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SOX10 is a transcription factor expressed in nerve cells and melanocytes. The aim of this study was to investigate the protein expression pattern of SOX10 in malignant melanoma tumors and to analyze whether the results correlated with clinical parameters and the proliferation marker Ki-67. Furthermore, proliferation and migration were analyzed in three different cell lines employing SOX10 small interfering RNA-mediated silencing. Expression patterns were determined in 106 primary tumors and 39 metastases in addition to 16 normal skin samples and six benign nevi employing immunohistochemistry and tissue microarrays. The immunohistochemical staining was evaluated manually and with an automated algorithm. SOX10 was strongly expressed in the benign tissues, but for the malignant tumors superficial spreading melanomas stained stronger than nodular malignant melanomas (P=0.008). The staining intensity was also inversely correlated with T-stage (Spearman's ρ=-0.261, P=0.008). Overall survival and time to recurrence were significantly correlated with SOX10 intensity, but not in multivariate analysis including T-stage. With the automated algorithm there was an inverse correlation between the SOX10 staining intensity and the proliferation marker, Ki-67 (ρ=-0.173, P=0.02) and a significant difference in the intensity signal between the benign tissues, the primary tumors and the metastases where the metastases stained the weakest (P≤0.001). SOX10 downregulation resulted in variable effects on proliferation and migration rates in the melanoma cell lines. In conclusion, the SOX10 intensity level differed depending on the tissue studied and SOX10 might have a role in survival. No conclusion regarding the role of SOX10 for in-vitro proliferation and migration could be drawn.

Tryptase is a tetrameric serine protease located within the secretory granules of mast cells. In the secretory granules, tryptase is stored in complex with negatively charged heparin proteoglycans and it is known that heparin is essential for stabilizing the enzymatic activity of tryptase. However, recent findings suggest that enzymatically active tryptase also can be found in the nucleus of murine mast cells, but it is not known how the enzmatic activity of tryptase is maintained in the nuclear milieu. Here we hypothesized that tryptase, as well as being stabilized by heparin, can be stabilized by DNA, the rationale being that the anionic charge of DNA could potentially substitute for that of heparin to execute this function. Indeed, we showed that double-stranded DNA preserved the enzymatic activity of human β-tryptase with a similar efficiency as heparin. In contrast, single-stranded DNA did not have this capacity. We also demonstrated that DNA fragments down to 400 base pairs have tryptase-stabilizing effects equal to that of intact DNA. Further, we showed that DNA-stabilized tryptase was more efficient in degrading nuclear core histones than heparin-stabilized enzyme. Finally, we demonstrated that tryptase, similar to its nuclear localization in murine mast cells, is found within the nucleus of primary human skin mast cells. Altogether, these finding reveal a hitherto unknown mechanism for the stabilization of mast cell tryptase, and these findings can have an important impact on our understanding of how tryptase regulates nuclear events. 

Background: Hyaluronic acid dermal fillers are used for multiple indications, including wrinkle correction and restoration of volume/fullness. Objectives: The aim of this study was to compare the efficacy and safety of 2 hyaluronic acid products for correcting moderate to severe nasolabial folds (NLFs). Methods: A prospective, randomized, double-blind, split-face study was undertaken. The subjects' left and right NLFs were randomly allocated for treatment with DKL23 or Juvederm Volift. Follow-up was conducted at 1, 3, 6, and 9 months. The changes from baseline on the Wrinkle Severity Rating Scale and the Global Aesthetics Improvement Scale were evaluated. Posttreatment adverse events (AEs) were recorded. Results: Forty-eight women (median age, 57.0 years) with Type I to VI skin were enrolled. Both treatments showed statistically significant improvement (P < .0001) in NLFs according to the Wrinkle Severity Rating Scale score from baseline to each of the time points assessed. The improvement in NLFs was maintained until the end of the study (9 months). Furthermore, the change from baseline to each of the time points assessed was similar between DKL23 and Juvederm Volift. Investigator- and subject-rated Global Aesthetics Improvement Scale scores showed similar rates of improvement (indicated by the sum of responses of improved, much improved, or very much improved) between the 2 products. The AEs reported in the study were in line with previous and expected experience after injection of hyaluronic acid dermal fillers. The types of AEs, their rates, intensity, and duration were comparable between the 2 products. Conclusions: DKL23 improved NLF severity from baseline and for up to 9 months, and the results were comparable to the improvement shown by Juvederm Volift. Treatment was safe and well tolerated.

