Spontaneous clinical remission of Nagashima-type palmoplantar keratoderma in a patient of Korean descent with a heterozygous SERPINB7 mutation.

Nagashima-type palmoplantar keratoderma (NPPK) is an autosomal recessive form of diffuse palmoplantar keratoderma (PPK) characterized by thickening and redness of palms and/or soles. In this report, we describe a female patient of Korean descent who had clinical remission of her adult-onset NPPK. To our knowledge, she is the first reported heterozygous SERBINB7 mutation carrier to present with classic NPPK who achieved spontaneous clinical remission.

Characterization of Hepatic Dysfunction in Subjects Diagnosed With Chronic GVHD by NIH Consensus Criteria.

Hepatic chronic graft-versus-host disease (cGVHD) causes morbidity and current diagnostic criteria are nonspecific. An accurate diagnosis is imperative because overdiagnosis can lead to unnecessary treatment with immunosuppressive agents and raising the risk of opportunistic infections. We aim to characterize different patterns of liver injury and cytokine profiles associated with hepatic dysfunction in cGVHD, to evaluate the accuracy of the NIH Consensus Criteria (NCC) for hepatic cGVHD and to explore predictors for hepatic cGHVD. Patients were evaluated in this prospective cross-sectional study of patients with cGVHD recruited under a natural history protocol. Laboratory tests and cytokines were measured. The cGVHD were diagnosed and scored based on NCC. Clinically indicated liver biopsy specimens or autopsies were reviewed by an expert hepatopathologist (D.E.K.). Comparisons were made between groups, and univariable and multivariable logistic regression were calculated. Of the 302 patients enrolled, 151 fulfilled hepatic cGVHD based on NCC; however, 69% had at least 1 abnormal liver test result. Abnormal alanine aminotransferase (ALT) and aspartate aminotransferase were associated with lower platelets, higher total bilirubin (TB), total cholesterol, serum amyloid A, and IL 15. Abnormal ALP and gamma-glutamyl transpeptidase were associated with higher cholesterol, and IL7. Lower platelet count was associated with higher ALT, TB, and triglycerides and lower albumin. Of the 27 with liver tissue, 16 had histologic features of GVHD, only eight met clinical criteria for hepatic GVHD. Sensitivity and specificity of NCC in identifying hepatic GVHD were 50% and 27% (Kappa = -0.23). Only 6 had only hepatic GVHD, whereas 10 had hepatic GVHD with either iron overload, nodular regenerative hyperplasia, or steatosis. Multivariable logistic regression showed that ALP and total cholesterol were associated with hepatic GVHD and total cholesterol >220 mg/dL increased the sensitivity for histologic hepatic GVHD. In conclusion, abnormal liver enzymes in cGVHD are nonspecific and have poor correlation with histologic evidence for hepatic GVHD, highlighting the importance of histology. Cytokines provide insight into the pathogenesis of hepatic cGVHD. Decreased platelet count was associated with factors associated with liver disease including portal vein diameter, which may suggest progression of liver disease. This highlights the need of incorporating these factors in natural history study and using liver biopsy to understand the development of liver dysfunction in hematopoietic stem cell transplantation and to develop better instruments to decreased hepatic cGVHD related morbidity and mortality. The study was registered with a ClinicalTrials.gov identifier NCT00092235.

Abnormal liver tests are not sufficient for diagnosis of hepatic graft-versus-host disease in critically ill patients.

Hepatic graft-versus-host disease (HGVHD) contributes significantly to morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Clinical findings and liver biomarkers are neither sensitive nor specific. The relationship between clinical and histologic diagnoses of HGVHD was assessed premortem and at autopsy. Medical records from patients who underwent HSCT at the National Institutes of Health (NIH) Clinical Center between 2000 and 2012 and expired with autopsy were reviewed, and laboratory tests within 45 days of death were divided into 15-day periods. Clinical diagnosis of HGVHD was based on Keystone Criteria or NIH Consensus Criteria, histologic diagnosis based on bile duct injury without significant inflammation, and exclusion of other potential etiologies. We included 37 patients, 17 of whom had a cholestatic pattern of liver injury and two had a mixed pattern. Fifteen were clinically diagnosed with HGVHD, two showed HGVHD on autopsy, and 13 had histologic evidence of other processes but no HGVHD. Biopsy or clinical diagnosis of GVHD of other organs during life did not correlate with HGVHD on autopsy. The diagnostic accuracy of the current criteria was poor (κ = -0.20). A logistic regression model accounting for dynamic changes included peak bilirubin 15 days before death, and an increase from period -30 (days 30 to 16 before death) to period -15 (15 days before death) showed an area under the receiver operating characteristic curve of 0.77. Infection was the immediate cause of death in 68% of patients. In conclusion, liver biomarkers at baseline and GVHD elsewhere are poor predictors of HGVHD on autopsy, and current clinical diagnostic criteria have unsatisfactory performance. Peak bilirubin and cholestatic injury predicted HGVHD on autopsy. A predictive model was developed accounting for changes over time. Further validation is needed.

