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Basma Haris,1 Idris Mohammed,1 Sara Al-Khawaga,2 Khalid Hussain1 1Department of Pediatric Endocrinology, Sidra Medicine, Education City, Doha, Qatar; 2Department of Dermatology, Hamad General Hospital, Doha, QatarCorrespondence: Khalid HussainDepartment of Pediatric Medicine, Sidra Medicine, Education City, OPC, C6-340 |PO Box 26999, Al Luqta Street, North Campus, Doha, Qatar, Tel +974-4003-7608, Email khussain@sidra.orgPurpose: To report a family with a homozygous INS promotor gene mutation causing permanent neonatal diabetes mellitus (PNDM) in one sibling and autoantibody negative childhood onset diabetes in another sibling.Case Presentation: Patient 1 is a 12-year-old girl born at term with low birth weight to a consanguineous family, diagnosed with PNDM at 26 days of life. She presented with ketoacidosis and has a severe course of disease with high insulin requirement. Patient 2 is a 9-year-old girl born at term with normal weight, who presented with ketoacidosis at 2 years of age. Both subjects have negative type 1 autoantibodies. On genetic testing, a mutation in the promoter region of INS gene c.-331 C>G was found in homozygous state in both subjects and in a heterozygous state in parents.Conclusion: Homozygous INS gene promotor mutations may present with either PNDM or later onset autoantibody negative diabetes in childhood. This suggests that homozygous INS gene promotor mutations show marked heterogeneity in clinical presentation within individuals in the same family. The pathophysiology of this is not well known but could be related to a number of factors, including the position of the variant, penetrance, other associated genetic defects, HLA etc. Premarital screening and genetic counselling is recommended for highly consanguineous families to reduce occurrence of such conditions.Keywords: pediatric diabetes, neonatal diabetes mellitus, type 1b diabetes, INS mutation

Atopic dermatitis (AD), also known as atopic eczema, is a common but also complex chronic, itchy skin condition with underlying inflammation of the skin. This skin ailment is prevalent worldwide and affects people of all ages, particularly children below five years of age. The itching and resulting rashes in AD patients are often the result of inflammatory signals, thus necessitating a closer look at the inflammation-regulating mechanisms for putative relief, care and therapy. Several chemical- as well as genetically-induced animal models have established the importance of targeting pro-inflammatory AD microenvironment. Epigenetic mechanisms are gaining attention towards a better understanding of the onset as well as the progression of inflammation. Several physiological processes with implications in pathophysiology of AD, such as, barrier dysfunction either due to reduced filaggrin / human β-defensins or altered microbiome, reprograming of Fc receptors with resulting overexpression of high affinity IgE receptors, elevated eosinophil numbers or the elevated IL-22 production by CD4 + T cells have underlying epigenetic mechanisms that include differential promoter methylation and/or regulation by non-coding RNAs. Reversing these epigenetic changes has been verified to reduce inflammatory burden through altered secretion of cytokines IL-6, IL-4, IL-13, IL-17, IL-22 etc, with benefit against AD progression in experimental models. A thorough understanding of epigenetic remodeling of inflammation in AD has the potential of opening avenues for novel diagnostic, prognostic and therapeutic options., Competing Interests: Conflict of Interest Dr. Steinhoff has performed consultancy services for which he received compensation from Pfizer, Sanofi, Regeneron, Lilly, Novartis, Galderma, Leo, Merck, Avon, Pierre-Fabre, L’Oreal, BMS, Maruho, Toray, Mitsubishi, Maruho, Kiniksa, ZymoGenetics, Almirall; he served on advisory board for Pfizer, Novartis, Galderma, Leo, Avon, Pierre-Fabre, L’Oreal, BMS, Maruho, Toray, Mitsubishi, Maruho, ZymoGenetics, Almirall; his research was supported by Pfizer, Novartis, Galderma, Leo, Avon, Pierre-Fabre, L’Oreal, BMS, Maruho, Toray, Mitsubishi, Maruho, ZymoGenetics, Almirall. None of the other authors have any other conflicts of interest to report., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

