Periocular Dark Circles: Correlates of Severity.

BACKGROUND: Periocular dark circles (PDCs) are a common cosmetic complaint. Grading systems based on objective measures have been used but no standard system is in place. OBJECTIVE: To determine factors associated with subjective and objective PDC severity. METHODS: Enrolled patients (n=100) completed a questionnaire comprised of demographic variables, medical history, and self-perception of PDC. Those perceiving PDC graded dissatisfaction on a 10-point scale. Clinical severity (grades 0~4) and subtype (constitutional, post-inflammatory, vascular, shadow effects, or others) were determined. A Konica Minolta CR-400 chromameter was used to obtain colorimetry measurements (L*a*b* values). The objective average difference in darkness (ΔL*) between the periocular region and the cheek was determined. Comparisons were made using Spearman correlation coefficients (r). RESULTS: Patient dissatisfaction correlated with both clinical severity (r=0.46, p<0.001) and the ΔL* by colorimetry (r=0.35, p=0.004). Factors associated with subjective dissatisfaction were female sex (r=0.38, p=0.002), higher Fitzpatrick skin type (r=0.42, p=0.001), fewer hours of sleep (r=-0.28, p=0.03), and use of concealer (r=0.35, p=0.004). Factors associated with objective measures were higher Fitzpatrick skin type (r=0.36, p=0.0007 and r=0.28, p=0.009, respectively), family history of PDC (r=0.34, p<0.001 and r=0.20, p=0.05), and history of eczema (r=0.45, p<0.001 and r=0.20, p=0.0504). Clinical severity grading correlated with colorimetric severity (r=0.36, p=0.0003). CONCLUSION: Overall, subjective dissatisfaction was associated with clinical severity. However, factors associated with subjective severity did not necessarily overlap with factors associated with objective severity. These findings highlight the importance of patient-reported grading. There may be added value in incorporating a component of subjective grading into the traditionally objective PDC grading scales.

Co-existence of multiple sclerosis and germinoma in an adult male: Case report.

BACKGROUND: Concurrent diagnosis of multiple sclerosis (MS) and the central nervous system (CNS) germinoma is rare. The diagnostic criteria for MS rely primarily on clinical presentation, and CNS germinoma can present as an MS mimic. These factors contribute to the rarity of dual diagnosis. CASE DESCRIPTION: A 28-year-old man presented initially with bilateral optic neuritis, manifesting as persistently worsening vision for 2 years, and demyelinating plaques identified within the corpus callosum on magnetic resonance imaging. Initial work-up, in addition to clinical presentation, led to diagnosis of MS. Three months following the diagnosis of MS, the patient then presented with obstructive hydrocephalus due to a newly diagnosed intraventricular mass. The patient underwent an endoscopic third ventriculostomy and biopsy which confirmed diagnosis of CNS germinoma. CONCLUSION: To the best of our knowledge, dual presentation of both MS and CNS germinoma has never been reported in the literature. The clinical presentation of bilateral optic neuritis (persisting for roughly 2 years before initial MS diagnosis), demyelinating plaques, and intrathecal oligoclonal bands before the development of an intraventricular mass indicates that both MS and CNS germinoma presented simultaneously in this patient. The treatment plan for this patient included carboplatin + etoposide, followed by adjuvant radiation and subsequent IVIG therapy.

Rosette-forming glioneuronal tumor: an illustrative case and a systematic review.

BACKGROUND: Rosette-forming glioneuronal tumors (RGNTs) are rare, low-grade, primary CNS tumors first described in 2002 by Komori et al. RGNTs were initially characterized as a World Health Organization (WHO) grade I tumors typically localized to the fourth ventricle. Although commonly associated with an indolent course, RGNTs have the potential for aggressive behavior. METHODS: A comprehensive search of PubMed and Web of Science was performed through November 2019 using the search term "rosette-forming glioneuronal tumor." Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. English, full-text case reports and series with histopathological confirmation were included. Patient demographics, presentations, MRI features, tumor location, treatment, and follow-up of all 130 cases were extracted. RESULTS: A 19-year-old man with a history of epilepsy and autism presented with acute hydrocephalus. MRI scans from 2013 to 2016 demonstrated unchanged abnormal areas of cortex in the left temporal lobe with extension into the deep gray-white matter. On presentation to our clinic in 2019, the lesion demonstrated significant progression. The patient's tumor was identified as RGNT, WHO grade I. One hundred thirty patients were identified across 80 studies. CONCLUSION: RGNT has potential to transform from an indolent tumor to a tumor with more aggressive behavior. The results of our systematic review provide insight into the natural history and treatment outcomes of these rare tumors.

