A practical approach to caring for atopic dermatitis in children.

PURPOSE OF REVIEW: Atopic dermatitis is a chronic, systemic disease with primary cutaneous clinical manifestations and is commonly attributed to an exaggerated Th2 inflammatory response. Recent research regarding risk factors, prevention, clinical features, and management of atopic dermatitis will be reviewed. RECENT FINDINGS: In the last decade, advances have been made in identifying the factors that either confer increased risk for or protection from atopic dermatitis and associated atopy. Progress has also been made in the clinical management of this disease. Promising biomarkers and therapeutically informative characteristics of this disease have been identified in young children with and without the presence of eczema, but much has yet to be elucidated. Progress has also been made in clarifying the advantages and disadvantages of respective medical managements, including but not limited to topical corticosteroids, topical calcineurin inhibitors, phototherapy, systemic immunosuppressants, and targeted immunotherapy. Given that medical management may show variable efficacy in a child, an optimized skin care regimen is of utmost importance as well. SUMMARY: Atopic dermatitis is a challenging, chronic systemic disease that incurs significant morbidity in affected children. Although management options have been somewhat disappointing in years past, promising results have been observed in recent advances in targeted immunotherapy.

Treatment options for necrobiosis lipoidica: a systematic review.

BACKGROUND: Necrobiosis lipoidica (NL) is a rare, idiopathic, and recalcitrant disease of collagen degeneration for which treatment options have been poorly studied. Due to its recurring nature, risk for ulceration, and high morbidity, there is a need to understand existing treatment modalities to better inform clinical care. OBJECTIVE: This review aims to describe the therapeutic modalities reported in the literature for the treatment of NL. METHODS: A literature search of treatments was performed by searching for publications between January 2016 and May 2022 on PubMed and Scopus. Given the limited high-quality evidence, case reports and series were included. Only publications presenting information on both attempted treatments and outcomes were included. RESULTS: A total of 60 novel articles were identified (54 case reports, two case series, and four retrospective cohort studies). These studies cumulatively reported on 274 patients and covered treatments including phototherapy, topical corticosteroids, topical calcineurin inhibitors, biologics, immunosuppressants, JAK inhibitors, combination therapies, and several others. The greatest amount of evidence was found for photodynamic therapy (improvement in 72 of 80 patients), UVA-based phototherapy (12 of 33), topical corticosteroids (21 of 46), compression therapy (15 of 20), and topical calcineurin inhibitors (11 of 17). Several newer treatments were also described, including ustekinumab and JAK inhibitors. CONCLUSIONS: This systematic review provides a comprehensive summary of recently published treatments for NL. As the existing data comes predominantly from case reports and series, statistical conclusions are not assessed. A greater number of randomized controlled trials with standardized endpoints are necessary to compare treatment efficacy.

New synthetic pharmacotherapeutic approaches to the treatment of moderate-to-severe plaque psoriasis in adults.

INTRODUCTION: Psoriasis is a chronic inflammatory and immune-mediated condition affecting 3.2% of the United States population. There are many options for psoriasis treatment including topicals, oral systemic agents, and biologics. A greater understanding of the pathophysiology of psoriasis has led to an increase in the therapeutic options for treatment. AREAS COVERED: In this review, we outline the novel synthetic agents for moderate-to-severe plaque psoriasis and discuss a strategy for implementing these agents in clinical practice. A literature search was performed using PubMed to identify articles relevant to the topic published before October 2022. EXPERT OPINION: Topicals are first-line for the treatment of moderate-to-severe plaque psoriasis, most commonly including topical steroids, vitamin D analogs, and topical calcineurin inhibitors. While new topical agents have favorable properties, they are not always effective and adherence to topical agents is poor. Biologics are safe and effective, but patients often prefer oral therapy as opposed to injectable medications. Additionally, anti-drug antibodies can reduce effectiveness of biologics over time. Oral medications are preferred, but we now have a high bar for efficacy and safety. Cost is also a barrier for many patients. Recent development of new synthetic treatment options is promising, and we recommend that providers consider these agents as they develop holistic and individualized treatment plans for their patients.

A review of JAK and IL-23 inhibitors to treat vitiligo.

