British Journal of Dermatology最新文献

Background: An increase in the incidence of melanoma has been reported globally since the late twentieth century, while mortality from melanoma is no longer increasing in England and other countries. Improved therapeutics have reduced mortality. However, this phenomenon implicates 'overdiagnosis', where thinner melanomas of unclear malignant potential are being diagnosed possibly due to 'diagnostic drift'.

Objectives: To assess the age-standardized and age-specific incidence and mortality trends for melanoma in situ (MIS) and malignant melanoma (MM) in England between 2001 and 2020 by age and gender.

Methods: We analysed routinely collected data from the National Disease Registration Service for MIS and MM in England between 2001 and 2020. We used joinpoint regression analysis to calculate the trends and average annual percentage change (APC) in age-standardized (using the 2013 European Standard Population) incidence (EASIR) and mortality (EASMR) and age-specific incidence (ASIR) and mortality (ASMR) rates, by age and gender per 100 000 person years (PYs).

Results: Between 2001 and 2020, 86 792 cases of MIS and 220 286 cases of MM were recorded in England. The EASIR (per 100 000 PYs) for MM increased most rapidly during 2001-6 (from 14.6 to 19.6; APC 6.3%); the rate of increase slowed during 2006-14 (APC 4.1%; EASIR2014 26.7) and decelerated further between 2014 and 2019 (APC 1.4%; EASIR2019 28.7). The EASIR for MIS (per 100 000 PYs) increased rapidly during 2001-15 (from 4.5 to 12.5; APC 7.5%) and subsequently slowed between 2015 and 2019 (to EASIR2019 13.3; APC 1.9%). In individuals 0-24 years old, the ASIR of MM and MIS has been decreasing since the late 2000s, whereas the ASIR of MM in those aged > 50 years is rising, with the greatest increases seen in those aged > 70 years. Since the early 2010s, EASMRs from MM have remained higher in men. ASMRs have reduced in adults < 74 years of age; however, rates have continued to increase in those > 75 years old.

Conclusions: The deceleration in the incidence rates of MM and MIS may be due to stabilization of any diagnostic drift, ethnicity diversity and reduced sun-seeking behaviours, particularly in younger generations. Mortality rates from MM have decreased since therapeutic developments in the early 2010s, and in younger generations before this. MM incidence and mortality are increasing most rapidly in men aged > 75 years, the age group with the highest incidence and expected growth in the future. These results support the importance of early melanoma detection, public health sun-awareness campaigns and better melanoma diagnostics.

Background: Ultraviolet radiation (UVR) is used as treatment for psoriasis and other skin diseases, but UVR can induce DNA mutations that may lead to skin cancer development. While skin cancers have been documented in patients treated with phototherapy, a limited number of epidemiological studies have examined the incidence of skin cancer in people receiving narrowband ultraviolet B (NB-UVB) treatment. Information on the mutagenicity of NB-UVB would help inform about the potential skin cancer risks of this treatment.

Objectives: To determine the mutation burden in human skin resulting from a NB-UVB treatment course and to use this data to estimate the total number of NB-UVB exposures whereupon skin cancer surveillance should begin.

Methods: Biopsies of normal skin were obtained before and after a course of NB-UVB from 16 patients with psoriasis. Epidermal DNA was sequenced using nanorate sequencing (NanoSeq) to determine the mutational signatures and mutation burden from NB-UVB.

Results: The NB-UVB treatment course increased the number of mutations in skin. Median increase in mutation burden was 0.55 substitutions per Mb in infrequently sun-exposed (buttock; n = 14) skin and 0.89 substitutions per Mb in frequently sun-exposed (forearm; n = 10) skin (P < 0.001). Change in mutation burden due to NB-UVB ranged from 1.16- to 10.50-fold in buttock skin and from 0.93- to 2.33-fold in forearm skin. This increase was mainly attributable to UVR exposure-linked mutational signatures, SBS7a and SBS7b, with some evidence that mutational burden was related to the genetic background of the individual. Modelling the change in mutation burden from NB-UVB relative to minimal erythema dose (MED) in comparison with average mutation burden in keratinocyte skin cancers allowed estimation of total lifetime exposures at which patients are likely to require skin cancer surveillance; for patients with a MED equal to 2 standard erythemal doses (SEDs), skin cancer surveillance should be offered at 422, 165 and 58 NB-UVB exposures for those receiving low, typical and high levels of sun exposure, respectively.

