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BACKGROUND: Cutaneous melanoma (CM) is a significant health concern because of its high metastatic potential. Gene Expression Profile (GEP) testing, particularly the 31-GEP test (DecisionDx-Melanoma), has been increasingly used for risk stratification in CM patients. This study aimed to evaluate the clinical utility and performance of the 31-GEP test in a real-world setting. METHODS: Patients with CM who underwent 31-GEP testing from August 2014 to August 2022 at our institution were identified through searches of electronic health records. The study analyzed the influence of 31-GEP testing on clinical decision-making related to sentinel lymph node biopsy (SLNB), medical oncology referral, and postdiagnosis surveillance. Kaplan-Meier curves and Cox proportional hazard models were used to elucidate the test's performance, focusing on relapse-free survival (RFS) and melanoma-specific survival (MSS). RESULTS: The study included 65 CM patients. Dermatologists ordered more than 80% of 31-GEP tests. In 81.5% of cases, 31-GEP results did not alter standard clinical management. SLNB decisions were unaffected in 92% of patients with pre-SLNB 31-GEP results. Among patients with stage I-IIA melanoma, 25% of those with high-risk 31-GEP results were referred to medical oncology. Contrary to expectations, the rate of nodal metastasis was higher in low-risk than in high-risk 31-GEP cases. Survival analysis showed overlapping RFS and MSS curves between different 31-GEP classes, suggesting limited prognostic value. CONCLUSIONS: The 31-GEP test has a limited impact on clinical management decisions and shows limited prognostic value.
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BACKGROUND: We aimed to investigate the prevalence of skin disease among patients with systemic lupus erythematosus (SLE) and determine whether LE skin disease had clinical or serologic correlates with SLE. METHODS: We reviewed records of 335 patients with SLE (seen at Mayo Clinic, Rochester, Minnesota, USA) and abstracted skin manifestations, fulfilled mucocutaneous SLE criteria, and clinical and serologic parameters. RESULTS: Of the 231 patients with skin manifestations, 57 (24.7%) had LE-specific conditions, 102 (44.2%) had LE-nonspecific conditions, and 72 (31.2%) had both. LE skin disease was associated with photosensitivity, anti-Smith antibodies, and anti-U1RNP antibodies (all P < 0.001). Patients without LE skin disease more commonly had elevated C-reactive protein levels (P = 0.01). Patients meeting 2-4 mucocutaneous American College of Rheumatology criteria less commonly had cytopenia (P = 0.004) or anti-double-stranded DNA antibodies (P = 0.004). No significant associations were observed for systemic involvement (renal, hematologic, neurologic, and arthritis) when comparing patients with or without LE skin involvement. LE skin involvement was not significantly associated with internal SLE disease flare, number of medications, or overall survival. CONCLUSIONS: LE skin disease commonly occurs in patients with SLE. The presence of LE skin disease had no mitigating impact on the severity of SLE sequelae, disease flares, number of medications, or overall survival.
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Anticuerpos Antinucleares , Lupus Eritematoso Cutáneo , Lupus Eritematoso Sistémico , Trastornos por Fotosensibilidad , Humanos , Femenino , Masculino , Adulto , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/epidemiología , Persona de Mediana Edad , Lupus Eritematoso Cutáneo/inmunología , Lupus Eritematoso Cutáneo/sangre , Lupus Eritematoso Cutáneo/epidemiología , Lupus Eritematoso Cutáneo/complicaciones , Trastornos por Fotosensibilidad/etiología , Trastornos por Fotosensibilidad/epidemiología , Trastornos por Fotosensibilidad/sangre , Trastornos por Fotosensibilidad/inmunología , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunología , Estudios Retrospectivos , Proteína C-Reactiva/análisis , Prevalencia , Adulto Joven , Índice de Severidad de la Enfermedad , Anciano , Ribonucleoproteína Nuclear Pequeña U1/inmunologíaRESUMEN
Necrobiosis lipoidica (NL) is a rare granulomatous disease. There are few effective treatments for NL. We sought to investigate the efficacy and safety of the Jak1/2 inhibitor, ruxolitnib, in the treatment of NL and identify the biomarkers associated with the disease and treatment response. We conducted an open-label, phase 2 study of ruxolitinib in 12 patients with NL. We performed transcriptomic analysis of tissue samples before and after treatment. At week 12, the mean NL lesion score decreased by 58.2% (SD = 28.7%, P = .003). Transcriptomic analysis demonstrated enrichment of type I and type II IFN pathways in baseline disease. Weighted gene coexpression network analysis demonstrated post-treatment changes in IFN pathways with key hub genes IFNG and signal transducer and activator of transcription 1 gene STAT1. Limitations include small sample size and a study group limited to patients with <10% body surface area. In conclusion, ruxolitinib is an effective treatment for NL and targets the key pathogenic mediators of the disease.
