Pruritic Dermatoses Research Articles

Inhibition of thymic stromal lymphopoietin production to improve pruritus and quality of life in infants and children with atopic dermatitis

BackgroundAtopic dermatitis (AD) is an inflammatory pruritic chronic dermatosis involving the alarmin thymic stromal lymphopoietin (TSLP), which is directly implicated in AD pruritus.AimsTo evaluate the efficacy of Tambourissa trichophylla leaf extract (TTLE) titrated in polyphenols and 18β‐glycyrrhetinic acid (GA) in vitro and in vivo for AD pruritus.Patients/MethodsInitially, in vitro assessment of TSLP production in keratinocytes was undertaken. In normal human keratinocytes in vitro, TSLP was induced by polyinosinic:polycytidylic acid (Poly:IC), tumor necrosis factor (TNF)‐α, and interleukin (IL)‐4 and then quantified by ELISA in supernatants. Some cells were pretreated with TTLE and/or GA. Thereafter, an in vivo clinical study was performed including 48 infants and children with mild to severe AD flare‐ups, some of which were treated with topical corticosteroids. A topical spray containing TTLE and GA was applied. After 21 days of topical spray application, pruritus, sleeplessness, the SCORing Atopic Dermatitis (SCORAD) index, the Infant's Dermatitis Quality of Life index (IDQOL), and the Dermatitis Family Impact Questionnaire (DFIQ) were assessed.ResultsThymic stromal lymphopoietin secretion was inhibited significantly in an AD environment by TTLE and GA by up to 57.2% and 73.3%, respectively. The use of the topical spray induced a significant reduction in pruritus and sleeplessness scores, as well as the SCORAD, IDQOL, and DFIQ indexes in the total group. Similar results were observed in patient subgroups with or without topical corticosteroid treatment.ConclusionsA topical spray containing TTLE and GA, which inhibit TSLP secretion, efficiently decreases AD pruritus and improves the quality of life of AD patients.

Self-reported generalised pruritus among community-dwelling older adults in Malaysia

BackgroundThe ageing skin is more susceptible to pruritic dermatoses, which are associated with adverse psychosocial effects and reduced quality of life among older adults. This cross-sectional study aimed to identify the burden of pruritus and factors associated with its presence and severity among older adults recruited to the Malaysian Elders Longitudinal Research study.MethodsSeven hundred seventy individuals aged 55 years (lower age limit) and above were interviewed as to whether they experienced pruritus during the preceding week and the locations involved if present. The association between generalised pruritus, sleep quality, and major systemic risk factors were explored.Results5.97% of respondents reported generalised pruritus. Generalised pruritus was associated with poorer sleep quality, with Pittsburgh Sleep Quality Index score above 6. Mean haemoglobin level was lower in subjects with generalised pruritus (13.14 g/dL) but there was no significant difference in the frequency of generalised pruritus and severe generalized pruritus between subjects with clinically defined anaemia. Also, there were no significant associations between other major systemic risk factors and generalised pruritus in this population-based study. There was no association between generalised pruritus with depression, anxiety or stress.ConclusionThe negative effect of pruritus on sleep quality suggests a possible deleterious effect of pruritus on health and quality of life. Further prospective research on the longer-term effects of pruritus on health status is now warranted.(222 words)

Keratin 17 is induced in prurigo nodularis lesions

AbstractPrurigo nodularis (PN) is a highly pruritic chronic inflammatory dermatosis with unknown pathogenesis. It is characterized by the existence of many hyperkeratotic, erosive papules and nodules, and the development of lesions may be associated with hyperproliferation and aberrant differentiation of keratinocytes. Keratin 17 (K17) is overexpressed selectively in human proliferative skin diseases, promoting keratinocyte proliferation not found in normal epidermis. In this study, we investigated the mRNA levels and protein levels of K17 in lesional and perilesional skin using quantitative real-time polymerase chain reaction and western blot. We demonstrate that K17 is induced in lesional and perilesional skin in PN. The mRNA expression level of K17 was upregulated in PN lesions (P < 0.01), with multifold changes in the PN lesion (normalized to glyceraldehyde-3-phosphate dehydrogenase as the housekeeping gene) showing a median positive correlation with PRUNOSI (P < 0.05). The protein level of K17 was also markedly increased in PN lesions (P < 0.01). In conclusion, K17 is highly induced in PN lesions, which may contribute to the proliferation of keratinocytes and the pathogenesis of PN.

