Delphi Consensus Statement on the Role of Probiotics in the Treatment of Atopic Dermatitis.

Background Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intense itching and recurrent eczematous lesions. Important factors in the etiopathogenesis of AD include genetic predisposition, epidermal barrier dysfunction, immune dysregulation, and gut and skin dysbiosis. Probiotics could be a potential preventive strategy for allergies including AD through immune system modulation as well as enhancement of the epithelial barrier integrity. To further understand the role of probiotics in the management of AD, a Knowledge, Attitude, and Practices (KAP) survey was conducted. Materials and methods A steering committee comprising nine experts formulated consensus recommendations on the role of probiotics in the management of AD and associated flare-ups through the use of the Knowledge, Attitude, and Practices questionnaire while analyzing literature reviews and responses from a national panel consisting of 175 members. The evidence strength and quality were evaluated based on the Agency for Healthcare Research and Quality (AHRQ) criteria. The acceptance of expert opinions as recommendations was considered upon receiving an endorsement from ≥70% of the panelists, as indicated by a Likert scale. Results The national panel emphasized that the improvement in nutritional status, immunomodulatory properties, and beneficial effects on the gastrointestinal (GI) tract and skin support the use of probiotics in AD. The panel agreed that probiotics should be a part of the complementary therapy in the management of AD and associated flare-ups. Mostly, a probiotics supplementation duration of eight to 12 weeks is preferred by dermatologists. Probiotics, when used as an adjuvant therapy, may serve as a strategy to reduce steroid usage or maintenance therapy in high-risk cases with flares. Conclusion A Delphi-mediated KAP response provides a real-life approach to the use of probiotics in the management of AD. It suggests that probiotics could be useful as an adjuvant therapy in the management of AD and associated flare-ups when used along with traditional treatment.

Impact of climate change on atopic dermatitis: A review by the International Eczema Council.

Atopic dermatitis (AD), the most burdensome skin condition worldwide, is influenced by climatic factors and air pollution; however, the impact of increasing climatic hazards on AD remains poorly characterized. Leveraging an existing framework for 10 climatic hazards related to greenhouse gas emissions, we identified 18 studies with evidence for an impact on AD through a systematic search. Most climatic hazards had evidence for aggravation of AD the impact ranged from direct effects like particulate matter-induced AD exacerbations from wildfires to the potential for indirect effects like drought-induced food insecurity and migration. We then created maps comparing the past, present, and future projected burden of climatic hazards to global AD prevalence data. Data are lacking, especially from those regions most likely to experience more climatic hazards. We highlight gaps important for future research: understanding the synergistic impacts of climatic hazards on AD, long-term disease activity, the differential impact on vulnerable populations, and how basic mechanisms explain population-level trends.

GLGAN-VC: A Guided Loss-Based Generative Adversarial Network for Many-to-Many Voice Conversion.

Many-to-many voice conversion (VC) is a technique aimed at mapping speech features between multiple speakers during training and transferring the vocal characteristics of one source speaker to another target speaker, all while maintaining the content of the source speech unchanged. Existing research highlights a notable gap between the original and generated speech samples in terms of naturalness within many-to-many VC. Therefore, there is substantial room for improvement in achieving more natural-sounding speech samples for both parallel and nonparallel VC scenarios. In this study, we introduce a generative adversarial network (GAN) system with a guided loss (GLGAN-VC) designed to enhance many-to-many VC by focusing on architectural improvements and the integration of alternative loss functions. Our approach includes a pair-wise downsampling and upsampling (PDU) generator network for effective speech feature mapping (FM) in multidomain VC. In addition, we incorporate an FM loss to preserve content information and a residual connection (RC)-based discriminator network to improve learning. A guided loss (GL) function is introduced to efficiently capture differences in latent feature representations between source and target speakers, and an enhanced reconstruction loss is proposed for better contextual information preservation. We evaluate our model on various datasets, including VCC 2016, VCC 2018, VCC 2020, and an emotional speech dataset (ESD). Our results, based on both subjective and objective evaluation metrics, demonstrate that our model outperforms state-of-the-art (SOTA) many-to-many GAN-based VC models in terms of speech quality and speaker similarity in the generated speech samples.

Use of Janus kinase inhibitors in atopic dermatitis - an update.

Atopic dermatitis is among the cutaneous inflammatory disorders whose pathophysiology is thought to be influenced by the JAK-STAT intracellular signalling system. The effectiveness of systemic and topical Janus kinase (JAK) inhibitors in the treatment of atopic dermatitis has been shown in clinical trials and case studies. At present, oral abrocitinib (Cibinqo), oral upadacitinib (Rinvoq), oral baricitinib (Olumiant) and topical ruxolitinib (Opzelura) have approval from the US-FDA for their use in the treatment of atopic dermatitis. The efficacy and safety of oral and topical Janus kinase inhibitors for the treatment of atopic dermatitis have been reviewed in this article.

A Clinicopathological and Immunohistochemical Profile of Primary Extra Mammary Paget's Disease in Skin of Colour: A Case Series.