Vitiligo is an autoimmune skin disorder resulting in the depigmentation of skin characterised by patches of varying sizes and shapes. A common disorder of pigmentation that affects 0.5%-2% of the global population. Despite its well-understood autoimmune pathogenesis, the targets for effective cytokine intervention remain unclear. Current first-line treatments include oral or topical corticosteroids, calcineurin inhibitors and phototherapy. These treatments are limited, have varying efficacies, and are associated with significant adverse events or can be time-consuming. Therefore, biologics should be explored as a potential treatment for vitiligo. There are currently limited data for the use of JAK and IL-23 inhibitors for vitiligo. A total of 25 studies were identified in the review. There is promising evidence regarding the use of JAK and IL-23 inhibitors for the treatment of vitiligo.

Biologic and targeted therapeutics in vitiligo.

BACKGROUND: Vitiligo is a long-standing progressive autoimmune disease with depigmented macules/patches with significant psychological morbidity to the patients. From being one of the most poorly understood diseases in the past, there has been a rampant advance in determining the molecular and genetic factors influencing the disease process. More light has been shed on the complex intracellular environment and interplay between innate and adaptive immunity. Numerous cytokines and signaling pathways have been associated with disease pathogenesis in the recent past. OBJECTIVE: The aim of this review the efficacy of biologic and targeted therapeutics in vitiligo. METHODS: A detailed literature search was conducted on databases like PubMed, COCHRANE Central, EMBASE and Google Scholar using keywords-"biologics," "vitiligo," "treatment," "repigmentation," "JAK inhibitors,", "TNF-ê­¤ inhibitors," and "IL17/23 inhibitors," Relevant studies and review articles in English were analyzed in detail and report was written. This article aimed at a comprehensive review of all the biologicals and newer targeted therapeutics tried in vitiligo and their efficacy with an insight into the potential complications arising as a result of the therapy. RESULTS: Most conventional vitiligo treatment modalities are restricted to generalized nonspecific immunosuppressants like topical and oral corticosteroids, calcineurin inhibitors, phototherapy, and surgical modalities. There have been reports and studies on the usage of biologicals in treating vitiligo. JAK inhibitors have shown good efficacy in vitiligo; however, it lacks substantial evidence in the form of randomized control trials. Similarly, the use of targeted therapeutics in treating vitiligo is substantiated by limited evidence and requires more randomized trials for further evidence. CONCLUSION: JAK inhibitors have shown promising results and good tolerability; Adjuvant phototherapy can achieve a superior response compared to monotherapy. Though TNF-ê­¤ has been tried in a few cases, it is best used if vitiligo is present in association with other chronic autoimmune diseases for which it is indicated. More in vitro studies and clinical research are required to understand the pathogenesis clearly, and therapy has to be targeted at specific pathways for a better approach toward vitiligo. Treatment aimed at induction and differentiation of melanocytes may be added to achieve faster repigmentation.

Advancement in therapeutic strategies for immune-mediated oral diseases.

BACKGROUND: Immune-mediated diseases are a diverse group of conditions characterized by alteration of cellular homeostasis and inflammation triggered by dysregulation of the normal immune response. Several immune-mediated diseases exhibit oral signs and symptoms. Traditionally, these conditions are treated with corticosteroids or immunosuppressive agents, including azathioprine, cyclophosphamide, and thalidomide. Recent research into the developmental pathways of these diseases has led to the exploration of novel approaches in treatment. This review examines newer treatment modalities for the management of immune-mediated diseases with oral presentations. Topical calcineurin inhibitors (TCIs) such as tacrolimus and pimecrolimus have been employed successfully in managing oral lichen planus and pemphigus vulgaris. Biologic agents, comprising monoclonal antibodies, fusion proteins, and recombinant cytokines, can provide targeted therapy with fewer adverse effects. Neutraceutical agents comprising aloe vera, curcumin, and honey are commonly used in traditional medicine and offer a holistic approach. They may have a place as adjuvants to current standard therapeutic protocols. Photodynamic therapy (PDT) and low-level laser therapy (LLLT) utilize a specific wavelength of light to achieve desired cellular change. While the use of PDT in immune-mediated diseases is contentious, LLLT has shown positive results. Newer therapeutic modalities involve kinase inhibitors, S1P1 receptor modulators, MSCs, and iRNA providing targeted treatment of specific diseases.