456 Sleep disturbances in chronic pruritic dermatoses are associated with increased C-reactive protein levels

Pruritus is a common symptom that can significantly reduce quality of life often through sleep disruption. We sought to investigate the features of disturbed sleep in patients with chronic pruritic dermatoses and test the hypothesis that increased systemic inflammation may serve as a biomarker for impaired sleep in these patients. We conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey data. Odds ratios (OR), 95% confidence intervals (95%CI), and p-values using logistic regression were calculated weighted to the US Census data. Model 1 was adjusted for demographic factors (sex, age, race, education, marital status, income) while model 2 was adjusted for medical comorbidities (age, sex, allergy history, heart disease, body mass index). Chronic pruritic dermatoses were associated with waking up during the night (Model 1: OR=1.646, 95%CI [1.031-2.627], p=0.038; Model 2: OR=1.329, 95%CI [0.888-1.989], p=0.031), waking up too early in the morning (Model 1: OR=1.669, 95%CI [1.118-2.493], p=0.016 ; Model 2: OR=1.582, 95%CI [1.008-2.481], p=0.046), feeling overly sleepy during the day (Model 1: OR=1.786, 95%CI [1.144-2.789], p=0.014; Model 2: OR=1.664 , 95%CI [1.073-2.581], p=0.026), and not getting enough sleep (Model 1: OR=1.603 , 95%CI [1.049-2.450], p=0.032; Model 2: OR=1.598, 95%CI [1.064-2.399], p=0.027). Mean C-reactive protein (CRP) levels were 52.8% higher among pruritic dermatoses patients reporting trouble sleeping compared to those who did not (0.663 vs 0.434 mg/dL; p=0.034). Pruritic dermatoses were also positively correlated with CRP levels with a β coefficient of 0.142 (p=0.025). In addition to confirming sleep disturbances with pruritic dermatoses, we found that sleep disturbances are more likely to present with elevated CRP levels. Thus, clinicians should consider the potential risk for sleep-related and cardiac comorbidities in patients diagnosed with itchy skin conditions.

841 Machine learning (ML) predictive algorithm for childhood-onset chronic pruritic dermatoses (CPD) identifies acrylamide and glycidamide as itch modulators

841 Machine learning (ML) predictive algorithm for childhood-onset chronic pruritic dermatoses (CPD) identifies acrylamide and glycidamide as itch modulators

419 Clinical characteristics and quality of life burden in aquagenic pruritus: A global questionnaire-based study

Aquagenic pruritus (AP) is a rare pruritic dermatosis characterized by intense itching following water exposure and often results in patients avoiding water contact. Limited epidemiologic studies describe the characteristics of AP and its impact on quality of life. Our objective was to characterize the demographics, itch, and quality of life of AP patients using a descriptive cross-sectional study design. An anonymous, online Qualtrics survey was developed and delivered to 1,829 patients via a Facebook AP support group in July 2019. The survey assessed symptoms associated with AP, but also utilized established quality of life measures including the Dermatology Life Quality Index (DLQI), the 5-D pruritus scale and the Pittsburgh Sleep Quality Index (PSQI). A total of 106 respondents from 16 countries completed the survey. The mean (SD) age of respondents was 41.4 (14.2) years with the majority being female (79.3%), and Caucasian (82.1%); 45.3% of respondents were Fitzpatrick skin type 3 and 31.1% were type 2. Itch was symmetrically distributed with the greatest prevalence reported on proximal ventral surfaces, including the thighs (90%, n = 99) and upper arms (80%, n=90). The top five triggers associated with itch onset included bathing, sweating, humidity, rain, and friction over the skin. Prickling was the most common sensation felt along with itch (n=80, 75.5%). AP patients had a mean (SD) DLQI of 11.1 (7.0), 5D pruritus score of 13.9 (2.8) and a PSQI of 8.4 (3.6). Compared to mean DLQI scores of psoriasis patients, the mean DLQI score in this study suggests that AP patients have a significantly decreased quality of life. With a better understanding of AP itch distribution, severity, and quality of life, physicians can provide tailored care for this subset of itch patients.

