Epidemiology of adult patients with atopic dermatitis in AWARE 1: A second international survey.

Background: There are gaps in our understanding of the epidemiology of atopic dermatitis (AD) in adults. Objective: To evaluate the prevalence and severity of AD in adults from countries/regions within Asia, Eurasia, Latin America, Middle East, and Russia. Methods: This international, web-based survey was performed in Argentina, Brazil, China, Colombia, Egypt, Hong Kong, Israel, Malaysia, Mexico, Russia, Kingdom of Saudi Arabia (KSA), Singapore, Taiwan, Thailand, Turkey, and United Arab Emirates. Questionnaires were sent to adult members of online respondent panels for determination of AD and assessment of severity. A diagnosis of AD required respondents to meet the modified United Kingdom (UK) Working Party criteria and to self-report they had a physician diagnosis of AD. Severity of AD was determined using Patient-Oriented Scoring of Atopic Dermatitis (PO-SCORAD), Patient-Oriented Eczema Measure (POEM), and Patient Global Assessment (PGA). Results: Among respondents by country/region the prevalence of AD ranged from 3.4% in Israel to 33.7% in Thailand. The prevalence was generally higher in females versus males. Severity varied by scale, although regardless of scale the proportion of respondents with mild and moderate disease was higher than severe disease. PGA consistently resulted in the lowest proportion of severe AD (range 2.4% China - 10.8% Turkey) relative to PO-SCORAD (range 13.4% China - 41.6% KSA) and POEM (range 5.1% China - 16.6% Israel). Conclusions: This survey highlights the importance of AD in adults, with high prevalence and high morbidity among respondents and emphasizes that AD is not just a disease of childhood-there is disease persistence and chronicity in adults.

Physician Perception of Disease Severity and Treatment Outcomes for Children and Adolescents with Atopic Dermatitis in Emerging Economies.

INTRODUCTION: Pediatric atopic dermatitis (AD) leads to a considerable reduction in quality of life for patients and their families. Therapeutic options for pediatric patients with moderate-to-severe disease are limited and treatment is challenging. As little is understood about physician perceptions of pediatric AD in countries with emerging healthcare, we conducted a questionnaire-based study to identify treatment patterns and gaps. METHODS: Physicians treating children (aged 6-11 years) and adolescents (aged 12-17 years) with AD in 11 emerging economy countries were interviewed regarding their beliefs and behaviors relating to the disease. Physicians gave an initial assessment of patient disease severity and control, which was then compared with patient records and pre-specified criteria to assess concordance and discordance between physician perception and recorded patient presentation. RESULTS: A total of 574 physicians completed the study, with an assessment of 1719 patients. Only 51% of patients whose disease criteria matched 'severe disease' to pre-specified criteria and SCORing Atopic Dermatitis scores (SCORAD) were also initially identified by physicians as having severe disease. Patients with moderate-to-severe disease experienced flares for an average of 263 days in the preceding year. Ninety and 74% of patients experienced chronic flares and unpredictable flares, respectively. Control of flares could only be achieved within 7 days in 14% (n = 153) of patients. Most physicians listed elimination of skin symptoms as their primary treatment goal, and for moderate and severe cases, 59% and 33% of physicians reported that they were able to achieve this respectively. Nearly 24% and 40% of physicians were slightly dissatisfied with the treatment options for moderate disease and severe disease and severe disease, respectively. CONCLUSIONS: AD severity of children (aged 6-11 years) and adolescents (aged 12-17 years) appears to be underestimated by physicians in emerging economy countries. Practical, easy-to-use, and validated objective measures for assessment of disease severity and control, as well as effective use of novel therapies, are essential to ensure that patients are appropriately managed.

Atopic dermatitis (AD) is a common childhood disease that occurs in up to 30% of individuals under 18 years of age. Although most forms are mild, more severe disease forms of AD including symptoms such as pruritus, xerosis, lichenification, and excoriation of the skin can cause significant problems, such as lack of sleep, lack of productivity, poor self-image, and mental health disorders among patients. It also places a burden on patients' families, which affects home, school, and work life. In children with moderate-to-severe disease, treatment options are limited especially since doctors may not be keen to prescribe high-dose treatments to children such as potent and super-potent topical corticoid steroids and progress to systemic therapies. Relatively little is understood about how doctors determine whether the disease is mild, moderate, or severe and what they consider to be the best treatment options for patients. Therefore, we conducted a series of interviews with doctors in 11 countries with emerging healthcare to better understand their beliefs and behaviors about treating childhood AD. Our results indicated that doctors tended to underestimate the severity of a patient's disease. Additionally, 59% of doctors felt that they were able to successfully eliminate itching and skin syndrome frequently (that is, in 70% or more of their patients) in patients with moderate disease and 33% of doctors for their patients with severe disease. These results suggest that there are many unmet needs in the treatment of children and adolescents with AD in emerging economies, whose treatment could be further optimized. Improving how doctors measure the severity of a patient's disease should help them select the most appropriate and effective treatments for their patients.

