Search

The recent interest and elucidation of the JAK/STAT signaling pathway created new targets for the treatment of inflammatory skin diseases (ISDs). JAK inhibitors in oral and topical formulations have shown beneficial results in psoriasis and alopecia areata. Patients suffering from other ISDs might also benefit from JAK inhibition. Given the development of specific JAK inhibitors, the expression patterns of JAKs in different ISDs needs to be clarified. We aimed to analyze the expression of JAK/STAT family members in a set of prevalent ISDs: psoriasis, lichen planus (LP), cutaneous lupus erythematosus (CLE), atopic dermatitis (AD), pyoderma gangrenosum (PG) and alopecia areata (AA) versus healthy controls for (p)JAK1, (p)JAK2, (p)JAK3, (p)TYK2, pSTAT1, pSTAT2 and pSTAT3. The epidermis carried in all ISDs, except for CLE, a strong JAK3 signature. The dermal infiltrate showed a more diverse expression pattern. JAK1, JAK2 and JAK3 were significantly overexpressed in PG and AD suggesting the need for pan-JAK inhibitors. In contrast, psoriasis and LP showed only JAK1 and JAK3 upregulation, while AA and CLE were characterized by a single dermal JAK signal (pJAK3 and pJAK1, respectively). This indicates that the latter diseases may benefit from more targeted JAK inhibitors. Our in vitro keratinocyte psoriasis model displayed reversal of the psoriatic JAK profile following tofacitinib treatment. This direct interaction with keratinocytes may decrease the need for deep skin penetration of topical JAK inhibitors in order to exert its effects on dermal immune cells. In conclusion, these results point to the important contribution of the JAK/STAT pathway in several ISDs. Considering the epidermal JAK3 expression levels, great interest should go to the investigation of topical JAK3 inhibitors as therapeutic option of ISDs. [ABSTRACT FROM AUTHOR]

The macrophage migration inhibitory factor (MIF) gene is located on human chromosome 22q11.2 and is linked to atopic phenotypes. Plasma MIF and log [total IgE] levels are significantly elevated in atopic dermatitis (AD) patients. The aim of this study was to evaluate the relationship between two MIF polymorphisms, −173 G to C and −794 CATT5–8, and total plasma IgE levels in AD patients in Korea. We performed PCR-RFLP analysis in 178 AD patients and 80 control subjects to determine whether MIF SNPs are associated with susceptibility to AD. Plasma total IgE and MIF levels were determined, and then logistic regression analyses were performed to determine the associations between a SNP or haplotype and plasma total IgE or MIF levels. The −173 G/C polymorphism, located in the MIF promoter, was significantly associated with AD; the odds ratios (ORs) for the CC homozygotes and GC heterozygotes were 9.3 and 2.5, respectively. The MIF C/5-CATT and the MIF C/7-CATT haplotypes were significantly associated with AD; the ORs for the MIF C/5-CATT and MIF C/7-CATT haplotypes were 9.7 and 4.5, respectively. Log [total IgE] levels were highly associated with the MIF −794 7-CATT polymorphism. Notably, the MIF C/7-CATT haplotype was associated with a decrease in plasma log [total IgE] levels in a gene dose-dependent manner. Although log [MIF] levels were not associated with the MIF polymorphisms, the frequencies of the MIF C/5-CATT haplotype-containing genotypes decreased in order of MIF levels. Our results demonstrate that MIF promoter polymorphisms in the −173 C allele and the MIF C/5-CATT and C/7-CATT haplotypes were significantly associated with an increased risk for AD. In particular, the −794 7-CATT locus and the MIF C/7-CATT haplotype were significantly associated with decreased total IgE levels in the plasma, suggesting that these polymorphisms might be a marker for intrinsic AD rather than extrinsic AD that shows high total IgE levels and presence of allergen-specific IgE. [ABSTRACT FROM AUTHOR]

Interleukin-31 (IL-31) is a type 2 helper T-cell-derived cytokine that has recently been shown to cause severe inflammation and tissue remodeling in multiple chronic diseases of the skin and lungs. IL-31 is upregulated in allergic and inflammatory diseases, including atopic dermatitis, asthma, cutaneous T-cell lymphomas, and allergic rhinitis, as well as autoimmune diseases such as systemic erythematosus. Overexpression of IL-31 in T cells causes severe inflammation, with histological features similar to skin lesions of patients with atopic dermatitis. However, the molecular mechanisms involved in IL31-driven pathological remodeling in skin diseases remain largely unknown. Here, we studied the role of IL-31 in skin damage as a result of intradermal administration of recombinant IL-31 into mice. Notably, IL-31 was sufficient to increase epidermal basal-cell proliferation and thickening of the epidermal skin layer. Our findings demonstrate a progressive increase in transepidermal water loss with chronic administration of IL-31 into the skin. Further, analysis of the skin transcriptome indicates a significant increase in the transcripts involved in epidermal-cell proliferation, epidermal thickening, and mechanical integrity. In summary, our findings demonstrate an important role for IL-31 signaling in epidermal cell proliferation and thickening that together may lead to impaired skin-barrier function in pathological remodeling of the skin. [ABSTRACT FROM AUTHOR]

Purpose: Nephrotic syndrome is a common chronic illness encountered during childhood. Infections have been identified as a cause of nephrotic syndrome. The aim of this study was to evaluate the association between enteroviral infection and nephrotic syndrome. Methods: A nationwide retrospective cohort study was conducted by analyzing data from the National Health Insurance Research Database in Taiwan. Children aged <18 years with enteroviral infection were enrolled. Non-enterovirus-infected children were randomly selected as the comparison cohort. The primary endpoint was the occurrence of nephrotic syndrome. Methods: This study included 280,087 enterovirus-infected children and 280,085 non-enterovirus-infected children. The mean age of the enterovirus-infected children was 2.38 years, and 53.7% of these children were boys. The overall incidence densities of nephrotic syndrome for enterovirus- and non-enterovirus-infected children were 2.65 and 2.21 per 10,000 person-years, respectively. The enterovirus-infected cohort had a higher cumulative incidence of nephrotic syndrome than did the non-enterovirus-infected cohort (log-rank test, p = 0.01). Multivariable analyses revealed that children with enteroviral infection were significantly associated with an increased risk of nephrotic syndrome compared with those without enteroviral infection (adjusted hazard ratio, 1.20; 95% confidence interval, 1.04–1.39; p = 0.01), particularly in children infected with coxsackievirus. Subgroup analyses revealed that enterovirus-infected girls, children of blue-collar workers, and children without allergies had a higher risk of nephrotic syndrome than did children in the non-enterovirus-infected cohort. Conclusion: This study revealed a significant association between enteroviral infection and nephrotic syndrome. Additional studies elucidating the role and pathogenesis of enterovirus in nephrotic syndrome are warranted. [ABSTRACT FROM AUTHOR]

The article presents abstracts on medical topics discussed at the congress of European Society for Dermatological Research held in Germany from September 7-10, 2016, which include insights into atopic dermatitis, scoring infantile haemangiomas, and endothelial dysfunction in patients with moderate and severe psoriasis.

