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Association of the Psoriatic Microenvironment With Treatment Response

期刊: JAMA DERMATOLOGY, 2020; 156 (10)

Key PointsQuestionCan the psoriatic microenvironment (PME) score, a novel bioinformatic analysis of the psoriatic microenvironment, be used to predict if psoriasis will respond to a new treatment before a clinical response is seen? FindingsAnalysis of whole-genome mRNA expression in skin biopsies identified 2 different immune profiles that correlate with psoriatic lesional and nonlesional skin; with systemic treatment, the immune phenotype of psoriatic lesional skin reverted to a nonlesional pattern. The PME score is a bioinformatic metric that encompasses these changes and correlates with future clinical responses 8 weeks prior to apparent clinical differences. MeaningThe PME score may predict the therapeutic efficacy of systemic psoriasis therapies prior to apparent clinical changes and may serve as an example of personalized medicine. This study examines a novel decision analytical model designed to measure mRNA gene expression changes to define the psoriatic microenvironment and assess medication response before a change in the Psoriasis Area and Severity Index score is evident. ImportanceThe ability to predict the efficacy of systemic psoriasis therapy based on immune profiles in skin biopsies could reduce the use of inappropriate treatment and its associated costs and adverse events. It could considerably decrease drug development trial costs as well. ObjectiveTo develop a bioinformatic gene signature score derived from skin mRNA to predict psoriasis treatment outcomes for a variety of therapies. Design, Setting, and ParticipantsIn this decision analytical model using 1145 skin samples from different cohorts of 12 retrospective psoriasis studies, samples were analyzed using the CIBERSORT algorithm to define the immune landscape of psoriasis lesions and controls. Random forest classification and principal component analysis algorithms were used to estimate psoriatic microenvironment (PME) signature genes and construct a PME score. Overall, 85 and 421 psoriasis lesions from 1 and 4 independent cohorts were used as discovery and validation studies, respectively. Among them, 157, 71, 89, and 90 psoriasis lesions were treated with etanercept, tofacitinib, adalimumab, and methotrexate, respectively. Main Outcomes and MeasuresNumber of weeks after treatment initiation when responders and nonresponders could be predicted. ResultsOverall, 22 immune cell subtypes formed infiltration patterns that differentiated psoriasis lesions from healthy skin. In psoriasis lesions, the expression of 33 PME signature genes defined 2 immune phenotypes and in aggregate could be simplified to a numerical PME score. A high PME score, characterized by keratinocyte differentiation, correlated with a better treatment response (Psoriasis Area and Severity Index [PASI] reduction, 75.8%; 95% CI, 69.4% to 82.2%; P=.03), whereas a low PME score exhibited an immune activation signature and was associated with a worse response (PASI reduction, 53.5%; 95% CI, 45.3% to 61.7%; P=.03). The PME score at week 4 after treatment initiation correlated with future responder vs nonresponder to treatment status 8 to 12 weeks earlier than PASI reduction for etanercept, methotrexate plus adalimumab, and tofacitinib. Conclusions and RelevanceThe PME score is a biometric score that may predict clinical efficacy of systemic psoriasis therapy in advance of clinical responses. As an application of personalized medicine, it may reduce the exposure of patients with psoriasis to ineffective and expensive therapies.

Frontline BRAF Testing-Guided Treatment for Advanced Melanoma in the Era of Immunotherapies: A Cost-Utility Analysis Based on Long-term Survival Data

期刊: JAMA DERMATOLOGY, 2020; 156 (11)

