Diet-Induced Mouse Model of Atopic Dermatitis.

Atopic dermatitis (AD) is a common skin disease characterized by chronic inflammation and itchiness. Although skin barrier dysfunction and immune abnormalities are thought to contribute to the development of AD, the precise pathogenic mechanism remains to be elucidated. We have developed a unique, diet-induced AD mouse model based on the findings that deficiencies of certain polyunsaturated fatty acids and starches cause AD-like symptoms in hairless mice. Here, we present a protocol and tips for establishing an AD mouse model using a custom diet modified from a widely used standard diet (AIN-76A Rodent Diet). We also describe methods for evaluating skin barrier dysfunction and analyzing itch-related scratching behavior. This model can be used not only to investigate the complex pathogenic mechanism of human AD but also to study the puzzling relationship between nutrition and AD development.

The effects of omega-3 on the sleep quality of patients with uremic pruritus undergoing hemodialysis: a randomized crossover study.

OBJECTIVES: Information on sleep quality and its effective factors in the patients undergoing hemodialysis are important factors in future planning for improving sleep quality and ultimately the quality of life in these patients. The present study investigated the effect of omega-3 on the sleep quality of hemodialysis patients. METHODS: The 52 hemodialysis patients were randomized into two groups and underwent two different treatment modes (A and B). The first group was given omega-3 and cetirizine and the second group only received cetirizine for six weeks. After one week wash out, the study was followed by crossover treatment in both groups for six weeks. Sleep quality and pruritus severity were evaluated in patients before the intervention and at the end of each treatment period using the Pittsburgh Sleep Quality Index and the Yosipovitch Itch Questionnaire. The collected data was analyzed using repeated measures ANOVA and the Pearson correlation coefficient. RESULTS: The results of the study showed that majority of the patients (94.2%) had poor sleep quality (sleep score > 5 based on the questionnaire) and 5.8% of the patients had favorable sleep quality (sleep score < 5). Repeated measures ANOVA showed that sleep quality scores were different in two groups in phases 0, I and II (p <0.001). CONCLUSIONS: Sleep quality improved in both modes but more improvement was observed in mode A. Therefore, omega-3 fatty acids can be used as a suitable method for improving sleep quality in hemodialysis patients.

Speech difficulties and patient health communication mediating effects on worry and health-related quality of life in children, adolescents, and young adults with Neurofibromatosis Type 1.

The objective was to investigate the serial mediating effects of speech difficulties, patient health communication, and disease-specific worry in the relationship between neurofibromatosis (NF) symptoms (pain and skin symptoms) and total generic health-related quality of life (HRQOL) in children, adolescents, and young adults with NF Type 1 (NF1) from the patient perspective. The Speech, Communication, Worry, Pain, Skin Itch Bother, and Skin Sensations Scales from the Pediatric Quality of Life Inventory (PedsQL) NF1 Module and the PedsQL 4.0 Generic Core Scales were completed in a multi-site national study by 305 patients ages 5-25 years. A serial multiple mediator model analysis was conducted to test the hypothesized sequential mediating effects of speech difficulties, health communication, and worry as intervening variables in the association between NF1 symptoms and HRQOL. Symptoms predictive effects on total generic HRQOL were serially mediated by speech difficulties, patient health communication, and worry. In predictive analytics models utilizing hierarchical multiple regression analyses with age and gender demographic covariates, the pain, skin itch bother, and skin sensations multiple mediator models accounted for 61%, 59%, and 56% of the variance in generic HRQOL (p < .001), reflecting large effect sizes. Speech difficulties, patient health communication, and disease-specific worry explain in part the mechanism of symptoms predictive effects on total generic HRQOL in pediatric patients with NF1. Identifying NF1-specific predictors and serial mediators of total generic HRQOL in pediatric patients with NF1 from the patient perspective enables a patient-centered comprehensive care approach for children, adolescents, and young adults with NF1.

Nationwide Online Survey to Complement the Current Voluntary Reporting System for Adverse Events Associated with Dietary Supplements: Application to the Case of Skin Manifestations.