The article presents the study of store-and-forward teledermatology at Clinique Olivia, a small clinic in Niamey, Niger which is an impoverished West African nation that has only four dermatologists serving a population of 20 million. The most common teleconsult diagnoses were atopic dermatitis and lichen simplex chronicus. One limitation was the lack of standardized information exchange during teleconsults and the other was poor patient follow-up.

Ceramides (CER) are essential sphingolipids of the stratum corneum (SC) that play an important role in maintaining cutaneous barrier function. Skin barrier defects occur in both human beings and dogs affected with atopic dermatitis, and have been associated with decreased CER concentrations and morphological alterations in the SC. The aim of the present study was to investigate the changes induced by three different sphingolipid extracts (SPE-1, SPE-2 and SPE-3) on the morphological structure and lipid composition of canine skin, using an in vitro model, whereby keratinocytes were seeded onto fibroblast-embedded collagen type I matrix at the air–liquid interface. Cell cultures were supplemented with SPE-1, SPE-2, SPE-3 or vehicle (control) for 14 days. The relative concentrations of lipids were determined by ultra-performance liquid chromatography coupled to mass spectrometry. The ultrastructural morphology of samples was examined by transmission electron microscopy. SPE-1 induced significant elevation in total CERs, CER[NS], CER[NDS], CER[NP], CER[AS], CER[AP], CER[EOS] and CER[EOP] subclasses, whereas SPE-2 induced a significant elevation in total CER, CER[AP] and CER[EOS] compared with control conditions. Ultrastructural analysis revealed an increase in lamellar-lipid structures in the SC of SPE-1-treated samples. The findings demonstrated that SPE-1 stimulates production of CERs, as shown by changes in lipid composition and ultrastructural morphology. Thus, SPE-1 contributes to the formation of a well-organised SC and represents a potential therapeutic target for improving skin barrier function in atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a complex chronic inflammatory disease where allergens can act as specific triggering factors. Aim: To characterize the specificities of IgE-reactivity in patients with AD to a broad panel of exogenous allergens including microbial and human antigens. Methodology: Adult patients with AD were grouped according to the SCORAD index, into severe (n = 53) and moderate AD (n = 126). As controls 43 patients were included with seborrhoeic eczema and 97 individuals without history of allergy or skin diseases. Specific IgE reactivity was assessed in plasma using Phadiatop®, ImmunoCap™, micro-arrayed allergens, dot-blotted recombinant Malassezia sympodialis allergens, and immune-blotted microbial and human proteins. Results: IgE reactivity was detected in 92% of patients with severe and 83% of patients with moderate AD. Sensitization to cat allergens occurred most frequently, followed by sensitization to birch pollen, grass pollen, and to the skin commensal yeast M. sympodialis. Patients with severe AD showed a significantly higher frequency of IgE reactivity to allergens like cat (rFel d 1) and house dust mite (rDer p 4 and 10), to Staphylococcus aureus, M. sympodialis, and to human antigens. In contrast, there were no significant differences in the frequencies of IgE reactivity to the grass pollen allergens rPhl p 1, 2, 5b, and 6 between the two AD groups. Furthermore the IgE reactivity profile of patients with severe AD was more spread towards several different allergen molecules as compared to patients with moderate AD. Conclusion: We have revealed a hitherto unknown difference regarding the molecular sensitization profile in patients with severe and moderate AD. Molecular profiling towards allergen components may provide a basis for future investigations aiming to explore the environmental, genetic and epigenetic factors which could be responsible for the different appearance and severity of disease phenotypes in AD. [ABSTRACT FROM AUTHOR]

Mutations in the epidermal filaggrin gene ( FLG) are associated with skin barrier dysfunction (dry skin, less acidic skin, and fissured skin), and atopic dermatitis ( AD) with a severe and persistent course. Because pregnancy and delivery further impairs normal skin barrier functions (immune suppression, mechanical stress), we studied the possible role of FLG mutations on the risk of AD flares, genital infections, and postpartum problems related to perineal trauma. FLG-genotyping was performed in a population-based sample of 1837 women interviewed in the 12th and 30th weeks of pregnancy and 6 months postpartum as part of the Danish National Birth Cohort study 1996-2002. We found that FLG mutations also influence pregnancy-related skin disease; thus, women with FLG mutations had an increased risk of AD flares during pregnancy ( OR 10.5, 95% CI 3.6-30.5) and of enduring postpartum physical problems linked to perineal trauma during delivery ( OR 11.1, 95% CI 1.1-107.7). [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is an intriguing clinical entity. Its clinical connotations are varied, the updates of which are required to be done periodically. An attempt to bring its various facets have been made highlighting its clinical features keeping in view the major and the minor criteria to facilitate the diagnosis, differential diagnosis, complications, and associated dermatoses. The benefit of the current dissertation may percolate to the trainees in dermatology, in addition to revelations that atopic undertones in genetic susceptibility and metabolic disorder may provide substantive insight for the future in the understanding of thus far enigmatic etiopathogenesis of AD. [ABSTRACT FROM AUTHOR]

There are several skin conditions that can be triggered by allergy. These allergies can be extremely uncomfortable, cause a great deal of distress, anxiety and embarrassment, and have a significant impact on patients' quality of life. This article describes the causes of skin allergies, highlights the importance of taking a thorough medical and allergy history, and outlines the principles of diagnosis and management. [ABSTRACT FROM AUTHOR]

Phototherapy is the use of non-ionizing radiation, primarily in the ultraviolet spectrum, to treat disease. In dermatology, ultraviolet ( UV) phototherapy remains an established, lower cost, and often preferred option for many common skin conditions, despite the introduction of newer potent biologics. This article introduces a principal therapeutic modality in the treatment of psoriasis, atopic dermatitis (eczema), vitiligo, and morphea among other diseases where oral manifestations may be present, providing basic information about the use of UVA, UVB, and PUVA. Practical considerations and side effects of phototherapy are described. Phototherapy is an effective treatment for many illnesses and carries a relatively benign side-effect profile. [ABSTRACT FROM AUTHOR]

