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Citric acid treatment of infected venous eczema refractory to conventional treatment: a novel approach

Brit J Dermatol - ср., 24/11/2021 - 17:49
British Journal of Dermatology, EarlyView.
Категории: Журналы

Autonomic denervation dermatitis following saphenous vein grafting: a case report

Int J Dermatol - ср., 24/11/2021 - 17:49
International Journal of Dermatology, EarlyView.
Категории: Журналы

The prevalence of third‐party tracking on patient‐searched dermatology related sites

Int J Dermatol - ср., 24/11/2021 - 17:49
International Journal of Dermatology, EarlyView.
Категории: Журналы

A comparative study on the measurement properties of Dermatology Life Quality Index (DLQI), DLQI‐Relevant and Skindex‐16

Brit J Dermatol - ср., 24/11/2021 - 17:35
Summary Background

Dermatology Life Quality Index (DLQI) and Skindex-16 are among the most commonly used dermatology-specific health-related quality-of-life (HRQoL) instruments. DLQI has two common scoring methods, the original and the DLQI-Relevant (DLQI-R) modification. Head-to-head comparisons of the measurement properties of the DLQI, DLQI-R and Skindex-16 are currently lacking.

Objectives

We aim to compare the measurement properties of the DLQI, DLQI-R and Skindex-16.

Methods

We analysed data from 618 patients with self-reported physician-diagnosed dermatological conditions from a cross-sectional survey carried out in Hungary in early 2020. DLQI, DLQI-R and Skindex-16 were compared in terms of ceiling and floor effects, informativity, convergent validity and known-group validity.

Results

Mean DLQI, DLQI-R and Skindex-16 total scores were 3·76 ± 5·03, 4·11 ± 5·34 and 29·36 ± 26·62, respectively. Among patients with a DLQI/DLQI-R total score of zero, 64% reported problems on Skindex-16. Overall, 23–38% of patients with ‘not relevant’ responses on DLQI items 3 (shopping/home/gardening), 7 (working/studying), 8 (interpersonal problems) and 9 (sexual difficulties) reported problems on their corresponding Skindex-16 items. Average relative informativity (Shannon’s evenness index) was the highest for Skindex-16 (0·85), followed by DLQI-R (0·66) and DLQI (0·54). DLQI, DLQI-R and Skindex-16 demonstrated similar convergent validity. DLQI was able to better discriminate between known groups of patients based on overall skin-related HRQoL impairment, whereas DLQI-R and Skindex-16 performed better with respect to self-perceived health status.

Conclusions

Skindex-16 seems to be more sensitive than DLQI/DLQI-R in capturing mild impairment in HRQoL. Our findings help to provide a fuller understanding of the difference between DLQI, DLQI-R and Skindex-16 and support the informed choice of instrument for clinical and research purposes.

Категории: Журналы

Three novel structural variations at the major histocompatibility complex and IL12B predispose to psoriasis

Brit J Dermatol - ср., 24/11/2021 - 16:55
Summary Background

Structural variations (SVs; defined as DNA variants ≥ 50 base pairs) have been associated with various complex human diseases. However, research to screen the whole genome for SVs predisposing to psoriasis is lacking.

Objectives

To investigate the association of SVs and psoriasis.

Methods

Using imputation, we performed a genome-wide screen of SVs on five independent cohorts with 45 386 participants from the Han Chinese population. Fine-mapping analysis, genetic interaction analysis and RNA expression analysis were conducted to explore the mechanism of SVs.

Results

In total, we obtained 4535 SVs and identified two novel deletions [esv3608550, odds ratio (OR) 2·73 (P < 2·00 × 10–308); esv3608542, OR 0·47 (P = 7·40 × 10–28)] at 6q21·33 (major histocompatibility complex), one novel Alu element insertion [esv3607339; OR 1·22 (P = 1·18 × 10–35)] at 5q33·3 (IL12B) and confirmed one previously reported deletion [esv3587563; OR 1·30 (P = 9·52 × 10–60)] at 1q21·2 (late cornified envelope) for psoriasis. Fine-mapping analysis including single-nucleotide polymorphisms (SNPs) and small insertions/deletions revealed that esv3608550 and esv3608542 were independently associated with psoriasis, and a novel independent SNP [rs9378188; OR, 1·65 (P = 3·46 × 10–38)] was identified at 6q21·33. By genetic interaction analysis and RNA expression analysis, we speculate that the association of two deletions at 6q21·33 with psoriasis might relate to their influence on the expression of HLA-C.

