Efficacy and safety of the oral JAK3/TEC family kinase inhibitor ritlecitinib over 24 months: integrated analysis of the ALLEGRO phase 2b/3 and long-term phase 3 clinical studies in alopecia areata.

BACKGROUND: The ALLEGRO phase 2a and 2b/3 studies demonstrated that ritlecitinib is efficacious and well tolerated in adult and adolescent patients with alopecia areata (AA) up to 48 weeks. OBJECTIVE: The efficacy of ritlecitinib through Month 24 and safety through data cutoff were assessed in the ALLEGRO phase 2b/3 study and the ongoing long-term, open-label, phase 3 ALLEGRO-LT study. METHODS: Patients aged ≥12 years with AA and ≥50% scalp hair loss from ALLEGRO-2b/3 who rolled over to ALLEGRO-LT after up to 48 weeks were included. Proportions of patients with responses based on clinician-reported Severity of Alopecia Tool (SALT) score of ≤20 and ≤10, eyebrow assessment (EBA) and eyelash assessment (ELA), patient global impression of change (PGI-C) and patient satisfaction with hair growth are reported through Month 24 for patients who received ritlecitinib 50 mg daily with or without a 200-mg 4-week daily loading dose. Observed and imputed data (last observation carried forward [LOCF]) were reported until December 9, 2022. Safety was assessed throughout. RESULTS: At Month 12, SALT score ≤20 was achieved by 45.1% and 45.9% (observed) and 40.3% and 41.8% (LOCF) of the 191 and 194 patients who received ritlecitinib 50 mg and ritlecitinib 200/50 mg, respectively. At Month 24, proportions increased to 60.8% and 63.1% (observed) and 46.1% and 50.8% (LOCF), respectively. Patients with abnormal EBA or ELA scores at baseline achieved responses at Month 24 (EBA observed: 57.6% [50 mg], 61.0% [200/50 mg]; EBA LOCF: 46.8% [50 mg], 50.9% [200/50 mg]; ELA observed: 51.2% [50 mg], 62.7% [200/50 mg]; ELA LOCF: 43.2% [50 mg], 51.7% [200/50 mg]). PGI-C response was achieved by patients at Month 24 (observed: 70.0% [50 mg], 76.4% [200/50 mg]; LOCF: 56.6% [50 mg], 65.5% [200/50 mg]). Safety profiles for both treatment groups were consistent with the known safety profile of ritlecitinib. CONCLUSION: Ritlecitinib has clinically meaningful and sustained efficacy beyond 1 year with a favourable safety and tolerability profile, supporting its long-term use in patients aged ≥12 years with AA. TRIAL REGISTRIES: ClinicalTrials.gov: NCT03732807, NCT04006457.

A study to understand the effect of ritlecitinib 50 milligrams once daily in people with alopecia areata treated for up to 2 years Alopecia areata (AA) is a condition where the immune system mistakenly attacks hair follicles, causing hair loss. It affects around 2% of people worldwide, including children and adults. AA may involve small patches or complete loss of hair on the scalp and/or body. People with AA may need to use medicines for a long time to manage hair loss. But there are not many options available. Ritlecitinib is a pill taken by mouth daily to treat severe AA. It blocks the steps that cause hair loss. In the ALLEGRO-LT study, we looked at how well ritlecitinib worked over 2 years in people aged 12 years and older with AA who had lost at least half of their scalp hair. We measured hair loss on the scalp, eyebrows and eyelashes, as well as how satisfied people were with their hair regrowth. We also looked at how safe ritlecitinib was when taken for 2 years. A total of 191 people from 17 countries took ritlecitinib 50 milligrams (the approved dose). After 1 year, 74 out of 164 people (45%) had scalp hair regrowth (20% or less scalp hair loss), increasing to 61% after 2 years. For every 8 out of 10 people, their scalp hair regrowth was maintained from 1 to 2 years. Eyebrow and eyelash hair regrowth also increased over 2 years. Around 8 out of 10 people were satisfied with their hair growth after 2 years, and the safety of ritlecitinib was as expected from the studies done before. The results show that ritlecitinib is effective and appropriate for long-term use in people aged 12 years and older with AA.

