Topical proactive therapy in dermatology. A scoping review.

The term 'proactive therapy' refers to a long-term management of clinically intact skin in previously disease-affected areas. This method was initially implemented in atopic dermatitis to maintain the remission and decrease the risk of exacerbations. Proactive therapy aims to limit the need for reactive treatment and improve the patients' quality of life. A proactive approach is likely to be adopted for other relapsing and inflammatory skin conditions in the future. This scoping review aims to identify dermatological conditions to be treated with the proactive approach, evaluate the available evidence for its efficacy and safety, as well as highlight the research gaps.

Immunopathogenesis of Atopic Dermatitis: Focus on Interleukins as Disease Drivers and Therapeutic Targets for Novel Treatments.

Atopic dermatitis is a chronic, recurrent inflammatory skin disorder manifesting by eczematous lesions and intense pruritus. Atopic dermatitis develops primarily as a result of an epidermal barrier defect and immunological imbalance. Advances in understanding these pathogenetic hallmarks, and particularly the complex role of interleukins as atopic dermatitis drivers, resulted in achieving significant therapeutic breakthroughs. Novel medications involve monoclonal antibodies specifically blocking the function of selected interleukins and small molecules such as Janus kinase inhibitors limiting downstream signaling to reduce the expression of a wider array of proinflammatory factors. Nevertheless, a subset of patients remains refractory to those treatments, highlighting the complexity of atopic dermatitis immunopathogenesis in different populations. In this review, we address the immunological heterogeneity of atopic dermatitis endotypes and phenotypes and present novel interleukin-oriented therapies for this disease.

The Role of the Cutaneous Mycobiome in Atopic Dermatitis.

Atopic dermatitis is a chronic inflammatory skin disorder characterized by eczematous lesions, itch, and a significant deterioration in the quality of life. Recently, microbiome dysbiosis has been implicated in the pathogenesis of atopic dermatitis. Changes in the fungal microbiome (also termed mycobiome) appear to be an important factor influencing the clinical picture of this entity. This review summarizes the available insights into the role of the cutaneous mycobiome in atopic dermatitis and the new research possibilities in this field. The prevalence and characteristics of key fungal species, the most important pathogenesis pathways, as well as classic and emerging therapies of fungal dysbiosis and infections complicating atopic dermatitis, are presented.

Insights into Modern Therapeutic Approaches in Pediatric Acute Leukemias.

Pediatric cancers predominantly constitute lymphomas and leukemias. Recently, our knowledge and awareness about genetic diversities, and their consequences in these diseases, have greatly expanded. Modern solutions are focused on mobilizing and impacting a patient's immune system. Strategies to stimulate the immune system, to prime an antitumor response, are of intense interest. Amid those types of therapies are chimeric antigen receptor T (CAR-T) cells, bispecific antibodies, and antibody-drug conjugates (ADC), which have already been approved in the treatment of acute lymphoblastic leukemia (ALL)/acute myeloid leukemia (AML). In addition, immune checkpoint inhibitors (ICIs), the pattern recognition receptors (PRRs), i.e., NOD-like receptors (NLRs), Toll-like receptors (TLRs), and several kinds of therapy antibodies are well on their way to showing significant benefits for patients with these diseases. This review summarizes the current knowledge of modern methods used in selected pediatric malignancies and presents therapies that may hold promise for the future.

Cyclosporine With and Without Systemic Corticosteroids in Treatment of Alopecia Areata: A Systematic Review.

INTRODUCTION: Cyclosporine is commonly used in treatment for alopecia areata. It can be administered as a monotherapy or in combination with systemic corticosteroids, with various outcomes. METHODS: Efficacy of cyclosporine with and without systemic corticosteroids for alopecia areata was evaluated by a systematic review. Cochrane, EBSCOhost, Pubmed, Scopus and Web of Science databases were searched. Only studies published before January 2020 were included. RESULTS: A total of 2104 studies were initially examined, of which 14 were eligible for the systematic review. Among 340 reported cases, 213 had focal, multifocal or ophiasis form of alopecia areata, 60 were diagnosed with alopecia totalis and 67 with alopecia universalis. The mean response rate in the whole group of patients at the end of treatment was 65.00% (221/340; range 25-100%). Hair regrowth rate was higher in the group with cases of alopecia areata limited to scalp (124/165; mean 75.15%; range 40-100%) than in the cases with alopecia totalis (30/46; mean 65.22%; range 25-100%) or alopecia universalis (24/52; mean 46.15%; range 25-100%). The combined therapy with systemic corticosteroids was superior to the monotherapy (152/219; mean 69.41%; 0-80% vs. 69/121; mean 57.02%; range 6.67-100%) and had a lower recurrence rate (39/108; mean 36.11% vs. 34/46; mean 73.91%, respectively). The combined treatment with methylprednisolone was significantly more effective when compared to the cyclosporine monotherapy (124/183; mean 67.76%; range 0-80% vs. 69/121; mean 57.02%; range 6.67-100%). The mean time of treatment was 6.75 months (range 2-36). LIMITATIONS: Limitations of our study were the retrospective character of included studies, differences in doses of prescribed drugs, and duration of the treatment and follow-up times. CONCLUSION: Cyclosporine in combination with oral systemic corticosteroids is more effective than in monotherapy for severe alopecia areata.

Looking for novel, brain-derived, peripheral biomarkers of neurological disorders.

The role of blood brain barrier (BBB) is to preserve a precisely regulated environment for proper neuronal signaling. In many of the central nervous system (CNS) pathologies, the function of BBB is altered. Thus, there is a necessity to evaluate a fast, noninvasive and reliable method for monitoring of BBB condition. It seems that revealing the peripheral diagnostic biomarker whose release pattern (concentration, dynamics) will be correlated with clinical symptoms of neurological disorders offers significant hope. It could help with faster diagnosis and efficient treatment monitoring. In this review we summarize the recent data concerning exploration of potential new serum biomarkers appearing in the peripheral circulation following BBB disintegration, with an emphasis on epilepsy, traumatic brain injury (TBI) and stroke. We consider the application of well-known proteins (S100ß and GFAP) as serum indicators in the light of recently obtained results. Furthermore, the utility of molecules like MMP-9, UCHL-1, neurofilaments, BDNF, and miRNA, which are newly recognized as a potential serum biomarkers, will also be discussed.