Extramammary Paget's disease is an intraepithelial neoplasm, usually found in areas rich in apocrine gland concentration. The clinical features, histopathology, immunohistochemistry and management details of five patients (F = 3, M = 2) have been described here. While a well-defined persistent plaque with crusting and erosion was the most common presentation, hyperpigmentation, hypopigmentation and depigmentation were also observed in two patients. Characteristic Paget's cells with cytokeratin 7 and EMA positivity were seen on histopathology examination. Authors conclude that pigmentary alterations may be under-reported in extra mammary Paget's disease in the skin of colour.

Co-Existence of Nodular Purpura and Vaccine Induced Panniculitis in a 4-Month-Old Baby-A Diagnostic Dilemma.

Vitamin K deficient bleeding (VKDB) disorder is a rare but fatal disorder that needs prompt diagnosis and timely intervention. Among its varied clinical manifestations, nodular purpura is rare one. Proper knowledge of this presentation helps clinicians to exclude other close differentials and avoid unnecessary delays in diagnosis. Though bleeding from the vaccination site could be a manifestation of VKDB, the concomitant presence of nodular purpura and vaccine-induced panniculitis in the same patient is rare. We report a case of a 4-month-old baby presenting with both, posing a diagnostic dilemma.

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.

The effects of systemic immunomodulatory treatments on COVID-19 outcomes in patients with atopic dermatitis: Results from the global SECURE-AD registry.

BACKGROUND: Limited data are available on the effects of systemic immunomodulatory treatments on COVID-19 outcomes in patients with atopic dermatitis (AD). OBJECTIVE: To investigate COVID-19 outcomes in patients with AD treated with or without systemic immunomodulatory treatments, using a global registry platform. METHODS: Clinicians were encouraged to report cases of COVID-19 in their patients with AD in the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Atopic Dermatitis (SECURE-AD) registry. Data entered from 1 April 2020 to 31 October 2021 were analysed using multivariable logistic regression. The primary outcome was hospitalization from COVID-19, according to AD treatment groups. RESULTS: 442 AD patients (mean age 35.9 years, 51.8% male) from 27 countries with strongly suspected or confirmed COVID-19 were included in analyses. 428 (96.8%) patients were treated with a single systemic therapy (n = 297 [67.2%]) or topical therapy only (n = 131 [29.6%]). Most patients treated with systemic therapies received dupilumab (n = 216). Fourteen patients (3.2%) received a combination of systemic therapies. Twenty-six patients (5.9%) were hospitalized. No deaths were reported. Patients treated with topical treatments had significantly higher odds of hospitalization, compared with those treated with dupilumab monotherapy (odds ratio (OR) 4.65 [95%CI 1.71-14.78]), including after adjustment for confounding variables (adjusted OR (aOR) 4.99 [95%CI 1.4-20.84]). Combination systemic therapy which did not include systemic corticosteroids was associated with increased odds of hospitalization, compared with single agent non-steroidal immunosuppressive systemic treatment (OR 8.09 [95%CI 0.4-59.96], aOR 37.57 [95%CI 1.05-871.11]). Hospitalization was most likely in patients treated with combination systemic therapy which included systemic corticosteroids (OR 40.43 [95%CI 8.16-207.49], aOR 45.75 [95%CI 4.54-616.22]). CONCLUSIONS: Overall, the risk of COVID-19 complications appears low in patients with AD, even when treated with systemic immunomodulatory agents. Dupilumab monotherapy was associated with lower hospitalization than other therapies. Combination systemic treatment, particularly combinations including systemic corticosteroids, was associated with the highest risk of severe COVID-19.

Intermittent or Sequential Topical Tacrolimus in Atopic Dermatitis: Systematic Review and Meta-Analysis.

Topical calcineurin inhibitors (TCIs) and topical corticosteroids (TCS) are the mainstays of flare management for atopic eczema or atopic dermatitis (AD). Tacrolimus (an immunomodulator), belongs to the class of calcineurin inhibitors, with promising efficacy in AD. We performed this systematic review to obtain an up-to-date coverage map of controlled clinical trials of sequential or intermittent treatments with TCI as a therapeutic intervention for AD. Articles of interest were retrieved from PubMed, Google Scholar, and EMBASE published between between January 2000 and March 2023. Key words were "calcineurin inhibitors," "corticosteroids," "atopic dermatitis," "pruritus," "sequential," "intermittent" and "consecutive" while fixed language search consisted of "Intermittent topical calcineurin inhibitors AND topical corticosteroids AND atopic dermatitis OR eczema" AD patients who were administered sequential and/or intermittent applications of TCI for management of atopic eczema were included. Outcome measures included but were not limited to Scoring of Atopic Dermatitis (SCORAD) and the Eczema Area Severity Score (EASI). Four clinical trials were considered for the purpose of review. A total of 101 patients with AD were analysed. The risk of bias was low in two studies, while the other two had an unclear risk of bias. Overall, pooled data from two trials revealed that sequential therapy with TCS/TCI was comparable to monotherapy or emollients, as the test for overall effect determined was non-significant with a p-value of 0.33. The two studies were highly heterogeneous, as indicated by a very high I2 of 92% and an extremely significant p-value (p=0.0005). Sequential therapy with TCS and TCIs was effective and well tolerated in the management of AD and it may be considered an important treatment approach during the initial period.

