JAMA dermatology最新文献

Importance: Therapies for individual keratinocyte carcinomas (KCs) do not prevent the onset of new KCs in a field of sun damage, and therefore the KC burden remains unchanged.

Objective: To investigate the association of immune checkpoint inhibitors (ICIs) with changes in field cancerization evaluated by the number of actinic keratoses (AKs) and KCs at baseline compared with 12 months after starting ICI therapy.

Design, setting, and participants: This prospective cohort study was performed at the outpatient oncology clinic of a single tertiary public hospital in Brisbane, Australia, from April 1, 2022, to November 30, 2023. Consecutive immunocompetent adults starting therapy with an inhibitor for programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PDL-1) for any active cancer, with a planned treatment duration of at least 6 months, and who exhibited clinical AKs on their forearms were eligible. Those with immunosuppression, concurrent chemotherapy or radiotherapy, or recent topical fluorouracil use were excluded.

Exposures: Intravenous ICI therapy, either PD-1 or PDL-1 inhibitors with or without a cytotoxic T-lymphocyte-associated protein 4 inhibitor, with therapy duration determined by the treating oncologist.

Main outcomes and measures: Clinical AKs were counted and photographed before and 3, 6, and 12 months after starting ICI therapy. KC numbers were evaluated based on histopathology reports of all skin lesions excised 12 months before and after starting ICI therapy. Participants' medical history, primary cancer tumor response using Response Evaluation Criteria in Solid Tumors, and adverse events were recorded.

Results: A total of 23 participants were recruited, of whom 17 (73.9%) were male, with a mean (SD) age of 69.7 (9.6) years. No participants withdrew; however, 4 died during the study due to disease progression. The mean (SD) AK number significantly decreased from 47.2 (33.8) at baseline to 14.3 (12.0) at 12 months (P < .001). Younger patients (8 of 12 [66.7%] vs 4 of 12 [33.3%]; P = .007) and those with a history of blistering sunburn (12 of 12 [100%] vs 0; P = .005) were more likely to reduce their AK numbers by 65% or greater. KC total numbers decreased from 42 in the 12 months before starting ICI therapy to 17 in the 12 months after. The number of cutaneous squamous cell carcinomas decreased from 16 to 5 in the same period.

Conclusions and relevance: This pilot cohort study found that ICIs used for any cancer were associated with a significant reduction of AKs, suggesting potential as an immunopreventive strategy for high-risk individuals. Given the known effects of other chemopreventive agents on KCs, further investigation into ICIs managing field cancerization is required, especially considering toxicity and cost.

Importance: Frontal fibrosing alopecia (FFA) is an inflammatory and scarring form of hair loss of increasing prevalence that most commonly affects women. An improved understanding of the genetic basis of FFA will support the identification of pathogenic mechanisms and therapeutic targets.

Objective: To identify novel genomic loci at which common genetic variation affects FFA susceptibility and assess nonadditive effects on genetic risk between susceptibility loci.

Design, setting, and participants: Four genome-wide association studies were combined using an SE-weighted meta-analysis. Within the major histocompatibility complex (MHC) locus, stepwise conditional analysis was undertaken to determine independently associated classical MHC class I alleles. Statistical tests for epistatic interaction were performed between risk alleles at the MHC and endoplasmic reticulum aminopeptidase 1 (ERAP1) loci.

Main outcomes and measures: Genome-wide significant locus associated with FFA and nonadditive effects on genetic risk between susceptibility loci.

Results: Of 6668 included patients, there were 1585 European female individuals with FFA and 5083 controls. Genome-wide significant associations were identified at 4 genomic loci, including a novel susceptibility locus at 5q15, and the association signal could be fine-mapped to a single nucleotide substitution (rs10045403) in the 5' untranslated region of ERAP1 (rs10045403; odds ratio, 1.30; 95% CI, 1.19-1.43; P = 3.6 × 10-8). Within the MHC, FFA risk was statistically independently associated with HLA-A*11:01, HLA-A*33:01, HLA-B*07:02, and HLA-B*35:01. FFA risk was affected by genetic variation at the ERAP1 locus only in individuals who carried at least 1 of the MHC class I risk alleles.

Conclusions and relevance: In this genome-wide meta-analysis, a supra-additive effect of genetic variation was found that affected peptide trimming and antigen presentation on FFA susceptibility. Patients with FFA may benefit from emerging therapeutic approaches that modulate ERAP-mediated processes.

Importance: Rituximab is approved for the treatment of moderate to severe pemphigus. However, 20% of patients in the RITUX 3 trial relapsed within the first year of treatment.

Objective: To assess the outcome of an additional rituximab infusion at month 6 in patients with pemphigus who were in complete remission (CR) after rituximab regimen but had 1 or more predictors of relapse at month 3.

