JAMA dermatology最新文献

Importance: The alpha-2 agonist xylazine is increasingly detected as an adulterant in illicitly manufactured fentanyl. There is concern that xylazine may be responsible for an emerging pattern of necrotizing wounds among people who use drugs, but the clinical features of wounds associated with xylazine remain poorly characterized.

Objective: To systematically characterize the location, wound bed surface, and chronicity of wounds among persons with confirmed xylazine exposure.

Design, setting, and participants: This case series at 3 academic medical hospitals in Philadelphia, Pennsylvania, included patients with emergency department or inpatient encounters from April 2022 to February 2023 who had a wound-related chief complaint and xylazine detected with urine gas chromatography-mass spectroscopy.

Exposure: Xylazine.

Main outcomes and measures: The location, size, wound bed, and chronicity of wounds associated with xylazine using electronic medical record abstraction and Fisher exact tests.

Results: Of 59 wounds from 29 unique patients with confirmed xylazine exposure (mean [SD] age, 39.4 [8.8] years; 15 [52%] male; all using fentanyl, and 23 [79%] routinely injecting opioids), 53 wounds (90%) were located on extremities, and 41 (69%) involved extensor surfaces. Five wounds (9%) involved exposed deep structures such as bone or tendon. Of 57 wounds with photographs, 34 (60%) had wound beds of predominantly devitalized tissue (eschar or slough). Based on patient report, 28 wounds (48%) were acute (<1 month old), 12 (20%) were subacute (present for 1-3 months), and 17 (29%) were chronic (developed ≥3 months prior). Subacute and chronic wounds were more often medium or large in size (odds ratio, 48.5; 95% CI, 8.2-1274.8; P < .001) and more frequently had devitalized wound beds (odds ratio, 9.5; 95% CI, 2.9-37.0; P < .001).

Conclusions and relevance: In this case series of hospitalized patients with confirmed xylazine exposure, wounds were commonly located on extensor surfaces of the extremities, frequently had devitalized tissue or exposed deep structures, and were more likely to have larger and necrotic wound beds the longer they had persisted. This systematic characterization of xylazine-associated wounds may inform identification, management, and research to address this emerging public health threat.

Importance: The results of small studies suggest that off-label use of low-dose oral minoxidil (LDOM) may be safe and effective for patients with hair loss, but larger trials and standardized guidelines are lacking.

Objective: To create an expert consensus statement for LDOM prescribing for patients with hair loss.

Evidence review: The current literature on the pharmacological properties, adverse effect profile, and use of LDOM for patients with hair loss was reviewed. Topics of interest were identified, and a modified Delphi consensus process was created. A total of 43 hair loss specialist dermatologists from 12 countries participated in a modified Delphi process. Consensus was reached if at least 70% agreed or strongly agreed on a 5-point Likert scale.

Findings: Over 4 survey rounds, 180 items in the first round, 121 items in the second round, 16 items in the third round, and 11 items in the fourth round were considered and revised. A total of 76 items achieved consensus including diagnoses for which LDOM may provide direct or supportive benefit, indications for LDOM compared to topical minoxidil, dosing for adults (18 years and older) and adolescents (aged 12 to 17 years), contraindications, precautions, baseline evaluation, monitoring, adjunctive therapy, and specialty consultation. Pediatric use and dosing items for children younger than 12 years, and LDOM titration protocols fell short of consensus.

Conclusions and relevance: This international expert consensus statement regarding the off-label prescribing of LDOM for patients with hair loss can help guide clinical practice until more data emerge. Hair loss experts with experience treating pediatric patients were underrepresented on this expert panel. Future research should investigate best practices for LDOM use in pediatric patients. Other critical topics for further investigation include the comparative efficacy of topical minoxidil vs oral minoxidil, the safety of oral minoxidil for patients with a history of allergic contact dermatitis to topical minoxidil, the long-term safety of LDOM, and the use of other off-label forms of minoxidil, such as compounded formulations of oral minoxidil and sublingual minoxidil. As additional evidence-based data emerge, these recommendations should be updated.

Importance: Hidradenitis suppurativa (HS) is associated with an increased prevalence of cardiovascular diseases compared with the general population. Any association between polygenic risk for HS, risk of incident cardiometabolic outcomes, and the plasma proteome is unclear.

Objective: To investigate the genetic correlation between HS and cardiometabolic disease.