Dermoscopic characteristics of cutaneous larva migrans in dark skin: a study from Banjul, The Gambia.

Cutaneous larva migrans (CLM) results from hookworm larvae infestation, mainly Ancylostoma braziliense or Ancylostoma caninum. It is common in Sub-Saharan Africa, often acquired through soil contact, especially in sandy beaches, manifesting as serpiginous, erythematous and intensely pruritic tracts within the epidermis, and presenting with diverse clinical appearances. Diagnosis is mostly clinical; however, dermoscopy can enhance diagnostic accuracy and distinction from mimics. The current body of literature is deficient in its representation of dermoscopic data for CLM in Black patients. This study explores dermoscopy in nine dark-skinned patients with 16 CLM lesions. Distinctive serpiginous structureless areas displaying a range of colours, peripheral scales surrounding brown areas and brown dots were predominant features, whereas vascular characteristics were less evident. This article highlights the presence of distinct reaction patterns, including brown dots, scales, and accentuated, often disrupted brown reticular lines in addition to the characteristic winding tracts in darker skin.

Consensus statement on the diagnosis and treatment of sclerosing diseases of the skin, Part 2: Scleromyxoedema and scleroedema.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 2 of this consensus provides clinicians with an overview of the diagnosis and treatment of scleromyxoedema and scleroedema (of Buschke).

HPV Infections-Classification, Pathogenesis, and Potential New Therapies.

To date, more than 400 types of human papillomavirus (HPV) have been identified. Despite the creation of effective prophylactic vaccines against the most common genital HPVs, the viruses remain among the most prevalent pathogens found in humans. According to WHO data, they are the cause of 5% of all cancers. Even more frequent are persistent and recurrent benign lesions such as genital and common warts. HPVs are resistant to many disinfectants and relatively unsusceptible to external conditions. There is still no drug available to inhibit viral replication, and treatment is based on removing lesions or stimulating the host immune system. This paper presents the systematics of HPV and the differences in HPV structure between different genetic types, lineages, and sublineages, based on the literature and GenBank data. We also present the pathogenesis of diseases caused by HPV, with a special focus on the role played by E6, E7, and other viral proteins in the development of benign and cancerous lesions. We discuss further prospects for the treatment of HPV infections, including, among others, substances that block the entry of HPV into cells, inhibitors of viral early proteins, and some substances of plant origin that inhibit viral replication, as well as new possibilities for therapeutic vaccines.

EGFR inhibitor-induced folliculitis decalvans: a case series and management guidelines.

Epidermal growth factor receptor (EGFR) is one of therapeutic targets in oncology for solid tumors originating from epithelial tissue, such as non-small-cell lung carcinoma (NSCLC) and breast cancer. EGFR inhibitors used in cancer treatment may cause a broad spectrum of dose-dependent cutaneous adverse events, including acneiform papulopustular rash, nail and hair disturbances, xerosis, and mucositis. The pathogenesis of the EGFR inhibitor-induced adverse reactions originates from disturbances in keratinocyte differentiation, cytokine secretion, and neutrophil chemotaxis. One of the rare, yet distressing adverse events may be folliculitis decalvans, a progressive neutrophil-driven scarring alopecia with hair tufts formation resembling doll's hair. Early diagnosis and introduction of treatment are crucial for disease prognosis since a long course of the disease leads to decreased quality of life. Here, we review the literature cases of EGFR inhibitor-induced folliculitis decalvans and provide guidance on management and prevention of this condition in oncologic patients. Furthermore, we report the first afatinib-associated folliculitis decalvans in three female patients with NSCLC.

Differential diagnosis of red scalp. The importance of trichoscopy.

