Human Polyomavirus 9-An Emerging Cutaneous and Pulmonary Pathogen in Solid Organ Transplant Recipients.

IMPORTANCE: We describe the first report to our knowledge of cutaneous and systemic pathogenicity of human polyomavirus 9 in solid organ transplant recipients. OBJECTIVE: Three solid organ transplant recipients developed a widespread, progressive, violaceous, and hyperkeratotic skin eruption. All died from pulmonary and multiorgan failure around 1 year from onset of the rash. Routine clinical diagnostic testing could not identify any causative agent; therefore, samples and autopsies were investigated for novel pathogens using high-throughput sequencing. DESIGN, SETTING, AND PARTICIPANTS: This case series, including 3 solid organ transplant recipients who developed characteristic pink, violaceous, or brown hyperkeratotic papules and plaques throughout the body, was conducted at the Columbia University Medical Center. Lesional skin biopsies were collected from all 3 patients and subjected to high-throughput illumina sequencing for identification of microbial pathogens. Human polyomavirus 9 was identified in lesional skin biopsies. We subsequently collected ocular swabs, oral swabs, urine samples, and blood samples from patients, and organ tissues at autopsy in 1 patient. We investigated these samples for the presence of human polyomavirus 9 using in situ hybridization and quantitative polymerase chain reaction (PCR) assays. MAIN OUTCOMES AND MEASURES: A description of the clinical and pathologic findings of 3 patients. RESULTS: This case series study found that human polyomavirus 9 was detected in the skin biopsies of all 3 patients by a capture-based high-throughput sequencing method platform (VirCapSeq-VERT). Human polyomavirus 9 was also detected in blood, oral, ocular swabs, and urine by real-time polymerase chain reaction (PCR) assay. In situ hybridization and quantitative PCR assays were performed on the skin biopsies from 3 patients and lung autopsy of 1 patient, which showed the presence of human polyomavirus 9 messenger RNA transcripts, indicating active viral replication and pathogenesis in the skin and lungs. CONCLUSIONS AND RELEVANCE: Human polyomavirus 9 was associated with the widespread cutaneous eruption. All 3 patients had progression of cutaneous disease, accompanied by clinical deterioration, pulmonary failure, and death. One patient underwent autopsy and human polyomavirus 9 was identified in the lungs and paratracheal soft tissue. These findings suggest that human polyomavirus 9 may be associated with cutaneous and possibly pulmonary infection and death in solid organ transplant recipients.

A newly described cutaneous reaction at sites of insulin pump use in a child with Type 1 diabetes.

Continuous subcutaneous insulin infusion (CSII), or insulin pumps, with or without continuous glucose monitoring (CGM) devices have become the standard of care for patients with type 1 diabetes. While increasingly popular, a wide range of reported skin reactions to CSII and CGM devices was found. We present this case of a pyogenic granuloma-like neutrophilic and granulomatous response to an insulin pump to increase awareness of a previously uncharacterized cutaneous adverse reaction at insulin pump infusion sites.

Prevalence, comorbidities and mortality of toxic shock syndrome in children and adults in the USA.

Toxic Shock Syndrome (TSS), a superantigen-mediated illness, is characterized by rash, hypotension and multi-organ dysfunction. Predictors of TSS and related morbidity and mortality are poorly defined. In this study, data on 61,959,084 hospitalizations from the 2003-2012 Nationwide Inpatient Sample, a 20% stratified sample of US hospitalizations, were analyzed and ICD-9-CM coding used to identify 4491 hospitalizations with a diagnosis of TSS. Incidence, in-hospital mortality rate, comorbidities, length of stay and costs of care attributable to TSS were determined. In multivariate survey logistic regression models, TSS was associated with female sex (adjusted odds ratio [95% confidence interval], 1.54 [1.48-1.60]), younger age (0-17 years, 2.17 [2.06-2.29]; 40-59: 0.53 [0.50-0.56]; 60-79: 0.28 [0.26-0.30]; 80+: 0.13 [0.11-0.14] compared with 18-39) and race/ethnicity (black, 0.63 [0.59-0.67]; Hispanic: 0.60 [0.56-0.64]; Asian, 1.11 [1.00-1.11]; and other, 0.83 [0.75-0.92] compared with white). Patients with TSS had a three-fold greater cost of care (mean: $36,656 ± 942) and length of stay (LOS) (mean: 10.65 ± 0.23 days) than patients without TSS. Shared predictors of increased LOS and costs in patients with TSS were male sex; age 40-79 years; Black, Hispanic, Asian and other race/ethnicity; and more than one chronic condition. Predictors of in-hospital mortality included respiratory failure (13.66 [11.37-16.43]), liver disease/failure (3.36 [2.59-4.34]), chickenpox (91.26 [27.74-300.25]), coagulopathy (2.14 [1.85-2.48]), and higher age. In conclusion, there are significant racial/ethnic, socioeconomic, and comorbid disparities in the incidence and mortality of TSS in adults and children in the USA.

