Contact hypersensitivity to Indian standard patch test series correlates with disease severity among children with atopic dermatitis.

Background There is emerging evidence of a relationship between atopic dermatitis (AD) and allergic contact dermatitis (ACD), though the data available are scarce with conflicting viewpoints. We explored the occurrence of contact hypersensitivity among children with atopic dermatitis by patch testing them with the Indian standard series and tried to correlate the presence of contact hypersensitivity with the clinical severity of AD in these children. Methods In this single-centre, cross-sectional study, children between 6 months and 12 years diagnosed with atopic dermatitis were included and patch tested with the Indian standard series. Outcome parameters were the proportion of patients having positive patch-test reactions, the proportion of positive patch-test reactions for each allergen and factors associated with patch test positivity in atopic dermatitis. Results Of the 136 patients, 80 were boys. The mean age of the study population was 5.6 ± 3.2 years. Twenty-eight (20.6%) patients had patch test positivity at 96 h. Fragrance mix was the commonest allergen, followed by potassium dichromate, cobalt chloride hexahydrate and nickel. SCORing atopic dermatitis (SCORAD) was significantly higher in patients with positive patch tests as compared to patients with negative patch tests (P = 0.009). Conclusion Greater disease severity in atopic dermatitis was found to be associated with patch test positivity. Limitations Inability to establish relevance in about 50% of the patients was a limitation of our study. Follow-up data regarding the impact of allergen avoidance is not available.

Filaggrin gene polymorphisms in Indian children with atopic dermatitis: A cross-sectional multicentre study.

Background Filaggrin (FLG) gene encoding the protein filaggrin plays an important role in barrier function of the skin and its alteration is a predisposing factor for atopic dermatitis. FLG gene variants result in absent or decreased filaggrin protein. Worldwide, the prevalence of FLG variants ranges from 14 to 56%. FLG null variants are distinct in each population. Objectives To study the FLG gene polymorphisms in Indian children and attempt a genotype-phenotype correlation in atopic dermatitis. Methods This was a cross-sectional, multicentre study conducted on 75 Indian children. Demographic details, clinical features and identified FLG null variants were recorded. We performed a whole gene sequencing of the entire FLG coding region using next-generation sequencing technology. Results The prevalence of FLG null variants was 34.7%. A total of 20 different FLG loss of function variants in 26 children were documented. Sixteen (80%) variants were novel and four (20%) were previously reported in Asian and European populations. We found a statistically significant association between FLG variants with early age of onset of atopic dermatitis (P = 0.016) and elevated serum IgE levels (P = 0.051). There was no significant difference between atopic dermatitis phenotypes in children having one variant as compared to children harbouring two or more null variants. Limitation Small sample size. Conclusion Our study reports a unique set of FLG variants different from Asian and European populations, with these variants being significantly associated with an early age of onset of atopic dermatitis and elevated serum IgE levels.

Critical role of epigenetic modification in the pathogenesis of atopic dermatitis.

Atopic dermatitis is a chronic inflammatory skin disease characterised by recurrent eczema-like lesions and severe pruritus, along with drying and decrustation of skin. Current research relates the pathogenesis of atopic dermatitis mainly to genetic susceptibility, abnormal skin barrier function, immune disorders, Staphylococcus aureus colonisation, microbiological dysfunction and vitamin D insufficiency. Epigenetic modifications are distinct genetic phenotypes resulting from environment-driven changes in chromosome functions in the absence of nuclear DNA sequence variation. Classic epigenetic events include DNA methylation, histone protein modifications and non-coding RNA regulation. Increasing evidence has indicated that epigenetic events are involved in the pathogenesis of atopic dermatitis by their effects on multiple signalling pathways which in turn influence the above factors. This review primarily analyses the function of epigenetic regulation in the pathogenesis of atopic dermatitis. In addition, it tries to make recommendations for personalised epigenetic treatment strategies for atopic dermatitis in the future.

Association between asthma, rhinitis and atopic dermatitis with leprosy: A case-control study.