The current adverse event reporting system for dietary supplements lacks the ability to collect and analyze ongoing case reports in sufficient numbers to detect health issues. We conducted an online survey to collect data on skin manifestations due to supplement use in consumers and to identify the suspected products and ingredients. An online survey was conducted among 63,737 dietary supplement users in 2016. Those who self-reported experiences of skin anthema or itching caused by supplement use and recognized a causal relationship as almost certain (0.8%) were invited to provide further details of symptoms and products. Most of the users experienced mild symptoms with "itching and/or rash of body part." After the onset of skin manifestations, 69.3% ceased supplement use, while 26.6% continued supplement use, including those who reduced the amount or frequency of use. Respondents who visited the hospital in response to symptoms accounted for 26.0%, while 53.3% did not seek treatment. The products used were identified in 155 of 300 eligible respondents. Although those products were composed of multiple ingredients, the accumulated data suggested that cutaneous symptoms were related to the following constituents: "Peptides or animal by-products" (31.0%), "Herbal/Botanical" (23.2%) and "Fats and lipid" (13.5%). Conducting an online survey to elicit information directly from consumers identified components of supplements that are involved in skin manifestations that could lead to serious damage, and may fill a void in the current adverse event reporting system.

Short- and long-term effects of two emollients on itching and skin restoration in xerotic eczema.

Pruritus is associated with various skin diseases, dry skin, and with it an impaired skin barrier function. The study objective was to investigate short-term and long-term effects of two emollients on symptoms and skin barrier functions in xerotic eczema. Randomized, double-blind, study enrolling females/males, with bilateral itching. Two emollients, containing lactic acid and refined almond oil with/without polidocanol were administered on left versus right body sides. Itching severity, skin moisture, lipid content, and pH were assessed on Day 1, within 30-120 min after first administration, and on Days 7 and 14, and compared with baseline assessments. Severity of itching decreased 30 min after first administration of both emollients compared with baseline (p < .0001) and reached a maximum reduction of 63% (p < .0001) and 69% (p < .0001) on Day 14. Skin moisture and lipid content increased after first application, and further ameliorated within 14 days of treatment (p < .0001). Both emollients were tolerated well, and only a few adverse events were reported. This study confirmed the clinical efficacy of the two study emollients to substantially reduce itching already after first administration, and restore skin barrier integrity and thus should be considered as therapeutic approach for xerotic eczema.

Modulation of Itch by Localized Skin Warming and Cooling.

Skin thermal changes modulate itch sensitivity. However, the mechanisms of this modulation are still unclear. Using mouse models of acute and chronic itch, we investigated whether local innocuous thermal stimulation of the skin alters itch sensitivity and if blockade of thermosensitive transient receptor potential (TRP) channels can reduce these changes. Localized thermal changes were achieved by placing a thermal probe in contact with the back skin for 30 s. Warming the skin significantly increased serotonin-evoked scratching and spontaneous scratching in the ovalbumin model of atopic dermatitis but decreased histamine-evoked scratching. These changes were blocked by a TRPV4 antagonist. Cooling the skin significantly increased serotonin-evoked scratching but reduced histamine-evoked scratching. The increase in serotonin-evoked scratching, but not the reduction of histamine-evoked scratching, was blocked by TRPM8 antagonism. Chloroquine-evoked scratching was unaffected by either warming or cooling. Our data indicate that different itch signaling pathways are differentially modulated by skin thermal changes.

Chronic Pruritus in the Geriatric Population.

Chronic pruritus (>6 week's duration) in the geriatric population (≥65 years old), is an increasing health care problem. The pathophysiologic predisposing factors are abnormalities of the epidermal barrier, immune system, and nervous system. Causes can be dichotomized into histaminergic and nonhistaminergic pruritus. Topical treatments are generally safe. Systemic treatments are chosen depending on the condition, comorbid diseases, and drug interactions. Treatment options are limited. Progress has been made in identifying itch-selective mediators over the last decade. Numerous new medications are currently undergoing clinical trials and they are anticipated to enter the clinics in the near future.

Diagnosis and Management of Neuropathic Itch.

Neuropathic pruritus is a challenging condition that can be caused by injury or dysfunction in any part of the nervous system. A vast array of clinical pictures exist, including both localized and generalized pruritus, and their principal entities are described in this article. Diagnosis is often difficult and depends on patient history, imaging, and neurophysiologic studies. Other causes of chronic itch should be excluded. The management of neuropathic itch is demanding and the majority of interventions are not curative. The best treatment options include anticonvulsants, topical anesthetics, and capsaicin.

End-Stage Renal Disease Chronic Itch and Its Management.