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Necrobiosis Lipoidea , Nitrilos , Pirazoles , Pirimidinas , Humanos , Pirimidinas/uso terapéutico , Pirazoles/uso terapéutico , Pirazoles/administración & dosificación , Femenino , Masculino , Necrobiosis Lipoidea/tratamiento farmacológico , Necrobiosis Lipoidea/genética , Necrobiosis Lipoidea/patología , Estudios Prospectivos , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Anciano , Perfilación de la Expresión Génica , Administración Tópica , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/administración & dosificaciónRESUMEN
Background: Cutaneous lichen planus (LP) is a recalcitrant, difficult-to-treat, inflammatory skin disease characterized by pruritic, flat-topped, violaceous papules on the skin. Baricitinib is an oral Janus kinase (JAK) 1/2 inhibitor that interrupts the signaling pathway of interferon (IFN)-γ, a cytokine implicated in the pathogenesis of LP. Methods: In this phase II trial, twelve patients with cutaneous LP received baricitinib 2 mg daily for 16 weeks, accompanied by in-depth spatial, single-cell, and bulk transcriptomic profiling of pre-and post-treatment samples. Results: An early and sustained clinical response was seen with 83.3% of patients responsive at week 16. Our molecular data identified a unique, oligoclonal IFN-γ, CD8+, CXCL13+ cytotoxic T-cell population in LP skin and demonstrate a rapid decrease in interferon signature within 2 weeks of treatment, most prominent in the basal layer of the epidermis. Conclusion: This study demonstrates the efficacy and molecular mechanisms of JAK inhibition in LP. Trial Registration Number : NCT05188521.
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This report evaluates the use of timolol in 2 patients with long-term hydroxyurea use and lower-extremity ulcers resistant to other treatments.
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Hidroxiurea , Úlcera de la Pierna , Humanos , Hidroxiurea/efectos adversos , Úlcera , Timolol/efectos adversos , Úlcera de la Pierna/inducido químicamenteRESUMEN
Lichen planus (LP) can affect multiple body sites including skin, mucosae, scalp and nails, causing considerable impact on patients' quality of life. Currently, there are no LP patient-reported outcome measures (PROMs) that address all body sites potentially affected by LP. We developed a LP Quality of Life Questionnaire (LPQoL), informed by an expert consortium and patient survey study, to address this gap. The study was approved by our institution's Institutional Review Board. First, a 22-item LPQoL was designed with input from LP experts at our institution. The tool was then optimized by garnering input from patients recently diagnosed with LP, who were asked to complete the LPQoL, as well as the Dermatology Life Quality Index (DLQI) and a feedback form about the LPQoL. Fifty-eight of 150 patients (39% response rate) returned the questionnaire. Mean DLQI score was 4.9 ± 5.6 SD (range 0-25) and mean LPQoL score was 13.6 ± 10.4 SD (range 0-54). LPQoL score was positively correlated with DLQI score (r = 0.79; p < 0.001). Forty-nine out of 56 (88%) and 6/56 (11%) rated the LPQoL as 'very easy' or 'fairly easy' to complete, respectively. Based on participants' feedback, we increased the recall period from one week to one month and added questions on esophageal involvement. With iterative input from LP experts and patients, we developed a LPQoL to address the gap in a multi-site PROM specific to LP. This is a pilot study and there is ongoing validation studies; therefore, this measure should not be used in clinical practice or research until validated.