Conclusions

We have constructed the most comprehensive SV map for psoriasis thus far and enriched the genetic architecture and pathogenesis of psoriasis, and highlight the non-negligible impact of SVs on complex diseases.

Категории: Журналы

Transcriptomic changes during stage progression of mycosis fungoides

Brit J Dermatol - ср., 24/11/2021 - 16:53
Summary Background

Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma, which in the early patch/plaque stages runs an indolent course. However, ˜25% of patients with MF develop skin tumours, a hallmark of progression to the advanced stage, which is associated with high mortality. The mechanisms involved in stage progression are poorly elucidated.

Objectives

We sought to address the hypothesis of MF cell trafficking between skin lesions by comparing transcriptomic profiles of skin samples in different clinical stages of MF.

Methods

We performed whole-transcriptome and whole-exome sequencing of malignant MF cells from skin biopsies obtained by laser-capture microdissection. We compared three types of MF lesions: early-stage plaques (ESP, n = 12) as well as plaques and tumours from patients in late-stage disease [late-stage plaques (LSP, n = 10) and tumours (TMR, n = 15)]. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to determine pathway changes specific for different lesions which were linked to the recurrent somatic mutations overrepresented in MF tumours.

Results

The key upregulated pathways during stage progression were those related to cell proliferation and survival (MEK/ERK, Akt-mTOR), T helper cell (Th)2/Th9 signalling [interleukin (IL)4, STAT3, STAT5, STAT6], meiomitosis (CT45A1, CT45A3, STAG3, GTSF1, REC8) and DNA repair (PARP1, MYCN, OGG1). Principal coordinate clustering of the transcriptome revealed extensive gene expression differences between early (ESP) and advanced-stage lesions (LSP and TMR). LSP and TMR showed remarkable similarities at the level of the transcriptome, which we interpreted as evidence of cell percolation between lesions via haematogenous self-seeding.

Conclusions

Stage progression in MF is associated with Th2/Th9 polarization of malignant cells, activation of proliferation, survival, as well as increased genomic instability. Global transcriptomic changes in multiple lesions may be caused by haematogenous cell percolation between discrete skin lesions.

Категории: Журналы

Identifying the best predictive diagnostic criteria for psoriasis in children (< 18 years): a UK multicentre case–control diagnostic accuracy study (DIPSOC study)

Brit J Dermatol - ср., 24/11/2021 - 16:53
 a UK multicentre case–control diagnostic accuracy study (DIPSOC study)

What is already known about this topic? A diagnosis of psoriasis may be delayed in children and young people, and psoriasis may be misdiagnosed in primary and secondary care. Diagnostic criteria for psoriasis in adults and children have been lacking. The development of criteria will aid recognition and clinical diagnosis of psoriasis, and provide a disease definition for clinical trials and epidemiological studies. Studies to develop diagnostic criteria should aim to minimize bias in the study design.

What does this study add? The consensus-agreed 16 diagnostic criteria and proposed scoring system demonstrated good diagnostic accuracy. Using statistical modelling, a shortlist of the seven best predictive diagnostic criteria was identified. The presence of two or more of these criteria had a sensitivity and specificity of over 70%. The criteria provide a reminder to clinicians that psoriasis in children can often develop in skin covered by hair and clothing.


Summary Background

In children, psoriasis can be challenging to diagnose. Difficulties arise from differences in the clinical presentation compared with adults.

Objectives

To test the diagnostic accuracy of previously agreed consensus criteria and to develop a shortlist of the best predictive diagnostic criteria for childhood psoriasis.

Methods

A case–control diagnostic accuracy study in 12 UK dermatology departments (2017–2019) assessed 18 clinical criteria using blinded trained investigators. Children (< 18 years) with dermatologist-diagnosed psoriasis (cases, N = 170) or a different scaly inflammatory rash (controls, N = 160) were recruited. The best predictive criteria were identified using backward logistic regression, and internal validation was conducted using bootstrapping.

Results

The sensitivity of the consensus-agreed criteria and consensus scoring algorithm was 84·6%, the specificity was 65·1% and the area under the curve (AUC) was 0·75. The seven diagnostic criteria that performed best were: (i) scale and erythema in the scalp involving the hairline, (ii) scaly erythema inside the external auditory meatus, (iii) persistent well-demarcated erythematous rash anywhere on the body, (iv) persistent erythema in the umbilicus, (v) scaly erythematous plaques on the extensor surfaces of the elbows and/or knees, (vi) well-demarcated erythematous rash in the napkin area involving the crural fold and (vii) family history of psoriasis. The sensitivity of the best predictive model was 76·8%, with specificity 72·7% and AUC 0·84. The c-statistic optimism-adjusted shrinkage factor was 0·012.