Single-cell analysis of human skin identifies CD14+ type 3 dendritic cells co-producing IL1B and IL23A in psoriasis.

Inflammatory skin diseases including atopic dermatitis (AD) and psoriasis (PSO) are underpinned by dendritic cell (DC)-mediated T cell responses. Currently, the heterogeneous human cutaneous DC population is incompletely characterized, and its contribution to these diseases remains unclear. Here, we performed index-sorted single-cell flow cytometry and RNA sequencing of lesional and nonlesional AD and PSO skin to identify macrophages and all DC subsets, including the newly described mature LAMP3+BIRC3+ DCs enriched in immunoregulatory molecules (mregDC) and CD14+ DC3. By integrating our indexed data with published skin datasets, we generated a myeloid cell universe of DC and macrophage subsets in healthy and diseased skin. Importantly, we found that CD14+ DC3s increased in PSO lesional skin and co-produced IL1B and IL23A, which are pathological in PSO. Our study comprehensively describes the molecular characteristics of macrophages and DC subsets in AD and PSO at single-cell resolution, and identifies CD14+ DC3s as potential promoters of inflammation in PSO.

Mixed Individual-Aggregate Data on All-Cause Mortality in Bullous Pemphigoid: A Meta-analysis.

Importance: The 1-year standardized mortality ratio (SMR) of bullous pemphigoid (BP) has been reported as 2.15 to 7.56 and lower in the US than in Europe. Objective: To estimate the worldwide 1-year SMR of BP. Data Sources: PubMed, Embase, Cochrane Library, Google Scholar, Lissa, and gray literature (eg, medRxiv) were screened for studies of BP published from inception to June 10, 2020, with review of reference lists. Study Selection: Retrospective and prospective studies reporting 1-year all-cause mortality rate in patients with BP and providing age statistics (eg, mean [SD]). Data Extraction and Synthesis: Two reviewers independently extracted the data. The 1-year SMR was computed in studies reporting 1-year mortality by combining information on age obtained from studies with aggregate data and individual data. Risk of representativity, misclassification, and attrition bias were assessed by a custom tool. Main Outcomes and Measures: The primary end point was the worldwide 1-year SMR. Secondary analysis included comparison of 1-year SMRs between continents in a meta-regression. Results: Three studies were performed in the US (n = 260), 1 in South America (n = 45), 16 in Asia (n = 1903), and 36 in Europe (n = 10 132) for a total of 56 unique studies and 12 340 unique patients included in the meta-analysis (mean [SD] age, 77.3 [12.7] years; 55.9% women). The mean (SD) patient age in the United States was 75.6 (13.7) years; in Asia, 73.8 (13.6) years; and in Europe, 78.1 (12.3) years. The worldwide 1-year SMR was estimated at 2.93 (95% CI, 2.59-3.28; I2 = 85.6%) for all 56 studies. The 1-year SMR in the US was 2.40 (95% CI, 0.89-3.90; I2 = 86.3%) for 3 studies; in Asia, 3.53 (95% CI, 2.85-4.20; I2 = 86.3%) for 16 studies; and in Europe, 2.77 (95% CI, 2.35-3.19; I2 = 86.3%) for 36 studies. After adjustment on the expected 1-year mortality rate, the European 1-year SMR did not differ significantly from the 1-year SMR in the United States (-0.48 vs Europe; 95% CI, -2.09 to 1.14; P = .56) and Asia (0.51 vs Europe; 95% CI, -0.56 to 1.58; P = .35). Risk of attrition bias was high (>10% censorship) in 16 studies (28.6%), low in 16 (28.6%), and unclear in 24 (42.9%). Only 4 studies (7.1%) had a sampling method guaranteeing the representativity of BP cases in a population. Conclusions and Relevance: Although heterogeneity was high and overall quality of follow-up was poor, this meta-analysis confirms the high mortality rate among patients with BP.