This cost-utility analysis compares the cost-utility of these novel agents and their combinations with or without BRAF gene testing guidance for treating newly diagnosed advanced melanoma with unknown BRAF status. Key PointsQuestionAre immune checkpoint inhibitors and BRAF plus MEK inhibitors cost-effective for treating newly diagnosed advanced melanoma with unknown BRAF status? FindingsThe nivolumab, pembrolizumab, and nivolumab plus ipilimumab strategies formed the cost-effective frontier, which showed that the ordered incremental cost-utility ratio was lower than $150000/quality-adjusted life-year. MeaningThe first-line treatment approaches of nivolumab plus ipilimumab and pembrolizumab were the more cost-effective alternative for newly diagnosed advanced melanoma with unknown BRAF pathogenic variant status; BRAF and MEK inhibitors might play a role in the second-line setting. ImportanceThe effectiveness of immune checkpoint inhibitors (ICIs) and BRAF and MEK inhibitors has improved advanced melanoma recovery. However, it is unknown whether these novel therapies are cost-effective for newly diagnosed advanced melanoma with unknown BRAF status. ObjectiveTo compare the cost-utility of these novel agents and their combinations with or without BRAF gene testing guidance for treating newly diagnosed advanced melanoma with unknown BRAF status. Design and SettingA decision-analytic model was adopted to project the outcomes of 8 strategies containing different ICIs and BRAF and MEK inhibitors for newly diagnosed advanced melanoma with unknown BRAF pathogenic variant status. The key clinical data were derived from the CheckMate 067, KEYNOTE-006, COMBI-d, and COMBI-v trials, and the cost and health preference data were derived from the literature. Costs were estimated from the US payer perspective. Main Outcomes and MeasuresCosts, quality-adjusted life-years (QALYs), incremental cost-utility ratio (ICUR), and incremental net health benefits were calculated. Subgroup, 1-way, and probabilistic sensitivity analyses were performed. ResultsOf the 8 competing strategies, nivolumab plus ipilimumab without patient selection based on BRAF pathogenic variant testing yielded the most significant health outcome, and the nivolumab strategy was the cheapest option. The nivolumab, pembrolizumab, and nivolumab plus ipilimumab strategies formed the cost-effective frontier, which showed the ordered ICURs were $8593 (SD, $592995)/QALY for pembrolizumab vs nivolumab and $125593 (SD, $5751223)/QALY for nivolumab plus ipilimumab vs pembrolizumab. Other strategies, including the BRAF testing-guided strategies (BRAF pathogenic variant testing followed by corresponding regimens for BRAF wild and pathogenic variant tumors), were dominated or extended dominated. The most influential parameters were the treatment efficacy of these new regimens. Conclusions and RelevanceFor newly diagnosed advanced melanoma with unknown BRAF pathogenic variant status, nivolumab plus ipilimumab and pembrolizumab strategies are likely to be the most cost-effective options. BRAF and MEK inhibitors might be productively placed in a second-line setting after BRAF pathogenic variant is confirmed.

Exogenous Pigmentation Presenting as Longitudinal Melanonychia in a Child

期刊: JAMA DERMATOLOGY, 2020; 156 (1)

This case report describes an 8-year-old girl who presented with a linear pigmented band on the nail of her right middle finger.

Global Prevalence and Incidence Estimates of Oral Lichen Planus A Systematic Review and Meta-analysis

期刊: JAMA DERMATOLOGY, 2020; 156 (2)

This systematic review and meta-analysis identifies the global prevalence and incidence of oral lichen planus in the overall population and among subgroups. Question What are the global prevalence and incidence of oral lichen planus? Findings In this systematic review and meta-analysis of 46 studies, 15 included general population data (n = 462& x202f;993), and 31 included information from clinical patients (n = 191& x202f;963). The overall estimated pooled prevalence of oral lichen planus was 0.89% among the general population and 0.98% among clinical patients. Meaning This study identified the global prevalence and incidence of oral lichen planus in terms of its spatial, temporal, and population distribution. Importance Integrated information on the global prevalence and incidence of oral lichen planus (OLP) is lacking. Objective To examine the global prevalence and incidence of OLP in a systematic review and meta-analysis. Data Sources A systematic review of population-based studies and clinic-based studies reporting the prevalence and incidence of OLP was performed using 3 electronic medical databases (Cochrane Database of Systematic Reviews, Embase, and MEDLINE) from their inception to March 2019. The search terms included "(lichen planus or LP) and (prevalence or incidence or epidemiology)." No language restriction was applied. Study Selection Observational descriptive studies investigating the prevalence and incidence of OLP were included. Data Extraction and Synthesis Data were extracted by continent, sex, and other characteristics. The risk of bias was assessed by the Joanna Briggs Institute Critical Appraisal Instrument for Studies Reporting Prevalence Data using random-effects models to synthesize available evidence. Main Outcomes and Measures The primary outcome was the prevalence (with 95% CIs) of OLP among the overall population and among subgroups. Between-study heterogeneity was assessed using the I-2 statistic. Results Among 46 studies, the overall pooled estimated prevalence of OLP was 0.89% (95% CI, 0.38%-2.05%) among the general population (n = 462& x202f;993) and 0.98% (95% CI, 0.67%-1.43%) among clinical patients (n = 191& x202f;963). Among the 15 population-based studies, the prevalence of OLP was 0.57% (95% CI, 0.15%-2.18%) in Asia, 1.68% (95% CI, 1.09%-2.58%) in Europe, and 1.39% (95% CI, 0.58%-3.28%) in South America. Among the 31 clinic-based studies, the prevalence was 1.43% (95% CI, 1.12%-1.83%) in Africa, 0.87% (95% CI, 0.61%-1.25%) in Asia, 1.03% (95% CI, 0.51%-2.09%) in Europe, 0.11% (95% CI, 0.07%-0.16%) in North America, and 3.18% (95% CI, 0.97%-9.95%) in South America. The pooled prevalence of OLP by sex was 1.55% (95% CI, 0.83%-2.89%) for women and 1.11% (95% CI, 0.57%-2.14%) for men in the population-based studies and 1.69% (95% CI, 1.05%-2.70%) for women and 1.09% (95% CI, 0.67%-1.77%) for men in the clinic-based studies. In 5 clinic-based studies providing the age distribution of patients with OLP, the prevalence by age was 0.62% (95% CI, 0.33%-1.13%) among patients younger than 40 years and 1.90% (95% CI, 1.16%-3.10%) among patients 40 years and older. Conclusions and Relevance This study identified the global prevalence and incidence of OLP in terms of its spatial, temporal, and population distribution. The overall estimated pooled prevalence of OLP was 0.89% among the general population and 0.98% among clinical patients. A higher prevalence of OLP was found in non-Asian countries, among women, and among people 40 years and older. The findings should be considered with caution because of the high heterogeneity of the included studies.