IL-36 is a most recent member of the IL-1 cytokine family, primarily expressed at barrier sites of the body such as the skin, lungs, and intestine. It plays a vital role in inflammation and is implicated in the development of various cutaneous; intestinal; and pulmonary disorders, including psoriasis, inflammatory bowel disease, and chronic obstructive pulmonary disease. IL-36 comprises 4 isoforms: the proinflammatory IL-36α, IL-36β, and IL-36γ and the anti-inflammatory IL-36R antagonist. An imbalance between proinflammatory and anti-inflammatory IL-36 isoforms can contribute to the inflammatory fate of cells and tissues. IL-36 cytokines signal through an IL-36R heterodimer mediating their function through canonical signaling cacade, including the NF-B pathway. Prominent for its role in psoriasis, IL-36 has recently been associated with disease mechanisms in atopic dermatitis, hidradenitis suppurativa, neutrophilic dermatoses, autoimmune blistering disease, and Netherton syndrome. The major cutaneous source of IL-36 cytokines is keratinocytes, pointing to its role in the communication between the epidermis, innate (neutrophils, dendritic cells) immune system, and adaptive (T helper [Th]1 cells, Th17) immune system. Thus, cutaneous IL-36 signaling is crucial for the immunopathological outcome of various skin diseases. Consequently, the IL-36/IL-36R axis has recently been recognized as a promising drug target for the treatment of inflammatory disorders beyond psoriasis. This review summarizes the current update on IL-36 cytokines in inflammatory skin diseases., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The 'GeriDerm' (geriatric dermatology) clinic, is a new dermatology-based service at Hamad Medical Corporation (HMC), accommodating the needs of our elderly population living in the State of Qatar. Due to the global demographic transition towards an elderly population (≥65 years of age), incidences of chronic diseases, including dermatologic conditions, rise in parallel. Patients of older age are at higher risk of using multiple medications, seeing multiple care providers, often receiving multiple diverging pieces of information, and feeling lost within the system. Taking into consideration the elderly unique characteristics, the Geriatric Dermatology telemedicine clinic is a novel approach to meeting the many challenges our elderly patients face via providing quick, accurate assessments of cognition, functional status, frailty screening, and assessment for polypharmacy. Methods: Data of 1080 elderly patients with various skin disorders from June 2020 to July 2021 was received from the Dermatology Geriatric clinic, and then reviewed. Results: There were 521(48.2%) new cases and 559(51.8%) follow-up cases who attended the clinic either virtually or face to face consultation. A total of 587(54.4%) female and 493(45.6%) male elderly patients attended the clinic. The mean age was 74.6, with a minimum age of 60 and a maximum age of 106 years. 57.9%(625) of GeriDerm patients were Qatari, followed by Palestinian 75(6.9%), Syrian 51(4.7%), Egyptian 46(4.3%), and Indian 44(4.1%); while other nationalities constituted 239(22.1%). The majority of the cases were Contact Dermatitis 146(13%), Bullous Pemphigoid 107 (10%), and Pruritis 101(9.4%). Conclusion: The 'GeriDerm' service at HMC aimed to achieve the best healthcare standards for the elderly population of Qatar during COVID-19 pandemic, and is now established as a continuous advanced technology-based framework facilitating caring for older patients with skin disease via providing a clear pathway for adequate triaging, identification of severe conditions (red flag) requiring in-person clinic visits, while managing non-life threatening dermatoses via a teledermatology based approach., (© 2023 Al-Khawaga, Akram, Hussain, Chandran, Buddenkotte, Joy, Manjooran, Kolaparambath, Mosaad, Al- Naama, AL Hamad, Steinhoff, HBKU Press.)

Atopic dermatitis (AD) is a common, chronic-relapsing inflammatory skin disease with significant disease burden. Genetic and environmental trigger factors contribute to AD, activating 2 of our largest organs, the nervous system and the immune system. Dysregulation of neuroimmune circuits plays a key role in the pathophysiology of AD, causing inflammation, pruritus, pain, and barrier dysfunction. Sensory nerves can be activated by environmental or endogenous trigger factors, transmitting itch stimuli to the brain. On stimulation, sensory nerve endings also release neuromediators into the skin, contributing again to inflammation, barrier dysfunction, and itch. In addition, dysfunctional peripheral and central neuronal structures contribute to neuroinflammation, sensitization, nerve elongation, and neuropathic itch, thus chronification and therapy resistance. Consequently, neuroimmune circuits in skin and central nervous system may be targets to treat pruritus in AD. Cytokines, chemokines, proteases, lipids, opioids, and ions excite/sensitize sensory nerve endings, which not only induces itch but further aggravates/perpetuates inflammation, skin barrier disruption, and pruritus as well. Thus, targeted therapies for neuroimmune circuits as well as pathway inhibitors (eg, kinase inhibitors) may be beneficial to control pruritus in AD either in systemic and/or in topical form. Understanding neuroimmune circuits and neuronal signaling will optimize our approach to control all pathological mechanisms in AD, inflammation, barrier dysfunction, and pruritus., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims/introduction: To study the epidemiology, genetic landscape and causes of childhood diabetes mellitus in the State of Qatar., Materials and Methods: All patients (aged 0-18 years) with diabetes mellitus underwent biochemical, immunological and genetic testing. American Diabetes Association guidelines were used to classify types of diabetes mellitus. The incidence and prevalence of all the different types of diabetes mellitus were calculated., Results: Total number of children with diabetes mellitus was 1,325 (type 1 n = 1,096, ≥1 antibody; type 2 n = 104, type 1B n = 53; maturity onset diabetes of the young n = 20; monogenic autoimmune n = 4; neonatal diabetes mellitus n = 10;, syndromic diabetes mellitus n = 23; and double diabetes mellitus n = 15). The incidence and prevalence of type 1 diabetes were 38.05 and 249.73 per 100,000, respectively, and for type 2 were 2.51 and 23.7 per 100,000, respectively. The incidence of neonatal diabetes mellitus was 34.4 per 1,000,000 live births, and in indigenous Qataris the incidence was 43.6 per 1,000,000 live births. The prevalence of type 1 diabetes and type 2 diabetes in Qatari children was double compared with other nationalities. The prevalence of maturity onset diabetes of the young in Qatar was 4.56 per 100,000., Conclusions: This is the first prospective and comprehensive study to document the epidemiology and genetic landscape of childhood diabetes mellitus in this region. Qatar has the fourth highest incidence of type 1 diabetes mellitus, with the incidence and prevalence being higher in Qatari compared with non-Qatari. The prevalence of type 2 diabetes mellitus is also higher in Qatar than in Western countries. The incidence of neonatal diabetes mellitus is the second highest in the world. GCK is the most common form of maturity onset diabetes of the young, and a large number of patients have type 1B diabetes mellitus., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)