Background: There is a demonstrated association between asthma and irritable bowel syndrome (IBS). In this study, we examined the bidirectional association between asthma and IBS using a nationwide database. Methods: We conducted two retrospective cohort studies using data obtained from the National Health Insurance of Taiwan. Study 1 included 29,648 asthma patients newly diagnosed between 2000 and 2010. Study 2 included 29,875 IBS patient newly diagnosed between 2000 and 2010. For each study, four subjects without asthma and IBS were selected, respectively, frequency-matched by sex, age, and the diagnosis date. All four cohorts were followed up until the end of 2011 to estimate incident IBS for Study 1 and incident asthma for study 2. Adjusted hazard ratios (aHRs) were estimated using the Cox proportional hazards model after controlling for sex, age and comorbidities. Results: The incidence of IBS was 1.89 times higher in the asthma cohort than in the comparison cohort (8.26 vs. 4.36 per 1,000 person-years), with an aHR of 1.57 [95% confidence interval (CI) = 1.47–1.68]. The aHRs remained significant in all subgroups measured by sex, age and the presence of comorbidities. In contrast, the incidence of asthma was 1.76 times higher in the IBS cohort than the comparison cohort (7.09 vs. 4.03 per 1,000 person-years), with an aHR of 1.54 (95% CI = 1.44−1.64). Similarly, aHRs remained significant in all subgroups measured by sex, age and the presence of comorbidities. Conclusion: The present study suggests a bidirectional association between asthma and IBS. Atopy could be a shared pathophysiology underlying this association, deserving a further investigation. [ABSTRACT FROM AUTHOR]

This review summarizes historical aspects, clinical expression and pathophysiology leading to coining of the terms atopy and atopic dermatitis, current diagnostic criteria and further explore the possibility of developing quantitative diagnostic criteria of atopic dermatitis ( AD) based on the importance of atopic features - subjective, objective, and those derived from laboratory tests - the new partly promising AD biomarkers. 'Atopy', introduced in 1923, denoted 'the sense of a strange disease without a precise place in the body'. A decade later, Sulzberger and Hill, first defined 'atopic dermatitis'. The pioneering well-recognized criteria, 'Hanifin & Rajka' ( Acta Derm Venereol, 92, 1980, 44), were developed empirically on 'clinical experience' and expert consensus. As opposed to the widely used, rather anamnestic ' UK Criteria' (1994), they have few formal validation studies, but appear to well embrace various atopic phenotypes. Pruritus, xerosis, typical morphology/distribution of dermatitis and tendency to a relapsing/chronic course are common basic features in AD criteria, whereas skin sensitivity, heredity and various ill-defined atopic stigmata also seem to comprise the atopic phenomenon. Specific pheno- and endotypes are now emerging potentially enabling us to better classify patients with AD, but the influence of these on the diagnosis of AD is so far unclear. Few diagnostic models use quantitative scoring systems to establish AD cases from normal population, which, however, may be useful to better study and manage this disease. Long-term prospective observational studies, from which few are available at this point, along with interventional studies, are a perquisite and will provide the best option to improve our understanding of its complex characteristics and etiology. [ABSTRACT FROM AUTHOR]

Objective:To determine the frequency of autoimmune disorders associated with alopecia areata in patients presenting in a tertiary care hospital. Methods: This study was conducted at the Dermatology Department, Unit II, KEMU/Mayo Hospital, Lahore.120 patients fulfilling the inclusion criteria were entered in the study during May 2013 to January 2014. After taking informed consent and recording demographic data, complete history was taken. Examination was performed and investigations were carried out where needed, for determination of factors associated with alopecia areata. Results: Out of 120 patients studied, 30.8% of patients had positive family history of alopecia areata. Atopic dermatitis was found in 29.2% of patients. Vitiligo and hypothyroidism were seen in 4.2% each. Diabetes mellitus was seen in 1.7% of the cases and 0.8% were hyperthyroid. Conclusion: Postive family history and atopic dermatitis were seen in one third of our patients with alopecia areata. Vitiligo and hypothyroidism were other important associations observed. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a complex disease that is caused by various factors, including environmental change, genetic defects, and immune imbalance. We previously showed that p-hydroxycinnamic acid (HCA) isolated from the roots of Curcuma longa inhibits T-cell activation without inducing cell death. Here, we demonstrated that oral administration of HCA in a mouse model of ear AD attenuates the following local and systemic AD manifestations: ear thickening, immune-cell infiltration, production of AD-promoting immunoregulatory cytokines in ear tissues, increased spleen and draining lymph node size and weight, increased pro-inflammatory cytokine production by draining lymph nodes, and elevated serum immunoglobulin production. HCA treatment of CD4+ T cells in vitro suppressed their proliferation and differentiation into Th1 or Th2 and their Th1 and Th2 cytokine production. HCA treatment of keratinocytes lowered their production of the pro-inflammatory cytokines that drive either Th1 or Th2 responses in AD. Thus, HCA may be of therapeutic potential for AD as it acts by suppressing keratinocyte activation and downregulating T-cell differentiation and cytokine production. [ABSTRACT FROM AUTHOR]

Objectives: Little is known about health outcomes related to electronic cigarette (EC) use, despite its growing popularity. The aim of this study is to investigate the association between EC use and asthma. Methods: The study design is a cross-sectional study. A total of 35,904 high school students were included as the final study population. The presence of asthma was based on a student’s self-reported doctor diagnosis of asthma in the past 12 months. Results: Prevalence rates of asthmatics in ‘current EC users’ (n = 2,513), ‘former EC users’ (n = 2,078), and ‘never EC users’ (n = 31,313), were 3.9% (n = 98), 2.2% (n = 46) and 1.7% (n = 530), respectively. Comparing ‘current EC’ users with ‘never EC’ users, the unadjusted OR for asthma was 2.36 (95% CI: 1.89–2.94). In order to control for the effect of conventional cigarette (CC) smoking, after stratifying the subjects by the three CC smoking categories (never CC, former CC, and current CC), within the ‘never CC’ category, the unadjusted OR for asthma for ‘current EC’ users was 3.41 (95% CI: 1.79–6.49), and the adjusted OR was 2.74 (95% CI: 1.30–5.78). Severe asthma was reflected by the number of days absent from school due to asthma symptoms; current EC users had the highest adjusted OR for severe asthma compared to ‘never EC’ users. Conclusions: When compared to a reference population of high school students in South Korea, EC users have an increased association with asthma and are more likely to have had days absent from school due to severe asthma symptoms. In conclusion, the results indicate that EC use may be a risk factor for asthma. The results may be useful in developing a scientific basis for the evaluation of a potential health hazard by EC. [ABSTRACT FROM AUTHOR]