Conclusions: A treatment course of NB-UVB causes UVR-induced mutations in the healthy skin of patients with psoriasis. Relating mutation burden to MED and sun behaviour habits allows estimation of when to begin skin cancer surveillance according to total lifetime NB-UVB exposures.

Background: The accurate diagnosis of cutaneous lymphomas (CLs) and lymphoproliferative disorders (LPDs) presents significant challenges due to their rarity, the diversity of clinicopathological entities, and the necessity of integrating clinical, immunophenotypic and molecular analyses with histopathology. Misdiagnosis and diagnostic delays are common, potentially leading to inappropriate treatments. The contribution of an expert centre specifically for the pathology of CL has not been previously investigated.

Objectives: To evaluate the value of pathology consultations at the Dutch national referral centre for CLs focusing on diagnostic agreement and identifying common diagnostic pitfalls.

Methods: We retrospectively reviewed all pathology consultations concerning CLs received at the Leiden University Medical Centre during 2020 and 2021. Cases were categorized into informative and ambiguous conclusions. Diagnostic agreement between submitting and expert pathologists was assessed and categorized as essential agreement, more specific conclusion, minor disagreement or major disagreement.

Results: A total of 239 consultations from 230 patients were analysed. The submitted conclusion was categorized as informative in 64% of the consultations and as ambiguous in 36%. Most (59%) consultations in our study exhibited essential agreement with the submitting pathologist. The expert centre reduced ambiguous conclusions from 36% to 13%, primarily by resolving differential diagnostic considerations between lymphoma and pseudolymphomatous infiltrates. However, major diagnostic disagreements, with a potentially significant impact on treatment or prognosis, were found in 12% of consultations mostly involving reclassification from benign dermatoses to lymphomas. Mycosis fungoides, primary cutaneous follicle centre lymphoma, CD30+ LPDs and pseudolymphomas were delineated as specific areas of diagnostic difficulty.

Conclusions: The findings indicate that a national referral and expertise centre for CL pathology contributes to ensuring accurate diagnoses and appropriate patient management. Our data encourage low-threshold consultation in an expert centre for all patients with clinical and/or histological suspicion of CL.

Background: Alopecia areata (AA) can significantly impact patients' quality of life (QoL) and mental health, leading to increased levels of anxiety and depression. It is unclear whether this impact is more strongly associated with disease severity or patients' disease perception, and which patients are more likely to have a greater psychological burden.

Objectives: To examine the psychosocial impact of AA, while focusing on illness perceptions and stigma, aiming to identify high-risk subgroups and key perceptions linked to worse QoL, anxiety and depression.

Methods: This was a UK cross-sectional online study. It comprised 596 patients with AA who self-reported disease severity and completed the Dermatology Life Quality Index (DLQI), EuroQol 5-Dimensional 5-Level (EQ-5D-5L), Hospital Anxiety and Depression Scale (HADS), Stigma Scale for Chronic Illnesses 8-Item (SSCI-8) and Brief Illness Perception Questionnaire (BIPQ).

Results: Patients with AA perceived their condition as chronic and life-impacting, with limited personal or treatment control, significant emotional effects and high concern. Many patients reported high levels of anxiety, depression, stigma and impaired QoL, all strongly associated with illness perceptions. Hierarchical regression analyses showed that illness perceptions and stigma explained a higher proportion of variance in QoL, anxiety and depression than disease severity. Cluster analysis identified two distinct patient groups based on illness perceptions, with different levels of QoL, anxiety, depression and stigma.

Conclusions: AA has a severe psychosocial impact, more strongly linked to patients' illness perceptions and stigma than disease severity. The identification of two distinct patient profiles based on illness perceptions reveals differences in psychosocial burden, highlighting those at risk of worse outcomes and underscoring the value of evaluating illness perceptions along with stigma in clinical practice to improve patient outcomes.

