Formulation and assessment of hydroxyzine HCL solid lipid nanoparticles by dual emulsification technique for transdermal delivery.

Hydroxyzine HCL (HHCL) is an antihistamine, used for the treatment of allergic skin conditions. The purpose of this study was to achieve a dual phase drug delivery rate across the intact skin, to enhance HHCL permeation through the stratum corneum, to assess the peripheral H1-antihistaminic activity and the extent to which HHCL was systemically absorbed from transdermal gel loaded with solid lipid nanoparticles (SLNs), as well as to avoid its extreme bitterness. According to 23 factorial design, eight formulations of HHCL-SLNs were prepared by the double emulsification method. Lipid type (XA), surfactant concentration (XB) and co-surfactant concentration (XC) were the independent variables. All formulations were characterized for their surface morphology, particle size, entrapment efficiency and in-vitro drug release study. The optimized formula that provides greater desirability was then incorporated into the transdermal gel. In addition, the efficacy of the developed gel was tested in-vivo using 2,4-Dinitrochlorobenzene induced atopic dermatitis as lesion model in mice. F4 showed an average diameter 111 nm ± 0.03, zeta potential - 30 MV ± 2.4 and EE 75.2% ± 4.4. TEM images showed spherical, smooth morphology with uniform particles distribution. In-vivo study demonstrated potent antipruritic efficacy of transdermal gel in atopic dermatitis such as induced lesions compared to HHCL gel. Hence, HHCL solid lipid nanoparticles transdermal gel may be considered as potential for delivery of HHCL and alternatively to traditional oral use.

Vitamin D supplementation and severity of atopic dermatitis: pre-post assessment.

BACKGROUND/OBJECTIVES: There is evidence that vitamin D (VD) supplementation may help in the management of atopic dermatitis (AD). The aim of this study was to assess the influence of VD supplementation on the severity of AD. METHODS: Pre-post interventional study with prospective data collection in patients younger than 14 years. The severity of AD was determined through SCORAD (SCORing Atopic Dermatitis) and classified as mild (SCORAD < 25), moderate (≥25 and <50), and severe (≥50). Skin prick test was performed in all patients. Serum VD levels were classified as sufficient (≥30 ng/mL), insufficient (29 to 21 ng/mL), and deficient (≤20 ng/mL); and those with inadequate levels received oral supplementation of VD for 3 months, and were reassessed after treatment. RESULTS: A total of 152 patients were included. Patients with sufficient vitamin levels had lower SCORAD values (p = 0.04). Further, 116 patients (76.3%) received VD supplementation and after 3 months, VD levels were significantly higher (35.9 ng/mL) compared to baseline levels (23.7 ng/mL, p < 0.001). At the same time, a reduction in the SCORAD index was observed (19.4 before vs 12.3 after supplementation, p < 0.001). Considering other factors that could influence the decrease in AD severity after VD supplementation, female gender was associated with a worse treatment response (p = 0.02). CONCLUSION: Vitamin D supplementation could be an adjuvant in reducing the severity of atopic dermatitis.

The characteristics and impact of pruritus in adult dermatology patients: A prospective, cross-sectional study.

BACKGROUND: Pruritus often accompanies chronic skin diseases, exerting considerable burden on many areas of patient functioning; this burden and the features of pruritus remain insufficiently characterized. OBJECTIVE: To investigate characteristics, including localization patterns, and burden of pruritus in patients with chronic dermatoses. METHODS: We recruited 800 patients with active chronic skin diseases. We assessed pruritus intensity, localization, and further characteristics. We used validated questionnaires to assess quality of life, work productivity and activity impairment, anxiety, depression, and sleep quality. RESULTS: Nine out of every 10 patients had experienced pruritus throughout their disease and 73% in the last 7 days. Pruritus often affected the entire body and was not restricted to skin lesions. Patients with moderate to severe pruritus reported significantly more impairment to their sleep quality and work productivity, and they were more depressed and anxious than control individuals and patients with mild or no pruritus. Suicidal ideations were highly prevalent in patients with chronic pruritus (18.5%) and atopic dermatitis (11.8%). CONCLUSIONS: Pruritus prevalence and intensity are very high across all dermatoses studied; intensity is linked to impairment in many areas of daily functioning. Effective treatment strategies are urgently required to treat pruritus and the underlying skin disease.

Symptom burden of atopic dermatitis in early childhood assessed from daily monitoring of symptoms and topical steroid use.