Drivers and sequelae of burnout in U.S. dermatology trainees.

BACKGROUND: Burnout is a health care epidemic. Although burnout has been shown to affect dermatologists in multispecialty studies, there are no such studies in dermatology trainees. OBJECTIVE: We conducted a survey-based study of burnout in U.S. dermatology trainees to identify its drivers and sequelae. METHODS: All residents enrolled in a U.S. dermatology training program were eligible. The 45-question survey included the Maslach Burnout Inventory, a validated quality of life index, and 31 questions based on known drivers of burnout and new research questions. No identifying data were collected. RESULTS: A total of 180 residents responded, for a response rate of 14.4%. Notably, an analysis of the cohort showed that our sample was not statistically different from the national complement of trainees based both on proportion of female respondents and mean age (p = .9449 and .2376, respectively). Of the respondents, 59% were female. The average age was 30.6 years. Sixty-nine percent of trainees (124 of 180) met the criteria for burnout. On univariate analysis, age, sex, training year, and relationship status were not associated with burnout. Good work-life balance (p = .032), autonomy in the workplace (p = .0027), intradisciplinary respect (p = .022), and increased work hours (p = .0110) were protective. On multivariate analysis, autonomy in the workplace (odds ratio: 3.580; confidence interval, 1.32-9.71; p = .012) and good work-life balance (odds ratio: 0.262; confidence interval, 0.095-0.722; p = .0097) remained significant. CONCLUSION: Improving control over working environment, as evidenced by the impact of work-life balance and autonomy, may lessen burnout in trainees. Further studies analyzing regional and program-specific variations will help improve trainee experience.

Authorship growth in contemporary medical literature.

OBJECTIVES: The aims of this study were to investigate authorship trends among publications in high-impact, peer-reviewed specialty journals published within the last decade and to assess how publication practices differ among medical specialties. METHODS: The National Institutes of Health's Portfolio Analysis platform, iCite, was queried for PubMed-indexed case reports, review articles, and original research articles published between 2005 and 2017 in 69 high-impact, clinical journals encompassing 23 medical specialties. Overall, 121,397 peer-reviewed publications were evaluated-of which, 45.1% were original research, 28.7% were review articles, and 26.3% were case reports. Multivariable regression was used to evaluate the magnitude of association of publication year on the number of authors per article by specialty and article type. RESULTS: Original research articles have the greatest increase in authorship (0.23 more authors per article per year), as compared with review articles (0.18 authors per article per year) and case reports (0.01 authors per article per year). Twenty-two of the 23 specialties evaluated had increase in authorship in high-impact specialty journals. Specialty growth rates ranged from 0.42 authors/year (Neurology), Psychiatry (0.35 authors/year), General Surgery (0.29 authors/year), Urology (0.27 authors/year), and Pathology (0.27 authors/year). Specialties with a greater percentage of graduates entering academics had more authors per article; surgical specialties and length of residency were not found to be predictive factors. CONCLUSION: There has been substantial growth in the authorship bylines of contemporary medical literature, much of which cannot be explained by increased complexity or collaboration alone.

Postinjection abscesses and granulomas in children adopted from Russia.

Up to 1.3 million children from the former Soviet Union (fSU) and Eastern Europe have been placed in institutional care worldwide. With the hope of ensuring the child's health in the immediate post-adoption period, these children are known to receive many injections of vaccines, vitamins, and medications, many unnecessary and often administered with unsafe technique. This practice can lead to formation of suppurative granulomas in these children. Though rare, dermatologists should be aware of these conditions in adoptees from Eastern Europe.

Cytomegalovirus Infection Incidence and Risk Factors Across Diverse Hematopoietic Cell Transplantation Platforms Using a Standardized Monitoring and Treatment Approach: A Comprehensive Evaluation from a Single Institution.

Human cytomegalovirus (CMV) infection and disease remains a significant cause of morbidity and mortality for hematopoietic cell transplantation (HCT) recipients. Disruption of or weak reconstitution of virus-specific cellular immune function, such as with certain HCT approaches, poses significant risk for CMV-related complications. The incidence of and risk factors for CMV infection and the nature of CMV disease were evaluated retrospectively among 356 consecutive HCT recipients transplanted at the National Institutes of Health using all graft sources, including bone marrow, peripheral blood stem cell (PBSC), and umbilical cord blood (UCB), and a range of in vivo and ex vivo approaches for graft-versus-host disease (GVHD) prophylaxis. The cumulative incidence of CMV infection was higher for CMV-seropositive recipients at 33%, regardless of donor CMV serostatus. Patients transplanted with CMV-seropositive donors had a significantly shorter duration of antiviral therapy. Among graft sources UCB was associated with the highest cumulative incidence of CMV infection at 65% and significantly longer treatment duration at a median of 36days, whereas PBSC HCT was associated with the lowest incidence at 26% and the shortest CMV treatment duration at a median of 21days. There were significant differences in the cumulative incidence of CMV infection by T cell manipulation strategy when systemic steroids were included as a risk-modifying event. Over one-third of CMV infections occurred in the setting of systemic steroid administration. CMV disease occurred in 5% of HCT recipients, with 70% of cases in the setting of treatment for GVHD. Although factors related to serostatus, graft source, and GVHD prophylaxis were associated with varied CMV infection incidence, unplanned post-HCT corticosteroid therapy contributed greatly to the incidence of both CMV infection and disease across HCT approaches, highlighting this post-HCT intervention as a key time to potentially tailor the approach to monitoring, preemptive therapy, and even prophylaxis.

