Acute Epstein-Barr virus infection resembling cutaneous T-cell lymphoma.

Primary, acute Epstein-Barr virus (EBV) infection is associated with a variety of cutaneous eruptions, including the viral exanthem of infectious mononucleosis and erythema multiforme. Latent, chronic EBV infection can rarely result in development of lymphoproliferative disorders with cutaneous manifestations; however, these disorders do not arise from primary infection. In this report, we present a case of primary, acute EBV infection presenting with histopathologic features closely mimicking aggressive cytotoxic cutaneous T-cell lymphoma.

Migraine among adults with atopic dermatitis: a cross-sectional study in the All of Us research programme.

Atopic dermatitis (AD) has been previously associated with migraine headaches in paediatric and adolescent populations, though there is less evidence for this relationship among adults. In this cross-sectional study, we investigated the association between AD and migraine among a cohort of US adults in the All of Us research programme. After controlling for common comorbidities, we found that adults with AD were 89% more likely to have a diagnosis of migraine (OR = 1·89, P < 0·001).

Vaccination Recommendations for Psoriasis and Atopic Dermatitis Patients on Biologic Therapy: A Practical Guide.

Novel biologic therapies have revolutionized the treatment of psoriasis and atopic dermatitis. Although they are generally safe, they are immunomodulatory and therefore unique considerations apply in regards to infections and vaccine administration. This review aims to provide a clear and practical guide for dermatologists or other healthcare providers to reference when caring for psoriasis or atopic dermatitis patients being treated with biologic therapies using currently available guidelines and clinical data. Vaccinations for approved biologics including TNFα, IL-12/23, IL-23, IL-17, and IL-4/13 inhibitors will be discussed, with a special note on current COVID-19 vaccination recommendations.

Lichen planus is associated with depression and anxiety: a cross-sectional study in the All of Us research program.

Lichen planus (LP) can be accompanied by psychiatric comorbidities. Studies investigating the relationship between LP and clinically diagnosed anxiety and depression are limited. We aimed to determine the association of LP with anxiety and depression by conducting a cross-sectional population study of the All of Us research database, a National Institutes of Health cohort. Patients with LP were identified through electronic health record data using codes from the International Classification of Diseases and Systematized Nomenclature of Medicine. We used multivariable logistic regression to assess associations between LP and anxiety and depression before and after controlling for relevant covariates. Among 239,552 participants, 1083 individuals with LP were identified, with an average age of 67.20 years (standard deviation, 11.79) and a female predominance (74% female). The prevalence of depression and anxiety were higher among individuals with LP than in those without (41.6% vs 27.7%, p < 0.001; 43.5% vs 29.6%, p < 0.001). LP remained significantly associated with depression (OR, 1.36; 95% CI, 1.20-1.56, p < 0.001) and anxiety (OR, 1.48; 95% CI, 1.30-1.68, p < 0.001) after controlling for age, sex, hypothyroidism, autoimmune diseases, hypertension, type II diabetes mellitus, cardiovascular disease, and hepatitis C infection. In this cross-sectional study, LP was associated with an increase in odds of having depression and anxiety in multivariable analysis. Further study is needed to better understand the relationship between mental health outcomes and LP to address the needs of patients with LP more completely.

Psoriasis associated with asthma and allergic rhinitis: a US-based cross-sectional study using the All of US Research Program.

Psoriasis is a common chronic inflammatory disease with multiple known comorbidities. Increasing evidence suggests some mechanistic overlap in the immunopathogenesis of psoriasis and some cases of asthma and allergic rhinitis (AR), but the potential association between psoriasis and asthma and AR has not been thoroughly investigated. The study aimed to investigate the association between psoriasis and asthma and AR. We used data from the NIH All of US Research Program, a nationwide longitudinal cohort of US adults, collected from 2018 to present. The source population comprised a demographically and socioeconomically diverse cohort of over 300,000 Americans. We used multivariable logistic regression models to examine the association between psoriasis and asthma and AR, after adjusting for sociodemographic variables, body mass index, and smoking status. In total, 235,551 participants (mean [SD] age, 54.7 [16.6] years; 59.3% female), including 5165 individuals with psoriasis and 230,386 individuals without psoriasis, were included in our analysis. Participants with psoriasis had significantly higher prevalence of asthma (26.1% vs. 12.9%; P < 0.001) and AR (31.8% vs. 13.4%; P < 0.001) compared to participants without psoriasis. Psoriasis was significantly associated with both asthma [adjusted odds ratio (aOR) 2.22; 95% confidence interval (CI) 2.08-2.37] and AR (aOR, 2.57; 95% CI 2.42-2.73). In subgroup analyses, associations remained stable in multivariable analyses after stratification by age, sex, and income. Psoriasis is associated with both asthma and AR in our sample of US adults. Further research is needed to explore potentially unifying inflammatory pathways among psoriasis, asthma, and AR.

Association between atopic dermatitis and COVID-19 infection: A case-control study in the All of Us research program.