Background Considering the cross-regulation of Th1 and Th2 responses, we hypothesised that atopic diseases (Th2) inhibit the protective Th1 immune response to Mycobacterium leprae and exacerbates leprosy. Objective In this study, we aimed to evaluate the association between leprosy and atopic diseases. Methods To evaluate the association of atopic diseases with leprosy, we conducted a case-control study that included leprosy patients (n = 333) and their household contacts (n = 93). The questionnaire from the International Study of Asthma and Allergies in Childhood, which is validated in several countries for epidemiological diagnosis of atopic diseases, was applied to determine the occurrence of atopic diseases, allergic rhinitis, asthma, and atopic dermatitis among leprosy patients and the household contacts. Results Considering clinical and epidemiological data, among the leprosy group 51.6% (n = 172) were determined to have at least one atopic disease, while atopy was observed less frequently at 40.86% among household contacts (n = 38). When two or more atopic diseases were assessed, the frequency was significantly higher among the leprosy patients than in the household contacts (21.9% vs. 11.8%; P-value = 0.03). Likewise, the frequency of asthma was significantly higher among leprosy patients (21%) than in the household contacts (10.8%; P-value = 0.02). Thus, our analyses revealed an association of atopic diseases with leprosy, with a significant linear increase in the occurrence of leprosy with an increase in the number of atopic diseases (P-value = 0.01). Limitation Due to the difficulties in recruiting household contacts that have prolonged contact with patients, but are not genetically related to the patient, the household contacts group is smaller than the leprosy patient group. Conclusion The data reveal an association between atopic diseases and leprosy outcomes. This knowledge could improve the treatment of leprosy patients with co-incident atopic diseases.

Granzyme B: A novel therapeutic target for treatment of atopic dermatitis.

Granzyme B is a serine protease that can play multiple roles in intracellular and extracellular perforin-dependent or non-perforin-dependent mechanisms. Granzyme B has been found to be an important factor involved in the pathogenesis of atopic dermatitis and is increased in both skin lesions and peripheral blood of atopic dermatitis patients. In this article, we review the correlation between granzyme B and atopic dermatitis to provide a novel therapeutic targeting option for clinical treatment of the latter.

JAK inhibitors and monoclonal antibodies for the treatment of atopic dermatitis: effectiveness and value.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from AbbVie, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Sun Life Financial, uniQure, and United Healthcare. Agboola, Herron-Smith, Nhan, Rind, and Pearson are employed by ICER. Through their affiliated institutions, Atlas, Brouwer, Carlson, and Hansen received funding from ICER for the work described in this summary.

Efficacy of moisturizers in paediatric atopic dermatitis: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Topical moisturizer is recommended for atopic dermatitis. AIMS: The aim of the study was to investigate the knowledge gap regarding the efficacy of moisturizer in young patients. METHODS: A systematic review and meta-analysis were conducted on randomised controlled trials comparing participant's ≤15 years with atopic dermatitis, receiving either topical moisturizer or no moisturizer treatment. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. RESULTS: Six trials were included (intervention n= 436; control n= 312). Moisturizer use extended time to flare by 13.52 days (95% confidence interval 0.05-26.99, I2 88%). Greater reduction in risk of relapse was observed during the first month of latency (pooled risk ratio 0.47, 95% confidence interval 0.31-0.72, I2 28%) compared to the second and third months (pooled risk ratio 0.65, 95% confidence interval 0.47-0.91, I2 35% and pooled risk ratio 0.63, 95% confidence interval 0.47-0.83, I2 33%, respectively).Treated patients were 2.68 times more likely to experience a three-six months remission (95% confidence interval1.18-6.09, I2 56%). Moisturizer minimally improved disease severity and quality of life. LIMITATIONS: There is a dire need to conduct randomised controlled trials with more robust and standardised designs. CONCLUSION: Moisturizer benefits young patients with atopic dermatitis. However, more research is needed to better estimate its efficacy.

Quality of life in children with atopic dermatitis: A one-year prospective cohort study.