End-stage renal disease chronic itch is a frequent symptom that bothers patients with advanced stages of chronic kidney disease. The pathogenesis of the chronic itch symptom is complex and not yet fully understood and includes many metabolic, immunologic, and neurogenic factors. A significant burden of the disease results in decreased quality of life with sleep impairment, depressive symptoms, and increased mortality of affected individuals. No treatment of choice is available; topical therapy (emollients), phototherapy (UV-B), and systemic therapy (antiepileptics, opioid agonists, and antagonists) provide significant relief in varying percentages of patients.

From Probiotic to Prebiotic Using Thermal Spring Water.

BACKGROUND: La Roche-Posay Thermal Spring Water (LRP-TSW) exhibits both probiotic and prebiotic properties enhancing the diversity of the skin microbiota. METHODS: A review was undertaken to explore the role of LRP-TSW as a topical probiotic and prebiotic therapy in improving the diversity of the skin microbiota and reducing dryness and pruritus in inflammatory skin diseases. RESULTS: The concentration of minerals and non-pathogenic microbes in LRP-TSW may explain its therapeutic benefit when used for inflammatory skin diseases. Clinical studies have shown that topical LRP-TSW treatment results in increases in Gram-negative bacteria with reduction of Gram-positive bacteria, and improvements in skin microbial diversity. At the same time skin condition in atopic dermatitis, psoriasis, and general dryness in otherwise healthy skin, has been shown to improve. CONCLUSIONS: Enhancement of skin microbiota diversity using topical LRP-TSW may offer a valuable option for the treatment and maintenance of inflammatory skin diseases. J Drugs Dermatol. 2018;17(6):657-662.

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A Systematic Review and Meta-analysis of Using Acupuncture and Acupressure for Uremic Pruritus.

INTRODUCTION: Uremic pruritus is characterized by an uncomfortable and unlimited sensation which leads to scratch, which strongly reduces the quality of life. Pruritus is a common symptom in patients with end-stage renal disease. Various clinical trial studies have examined the effects of acupuncture and acupressure on treatment of uremic pruritus. This systematic review meta-analysis aimed to evaluate the effectiveness based on published studies. MATERIALS AND METHODS: An electronic literature search was conducted to identify appropriate trial studies. The results for continuous outcomes were presented as weighted mean difference, with 95% confidence intervals. RESULTS: A total of 5 articles, including 6 trials, were enrolled in this systematic review. Only 3 of the six trial studies used a visual analogue scale score for assessing pruritus and acupressure for intervention regime, which were considered for meta-analysis. The combined results showed that acupuncture or acupressure was effective in treatment of uremic pruritus (pooled mean difference, -1.994; 95% confidence interval, -2.544 to -1.445). CONCLUSIONS: This study confirms that using acupuncture and acupressure is effective in treatment of uremic pruritus. However, further vigorous studies are needed to verify these findings.

Influence on clinical parameters of depressomassage (part I): The effects of depressomassage on color and transepidermal water loss rate in burn scars: A pilot comparative controlled study.

OBJECTIVE: Depressomassage is a non-invasive massage technique using a mechanical suction device that is used in the treatment of traumatic or burn scars. Since color and transepidermal water loss (TEWL) are respectively the most important physical and physiological characteristic of hypertrophic scar formation, we wanted to investigate the effects of depressomassage on the recovery of color and TEWL in burn scars compared to the traditional physiotherapy. METHODS: In this pilot comparative controlled study a total 43 burn patients were included and allocated into 2 groups. All patients received standard physical therapy, and the test group received additional depressomassage during 6 months. Color was assessed using the POSAS questionnaire (for color, vascularity and pigmentation) and the Minolta Chromameter. TEWL was measured using DermaLab. RESULTS: Patients of both groups were evaluated at baseline, after 1, 3 and 6 months and after 1year. The evidence for a difference in evolution of color and TEWL between both groups in our study was minimal. CONCLUSIONS: In practice, precise indications to begin depressomassage have to be kept in mind. Perhaps other scar abnormalities such as decreased elasticity, increased thickness, excessive pain or itching could be sufficient reasons to begin depressomassage and should be assessed.

Management of Menopausal Symptoms for Women Who Are at High Risk of Thrombosis.

For women at elevated risk of thrombosis, clinicians are challenged to relieve menopausal symptoms without increasing the risk of thrombosis. Oral menopausal hormone therapy increases the risk of venous thromboembolism by 2-fold to 3-fold. Observational studies suggest less thrombotic risk with transdermal therapies and with progesterone over synthetic progestogens (progestins), but the data are limited. Beneficial nonpharmacologic therapies include cognitive behavioral therapy and clinical hypnosis, whereas beneficial nonhormonal pharmacologic therapies include selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors. For treatment of the genitourinary syndrome of menopause, vaginal lubricants and moisturizers, low-dose vaginal estrogen, and intravaginal dehydroepiandrosterone are options.