BACKGROUND: There is an incomplete understanding of the risk of COVID-19 infection in atopic dermatitis (AD) patients. OBJECTIVE: To evaluate the risk of COVID-19 infection in AD patients in a large, diverse cohort. METHODS: A case-control study of the All of Us cohort to analyze the association between AD and COVID-19. Comorbidities and risk factors were compared between cases and controls using multivariable analyses. RESULTS: In a cohort of 11,752 AD cases with 47,008 matched controls, AD patients were more likely to have a COVID-19 diagnosis (4.2% vs 2.8%, P < .001). AD remained significantly associated with COVID-19 in multivariable analysis (odds ratio, 1.29; P < .001) after adjusting for demographic factors and comorbidities. LIMITATIONS: Ascertainment of AD and COVID-19 cases using electronic health records and lack of clinical data on AD severity or therapy and COVID-19 outcomes. CONCLUSION: AD is associated with increased odds of COVID-19 infection even after controlling for common comorbidities.

Antibiotic Resistance Risk with Oral Tetracycline Treatment of Acne Vulgaris.

Almost 1 billion people worldwide have acne, and oral tetracyclines, including doxycycline and minocycline, are effective and frequently prescribed treatments for acne. However, there is growing concern for the development of antibiotic resistance with such widespread utilization by dermatologists. Additionally, tetracyclines are known to have various potential side effects, including gut dysbiosis, gastrointestinal upset, photosensitivity, dizziness, and vertigo. However, in 2018 a novel narrow-spectrum tetracycline, sarecycline, was Food and Drug Administration-approved to treat moderate-to-severe acne vulgaris in patients 9-years-old and above. Sarecycline was designed to target Cutibacterium acnes, the pathogenic bacterium in acne vulgaris, which may reduce the risk of resistance. This paper examines the growing concerns of antibiotic resistance due to oral tetracycline usage in the treatment of acne vulgaris, with a focus on the promising third-generation, narrow-spectrum tetracycline, sarecycline.

The Genomic and Phenotypic Landscape of Ichthyosis: An Analysis of 1000 Kindreds.

IMPORTANCE: Ichthyoses are clinically and genetically heterogeneous disorders characterized by scaly skin. Despite decades of investigation identifying pathogenic variants in more than 50 genes, clear genotype-phenotype associations have been difficult to establish. OBJECTIVE: To expand the genotypic and phenotypic spectra of ichthyosis and delineate genotype-phenotype associations. DESIGN, SETTING, AND PARTICIPANTS: This cohort study recruited an international group of individuals with ichthyosis and describes characteristic and distinguishing features of common genotypes, including genotype-phenotype associations, during a 10-year period from June 2011 to July 2021. Participants of all ages, races, and ethnicities were included and were enrolled worldwide from referral centers and patient advocacy groups. A questionnaire to assess clinical manifestations was completed by those with a genetic diagnosis. MAIN OUTCOMES AND MEASURES: Genetic analysis of saliva or blood DNA, a phenotyping questionnaire, and standardized clinical photographs. Descriptive statistics, such as frequency counts, were used to describe the cases in the cohort. Fisher exact tests identified significant genotype-phenotype associations. RESULTS: Results were reported for 1000 unrelated individuals enrolled from around the world (mean [SD] age, 50.0 [34.0] years; 524 [52.4%] were female, 427 [42.7%] were male, and 49 [4.9%] were not classified); 75% were from the US, 12% from Latin America, 4% from Canada, 3% from Europe, 3% from Asia, 2% from Africa, 1% from the Middle East, and 1% from Australia and New Zealand. A total of 266 novel disease-associated variants in 32 genes were identified among 869 kindreds. Of these, 241 (91%) pathogenic variants were found through multiplex amplicon sequencing and 25 (9%) through exome sequencing. Among the 869 participants with a genetic diagnosis, 304 participants (35%) completed the phenotyping questionnaire. Analysis of clinical manifestations in these 304 individuals revealed that pruritus, hypohydrosis, skin pain, eye problems, skin odor, and skin infections were the most prevalent self-reported features. Genotype-phenotype association analysis revealed that the presence of a collodion membrane at birth (odds ratio [OR], 6.7; 95% CI, 3.0-16.7; P < .001), skin odor (OR, 2.8; 95% CI, 1.1-6.8; P = .02), hearing problems (OR, 2.9; 95% CI, 1.6-5.5; P < .001), eye problems (OR, 3.0; 95% CI, 1.5-6.0; P < .001), and alopecia (OR, 4.6; 95% CI, 2.4-9.0; P < .001) were significantly associated with TGM1 variants compared with other ichthyosis genotypes studied. Skin pain (OR, 6.8; 95% CI, 1.6-61.2; P = .002), odor (OR, 5.7; 95% CI, 2.0-19.7; P < .001), and infections (OR, 3.1; 95% CI, 1.4-7.7; P = .03) were significantly associated with KRT10 pathogenic variants compared with disease-associated variants in other genes that cause ichthyosis. Pathogenic variants were identified in 869 (86.9%) participants. Most of the remaining individuals had unique phenotypes, enabling further genetic discovery. CONCLUSIONS AND RELEVANCE: This cohort study expands the genotypic and phenotypic spectrum of ichthyosis, establishing associations between clinical manifestations and genotypes. Collectively, the findings may help improve clinical assessment, assist with developing customized management plans, and improve clinical course prognostication.

