Emerging Treatment Regimens in Psoriasis: Are There Advantages Over Current Biologic Therapies?

Psoriasis is a chronic inflammatory skin condition that impacts patients’ quality of life and has large economic consequences. While current biologics are remarkable for their efficacy and safety, opportunities for improvement exist due to their rare side effects, fading efficacy, method of delivery, and expense. Biologics such as bimekizumab offer high likelihood of clearance, while oral options (e.g., deucravacitinib) allow patients to avoid injections and achieve efficacies similar to adalimumab or ustekinumab. As a result, there is limited room for the development of new biologics. Several oral therapies such as the oral monoclonal microbial EDP1815 have the potential to meet patient expectations for efficacy and convenient administration. However, emerging treatment regimens for plaque psoriasis will increasingly require a multimodal approach, addressing patient adherence, lifestyle choices, and awareness of the individual’s underlying pathophysiological processes. In this narrative review, the authors discuss recent advances in the development of biologic and oral small molecules for plaque psoriasis.

Mosaicism in Tuberous Sclerosis Complex: A Case Report, Literature Review, and Original Data from Danish Hospitals

Tuberous sclerosis complex (TSC) is an autosomal dominant hereditary disease with hamartomatous growths in multiple organs due to loss-of-function variants in TSC1 or TSC2. In approximately 15% of patients with clinical TSC, no pathogenic variant can be identified, and low-level mosaicism is suggested to be one of the reasons. Mosaicism is well-known in TSC and challenges the molecular genetic diagnosis. The advent of next-generation sequencing has improved the diagnostics in TSC including in patients with mosaicism. The TSC phenotype varies widely, and mosaic patients with TSC are often considered to have a milder phenotype. Here, the authors describe a patient with mosaic TSC with a 10% variant allele fraction and manifestations in three organ systems (skin, eyes, and kidneys). Furthermore, the authors studied existing literature about phenotypic organ manifestations in patients with mosaic TSC. No clear definition of the phenotype of patients with mosaic TSC could be established, but unilateral angiofibromas and the absence of tubers and a subependymal nodule could indicate mosaicism. The case shows that patients with low-level mosaic TSC can have multiple affected organ systems though still a mild clinical picture.

Celebrating Outstanding Science at the European Academy of Dermatology and Venereology’s 30th Anniversary Congress

THE ANNIVERSARY edition of the European Academy of Dermatology and Venereology’s (EADV) 30th Congress was held between 29th September and 2nd October 2021. As COVID-19 remains a barrier to global travel, the EADV’s 30th Anniversary Congress was staged virtually, providing access to the latest research, breakthroughs, and scientific advances to dermato-venereology professionals.

Emerging Drugs in Dermatology

The ANNUAL European Academy of Dermatology and Venereology (EADV) Virtual Congress 2021 featured the latest updates on emerging drugs in dermatology. Presentations covered a wide range of topics such as immunotherapy versus targeted therapy in melanoma, targeting cytokine pathways in psoriasis, emerging biologics, and the promise of personalised medicine in dermatology.

Eleven Myths on Nail Melanoma

Tuberous sclerosis complex (TSC) is an autosomal dominant hereditary disease with hamartomatous growths in multiple organs due to loss-of-function variants in TSC1 or TSC2. In approximately 15% of patients with clinical TSC, no pathogenic variant can be identified, and low-level mosaicism is suggested to be one of the reasons. Mosaicism is well-known in TSC and challenges the molecular genetic diagnosis. The advent of next-generation sequencing has improved the diagnostics in TSC including in patients with mosaicism. The TSC phenotype varies widely, and mosaic patients with TSC are often considered to have a milder phenotype. Here, the authors describe a patient with mosaic TSC with a 10% variant allele fraction and manifestations in three organ systems (skin, eyes, and kidneys). Furthermore, the authors studied existing literature about phenotypic organ manifestations in patients with mosaic TSC. No clear definition of the phenotype of patients with mosaic TSC could be established, but unilateral angiofibromas and the absence of tubers and a subependymal nodule could indicate mosaicism. The case shows that patients with low-level mosaic TSC can have multiple affected organ systems though still a mild clinical picture.

Botulinum Toxins in Medical and Cosmetic Dermatology

Background: Botulinum toxin (BoNT), a bacterially produced neurotoxin, is a mainstay in the dermatologic armamentarium. Although BoNT is commonly used to treated rhytides associated with ageing, it can be employed for a variety of other cosmetic purposes and medical disorders. Objective: In this review, the authors aim to describe the multitude of uses for BoNT in the dermatologic field. Materials and Methods: This manuscript was designed as a retrospective review of the on- and off-label applications of BoNT in dermatology.Results: In addition to treatment of rhytides, BoNT has been shown to decrease rosacea, menopause-associated flushing, and facial sebum production, while improving patient confidence in their appearance. Furthermore, BoNT has been successfully used to treat primary hyperhidrosis, hair loss, aberrant scarring, Raynaud’s phenomenon-associated vasospasm, as well as a variety of skin diseases. Side effects of BoNT include pain or discomfort associated with injections during treatment, bruising, asymmetry, and swelling. Patients are generally satisfied with clinical results after BoNT treatment. Conclusion: Dermatologists should be aware of all on- and off-label applications of BoNT to provide patients with timely and appropriate medical care. Further research must be completed to fully characterise the safety and use of BoNT for off-label purposes.