Atopic dermatitis microbiomes stratify into ecologic dermotypes enabling microbial virulence and disease severity.

BACKGROUND: Atopic dermatitis (AD) is a common skin disease affecting up to 20% of the global population, with significant clinical heterogeneity and limited information about molecular subtypes and actionable biomarkers. Although alterations in the skin microbiome have been described in subjects with AD during progression to flare state, the prognostic value of baseline microbiome configurations has not been explored. OBJECTIVE: Our aim was to identify microbial signatures on AD skin that are predictive of disease fate. METHODS: Nonlesional skin of patients with AD and healthy control subjects were sampled at 2 time points separated by at least 4 weeks. Using whole metagenome analysis of skin microbiomes of patients with AD and control subjects (n = 49 and 189 samples), we identified distinct microbiome configurations (dermotypes A and B). Blood was collected for immunophenotyping, and skin surface samples were analyzed for correlations with natural moisturizing factors and antimicrobial peptides. RESULTS: Dermotypes were robust and validated across 2 additional cohorts (63 individuals), with strong enrichment of subjects with AD in dermotype B. Dermotype B was characterized by reduced microbial richness, depletion of Cutibacterium acnes, Dermacoccus and Methylobacterium species, individual-specific outlier abundance of Staphylococcus species (eg, S epidermidis, S capitis, S aureus), and enrichment in metabolic pathways (eg, branched chain amino acids and arginine biosynthesis) and virulence genes (eg, ß-toxin, δ-toxin) that defined a pathogenic ecology. Skin surface and circulating host biomarkers exhibited a distinct microbial-associated signature that was further reflected in more severe itching, frequent flares, and increased disease severity in patients harboring the dermotype B microbiome. CONCLUSION: We report distinct clusters of microbial profiles that delineate the role of microbiome configurations in AD heterogeneity, highlight a mechanism for ongoing inflammation, and provide prognostic utility toward microbiome-based disease stratification.

Belinostat resolves skin barrier defects in atopic dermatitis by targeting the dysregulated miR-335:SOX6 axis.

BACKGROUND: Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Skin barrier defects contribute to disease initiation and development; however, underlying mechanisms remain elusive. OBJECTIVE: To understand the underlying cause of barrier defect, we investigated aberrant expression of specific microRNAs (miRNAs) in AD. Delineating the molecular mechanism of dysregulated miRNA network, we focused on identification of specific drugs that can modulate miRNA expression and repair the defective barrier in AD. METHODS: A screen for differentially expressed miRNAs between healthy skin and AD lesional skin resulted in the identification of miR-335 as the most consistently downregulated miRNA in AD. Using in silico prediction combined with experimental validation, we characterized downstream miR-335 targets and elucidated the molecular pathways by which this microRNA maintains epidermal homeostasis in healthy skin. RESULTS: miR-335 was identified as a potent inducer of keratinocyte differentiation; it exerts this effect by directly repressing SOX6. By recruiting SMARCA complex components, SOX6 suppresses epidermal differentiation and epigenetically silences critical genes involved in keratinocyte differentiation. In AD lesional skin, miR-335 expression is aberrantly lost. SOX6 is abnormally expressed throughout the epidermis, where it impairs skin barrier development. We demonstrate that miR-335 is epigenetically regulated by histone deacetylases; a screen for suitable histone deacetylase inhibitors identified belinostat as a candidate drug that can restore epidermal miR-335 expression and rescue the defective skin barrier in AD. CONCLUSION: Belinostat is of clinical significance not only as a candidate drug for AD treatment, but also as a potential means of stopping the atopic march and further progression of this systemic allergic disease.

Anti-BP180 NC16A IgG Titres as an Indicator of Disease Activity and Outcome in Asian Patients with Bullous Pemphigoid.