The history of atopic dermatitis.

Fred Wise (1881-1950) and Marion Sulzberger (1895-1983) are often credited with introducing the term atopic dermatitis to dermatology in 1933. This definition was based on atopy, a term first created by Arthur Coca (1875-1959) and Robert Cooke (1880-1960) in 1923, when they recognized an association between allergic rhinitis and asthma. Despite its recent introduction into our medical lexicon, historical precursors of atopic dermatitis date back to at least as early as 69-140 ce. In this contribution, we highlight both the prominent individuals credited with shaping the disorder into our current interpretation and the suspected historical precursors of this disease and reported treatments.

Therapeutic Synergy, Neutrality, and Antagonism: Combination Treatment in Dermatology.

Dermatologists frequently employ combination therapy to treat various diseases, but the evidence to support the use of such combinations is often lacking. Synergy is an appealing although somewhat ambiguous concept in medicine. Utilizing synergy allows clinicians to provide the most efficacious combination of treatments to patients, while potentially minimizing adverse effects and reducing the development of drug resistance. Definitions of synergy vary, but ultimately converge on finding a therapeutic advantage in combining treatments. Here we discuss the concept of 'therapeutic synergy', which can be defined as an increase in the efficacy of a combination of treatments in comparison to any of its individual parts alone. We review the concept of therapeutic synergy in dermatology by discussing some of the evidence regarding combination therapies utilized in the management of atopic dermatitis, acne vulgaris, psoriasis, and cutaneous lupus erythematosus. Further meaningful investigation of therapeutic synergy and its applications in dermatology should be undertaken.

J Drugs Dermatol. 2016;15(10):1203-1207.

Associations of Physical Activity and Sedentary Behavior with Atopic Disease in United States Children.

OBJECTIVES: To determine if eczema, asthma, and hay fever are associated with vigorous physical activity, television/video game usage, and sports participation and if sleep disturbance modifies such associations. STUDY DESIGN: Data were analyzed from 2 cross-sectional studies including 133 107 children age 6-17 years enrolled in the 2003-2004 and 2007-2008 National Survey of Children's Health. Bivariate and multivariate survey logistic regression models were created to calculate the odds of atopic disease and atopic disease severity on vigorous physical activity, television/video game use, and sports participation. RESULTS: In multivariate logistic regression models controlling for sociodemographic factors, lifetime history of asthma was associated with decreased odds of ≥1 days of vigorous physical activity (aOR, 0.87; 95% CI, 0.77-0.99) and decreased odds of sports participation (0.91; 95% CI, 0.84-0.99). Atopic disease accompanied by sleep disturbance had significantly higher odds of screen time and lower odds of sports participation compared with children with either atopic disease or sleep disturbance alone. Severe eczema (aOR, 0.39; 95% CI, 0.19-0.78), asthma (aOR, 0.29; 95% CI, 0.14-0.61), and hay fever (aOR, 0.48; 95% CI, 0.24-0.97) were all associated with decreased odds of ≥1 days of vigorous physical activity. Moderate (aOR, 0.76; 95% CI, 0.57-0.99) and severe eczema (aOR, 0.45; 95% CI, 0.28-0.73), severe asthma (aOR, 0.47; 95% CI, 0.25-0.89), and hay fever (aOR, 0.53; 95% CI, 0.36-0.61) were associated with decreased odds of sports participation in the past year. CONCLUSIONS: Children with severe atopic disease, accompanied by sleep disturbance, have higher risk of sedentary behaviors.

Asthma, hay fever, and food allergy are associated with caregiver-reported speech disorders in US children.

BACKGROUND: Children with asthma, hay fever, and food allergy may have several factors that increase their risk of speech disorder, including allergic inflammation, ADD/ADHD, and sleep disturbance. However, few studies have examined a relationship between asthma, allergic disease, and speech disorder. We sought to determine whether asthma, hay fever, and food allergy are associated with speech disorder in children and whether disease severity, sleep disturbance, or ADD/ADHD modified such associations. METHODS: We analyzed cross-sectional data on 337,285 children aged 2-17 years from 19 US population-based studies, including the 1997-2013 National Health Interview Survey and the 2003/4 and 2007/8 National Survey of Children's Health. RESULTS: In multivariate models, controlling for age, demographic factors, healthcare utilization, and history of eczema, lifetime history of asthma (odds ratio [95% confidence interval]: 1.18 [1.04-1.34], p = 0.01), and one-year history of hay fever (1.44 [1.28-1.62], p < 0.0001) and food allergy (1.35 [1.13-1.62], p = 0.001) were associated with increased odds of speech disorder. Children with current (1.37 [1.15-1.59] p = 0.0003) but not past (p = 0.06) asthma had increased risk of speech disorder. In one study that assessed caregiver-reported asthma severity, mild (1.58 [1.20-2.08], p = 0.001) and moderate (2.99 [1.54-3.41], p < 0.0001) asthma were associated with increased odds of speech disorder; however, severe asthma was associated with the highest odds of speech disorder (5.70 [2.36-13.78], p = 0.0001). CONCLUSION: Childhood asthma, hay fever, and food allergy are associated with increased risk of speech disorder. Future prospective studies are needed to characterize the associations.