Retinal infarction and scalp necrosis are described as unusual but devastating complications of giant-cell arteritis. We report a patient with this rare complication and emphasize the importance of timely diagnosis and treatment of giant-cell arteritis.

Botulinum toxin (BoNT) injections into facial and bulbar muscles are widely and increasingly used as medical treatments for cervical and facial dystonia, facial hemispasm, correction of facial palsy, hyperhidrosis, as well as cosmetic treatment of glabellar lines associated with grief and anger. Although BoNT treatment is generally considered safe, the diffusion of the toxin to surrounding muscles may result in complications, including difficulties swallowing, in a dose-dependent manner. The sensitivity of clinical examination for detecting adverse events after BoNT treatment is limited. Few reports have highlighted the potential effects on other muscles in the facial area due to the spreading of the toxin. The possibilities of spreading and thus unknown pharmacological BoNT effects in non-targeted muscles emphasise the importance of correct administration of BoNT in terms of dose selection, injection points, and appropriate effect surveillance. In this review article, we will focus on novel objective measures of efficacy and safety regarding BoNT treatment of facial muscles and the reasons why this is important.

Single-cell technologies have become essential to driving discovery in both basic and translational investigative dermatology. Despite the multitude of available datasets, a central reference atlas of normal human skin, which can serve as a reference resource for skin cell types, cell states, and their molecular signatures, is still lacking. For any such atlas to receive broad acceptance, participation by many investigators during atlas construction is an essential prerequisite. As part of the Human Cell Atlas project, we have assembled a Skin Biological Network to build a consensus Human Skin Cell Atlas and outline a roadmap toward that goal. We define the drivers of skin diversity to be considered when selecting sequencing datasets for the atlas and list practical hurdles during skin sampling that can result in data gaps and impede comprehensive representation and technical considerations for tissue processing and computational analysis, the accounting for which should minimize biases in cell type enrichments and exclusions and decrease batch effects. By outlining our goals for Atlas 1.0, we discuss how it will uncover new aspects of skin biology.

SwedAD, a Swedish nationwide registry for patients with atopic dermatitis receiving systemic pharma-cotherapy, was launched on 1 September 2019. We describe here the establishment of a user-friendly re-gistry to the benefit of patients with atopic dermati-tis. By 5 November 2022, 38 clinics had recorded 931 treatment episodes in 850 patients with an approxi-mate national coverage rate of 40%. Characteristics at enrolment included median Eczema Area and Seve-rity Index (EASI) 10.2 (interquartile range 4.0, 19.4), Patient-Oriented Eczema Measure (POEM) 18.0 (10.0, 24.0), Dermatology Life Quality Index (DLQI) 11.0 (5.0, 19.0) and Peak Itch Numerical Rating Scale-11 (NRS-11) 6.0 (3.0, 8.0). At 3 months, median EASI was 3.2 (1.0, 7.3) and POEM, DLQI, and NRS-11 were im-proved. Regional coverage varied, reflecting the distri-bution of dermatologists, the ratio of public to private healthcare, and difficulties in recruiting certain clinics. This study highlights the importance of a nationwide registry when managing systemic pharmacotherapy of atopic dermatitis.

Background Acne is a very common skin disease that has major impact on the patients' quality of life. Although the disease has been extensively studied we still need more knowledge of factors influencing the decisions for choice of therapy. Objective To evaluate the relationships between clinical severity, patients' self-reported quality of life, treatment choice and the outcome of therapy in a structured out-patient acne clinic. Methods In total 211 consecutive patients (143 females, 68 males) at a structured acne clinic were included. At the first visit a clinical assessment was conducted, therapy was initiated and the patients answered a quality-of-life questionnaire (Dermatology Life Quality Index, DLQI). A follow up was performed after six months, when patients once again answered the DLQI questionnaire and the clinical outcome was assessed by the physician. Results The quality of life was improved after treatment at a group level. At the first visit, the quality of life showed a gender difference (females scoring worse) but did not correlate to the clinical grading nor to the choice of therapy. At six months the DLQI correlated with clinical outcome. Patients with isotretinoin therapy showed a significantly greater improvement in quality of life. There was a tendency to gender difference in the choice of therapy, as in females 32% of the patients were treated with isotretinoin although they were clinically graded as moderate. The corresponding figure for males was 23%. A correlation was found between the initial clinical grading and gender, age and the choice of therapy. Conclusion DLQI can be used to evaluate treatment effects in acne. However, the self-reported quality of life will depend on several factors including age, gender, psychosocial factors and clinical severity.