INTRODUCTION: Anti-BP180 IgG titres were observed to parallel disease activity in case series of bullous pemphigoid (BP). This study aimed to examine whether anti-BP180 titres are an indicator of disease severity, clinical course and outcome in Asian patients with BP. MATERIALS AND METHODS: This was a prospective observational study conducted between March 2005 and March 2008 in the Immunodermatology Clinic at the National Skin Centre, Singapore. Disease activity and anti-BP180 IgG titres were measured 4-weekly for 12 weeks and during disease flares and clinical remission. Associations between anti-BP180 titres and disease activity, disease flare, clinical remission and cumulative prednisolone dose were examined. RESULTS: Thirty-four patients with newly diagnosed BP were recruited. Median follow-up duration was 3 years. Notable correlations between disease activity and anti-BP180 titres were at baseline (r = 0.51, P = 0.002), and disease flare (r = 0.85, P <0.001). Lower titres at Week 12 were associated with greater likelihood of clinical remission (P = 0.036). Post hoc, patients with anti-BP180 titres above 87.5 U/mL at time of diagnosis who reached remission within 2 years of diagnosis received significantly higher cumulative doses (mg/kg) of prednisolone (median, 72.8; range, 56.5 to 127.1) than those with titres <87.5 U/mL (median, 44.6; range, 32.5 to 80.8); P = 0.025). CONCLUSION: Anti-BP180 titres may be a useful indicator of disease activity at time of diagnosis and at disease flare. Lower titres at Week 12 may predict greater likelihood of clinical remission. Titres above 87.5 U/mL at time of diagnosis may suggest the need for higher cumulative doses of prednisolone to achieve remission within 2 years.

A prospective study on the use of teledermatology in psychiatric patients with chronic skin diseases.

BACKGROUND: To compare the use of live interactive teledermatology versus conventional face-to-face consultation in long-term, institutionalised psychiatric patients with chronic skin diseases. METHODS: All institutionalised psychiatric patients at the Institute of Mental Health with follow-up appointments at the National Skin Centre were assessed for eligibility and invited to participate. Recruited patients were first seen by a dermatologist via videoconferencing, and then by another dermatologist in person, within 1 week. Clinical outcome measures were then assessed by a third independent dermatologist. The following outcome measures were assessed for each paired patient visit: inter-physician clinical assessment, diagnosis, management plan, adverse events and total patient turnaround time (PTAT) for each consultation. RESULTS: There were a total of 13 patients (mean age, 64.6 years; range 44-80) with 27 patient visits. All were male patients with chronic schizophrenia. The predominant skin condition was chronic eczema and its variants (62%), followed by cutaneous amyloidosis (23%) and psoriasis (15%). The level of complete and partial agreement between the teledermatology and face-to-face consultation was 100% for history-taking and physical examination and 96% for the investigations, diagnosis, management plan and the treatment prescribed. The PTAT for teledermatology was 23 min, compared to 240 min for face-to-face consultations. No adverse events were reported. CONCLUSION: Teledermatology was as effective as face-to-face consultation and reduced the PTAT by 90%, resulting in increased patient convenience, operational efficiency and reduced manpower need. Our study supports the safe and cost-effective use of teledermatology for the follow-up of chronic skin conditions in psychiatric patients.

Cost-effectiveness study of pediatric atopic dermatitis in Asia: atopiclair vs. regular emollient (AD-ATOP).

BACKGROUND: Atopic dermatitis (AD) is a highly prevalent, chronic relapsing condition in childhood with significant financial burden and impact on the quality of life of patients and caregivers. Proactive maintenance treatment with moisturizing agents is the mainstay AD therapy. OBJECTIVES: The aim of this study was to assess the cost-effectiveness of a non-steroidal barrier cream (Atopiclair), compared to regular emollient in pediatric patients with mild-to-moderate AD. METHODS: A Markov decision model was developed to evaluate the cost-effectiveness of Atopiclair versus regular emollient in 12 Asia-Pacific countries, grouped by income categories based on gross domestic product (GDP) per capita. Data was obtained from structured literature review, expert opinion, fee schedules, and findings from a 2012 survey of 12 Asia-Pacific countries. Analysis was performed a societal perspective. RESULTS: In the base case analysis, Atopiclair was cost-effective against regular emollient, with USD786, USD499, and USD289 in cost savings per year for high, middle, and low-income countries, respectively. Sensitivity analyses showed that Atopiclair remained cost-effective versus regular emollient. CONCLUSIONS: Modelling analysis showed that Atopiclair is a cost-effective treatment compared to regular emollient for mild-to-moderate pediatric AD in the countries included in the study.

Gram-positive antimicrobial activity of amino acid-based hydrogels.

Antimicrobial hydrogels are prepared based on the co-assembly of commercial Fmoc-phenylalanine and Fmoc-leucine, which act as the hydrogelator and antimicrobial building block, respectively. This co-assembled antimicrobial hydrogel is demonstrated to exhibit selective bactericidal activity for gram-positive bacteria while being biocompatible with normal mammalian cells, showing great potential as an antimicrobial coating for clinical anti-infective applications.