Association of Clinical Markers With Disease Progression in Patients With Vitiligo From China

期刊: JAMA DERMATOLOGY, 2020; 156 (3)

Question Can the clinical markers of vitiligo be used to assess disease progression, severity, and patient prognosis? Findings In this cohort study of 458 patients with vitiligo from China, among 425 patients who completed 12-month follow-up, 224 (52.7%) did not have any clinical marker and 201 (47.3%) had at least 1 clinical marker at the first visit. The proportion of patients in the active stage was significantly higher in the cohort with clinical markers compared with the cohort without any marker at the baseline examination and at 3-month follow-up; presence of clinical markers was also associated with disease progression at 1- and 3-month follow-up Meaning The findings suggest that clinical markers, including trichrome sign, confetti-like depigmentation, and Koebner phenomenon, are associated with vitiligo progression and prognosis and that patients with multiple clinical markers may require more intensive treatment. This cohort study evaluates the utility of clinical markers of vitiligo, such as trichrome sign, confetti-like depigmentation, and Koebner phenomenon, in assessing disease progression, severity, and prognosis in patients from China. Importance It is necessary to determine whether established clinical markers of vitiligo are associated with disease progression, severity, and patient prognosis. Objective To evaluate the utility of trichrome sign, confetti-like depigmentation, and Koebner phenomenon in assessing disease progression, severity, and prognosis in patients with vitiligo. Design, Setting, and Participants In this prospective cohort study, 425 patients with vitiligo were recruited from the outpatient department of Huashan Hospital, Fudan University in Shanghai, China, from September 1, 2016, to May 13, 2019. Main Outcomes and Measures Disease progression, severity, and prognosis during a 12-month period. The active stage of vitiligo was defined as Vitiligo European Task Force spreading score of at least 1 or more lesions appearing as hypomelanotic with poorly defined borders using a Wood light. Progression was assessed using the Vitiligo Area Scoring Index (VASI) and serum CXCL10 level measurement. Results Of the 458 enrolled patients, 425 (235 female [55.3%]; mean [SD] age, 30.9 [10.2] years) completed the 12-month follow-up. Of the 425 patients (224 with no clinical marker and 201 with at least 1 clinical marker) included in this analysis, the proportion in the active stage of the disease was significantly higher in the cohort with at least 1 clinical marker compared with the cohort without any clinical marker at the first visit (196 of 201 [97.5%] vs 159 of 224 [71.0%]; P < .001) and at 3-month follow up (91 of 201 [45.3%] vs 52 of 224 [23.2%]; P < .001). The proportion of patients with rapid disease progression was also higher in the group with at least 1 clinical marker at 1-month follow-up (142 of 201 [70.6%] vs 60 of 224 [26.8%]; P < .001) and 3-month follow-up (63 of 201 [31.3%] vs 9 of 224 [4.0%]; P < .001). The improvement in VASI score (SD) was significantly smaller among patients with at least 1 clinical marker compared with those without any clinical marker at 6 months (mean [SD], 0.14 [0.12] vs 0.23 [0.21]; P = .02), at 9 months (mean [SD], 0.29 [0.19] vs 0.44 [0.25]; P = .03), and at 12 months (mean [SD], 0.47 [0.21] vs 0.63 [0.23]; P = .03). Conclusions and Relevance The presence of a clinical marker in patients with vitiligo may be associated with worse prognosis and rapid disease progression. Patients with multiple clinical markers may require more intensive treatment.