BACKGROUND: Literature on the quality of life trends across time in children with atopic dermatitis are scarce. AIMS: To assess factors associated with quality of life of children with atopic dermatitis after a one-year follow-up and to examine the factors contributing to greater improvement in the atopic dermatitis-related quality of life over one year. METHODS: Our cohort consisted of 98 children who were treated for atopic dermatitis at the clinic of dermatovenereology. Data collection included atopic dermatitis scoring using the SCORing Atopic Dermatitis (SCORAD) index, Children's Dermatology Life Quality Index (CDLQI) for children aged > four years and Infants' Dermatitis Quality of Life Index (IDLQI) for children aged 0-4 years. Categorization of the impairment of quality of life score due to atopic dermatitis was as follows: mild (score from 0 to 6), moderate (score from 7 to 12) and severe (score from 13 to 30). The cohort was followed for one year after which a total of 80 children were reassessed. RESULTS: Improvements of both CDLQI and IDLQI were observed in children whose impairment of quality of life due to atopic dermatitis after one year was 'mild'. This was not observed in children whose atopic dermatitis caused either 'moderate' or 'severe impairment' of their quality of life. Adjusted analysis showed that lower initial SCORAD and greater improvement in SCORAD after the one-year follow-up were associated with a better quality of life at follow-up. LIMITATIONS: The size of our cohort was relatively small. Study participants were recruited from the largest urban and medical referral center in Serbia. Persons from suburban or rural regions may have had different perceptions of atopic dermatitis-related quality of life. CONCLUSION: Children with less severe atopic dermatitis were more likely to improve their atopic dermatitis-related quality of life. Lower SCORAD was associated with both better quality of life initially and greater improvement in quality of life after one year of follow-up.

Schwann cells as underestimated, major players in human skin physiology and pathology.

Schwann cells (SCs) have long been recognized for their ability to support repair and promote axon regeneration following injury to the peripheral nervous system. In response to nerve injury, they rapidly dedifferentiate into a precursor-like state, secrete an array of inflammatory mediators and growth factors, proliferate, undergo epithelial-to-mesenchymal-like transformation to facilitate migration, phagocytose cellular debris and remodel the extracellular environment to promote regeneration of axons through the site of injury. However, even though a cutaneous role for SCs is becoming increasingly recognized, we argue in this Viewpoint essay that the likely complex functions of SCs in skin physiology and pathology beyond skin sensation and nerve repair deserve more attention and systemic research than they have received so far. For example, SCs promote wound healing, disseminate infection in leprosy, support the growth of neurofibromas/schwannomas and facilitate/accelerate the growth and invasion of melanoma. Despite representing a major dermal cell population, comparatively little is still known about the role of SCs in other dermatoses. To quintessentially illustrate the opportunities that promise to arise from a new skin research focus on SCs, we focus on two dermatoses that are not traditionally associated with SCs, that is, psoriasis and atopic dermatitis (AD), since both show distinct SC changes along with continuous nerve fibre degeneration and regeneration, and an impact of denervation on skin lesions. Specifically, we critically discuss the hypothesis that repeated activation of the SC repair programme occurs in and contributes to psoriasis and AD and delineate experimental approaches how to probe this clinically relevant hypothesis.

The impact of skin diseases on quality of life: a multicenter study / El impacto de las enfermedades cutáneas en la calidad de vida: un estudio multicéntrico

INTRODUCTION: To date, no formal study has been published regarding how Colombian patients with skin disorders could be affected according to their perception of disease. OBJECTIVE: To determine the impact in quality of life of skin diseases in a Colombian population. METHODS: This multicenter study included patients with skin disease from almost the whole country. Individuals >18 years old; of any gender; with any skin disease and who signed informed consent, were included. We applied the Colombian validated version of the Skindex-29 instrument. RESULTS: A total of 1896 questionnaires had sufficient information for the analyses. No significant differences in sociodemographic characteristics of patients who returned the questionnaire incomplete vs. complete, were found. Participants mean age was 41.5 years. There were no statistical differences in men vs. women regarding the global (p = 0.37), symptoms (p = 0.71) and emotions (p = 0.32) domains, whereas statistical differences were found in the function domain (p = 0.04; Mann-Whitney U test). Psoriasis, contact dermatitis, atopic dermatitis, urticaria, hair disorders, Hansen's disease, scars, hyperhidrosis and genital human papillomavirus disease scored the highest. Limitations. Skindex-29 score variability as a result of differences in the location of the skin lesions, their inflammatory or non-inflammatory nature, and the start of therapy. CONCLUSIONS: Even the most localized or asymptomatic skin lesion in our population leads to a disruption at some level of patient's wellness. This study adds well supported scientific data of the burden of skin diseases worldwide

