JAMA dermatology最新文献

Importance: BRCA1-associated protein (BAP1) tumor predisposition syndrome (TPDS) is a cancer genodermatosis associated with high risk of uveal and cutaneous melanoma, basal cell carcinoma, and multiple internal malignant neoplasms, including mesothelioma and renal cell carcinoma. Early detection of the syndrome is important for cancer surveillance and genetic counseling of family members who are at risk.

Objective: To determine the prevalence of nail abnormalities in individuals with pathogenic germline variants in BAP1.

Design, setting, and participants: In this prospective cohort study, individuals who were known carriers of pathogenic BAP1 germline variants were consecutively enrolled between October 10, 2023, and March 15, 2024. Dermatologic evaluation for nail abnormalities was performed, including a history of nail abnormalities and associated symptoms, physical examination, medical photography, and nail biopsy for histopathology. This was a single-center study conducted at the National Institutes of Health Clinical Center.

Main outcomes and measures: Primary outcomes were the prevalence and spectrum of nail changes and histopathologic characterization.

Results: Among 47 participants (30 female [63.8%]; mean [SD] age, 46.4 [15.1] years) ranging in age from 13 to 72 years from 35 families, nail abnormalities were detected in 41 patients (87.2%) and included leukonychia, splinter hemorrhage, onychoschizia, and distal nail hyperkeratosis. Clinical findings consistent with onychopapilloma were detected in 39 patients (83.0%), including 35 of 40 individuals aged 30 years or older (87.5%). Nail bed biopsy was performed in 5 patients and was consistent with onychopapilloma. Polydactylous involvement with onychopapillomas was detected in nearly all patients who had nail involvement (38 of 39 patients [97.4%]).

Conclusions and relevance: This study found that BAP1 TPDS was associated with a high rate of nail abnormalities consistent with onychopapillomas in adult carriers of the disease. Findings suggest that this novel cutaneous sign may facilitate detection of the syndrome in family members who are at risk and patients with cancers associated with BAP1 given that multiple onychopapillomas are uncommon in the general population and may be a distinct clue to the presence of a pathogenic germline variant in the BAP1 gene.

Importance: Outcome measurement is an essential component of value-based health care and can aid patient care, quality improvement, and clinical effectiveness evidence generation. The Harmonising Outcome Measures for Eczema Clinical Practice initiative aims to identify a list of validated, feasible, outcome measurement instruments recommended to measure atopic dermatitis (AD) in the clinical practice setting. The clinical practice set is a list of instruments that clinicians can pick and choose from to suit their needs in the context of clinical care.

Objective: To recommend instruments to measure clinical signs of AD in clinical practice.

Evidence review: Following the predefined roadmap, a mixed methods design was implemented and incorporated systematic reviews and qualitative consensus methods. Previous systematic reviews identified few clinical signs instruments with sufficient validation for recommendation. An updated systematic review evaluating the validity of clinical signs instruments informed an international meeting to reach consensus on recommended instruments to measure AD clinical signs in clinical practice. Consensus was defined as less than 30% disagreement. An in-person consensus exercise was held in Montreal, Canada, on October 16, 2022. The 34 attendees included patient and patient advocate research partners, health care professionals, researchers, methodologists, and industry representatives.

Findings: The updated systematic review found that the Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis, and objective Scoring Atopic Dermatitis were the only instruments that demonstrated sufficient performance in all assessed measurement properties. The modified EASI and Signs Global Assessment × Body Surface Area instruments were also recommended. The EASI, Validated Investigator Global Assessment, and Investigator's Global Assessment multiplied by or measured concurrently with a body surface area measure achieved consensus in criteria and were adopted.

Conclusions and relevance: This consensus statement by the Harmonising Outcome Measures for Eczema initiative suggests that when assessing and documenting clinical signs of AD, there are several valid and feasible instruments that can best fit a clinician's specific practice needs. These instruments should improve and standardize the documentation of signs severity, help determine the effect of treatment, facilitate the generation of clinical effectiveness evidence, and enhance the implementation of value-based health care.

Importance: Lichen planopilaris (LPP) is a form of scarring alopecia associated with progressive, permanent hair loss. Symptoms range from burning pain to itching, also carrying substantial psychological morbidity. Yet, disease characteristics, pathophysiology, and effective treatment data are limited, making treatment a challenge.

Objective: To describe the prevalence and dermatologist-prescribed treatment patterns of LPP among US adults.