Red scalp is a common complaint which may constitute a diagnostic and therapeutic challenge in daily clinical practice. Among the numerous diseases which cause diffuse scalp erythema are psoriasis, seborrheic dermatitis, contact dermatitis, diffuse lichen planopilaris, dermatomyositis and scalp rosacea. Accurate diagnosis is crucial for optimal treatment outcomes. Histology most frequently discriminates the underlying condition, but it requires scalp biopsy. In many cases the combination of clinical examination and trichoscopy is sufficient for establishing the correct diagnosis. The main trichoscopic features of psoriasis are silver-white scaling, regular distributed dotted (glomerular) vessels or twisted red loops and punctate hemorrhages. Yellowish-white scaling and thin arborizing vessels are typical features of seborrheic dermatitis. Contact dermatitis is characterized by the presence of yellow exudate and polymorphic vessels, while perifollicular scaling and erythema with the lack of follicular openings are typical findings in lichen planopilaris. In scalp dermatomyositis, tortuous and arborizing vessels with interfollicular and perifollicular pigmentation may be detected. The most characteristic features of scalp rosacea are perifollicular scaling and arborizing vessels. This review also summarizes histologic features and therapeutic options for these conditions.

Multilocus-sequence typing reveals clonality of Staphylococcus aureus in atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is exacerbated by Staphylococcus aureus, which is capable of displacing not only the physiological microbiota, but also other strains of its own species. Analyses of the molecular characteristics and relationships of S. aureus strains present in different microniches are lacking. OBJECTIVES: To determine, using multilocus sequence typing (MLST), the relationship of S. aureus isolates from the lesional and nonlesional skin and anterior nares of patients with AD, and to review the characteristics of the dominant clones. METHODS: Sixty-three individuals with active AD were enrolled. Ten patients with moderate-to-severe AD (SCoring of Atopic Dermatitis score ≥ 25) colonized by S. aureus in all analysed locations were included in the MLST analysis. RESULTS: The most prevalent sequence types were 7 (10/30 strains; 33.3%), 15 and 97 (both 5/30 strains; 16.7%) all of which were associated with the expression of adhesins and toxins promoting chronic microbial dysbiosis, skin barrier damage and inflammation. Six patients (60%) were carriers of clonal S. aureus strains at all analysed locations, three (30%) carriers in lesional and nonlesional skin, and one (10%) was a carrier in nonlesional skin and the anterior nares. CONCLUSIONS: The results imply that the identified S. aureus lineages are better adapted to dominate the microbiota in AD. Decontaminating the identified reservoirs of S. aureus (i.e. anterior nares and nonlesional skin) could reduce the severity of AD.

The role of trichoscopy beyond hair and scalp diseases. A review.

Trichoscopy is a diagnostic tool for hair and scalp diseases. It was recently shown that it also allows the identification of features associated with disorders that typically do not affect the scalp. The aim of this article was to analyse and outline the usefulness of trichoscopy in suspecting such diseases. Connective tissue diseases were the most investigated systemic disorders in regard to trichoscopy. The most common features of systemic lupus erythematosus, systemic sclerosis and dermatomyositis are thick arborizing and tortuous vessels. Avascular areas are present in systemic sclerosis. Spermatozoa-like vessels may be observed in cutaneous T-cell lymphomas, while salmon-coloured areas with arborizing and linear vessels may be seen in patients with cutaneous B-cell lymphomas. In patients with advanced multiple myeloma, follicular spicules may be observed. Trichoscopic features of angiosarcomas include pink areas, red, polymorphic areas and dark red to purple areas. Polymorphous vessels and whitish areas on a pink background are the predominating trichoscopic features of metastases of malignant tumours to the scalp. Cutaneous sarcoidosis is characterized by orange-coloured areas and telangiectasias. Systemic amyloidosis may manifest with salmon-coloured perifollicular halos, while the most common trichoscopic features of syphilitic alopecia are as follows: decreased number of hairs per follicular unit, vellus hairs, background erythema, focal atrichia and yellow dots. In conclusion, dermatologists may suspect some systemic diseases on the basis of trichoscopic findings.