Objective: The impact of occupational contact dermatitis (OCD) is often underestimated because of underreporting, and its management is also inadequate, especially in developing countries. Topical corticosteroids have remained the first line treatment but till date, there is no study on efficacy and safety of halometasone in OCD, and there is a paucity of data on its comparative efficacy in allergic and irritant variety. This study aims to evaluate the efficacy and safety of halometasone in OCD and to compare its effect in allergic and irritant types of OCD. Methods: The present study is a prospective, interventional, single arm clinical study conducted on 150 patients of OCD. Detailed history and clinical examination was done at baseline, and all enrolled patients underwent patch test with the Indian Standard Battery of allergens. Eczema severity was assessed by the Investigator's Global Assessment (IGA) scale, SCORing Atopic Dermatitis (SCORAD) index, and patient-oriented eczema measure (POEM). Change in quality of life was assessed by using the Dermatology Life Quality Index (DLQI). After baseline assessments, they were prescribed halometasone 0.05% ointment and were followed up after 4 weeks, and efficacy variables were evaluated. Results: At follow-up, 19 patients were lost, and data of 131 patients were analyzed. After 4 weeks of halometasone therapy, there was statistically significant (P < 0.001) improvement in SCORAD index, IGA, POEM, and DLQI. Considering improvement in IGA as treatment success criteria, treatment was found to be successful in 87.8%. Subgroup analysis revealed no significant difference in effect of halometasone in allergic and irritant OCD. Conclusions: Halometasone is efficacious with a good safety profile in patients with OCD, and there is no significant difference in efficacy of the drug in allergic and irritant OCD. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have suggested that nutritional intake is related to allergic diseases. Although conflicting results exist, fat intake is often associated with allergic diseases. We investigated the relationship between allergic diseases and nutritional intake after adjusting for various demographic and socioeconomic factors in a large, representative sample of Korean children. Methods: A total of 3,040 participants, aged 4 to 13 years old, were enrolled in the present study from the Korean National Health and Nutrition Examination Survey (KNHANES), 2010–2012. Nutritional intake data, including total calories, protein, fat, carbohydrate, vitamin A, vitamin C, thiamine, riboflavin, and niacin, were retrieved from the survey using the complete 24-hour recall method. The associations between each nutritional factor and allergic rhinitis/asthma/atopic dermatitis were analyzed using simple and multiple logistic regression analyses with complex sampling. Age, sex, body mass index (BMI), number of household members, income level, and region of residence were adjusted for as covariates. Results: Of the participants, 22.1%, 6.0%, and 15.5% suffered from allergic rhinitis, asthma, and atopic dermatitis, respectively. Allergic rhinitis was significantly correlated with high-fat and low-carbohydrate diets. The adjusted odds ratio (AOR) was 1.25 (95% CIs = 1.06–1.46, P = 0.007) for fat intake, denoting a 10% increase. Carbohydrate intake (10% increase) was negatively related to allergic rhinitis with an AOR of 0.84 (95% CIs = 0.74–0.95, P = 0.004). No other significant relationships were found between the retrieved nutritional factors and either asthma or atopic dermatitis. Conclusion: Allergic rhinitis was related to high-fat and low-carbohydrate diets. Although the underlying mechanisms and causal relationships remain elusive, the present study provides reliable evidence regarding the associations between nutritional factors and allergic rhinitis by considering numerous factors within a large and representative population. [ABSTRACT FROM AUTHOR]

Background: Human-associated bacterial communities on the skin, skin microbiome, likely play a central role in development of immunity and protection from pathogens. In atopic patients, the skin bacterial diversity is smaller than in healthy subjects. Objective: To review treatment strategies for atopic dermatitis in Canada, taking the skin microbiome concept into account. Methods: An expert panel of 8 Canadian dermatologists explored the role of skin microbiome in clinical dermatology, specifically looking at atopic dermatitis. Results: The panel reached consensus on the following: (1) In atopic patients, the skin microbiome of lesional atopic skin is different from nonlesional skin in adjacent areas. (2) Worsening atopic dermatitis and smaller bacterial diversity are strongly associated. (3) Application of emollients containing antioxidant and antibacterial components may increase microbiome diversity in atopic skin. Conclusion: The skin microbiome may be the next frontier in preventive health and may impact the approach to atopic dermatitis treatment. [ABSTRACT FROM AUTHOR]

Background The Atopic Dermatitis Antecubital Severity ( ADAS) score is a new objective scale for the assessment of the severity of atopic dermatitis ( AD). It is calculated by multiplying the intensity of inflammatory signs by the size of an antecubital eczema lesion. Aim To test the validity, reliability, and sensitivity to changes of the ADAS score compared with those of the Eczema Area and Severity Index ( EASI) score. Methods Forty patients with AD were enrolled and treated with a moisturizer. At baseline, and in weeks 1 and 2, two independent evaluators measured the ADAS score, the EASI score, and the investigator's global assessment score rated on a six-point scale. Results The ADAS score showed a higher validity than the EASI score. The superiority of the ADAS to the EASI was prominent in mild AD. Inter-evaluator reliability was excellent in both the ADAS score and the EASI. The sensitivity to changes was higher in the ADAS score than in the EASI score. Conclusions The ADAS score may be used as a simple scoring system with good validity, reliability, and sensitivity to changes, especially in patients with mild-to-moderate AD. [ABSTRACT FROM AUTHOR]

A single square centimetre of the human skin can contain up to one billion microorganisms. These diverse communities of bacteria, fungi, mites and viruses can provide protection against disease, but can also exacerbate skin lesions, promote disease and delay wound healing. This review addresses the current knowledge surrounding the healthy skin microbiome and examines how different alterations to the skin microbial communities can contribute to disease. Current methodologies are considered, changes in microbial diversity and colonisation by specific microorganisms are discussed in the context of atopic dermatitis, psoriasis, acne vulgaris and chronic wounds. The recent impact of modern Westernised lifestyles on the human skin microbiome is also examined, as well as the potential benefits and pitfalls of novel therapeutic strategies. Further analysis of the human skin microbiome, and its interactions with the host immune system and other commensal microorganisms, will undoubtedly elucidate molecular mechanisms for disease and reveal gateways for novel therapeutic treatment strategies. [ABSTRACT FROM AUTHOR]