Therapeutic strategies for post-transplant recurrence of hepatocellular carcinoma.

Despite stringent selection criteria, hepatocellular carcinoma recurrence after liver transplantation (LT) still occurs in up to 20% of cases, mostly within the first 2-3 years. No adjuvant treatments to prevent such an occurrence have been developed so far. However, a balanced use of immunosuppression with minimal dose of calcineurin inhibitors and possible addition of mammalian target of rapamycin inhibitors is strongly advisable. Moreover, several pre- and post-transplant predictors of recurrence have been identified and may help determine the frequency and duration of post-transplant follow-up. When recurrence occurs, the outcomes are poor with a median survival of 12 mo according to most retrospective studies. The factor that most impacts survival after recurrence is timing (within 1-2 years from LT according to different authors). Several therapeutic options may be chosen in case of recurrence, according to timing and disease presentation. Surgical treatment seems to provide a survival benefit, especially in case of late recurrence, while the benefit of locoregional treatments has been suggested only in small retrospective studies. When systemic treatment is indicated, sorafenib has been proved safe and effective, while only few data are available for lenvatinib and regorafenib in second line. The use of immune checkpoint inhibitors is controversial in this setting, given the safety warnings for the risk of acute rejection.

Targeting inflammation and immune activation to improve CTLA4-Ig-based modulation of transplant rejection.

For the last few decades, Calcineurin inhibitors (CNI)-based therapy has been the pillar of immunosuppression for prevention of organ transplant rejection. However, despite exerting effective control of acute rejection in the first year post-transplant, prolonged CNI use is associated with significant side effects and is not well suited for long term allograft survival. The implementation of Costimulation Blockade (CoB) therapies, based on the interruption of T cell costimulatory signals as strategy to control allo-responses, has proven potential for better management of transplant recipients compared to CNI-based therapies. The use of the biologic cytotoxic T-lymphocyte associated protein 4 (CTLA4)-Ig is the most successful approach to date in this arena. Following evaluation of the BENEFIT trials, Belatacept, a high-affinity version of CTLA4-Ig, has been FDA approved for use in kidney transplant recipients. Despite its benefits, the use of CTLA4-Ig as a monotherapy has proved to be insufficient to induce long-term allograft acceptance in several settings. Multiple studies have demonstrated that events that induce an acute inflammatory response with the consequent release of proinflammatory cytokines, and an abundance of allograft-reactive memory cells in the recipient, can prevent the induction of or break established immunomodulation induced with CoB regimens. This review highlights advances in our understanding of the factors and mechanisms that limit CoB regimens efficacy. We also discuss recent successes in experimentally designing complementary therapies that favor CTLA4-Ig effect, affording a better control of transplant rejection and supporting their clinical applicability.

[Update on the treatment of chronic prurigo]. / Update zur Therapie der chronischen Prurigo.

Chronic prurigo is an inflammatory dermatosis defined by the presence of chronic pruritus and single to multiple symmetrically distributed pruriginous lesions such as nodules, papules, and plaques. Various dermatological, systemic, neurological, and/or psychiatric diseases are associated with chronic prurigo. The care of these patients is very complex due to the multifactorial character and also because of the sometimes very pronounced consequences such as an impairment of quality of life with sleep disorders. Furthermore, there are no approved therapies. The current guideline-based treatment recommendations include topical application of steroids, capsaicin, calcineurin inhibitors, phototherapy, and systemic use of gabapentinoids, µ­opioid receptor antagonists, immunosuppressants, or dupilumab. Results from randomized controlled trials and case series on new therapies including biologics (e.g., nemolizumab) and Janus kinase inhibitors are promising. This article provides an overview of currently available treatment options and discusses the latest data on the efficacy of future therapies.