Conclusions

This study provides examination- and history-based data on the clinical features of psoriasis in children and proposes seven diagnostic criteria with good discriminatory ability in secondary-care patients. External validation is now needed.

Категории: Журналы

The mucin protein MUCL1 regulates melanogenesis and melanoma genes in a manner dependent on threonine content

Brit J Dermatol - ср., 24/11/2021 - 16:52
Summary Background

The regulation of melanogenesis has been investigated as a long-held aim for pharmaceutical manipulations with denotations for malignancy of melanoma. Mucins have a protective function in epithelial organs; however, in the most outer organ, the skin, the role of mucins has not been studied enough.

Objectives

Our initial hypothesis developed from the identification of correlations between pigmentation and expressions of skin mucins, particularly those existing in skin tissue. We aimed to investigate the action of mucins in human melanocytic cells.

Materials and methods

The expression of mucin proteins in human skin was investigated using microarray data from the Human Protein Atlas consortium (HPA) and the Genotype-Tissue Expression consortium (GTEx) database. Mucin expression was measured at RNA and protein levels in melanoma cells. The findings were further validated and confirmed by analysis of independent experiments.

Results

We found that the several mucin proteins showed expression in human skin cells and among these, mucin-like protein 1 (MUCL1) showed the highest expression and also clear negative correlation with melanogenesis in epidermal melanocytes. We confirmed the correlations between melanogenesis and MUCL1 by revealing negative correlations in melanocytes with different melanin production, resulting from increased composition of threonine, mucin-conforming amino acid, and increased autophagy-related forkhead-box O signalling. Furthermore, threonine itself affects melanogenesis and metastatic activity in melanoma cells.

Conclusions

We identified a significant association between MUCL1 and threonine with melanogenesis and metastasis-related genes in melanoma cells. Our results define a novel mechanism of mucin regulation, suggesting diagnostic and preventive roles of MUCL1 in cutaneous melanoma.

Категории: Журналы

Dermatological emergency unit, day‐care hospital and consultations in time of COVID‐19: the impact of teledermatology

JEADV - ср., 24/11/2021 - 15:08
Journal of the European Academy of Dermatology and Venereology, EarlyView.
Категории: Журналы

Lymphomatoid drug reaction developed after BNT162b2 (Comirnaty) COVID‐19 vaccine manifesting as pityriasis lichenoides et varioliformis acuta‐like eruption

JEADV - ср., 24/11/2021 - 15:06
Journal of the European Academy of Dermatology and Venereology, EarlyView.
Категории: Журналы

Innovation in the treatment of atopic dermatitis: Emerging topical and oral Janus kinase inhibitors

Allergol Int. 2021 Nov 20:S1323-8930(21)00139-8. doi: 10.1016/j.alit.2021.10.004. Online ahead of print.

ABSTRACT

Atopic dermatitis (AD) is characterized by chronic, eczematous, severe pruritic skin lesions. The knowledge on the pathogenesis of AD is driving the development of new drugs. From the research results, it has been revealed that Th2 cell-mediated immunity, skin barrier dysfunction, and pruritus cause a vicious cycle of AD. On the other hand, the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway are one of the essential signaling pathways in various inflammatory diseases including AD. In particular, TSLP, IL-4, IL-13 and IL-22 occupy an important position for Th2 cell-mediated immune reaction. Moreover, experimentally pan-JAK inhibitor suppress the STAT3 activation and improved the skin barrier function. Furthermore TSLP, IL-4, IL-13 and IL-31 contribute a lot to chronic pruritus of AD, and transmitted via JAK-STAT pathway. Therefore, JAK inhibitors are promising candidates for the treatment of severe AD. Here we review clinical trials of topical dergocitinib; a pan-JAK inhibitor, ruxolitinib; a JAK1 and JAK2 inhibitor, and tofacitinib; a JAK1, JAK2, and JAK3 inhibitor and oral baricitinib; a JAK1 and JAK2 inhibitor, abrocitinib and upadacitinib; JAK1 inhibitor. Significant improvements in the symptoms were obtained by each drug with low frequency of adverse events. In particular, oral JAK inhibitors have the ability to improve the pruritus and skin symptoms quickly. Therefore, the emergence of these topical and oral JAK inhibitors would be regarded as an innovation in the treatment of atopic dermatitis.