Atopic dirty neck or acquired atopic hyperpigmentation? An epidemiological and clinical study from the National Skin Centre in Singapore.

BACKGROUND: 'Atopic dirty neck' is a poorly understood acquired hyperpigmentation in patients with atopic dermatitis (AD). OBJECTIVE: To report a single-centre experience with synthesis of this entity's features. METHODS: All patients with AD with dirty neck seen over a 5-month period at the National Skin Centre were invited to participate. RESULTS: Out of 544 AD patients examined, 78 (14.3%) had acquired pigmentation of the neck. The majority had moderate-to-severe underlying eczema. Histopathology showed increased epidermal melanin and dermal melanophages, a thickened basement membrane and a dense superficial perivascular infiltrate. CONCLUSION: Acquired atopic hyperpigmentation has a high prevalence, particularly in adolescent Asian males. Clinico-pathological correlation suggests it results from both frictional melanosis and post-inflammatory hyperpigmentation. The rippled appearance and the onset in adolescence are probably due to accentuation of the juxta-clavicular beaded lines. Optimal control of eczema may improve and potentially prevent the development, which is of importance considering the psychosocial impact of the condition.

A retrospective review of the therapeutic response with remission in patients with newly diagnosed bullous pemphigoid.

We reviewed the clinical characteristics and therapeutic response in cases of newly diagnosed bullous pemphigoid at the National Skin Centre between June 2009 and December 2010. Most (76%, n = 68/90) achieved clinical remission within 6 months of commencement of therapy. Oral mucosal involvement was identified as a risk factor associated with a prolonged duration of treatment beyond 6 months.

Chronic leg ulcers in adult patients with rheumatological diseases - a 7-year retrospective review.

Chronic leg ulcers in patients with rheumatological diseases can cause significant morbidity. We performed a retrospective case review to describe the epidemiology, clinical features and outcome of chronic leg ulcers in this group of patients. Twenty-nine patients with underlying rheumatological conditions, such as, rheumatoid arthritis (15 patients), systemic lupus erythematosus (8 patients), overlap syndromes (3 patients), systemic sclerosis (1 patient) and ankylosing spondylitis (1 patient) were included. The ulcers were mostly located around the ankle (55·2%) and calves (37·9%). The predominant aetiology of the ulcers, in decreasing order of frequency, was venous disease, multifactorial, vasculitis or vasculopathy, infective, pyoderma gangrenosum, ischaemic microangiopathy and iatrogenic. Treatment modalities included aggressive wound bed preparation, compression therapy (17 patients), changes in immunosuppressive therapy (15 patients), hyperbaric oxygen therapy (4 patients) and cellular skin grafting (2 patients). Management of chronic leg ulcers in rheumatological patients is challenging and the importance of careful clinicopathological correlation and treatment of the underlying cause cannot be overemphasised.

A ten-year retrospective study on livedo vasculopathy in Asian patients.

INTRODUCTION: This study aims to analyse the clinico-epidemiological characteristics of Asian patients diagnosed with livedo vasculopathy (LV). MATERIALS AND METHODS: We performed a retrospective analysis of all patients diagnosed with LV from 1997 to 2007 at our centre. RESULTS: Seventy patients were diagnosed with LV with a mean age of 39 years, female: male ratio of 3:1 and no racial predilection. Most cases remained purely cutaneous, presenting with painful leg ulcers and atrophie blanche. Peripheral neuropathy was the only extra-cutaneous complication (9%). In patients who were screened, associations included hepatitis B (7%) and hepatitis C (4%), positive anti-nuclear antibody (14%), positive anti-myeloperoxidase antibody (5%), positive anti-cardiolipin antibodies (7%) and positive lupus anticoagulant (2%). In 49 patients who achieved remission, 55% required combination therapy, most commonly with colchicine, pentoxifylline and prednisolone. In those treated successfully with monotherapy, colchicine was effective in 59% followed by prednisolone (17.5%), pentoxifylline (17.5%) and aspirin (6%). Mean follow-up period was 50 months. CONCLUSION: LV in Asian patients is a high morbidity, chronic relapsing ulcerative skin condition. Most patients require induction combination therapy for remission. As further evidence emerges to support a procoagulant pathogenesis, a standardised protocol is needed to investigate for prothrombotic disorders during diagnosis.