Eficacia y seguridad del calcipotriol y el dipropionato de betametasona en pacientes adultos con psoriasis vulgar en placas moderada o severa, no respondedores a la terapia tópica y sistémica convencional, y no tributarios a terapia biológica / Efficacy and safety of calcipotriol and betamethasone dipropionate in adult patients with moderate or severe plaque psoriasis vulgaris, unresponsive to conventional topical and systemic therapy, and not amenable to biological therapy

ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Institución de Evaluación de Tecnologías en Salud e Investigación N° 111-IETSI-ESSALUD-2021, se ha elaborado el presente dictamen que expone la evaluación de la eficacia y seguridad del calcipotriol y dipropionato de betametasona (DB) en pacientes adultos con psoriasis vulgar en placas moderada o severa, no respondedores a la terapia tópica y sistémica convencional, y no tributarios a terapia biológica. Así, la médico dermatóloga, Dra. Lorraine Lía Málaga Medina del Servicio de Dermatología del Hospital Nacional Carlos Seguin Escobedo, siguiendo la Directiva N.° 003-IETSI-ESSALUD-2016, envió al Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI la solicitud de uso por fuera del petitorio farmacológico de EsSalud el producto farmacéutico calcipotriol en combinación con el (DB), para el tratamiento de los pacientes adultos con psoriasis vulgar en placas moderada o severa, no respondedores a la terapia tópica y sistémica convencional, y no tributarios a terapia biológica. ASPECTOS GENERALES: La psoriasis vulgar en placas es una enfermedad crónica de la piel que se presenta como placas eritematosas y escamosas que aparecen, mayoritariamente, en el cuero cabelludo, el tronco, los glúteos, y los miembros inferiores y superiores (de Rie et al., 2004). Esta enfermedad es considerada como un problema de salud pública por su alta prevalencia, alto riesgo de morbilidad y porque deteriora la calidad de vida y salud mental en los pacientes que la padecen (Boehncke & Schón, 2015). La psoriasis afecta del 1 % al 3 % de la población mundial; y la psoriasis vulgar en placas representa hasta el 90 % de todas las manifestaciones de la psoriasis (Augustin et al., 2010). Además, la presencia de esta enfermedad se asocia a mayor riesgo de sufrir artritis psoriásica, enfermedades cardiovasculares, diabetes mellitus, obesidad, enfermedad del hígado graso no alcohólico y enfermedades inflamatorias del intestino (Gisondi et al., 2020). Asimismo, el 75 % de estos pacientes percibe un deterioro en su calidad de vida y cerca del 10 % ha tenido ideación suicida (Bhosle et al., 2006). METODOLOGÍA: Se llevó a cabo una búsqueda bibliográfica exhaustiva con el objetivo de identificar la mejor evidencia disponible sobre la eficacia y seguridad del CAL-DB, en comparación con mejor terapia de soporte, en pacientes adultos con psoriasis vulgar en placas moderada o severa no respondedores a la terapia tópica y sistémica convencional y no tributarios a terapia biológica. La búsqueda se realizó en las bases de datos bibliográfica de PubMed, The Cochrane Library y LILACS. Asimismo, se realizó una búsqueda manual dentro de las páginas web pertenecientes a grupos que realizan evaluación de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC) incluyendo el National Institute for Health and Care Excellence (NICE), la Agency for Healthcare Research and Quality's (AHRQ), la Scottish I ntercollegiate Guidelines Network (SIGN), la New Zealand Guidelines Group (NZGG), la National Health and Medical Research Council (NHMRC), el Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI), el Centro Nacional de Excelencia Tecnológica en Salud (CENETEC), la Canadian Agency for Drugs and Technologies in Health (CADTH), el Institute for Quality and Efficiency in Health Care (IQWIG), el Scottish Medicines Consortium (SMC), la Comissáo Nacional de I ncorpornáo de Tecnologías no Sistema Único de Saúde (CONITEC), el Instituto de Evaluación Tecnológica en Salud (IETS) y el Instituto de Efectividad Clínica y Sanitaria (IECS). Finalmente, se realizó una búsqueda adicional en la página web de registro de ensayos clínicos (EC) www.clinicaltrials.gov, para identificar EC en curso o aún no publicados. RESULTADOS: Tras ampliar los criterios de selección de documentos, se incluyó una GPC publicada por el NICE (2012) que realiza recomendaciones sobre la evaluación y el tratamiento de pacientes con psoriasis vulgar de severidad moderada o severa. Además, se incluyeron dos ETS publicadas por la CONITEC (2012), y la HAS (2019) que tuvieron como objetivo evaluar la evidencia disponible acerca de la eficacia y seguridad del uso del Cal-DB en pacientes adultos con psoriasis vulgar en placas e incluyeron, en su cuerpo de evidencia, ECA donde participaron pacientes con psoriasis vulgar de severidad moderada a severa. También, se incluyó el estudio pivotal citado en la ficha técnica del Daivobet ® aprobada por DIGEMID (2018), el cual es un ECA de fase II que comparó la eficacia y seguridad del uso del CAL-DB versus el calcipotriol en monoterapia, el DB en monoterapia y placebo, en pacientes con psoriasis vulgar de cualquier severidad de enfermedad (Fleming et al., 2010). Por último, se incluyó un estudio observacional que comparó el uso de la fototerapia y el CAL-DB en pacientes con severidad de enfermedad de moderada a severa (Polanska et al., 2019). ONCLUSIÓN: Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación no aprueba el uso combinado del calcipotriol y el dipropionato de betametasona en pacientes adultos con psoriasis vulgar moderada o severa, no respondedores a la terapia tópica y sistémica convencional y no tributarios a terapia biológica, como producto farmacéutico no incluido en el Petitorio Farmacológico de EsSalud.