BACKGROUND: To our knowledge, disease burden of atopic dermatitis (AD) as number of days with symptoms and medical treatment has never been studied as measure of severity. OBJECTIVES: To investigate risk factors for AD burden in the first 3 years of life. METHODS: The Copenhagen Prospective Studies on Asthma in Childhood2010 included 700 children. AD burden was assessed by daily diary entries with information on AD and steroid days measuring 18 possible heritable, prenatal, and postnatal environmental exposures. RESULTS: The children with AD had a median (interquartile range) of 136 symptom days (61-294 days) and 72 steroid days (27-145 days) during the first 3 years of life, with the highest disease burden in the second year of life. The multivariable risk factor analysis showed that maternal AD and childhood allergic sensitization were associated with a higher number of AD days and maternal AD, filaggrin mutation, and allergic sensitization were associated with a higher number of steroid days. LIMITATIONS: Participants with a personal interest in atopic diseases could be more likely to participate. CONCLUSION: Children's burden of AD, assessed quantitatively as AD and steroid days, demonstrated positive associations with maternal AD, filaggrin mutation, and early-life allergic sensitization, with the highest disease burden in the second year of life.

Clinical Relevance of Skin Pain in Atopic Dermatitis.

Skin pain is increasingly recognized as an impactful symptom in atopic dermatitis (AD) because of its association with patient discomfort, disease burden, and reduced quality of life. Although the nature of skin pain in AD has not been systematically studied and is therefore not well understood, patients report soreness, discomfort, and tenderness that may reflect peripheral and central pain sensitization. The high prevalence of skin pain suggests that it is not adequately addressed by current therapies for AD and may be undertreated compared with other symptoms. This review discusses the clinical relevance of skin pain with respect to its experience, pathophysiology, relationship with itch, and treatment implications. Recent studies suggest that skin pain presents as a neuropathic symptom independent from itch and the “itch-scratch cycle”, and poses a unique burden to patients. Recognition of the significant consequences of skin pain and discomfort should reinforce the need to assess and treat this symptom in patients with moderate-to-severe AD. J Drugs Dermatol. 2020;19(10)921-926. doi:10.36849/JDD.2020.5498.

Handheld confocal Raman spectroscopy (CRS) for objective assessment of skin barrier function and stratification of severity in atopic dermatitis (AD) patients.

BACKGROUND: We developed the first-of-its-kind handheld confocal Raman spectroscopy (CRS) system to quantify the concentration of natural moisturizing factors in the skin. OBJECTIVE: To evaluate the feasibility of our handheld CRS system and propose a novel quantitative index to measure skin barrier function. METHODS: This prospective study included 30 atopic dermatitis (AD) patients and 14 healthy volunteers. All AD participants were assessed using the Scoring Atopic Dermatitis (SCORAD) severity instrument, a vapometer for trans-epidermal water loss and a moisture meter for skin surface moisture. A handheld CRS operating at 785 nm laser was used to measure the biochemical constituents of the skin up to a depth of ∼100 µm. We trained a linear kernel-based support vector machine (SVM) model for eczema classification based on the water, ceramide and urocanic acid content. A novel Eczema Biochemical Index (EBI) was then formulated using the skin constituents measured from the AD participants to stage disease severity. RESULTS: The SVM model used to classify healthy participants and AD patients obtained high cross-validated area under the curve of 0.857 and accuracy of 0.841, with high sensitivity and specificity values of 0.857 and 0.833 respectively. EBI can be used to stratify AD patients of varying severity, based on the biochemical constituents in the skin. CONCLUSION: As compared to the standard CRS system, the handheld CRS offers higher portability and provides Raman measurements at various body regions with similar sensitivity. This suggests that a handheld CRS device could be a valuable point-of-care resource in both research and clinical use.

Economic Burden of Adult Patients with Moderate to Severe Atopic Dermatitis Indicated for Systemic Treatment.

Given the introduction of new therapies targeting specific immune pathways for atopic dermatitis (AD), information on the economic burden of AD patients is needed. Direct costs (medication use and healthcare resource utilization) and costs of productivity loss were studied in 90 adult patients with AD indicated for systemic treatment. Costs were calculated for patients with controlled (Investigator Global Assessment (IGA) 0-2) and uncontrolled (IGA 3-5) disease at inclusion. Mean (95% confidence interval (95% CI)) total direct costs were €5,191 (€4,382-6,019) per patient per year (PPY), €4,401 (€3,695-5,215) for patients with controlled AD vs. €6,993 (€5,552-8,406), mean difference €2,593 (€820-4,282) (p=0.014) for patients with uncontrolled AD. Costs of productivity loss were €10,040 (€6,260-14,012) PPY for the total group, €6,886 (€4,188-10,129) PPY for patients with controlled AD vs. €13,702 (€6,124-22,996) for patients with uncontrolled AD, mean difference €6,816 (-€1,638-16,677; p=0.148). Total costs (direct costs+costs of productivity loss) were €15,231 (€11,487-19,455) PPY for the total group, €11,287 (€7,974-15,436) for patients with controlled AD vs. €20,695 (€14,068-34,564), mean difference €9,408 (-€119-19,964) (p=0.077) for patients with uncontrolled AD. Patients with AD using systemic immunosuppressive treatment incur considerable direct costs and costs of productivity loss.