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Liquen Plano , Calidad de Vida , Humanos , Estudios Retrospectivos , Retroalimentación , Proyectos Piloto , Liquen Plano/diagnóstico , Encuestas y CuestionariosAsunto(s)
Liquen Plano Oral , Liquen Plano , Humanos , Liquen Plano/complicaciones , Liquen Plano/diagnósticoRESUMEN
Hispanics are more likely to be diagnosed with skin cancer at a later stage and experience worse overall survival than Whites. The objective of this cross-sectional study was to assess the skin cancer knowledge, attitudes, perceived risk, and sun protection practices among an underserved population in the Phoenix area. We recruited participants from the greater Phoenix area to undergo skin examination and complete a questionnaire. 208 participants were included. The majority were Hispanic (64.9%). Of this Hispanic group, most were from Mexico (87.9%). The Hispanic cohort had an overall mean skin cancer knowledge score of 3.68/6, the lowest of any other racial/ethnic group, but had the highest desire to learn more about skin cancer (64.6%, "strongly agree"). They were the most concerned about developing skin cancer (50.4%, "very concerned") but had relatively lower rates of sun protection practices (7.9% "always use" sunscreen, 22.0% "always use" sun-protective clothing). Limitations of this study include a small sample size, lack of validation for the skin cancer knowledge score, lack of season as a covariate in the multivariate analysis, lack of follow-up, and lack of robust skin cancer risk assessment. In conclusion, despite poorer skin cancer knowledge and sun protection practices, the Hispanic population had the highest concern for developing skin cancer and desire to learn more about skin cancer. Targeted and culturally relevant skin cancer and sun protection education for this group is needed.
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Conductas Relacionadas con la Salud , Neoplasias Cutáneas , Humanos , Estudios Transversales , Conocimientos, Actitudes y Práctica en Salud , Neoplasias Cutáneas/prevención & control , Hispánicos o LatinosRESUMEN
BACKGROUND: Necrobiosis lipoidica (NL) is complicated by ulceration in up to 35% of cases. METHODS: Retrospective study of patients with NL seen at our institution between January 1, 1992, and May 25, 2021, was conducted. Ulcerated NL (UNL, n = 83) and non-ulcerated NL (NUNL, n = 233) groups were compared. RESULTS: Twenty-six percent (83/316) of patients with NL experienced ulceration. UNL was significantly more likely to be painful (52% vs. 36%, P = 0.01), was more likely to have a lesion-associated cutaneous malignancy (7% vs. 0%, P < 0.001), and had a larger median size (7 vs. 5 cm, P = 0.004) compared to NUNL. Vascular studies were performed on a subset of patients and revealed transcutaneous oxygen pressure (TcPO2) < 40 mm Hg in 53% and venous insufficiency in 62% with no significant differences between UNL and NUNL groups. In patients with unilateral ulceration, mean TcPO2 values (39.7 vs. 46.6 mm Hg), regional perfusion index <0.6 (29% vs. 14%), and TcPO2 < 40 mm Hg (43% vs. 14%) were worse in the ulcerated leg compared to the non-ulcerated leg, but these differences were not statistically significant. CONCLUSIONS: UNL was more likely to be painful, develop lesion-associated malignancy, and be larger in size compared to NUNL. There were no statistically significant differences in venous insufficiency, arterial Doppler/ankle brachial index, or TcPO2 values between UNL and NUNL patients, however, a significant portion of the cohort demonstrated abnormal vascular studies, particularly on TcPO2 and venous insufficiency testing.
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Necrobiosis Lipoidea , Insuficiencia Venosa , Humanos , Necrobiosis Lipoidea/diagnóstico , Necrobiosis Lipoidea/etiología , Estudios Retrospectivos , Insuficiencia Venosa/complicaciones , Insuficiencia Venosa/diagnósticoRESUMEN
OBJECTIVE: Even with our best practices, we are frequently unable to prevent slow and stalled wound healing-particularly in people with impaired circulation and conditions such as diabetes. As a result, greater insight into the nature of wound healing and alternative treatment approaches is needed. An avenue that may be of particular promise is increasing understanding of the role of secretory leukocyte protease inhibitor (SLPI) as there is evidence that it enhances wound healing, its expression increases in response to inflammation and infection, and it exhibits anti-protease, anti-inflammatory, antiviral antibacterial and antifungal activities. METHOD: The response of SLPI levels to wounding and skin injury was assessed by taking punch skin biopsies from healthy volunteers and assessing the levels of SLPI at the site of injury at the time of wounding (baseline) as well as one, two, three, four, seven, nine and 12 weeks later. RESULTS: A total of 35 volunteers took part in the study. Significant elevations were found: levels of SLPI were greatly increased, 12 times that at baseline, and remained elevated at three weeks despite re-epithelialisation having occurred. CONCLUSION: These findings not only suggest that levels of SLPI rise rapidly following wounding, but that these elevations are sustained, and continue to increase even when re-epithelialisation has occurred. These results suggest that the role and potential benefits of this protease inhibitor deserve further exploration.