Calcineurin Controls Hypothalamic NMDA Receptor Activity and Sympathetic Outflow.

RATIONALE: Hypertension is a common and serious adverse effect of calcineurin inhibitors, including cyclosporine and tacrolimus (FK506). Although increased sympathetic nerve discharges are associated with calcineurin inhibitor-induced hypertension, the sources of excess sympathetic outflow and underlying mechanisms remain elusive. Calcineurin (protein phosphatase-2B) is broadly expressed in the brain, including the paraventricular nuclear (PVN) of the hypothalamus, which is critically involved in regulating sympathetic vasomotor tone. OBJECTIVE: We determined whether prolonged treatment with the calcineurin inhibitor causes elevated sympathetic output and persistent hypertension by potentiating synaptic N-methyl-D-aspartate (NMDA) receptor activity in the PVN. METHODS AND RESULTS: Telemetry recordings showed that systemic administration of FK506 (3 mg/kg per day) for 14 days caused a gradual and profound increase in arterial blood pressure in rats, which lasted at least 7 days after discontinuing FK506 treatment. Correspondingly, systemic treatment with FK506 markedly reduced calcineurin activity in the PVN and circumventricular organs, but not rostral ventrolateral medulla, and increased the phosphorylation level and synaptic trafficking of NMDA receptors in the PVN. Immunocytochemistry labeling showed that calcineurin was expressed in presympathetic neurons in the PVN. Whole-cell patch-clamp recordings in brain slices revealed that treatment with FK506 increased baseline firing activity of PVN presympathetic neurons; this increase was blocked by the NMDA or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist. Also, treatment with FK506 markedly increased presynaptic and postsynaptic NMDA receptor activity of PVN presympathetic neurons. Furthermore, microinjection of the NMDA or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist into the PVN of anesthetized rats preferentially attenuated renal sympathetic nerve discharges and blood pressure elevated by FK506 treatment. In addition, systemic administration of memantine, a clinically used NMDA receptor antagonist, effectively attenuated FK506 treatment-induced hypertension in conscious rats. CONCLUSIONS: Our findings reveal that normal calcineurin activity in the PVN constitutively restricts sympathetic vasomotor tone via suppressing NMDA receptor activity, which may be targeted for treating calcineurin inhibitor-induced hypertension.

Evaluation of combination use of phenytoin cream 1% and fractional CO2 laser in treatment of stable nonsegmental vitiligo: A pilot study.

