Faculty Bibliography

BACKGROUND:Accurate diagnosis of epidermolysis bullosa (EB) has significant implications for prognosis, management, and genetic counseling. OBJECTIVE:To describe diagnostic testing patterns and assess diagnostic concordance of transmission electron microscopy (TEM), immunofluorescence mapping (IFM), and genetic analysis for EB. METHODS:A retrospective cohort included patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2004, to July 8, 2019. Tests concluding the same EB type (EB simplex, junctional EB, dominant dystrophic EB, and recessive dystrophic EB) were considered concordant; those concluding different EB types were considered discordant; and those with nonspecific/nondefinitive results were equivocal. RESULTS:A total of 970 diagnostic tests were conducted from 1984 to 2018 in 771 patients. Genetic analyses were performed chronologically later than IFM or TEM (P < .001). The likelihood of undergoing genetic analysis was greater for junctional EB and recessive dystrophic EB, and the same for dominant dystrophic EB as compared with EB simplex. TEM results in 163 patients were equivocal (55%), concordant (42%), and discordant (3%). IFM results in 185 patients were equivocal (54%), concordant (42%), and discordant (4%). LIMITATIONS:Retrospective design. CONCLUSIONS:Diagnostic testing has shifted in favor of genetic analysis. TEM and IFM frequently offer equivocal findings when compared to the specificity afforded by genetic analysis.

BACKGROUND/OBJECTIVE/OBJECTIVE:Herpes simplex virus (HSV) infection acquired in utero may present with non-vesicular dermatologic findings in affected newborns, which may pose a diagnostic dilemma. We aimed to describe and assess the range of non-vesiculobullous skin lesions that neonates with intrauterine HSV infection may manifest at birth. METHODS:We collected a multicenter case series and conducted a literature review of neonates with intrauterine HSV infection presenting with non-vesiculobullous cutaneous lesions. RESULTS:Twenty-two cases were reviewed, including six managed clinically by members of our team and 16 identified in the literature. Four (18%) were associated with twin pregnancies, and thirteen (59%) cases occurred in premature infants. Only four (18%) mothers had a documented history of HSV infection. Twelve (55%) cases resulted in poor outcomes, including long-term neurologic sequelae or death. Cutaneous manifestations included erosions, ulcerations, crusted papules or plaques, calcinosis cutis, excoriations, macules (erythematous, hypopigmented, or hyperpigmented), cutaneous atrophy, contractures, and bruising. About one-third of neonates developed new-onset vesicular lesions within a week of birth; in each of these cases, accurate diagnosis and therapy were delayed until appearance of vesicles. CONCLUSIONS:The range of dermatologic findings associated with intrauterine HSV is extremely broad, and the various morphologies present at birth likely reflect different stages of the ongoing evolution of an HSV infection that began in utero. Clinicians should have a low threshold for HSV testing in premature neonates born with atypical cutaneous lesions, since early detection and treatment of HSV may reduce morbidity and mortality from systemic complications.

BACKGROUND:Atypical spiradenoma and spiradenocarcinoma present a diagnostic challenge. We aim to assess the significance of certain histologic features, which may facilitate diagnosis of these tumors. METHODS:A natural language search for cases of "atypical spiradenoma" and "spiradenocarcinoma" diagnosed between 2009 and 2018 was performed. Original slides were retrieved and a subset of cases (n = 5) were stained for Ki-67, p53, carcinoembryonic antigen (CEA), and S100. All cases (n = 7) were assessed for overall architecture, atypical mitotic figures, abnormal cytology, necrosis, ductal proliferation, dilated vessels, and loss of dual cell population. RESULTS:All our cases showed an abrupt transition from benign to malignant morphology, nuclear atypia, atypical mitotic figures, and a monomorphic loss of the dual cell population (7/7; 100%). The majority also had dilated vessels (6/7; 85.7%), and ductal dilation or proliferation (5/7; 71.4%). Fewer cases showed tumor encapsulation (3/7; 43%), massive necrosis (3/7; 43%), and focal cellular necrosis (1/7; 14%). All cases showed a relatively increased Ki-67 proliferation index at the transitional interface (5/5; 100%). Almost all cases stained positively for p53 (4/5; 80%). Malignant areas of tumor or at the transitional interface showed more intense S100 staining (3/5; 60%). All cases were negative for CEA. CONCLUSION/CONCLUSIONS:Histologic features that strongly favor atypical spiradenoma or spiradenocarcinoma include abrupt transition to malignant foci, atypical mitotic figures, and monomorphic loss of the dual cell population. Ki-67, p53, and S100 may help delineate areas of atypical or malignant transformation in spiradenomas.

Introduction/UNASSIGNED:Severe intracranial stenosis might lead to acute cerebral ischemia. It is imperative to better assess patients who may benefit from immediate reperfusion and blood pressure management to prevent injury to peri-infarct tissue. Methods/UNASSIGNED:We assessed cerebral autoregulation using static and dynamic methods in an 81-year-old woman suffering acute cerebral ischemia from severe intracranial stenosis in the petrous segment of the left internal carotid artery (LICA). Results/UNASSIGNED:Static cerebral autoregulation, which is evaluated by magnetic resonance imaging and magnetic resonance perfusion studies showed a progression of infarcts and a large perfusion-diffusion mismatch in the entire LICA territory between the second and third days after onset despite maximized medical therapy. Dynamic methods, including transfer function analysis and mean velocity index, demonstrated an increasingly impaired dynamic cerebral autoregulation (DCA) on the affected side between these days. Revascularization through acute intracranial stenting resulted in improved perfusion in the LICA territory and normalization of both dynamic and static cerebral autoregulation. Conclusion/UNASSIGNED:Thus, DCA, a noninvasive bedside method, may be useful in helping to identify and select patients with large-vessel flow-failure syndromes that would benefit from immediate revascularization of intracranial atherosclerotic disease.

OBJECTIVES/OBJECTIVE:Our skin is constantly exposed to light from solar radiation and electronic devices, which impact skin physiology and aging. The biological altering properties of ultraviolet (UV) solar radiation on skin have been well established. There is significant scientific and public interest on the effects of electronic device generated light (EDGL) on skin. Currently, the effects of EDGL on skin are largely unknown. EDGL includes UV, visible, and infrared light from consumer electronics such as smartphones, computers, and televisions. In this study, we measured the wavelength specific irradiance from electronic devices, and irradiated fibroblasts with white EDGL to determine changes in reactive oxygen species generation, apoptosis, and necrosis. METHODS:To determine the EDGL output of commonly used consumer electronic devices, we measured the irradiance from electronic devices at the manufacturers' recommended reading distances and at 1 cm. To determine the effect of EDGL on human skin cells, we irradiated AG13145 fibroblasts with EDGL for 1 hour at a distance of 1 cm and measured changes in reactive oxygen species generation, apoptosis, and necrosis. RESULTS:ROS increased significantly by 81.71%, 85.79%, and 92.98% relative to control following 1 hour of white EDGL from iPhone 8+, iPhone 6, and iPad (first generation), respectively. There was a non-significant change in apoptosis following irradiation with an iPhone 8+, iPhone 6, and iPad. Total necrosis was less than 2% for all treatment and control groups. CONCLUSIONS:Our results suggest that short exposures of EDGL increase ROS generation, but the long-term effects associated with repeated exposures of EDGL are unknown. As electronic devices become more widely used and integrated into society globally, we anticipate greater scientific research and general public interest on the effects of visible EDGL on skin. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.