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.

Bacterial Metabolites: A Link between Gut Microbiota and Dermatological Diseases.

Dysbiosis has been identified in many dermatological conditions (e.g., psoriasis, atopic dermatitis, systemic lupus erythematosus). One of the ways by which the microbiota affect homeostasis is through microbiota-derived molecules (metabolites). There are three main groups of metabolites: short-chain fatty acids (SCFAs), tryptophan metabolites, and amine derivatives including trimethylamine N-oxide (TMAO). Each group has its own uptake and specific receptors through which these metabolites can exert their systemic function. This review provides up-to-date knowledge about the impact that these groups of gut microbiota metabolites may have in dermatological conditions. Special attention is paid to the effect of microbial metabolites on the immune system, including changes in the profile of the immune cells and cytokine disbalance, which are characteristic of several dermatological diseases, especially psoriasis and atopic dermatitis. Targeting the production of microbiota metabolites may serve as a novel therapeutic approach in several immune-mediated dermatological diseases.

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.

Digital pitting scars are associated with a severe disease course and death in systemic sclerosis: a study from the EUSTAR cohort.

OBJECTIVE: Digital pitting scars (DPS) are frequent, but little studied in SSc to date. METHODS: An analysis of SSc patients enrolled in the EUSTAR database. Primary objectives were to (i) examine DPS prevalence; (ii) examine whether DPS are associated with digital ulcers (DUs) and active digital ischaemia (DUs or gangrene); and (iii) describe other associations with DPS including internal organ complications. Secondary objectives were whether DPS are associated with (i) functional impairment; (ii) structural microvascular disease; and (iii) mortality. Descriptive statistics and parametric/non-parametric tests were used. Binary logistic regression was used to examine the association between DPS and DUs, active digital ischaemia and mortality. RESULTS: A total of 9671 patients were included with reported DPS at any time point (n = 4924) or 'never' DPS (n = 4747). The majority (86.9%) were female and mean age was 55.7 years. DPS were associated with longer disease and Raynaud's duration (both P ≤ 0.001). DPS were associated with interstitial lung disease, pulmonary hypertension, conduction blocks, telangiectases, calcinosis (all P ≤ 0.001) and joint synovitis (P = 0.021). Patients were more likely to have more severe capillaroscopic abnormality and greater hand functional impairment. Multivariable logistic regression analyses showed that DPS were associated (odds ratio) with DUs: 22.03 (19.51-24.87), active digital ischaemia: 6.30 (5.34-7.42) and death: 1.86 (1.48-2.36). CONCLUSION: DPS are associated with a severe disease course including death. The impact of DPS on hand function and ischaemia is significant. The presence of DPS should alert the clinician to a poor prognosis and need to optimize the therapeutic strategy.

Diagnostic Accuracy of Trichoscopy in Inflammatory Scalp Diseases: A Systematic Review.

BACKGROUND: The common inflammatory scalp diseases, such as psoriasis, seborrheic dermatitis, lichen planopilaris, discoid lupus erythematosus, contact dermatitis, or pemphigus may share similar clinical features. OBJECTIVE: To identify and systematically review the available evidence on the accuracy of trichoscopy in inflammatory scalp disorders. METHODS: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 58 articles were included in the analysis. RESULTS: The following trichoscopy features were found to show the highest specificity for the respective diseases: in psoriasis: diffuse scaling, simple and twisted red loops, red dots and globules, and glomerular vessels; in seborrheic dermatitis: atypical vessels, thin arborizing vessels, and structureless red areas; in discoid lupus erythematosus: follicular plugs and erythema encircling follicles; in lichen planopilaris: milky red areas or fibrotic patches; in contact dermatitis: twisted red loops; in pemphigus foliaceus: white polygonal structures and serpentine vessels; in pemphigus vulgaris: red dots with whitish halo and lace-like vessels; and in dermatomyositis: lake-like vascular structures. LIMITATIONS: Different nomenclature and variability in parameters, which were analyzed in different studies. CONCLUSION: This systemic analysis indicates that trichoscopy may be used with high accuracy in the differential diagnosis of inflammatory scalp diseases.