Background There is limited information on clinical manifestations of atopic eczema ( AE) and non- AE in teenagers. Objectives To describe the characteristics of adolescent eczema in the general population and to identify potential differences between AE and non- AE in teenagers. Methods Overall, 3108 teenagers were included from the population-based BAMSE cohort and 2529 of these teenagers provided blood samples for analysis of specific IgE. At age 16 years, the teenagers answered questionnaires regarding the symptoms of eczema, asthma and rhinitis for the previous year. Results The prevalence of eczema in adolescence was 9·6% ( n = 297). More girls than boys had eczema (12·5% vs. 6·5%; P < 0·001). The age at onset was usually within the first 2 years of life (48·8%), but onset in adolescence was also common (25·6%). Eczema was mild in 72·7% of cases, moderate in 16·8% and severe in 10·4%. Body folds were most frequently affected (73·4%). More than half of the teenagers with eczema had AE (59%). The teenagers with AE had more severe and more chronic eczema. Onset in infancy was most common in AE and onset in adolescence was most common in non- AE. There were no major differences in location or seasonal variance between AE and non- AE in adolescence. Conclusions AE is more common than non- AE among teenagers. More than one in four teenagers with eczema has moderate-to-severe disease. Onset in adolescence is common, especially for non- AE. AE in adolescence has an earlier onset and is more chronic and more severe than non- AE. [ABSTRACT FROM AUTHOR]

Background Patients’ high adherence to medication is indispensable for the management of skin diseases including atopic dermatitis. We previously showed poor medication adherence in Japanese dermatological patients. Objective This study was conducted to determine the level of adherence to oral or topical medication in Japanese patients with atopic dermatitis, attempting to characterize the socioeconomic status of those patients with poor adherence. Methods A web questionnaire survey on demographic data as well as adherence level was conducted on patients registered in the monitoring system. Adherence level was assessed with Morisky Medication Adherence Scale-8 (MMAS-8). Among a total of 3096 respondents with dermatological disorders, data of 1327 subjects with atopic dermatitis were extracted and analyzed. Results More than 80% of subjects felt that both oral and topical medications were safe and efficacious, while less than 60% of them were satisfied with their treatment. Levels of adherence to oral and topical treatments were evaluated with MMAS-8, giving scores of 4.6 and 4.2, respectively. Demographic factors such as gender, marital status, state of employment, alcohol consumption, frequency of hospital visits, and experience of drug effectiveness had a significant impact on the degree of adherence to treatment. Conclusion Medication adherence level in Japanese subjects with atopic dermatitis was relatively low compared with that of other chronic diseases. Our survey has characterized patients with poor adherence, who are good targets for interventions to maximize potentially limited healthcare resources. [ABSTRACT FROM AUTHOR]

Interdigital psoriasis of the feet ('psoriasis alba') is a rare form of inverse psoriasis. We conducted a cross-sectional study of the prevalence of interdigital psoriasis in mild, moderate, and severe psoriasis, compared to atopic dermatitis and normal controls. Data were collected during 2010-2013 from 232 psoriatic patients, 190 patients with atopic dermatitis, and 202 normal controls. The psoriatic and atopic dermatitis patients were from the dermatology department and outpatient clinic of the Hadassah-Hebrew University Medical Center in Jerusalem, Israel. The normal controls were healthy workers and volunteers from Hadassah Hospital who were not aware of any dermatological disease and had never consulted a general practitioner or dermatologist for skin problems of the feet. Our study revealed a prevalence of 2.6% of interdigital psoriasis of the feet in psoriatic patients, especially in men, and none in atopic dermatitis and normal controls. Three of the six affected patients with interdigital psoriasis of the feet complained of itching, both feet were involved in four patients, while two presented with additional palmoplantar psoriasis. The hematoxylin and eosin histopathological findings were in line with those found in inverse psoriasis. Dermatologists should be aware of this entity and treat it correctly. The diagnosis should be considered in psoriatic patients presenting with whitish plaque or patches in the toe-webs, in whom the fungal test is negative and are not responding to antimycotic treatment. [ABSTRACT FROM AUTHOR]

Topical corticosteroids are used frequently in dermatology and atopic dermatitis without significant adverse effects. Though ocular diseases such as glaucoma and cataracts are known complications of systemic corticosteroids, the role of topical corticosteroids is limited to case reports. This review assesses the literature regarding topical steroids and their role in ocular diseases. There is evidence of harm to vision when potent topical corticosteroids are inappropriately used for prolonged periods to periorbital sites. There is no evidence to date that weak TCS to the face or potent TCS to areas other than the eyes results in ocular complications. Further research trials are required in this area. [ABSTRACT FROM AUTHOR]

Atopic dermatitis ( AD) is a debilitating disease that significantly alters the quality of life for one in four children and one in 10 adults. Current management of AD utilizes combinations of treatments to symptomatically alleviate disease by suppressing the inflammatory response and restoring barrier function in the skin, reducing disease exacerbation and flare, and preventing secondary skin infections. Resolution is temporary and long-term usage of these treatments can be associated with significant side-effects. Antibody therapies previously approved for inflammatory diseases have been opportunistically evaluated in patients with atopic dermatitis; however, they often failed to demonstrate a significant clinical benefit. Monoclonal antibodies currently in development offer hope to those individuals suffering from the disease by specifically targeting immune and molecular pathways important for the pathogenesis of atopic dermatitis. Here, we review the underlying biological pathways and the state of the art in therapeutics in AD. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated human manganese superoxide dismutase (hMnSOD) autoallergy in individuals with atopic dermatitis (AD). Topics explored include the clinical characteristics of AD patients recruited for the study, results of the skin prick tests and atopy patch tests performed, and the recorded positive reactions to patch tests involving nickel sulfate and potassium dichromate.

Managing a pet's chronic dermatologic conditions can be frustrating for both clients and clinicians, but there are steps to making the process easier for everyone. Avoid the following seven mistakes sometimes made in managing dermatology cases and you will find the process considerably easier in the future. [ABSTRACT FROM AUTHOR]

The article focuses on effectiveness of Amerchol L101, a preparation of lanolin alcohols, and tested children and adolescents, particularly in those with atopic dermatitis. It mentions Information Network of Departments of Dermatology (IVDK) data for cross-reactivity between the two derivatives, and associations with patients' profiles. It also mentions positive patch test reactions than lanolin alcohols in aimed testing and the atopic eczema.

The article comments on the research study "Use of the hCONSORT criteria as a reporting standard for herbal interventions for common dermatoses: a systematic review," by J. Ornelas et al., published in the journal. Complementary alternative medicine (CAM) seeks provide health maintenance, illness prevention and non-invasive illness treatment as part of an integrated package.