Background: There is a growing trend towards interdisciplinary care (IC) for the management of immune-mediated inflammatory skin diseases (skIMIDs). However, an overview of instruments used to evaluate whether IC is superior to usual care is currently lacking.

Objectives: This scoping review aims to gain insight into clinician- and patient-reported outcome measures (ClinROMs and PROMs) used in IC for skIMIDs.

Methods: A comprehensive literature search was conducted by screening PubMed, Web of Science and Embase databases from their inception until October 2024. To be eligible, studies needed to have investigated IC for skIMIDs involving dermatologists, and have reported either ClinROMs or PROMs. Two independent reviewers screened all records by title, abstract and full text, with conflicts resolved by a third reviewer.

Results: Fourteen studies were included in this review. Nine investigated IC for psoriasis (PsO), four for atopic dermatitis (AD) and one for hidradenitis suppurativa. Six PsO studies examined combined dermatology-rheumatology clinics, while four studies explored collaborations with psychiatrists or psychologists for PsO or AD. The remaining IC models were diverse. A total of 49 different ClinROMs and PROMs were reported across the included studies, with 38 being reported by only one study. Except for the Dermatology Life Quality Index (used by 12 studies), body surface area (used by four studies), Psoriasis Area and Severity Index (used by all PsO studies), and Eczema Area and Severity Index or SCORing Atopic Dermatitis (used by all AD studies), the reported ClinROMs and particularly PROMs vary widely.

Conclusions: Although several studies describe IC models for skIMIDs, few investigated their impact on ClinROMs or PROMs. The heterogeneous outcomes used pose a challenge for comparison across studies. This review highlights the need for consensus on a core set of outcome measures for IC in skIMIDs to create a common language among the healthcare providers involved, and enhance comparability between studies. Implementing standardized outcome measures for IC in skIMIDs could contribute to the development of evidence-based guidelines and ultimately, improve patient care.

Graphical abstract:

Background: The accurate diagnosis of melanoma significantly improves patient survival rates. Distinguishing melanomas from naevi purely by morphology can be challenging when neoplastic cells are confined to the epidermis or lack marked nuclear pleomorphism.

Objectives: To investigate candidate DNA methylation alterations that can distinguish melanoma from naevus; to develop an efficient and convenient methylation-specific quantitative real-time polymerase chain reaction assay (MS-qPCR) for the diagnosis of melanoma; and to validate the diagnostic performance of the MS-qPCR.

Methods: We collected 145 formalin-fixed paraffin embedded tissue (FFPE) samples of malignant melanoma, 143 FFPE samples of benign naevus, 31 plasma samples from patients with melanoma and 37 plasma samples from healthy control skin between March 2018 and July 2024. The FFPE samples were divided into a discovery set, a training set and a validation set. PRAME, CLDN11 and SHOX2 promoter methylation levels were detected in the discovery set by pyrosequencing, to identify melanoma-specific methylation markers. Using these genes, we developed an efficient and convenient MS-qPCR diagnostic model and validated its diagnostic performance in the training set, validation set and plasma samples.

Results: Pyrosequencing in the discovery set showed that PRAME and CLDN11 promoter methylation levels were significant diagnostic biomarkers of melanoma; no significant differences in SHOX2 promoter methylation were found between melanoma and naevi. MS-qPCR for the detection of PRAME and CLDN11 methylation levels was established. A diagnostic algorithm based on cycle threshold values was constructed and achieved high accuracy in the training set (sensitivity 94.3%, specificity 85.6%), validation set (sensitivity 84.5%, specificity 88.7%) and plasma samples (sensitivity 51.6%, specificity 83.8%). In terms of melanoma subtypes, the diagnostic algorithm enabled a high degree of discrimination between acral (sensitivity 89.9%, specificity 86.4%) and mucosal melanoma (sensitivity 100%, specificity 83.3%). More importantly, the diagnostic algorithm was able to distinguish early-stage melanoma from normal naevus, with an area under the curve of 0.879 and sensitivity of 77.3%.

Conclusions: The approach to detecting PRAME and CLDN11 methylation levels using MS-qPCR has high sensitivity and specificity in the differential diagnosis between benign and malignant melanocytic tumours. Using this approach in plasma is a promising and easily implementable strategy for early melanoma screening.