INTRODUCCIÓN: En Colombia se carece de estudios que hayan evaluado formalmente el impacto de las enfermedades dermatológicas en la calidad de vida de los pacientes que las padecen. OBJETIVO: Determinar el impacto en la calidad de vida de las enfermedades cutáneas en una población colombiana. MÉTODOS: Estudio multicéntrico que incluyó a individuos>18 años de edad; de cualquier sexo, con cualquier trastorno cutáneo y que firmaron el consentimiento informado. Se aplicó la versión validada en Colombia del instrumento Skindex-29. RESULTADOS: Un total de 1.896 cuestionarios se incluyeron en el análisis. No se observaron diferencias significativas en las características sociodemográficas entre los que devolvieron el cuestionario incompleto vs. completo. La edad promedio fue de 41,5 años. No hubo diferencias significativas entre hombres y mujeres con respecto al puntaje global del instrumento, ni de los dominios sintomático o emocional, mientras que sí las hubo en el dominio funcional. Entre las enfermedades que más afectaron la calidad de vida se incluyen: psoriasis, dermatitis de contacto, dermatitis atópica, urticaria, trastornos capilares, lepra, cicatrices, hiperhidrosis y las verrugas genitales. Limitaciones. Las puntuaciones del Skindex-29 mostraron una gran variabilidad explicable por diferencias en la localización de las lesiones de la piel, su naturaleza inflamatoria/no inflamatoria, y la iniciación o no del tratamiento. CONCLUSIONES: Cualquier lesión dermatológica por más localizada o asintomática que sea, condujo a una alteración en algún grado de la calidad de vida dermatológica. Este estudio añade soporte científico a la carga de enfermedad que generan los trastornos cutáneos en el mundo

Erectile Dysfunction in Male Adults With Atopic Dermatitis and Psoriasis.

INTRODUCTION: Patients with psoriasis have increased risk of cardiovascular disease, but data on atopic dermatitis (AD) are less clear-cut. However, it is well-established that erectile dysfunction (ED) can serve as a risk marker for coronary disease. AIM: To investigate the incidence, prevalence, and risk of ED in men with psoriasis and AD. METHODS: The sample included all Danish men at least 30 years old. In patients with AD and psoriasis, we determined disease severity based on use of systemic therapy. We performed a cross-sectional study (January 1, 2008) using logistic regression to estimate the prevalence and odds ratio of ED. Moreover, in a cohort study design, patients were followed from January 1, 2008 through December 31, 2012, and Cox regression models were used to estimate adjusted hazard ratios of new-onset ED. Models were adjusted for potential confounding factors, including age, socioeconomic status, health care consumption, smoking, alcohol abuse, diabetes, and cholesterol-lowering drug use. MAIN OUTCOME MEASURES: The outcome was initiation of pharmacotherapy used for treatment of ED. RESULTS: The sample consisted of 1,756,679 Danish men (age range = 30-100 years), of which 2,373 and 26,536 had adult AD (mild = 1,072; severe = 1,301) and psoriasis (mild = 21,775; severe = 4,761), respectively. Mean ages (SDs) were 53.0 (14.6), 46.7 (12.0), and 56.3 (13.8) years for the general population, patients with AD, and patients with psoriasis, respectively. Prevalences of ED were 8.7%, 6.7%, and 12.8% for the general population, patients with AD, and patients with psoriasis, respectively. Adjusted odds ratios (logistic regression) of ED were decreased in patients with AD (0.68; 0.57-0.80) but increased in those with psoriasis (1.15; 1.11-1.20). Adjusted odds ratios for mild and severe AD were 0.63 (0.48-0.82) and 0.72 (0.58-0.88), respectively, and those for psoriasis these were 1.16 (1.11-1.21) and 1.13 (1.03-1.23). Adjusted hazard ratios (Cox regression) were 0.92 (0.76-1.11) for AD and 1.14 (1.08-1.20) for psoriasis. The ED risk was not increased in men with mild AD (0.85; 0.63-1.14) or severe AD (0.97; 0.76-1.24) but was significantly increased in men with mild psoriasis (1.13; 1.09-1.20) and severe psoriasis (1.17; 1.04-1.32). CONCLUSION: We found an increased prevalence and risk of ED in men with psoriasis, whereas the risk was comparable to (and even slightly lower than) the general population for men with AD. Egeberg A, Hansen PR, Gislason GH, et al. Erectile Dysfunction in Male Adults With Atopic Dermatitis and Psoriasis. J Sex Med 2017;14:380-386.