A review of IL-36: an emerging therapeutic target for inflammatory dermatoses.

BACKGROUND: IL-36 cytokines are members of the IL-1 superfamily. Increasing evidence in the IL-36 pathway demonstrates their potential as a therapeutic target for treating inflammatory skin diseases, such as generalized pustular psoriasis (GPP). OBJECTIVE: A narrative review was written to further study preclinical and clinical evidence for the role of IL-36 in psoriasis, atopic dermatitis (AD), hidradenitis suppurativa (HS), acne, autoimmune blistering diseases, and neutrophilic dermatoses. RESULTS: IL-36 has important downstream effects such as inducing expression of inflammatory cytokines, antimicrobial peptides, and growth factors. Increased expression of IL-36 cytokines has been observed in the lesional skin of patients with psoriasis. Studies of other inflammatory skin diseases have also noted similar findings, albeit to a lesser extent. IL-36 inhibition has been shown to be effective in GPP and is currently being studied for other inflammatory skin diseases. CONCLUSIONS: The IL-36 pathway contributes to pathogenesis of many inflammatory skin diseases and is a promising therapeutic target.

Aryl hydrocarbon receptor/nuclear factor E2-related factor 2 (AHR/NRF2) signalling: A novel therapeutic target for atopic dermatitis.

Aryl hydrocarbon receptor (AHR)/nuclear factor-erythroid 2-related factor 2 (NRF2) modulation is emerging as novel targets in the treatment of atopic dermatitis and other inflammatory skin disorders. Agonist activation of this pathway has downstream effects on epidermal barrier function, immunomodulation, oxidative stress reduction and cutaneous microbiome modulation. Tapinarof, a dual agonist of the AHR/NRF2 signalling pathway, has shown promise in phase 2 trials for atopic dermatitis. In this review, we summarize current knowledge of the AHR/NRF2 pathway and implications in skin disease process. We also review the therapeutic potential of current AHR agonists and propose future directions to address knowledge gaps.

Topical corticosteroid withdrawal ('steroid addiction'): an update of a systematic review.

BACKGROUND: Topical corticosteroid withdrawal is an entity associated with chronic steroid use and misuse that has not been fully described. OBJECTIVE: To further characterize this entity, elucidate relevant clinical features, and investigate possible treatments we provided an update to a systematic review done in 2015. METHODS: We searched Ovid Medline, Pubmed, and Cochrane library for terms related to topical corticosteroid withdrawal from April 2014 to September 2020. RESULTS: This entity usually occurs after prolonged use of moderate- to high-intensity topical steroid usage usually on the face. It is most common in women and many patients present due to improper use such as for cosmetic reasons. Symptoms include erythema, itchiness, and burning; secondary lesions are common scales. LIMITATIONS: Due to the paucity of available study, we elected to include all articles found which led to limitations being lack of heterogeneity, diversity of outcome measures reported, and a higher risk of bias in some included studies. CONCLUSION: Topical corticosteroid withdrawal should be suspected in patients presenting with prolonged usage, erythema, and burning or itch. Patient education and follow up is important to address improper usage. Future studies should focus on comparison group studies to investigate treatment and risk factors.

Updated understanding of Staphylococcus aureus in atopic dermatitis: From virulence factors to commensals and clonal complexes.

Atopic dermatitis (AD) is a common inflammatory dermatosis that has multiple contributing factors including genetic, immunologic and environmental. Staphylococcus aureus (SA) has long been associated with exacerbation of AD. SA produces many virulence factors that interact with the human skin and immune system. These superantigens and toxins have been shown to contribute to adhesion, inflammation and skin barrier destruction. Recent advances in genome sequencing techniques have led to a broadened understanding of the multiple ways SA interacts with the cutaneous environment in AD hosts. For example, temporal shifts in the microbiome, specifically in clonal complexes of SA, have been identified during AD flares and remission. Herein, we review mechanisms of interaction between the cutaneous microbiome and SA and highlight known differences in SA clonal complexes that contribute to AD pathogenesis. Detailed knowledge of the genetic strains of SA and cutaneous dysbiosis is becoming increasingly relevant in paving the way for microbiome-modulating and precision therapies for AD.

Acupuncture in Dermatology: An Update to a Systematic Review.

Objectives: Acupuncture is an important Traditional Chinese Medicine modality based on the fundamental theory that disease is caused by disruptions in the body's qi. Understanding the use of acupuncture in dermatology is important due to the rising prevalence of complementary and alternative medicine use. A systematic review published in 2015 found that acupuncture improves outcomes in several dermatological diseases. We performed a systematic review of studies that have been done since then to present updated evidence. Methods: A systematic search of MEDLINE, EMBASE, and the Cochrane Central Register was performed. Studies were limited to clinical trials, controlled studies, case reports, comparative studies, and systematic reviews published in the English language. Studies involving moxibustion, electroacupuncture, or blood-letting were excluded. Results: Results showed that acupuncture improves clinical outcomes in uremic pruritus, atopic dermatitis, urticaria, and itch. Acupuncture does not significantly reduce postoperative itch in patients undergoing cesarean section under spinal anesthesia. Conclusions: While there are some promising studies that support the use of acupuncture for skin diseases, additional large-scale, randomized, sham-controlled trials need to be performed to present consistent high-level evidence of acupuncture's role in dermatology.

Staphylococcus aureus in Atopic Dermatitis: Past, Present, and Future.

: The role of Staphylococcus aureus (SA) in the pathogenesis and management in atopic dermatitis is rapidly evolving. The modern understanding of SA in atopic dermatitis now includes an expanded array of virulence factors, the interplay of clonal and temporal shifts in SA populations, and host factors such as filaggrin and natural moisturizing factor. New, emerging therapies that focus on long-term, targeted elimination of SA colonization are currently under investigation (Br J Dermatol 2017;17(1)63-71). Herein, we discuss and review the latest staphylococcal and microbiome-modifying therapies including topical antibiotics, topical natural oil fatty acids, anti-SA vaccines, microbial transplantation, vitamin D supplementation, dupilumab and proposed future investigative directions.