JAMA dermatology最新文献

Importance: Prurigo nodularis (PN) and chronic pruritus of unknown origin (CPUO) are chronic pruritic diseases that dramatically impair quality of life, but therapeutic options are limited. Abrocitinib, a Janus kinase 1 inhibitor, represents a promising therapy for both conditions.

Objective: To assess the efficacy and safety of 200-mg oral abrocitinib administered once daily in adults with moderate to severe PN or CPUO.

Design, setting, and participants: This phase 2, open-label, nonrandomized controlled trial conducted between September 2021 and July 2022 took place at a single center in the US. A total of 25 adult patients with moderate to severe PN or CPUO were screened. Ten patients with PN and 10 patients with CPUO were enrolled. All 20 patients completed the 12-week treatment period, 18 of whom completed the 4-week follow-up period.

Intervention: Abrocitinib, 200 mg, by mouth once daily for 12 weeks.

Main outcomes and measures: The primary efficacy end point was the percent change in weekly Peak Pruritus Numerical Rating Scale (PP-NRS) scores from baseline to week 12. Key secondary end points included the percentage of patients achieving at least a 4-point reduction in weekly PP-NRS score from baseline to week 12 and the percent change in Dermatology Life Quality Index (DLQI) scores.

Results: A total of 10 patients with PN (mean [SD] age, 58.6 [13.1] years; all were female) and 10 patients with CPUO (mean [SD] age, 70.7 [5.6] years; 2 were female) enrolled in the study. The mean (SD) baseline PP-NRS score was 9.2 (1.0) for PN and 8.2 (1.2) for CPUO. PP-NRS scores decreased by 78.3% in PN (95% CI, -118.5 to -38.1; P < .001) and 53.7% in CPUO (95% CI, -98.8 to -8.6; P = .01) by week 12. From baseline to week 12, 8 of 10 patients with PN and 6 of 10 patients with CPUO achieved at least a 4-point improvement on the PP-NRS. Both groups experienced significant improvement in quality of life as demonstrated by percent change in DLQI scores (PN: -53.2% [95% CI, -75.3% to -31.1%]; P = .002; CPUO: -49.0% [95% CI, -89.6% to -8.0%]; P = .02). The most common adverse event among patients was acneiform eruption in 2 of 20 patients (10%). No serious adverse events occurred.

Conclusions and relevance: The results of this nonrandomized controlled trial suggest that abrocitinib monotherapy may be effective and tolerated well in adults with PN or CPUO. Randomized, double-blind, placebo-controlled trials are warranted to validate these findings.

Trial registration: ClinicalTrials.gov Identifier: NCT05038982.

Importance: Trichophyton indotineae is an emerging dermatophyte causing outbreaks of extensive tinea infections often unresponsive to terbinafine. This species has been detected worldwide and in multiple US states, yet detailed US data on infections with T indotineae are sparse and could improve treatment practices and medical understanding of transmission.

Objective: To correlate clinical features of T indotineae infections with in vitro antifungal susceptibility testing results, squalene epoxidase gene sequence variations, and isolate relatedness using whole-genome sequencing.

Design, setting, and participants: This retrospective cohort study of patients with T indotineae infections in New York City spanned May 2022 to May 2023. Patients with confirmed T indotineae infections were recruited from 6 New York City medical centers.

Main outcome and measure: Improvement or resolution at the last follow-up assessment.

Results: Among 11 patients with T indotineae (6 male and 5 female patients; median [range] age, 39 [10-65] years), 2 were pregnant; 1 had lymphoma; and the remainder were immunocompetent. Nine patients reported previous travel to Bangladesh. All had widespread lesions with variable scale and inflammation, topical antifungal monotherapy failure, and diagnostic delays (range, 3-42 months). Terbinafine treatment failed in 7 patients at standard doses (250 mg daily) for prolonged duration; these patients also had isolates with amino acid substitutions at positions 393 (L393S) or 397 (F397L) in squalene epoxidase that correlated with elevated terbinafine minimum inhibitory concentrations of 0.5 μg/mL or higher. Patients who were treated with fluconazole and griseofulvin improved in 2 of 4 and 2 of 5 instances, respectively, without correlation between outcomes and antifungal minimum inhibitory concentrations. Furthermore, 5 of 7 patients treated with itraconazole cleared or had improvement at the last follow-up, and 2 of 7 were lost to follow-up or stopped treatment. Based on whole-genome sequencing analysis, US isolates formed a cluster distinct from Indian isolates.

Conclusion and relevance: The results of this case series suggest that disease severity, diagnostic delays, and lack of response to typically used doses and durations of antifungals for tinea were common in this primarily immunocompetent patient cohort with T indotineae, consistent with published data. Itraconazole was generally effective, and the acquisition of infection was likely in Bangladesh.

Importance: Access to timely dermatologic care remains a challenge, especially for patients with new skin lesions. Assessing the efficiency of new triage pathways may assist in better resource allocation and shorter time to care.

Objective: To evaluate whether a rule-based triage system was associated with better skin cancer risk stratification of patients and reduced wait times.

Design, setting, and participants: This retrospective quality improvement cohort study of patients referred to Stanford University dermatology clinics was conducted between November 2017 and January 2023. A rules-based triage system based on a priori-determined high-risk lesion characteristics was implemented.

Exposures: Referral reasons and risk factors of patients provided by their primary care physicians.

Main outcomes and measures: Biopsy results of patients (diagnosis of any skin cancer and melanoma) at their visit or within 6 months after the visit. Regression models were used to assess the association between risk factors at referral and (1) biopsy outcomes and (2) time to first visit, adjusting for sociodemographic factors.

Results: Among 37 478 patients (mean [SD] age, 54 (18) years; 21 292 women [57%]), the rates of aggregate biopsy, malignant biopsy specimens, and melanoma were comparable across patients seen after (n = 12 302) and before (n = 25 176) the implementation of the new triage pathway. Patients seen through the lesion pathway had a higher risk of having malignant biopsy results (adjusted risk ratio [aRR], 1.6; 95% CI, 1.4-1.9) and melanoma (aRR, 2.0; 95% CI, 1.2-3.2) than those not seen through the pathway. Lesions that were concerning to referring clinicians for skin cancer were associated with an increased risk of skin cancer (all skin cancer: aRR, 2.8; 95% CI, 2.2-3.5; melanoma: aRR, 2.02; 95% CI, 1.1-3.7). Patients in the 3 high-risk lesion groups were seen faster in the new triage pathway (mean reduction, 26 days; 95% CI, 18-34 days).

Conclusions and relevance: In this study, a new automated, rules-based referral pathway was implemented that expedited care for patients with high-risk skin cancer. This reform may have contributed to improving patient stratification, reducing the time from referral to first encounter, and maintaining accuracy in identifying malignant lesions. The findings highlight the potential to optimize clinical resource allocation by better risk stratification of referred patients.