Background: Mastocytosis is a disease characterized by accumulation of aberrant mast cells and mediator-related symptoms and is divided into systemic mastocytosis (SM) and cutaneous mastocytosis (CM). The epidemiology of mastocytosis remains incompletely understood. Objective: To estimate the incidence, prevalence, overall survival (OS) and burden of comorbidities in adult mastocytosis patients identified in Swedish population-based registries. Methods: Individuals (>= 20 years of age) with a mastocytosis diagnosis in the National Patient Register (NPR) and/or the Swedish Cancer Register (SCR) between 2001 and 2018, were identified. In a matched cohort design, for each case five randomly selected mastocytosis-free comparators matched on age, sex, and county of residence were chosen from the Population Register. The Kaplan-Meier method was used to compare OS between individuals with mastocytosis and comparators. Information on concomitant disease at baseline was assessed by use of the Charlson Comorbidity Index (CCI). Results: We identified 2,040 adults with a mastocytosis diagnosis yielding an annual incidence of 1.56 per 100,000 (95% CI 1.29-1.87) and a prevalence of 23.9 per 100,000 (95% CI 22.8-25.0). The comorbidity burden was higher, and the OS lower, in patients with mastocytosis compared to comparators. Interpretation: We found a higher incidence and prevalence of mastocytosis compared to assessments in other settings and confirmed that the prognosis generally is favorable. Of special note was evidence of a higher comorbidity burden in mastocytosis patients compared to the background population. Limitations: Underreporting and inconsistencies in the use of diagnostic codes.

BACKGROUND: The use of cosmetics is rising, and adverse reactions to these products are increasing. In Sweden, the Medical Products Agency (MPA) keeps a voluntary reporting system for such adverse reactions. However, the reporting is sparse, consisting almost only of cases with test-proven allergic contact dermatitis, thus under-reporting the more common irritant reactions. OBJECTIVE: The aim of the study was to try to improve the reporting system. PATIENTS AND METHODS: Dermatologists at 3 dermatology departments used a structured protocol during the clinical investigation of 151 consecutive patients reporting skin reactions to cosmetics. The protocol included symptoms, signs, affected body site, suspected products, and final diagnosis after patch testing. Based on clinical data and patch test results, a causality assessment for each product was made according to a protocol used at the MPA. Results: Allergic contact dermatitis was found in 28% of the patients, and irritant reactions were equally common at 27%. CONCLUSIONS: Using this structured protocol, the cases of irritant dermatitis were also reported, and it is recommended that such a protocol is used as a standard to improve the reporting of adverse reactions to skin care products.

In this prospective, cross-sectional, multicenter study, we assessed clinical and laboratory characteristics from patients with cutaneous lupus erythematosus (CLE) using the Core Set Questionnaire of the European Society of Cutaneous Lupus Erythematosus (EUSCLE). 1002 (768 females, 234 males) patients with different subtypes of CLE, such as acute CLE (ACLE, 304 patients), subacute CLE (SCLE, 236 patients), chronic CLE (CCLE, 397 patients), and intermittent CLE (ICLE, 65 patients), from 13 European countries were collected and statistically analyzed by an SPSS database. The main outcome measures included gender, age at onset of disease, LE-specific and LE-nonspecific skin lesions, photosensitivity, laboratory features, and the criteria of the American College of Rheumatology (ACR) for the classification of systemic lupus erythematosus. The mean age at onset of disease was 43.0±15.7 years and differed significantly between the CLE subtypes. In 347 (34.6%) of the 1002 patients, two or more CLE subtypes were diagnosed during the course of the disease and 453 (45.2%) presented with LE-nonspecific manifestations. Drug-induced CLE and SjögrenD́s Syndrome had the highest prevalence in SCLE patients (13.1% and 14.0%, respectively). Photosensitivity was significantly more frequent in patients with ACLE, SCLE, and ICLE compared with those with CCLE. The detection of antinuclear antibodies such as anti-Ro/SSA and anti-La/SSB antibodies revealed further significant differences between the CLE subtypes. In summary, the EUSCLE Core Set Questionnaire and its database facilitate the analysis of clinical and laboratory features in a high number of patients with CLE and will contribute to standardized assessment and monitoring of the disease in Europe.