Pemphigoid gestationis – A rare case report

A number of physiologic cutaneous changes occurs during pregnancy due to immunologic, hormonal or metabolic factors. Pathologic skin lesions are rare but its important to distinguish due to potentially detrimental effects on both mother & fetus. Pemphigoid gestationis is a rare pruritic autoimmune dermatosis associated with several adverse fetal outcomes. 30yrs old primigravida at 22weeks gestation presented to us with an intensely pruritic vesicobullous lesion which was further diagnosed as pemphigoid gestationis. Hence patient was started on Prednisone & Azathioprine, then gradually tapered to appropriate maintainance dose. Patient had preterm rupture of membranes and delivered a healthy baby vaginally. Proper management of this dermatological condition requires a suitable drug therapy, close monitoring and multi disciplinary team approach which is essential to reduce maternal and neonatal morbidity and to achieve favourable obstetric outcome.

720-P: Prurigo Pigmentosa: An Acute Complication of Ketogenic Diet

A 22-year old female with type 1 diabetes (T1DM) presented with generalized rash. She was diagnosed at the age of 9 years and is treated with insulin pump and CGMS (continues glucose monitoring sensors), her recent HbA1c was 7.4%. Four weeks prior to her rash presentation she started a low carbohydrate diet (50 gr of carbs per day) in order to improve her glycemic control. Pruritic erythematous papules, papulovesicular, and vesicles appeared on her axillary region, upper back and groins. Lesions were associated with severe pruritus and negatively affected her quality of life. Various therapies were initiated by dermatologist as: antifungal agent, Itraconazole, and Betamethasone Esters, without any improvement. Her serum beta-hydroxybutyrate levels were between 1.1-1.2 mmol/l. Prurigo pigmentosa, a rare pruritic inflammatory dermatosis secondary to her high ketones levels was diagnosed. Her condition resolved after she increased her carbohydrate intake to 75 gr per day. Beta-hydroxybutyrate level decreased concomitantly to 0.1-0.2 mmol/l. When carbohydrate restriction was rechallenged, she again entered ketosis, followed by recurrence of the pruritic lesions. Carbohydrate intake was increased and subsequently all lesions resolved with remaining reticular hyperpigmentation. During the last few years low carb diets have gained popularity among patients with T1DM. This case illustrates the rare side effect of high ketones body levels. Health care providers should be familiar with this side effect. Disclosure N. levran: None. K. Mazor-Aronovitch: None. S. Grenberger: None. N. Levek: None. B. Sher: None. E. Mauda: None. Z. Landau: None. E. Monsonego-Ornan: None. O. Pinhas-Hamiel: None.

Treatment and Burden of Disease in a Cohort of Patients with Prurigo Nodularis: A Survey-based Study

Prurigo nodularis is a pruritic dermatosis with poor treatment options. To describe treatment patterns, comorbidities, pruritus, and quality of life a survey was administered to 92 patients with prurigo nodularis. A total of 52 patients completed the survey. The most frequently used treatments were topical corticosteroids, which were prescribed to 49/52 patients, with positive effect in 13/49. A total of 46/52 patients were treated with ultraviolet B, and 9/46 reported a positive effect. A positive effect was reported for topical corticosteroids under occlusion in 21/40, for zinc dressing treatment in 17/37, for steroid injection in 9/14, for methotrexate in 5/16, and for thalidomide in 4/12 of treated patients. Thirty-six patients reported a Pittsburgh Sleep Quality Index >5, indicating poor sleep. Patients with prurigo nodularis are severely bothered by pruritus negatively affecting quality of life. Various treatments are prescribed; most frequently topical corticosteroids and ultraviolet B. Surprisingly, patients reported topical corticosteroids under occlusion, zinc-dressing treatment and steroid injection as the most effective.

Treatment and Burden of Disease in a Cohort of Patients with Prurigo Nodularis: A Survey-based Study.