Career satisfaction of leaders in academic dermatology: Results from a national survey.

BACKGROUND: A positive correlation between leadership roles and job satisfaction has been noted in some areas of business. Since senior leaders in academic dermatology appear to be more satisfied than their junior colleagues, a similar relationship may be important in dermatology. OBJECTIVE: To determine if there is an association between leadership roles and career satisfaction of academic dermatologists. METHODS: A cross-sectional, anonymous survey was mailed to 1263 academic dermatologists across the US. Participants were questioned on demographics and career satisfaction. Academic rank and position was compared with career satisfaction. RESULTS: The leadership cohort was comprised of 140 (77%) men and 41 (23%) women (p < 0.01). Leaders were significantly more satisfied in their careers than non-leaders (65% versus 36%, p < 0.01), and were also less likely to leave academia. Factors related to career satisfaction included satisfaction with the promotion process (p < 0.01), presence of career development programs (p < 0.02), physician health (p < 0.01), and the ability to achieve balance in one's personal and professional lives (p = 0.01). Our analysis also demonstrated a gender gap within the leadership sector, with female leaders reporting less satisfaction overall with their career (44% versus 71%, p < 0.01), with the tenure/promotion process at their institutions (89% vs. 68%, respectively, p < 0.01), as well as their personal and professional balance (49% vs. 80%, p < 0.01) compared to their male leaders counterparts respectively. However, there was no difference in the likelihood of leaving academia between male and female leaders. CONCLUSION: Academic leaders overall had higher career satisfaction than non-leaders, and were more likely to stay within academia. Despite this, patterns of gender disparities in the academic dermatology leadership persist with males outnumbering females in the leadership pool, and male leaders reporting higher levels of satisfaction compared to their female counterparts, as well as perceiving fewer challenges in finding balance between their personal and professional lives.

Myxoid glioneuronal tumor, PDGFRA p.K385-mutant: clinical, radiologic, and histopathologic features.

"Myxoid glioneuronal tumor, PDGFRA p.K385-mutant" is a recently described tumor entity of the central nervous system with a predilection for origin in the septum pellucidum and a defining dinucleotide mutation at codon 385 of the PDGFRA oncogene replacing lysine with either leucine or isoleucine (p.K385L/I). Clinical outcomes and optimal treatment for this new tumor entity have yet to be defined. Here, we report a comprehensive clinical, radiologic, and histopathologic assessment of eight cases. In addition to its stereotypic location in the septum pellucidum, we identify that this tumor can also occur in the corpus callosum and periventricular white matter of the lateral ventricle. Tumors centered in the septum pellucidum uniformly were associated with obstructive hydrocephalus, whereas tumors centered in the corpus callosum and periventricular white matter did not demonstrate hydrocephalus. While multiple patients were found to have ventricular dissemination or local recurrence/progression, all patients in this series remain alive at last clinical follow-up despite only biopsy or subtotal resection without adjuvant therapy in most cases. Our study further supports "myxoid glioneuronal tumor, PDGFRA p.K385-mutant" as a distinct CNS tumor entity and expands the spectrum of clinicopathologic and radiologic features of this neoplasm.

Adult autoimmune enteropathy presenting initially with acquired Acrodermatitis Enteropathica: a case report.