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Inhibidor Secretorio de Peptidasas Leucocitarias , Cicatrización de Heridas , Heridas y Lesiones , Biopsia , Humanos , Proteínas Inhibidoras de Proteinasas Secretoras/metabolismo , Inhibidor Secretorio de Peptidasas Leucocitarias/metabolismo , Piel/metabolismo , Heridas y Lesiones/metabolismoRESUMEN
BACKGROUND: The pathogenesis of pityriasis rubra pilaris (PRP) is not completely understood, but interleukin (IL)-17 has been shown to play a critical role. There are no reliable immunomodulatory agents to treat PRP. We conducted an open-label, single-arm clinical trial of secukinumab, a monoclonal antibody that inhibits IL-17A, for the treatment of PRP. OBJECTIVES: To evaluate the clinical efficacy of secukinumab and define the transcriptomic landscape of PRP and its response to IL-17A blockade. METHODS: Twelve patients with PRP were recruited for an open-label trial of secukinumab. Patients received a 24-week course of secukinumab. The primary endpoint was a ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75) from baseline to week 28. Secondary endpoints included PASI 90, change in Physician's Global Assessment (PGA), and change in Dermatology Life Quality Index (DLQI). RNA sequencing was performed on lesional and nonlesional skin biopsies obtained at baseline and week 2. Sample groups were compared to identify differential gene expression and pathway enrichment. This trial was registered with ClinicalTrials.gov: 'Cosentyx (secukinumab) for the treatment of adult onset pityriasis rubra pilaris' - NCT03342573. RESULTS: At week 28, six of 11 patients (55%) achieved PASI 75, and three patients (27%) achieved PASI 90. PGA (P = 0.008) and DLQI scores (P = 0.010) showed significant improvement with treatment. No serious treatment-related adverse events were encountered. Treatment with secukinumab normalized transcriptional differences between lesional and nonlesional skin. Transcriptomic data from nonresponsive patients suggest that overactivity of innate immune pathways may be driving resistance to secukinumab. CONCLUSIONS: Secukinumab appears to be an effective treatment for PRP and warrants further investigation. PRP is a transcriptionally heterogeneous disease, reflecting its variable response to therapy. Agents targeting other IL-17 isoforms and innate immune mediators should be considered for future clinical trials. What is already known about this topic? The pathogenesis of pityriasis rubra pilaris is incompletely understood. Successful treatment has been reported with a variety of immunomodulatory agents, but disease is often refractory to therapy. Interleukin (IL)-17 is thought to drive keratinocyte proliferation and vascular dysfunction in this disease. A previous trial demonstrated efficacy of the anti-IL-17A drug ixekizumab for pityriasis rubra pilaris. What does this study add? Herein we describe the findings of a clinical trial of secukinumab, an anti-IL-17A monoclonal antibody, for the treatment of pityriasis rubra pilaris. Secukinumab was effective in treating pityriasis rubra pilaris. Our transcriptomic data give new insight into the expressional changes that occur in response to secukinumab and suggest mechanisms of treatment resistance.
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Anticuerpos Monoclonales , Pitiriasis Rubra Pilaris , Adulto , Humanos , Anticuerpos Monoclonales/efectos adversos , Interleucinas , Pitiriasis Rubra Pilaris/tratamiento farmacológico , Pitiriasis Rubra Pilaris/genética , TranscriptomaRESUMEN
BACKGROUND: Necrobiosis lipoidica (NL) is an uncommon granulomatous dermatosis that can occur in patients with or without associated diabetes mellitus (DM). Prior studies have attempted to determine distinctive histopathologic features of NL in patients with and without DM. METHODS: A retrospective review of 97 patients with NL was performed to determine the similar and distinctive histopathologic features in patients with DM and without DM. RESULTS: Of the 97 patients, 32% (n = 31) had DM. Epidermal acanthosis was seen more commonly in diabetics than nondiabetics (32.3% vs. 12.1%; p = 0.017). Naked (sarcoidal/tuberculoid) granulomas were more frequently observed in nondiabetics than diabetics (22.7% vs. 3.2%; p = 0.016). Eosinophils were more common in nondiabetics than diabetics (38.5% vs. 9.7%; p = 0.004), while neutrophilic infiltration was more common in diabetics than nondiabetics (45.2% vs. 17.5%; p = 0.004). CONCLUSIONS: This study corroborates well-documented histopathologic features of NL and shows distinctive histopathologic features of NL among patients with DM-I, DM-II, and without DM. These results support the hypothesis that there are different underlying drivers of NL between diabetics and nondiabetics.