Vitiligo is an autoimmune disorder of melanocyte characterized by macular and depigmented patches. There are several treatment modalities for this disease, including the use of corticosteroids, calcineurin inhibitors, vitamin D analogous and topical phenytoin. Combination therapy utilizing fractional CO2 laser with different topical agents has been used to enhance treatment response with promising results. In this study, we aimed to evaluate the effect of fractional CO2 laser in combination with topical phenytoin. In this study, 25 patients (11 females and 14 males) with age of 18-59 (mean age of 31.12) with nonsegmental stable vitiligo were recruited with insufficient response to at least 1-year treatment with a monotherapy using topical corticosteroids, calcineurin inhibitors, and/or NB-UVB phototherapy. Patients were treated with a combination of fractional CO2 laser (10,600 nm, pulse energy 30-50 mJ, MIXEL, South Korea, Rating: 220VAC, 3A, 50/60 Hz) with monthly intervals for six sessions and application of phenytoin 1% cream twice daily. Photography was done before and after treatment with Wood's lamp. The severity of disease using VASI score was calculated and compared before and after treatment. The mean VASI score before treatment was 0.55, and sixth month after treatment increased to 1.97 (p-value < 0.001). Patients were divided into three groups based on the vitiligo subtype: acral, upper extremities, and trunk. VASI score was measured in each group: VASI score before and after treatment was 0.50 and 1.48 in acral areas, 0.45 and 2.04 in upper extremities and 0.79 and 3.39 in trunk, respectively. This study revealed that combination therapy with phenytoin and fractional CO2 laser is effective in treatment of vitiligo not only in the upper extremities and trunk, but also interestingly in the acral areas.

Oral lichen planus: comparative efficacy and treatment costs-a systematic review.

OBJECTIVE: To compare the reported efficacy and costs of available interventions used for the management of oral lichen planus (OLP). MATERIALS AND METHODS: A systematic literature search was performed from database inception until March 2021 in MEDLINE via PubMed and the Cochrane library following PRISMA guidelines. Only randomized controlled trials (RCT) comparing an active intervention with placebo or different active interventions for OLP management were considered. RESULTS: Seventy (70) RCTs were included. The majority of evidence suggested efficacy of topical steroids (dexamethasone, clobetasol, fluocinonide, triamcinolone), topical calcineurin inhibitors (tacrolimus, pimecrolimus, cyclosporine), topical retinoids, intra-lesional triamcinolone, aloe-vera gel, photodynamic therapy, and low-level laser therapies for OLP management. Based on the estimated cost per month and evidence for efficacy and side-effects, topical steroids (fluocinonide > dexamethasone > clobetasol > triamcinolone) appear to be more cost-effective than topical calcineurin inhibitors (tacrolimus > pimecrolimus > cyclosporine) followed by intra-lesional triamcinolone. CONCLUSION: Of common treatment regimens for OLP, topical steroids appear to be the most economical and efficacious option followed by topical calcineurin inhibitors. Large-scale multi-modality, prospective trials in which head-to-head comparisons interventions are compared are required to definitely assess the cost-effectiveness of OLP treatments.

Phototherapy and topical treatments for cutaneous graft vs. host disease in haematopoietic stem cell transplantation patients: a scoping review.

Skin is usually the first and most affected organ involved in graft-versus-host disease (GvHD), and treatment is still a clinical challenge. Although the need for skin-directed treatments such as physical treatments and topical medications are generally agreed on, what the gold standard treatment strategy should be remains open to debate. The aim of this scoping review was to synthesize the current knowledge on the topical and physical treatments of cutaneous GvHD in haematopoietic stem cell transplantation patients and to highlight the best evidence available so as to reduce the gap between 'what is known' and 'what is done' in the clinical practice. Twenty-eight studies were included in this qualitative synthesis. Photo-biomodulation with psoralen was not included in this review. Phototherapy (ultraviolet A or B or narrowband B) was the physical treatment most described in the literature in both acute GvHD and chronic GvHD. Topical calcineurin inhibitors such as tacrolimus ointment and pimecrolimus cream as well as corticosteroid creams such as clobetasol and triamcinolone are mainly used in case of chronic GvHD. In all of the studies included in the review, topical treatments were always associated with systemic therapy. None of the topical interventions identified in our review provided strong evidence supporting its use, and the topical approaches seemed to have an adjuvant role in the treatment of cutaneous GvHD.

Optimizing topical management of atopic dermatitis.