Case Report: Suspected Case of Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis Overlap Due to Ursodeoxycholic Acid

Stevens–Johnson syndrome and toxic epidermal necrolysis are well-known severe cutaneous adverse reactions, with >100 medications previously implicated, most frequently sulfonamide antibiotics. Ursodeoxycholic acid (UDCA), normally present in human bile at a low concentration, is used for the treatment of various cholestatic disorders. Reports of UDCA causing cutaneous complications are, however, rare. The present report describes a suspected case of UDCA-induced Stevens–Johnson syndrome–toxic epidermal necrolysis overlap in a 24-year-old female, admitted with a whole-body maculopapular rash with oromucocutaneous ulceration and skin desquamation. The patient was managed with supportive care, including fluid and electrolyte replacement, corticosteroids, antibiotics, antihistamines, and intravenous Ig. Early identification, prompt intervention with effective care, and support are the key action points in these severe cutaneous adverse reactions.

Impaired Mitochondrial and Metabolic Function of Fibroblasts Derived from Patients with Recessive Dystrophic and Junctional Epidermolysis Bullosa

Background: Recessive dystrophic epidermolysis bullosa (RDEB) and junctional EB (JEB) are inherited disorders characterised by fragility and blistering of epithelial tissues leading to pain, pruritus, and adherent scarring. The severity and chronic nature of the resultant skin wounds significantly reduces quality and length of life. Current therapies primarily consist of protective bandaging and nutritional supplementation; there is no cure for these disorders. Although the skin fragility results from a lack of C7 protein (RDEB) and laminin-332 (JEB), other serious aspects of these disorders, such as inflammation that interferes with healing and aggressive squamous cell carcinoma, have not been completely elucidated. Recent research has suggested that mitochondrial function plays a significant role in skin healing. Objective: To evaluate how mitochondrial function differs in patients with RDEB and JEB. Method: The energy status of RDEB and JEB patient-derived fibroblasts was determined by Seahorse analysis and metabolite production. The energetics and overall morphology of RDEB and JEB patient-derived fibroblasts were assayed as a measure of metabolic stress. Results: EB patient-derived fibroblasts showed impaired oxidative phosphorylation with concomitant compensation by glycolysis. Morphological parameters were altered in RDEB and JEB fibroblasts compared with controls. Conclusion: This is the first study to describe changes in mitochondrial energy metabolism, metabolic profile, and mitochondrial morphology of EB patients.

Managing Chronic Urticaria: Quo Vadis?

Chronic urticaria (CU) is one of the most commonly diagnosed skin conditions. CU is characterised by the presence of recurrent wheals and/or angioedema and intense pruritus persisting for at least 6 weeks. Subtypes of CU include chronic spontaneous urticaria and chronic inducible urticaria. Following diagnosis, adequate trigger identification and appropriate treatment can significantly reduce disease activity and improve the patient’s quality of life and disease outcomes. Current guidelines recommend a stepwise approach in the management of CU, including non-sedating oral antihistamines, administered in up to four times the conventional dose, the monoclonal antibody omalizumab (anti-IgE), and eventually cyclosporine as an add-on therapy for patients with antihistamine-refractory CU. Potential disease-related biomarkers are needed to predict the therapeutic response that would lead to establishment of personalised regimens and treatment plans. This paper reviews the current perspectives and guidelines for classification, diagnosis, and management of CU.

Differential Diagnosis of Nail Psoriasis and Onychomycoses: A Report Based on 40 Years of Specialised Nail Consultations

Ungual psoriasis and onychomycosis are common nail diseases. Despite their different aetiology and course, surprisingly they have much in common both clinically and histopathologically, rendering their distinction often very challenging. Because their treatments are fundamentally different, anti-inflammatory–immunosuppressive for psoriasis and anti-infective for onychomycoses, an exact diagnosis is crucial for their management. Psoriasis is the dermatosis with the most frequent nail involvement. Pits, ivory-coloured spots, salmon or oil spots, subungual hyperkeratosis, onycholysis, and splinter haemorrhages are the most common nail signs. Onychomycoses are thought to be the most frequent nail diseases. This statement is disputed for toenails, for which orthopaedic abnormalities are said to be even more frequent and mimic fungal nail infections.