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Necrobiosis Lipoidea , Diabetes Mellitus , Humanos , Necrobiosis Lipoidea/patología , Estudios RetrospectivosRESUMEN
Ruxolitinib is a Janus kinase 1/2 inhibitor that blocks signal transduction of interferon-gamma, a critical cytokine involved in the pathogenesis of cutaneous lichen planus (LP). In this prospective phase II study, we investigated the efficacy of topical ruxolitinib in cutaneous LP and performed transcriptomic analysis before and after therapy. Twelve patients with cutaneous LP applied topical ruxolitinib twice daily for 8 weeks. Primary endpoints were changes in total lesion count and changes in modified Composite Assessment of Index Lesion Severity score in index treated and untreated index control lesions at week 4. Total lesion count decreased by a median of 50 lesions (interquartile range 25, 723; P < 0.001). modified Composite Assessment of Index Lesion Severity scores decreased by a mean difference of 7.6 (standard deviation 8.8, P = 0.016) between index treated and control lesions. Type I and II interferon pathways were enriched in LP, and responsive disease displayed downregulation of interferon-stimulated genes. In this small pilot study, topical ruxolitinib was highly effective in the treatment of cutaneous LP. Transcriptomic analysis confirmed LP as an interferon-driven disease and downregulation of interferon-stimulated genes correlated with disease response.
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Inhibidores de las Cinasas Janus , Liquen Plano , Antivirales/uso terapéutico , Emolientes , Humanos , Interferón gamma , Inhibidores de las Cinasas Janus/uso terapéutico , Liquen Plano/tratamiento farmacológico , Liquen Plano/patología , Nitrilos , Proyectos Piloto , Estudios Prospectivos , Pirazoles , PirimidinasRESUMEN
The number of patients with primary cutaneous lymphoma (PCL) relative to other non-Hodgkin lymphomas (NHLs) is small and the number of subtypes large. Although clinical trial guidelines have been published for mycosis fungoides/Sézary syndrome, the most common type of PCL, none exist for the other PCLs. In addition, staging of the PCLs has been evolving based on new data on potential prognostic factors, diagnosis, and assessment methods of both skin and extracutaneous disease and a desire to align the latter with the Lugano guidelines for all NHLs. The International Society for Cutaneous Lymphomas (ISCL), the United States Cutaneous LymphomaConsortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organization for the Research and Treatment of Cancer (EORTC) now propose updated staging and guidelines for the study design, assessment, endpoints, and response criteria in clinical trials for all the PCLs in alignment with that of the Lugano guidelines. These recommendations provide standardized methodology that should facilitate planning and regulatory approval of new treatments for these lymphomas worldwide, encourage cooperative investigator-initiated trials, and help to assess the comparative efficacy of therapeutic agents tested across sites and studies.
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Linfoma Cutáneo de Células T , Micosis Fungoide , Síndrome de Sézary , Neoplasias Cutáneas , Ensayos Clínicos como Asunto , Humanos , Linfoma Cutáneo de Células T/diagnóstico , Linfoma Cutáneo de Células T/patología , Linfoma Cutáneo de Células T/terapia , Micosis Fungoide/diagnóstico , Micosis Fungoide/patología , Micosis Fungoide/terapia , Estadificación de Neoplasias , Síndrome de Sézary/diagnóstico , Síndrome de Sézary/patología , Síndrome de Sézary/terapia , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , Estados UnidosRESUMEN
Because of a convergence of the availability of large data sets, graphics-specific computer hardware, and important theoretical advancements, artificial intelligence has recently contributed to dramatic progress in medicine. One type of artificial intelligence known as deep learning has been particularly impactful for medical image analysis. Deep learning applications have shown promising results in dermatology and other specialties, including radiology, cardiology, and ophthalmology. The modern clinician will benefit from an understanding of the basic features of deep learning to effectively use new applications and to better gauge their utility and limitations. In this second article of a 2-part series, we review the existing and emerging clinical applications of deep learning in dermatology and discuss future opportunities and limitations. Part 1 of this series offered an introduction to the basic concepts of deep learning to facilitate effective communication between clinicians and technical experts.