Assessment of serum allergen-specific IgE levels in horses with seasonal allergic dermatitis and recurrent airway obstruction in Spain.

Allergic conditions are prevalent equine diseases that can be diagnosed by clinical examination alone, but definitive diagnosis is more likely with laboratory testing. The ELISA Allercept© test was used to analyse the serum samples of 73 horses with allergic diseases. Sixty-one horses (83.5%) had allergen-specific IgE levels ≥ 150 ELISA Units (EU), the cut-off defined by the assay. Fifty-four horses had allergic dermatitis (AD) with high IgE levels to Tyrophagus putrescentiae (51.9%), Rumex crispus (48.1%), Tabanus (46.3%) and Dermatophagoides farinae/ D. pteronyssinus (40.7%). Seven horses with recurrent airway obstruction (RAO) had a high prevalence of T. putrescentiae (85.7%), followed by that of Acarus siro (57.1%) and D. farinae/D. pteronyssinus (57.1%). Horses affected with RAO had more positive reactions to mites (2.22 ± 0.84) than did horses with AD (1.51 ± 0.61, P < 0.05). A strong correlation of serum allergen-specific IgE level was found between Culex tarsalis and Stomoxys (r = 0.943) and between Dactylis glomerata and both Secale cereale (r = 0.79) and R. crispus (r = 0.696). These results indicate that among horses with allergic diseases in Spain, ELISA tests demonstrated a high prevalence of serum allergen-specific IgE in response to mites. Our study emphasises the importance of laboratory testing and updating allergy panels to improve the likelihood of a definitive diagnosis and the identification of allergens that should be included in allergic disease treatment.

African American ancestry contribution to asthma and atopic dermatitis.

OBJECTIVE: Asthma and atopic dermatitis (AD) are complex diseases with striking disparities across racial and ethnic groups, which may be partly attributable to genetic factors. Here we summarize current knowledge from asthma and AD genome-wide association studies (GWAS) and pharmacogenetic studies in African ancestry populations. DATA SOURCES: GWAS catalog; PUBMed. STUDY SELECTIONS: GWAS catalog studies with trait annotations "asthma" and "atopic eczema" and African ancestry individuals in the discovery dataset; the recent CAAPA asthma GWAS; reports on pharmacogenetic studies in asthma and AD. RESULTS: Although GWASs have revolutionized gene discovery for multiple complex traits, African Americans continue to be severely underrepresented in sufficiently powered genetics studies. Indeed, of the 16 asthma and 21 AD loci that reached genomewide significance in Europeans, very few have replicated in African ancestry populations. Challenges in comparing results from European vs African ancestry cohorts include modest sample size, differences in risk allele frequency, effect size, correlation between genetic variants, and environmental exposure in evolutionary history. African Americans also constitute a small percentage of dermatological and respiratory-focused clinical trials. Pharmacogenetic studies have similarly been focused largely on non-Hispanic whites, despite compelling evidence that genetic variation from different ancestral backgrounds may alter therapeutic efficacy of asthma and AD drugs. CONCLUSION: Large-scale genetic studies of asthma and AD in African Americans are essential to reduce research and health disparities and empower scientific discoveries.

TREatment of ATopic eczema (TREAT) Registry Taskforce: an international Delphi exercise to identify a core set of domains and domain items for national atopic eczema photo- and systemic therapy registries.

BACKGROUND: Evidence of immunomodulatory therapies to guide clinical management of atopic eczema (AE) is scarce, despite frequent and often off-label use. Patient registries provide valuable evidence for the effects of treatments under real-world conditions that can inform treatment guidelines, give the opportunity for health economic evaluation and the evaluation of quality of care, as well as pharmacogenetic and dynamic research, which cannot be adequately addressed in clinical trials. OBJECTIVES: The TREatment of ATopic eczema (TREAT) Registry Taskforce aims to seek international consensus on a core set of domains and items ('what to measure') for AE research registries, using a Delphi approach. METHODS: Participants from six stakeholder groups were included: doctors, nurses, nonclinical researchers, patients, industry and regulatory body representatives. The eDelphi comprised three sequential online rounds, requesting participants to rate the importance of each proposed domain item. Participants could add domain items to the proposed list in round 1. A final consensus meeting was held to ratify the core set. RESULTS: Participants (n = 479) from 36 countries accessed the eDelphi platform, of whom 86%, 79% and 74% completed rounds 1, 2 and 3, respectively. At the face-to-face consensus meeting attended by 42 participants the final core set was established containing 19 domains with 69 domain items (49 baseline and 20 follow-up items). CONCLUSIONS: This core set of domains and items to be captured by national AE systemic therapy registries will standardize data collection and thereby allow direct comparability across registries and facilitate data pooling between countries. Ultimately, it will provide greater insight into the effectiveness, safety and cost-effectiveness of photo- and systemic immunomodulatory therapies.

