British Journal of Dermatology最新文献

Mycosis fungoides (MF) is a rare malignancy characterized by the presence of circulating tumor cells (CTCs) in a subgroup of patients. Reliably distinguishing MF from inflammatory skin conditions (IF) is a challenging task. This study aimed to evaluate the potential benefits of next-generation sequencing (NGS)-based T-cell receptor (TR) rearrangement repertoire analysis for detecting clonal rearrangements in MF and IF. Skin biopsies and blood samples from 33 MF patients (diagnosed according to WHO-EORTC criteria) and 10 IF patients were analyzed using TRB- and TRG-NGS. 27/33 MF patients were early-stage IA (n=19), IB (n=8), and six had advanced stages (IIB, n=5; IIIA, n=1). Analysis applying the standard abundance thresholds identified at least one clonal rearrangement in the skin DNA of 32/33 MF (97%) and 9/10 IF cases (90%). To enhance specificity, an abundance- and distribution-based approach was applied, considering only rearrangements that significantly stood out from the physiological background as clonal (MF 29/33, IF 1/10), allowing for a highly sensitive (88%) and specific (90%) discrimination between MF and IF. CTCs were detected in 11/24 (46%) early-stage and 3/5 (60%) late-stage MF patients. NGS-based TR repertoire analysis is a highly sensitive and specific method for the differential diagnosis of early-stage MF compared to IF, and for the sensitive molecular detection of CTCs.

Background: Congenital ichthyoses (CI) comprise a heterogeneous group of genetic diseases requiring lifelong treatment and having a major effect on quality of life. Conventional treatments reduce scaling and skin discomfort; however, they usually have little or no effect on erythema and pruritus. The identification of cytokine alterations in CI raised the possibility of repurposing available biologics. Several case reports in the literature report successes using different biologics.

Objective: We aimed to report the effects of biologics in real life.

Methods: This was a retrospective, observational, international multicenter study of patients with CI treated with at least one biologic for a minimum of 3 months. The effect of the biologics was evaluated using an Investigator Global Assessment-Change (IGA-C) scale. A comprehensive literature search was performed in parallel.

Results: A total of 98 patients were included, with a mean age of 19.7 years and both sexes equally represented. Patients with Netherton syndrome (NS) or congenital ichthyosiform erythroderma (CIE) represented the majority of patients (30% and 21.4%, respectively). Most patients (84.7%) had a severe or very severe form of CI. The most frequently used biologics were inhibitors targeting interleukin-17 (IL-17), IL-12/IL-23, or the IL-4 receptor. The mean duration of treatment was 22+20.1 months. There were 45 responders (45.9%), including 18 patients (18.3%) who were good responders; all had an erythrodermic CI subset and received one of the three main biologics. In 2 NS and CIE, IL-12/IL-23 and IL-4 receptor inhibitors tended to be most effective. Review of the literature revealed a shorter mean duration of use of biologics (11.5+8.5 months) and higher percentage of responders (85.7%), suggesting reporter bias.

Conclusion: This series identified subsets of CI that may respond to biologics and will aid in designing future clinical trials of biologics for CI.

Background: The Hyperhidrosis Quality of Life Index (HidroQoL ©) is a well-developed patient-reported outcome measure assessing the quality of life (QoL) impacts in hyperhidrosis, which has proven very good measurement properties, such as structural validity and internal consistency.

Objectives: We aimed to investigate responsiveness over time and estimate values for meaningful within-person change (MWPC) towards symptom improvement for different measurement time points (4 and 12 weeks), extending the existing validity evidence in patients with primary axillary hyperhidrosis.

Methods: Data (from a phase IIIb clinical trial) was collected at baseline, week 4, week 8, week 12, week 28, week 52, and week 72. For the assessment of responsiveness, HidroQoL change scores were correlated with corresponding change scores of the Hyperhidrosis Disease Severity Scale (HDSS), the Dermatology Life Quality Index (DLQI), and the gravimetric sweat production based on a-priori formulated hypotheses. Furthermore, it was tested whether the different HDSS change score groups differed significantly from each other over time and whether the HidroQoL was sensitive towards these group differences over time. This was extended by the calculation of matched-pair tests and effect sizes to test significance for each change group separately. For the estimation of MWPC thresholds towards symptom improvement, different anchor-based and integrated approaches were used.

Results: In total, the sample was composed of 357 patients with primary axillary hyperhidrosis. For the assessment of responsiveness, 5 out of 14 a-priori hypotheses regarding the correlation of the change scores could be confirmed, whereas the rejected hypotheses only marginally differed from the expected values. Furthermore, regarding responsiveness, the HidroQoL showed sensitivity towards symptom improvement at each measurement time point. Effect sizes were large as expected (d ≥ 0.806). MWPC thresholds towards symptom improvement were proposed for two measurement time points: 5 (week 4) and 6 (week 12). Increasing MWPC values over time were observed.

Conclusion: This study extends the evidence for the longitudinal validity of the HidroQoL up to 72 weeks and proposed MWPC thresholds for different time intervals (4 and 12 weeks) after baseline, aiding interpretability. Results concur with findings from previous validation studies.

Background: Bullous pemphigoid (BP) is an autoimmune skin disease that affects mainly older people. Numerous drugs have been previously associated with BP based on case series and small hospital-based studies. More reliable and precise estimates of associations between a broad selection of drugs/vaccines and BP will enable greater awareness of potential increased risk of BP following certain medicines and help identify clinical, histological and genomic characteristics of drug-induced BP for different types of culprit drugs. Greater awareness could lead to earlier recognition or suspicion of BP and referral to a dermatologist for diagnosis. Earlier diagnosis may lead to less aggressive treatment and improved well-being.

Objectives: To determine the association between drugs/vaccines commonly prescribed to older people and BP risk.

Methods: We conducted a population-based nested case-control study between 1998-2021 using electronic primary care records from the Clinical Practice Research Datalink. We matched BP cases with up to 5 controls. Exposures were drugs/vaccines commonly prescribed to older people. We used multivariable conditional logistic regression adjusting for multiple drug use. For antibiotics, we considered prescriptions may be prescribed for undiagnosed symptoms of BP which resemble skin infection (protopathic bias) in a sensitivity analysis.

Results: Antibiotics were the therapeutic group associated with the highest risk of BP (OR: 4.60; 95%CI 4.40-4.80). However, after adjusting for protopathic bias, the OR reduced to 2.08 (95%CI 1.99-2.17). After adjusting for protopathic bias, of all antibiotic classes and subclasses, penicillins and penicillinase-resistant penicillins had the strongest associations with BP risk (OR: 3.44; 95%CI 3.29-3.60; sensitivity analysis OR; 1.74; 1.66-1.84 and OR: 7.56; 95%CI 7.15-8.00; sensitivity analysis OR: 2.64; 95%CI 2.45-2.85, respectively). Other drugs strongly associated with increased risk were gliptins (OR: 2.77; 95% CI 2.37-3.23), and second-generation antipsychotics (OR: 2.58; 95%CI 2.20-3.03).

Conclusions: Healthcare professionals need to be aware of BP risk in older people particularly when prescribing penicillinase-resistant penicillins, gliptins, and second-generation antipsychotic drugs to recognise and manage BP early. Due to the low prevalence of disease, we do not suggest avoidance of drugs/vaccines to prevent BP. Further research should consider recency, dosage, and duration of antibiotic treatments.