PMID:34815171 | DOI:10.1016/j.alit.2021.10.004

Категории: MedLine

Innovation in the treatment of atopic dermatitis: Emerging topical and oral Janus kinase inhibitors

Pubmed free full-text with abstracts - ср., 24/11/2021 - 14:00

Allergol Int. 2021 Nov 20:S1323-8930(21)00139-8. doi: 10.1016/j.alit.2021.10.004. Online ahead of print.

ABSTRACT

Atopic dermatitis (AD) is characterized by chronic, eczematous, severe pruritic skin lesions. The knowledge on the pathogenesis of AD is driving the development of new drugs. From the research results, it has been revealed that Th2 cell-mediated immunity, skin barrier dysfunction, and pruritus cause a vicious cycle of AD. On the other hand, the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway are one of the essential signaling pathways in various inflammatory diseases including AD. In particular, TSLP, IL-4, IL-13 and IL-22 occupy an important position for Th2 cell-mediated immune reaction. Moreover, experimentally pan-JAK inhibitor suppress the STAT3 activation and improved the skin barrier function. Furthermore TSLP, IL-4, IL-13 and IL-31 contribute a lot to chronic pruritus of AD, and transmitted via JAK-STAT pathway. Therefore, JAK inhibitors are promising candidates for the treatment of severe AD. Here we review clinical trials of topical dergocitinib; a pan-JAK inhibitor, ruxolitinib; a JAK1 and JAK2 inhibitor, and tofacitinib; a JAK1, JAK2, and JAK3 inhibitor and oral baricitinib; a JAK1 and JAK2 inhibitor, abrocitinib and upadacitinib; JAK1 inhibitor. Significant improvements in the symptoms were obtained by each drug with low frequency of adverse events. In particular, oral JAK inhibitors have the ability to improve the pruritus and skin symptoms quickly. Therefore, the emergence of these topical and oral JAK inhibitors would be regarded as an innovation in the treatment of atopic dermatitis.

PMID:34815171 | DOI:10.1016/j.alit.2021.10.004

Категории: MedLine

The Personalised Acne Care Pathway-Recommendations to guide longitudinal management from the Personalising Acne: Consensus of Experts

JAAD Int. 2021 Oct 18;5:101-111. doi: 10.1016/j.jdin.2021.09.006. eCollection 2021 Dec.

ABSTRACT

BACKGROUND: Acne is a chronic disease with a varying presentation that requires long-term management. Despite this, the clinical guidelines for acne offer limited guidance to facilitate personalized or longitudinal management of patients.

OBJECTIVES: To generate recommendations to support comprehensive, personalized, long-term patient management that address all presentations of acne and its current and potential future burden.

METHODS: The Personalising Acne: Consensus of Experts panel consisted of 13 dermatologists who used a modified Delphi approach to reach consensus on statements related to longitudinal acne management. The consensus was defined as ≥75% voting "agree" or "strongly agree." All voting was electronic and blinded.

RESULTS: Key management domains, consisting of distinct considerations, points to discuss with patients, and "pivot points" were identified and incorporated into the Personalised Acne Care Pathway. Long-term treatment goals and expectations and risk of (or fears about) sequelae are highlighted as particularly important to discuss frequently with patients.

LIMITATIONS: Recommendations are based on expert opinion, which could potentially differ from patients' perspectives. Regional variations in health care systems may not have been captured.

CONCLUSIONS: The Personalised Acne Care Pathway provides practical recommendations to facilitate the longitudinal management of acne, which can be used by health care professionals to optimize and personalize care throughout the patient journey.

PMID:34816135 | PMC:PMC8593752 | DOI:10.1016/j.jdin.2021.09.006

Категории: MedLine

Pediatric basal cell carcinoma burden and management preferences in Gorlin syndrome: A survey study

JAAD Int. 2021 Aug 17;5:49-51. doi: 10.1016/j.jdin.2021.07.003. eCollection 2021 Dec.

NO ABSTRACT

PMID:34816134 | PMC:PMC8593749 | DOI:10.1016/j.jdin.2021.07.003

Категории: MedLine

Identifying gaps and providing recommendations to address shortcomings in the investigation of acne sequelae by the Personalising Acne: Consensus of Experts panel

JAAD Int. 2021 Aug 17;5:41-48. doi: 10.1016/j.jdin.2021.06.006. eCollection 2021 Dec.