Prurigo nodularis is a pruritic dermatosis with poor treatment options. To describe treatment patterns, comorbidities, pruritus, and quality of life a survey was administered to 92 patients with prurigo nodularis. A total of 52 patients completed the survey. The most frequently used treatments were topical corticosteroids, which were prescribed to 49/52 patients, with positive effect in 13/49. A total of 46/52 patients were treated with ultraviolet B, and 9/46 reported a positive effect. A positive effect was reported for topical corticosteroids under occlusion in 21/40, for zinc dressing treatment in 17/37, for steroid injection in 9/14, for methotrexate in 5/16, and for thalidomide in 4/12 of treated patients. Thirty-six patients reported a Pittsburgh Sleep Quality Index >5, indicating poor sleep. Patients with prurigo nodularis are severely bothered by pruritus negatively affecting quality of life. Various treatments are prescribed; most frequently topical corticosteroids and ultraviolet B. Surprisingly, patients reported topical corticosteroids under occlusion, zinc-dressing treatment and steroid injection as the most effective.

Can we treat scabies adequately using topical medication? Retrospective analysis of 74 patients

Aim: Scabies is a contagious parasitic skin disorder, which is characterized by severe pruritus. Scabies usually presents with papules and excoriations on hands, feet, axillae, umbilicus and genitalia. Recently, both increased prevalence of the disease and resistance to anti-scabies treatment have been reported. Therefore, early diagnosis and appropriate treatment of scabies are crucial. The aim of this study was to evaluate the characteristics of patients with scabies and treatments that the patients received in order to provide successful management of scabies.Material and Methods: Medical records of the patients who were diagnosed with scabies between June 2019 and February 2020 were reviewed retrospectively. Age, gender, disease duration, similar symptoms in household members, dermatological examination, prior treatments and treatments that we recommended were recorded.Results: The study included 74 patients (39 female, 35 male) with scabies. The mean age of the patients was 40.6±16.7 years. The mean disease duration was 53.5±5.5 days. Pruritus was observed in the household members of 37 (50%) patients. 18 (24.3%) patients received only symptomatic treatment since they were diagnosed as other pruritic dermatoses including xerosis or dermatitis, previously. However, we treated 58 (78.4%) patients using topical permethrin 5%. In addition, 4 (5.4%) patients were treated with topical sulfur 12.5% and 3 (4.1%) patients were treated with balsam of Peru. 9 (12.2%) patients who were resistant to topical treatment received oral ivermectin for complete cure of scabies. Conclusion: The results indicated that most of the patients with scabies (78.4%) were treated with topical permethrin successfully, whereas 12.2% patients required oral ivermectin in addition to topical anti-scabies treatment. Nevertheless, delay in diagnosis of 24.3% patients might increase the risk of spread of scabies. Therefore, we recommend topical permethrin, oral ivermectin and immediate further clinical and laboratory evaluation for indeterminate cases.

Elevated Blood Cadmium and Lead Levels in Chronic Pruritic Dermatoses

Elevated Blood Cadmium and Lead Levels in Chronic Pruritic Dermatoses

Dupilumab for atopic dermatitis: evidence to date.

Atopic dermatitis (AD) is a common chronic, pruritic inflammatory dermatosis. The inflammatory response is characterized by a T helper 2 (Th2) immune response phenotype. To assess current available data on dupilumab, the writers of this article did a comprehensive search in different databases, including Medline, EMBASE, SCOPUS, and clinical trial registries. All relevant articles identified were then manually reviewed. Information regarding dupilumab mechanism of action, pharmacokinetics, clinical efficacy, safety, and future trends was then summarized. Topical therapy is the main treatment in mild-to-moderate AD, but many cases of moderate-to-severe require systemic treatments. Dupilumab is the first biologic approved for the treatment of adults with moderate-to-severe AD. It inhibits IL-4 and IL-13 signaling pathways and reduces Th2 response. Clinical trials have demonstrated significantly improved clinical and patient-reported outcomes. The addition of application of topical corticosteroids results in a more significant improvement in signs and symptoms of AD than with use of dupilumab in monotherapy. The vast majority of patients improves under dupilumab, and almost 40% of patients achieve clear or nearly clear skin. In addition to its effectiveness, dupilumab also has a favorable safety profile. Frequent adverse events reported in the clinical trials were mostly mild-to-moderate and included nasopharyngitis, upper respiratory tract infection, injection site reactions, and conjunctivitis. In general, rates of adverse events occurred with similar frequency between the treatment and placebo groups. Conjunctivitis seems to be a dupilumab-specific side effect and so far has only been observed in atopic dermatitis patients (not in asthma or nasal polyposis). There were no major serious safety concerns identified in phase III clinical trials. Trials in the pediatric population are ongoing and are highly awaited.