Background: Results of preventative emollient therapy on atopic dermatitis and food allergy trials are inconsistent. In addition to the ingredients considered beneficial, the moisturizers may contain potentially harmful haptens. This study aimed to assess the prevalence of haptens in moisturizers used in studies to prevent atopic dermatitis or food allergy and assess their correlations to the trial results. Methods: A systematic search of studies investigating the role of emollient usage in preventing atopic dermatitis or food allergy in infants was performed from inception to December 2020. Haptens were identified based on the nine common patch test series (European, American, and Australian). Results: 12 clinical trial studies were included in the review. In total, 16 different emollients were applied as an intervention. The vast majority (75%) of preparations contained at least one hapten from which several substances pose high allergic or irritant potential. Quantitative data synthesis of the findings regarding food allergy and atopic dermatitis prevention was not possible due to the significant heterogeneity of preparations used. Conclusions: Careful selection of emollient should consider the absence of potentially harmful ingredients, particularly when used in youngest children. Chronic skin exposure to haptens promotes the development of allergic contact dermatitis and moreover, via deterioration of the skin barrier and subclinical inflammation, may facilitate epicutaneous sensitization and promote atopic dermatitis; however further research is needed to validate our suppositions. [ABSTRACT FROM AUTHOR]

Introduction: Atopic dermatitis and different constellations and the severity of symptoms that not meet the criteria for this diagnosis are a common skin disturbances. An important component of the treatment of these diseases and the proper care of sensitive and dry skin is local dermocosmetics use. Aim: To assess the frequency of skin disturbances and the effect and satisfaction with Atoperal products use as well as the source of information about these products. Material and methods: A questionnaire survey about the type of skin disturbances, the subjective assessment of the effect and satisfaction with Atoperal products use and source of information about these products was performed by 787 general practitioners, internists, pediatricians, dermatologists, allergists and pulmonologists and 252 pharmacists in a group of 51 085 subjects with skin disturbances. Results: In the group interviewed by doctors, the most common skin problem was atopic dermatitis (52.5%) and in the group interviewed by pharmacists, pruritus (70.0%). In both groups, respondents after Atoperal products use most frequently reported improving of the skin hydration and greasiness of the skin and reduction of itching. In both groups, over 90.0% of respondents were satisfied or very satisfied with Atoperal products use. In the group surveyed by doctors, 75.5% of respondents obtained information about these products from doctors and 17.4% from pharmacists, while in the group surveyed by pharmacists, 48.9% from pharmacists and 36.1% from doctors. Conclusions: Atopic dermatitis was most frequently diagnosed in a group surveyed by doctors. The main skin disturbance that occurred in a group surveyed by pharmacists was skin pruritus. The main effect of Atoperal products use, independent of the place of the survey, included improving of skin hydration and greasiness of the skin and reduction of itching. In a study population, there was a high level of satisfaction from the use of Atoperal products. Doctors and pharmacists were the main sources of information about Atoperal products depending on the place of the survey. [ABSTRACT FROM AUTHOR]

Although placebo contributes to the effects of treatment for various symptoms and conditions, its effect on itch has rarely been investigated. In this meta-analysis, the magnitude of the placebo effect on itch was systematically investigated in clinical trials including patients with chronic itch due to atopic dermatitis, psoriasis, or chronic idiopathic urticaria. From searches in four databases, 34 articles were included in the quantitative analyses. Placebo treatment significantly decreased itch (1.3 out of 10, 95% confidence interval 1.02-1.61) compared with baseline itch (effect size 0.55), indicating that placebo effects have a considerable role in these patients' treatment. [ABSTRACT FROM AUTHOR]

Background: Dermatological patients invariably suffer one or the other psychological problems which may escalate to the extent of a mental disorder. One of the most common dermatological disorders is atopic dermatitis (AD), but the literature has limited data on gender differences for psychiatric morbidity in such patients. Aims: To evaluate and compare gender differences in the prevalence of depression and anxiety in AD. Materials and Methods: This cross‑sectional study with consecutive sampling was done in an outpatient clinic of Dermatology at a Tertiary Care Center. AD subjects giving informed consent were evaluated on a brief semi‑structured performa for collecting demographic and clinical information. Primary Care Evaluation of Mental Disorders (PRIME‑MD) was used to assess the presence of psychiatric symptoms in these patients. Descriptive analysis was done for the socio‑demographic profile and independent sample t‑test, Chi‑square and Cramer's V test was carried out to find in‑between group differences for males and females. Results: A total of 81 patients were included in the final analysis (males = 36, females = 45) with no significant difference in mean age between male and female subjects (36.14 ± 17.62 and 33.98 ± 14.49 years, respectively; P = 0.54). When including moderate to severe grade of depression or anxiety, the current study found prevalence rates of 15% and 12% respectively. Females had significantly more anxiety and depression scores than males (P = 0.04 and P = 0.03 respectively). Conclusions: There is a female preponderance of depression and anxiety disorder in AD patients. [ABSTRACT FROM AUTHOR]

Only few population-based data exist on the association of food hypersensitivity reactions and atopic diseases. The objective of this study was to evaluate the dependence between the occurrence of food hypersensitivity reactions and other atopic diseases and parameters. Complete dermatological and allergological examination was performed. Statistical evaluation of the relations between the occurrence of food hypersensitivity reactions and the occurrence of asthma bronchiale, rhinitis, duration of atopic dermatitis, family history and onset of atopic dermatitis was performed. Two hundred and thirty-five patients were examined – 75 men and 160 women, average age 26.2 years (SD = 9.5). Patients suffering from food hypersensitivity reactions, in general, suffer significantly more often from rhinitis and from persistent eczematic lesions; the dependence was confirmed in patients with hypersensitivity reactions to nuts, kiwi, fishes and apple. Atopic march was confirmed in patients suffering from atopic dermatitis and from food hypersensitivity reactions. [ABSTRACT FROM PUBLISHER]

Background: Mycophenolate mofetil (MMF) is increasingly being used by dermatologists to treat various skin conditions, but limited evidence exists regarding its efficacy. Objective: To evaluate safety and efficacy of MMF in the treatment of dermatological conditions. Methods: A retrospective chart review of all the dermatology patients treated with MMF between October 1999 and July 2008 at a university-based teaching hospital in Australia. Results: Sixty-nine patients included 43 females (62%) and 26 males. Nineteen patients (27%) achieved complete remission (CR) and 14 (20%) had no response to therapy. The average duration of treatment was 18.4 months and the mean daily dose was 2 g. Thirty-two patients (47%) experienced side effects, though most were mild. Factors influencing response to MMF were studied, and older age ( p = 0.005), diagnosis ( p = 0.008) and duration of treatment ( p = 0.02) were found significant. In a multivariate analysis, only the diagnosis remained statistically significant. There was a differential response to MMF between the various dermatological disorders studied. Complete response was achieved in 56%, 53% and 46% of the patients with atopic dermatitis (AD), immunobullous disorders and neutrophilic dermatoses, respectively, while none of the patients with psoriasis achieved CR. Conclusion: Our study shows that MMF is more effective in AD and immunobullous disorders than in psoriasis and pyoderma gangrenosum. [ABSTRACT FROM AUTHOR]