ABSTRACT

BACKGROUND: The physical sequelae of acne include erythema, hyperpigmentation, and scarring, which are highly burdensome for patients. Early, effective treatment can potentially limit and prevent sequelae development, but there is a need for guidance for and evidence of prevention-oriented management to improve patient outcomes.

OBJECTIVE: To identify unmet needs of acne sequelae and generate expert recommendations to address gaps in clinical guidance.

METHODS: The Personalizing Acne: Consensus of Experts panel of 13 dermatologists used a modified Delphi approach to achieve a consensus on the clinical aspects of acne sequelae. A consensus was defined as ≥75% of the dermatologists voting "agree" or "strongly agree." All voting was electronic and blinded.

RESULTS: The panel identified gaps in current guidance and made recommendations related to acne sequelae. These included identification and classification of sequelae, pertinent points to consider for patient consultations, and management aimed at reducing the development of sequelae.

LIMITATIONS: The recommendations are based on expert opinion and made in the absence of high-quality evidence.

CONCLUSIONS: The identified gaps should help inform future research and guideline development for acne sequelae. The consensus-based recommendations should also support the process of consultations throughout the patient journey, helping to reduce the development and burden of acne sequelae through improved risk factor recognition, early discussion, and appropriate management.

PMID:34816133 | PMC:PMC8593750 | DOI:10.1016/j.jdin.2021.06.006

Категории: MedLine

Gaps and recommendations for clinical management of truncal acne from the Personalising Acne: Consensus of Experts panel

JAAD Int. 2021 Aug 17;5:33-40. doi: 10.1016/j.jdin.2021.06.007. eCollection 2021 Dec.

ABSTRACT

BACKGROUND: Truncal acne is common and burdensome for patients; however, there is paucity of evidence and guidance for the management of truncal acne. Currently, clinical practice guidelines provide very little guidance on the assessment or management of truncal acne.

OBJECTIVES: To identify unmet needs in truncal acne and make recommendations to address clinical and management gaps using an international consensus.

METHODS: The Personalising Acne: Consensus of Experts panel consisted of 13 dermatologists, who used a modified Delphi approach to reach a consensus on statements related to clinically relevant aspects of truncal acne evaluation and management. A consensus was defined as ≥75% of the panelists voting "agree" or "strongly agree." The voting was electronic and blinded.

RESULTS: The panel identified gaps and made recommendations related to truncal acne identification, assessment, and grading; the evaluation of the impact on patients; and treatment goals and factors to be considered for its management.

LIMITATIONS: The recommendations are based on expert opinion, in the absence of high-quality evidence.

CONCLUSIONS: We highlighted addressing not just facial acne but also truncal acne during patient consultations. The recommendations made herein may help facilitate the care of patients who present with truncal acne, with or without facial acne.

PMID:34816132 | PMC:PMC8593751 | DOI:10.1016/j.jdin.2021.06.007

Категории: MedLine

Use of technology for the objective evaluation of scratching behavior: A systematic review

JAAD Int. 2021 Aug 17;5:19-32. doi: 10.1016/j.jdin.2021.06.005. eCollection 2021 Dec.

ABSTRACT

INTRODUCTION: Pruritus is a common symptom across various dermatologic conditions, with a negative impact on quality of life. Devices to quantify itch objectively primarily use scratch as a proxy. This review compares and evaluates the performance of technologies aimed at objectively measuring scratch behavior.

METHODS: Articles identified from literature searches performed in October 2020 were reviewed and those that did not report a primary statistical performance measure (eg, sensitivity, specificity) were excluded. The articles were independently reviewed by 2 authors.

RESULTS: The literature search resulted in 6231 articles, of which 24 met eligibility criteria. Studies were categorized by technology, with actigraphy being the most studied (n = 21). Wrist actigraphy's performance is poorer in pruritic patients and inherently limited in finger-dominant scratch detection. It has moderate correlations with objective measures (Eczema and Area Severity Index/Investigator's Global Assessment: rs(ρ) = 0.70-0.76), but correlations with subjective measures are poor (r2 = 0.06, rs(ρ) = 0.18-0.40 for itch measured using a visual analog scale). This may be due to varied subjective perception of itch or actigraphy's underestimation of scratch.

CONCLUSION: Actigraphy's large variability in performance and limited understanding of its specificity for scratch merits larger studies looking at validation of data analysis algorithms and device performance, particularly within target patient populations.

PMID:34816131 | PMC:PMC8593746 | DOI:10.1016/j.jdin.2021.06.005

Категории: MedLine
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