Association between atopic dermatitis and autoimmune disorders in US adults and children: A cross-sectional study.

BACKGROUND: Little is known about the risk and predictors of autoimmune diseases in children and adults. OBJECTIVE: To determine the prevalence, predictors, and excess costs of autoimmune disease in atopic dermatitis (AD) patients. METHODS: Cross-sectional study of the 2002-2012 National Inpatient Sample, which includes a ∼20% sample of all US hospitalizations (n = 87,053,155 adults and children). RESULTS: The prevalence of autoimmune disease was higher in adults with AD (7.9%, 95% confidence interval [95% CI] 7.3-8.5%) than without AD (5.7%, 95% CI 5.7%-5.8%) and higher in children with AD (2.0%, 95% CI 1.7%-2.3%) than without AD (1.0%, 95% CI 0.9%-1.1%). In multivariable logistic regression models controlling for sociodemographics, adult (adjusted odds ratio 1.45, 95% CI 1.32-1.58) and pediatric (adjusted odds ratio 2.08, 95% CI 1.73-2.50) AD were associated with any autoimmune disorder. In particular, AD was associated with 18 of 32 autoimmune disorders examined in adults and 13 of 24 examined in children, including disorders of the skin, endocrine, gastrointestinal, hematologic, and musculoskeletal systems. AD patients hospitalized with any autoimmune disorder had a higher cost of inpatient care, with $2.5-$50 million excess annual costs. CONCLUSIONS: Adults and children with AD had increased cutaneous and extracutaneous autoimmune disorders, which were associated with a considerable cost burden.

Assessment of IL-31 levels and disease severity in children with atopic dermatitis.

INTRODUCTION AND OBJECTIVES: Atopic dermatitis is a chronic, relapsing, highly pruritic, inflammatory skin disease characterized by typical localization with increasing prevalence of 10-20% in children. Pruritus is one of the major diagnostic criteria of atopic dermatitis and also the main complaint altering quality-of-life of affected patients, inducing and aggravating inflammation. Although pruritus is the absolute symptom of AD, the etiology has not been fully explained yet and current antihistamine therapies are ineffective. The aim of the study was to assess the correlation between IL-31 level and disease severity in patients with atopic dermatitis through Severity SCORing of Atopic Dermatitis (SCORAD) index and the degree of itching assessed subjectively. MATERIAL AND METHODS: One hundred thirty-five children were enrolled in the study in total, 70 children with diagnosis of atopic dermatitis and 65 healthy children in control group. Data on demographic features (age, gender, family history of atopy) and laboratory values of serum eosinophil, total IgE, IgM, IgA, IgG levels and skin prick test results were collected through patient files. The disease severity was assessed by SCORAD index. IL-31 levels were measured with human IL-31 ELISA kit. RESULTS: The statistical analysis showed that IL-31 level was significantly higher in AD patients than in the control group (AD vs CG, p 0.0001). There was no significant difference in IL-31 levels between the three subgroups divided according to the SCORAD severity score (p:0.27). CONCLUSION: IL-31 levels were significantly higher in AD patients compared to control group but irrelevant to the disease severity.

Assessment of allergen-specific IgE by immunoblotting method in atopic dermatitis.