OBJECTIVE: Provide a review of atopic dermatitis management, focusing on optimizing topical therapy, creating a stepwise approach for treatment plans, and providing guidance on when to start systemic therapy. DATA SOURCES: PubMed search of articles in the English language regarding atopic dermatitis in all ages. STUDY SELECTION: Articles on the subject matter were selected and reviewed. RESULTS: Topical corticosteroids are the first-line treatment for managing atopic dermatitis. Topical nonsteroidal agents, calcineurin inhibitors, crisaborole, and recently, ruxolitinib, which cause no cutaneous atrophy, are options for reducing the use of topical corticosteroids, including on sensitive sites. Emerging topical agents are in clinical trials. Proactive management, with continued application 2 to 3 times weekly of a midpotency topical corticosteroid or tacrolimus, may maintain control for clear (or almost clear) localized sites of dermatitis that rapidly recur when topical anti-inflammatory medication is stopped. If topical therapy alone cannot control disease and quality of life is impacted, reevaluation to confirm the diagnosis, manage comorbid conditions, address compliance and patient-specific concerns, and optimize topical therapy must be undertaken before deciding to advance to systemic medication. Dupilumab, an interleukin-4 receptor inhibitor, has become first-line systemic therapy given its efficacy and safety, allowing long-term treatment without laboratory monitoring. Other biologics and Janus kinase inhibitors are emerging as alternatives that could eliminate the need for immunosuppressants with their higher risks. CONCLUSION: Several options are now available for topical treatment. A stepwise approach is needed to consider alternative therapies and diagnoses before advancing to systemic treatment, but the safety of newer immunomodulators will lower the threshold for more aggressive intervention.

Emerging systemic therapies for atopic dermatitis: oral small molecules and targeted topical agents.

BACKGROUND: Until recently, treatment of atopic dermatitis has been limited to topical corticosteroids, calcineurin inhibitors, phototherapy, and systemic immunomodulatory agents. With improved understanding of the pathogenesis underlying atopic dermatitis, targeted oral small molecules and topical agents are being developed. OBJECTIVE: Discuss efficacy and safety profiles of emerging oral small molecules and targeted topical agents in phase 2 and 3 clinical trials. METHODS: A systemic literature review was conducted to identify results of randomized, placebo-controlled trials of oral small molecules and topical Janus kinase inhibitors up to March 1 2020 for the treatment of atopic dermatitis. RESULTS: Three novel oral small molecules, abrocitinib, upadacitinib, and baricitinib, demonstrated improvement of clinical severity, pruritus, and quality of life with acceptable safety profiles. Apremilast, a phosphodiesterase inhibitor, was less efficacious with use limited by adverse effects. Two novel topical agents, ruxolitinib and delgocitinib, were effective and well-tolerated. CONCLUSIONS: Targeted therapeutics including oral small molecules and topical agents show promise for the treatment of atopic dermatitis. The use of validated core measures is necessary for future trials in order to adequately compare agents and progress evidence-based medicine.

Comorbidity and Therapeutic Approaches in Patients with Necrobiosis Lipoidica.

BACKGROUND: Necrobiosis lipoidica (NL) is a rare granulomatous disorder of unknown aetiology. Randomized controlled studies are not available due to it being an orphan disease. OBJECTIVES: We evaluated patients in 2 dermatological centres to cluster data about epidemiology, the therapeutic approaches for NL, and their efficacy. MATERIALS AND METHODS: Comorbidity and the efficacy of the applied treatment was assessed for 98 patients. RESULTS: We identified 54% of patients with concomitant diabetes and 19% with thyroidal disorders. Topical steroids (85.7%) were predominantly used followed by calcineurin inhibitors (31%) and phototherapy (41.8%). Systemically, fumaric acid esters were more frequently applied (26.8%) than steroids (24.4%) and dapsone (24.4%). Steroids, compression therapy, calcineurin inhibitors, phototherapy, fumaric acid esters, and dapsone showed remarkable efficacy. CONCLUSION: Therapeutic options were chosen individually in accordance with the severity of NL and presence of ulceration. Topical calcineurin inhibitors, systemic application of fumaric acid esters, and dapsone represent effective alternatives to the use of steroids.