Upper Extremity Friction Burns in the Pediatric Patient: A 10-year Review.

BACKGROUND: Upper extremity friction burn due to powered home equipment is a growing problem in the pediatric population. The purpose of this study was to review the etiology, presentation, characteristics, and treatment of this particular type of pediatric mechanism of injury. METHODS: A retrospective chart review using International Classification of Diseases, version 9, codes for patients treated at a large tertiary care, free-standing children's hospital was performed to identify all patients presenting with an upper extremity friction burn from 2003 to 2012. RESULTS: Sixty-nine patients sustained upper extremity friction burns. The average age at the time of injury was 3.3 years (range, 0.7-10.6) with presentation to our center occurring 16.6 days (range, 0-365 days) following injury. Mean follow-up was 23.3 months (range, 2-104). Mechanism of injury included treadmills (n = 63) and vacuum cleaners (n = 6). Twenty-eight operations were performed on 21 patients (30%). All patients requiring a surgical intervention sustained injury via treadmill mechanism (P = 0.0001). Unlike treadmill burns, vacuum cleaner injuries affected the dorsal hand or a single digit (P = 0.00004). Scar hyperpigmentation was more prevalent in these patients compared with the treadmill group (P = 0.003). All vacuum-induced burn patients had full range of motion and function with conservative treatment alone, whereas only 55.6% of treadmill burn patients had full recovery of range of motion and 50.8% recovery of full hand function. CONCLUSIONS: Friction burns from vacuum cleaners are less prevalent, have different injury patterns, and can be treated conservatively with excellent functional outcomes. Treadmill friction burns result in more significant injury and risk for dysfunction, requiring surgical intervention.

Mouse models of UV-induced melanoma: genetics, pathology, and clinical relevance.

Melanocytes, a neural crest cell derivative, produce pigment to protect keratinocytes from ultraviolet radiation (UVR). Although melanocytic lesions such as nevi and cutaneous malignant melanomas are known to be associated with sun exposure, the role of UVR in oncogenesis is complex and has yet to be clearly elucidated. UVR appears to have a direct mutational role in inducing or promoting melanoma formation as well as an indirect role through microenvironmental changes. Recent advances in the modeling of human melanoma in animals have built platforms upon which prospective studies can begin to investigate these questions. This review will focus exclusively on genetically engineered mouse models of UVR-induced melanoma. The role that UVR has in mouse models depends on multiple factors, including the waveband, timing, and dose of UVR, as well as the nature of the oncogenic agent(s) driving melanomagenesis in the model. Work in the field has examined the role of neonatal and adult UVR, interactions between UVR and common melanoma oncogenes, the role of sunscreen in preventing melanoma, and the effect of UVR on immune function within the skin. Here we describe relevant mouse models and discuss how these models can best be translated to the study of human skin and cutaneous melanoma.

Painful subcutaneous nodules on the thigh.

Osteoma cutis is the presence of bone within the dermis or subcutaneous tissue. This condition may occur sporadically or secondary to other dermatologic or genetic conditions. We present a 12-year-old girl with pseudohypoparathyroidism type-Ia who developed osteoma cutis on the right thigh.

Pemphigus vegetans with coexistent herpes simplex infection and deep venous thrombosis of the lower extremities.

An elderly patient presented with a 4-month history of eroded hypertrophic condylomatous plaques with areas of vesiculation on the groin and lower extremities bilaterally, associated with swelling. Biopsy and immunofluorescence studies confirmed the diagnosis of pemphigus vegetans (PVeg). Further clinical evaluation revealed deep venous thrombosis of the lower extremities and septic shock from secondarily infected pemphigus lesions. Fluid obtained from vesicles was positive for herpes simplex virus (HSV) via PCR-based testing. The patient was therapeutically anticoagulated, treated with high-dose corticosteroid therapy, broad-spectrum intravenous antibiotics and acyclovir. This case represents a constellation of diagnoses not previously described. Although pemphigus vulgaris has been linked to thromboembolic events and has been associated with HSV, these associations have not been previously reported in PVeg. The coexistence of these diseases should encourage vigilance in the clinical work up of a patient with PVeg.