Design, setting, and participants: This cohort study used a polygenic risk score (PRS) for HS to examine the risks of coronary artery disease (CAD) and diabetes and identify changes in the plasma proteome in individuals of European ancestry from the UK Biobank. Participants were enrolled from January 1, 2006, to December 31, 2010. End of follow-up was January 1, 2023. Correlations were assessed between HS susceptibility and cardiometabolic traits using linkage disequilibrium score regression. Odds ratios were assessed in logistic regressions. The risk of incident CAD and diabetes was estimated in cause-specific survival models designed as time-to-event analyses.

Exposure: The PRS for HS.

Main outcomes and measures: Main outcomes were CAD and diabetes diagnosis measured by logistic regressions and incident disease measured by Cox proportional hazards regression models adjusted for sex, age, body mass index, and smoking status.

Results: The study included 391 481 individuals (median [IQR] age, 58 [51-64] years; 209 235 [53%] female). Genetic variants for HS correlated significantly with variants associated with CAD, diabetes, and plasma levels of high-density lipoprotein cholesterol, triglycerides, and C-reactive protein. Compared with the low-risk group, a high PRS for HS (≥75th percentile) conferred odds ratios of 1.09 (95% CI, 1.06-1.12; P < .001) for CAD and 1.13 (95% CI, 1.10-1.17; P < .001) for diabetes. Estimates remained consistent when examining only incident CAD and diabetes. The PRS for HS was significantly associated with altered expression of 58 plasma proteins. Integrating this proteomic profile and the PRS for HS in a machine learning model improved prediction of CAD and diabetes compared with a reference model based on sex, age, and body mass index.

Conclusions and relevance: These findings suggest that a high genetic risk of HS is associated with increased risk of subsequent CAD and diabetes and altered composition of the plasma proteome. Additional investigation into the identified proteins and their potential roles as drug targets is warranted.

Importance: Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer. Quantifying the contribution of major potentially modifiable risk factors to the burden of MCC may inform prevention efforts.

Objective: To estimate the population attributable fraction of MCC cases in the US that were attributable to major immunosuppressing conditions (eg, HIV, solid organ transplant, chronic lymphocytic leukemia [CLL]), ambient UV radiation [UVR] exposure, and Merkel cell polyomavirus [MCPyV]).

Design, setting, and participants: This epidemiological assessment combined data from population-based registries and case series and included cases of MCC that were diagnosed from January 2001 to December 2019 diagnosed in people with HIV, solid organ transplant recipients, and patients with CLL who were identified through population-based cancer registries and linkages with HIV and transplant registries. UVR-based on cloud-adjusted daily ambient UVR irradiance was merged with cancer registry data on the county of residence at diagnosis. Studies reporting the prevalence of MCPyV in MCC specimens collected in the US were combined via a meta-analysis.

Exposures: HIV, solid organ transplant, CLL, UVR, and MCPyV.

Main outcomes and measures: Population attributable fraction of MCC cases attributable to major risk factors.

Results: A total of 38 020 MCCs were diagnosed in the US among xx patients (14 325 [38%] female individuals; 1586 [4%] Hispanic, 561 [1%] non-Hispanic Black, and 35 171 [93%] non-Hispanic White individuals). Compared with the general US population, MCC incidence was elevated among people with HIV (standardized incidence ratio [SIR], 2.78), organ transplant recipients (SIR, 13.1), and patients with CLL (SIR, 5.75). Due to the rarity of these conditions, only 0.2% (95% CI, 0.1%-0.3%) of MCC cases were attributable to HIV, 1.5% (95% CI, 1.4%-1.7%) to solid organ transplant, and 0.8% (95% CI, 0.5%-1.3%) to CLL. Compared with individuals of racial and ethnic minority groups, MCC incidence was elevated among non-Hispanic White individuals at lower and higher ambient UVR exposure levels (incidence rate ratios: 4.05 and 4.91, respectively, for MCC on the head and neck). Overall, 65.1% (95% CI, 63.6%-66.7%) of MCCs were attributable to UVR. Based on a meta-analysis of 19 case series, 63.8% (95% CI, 54.5%-70.9%) of MCCs were attributable to MCPyV. Studies were identified from a MEDLINE search performed on October 12, 2023.

Conclusions and relevance: The results of this study suggest that most MCC cases in the US were attributable to ambient UVR exposure or MCPyV, with a small fraction due to immunosuppressive conditions. Efforts to lower MCC incidence could focus on limiting UVR exposure.