis with regard to alexithymia, somatization symptoms, hypochondriasis, anxiety and depression, with 18% cases of anxiety and 22% cases of depression. CONCLUSIONS: The hypotheses formulated in the literature on the specific aetiology of PN could not be proven for the majority of patients with PN in our study. Concerning their psychopathology, patients with PN were comparable with those with psoriasis. Therefore the clinical management of PN should include psychosomatic assessment.

[Changeability of respiratory tract and skin symptoms in patients with asthma-prurigo syndrome under the influence of emotional and environmental factors]. / Zmiennosc nasilenia objawów ze strony dróg oddechowych i skóry u chorych z zespolem asthma-prurigo pod wplywem czynników emocjonalnych i srodowiskowych.

In a group of 228 patients suffering from asthma-prurigo syndrome the influence of emotional state, permanent residence and season time on dynamic of the clinical symptoms were studied. The evaluation of emotional state in 80 adult patients was carried-out by means of Eysenck Personality Inventory. The emotional state had less negative influence on the exacerbation of the symptoms upon children then in adults (especially on their skin symptoms). It was confirmed that the patients with high level of neurotic symptoms revealed easier the exacerbation of asthma and skin disorders under the influence of emotional stress. The climatic treatment on the sea-side was more efficient for them than any mountain climatic cure, especially in the treatment of airways symptoms. Similarly, the summer season brought the relief of their symptoms from both the respiratory and skin symptoms.

Does psychological intervention help chronic skin conditions?

The objective of the study was to assess the impact of psychological/psychiatric assessment in patients with chronic or intractable dermatological conditions. A diagnostic interview was undertaken in order to pin-point any temporal connection between an adverse life-event and the first appearance of the skin disorder. Following this, the dermatologist's assessment of subsequent changes in the skin disorder were noted. The three main dermatological diagnoses were atopic eczema (10), prurigo (10), and psoriasis (nine). Follow-up was for up to 5 years. A favourable response was noted in 40 out of the 64 patients who participated in the study; this was usually evident within a few weeks and maintained thereafter. Remission was achieved in 12, while 28 showed some improvement. We conclude that this liaison between dermatology and psychiatry proved a valuable adjunct to normal dermatological treatment and was followed by improvement in the majority of patients.

[Hyde's nodular prurigo--preference for creases of the skin]. / Prurigo nodularis Hyde--Bevorzugung der Hautspaltlinien.

The arrangement of papules in prurigo nodularis Hyde along the cleavage lines of the skin, but not Blaschko's lines, supports the classification of prurigo nodularis Hyde as a traumatic chronic papulosis with cutaneous neural hyperplasia of xerodermal skin.