Measurement and immunophenotyping of pleural fluid EpCAM-positive cells and clusters for the management of non-small cell lung cancer patients.

OBJECTIVES: A malignant pleural effusion (MPE) is a common complication in non-small cell lung cancer (NSCLC) with important staging and prognostic information. Patients with MPEs are often candidates for advanced therapies, however, the current gold standard, cytological analysis of pleural fluid samples, has limited sensitivity. We aimed to demonstrate the feasibility of non-invasive enumeration and immunophenotyping of EpCAM-positive cells in pleural fluid samples for the diagnosis of a MPE in NSCLC patients. MATERIALS AND METHODS: Pleural fluid specimens were prospectively collected from patients with NSCLC and the CellSearch® technology was utilized for the enumeration of pleural EpCAM-positive cells (PECs) and determination of PD-L1 expression on PECs from pleural fluid samples. The diagnostic performance of the enumeration of single PECs and PEC clusters was assessed using receiver operating characteristic (ROC) curves. The Kaplan-Meier method and Cox proportional hazards model was used to assess the impact of PECs and PEC clusters on overall survival (OS). RESULTS: 101 NSCLC patients were enrolled. The median number of PECs was significantly greater in the malignant (n = 84) versus non-malignant group (n = 17) (730 PECs/mL vs 1.0 PEC/mL, p < 0.001). The area under the ROC curve was 0.91. A cutoff value of 105 PECs/mL had a sensitivity and specificity of 73% and 100% for the diagnosis of a MPE, respectively. Among 69 patients with a pathology-confirmed MPE and tissue immunohistochemistry (IHC) results, 15 (22%) had greater than 50% PD-L1+ PECs. Overall concordance between tissue and PEC PD-L1 expression was 76%. Higher numbers of pleural effusion single PECs were associated with inferior overall survival (Cox adjusted HR 1.8, 95% CI: 1.02-3.05 p = 0.043). CONCLUSION: Non-invasive measurement of PECs in NSCLC patients, using an automated, clinically available approach, may improve the diagnostic accuracy of a MPE, allow for immunophenotyping of PECs, and provide prognostic information.

Clinical Implications of Plasma-Based Genotyping With the Delivery of Personalized Therapy in Metastatic Non-Small Cell Lung Cancer.

Importance: The clinical implications of adding plasma-based circulating tumor DNA next-generation sequencing (NGS) to tissue NGS for targetable mutation detection in non-small cell lung cancer (NSCLC) have not been formally assessed. Objective: To determine whether plasma NGS testing was associated with improved mutation detection and enhanced delivery of personalized therapy in a real-world clinical setting. Design, Setting, and Participants: This prospective cohort study enrolled 323 patients with metastatic NSCLC who had plasma testing ordered as part of routine clinical management. Plasma NGS was performed using a 73-gene commercial platform. Patients were enrolled at the Hospital of the University of Pennsylvania from April 1, 2016, through January 2, 2018. The database was locked for follow-up and analyses on January 2, 2018, with a median follow-up of 7 months (range, 1-21 months). Main Outcomes and Measures: The number of patients with targetable alterations detected with plasma and tissue NGS; the association between the allele fractions (AFs) of mutations detected in tissue and plasma; and the association of response rate with the plasma AF of the targeted mutations. Results: Among the 323 patients with NSCLC (60.1% female; median age, 65 years [range, 33-93 years]), therapeutically targetable mutations were detected in EGFR, ALK, MET, BRCA1, ROS1, RET, ERBB2, or BRAF for 113 (35.0%) overall. Ninety-four patients (29.1%) had plasma testing only at the discretion of the treating physician or patient preference. Among the 94 patients with plasma testing alone, 31 (33.0%) had a therapeutically targetable mutation detected, thus obviating the need for an invasive biopsy. Among the remaining 229 patients who had concurrent plasma and tissue NGS or were unable to have tissue NGS, a therapeutically targetable mutation was detected in tissue alone for 47 patients (20.5%), whereas the addition of plasma testing increased this number to 82 (35.8%). Thirty-six of 42 patients (85.7%) who received a targeted therapy based on the plasma result achieved a complete or a partial response or stable disease. The plasma-based targeted mutation AF had no correlation with depth of Response Evaluation Criteria in Solid Tumors response (r = -0.121; P = .45). Conclusions and Relevance: Integration of plasma NGS testing into the routine management of stage IV NSCLC demonstrates a marked increase of the detection of therapeutically targetable mutations and improved delivery of molecularly guided therapy.