Design, setting, and participants: This cross-sectional study used the Explorys database. The prevalence analysis used a 15% random sample and identified US adults with LPP diagnoses between 2017 and 2019. The LPP treatment analysis included all patients with LPP diagnoses between 2016 and 2020 and a dermatologist encounter in the first year after diagnosis. Data were analyzed from January 2023 to April 2023.

Main outcomes and measures: The main outcomes of the prevalence analysis were the crude and standardized prevalence estimates of US adults with LPP across age, sex, and racial groups. The main outcomes of the treatment analysis were the frequency of LPP treatments within 1 year of diagnosis, and the number of patients who continued treatment beyond 1 year, switched treatments, and combined treatments.

Results: Among 1 466 832 eligible patients analyzed for prevalence, 241 patients had an LPP diagnosis (222 [92.1%] female; median [IQR] age, 64 [54-73] years). Standardized overall prevalence was 13.4 per 100 000 (95% CI, 11.7-15.1). In the treatment analysis, 991 patients had an LPP diagnosis (907 [91.5%] female; median (IQR) age, 60 [47-69] years). Most received at least 1 type of medication (635 [64.1%]), most frequently intralesional corticosteroids (370 [37.3%]) and topical corticosteroids (342 [34.5%]), followed by doxycycline (104 [10.5%]) and hydroxychloroquine (72 [7.3%]). Treatment continued beyond 1 year in 71 of 200 patients (35.5%) prescribed intralesional corticosteroids and 7 of 29 patients (24.1%) prescribed hydroxychloroquine. Treatment switching at 1 year occurred in 32 of 254 patients (12.6%) first prescribed an intralesional corticosteroid and in 44 of 194 (22.7%) first prescribed a topical corticosteroid. Combinations of 2 or 3 treatment types were given to 137 (13.8%) and 74 (7.5%) patients, respectively.

Conclusions and relevance: This cross-sectional study reported prevalence and treatment patterns for US adults with LPP in a representative sample. Most patients with LPP received treatment, and many received multiple treatment types and switched treatments, suggesting further research into medication selection offers clinical benefit.

Importance: Prurigo nodularis (PN) is a debilitating skin disease characterized by the hallmark symptom of chronic itch; the intensity of itch in PN was assessed using the Worst Itch Numeric Rating Scale (WI-NRS) to evaluate the primary efficacy end point of 2 recent phase 3 studies of dupilumab treatment for PN.

Objective: To validate the psychometric properties and to determine the clinically meaningful improvement threshold for WI-NRS in patients with moderate to severe PN.

Design, setting, and participants: In this secondary analysis of the PRIME and PRIME2 trials, content validity of WI-NRS was assessed through in-depth patient interviews. Psychometric assessments used pooled data from masked, intention-to-treat (ITT) patients with PN from randomized, double-masked, and placebo-controlled studies. Psychometric assessments included test-retest reliability, construct validity, known-groups validity, and sensitivity to change in adult patients with moderate-to-severe PN. Thresholds for meaningful within-patient improvement in the WI-NRS score were determined using anchor and distribution-based approaches. Data were analyzed after completion of each study, December 2019 to November 2021 for PRIME and January 2020 to August 2021 for PRIME2.

Exposures: Dupilumab (300 mg) or placebo subcutaneously every 2 weeks for 24 weeks.

Main outcomes and measures: WI-NRS score at specified time points up to 24 weeks after randomization.

Results: A total of 20 patients were included across the 2 studies (mean [SD] age, 49.3 [17.2] years; 11 female [55%]); 311 patients were included in the pooled intention-to-treat analysis (mean [SD] age, 49.5 [16.1] years; 203 female [65.3%]). The WI-NRS questions (20 of 20 patients), recall period (19 of 20 patients), and response scale (20 of 20 patients) were easy to understand and relevant for patients with PN. Adequate test-retest reliability was observed between screening and baseline (intraclass correlation coefficient = 0.72, using Patient Global Impression of Severity [PGIS] to define stable patients). Convergent and discriminant validity was supported by moderate to strong correlations (absolute r range = 0.34-0.73) with other conceptually related measures and weaker correlations (absolute r range = 0.06-0.32) with less-related measures, respectively. WI-NRS was sensitive to change, as demonstrated by differences in change from baseline among groups (per PGIS change and PGI of Change [PGIC]). Using anchor-based approach with PGIS and PGIC, the clinically meaningful improvement threshold was 4 points (range, 3.0-4.5), which was also supported by distribution-based methods.

Conclusion and relevance: This study found that WI-NRS may be a fit-for-purpose instrument to support efficacy end points measuring the intensity of itching in adults with PN.

Tri