Оценка эффективности шампуня с хлоргексидином 4 %при вторичных микробных поражениях у собак с хроническими аллергическими дерматозами

In overcoming of antibiotic resistance in patients with chronic pruritic dermatoses, which often need lifelong monitoring and anti-inflammatory and antimicrobial therapy, topical using of shampoo with chlorhexidine 4% might be the optimal solution. Aim of research. To study the clinical efficacy of shampoo with chlorhexidine 4% (API-SAN, Russia) in dogs with chronic allergic dermatosis and secondary microbial diseases. Materials and methods. Experimental groups were formed: dogs with superficial pyoderma (1st), microbial pododermatitis (2nd) and malassesia dermatitis (3rd), as well as the control group. Results. In this study, we noticed that the pedigree and age sensitivity to dermatological problems was absent. The usual type of dog nutrition was not clearly correlated with the frequency of contacting with dermatologist. The result of the study was taken into account after the 14-day course of treatment in animals with an antimicrobial shampoo with 4 % chlorhexidine and was based in a decrease in the inflammatory (pruritus, skin erythema, exudation), reduction of lesions during planimetric measurement and detection of persistent restorative dynamics of the skin and hair. It was found that against the use of antimicrobial shampoo resistant clinical remission was observed within 7 days in the experimental groups and for 9-9.5 days in the control group. The clinical efficacy of anti-microbial shampoo with 4% chlorhexidine was shown by the results of negative сytology in the most of animals in the experimental groups.

Willingness to pay and quality of life in patients with pruritic skin disorders.

Pruritic dermatosis is a frequent and burdensome disease. The objectives of this study were (1) to assess the willingness to pay (WTP) and the health-related quality of life (HRQoL) in patients with pruritic dermatoses and (2) to compare the results with data on socio-demographic data, and clinical features/symptoms of the patients. One hundred and three patients with pruritic dermatosis had participated in a non-interventional, cross-sectional study. Socio-demographic data, clinical features/symptoms, a health-related quality of life (HRQoL)-based and a dermatology-specific instrument (SF-6D and DLQI, respectively), and two utility indicators such as rating scale (RS) and time-trade-off (TTO) as well as willingness to pay (WTP) were recorded. In our study, there was a significant correlation between DLQI scores and WTP (p < 0.001). Time-trade-off (TTO) was also statistically correlated with SF-6D (p = 0.001). Regression models showed that daily duration and pruritus intensity were associated with lower HRQoL. Furthermore, WTP was the only measure revealing demographic and socio-economic characteristics such as age, education level, family status and income as predicting factors. No significant differences between groups of varying skin diseases were observed. HRQoL and WTP proved to be valid tools to assess the burden of disease in patients with pruritic dermatosis. However, further research with a larger number of patients is needed to validate the present findings.

Treatment Options for Pruritic Dermatosis Recalcitrant to Customary Dosage of Bepotastine Besilate : Updosing or Combining with a Sedative Antihistamine

Treatment Options for Pruritic Dermatosis Recalcitrant to Customary Dosage of Bepotastine Besilate : Updosing or Combining with a Sedative Antihistamine

Consensus on the therapeutic management of atopic dermatitis - Brazilian Society of Dermatology.