Calcineurin inhibitor therapy in combination with Tripterygium wilfordii polyglycoside tablets for idiopathic membranous nephropathy: A retrospective clinical observation.

ABSTRACT: To compare the efficacy and safety of calcineurin inhibitor (CNI) and Tripterygium wilfordii polyglycoside tablets (TWPs) in treating idiopathic membranous nephropathy (IMN) with CNI and glucocorticoids (GCs).Data of patients with IMN who were treated with CNI+TWPs (TWP group) or CNI+GCs (GC group) and followed up for more than 12 months at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from 2017 to 2020 were retrospectively analyzed. The 24-h urine protein (24hUP), serum albumin (ALB), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), serum creatinine, alanine aminotransferase, and aspartate transaminase levels on the third, sixth, ninth, and twelfth months of treatment and phospholipase A2 receptor (PLA2R) level before and after treatment were compared in both groups.We recruited 64 patients who were assigned to either the GC group (n = 31) or TWP group (n = 33). No difference in baseline indicators between the two groups were observed (P > .05). After 12 months, the 24hUP levels of both groups significantly decreased compared with that at baseline (P < .01). At the end of the sixth month, 24hUP of the TWP group were less and reduced more quickly than those in the GC group (P < .05), but there is no difference at the other time point (P > .05). After treatment, the number of patients who up to the standard of TG and the ALB levels in both groups increased (P < .05), the LDL-C levels and the number of patients positive for PLA2R in both groups were reduced (P < .05), and no significant difference was observed in the overall changes of 24hUP, ALB and LDL-C levels, TG compliance rate, and PLA2R positive rate between both groups (P > .05). During treatment, no patient in either group had hepatorenal dysfunction, one case in the TWP group and two cases in the GC group experienced side effects, but no apparent difference in the side effects were observed between both groups (P > .05).Two therapeutic schemes have the advantage of reducing urinary protein excretion in patients with IMN. Compared with CNI+GCs, CNI+TWPs have high efficiency and is widely applied, which might be considered as an optimum therapy in the future.

Clinical practice guidelines for the diagnosis and management of atopic dermatitis.

Atopic dermatitis (AD), a chronic, relapsing dermatitis, is characterized by dry and pruritus skin in patients with a personal or family history of atopy. It affects up to 20% of children and 1-3% of adults in most countries worldwide, and leads to significant treatment costs and morbidity. These guidelines are developed in accordance with evidence-based publications and expert opinions. Following simple algorithms, the guidelines aim to assist adult and pediatric physicians in the better care of patients with AD. As with other diseases, there have been several diagnosis criteria proposed over time. Nonetheless, the classical Hanifin and Rajka criterion with no pathognomonic laboratory biomarkers is still the most widely used worldwide for the diagnosis of AD. The management of AD must be considered case by case to provide suitable care for each patient. Basic therapy is focused on avoiding specific/unspecific provoking factors and hydrating skin. Topical anti-inflammatory treatments such as glucocorticoids and calcineurin inhibitors are suggested for disease flare, and proactive therapy is best for long-term control. Other therapies, including antimicrobial agents, systemic antihistamines, systemic anti-inflammatory agents, immunotherapy, phototherapy, and psychotherapy, are reviewed in these guidelines. Crisaborole, a new topical phosphodiesterase 4 inhibitor, can be used twice daily in AD patients over three months old. Dupilumab, a biological drug for patients with moderate-to-severe AD, may be considered in patients with no improvement from other systemic treatments.

Diagnosis and Management of Dermatitis, Including Atopic, Contact, and Hand Eczemas.

This is a comprehensive and current guide for the diagnosis, differential diagnosis, treatment, and management of eczematous dermatitis, with a focus on atopic dermatitis, irritant and allergic contact dermatitis, hand dermatitis including recurrent vesicular and hyperkeratotic types, asteatotic dermatitis, and nummular or discoid dermatitis. Diagnostic options highlighted are clinical history, physical examination, and patch testing. Therapeutic options highlighted are moisturizers, topical corticosteroids, topical calcineurin inhibitors, crisaborole, phototherapy, and systemic medications including biologics.