Design, settings, and participants: This multicenter cohort study was conducted in France from September 2018 to June 2023 to assess patients with newly diagnosed pemphigus who were in CR after treatment with the RITUX 3 regimen but had predictors of relapse at month 3. Relapse factors were a Pemphigus Disease Area Index (PDAI) score of 45 or higher, desmoglein 1 (DSG1) antibodies greater than 20 IU/mL, and/or DSG3 antibodies greater than 130 IU/mL.

Exposure: Patients in CR at month 6 with at least 1 predictor of relapse were treated with an additional rituximab infusion at month 6.

Main outcomes and measures: Primary end point was the rate of CR without corticosteroid therapy for 2 months at month 12. Secondary end points were the rate of relapse, number of patients needing to be re-treated (NNT) with rituximab to avoid a relapse, and safety.

Results: The study population comprised 87 patients (44 females [50.6%] and 43 [49.4%] males), with a mean (SD [range]) age of 55.3 (15.2 [24-92]) years at pemphigus diagnosis. Of these, 64 patients (73.6%) had pemphigus vulgaris and 23 (26.4%) had pemphigus foliaceus. At month 6, CR had been achieved by 77 patients (88.5%), and 10 (11.5%) had persistent disease activity. Of the 77 patients in CR, 30 (39.0%) had at least 1 predictor of relapse and received an additional infusion of rituximab; 47 patients (61.0%) without a predictor did not. Two patients without a predictor and no patients with a predictor experienced relapse-an overall relapse rate of 2.6% and an NNT of 3.6 (95% CI, 1.6-46.5). The 10 patients (11.5%) with persistent disease activity at month 6 were re-treated with rituximab, 1000 mg. At month 12, the rate of CR without corticosteroid therapy for a minimum of 2 months was 72 of 77 (93.5%) among patients who had achieved CR at month 6, and 72 of 87 (82.7%) for the whole study population. Eight serious adverse effects were reported among 5 patients; there were no deaths.

Conclusion and relevance: This multicenter cohort study indicates that using predictors such as baseline PDAI score, anti-DSG1 antibodies, and/or anti-DSG3 antibodies to initiate preemptive treatment with additional rituximab may reduce the rate of short-term relapse.

Importance: Although more than 1 in 10 people experience pruritus, there are limited medical technologies that can accurately and continuously quantify and simultaneously reduce scratching behaviors through nonpharmacological methods.

Objective: To evaluate the accuracy and efficacy of an artificial intelligence-enabled wearable sensor with closed-loop haptic feedback to decrease nocturnal scratch in patients with mild atopic dermatitis who report a moderate to severe degree of scratching.

Design, setting, and participants: This single-arm 2-stage cohort study with a within-participants design was conducted at a single center and carried out in an at-home environment. Adult patients with atopic dermatitis were recruited from the Northwestern University Department of Dermatology in Chicago, Illinois. Participants were fluent in English, 18 years old or older, had a diagnosis of atopic dermatitis, and self-reported moderate or severe scratching behaviors. Each participant's disease at time of recruitment was scored via the Validated Investigator Global Assessment for Atopic Dermatitis. Data were collected from April to July 2023.

Exposures: Haptic feedback delivered by a wearable sensor mounted on the hand triggered whenever nocturnal scratch was detected by an artificial intelligence algorithm. Participants initially wore the sensor for sensing only for 7 nights to assess baseline nocturnal scratching and sleep parameters. This was followed by an additional 7 nights of wearing the sensor with haptic feedback activated.

Main outcomes and measures: Retrospective analysis was performed for scratch events and scratch duration per night and per hour of sleep opportunity. Paired t tests were used to compare changes in patient scratching behaviors before and after use of the artificial intelligence-enabled haptic feedback devices.

Results: Of 10 included patients, 6 were female, and the mean (SD) age was 36 (12) years. All patients had a Validated Investigator Global Assessment for Atopic Dermatitis score of 0 to 2 (clear to mild) who contributed a total of 104 sleep nights and 831 monitoring hours. No patients were lost to follow-up. There was a significant decrease in mean (SD) scratch events nightly (45.6 [24.0] vs 32.8 [13.0]; P = .03), a 28% difference, and mean (SD) scratch duration per hour of sleep opportunity (15.8 [10.7] seconds vs 7.9 [3.7] seconds; P = .01), a 50% difference, when haptic feedback was activated in the second week without a decrease in total sleep opportunity.

Conclusions and relevance: This study found that haptic feedback may be used as a nonpharmacological intervention to reduce nocturnal scratching in patients with mild atopic dermatitis. Future randomized studies are needed to confirm.