BACKGROUNDAtopic dermatitis is a highly prevalent inflammatory and pruritic dermatosis with a multifactorial etiology, which includes skin barrier defects, immune dysfunction, and microbiome alterations. Atopic dermatitis is mediated by genetic, environmental, and psychological factors and requires therapeutic management that covers all the aspects of its complex pathogenesis.OBJECTIVESThe aim of this article is to present the experience, opinions, and recommendations of Brazilian dermatology experts regarding the therapeutic management of atopic dermatitis.METHODSEighteen experts from 10 university hospitals with experience in atopic dermatitis were appointed by the Brazilian Society of Dermatology to organize a consensus on the therapeutic management of atopic dermatitis. The 18 experts answered an online questionnaire with 14 questions related to the treatment of atopic dermatitis. Afterwards, they analyzed the recent international guidelines on atopic dermatitis of the American Academy of Dermatology, published in 2014, and of the European Academy of Dermatology and Venereology, published in 2018. Consensus was defined as approval by at least 70% of the panel.RESULTS/CONCLUSIONThe experts stated that the therapeutic management of atopic dermatitis is based on skin hydration, topical anti-inflammatory agents, avoidance of triggering factors, and educational programs. Systemic therapy, based on immunosuppressive agents, is only indicated for severe refractory disease and after failure of topical therapy. Early detection and treatment of secondary bacterial and viral infections is mandatory, and hospitalization may be needed to control atopic dermatitis flares. Novel target-oriented drugs such as immunobiologicals are invaluable therapeutic agents for atopic dermatitis.

Aberrant Expression of Histamine-independent Pruritogenic Mediators in Keratinocytes may be Involved in the Pathogenesis of Prurigo Nodularis.

Prurigo nodularis is a highly pruritic and hyperplastic chronic dermatosis with unknown pathogenesis. Many pruritogenic mediators, including nerve growth factor, interleukin (IL)-31, thymic stromal lymphopoietin, and endothelin-1, are implicated in chronic itch and inflammation. This study investigated the mRNA levels and immunoreactivity of the nerve growth factor, IL-31, thymic stromal lymphopoietin, and endothelin axes in both lesional and perilesional skin in prurigo nodularis by using quantitative real-time PCR and immunohistochemistry studies. The nerve growth factor high-affinity receptor tyrosine kinase receptor A was upregulated while the low affinity receptor p75 neurotrophin receptor was downregulated in prurigo nodularis lesions. Downregulated expression of IL-31/IL-31 receptor A and endothelin-3/endothelin receptor B and upregulation of thymic stromal lymphopoietin receptor were found in prurigo nodularis lesions. Aberrant expression of nerve growth factor, IL-31, thymic stromal lymphopoietin and endothelin axes was found in prurigo nodularis lesions, especially in the epidermis, indicating the importance of keratinocytes in prurigo nodularis pathogenesis.

Staphylococcus aureus: an underestimated factor in the pathogenesis of atopic dermatitis?

Atopic dermatitis is a common, recurrent pruritic dermatosis with a complex pathogenesis. It has been associated with disordered patterns of immunological response and impaired epithelial barrier integrity. These features predispose the patients to robust colonization of skin lesions by Staphylococcus aureus. Virulence factors of S. aureus (e.g. superantigens, α- and δ-toxin, protein A) have been shown to exacerbate and perpetuate the course of atopic dermatitis. Novel therapeutic options with potential for restoring natural microbiome composition are being elaborated and may enter clinical practice in the future.

Human polyomavirus 7 (HPyV7)-associated dermatoses: novel molecular mechanism driven by viral activation of 4E-BP1 and MEK-ERK-cJun.

A number of pruritic skin conditions arising in immunocompromised patients are associated with viral infection. Recently, human polyomavirus 7 (HPyV7) has been implicated in the pathogenesis of eruptive pruritic parakeratotic and dyskeratotic dermatoses with distinct "peacock plumage" histology. While expression of HPyV7 viral protein, namely small tumor (sT) antigen, is prominent within lesional tissue, the functional role of HPyV7 in cutaneous pathobiology is not yet known. In this study, we demonstrate a novel role for HPyV7 sT antigen in pathways important for the maintenance of keratinocyte structure and function. In particular, HPyV7 sT was found to dysregulate protein phosphatase 2A through physical interactions that led to activation of MEK/ERK/c-Jun and 4E-BP1 (proteins that contribute to disorganized keratinocyte growth as well as hyperproliferative and inflammatory states). Given that HPyV7 actively infects keratinocytes and sT antigen is highly expressed in pruritic dyskeratotic/parakeratotic dermatoses, our data provide important mechanistic evidence supporting a pathogenic role for HPyV7 in cutaneous disease.