Does topical minoxidil at concentrations higher than 5% provide additional clinical benefit?

Minoxidil solution is used for the treatment of androgenetic alopecia (AGA). Minoxidil 5% solution has been shown to have superior efficacy to minoxidil 2% solution, it is unknown whether concentrations of minoxidil > 5% provide additional clinical benefit. We performed a review of the literature to examine the evidence on the efficacy and safety of higher concentrations of minoxidil in AGA. A search of the PubMed database was performed using the keywords 'minoxidil', 'androgenic alopecia' and 'pattern hair loss'. Relevant articles, including clinical trials, other clinical studies, case series and case reports published in English were considered for review. In addition, relevant references from the bibliography section of the retrieved articles were also reviewed.

Patients with alopecia areata are at risk of endothelial dysfunction: results of a case-control study.

BACKGROUND: Alopecia areata (AA) is an autoimmune form of hair loss, which may affect any hair-bearing area. It has been suggested that AA is associated with an increased risk of metabolic and cardiovascular comorbidities. AIM: To evaluate the early predictors of cardiovascular disease [endothelial function (EF) and arterial stiffness (AS)] in patients with AA without prior cardiovascular disease, and compare with healthy controls (HCs). METHODS: In total, 52 patients with AA (38 women and 14 men; mean age 41 years, range 30-52 years) and 34 HCs, matched for age, sex and body mass index, were enrolled in the study. EF, expressed as reactive hyperaemia index (RHI), and AS, identified by augmentation index at 75 beats/min (AI@75) were assessed with the use of the Endo-PAT 2000 device. Endothelial dysfunction (ED) was defined as RHI value ≤1.67. RESULTS: ED was observed in 22 of 52 patients with AA (42%) and in 4 of 34 HCs (12%) (P < 0.01). Moreover, mean RHI was lower in patients with AA compared with HCs (1.90 ± 0.31 vs. 2.11 ± 0.45; P = 0.03). There was no significant difference in AI@75 between patients with AA and HCs. CONCLUSIONS: Patients with AA show abnormalities in early predictors of cardiovascular diseases. Regular cardiovascular screening might be appropriate for patients with AA.

Artificial Intelligence in Hair and Nail Disorders.

Artificial intelligence (AI), a field of computer science, aims at simulating human intelligence with computers. Though AI has surpassed dermatologists in skin cancer detection, it still lags behind various other specialties like radiologists in broader adoption. Newer AI applications are becoming increasingly accessible. AI plays a role in various areas, such as medical image recognition, auxiliary diagnosis, and drug research and development. Dermatology has a prime position in implementation of AI in medical research due to its larger clinical, dermoscopic, and histopathological image database. Hence, it is crucial to consider the potential and emerging role of AI in dermatology clinical practice. There are already studies focusing on various skin disorders like cancer, psoriasis, atopic dermatitis, etc. This article provides an overview of AI and its applications in hair and nail disorders at present and its future potential. J Drugs Dermatol. 2022;21(10):1049-1052. doi:10.36849/JDD.6519.

Treatment of Alopecia in Children.

Alopecia or hair loss in children is an important and often challenging problem to diagnose and treat. Early diagnosis and treatment is the key because hair loss in children has a significant physical as well as psychological impact on their development. Alopecia in children are mainly non-scarring, but cicatricial alopecia can also be seen. The diagnosis can usually be made by direct examination of the scalp. Potassium hydroxide (KOH) examination of plucked hair and scalp scrapings, woods lamp examination and trichoscopy are useful diagnostic aids. When a cicatricial alopecia is suspected, scalp biopsy is recommended. Disease specific treatment should be initiated early and adequate counselling provided to both the patient and their parents. This review focuses on the treatment options available for various types of alopecia in children and their safety and efficacy data, analyzing the available literature evidences. J Drugs Dermatol. 2022;21(1):49-53. doi:10.36849/JDD.6096.