Adjunctive Management of Itch in Atopic Dermatitis.

Itch, or pruritus, is a hallmark feature of atopic dermatitis (AD). The impact of AD-related pruritus can range from mildly distressing or distracting to completely disabling. Traditionally, management of itch in AD patients has focused on restoring the altered skin barrier with topical emollients and/or reducing inflammation. A growing emphasis has been placed on directly targeting the neural transmission pathways that mediate itch signaling. Off-label use of neuromodulatory agents has helped reduce this aggravating symptom in atopic patients. This article reviews the current literature on the use of neuromodulatory agents and nonpharmacologic alternative therapies used to treat AD-related pruritus.

Mediators of Chronic Pruritus in Atopic Dermatitis: Getting the Itch Out?

For centuries, itch was categorized as a submodality of pain. Recent research over the last decade has led to the realization that itch is in fact a separate and distinct, albeit closely related, sensation. Chronic itch is a common complaint and has numerous etiologies. Various receptors (TRPA1, TRPV1, PAR2, gastrin-releasing peptide receptor (GRPR), Mas-related G proteins), secreted molecules (histamine, nerve growth factor (NGF), substance P (SP), proteases), and cytokines/chemokines (thymic stromal lymphopoietin (TSLP), IL-2, IL-4, IL-13, and IL-31) are implicated as mediators of chronic pruritus. While much remains unknown regarding the mechanisms of chronic itch, this much is certain: there is no singular cause of itch. Rather, itch is caused by a complex interface between skin, keratinocytes, cutaneous nerve fibers, pruritogenic molecules, and the peripheral and central nervous systems. Atopic dermatitis is one of the most itchy skin dermatoses and affects millions worldwide. The sensation of atopic itch is mediated by the interplay between epidermal barrier dysfunction, upregulated immune cascades, and the activation of structures in the central nervous system. Clinicians are in possession of an arsenal of different treatment options ranging from moisturizers, topical immunomodulators, topical anesthetic ion channel inhibitors, systemic immunomodulators, as well as oral drugs capable of reducing neural hypersensitization. Emerging targeted therapies on the horizon, such as dupilumab, promise to usher in a new era of highly specific and efficacious treatments. Alternative medicine, stress reduction techniques, and patient education are also important treatment modalities. This review will focus on the mediators of chronic pruritus mainly associated with atopic dermatitis (atopic itch), as well as numerous different therapeutic options.

Pathogenesis and Management of Pruritus in PBC and PSC.

Pruritus is a preeminent symptom in patients with chronic cholestatic liver disorders such as primary biliary cirrhosis and primary sclerosing cholangitis. More than two-thirds of these patients experience itching during the course of their disease. This symptom is also frequently observed in patients with other causes of cholestasis such as cholangiocarcinoma, inherited forms of cholestasis and intrahepatic cholestasis of pregnancy, but may accompany almost any other liver disease. The pathogenesis of pruritus of cholestasis remains largely elusive. Increased concentrations of bile salts, histamine, serotonin, progesterone metabolites and endogenous opioids have been controversially discussed as potential pruritogens. However, for these molecules, neither a correlation with itch intensity nor a causative link could be established. The G protein-coupled receptor for bile salts, TGR5, has been shown to be expressed in dorsal root ganglia and give rise to itch in rodents, albeit upon stimuli with suprapathological concentrations of bile salts. The potent neuronal activator lysophosphatidic acid (LPA) and its forming enzyme, autotaxin (ATX), could be identified in the serum of patients with cholestatic pruritus. ATX activity correlated with itch severity and effectiveness of several anti-pruritic therapeutic interventions in cholestatic patients. Thus, the ATX-LPA-axis may represent a key element in the pathogenesis of this agonizing symptom. Treatment options for pruritus of cholestasis remain limited to a few evidence-based and several experimental medical and interventional therapies. The current guideline-based recommendations include the anion exchange resins colestyramine, the pregnane X receptor-agonist and enzyme inducer rifampicin, the µ-opioid antagonist naltrexone, and the selective serotonin reuptake inhibitors sertraline. Still, a considerable part of patients is unresponsive to these drugs and requires experimental approaches including phototherapy, plasmapheresis, albumin dialysis or nasobiliary drainage. This review outlines the current knowledge on pathogenesis of cholestatic pruritus and summarizes evidence-based and experimental therapeutic interventions for cholestatic patients with itch.