Managing a pet's chronic dermatologic conditions can be frustrating for both clients and clinicians, but there are steps to making the process easier for everyone. Avoid the following seven mistakes sometimes made in managing dermatology cases and you will find the process considerably easier in the future. [ABSTRACT FROM AUTHOR]

Core outcome sets (COSs) are consensus-derived minimum sets of outcomes to be assessed in a specific situation. COSs are being increasingly developed to limit outcome-reporting bias, allow comparisons across trials, and strengthen clinical decision making. Despite the increasing interest in outcomes research, methods to develop COSs have not yet been standardized. The aim of this paper is to present the Harmonizing Outcomes Measures for Eczema (HOME) roadmap for the development and implementation of COSs, which was developed on the basis of our experience in the standardization of outcome measurements for atopic eczema. Following the establishment of a panel representing all relevant stakeholders and a research team experienced in outcomes research, the scope and setting of the core set should be defined. The next steps are the definition of a core set of outcome domains such as symptoms or quality of life, followed by the identification or development and validation of appropriate outcome measurement instruments to measure these core domains. Finally, the consented COS needs to be disseminated, implemented, and reviewed. We believe that the HOME roadmap is a useful methodological framework to develop COSs in dermatology, with the ultimate goal of better decision making and promoting patient-centered health care. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin disease in children characterized by dermatitis and pruritus. MicroRNAs (miRNAs) have been shown as great potential biomarkers for disease fingerprints to predict prognostics. We aimed to identify miRNA signature from serum and urine for the prognosis of AD patient by genome-wide miRNA profiling analysis. Methods: Serum and urine from 30 children with AD and 28 healthy children were collected and their genome-wide miRNA expression profiles were measured by TaqMan-based array and confirmed by quantitative real-time PCR. Inflammatory factors in serum were detected by Antibody Array System. Results: miR-203 and miR-483-5p were significantly up-regulated in serum of children with AD compared with healthy children. The level of miR-483-5p in serum was significantly associated with other atopic conditions, such as rhinitis and/or asthma. However, miR-203 was markedly decreased in urine of children with AD compared with healthy children. Down-regulated miR-203 in urine was significant associated with abnormal level of serum IgE in AD patients. 7 inflammatory factors in serum were altered in children with AD compared with healthy children. Up-regulated miR-203 in serum was significantly associated with increased sTNFRI and sTNFRII. Conclusions: Up-regulated miR-483-5p in serum may be indicative of other atopic conditions in children with AD. Down-regulated miR-203 in urine may serve as a biomarker for the severity of inflammation in children with AD. [ABSTRACT FROM AUTHOR]

The present study was conducted with the aim to investigate the immuno-modulatory and histological stabilization effects of nanocarrier–based transcutaneous co-delivery of hydrocortisone (HC) and hydroxytyrosol (HT). In this investigation, the clinical and pharmacological efficacies of nanoparticle (NP)-based formulation to alleviate 2,4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis (AD) was explored by using an NC/Nga mouse model. Ex vivo visual examination of AD induction in experimental mice indicated remarkable control of NP-based formulations in reducing pathological severity of AD-like skin lesions. Therapeutic effectiveness of NP-based formulations was also evaluated by comparing skin thickness of AD-induced NP-treated mice (456±27 µm) with that of atopic mice (916±37 µm). Analysis of the immuno-spectrum of AD also revealed the dominance of NP-based formulations in restraining immunoglobulin-E (IgE), histamine, prostaglandin-E2 (PGE2), vascular endothelial growth factor-α (VEGF-α), and T-helper cells (TH1/TH2) producing cytokines in serum and skin biopsies of tested mice. These anti-AD data were further supported by histological findings that revealed alleviated pathological features, including collagen fiber deposition, fibroblasts infiltration, and fragmentation of elastic fibers in experimental mice. Thus, NP-mediated transcutaneous co-delivery of HC and HT can be considered as a promising therapy for managing immunological and histological spectra associated with AD. [ABSTRACT FROM AUTHOR]

Aims A discussion on the reasons educational interventions about eczema, by nurses, are successful, with the subsequent development of a theoretical framework to guide nurses to become effective patient educators. Background Effective child and parent education is the key to successful self-management of eczema. When diagnosed, children and parents should learn to understand the condition through clear explanations, seeing treatment demonstrations and have ongoing support to learn practical skills to control eczema. Dermatology nurses provide these services, but no one has proposed a framework of the concepts underpinning their successful eczema educational interventions. Design A discussion paper. Data Sources A literature search of online databases was undertaken utilizing terms 'eczema OR atopic dermatitis', 'education', 'parent', 'nurs*', 'framework', 'knowledge', motivation', in Scopus, CINAHL, Web of Science, Medline and Pubmed. Limits were English language and 2003-2013. Implications for Nursing The framework can inform discussion on child and parent education, provide a scaffold for future research and guide non-specialist nurses, internationally, in providing consistent patient education about eczema. Conclusion Founded on an understanding of knowledge, the framework utilizes essential elements of cognitive psychology and social cognitive theory leading to successful self-management of eczema. This framework may prove useful as a basis for future research in child and parent education, globally, in the healthcare community. A framework has been created to help nurses understand the essential elements of the learning processes at the foundation of effective child and parent education. The framework serves to explain the improved outcomes reported in previous nurse-led eczema educational interventions. [ABSTRACT FROM AUTHOR]

Prevalence of atopic dermatitis (AD) has been studied mainly in infants and young children. Surveys on AD in adolescents and adults are based largely on self-reported questionnaires and cohorts of different ages, precluding meaningful comparisons and conclusions. We aimed to provide data on the prevalence of AD and its relation to demographic factors in adolescents. A large database of youths eligible for military service was searched for subjects one year before service at the age of 18. Parameters included country of origin, age of immigration to Israel, education, and presence and severity of AD. AD rose 3-fold for both genders over the study period 1998-2008 (0.4-1%). The increase was higher in females (0.5-1.2%) than males (0.3-0.9%). Mild and moderate disease was higher in females than males. Severe AD was rarely noted. Russian (OR 1.47), Asian (OR 1.15) and Euro-American (OR 1.26) origins had highest association with AD. Immigrants after age 7 had higher association with AD than Israeli-born subjects and immigrants before age 7 (OR 1.88 vs. 1.33). More years of education was significantly associated with high prevalence of AD. The increased prevalence of AD during the 11-year period underscores the need for awareness of the condition in this population, in which AD affects health and quality of life. [ABSTRACT FROM AUTHOR]