Mikulicz Disease

期刊: JAMA DERMATOLOGY, 2020; 156 (4)

This case report describes a man in his 60s with a history of bilateral swelling of the upper and lower eyelids.

An Indurated Plaque on the Eyelid

期刊: JAMA DERMATOLOGY, 2020; 156 (7)

A man in his 60s presented with a pruritic, red plaque on his eyelid; biopsy results showed perifollicular lymphocytic infiltrates and exocytosis of atypical lymphocytes, as well as mild follicular mucin deposition. What is your diagnosis?

Association Between Medication Use and Bullous Pemphigoid A Systematic Review and Meta-analysis

期刊: JAMA DERMATOLOGY, 2020; 156 (8)

This systematic review and meta-analysis assesses the association of the use of certain classes of medications among patients and the development of bullous pemphigoid. Question Is there an association between use of medications and the development of bullous pemphigoid? Findings In this systematic review and meta-analysis of 13 case-control studies, 1 cohort study, and 1 randomized clinical trial with 285.884 participants, there was a significant association of the development of bullous pemphigoid with the prescribed use of aldosterone antagonists, dipeptidyl peptidase 4 inhibitors, anticholinergics, and dopaminergic medications. Meaning The findings of this systematic review and meta-analysis suggest that medications should be prescribed judiciously, particularly in high-risk patients who are elderly and have disabling neurologic disorders. Importance The association between the use of medications and the development of bullous pemphigoid (BP) is unclear. Objective To assess the associations between previous exposure to certain medications and BP. Data Sources For this systematic review and meta-analysis, PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched for relevant studies from inception to February 20, 2020. Study Selection Case-control or cohort studies and randomized clinical trials that examined the odds or risk of BP in patients with previous medication use were included. No geographic or language limitations were imposed. Data Extraction and Synthesis The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline was followed. The Newcastle-Ottawa Scale was used to evaluate the risk of bias of included observational studies; Cochrane Collaboration's tool was used for randomized clinical trials. Aggregate data were used to conduct a random-effects model meta-analysis if the included studies were sufficiently homogenous. Subgroup analyses were performed for use of various medications of the same category. Main Outcomes and Measures Odds ratio (OR), hazard ratio, and risk ratio of bullous pemphigoid in association with medication use. Results This meta-analysis included 13 case-control studies, 1 cohort study, and 1 randomized clinical trial with a total of 285.884 participants. The meta-analysis of case-control studies showed a significant association of BP with previous use of aldosterone antagonists (pooled OR, 1.75; 95% CI, 1.28-2.40), dipeptidyl peptidase 4 inhibitors (pooled OR, 1.92; 95% CI, 1.55-2.38), anticholinergics (pooled OR, 3.12; 95% CI, 1.54-6.33), and dopaminergic medications (pooled OR, 2.03; 95% CI, 1.34-3.05). One cohort study found an increased risk of BP among patients receiving dipeptidyl peptidase 4 inhibitors (hazard ratio, 2.38; 95% CI, 1.16-4.88; P = .02). One trial found a higher occurrence of BP in patients with diabetes receiving linagliptin (0.2% in diabetes group vs 0% in the placebo group). Conclusions and Relevance The findings of this systematic review and meta-analysis suggest that aldosterone antagonists, dipeptidyl peptidase 4 inhibitors, anticholinergics, and dopaminergic medications are associated with BP. These medications should be judiciously prescribed, particularly in high-risk patients who are elderly and have disabling neurologic disorders.

Bullous and Exanthematous Lesions Associated With Chimeric Antigen Receptor T-Cell Therapy in a Patient With Diffuse Large B-Cell Lymphoma

期刊: JAMA DERMATOLOGY, 2020; 156 (9)

This case report describes a man in his 40s who developed a painful maculopapular rash on his trunk and upper and lower extremities following chimeric antigen receptor T-cell therapy for lymphoma.

Coinfection With Talaromyces marneffei and Other Pathogens Associated With Acquired Immunodeficiency

期刊: JAMA DERMATOLOGY, 2019; 155 (10)

This case report describes a woman in her 40s who became infected with Talaromyces marneffei and other pathogens after developing an adult-onset immunodeficiency syndrome.

JIF:7.99

Dry Scaly Patches and Nodules in a Middle-aged Man

期刊: JAMA DERMATOLOGY, 2019; 155 (10)

A man in his 50s with a history of itchy eruptions presented with extensive dry, scaly patches and nodules on his trunk and extremities. What is your diagnosis?

JIF:7.99

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