The Analysis of a Genome-Wide Association Study (GWAS) of Overweight and Obesity in Psoriasis.

There is evidence that the concomitance of psoriasis and obesity may originate from the interplay between multiple genetic pathways and involve gene−gene interactions. The aim of this study was to compare the genetic background related to obesity among psoriatic patients versus healthy controls by means of a Genome-Wide Association Study (GWAS). A total of 972 psoriatic patients and a total of 5878 healthy donors were enrolled in this study. DNA samples were genotyped for over 500,000 single nucleotide polymorphisms (SNPs) using Infinium CoreExome BeadChips (Illumina, San Diego, CA, USA). Statistical analysis identified eleven signals (p < 1 × 10−5) associated with BMI across the study groups and revealed a varying effect size in each sub-cohort. Seven of the alternative alleles (rs1558902 in the FTO gene, rs696574 in the CALCRL gene, as well as rs10968110, rs4551082, rs4609724, rs9320269, and rs2338833,) are associated with increased BMI among all psoriatic patients and four (rs1556519 in the ITLN2 gene, rs12972098 in the AC003006.7 gene, rs12676670 in the PAG1 gene, and rs1321529) are associated with lower BMI. The results of our study may lead to further insights into the understanding of the pathogenesis of obesity among psoriatic patients.

Contact eczema induced by hybrid manicure. The role of acrylates as a causative factor.

Introduction: Acrylates are widespread plastic materials, known for their sensitizing properties. So far, allergy to acrylate monomers has been known as occupational eczema, mainly concerning dentists and manicurists. However, a surge of allergic contact dermatitis (ACD) cases related to acrylates among users of hybrid varnishes have recently been reported. Aim: This article reviews the pathogenesis, clinical manifestations, and dermoscopic features of contact eczema induced by hybrid manicure. Material and methods: The study was performed on a group of 8 women. Clinical and dermoscopic features were evaluated and correlated with the period of exposure to acrylates. In addition, all patients underwent mycological examination to exclude fungal co-infection. Results: Mycological examinations in all patients gave negative results, although 1 patient developed local secondary mixed supra-infection due to Pseudomonas aeruginosa and Candida spp. Distribution of clinical manifestations corresponded to the area of contact with the allergen and comprised both skin and nail changes. The severity of inflammation correlated positively with the exposure period. Subungual hyperkeratosis and onycholysis were the most common findings (8/8 patients), and eczematous finger pulp fissuring was a rarer sign (2/8 patients) but more specific clinically. Conclusions: The surge of contact dermatitis related to acrylates seen in recent years requires dermatologists' awareness. Nail changes induced by hybrid manicure can mimic onychomycosis or nail psoriasis. Therefore comprehensive patch testing should be performed in doubtful cases. Due to the lack of patch tests in our study, we can only suspect that we were dealing with allergic contact dermatitis. In case of confirmed allergy to acrylates, the patient should be aware of this and avoid them.

3D skin bioprinting: future potential for skin regeneration.

Skin provides protection against external agents and plays an essential role in maintaining the body homeostasis. Bioprinting as a novel strategy involves computer-controlled deposition of cells and scaffolds into a three-dimensional (3D) construction of skin. 3D bioprinting gives an opportunity to generate multi-layered vascularized skin grafts that can overcome the limitations of current skin substitutes. The main indication is treatment of troublesome wounds, especially severe burns and non-healing chronic lesions. Bioprinted skin equivalents offer a promising approach in the field of regenerative medicine. This review presents and discusses 3D skin construct formation, its limitations and modifications, and its usefulness.