Dermal exposure to alkaline agents may lead to skin barrier damage and irritant contact dermatitis. The objective of this study was to investigate the effects of cumulative exposure to 0.5% sodium lauryl sulphate (SLS) and 0.15% NaOH on the barrier function and natural moisturising factor (NMF) levels in atopic dermatitis and healthy volunteers with known filaggrin genotype. The skin response was monitored by measurement of erythema and transepidermal water loss. The stratum corneum NMF levels were determined by high-performance liquid chromatography. Repeated exposure to 0.5% SLS and/or 0.15% NaOH in atopic dermatitis resulted in more severe impairment of the skin barrier function. Cumulative exposure to the irritants reduced significantly NMF in both the atopic and healthy controls group. The pronounced decrease of NMF after repeated single and sequential irritant exposure may be a pathogenetically relevant factor for development of chronic irritant contact dermatitis in both healthy and atopic individuals. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease resulting from excessive stimulation of immune cells. Traditionally, reactive oxygen species (ROS) have been implicated in the progression of inflammatory diseases, but several opposing observations suggest the protective role of ROS in inflammatory disease. Recently, we demonstrated ROS prevented imiquimod-induced psoriatic dermatitis through enhancing regulatory T cell function. Thus, we hypothesized AD might also be attenuated in elevated levels of ROS through tissue hyperoxygenation, such as by hyperbaric oxygen therapy (HBOT) or applying an oxygen-carrying chemical, perfluorodecalin (PFD). Elevated levels of ROS in the skin have been demonstrated directly by staining with dihydroethidum as well as indirectly by immunohistochemistry (IHC) for indoleamine 2,3-dioxygenase (IDO). A murine model of AD was developed by repeated application of a chemical irritant (1% 2,4-dinitrochlorobenzene) and house dust mite (Dermatophagoide farinae) extract on one ear of BALB/c mice. The results showed treatment with HBOT or PFD significantly attenuated AD, comparably with 0.1% prednicarbate without any signs of side effects, such as telangiectasia. The expressions of interleukin-17A and interferon-γ were also decreased in the AD lesions by treatment with HBOT or PFD. Enhanced expression of IDO and reduced level of hypoxia-inducible factor-1α, in association with increased frequency of FoxP3+ regulatory T cells in the AD lesions, might be involved in the underlying mechanism of oxygen therapy. Taken together, it was suggested that tissue hyperoxygenation, by HBOT or treatment with PFD, might attenuate AD through enhancing skin ROS level. [ABSTRACT FROM AUTHOR]

Background: Options are limited for patients with atopic dermatitis (AD) who do not respond to topical treatments. Antifolate therapy with systemic methotrexate improves the disease, but is associated with adverse effects. The investigational antifolate LD-aminopterin may offer improved safety. It is not known how antifolate dose and dosing frequency affect efficacy in AD, but a primary mechanism is thought to involve the antifolate-mediated accumulation of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). However, recent in vitro studies indicate that AICAR increases then decreases as a function of antifolate concentration. To address this issue and understand how dosing affects antifolate efficacy in AD, we examined the efficacy and safety of different oral doses and schedules of LD-aminopterin in the canine model of AD. Methods and Findings: This was a multi-center, double-blind trial involving 75 subjects with canine AD randomized to receive up to 12 weeks of placebo, once-weekly (0.007, 0.014, 0.021 mg/kg) or twice-weekly (0.007 mg/kg) LD-aminopterin. The primary efficacy outcome was the Global Score (GS), a composite of validated measures of disease severity and itch. GS improved in all once-weekly cohorts, with 0.014 mg/kg being optimal and significant (43%, P<0.01). The majority of improvement was seen by 8 weeks. In contrast, GS in the twice-weekly cohort was similar to placebo and worse than all once-weekly cohorts. Adverse events were similar across all treated cohorts and placebo. Conclusions: Once-weekly LD-aminopterin was safe and efficacious in canine AD. Twice-weekly dosing negated efficacy despite having the same daily and weekly dose as effective once-weekly regimens. Optimal dosing in this homologue of human AD correlated with the concentration-selective accumulation of AICAR in vitro, consistent with AICAR mediating LD-aminopterin efficacy in AD. [ABSTRACT FROM AUTHOR]

In the skin lesions of atopic dermatitis (AD), keratinocytes release large quantities of thymic stromal lymphopoietin (TSLP), causing unfavorable inflammation along with skin damage. Nevertheless, how TSLP influences keratinocytes themselves is still unknown. In this study, we showed that ΔNp63, a p53-homologue, predominantly expressed in keratinocytes regulated the receptor complex of TSLP, which determines susceptibility to self-derived TSLP. Expression of TSLP receptors in skin tissues and keratinocytes was assessed by immunohistochemistry and quantitative RT-PCR, and in vitro studies were also performed to examine the functional relevance of ΔNp63 in the expression of TSLP receptors and the constituting autocrine and/or paracrine pathway of TSLP under the condition of stimuli to innate receptors sensing cell damage. The results showed that normal keratinocytes in the upper epidermis preferentially expressed TSLP receptors and conversely lacked ΔNp63, which has an inhibitory effect on the expression of TSLP receptors. Interestingly, the epidermis of AD lesions was found to abundantly contain keratinocytes with low or undetectable levels of ΔNp63 (ΔNp63lo/-). Moreover, in the absence of ΔNp63, keratinocytes readily presented TSLP and other cytokines by stimuli through Toll-like receptor 3 (TLR3). Together with the evidence that extrinsic TSLP itself augments TSLP production by keratinocytes without ΔNp63, the results indicate that ΔNp63lo/- keratinocytes generate TSLP through a putative autocrine and/or paracrine pathway upon TLR3 stimulation within AD lesions, since moieties of damaged cells and pathogens stimulate TLR3. [ABSTRACT FROM AUTHOR]

This review focuses on treatment targets for the most common inflammatory skin diseases, eczema and psoriasis with an emphasis on cytokines expressed in the uppermost layer of the skin which is easily accessible for diagnostic and therapeutic approaches. Recently, a significant body of research has highlighted the influence of the skin barrier and the patients’ microbiome on skin inflammatory responses and we will comment on their impact on mediator regulation. Itch is a prominent dermatology symptom which is influenced by cytokines and can via itch–scratch cycle impact on the skin barrier and mediator expression associated with damage. Taking the contribution of pruritus and superficial skin damage into account, we address cytokines as targets for stratified treatment approaches in subgroups of eczema and psoriasis. [ABSTRACT FROM AUTHOR]