Historical Perspectives on Atopic Dermatitis: Eczema Through the Ages.

Throughout history, individuals have had a myriad of dermatologic conditions characterized as chronic pruritic dermatoses. The term atopic dermatitis was not coined until the early 20th century. Many diseases typical of this condition were reported using a variety of eponyms and descriptive terms. Even as the incidence of atopic dermatitis rises, it remains poorly understood in the modern era, and viewing the disease from a historical perspective provides useful insight into its nature. This article highlights the evolution of concepts related to the pathogenesis of and recommended treatments for atopic dermatitis.

Utilization of Preventive Health Care in Adults and Children With Eczema.

INTRODUCTION: Chronic disease is a barrier to delivery of preventive health care and health maintenance. However, health behaviors of adults and children with eczema, a chronic skin disorder, have not been examined. This study examined associations of eczema with vaccination, disease screening, health maintenance, and healthcare utilization. METHODS: This study investigated 34,613 adults and 13,298 children from the 2012 National Health Interview Survey, a prospective questionnaire-based study. Data were analyzed between August 2014 and January 2015. RESULTS: Adult eczema was associated with higher odds of vaccination for tetanus (OR [95% CI]=1.37 [1.22, 1.54]); influenza (1.23 [1.10, 1.37]); hepatitis A (1.21 [1.04, 1.41]) and B (1.21 [1.07, 1.35]); human papilloma virus (1.66 [1.32, 2.08]); and pneumonia (1.35 [1.19, 1.54]), but not herpes zoster virus (1.07 [0.87, 1.31]). Adult eczema was associated with increased measurement of blood glucose (1.29 [1.16, 1.44]); cholesterol (1.19 [1.06, 1.34]); blood pressure (1.84 [1.56, 2.08]); and HIV infection (1.50 [1.34, 1.70]), but not Pap smears (1.11 [0.95, 1.30]); colon cancer screening (p=0.17); or mammograms (p=0.63). Adults with eczema were more likely to interact with general doctors, mid-level providers, mental health professionals, eye doctors, podiatrists, chiropractors, therapists, obstetrician/gynecologists, and other specialists (p≤0.01). Childhood eczema was associated with higher rates of vaccination for influenza (p<0.0002); well child checkups (p=0.002); and interaction with most types of healthcare providers (p≤0.01). Many associations remained significant in multivariate models controlling for sociodemographics and healthcare interaction frequency. CONCLUSIONS: Eczema in adults and children is associated with greater utilization of preventive health care and health maintenance, but not cancer screening.

Eczema Is Associated with Childhood Speech Disorder: A Retrospective Analysis from the National Survey of Children's Health and the National Health Interview Survey.

OBJECTIVE: To determine if eczema is associated with an increased risk of a speech disorder. STUDY DESIGN: We analyzed data on 354,416 children and adolescents from 19 US population-based cohorts: the 2003-2004 and 2007-2008 National Survey of Children's Health and 1997-2013 National Health Interview Survey, each prospective, questionnaire-based cohorts. RESULTS: In multivariate survey logistic regression models adjusting for sociodemographics and comorbid allergic disease, eczema was significantly associated with higher odds of speech disorder in 12 of 19 cohorts (P < .05). The pooled prevalence of speech disorder in children with eczema was 4.7% (95% CI 4.5%-5.0%) compared with 2.2% (95% CI 2.2%-2.3%) in children without eczema. In pooled multivariate analysis, eczema was associated with increased odds of speech disorder (aOR [95% CI] 1.81 [1.57-2.05], P < .001). In a single study assessing eczema severity, mild (1.36 [1.02-1.81], P = .03) and severe eczema (3.56 [1.70-7.48], P < .001) were associated with higher odds of speech disorder. History of eczema was associated with moderate (2.35 [1.34-4.10], P = .003) and severe (2.28 [1.11-4.72], P = .03) speech disorder. Finally, significant interactions were found, such that children with both eczema and attention deficit disorder with or without hyperactivity or sleep disturbance had vastly increased risk of speech disorders than either by itself. CONCLUSIONS: Pediatric eczema may be associated with increased risk of speech disorder. Further, prospective studies are needed to characterize the exact nature of this association.