SUMMARY: Background and Objectives. Stimulating the immune system by exposure to various allergens to produce specific IgE has a significant role in the pathogenesis of atopic dermatitis. Identifying disease-causing allergens, prevention of exposure to those allergens, and immunotherapy will play an important role in the treatment of Atopic Disease. The purpose of this study was to determine the common allergens of northwest of Iran in patients with atopic dermatitis that are resistant to treatment. Materials and methods. In this descriptive-analytical study, serum levels of total IgE and frequency of specific IgE were measured by Immunoblotting against 20 common allergens in 150 cases of patients with atopic dermatitis, attending to dermatology and asthma and allergy clinics from 2010 to 2011. The control group consisted of individuals who had been clinically healthy. Results. In the 90% of patients that were included in this study, total IgE levels were higher than in healthy people with mean serum levels of total IgE 227.51 ± 103 IU/ml. 136 patients (90.6%) had specific IgE for at least one allergen. The frequency of positive allergens among the patients who were included in this study were 53.34%, 26.8%, and 19.56% respectively in plants and fungus allergens group, animal allergens group and food allergens group. After avoiding of the allergens (which they had been sensitized to), 60% of patients were cured with immune therapy, and total IgE serum levels in the control group were not increased. Conclusion. Identifying the abundant allergens such as cultivated rye, Timothy grass, house dust mite, birch, cat, horse, potato, dog, egg white, cow milk, in order to advise patients to avoid them or to do immunotherapy and desensitization, is useful in this area.

Evolving Concepts in Atopic Dermatitis.

PURPOSE OF REVIEW: Tremendous advances have been made in the field of atopic dermatitis in the past 5 years. We will explore developments in burden of disease, co-morbidities, pathogenesis, prevention, and management. RECENT FINDINGS: The tremendous burden moderate to severe atopic dermatitis (AD) places on families from a medical, psychosocial, and financial perspective has been characterized. Epidemiologic studies have identified intriguing new associations beyond the well-characterized "atopic march" of food allergies, asthma, and hay fever. Studies of primary prevention have gained traction including the remarkable impacts of early emollient therapy. Basic advances have simultaneously elucidated the nature of atopic inflammation, setting the stage for an explosion of new potential therapeutic targets. After a fallow period of nearly 15 years without a substantial therapeutic advance, this year has already seen two new FDA-approved treatments for AD. AD has a tremendous impact on quality of life with an underappreciated burden of disease; there are important newly described co-morbidities including ADHD and anemia; new insights into etio-pathogenesis have paved the way for novel topical therapies like crisaborole, and new systemic interventions like dupilumab.

The Future of Sublingual Immunotherapy in the United States.

Sublingual immunotherapy (SLIT) is a safe and effective treatment for allergic rhinitis (AR) and allergic rhinoconjunctivitis (ARC). The Food and Drug Administration (FDA) in the USA has approved three SLIT tablets for the treatment of AR and ARC in relation to pollen. Specifically, Grastek® and Oralair® are two formulations approved to treat patients suffering with AR/ARC to grass pollen, and Ragwitek™ is a formulation approved to treat patients suffering with AR/ARC to ragweed pollen. Although these approvals provide support for physicians to prescribe SLIT, barriers to prescribing SLIT still remain such as FDA approval for additional formulations, a standard dose and dosing schedule, and cost/insurance coverage. In order to further support the use of SLIT, research is currently being conducted to expand the indication for SLIT to other common comorbidities to AR/ARC. For example, allergic asthma, food allergies, and atopic dermatitis are other diseases which are being explored. The future of SLIT in the USA is unknown; however, education will be necessary for both providers and patients.

Use of activity monitors for assessment of pruritus in an acute model of canine atopic dermatitis.

BACKGROUND: We developed a canine model of acute atopic dermatitis to evaluate the potential of compounds to treat pruritus and skin lesions induced in Dermatophagoides farinae (Df)-sensitized dogs. HYPOTHESIS/OBJECTIVES: The aim was to investigate the effectiveness of long-term recording activity monitors to assess pruritus induced by allergen challenges. ANIMALS: Thirty-two Df-sensitized laboratory dogs. METHODS: In two blinded crossover studies, 28 Df-sensitized dogs were challenged on 3 days with a Df slurry applied to clipped abdominal skin. Dogs were treated with a positive control (prednisolone 1 mg/kg once daily for 5 days, starting 1 day before challenge) or left untreated; all were fitted with activity monitors. To confirm pruritus, a parallel study with four dogs was conducted, filming the dogs before and during challenge and assessing the film for pruritic behaviour. RESULTS: The activity of dogs treated with prednisolone was significantly lower between 00.00 and 03.00 h and between 03.00 and 06.00 h compared with untreated dogs (repeated-measures ANCOVA; P < 0.0001). To determine whether the recorded night-time activity corresponded to pruritic manifestations, we compared activity monitor and video recordings of four dogs for two periods (16.30-20.30 and 24.00-03.00 h) before and during a Df challenge. The correlation between night-time activity monitor activity and observed pruritic behaviour was highly significant (test of correlation coefficient versus zero: r = 0.57, P < 0.0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Determination of night-time activity with activity monitors after allergen challenge appears to be an objective and practical way to assess pruritus in this experimental model of canine atopic dermatitis.