Psoriasis in Pediatric Age Group.

Psoriasis is a common, chronic, immune-mediated, multisystem, inflammatory disorder. It affects all age groups, including infancy. In one-third of the cases, the onset of the disease is in the first and second decades of life. Childhood psoriasis significantly affects the quality of life of the child as well as that of the entire family. Pediatric psoriasis has distinct clinical presentations and evolves with time. Like in adults, chronic plaque psoriasis has been found to be the most common type of childhood psoriasis. Psoriatic plaques in children are less pruritic, smaller and thinner with less prominent scaling. In pigmented skin, the erythema is less prominent and plaques appear violaceous or hyperpigmented. Pediatric psoriasis can be associated with arthritis, metabolic syndrome, depression and anxiety. Hence all children should be screened routinely for associated comorbidities. Management of pediatric psoriasis is challenging owing to the limitation of approved therapies. 'Proactive therapy' is a recent approach in childhood-onset psoriasis that would help to prevent the severity of flare-ups, thus improving the quality of life.

Use of Bleach Baths for Atopic Dermatitis: An Indian Perspective.

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder affecting 15-20% of children and 1-10% of adults. Staphylococcus aureus (S. aureus) infection is the most frequent complication of AD and is involved in the worsening of the disease. Systemic and topical antibiotics are used in the treatment for AD but there are concerns over increasing resistance. Bleach (sodium hypochlorite, NaOCl) baths are an inexpensive, widely accessible, alternative antibiotic treatment that may not worsen antibiotic resistance. Bleach baths are used as adjunctive treatment in AD patients to treat superinfections, although their mechanism of action is not well understood. Balancing safety concerns with efficacious treatment should be important especially for AD where the majority of patients are in pediatrics age groups. Studies available in PubMed databases were included in this review. Most suggested bleach bath improves clinical symptoms of AD and restores surface microbiome by eradicating bacteria, most notably S. aureus. Some studies have noted that this antimicrobial effect has reduced the need for topical corticosteroids. In addition, bleach seems to have strong anti-inflammatory and antipruritic effects. Overall, bleach baths seem to be safe on human skin, without disrupting the epidermal barrier function. The review concluded, although there are some advantages of use of bleach baths, more studies to investigate long-term efficacy and safety of bleach baths are required before fixing its role in the treatment of AD especially in the context of the Indian scenario.

Atopic March: Dermatologic Perspectives.

The progression of allergic diseases with the development of atopic dermatitis and food allergy in infancy and subsequent asthma and allergic rhinitis in the later childhood is known as 'atopic march'. There have been many arguments in favour of and against this concept. This article reviews the latest epidemiology, immunological mechanisms and translational implications in clinical practice and research, which is relevant to the dermatologists. The role of skin as a site of initiation and the potential for interventions on skin that may prevent subsequent allergic diseases is also highlighted.

Evidence-Based Guidelines for SARS-COV-2 Vaccination of Patients of Skin Allergic Diseases and Patients on Immuno-Therapeutics.

There is a dearth of data regarding the safety and timing of the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) vaccination of patients on immunosuppressive or immunomodulatory therapies. However, data from other vaccine trials may be extrapolated to get an idea regarding the recommendation of SARS-COV-2 vaccines. All the novel SARS-COV-2 vaccines are non-live, thus ensuring the safety of the vaccines. However, the vaccines may not be able to generate an equipotent immunogenic response in patients receiving immunotherapeutics, in comparison to those who are not. We have attempted to put forward certain statements, with respect to SARS-COV-2 vaccination of patients who are on treatment for different dermatological conditions. However, the risk-benefit ratio must be discussed between the patient and the physician, and the final call should be individualized.

Role of Cyclosporine (CsA) in Immuno-dermatological Conditions.

Cyclosporine (CsA) is a calcineurin inhibitor that acts selectively on T cells. It has been used in dermatology since 1997 for its US Food and Drug Administration indication of psoriasis and off-label for various other inflammatory skin conditions, including atopic dermatitis, alopecia areata, urticaria, lichen planus and many others in pediatric, adults as well as in pregnant women. However, clinicians' preferences for management differ, which may have a bearing on the treatment selection. Hence, the purpose of this review is to outline the role of CsA in various skin conditions through consensus statement from six national experts in the field of dermatology.

Lynch syndrome: An unusal case of familial cancer unearthed.

Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) is a type of inherited cancer syndrome with a genetic predisposition to different types of cancer. There is an increased predisposition to cancers in the endometrium, colon, stomach, ovary, uterus, skin, kidney, and brain in patients of Lynch syndrome. We are reporting a 48-year-old male who presented with a pea-sized growth in his left arm which was found to be sebaceoma on histopathology. On further detailed history, examination, and genetic study, it was proved to be a familial case of Lynch syndrome. The case is being reported to stress the importance of knowledge about clinical manifestation, associated neoplasms, and molecular genetic profile of Lynch syndrome which will enable physicians and pathologists to provide highly targeted surveillance and management for patients with high cancer risk.