Inducing Expectations for Health: Effects of Verbal Suggestion and Imagery on Pain, Itch, and Fatigue as Indicators of Physical Sensitivity.

UNLABELLED: Research into placebo effects has convincingly shown that inducing positive outcome expectations can reduce pain and other physical sensations. However, the comparative effects of different expectation inductions, such as verbal suggestion or mental imagery, and their generic effects on physical sensitivity, to different sensations such as pain, itch, and fatigue, are still largely unknown. In the current study, we assessed the individual and combined effects of verbal suggestion and imagery on pain, itch, and fatigue as indicators of physical sensitivity in a randomized study design. Healthy participants (n = 116) were given an inert (placebo) capsule that was said to be effective for reducing physical sensitivity in either the majority (positive verbal suggestion) or the minority (control verbal suggestion) of users. Subsequently, they imagined either their best possible health (positive imagery) or a typical day (control imagery). Sensitivity to pain, itch, and fatigue was tested using a cold pressor test, histamine iontophoresis, and a bicycle test, respectively. Heart rate and skin conductance were recorded continuously. Results showed that positive verbal suggestion and imagery successfully induced positive expectations, but they did not affect physical sensitivity, as indicated by sensitivity to pain, itch, or fatigue, or concurrent physiological responses. These results could indicate that the specificity and concreteness of expectation inductions might be important for their applicability in the treatment of physical symptoms. TRIAL REGISTRATION: Nederlands Trial Register NTR3641.

Pruritus in Kidney Disease.

Pruritus is a common and distressing symptom in patients with chronic kidney disease. The most recent epidemiologic data have suggested that approximately 40% of patients with end-stage renal disease experience moderate to severe pruritus and that uremic pruritus (UP) has a major clinical impact, being associated strongly with poor quality of life, impaired sleep, depression, and increased mortality. The pathogenesis of UP remains largely unclear, although several theories on etiologic or contributing factors have been proposed including increased systemic inflammation; abnormal serum parathyroid hormone, calcium, and phosphorus levels; an imbalance in opiate receptors; and a neuropathic process. UP can present somewhat variably, although it tends to affect large, discontinuous, but symmetric, areas of skin and to be most symptomatic at night. A variety of alternative systemic or dermatologic conditions should be considered, especially in patients with asymmetric pruritus or other atypical features. Treatment initially should focus on aggressive skin hydration, patient education on minimizing scratching, and optimization of the aspects of chronic kidney disease care that are most relevant to pruritus, including dialysis adequacy and serum parathyroid hormone, calcium, and phosphorus management. Data for therapy specifically for UP remain limited, although topical therapies, gabapentin, type B ultraviolet light phototherapy, acupuncture, and opioid-receptor modulators all may play a role.

Oral supplementation with fish oil reduces dryness and pruritus in the acetone-induced dry skin rat model.

BACKGROUND: Pruritus and discomfort are often present in patients with xerosis and atopic dermatitis. Several studies suggest an important role of diet in skin pathophysiology. OBJECTIVE: This study evaluated the effect of dietary fatty acids in the skin physiology via an itch-related animal model with and without supplementation with fish oil (FO), a source of polyunsaturated fatty acids (PUFA), especially omega 3 (n-3). METHODS: Male Wistar rats were divided into two groups-non-supplemented (control) and supplemented with FO (3g/kg/day) by gavage for 90 days. Every 30 days, scratching and skin parameters (transepidermal water loss (TEWL), hydration, and local blood flow) were evaluated before and after dorsal skin exposure to acetone to induce the itch-related dry skin. At the end of the study, animals were sacrificed, and skin samples collected for fatty acids composition analysis by GC-FID. RESULTS: FO supplementation reduced the TEWL and increased the skin hydration, with significant changes from day 60 on, while skin microcirculation registered no changes. It also alleviated the acetone induced skin barrier alteration, revealed by a faster resolution of TEWL and hydration, and elimination of itch-related scratching induced by dry skin. These changes were associated with the shift in the skin fatty acids incorporation pattern (richer in n-3 with n-6/n-3<5) resulting from the FO supplementation. CONCLUSION: Skin barrier dynamics seem to be influenced by FO n-3 PUFA, with suppressive effects on the scratching behaviour induced by dry skin. Hence, long-term supplementation with n-3 PUFA rich nutrients might reinforce and restore cutaneous integrity and function.