BACKGROUND: Acrodermatitis enteropathica (AE) is a rare dermatitis secondary to zinc deficiency most commonly seen as an inherited disease in infants. In the last decade, increased number of reports have been published on the acquired form that presents in adulthood. Unlike its inherited counterpart, acquired AE (AAE) is often secondary to underlying pathologic or iatrogenic etiologies that interfere with nutritional absorption, such as inflammatory bowel disease or alcoholism. Various gastrointestinal pathologies have been associated with AAE, but there is currently no report on its association with adult autoimmune enteropathy (AIE), a rare gastrointestinal disorder commonly seen in infants, with limited cases reported in adults. Here we present a case in which AAE was the initial clinical manifestation in an adult patient subsequently diagnosed with AIE. CASE PRESENTATION: A 41-year-old African American female presented to our emergency department at the Johns Hopkins Hospital with several months of progressively worsening dermatitis in the legs and acral regions, along with worsening symptoms of diarrhea, alopecia, poor oral intake, lethargy, hematochezia, peripheral edema, and weight loss. Our dermatology team was consulted given a presentation of exquisitely tender, erythematous, and diffusely desquamating skin lesions in the setting of two prior outside hospitalizations in the last 3 months with the same dermatitis that was refractory to topical and oral corticosteroids. Low serum zinc level and positive response to zinc supplementation confirmed the diagnosis of AAE. However, persistent hypovitaminosis and mineral deficiency despite aggressive nutritional supplementation prompted further investigation for an underlying malabsorption etiology. Jejunal biopsy and associated autoantibodies confirmed a diagnosis of adult AIE. CONCLUSION: This case highlights the fact that adult AIE can present initially with clinical findings of AE. While proper zinc supplementation can resolve the latter, recognizing this association can trigger earlier diagnosis, minimize unnecessary tests, and establish earlier intervention to improve quality of life and prevent recurrence of AAE. The case also highlights the importance of collaboration between general and subspecialist physicians in identifying a primary etiology to a secondary clinical presentation. This report can be beneficial to general internists and emergency physicians, as much as it can be to dermatologists, rheumatologists, and gastroenterologists.

Randomized, split-body, single-blinded clinical trial of topical broccoli sprout extract: Assessing the feasibility of its use in keratin-based disorders.

BACKGROUND: Epidermolysis bullosa simplex is a skin-blistering disorder caused by mutations in keratin (K)14 or K5. Treatment with nuclear factor (erythroid-derived 2)-like 2 inducer sulforaphane ameliorated skin blistering in Krt14-null mice, correlating with induction of K17. To be therapeutically useful for epidermolysis bullosa simplex, topical broccoli sprout extract (BSE), enriched for sulforaphane, would ideally induce the expression of homologous keratins (eg, K6, K17, K16) in the basal layer of human epidermis without impacting expression of defective keratins (K5/K14). OBJECTIVE: The purpose of this 1-week, randomized, split-body, single-blinded, placebo-controlled trial was to assess the impact of BSE on keratin expression. METHODS: Five subjects (34-71 years old) applied BSE (500 nmol of sulforaphane/mL) or vehicle alone to the inner aspect of the arm daily. Expression of keratin, nuclear factor (erythroid-derived 2)-like 2, and other markers was assessed using reverse transcription-polymerase chain reaction and indirect immunofluorescence. RESULTS: One subject (age 71 years) was excluded a posteriori because of poor tissue quality. Topical BSE activated nuclear factor (erythroid-derived 2)-like 2 and up-regulated K17 in the epidermis of all subjects, had variable effects on K16 and K6 expression, and did not alter expression of K14 or K5. LIMITATIONS: Small sample size is a limitation. CONCLUSION: BSE represents an attractive therapeutic candidate for K14-associated epidermolysis bullosa simplex.

Selective suppression of the human aryl hydrocarbon receptor function can be mediated through binding interference at the C-terminal half of the receptor.

The human aryl hydrocarbon receptor is a cytosolic signaling molecule which affects immune response and aberrant cell growth. Canonical signaling of the receptor requires the recruitment of coactivators to the promoter region to remodel local chromatin structure. We predicted that interference of this recruitment would block the aryl hydrocarbon receptor function. To prove that, we employed phage display to identify nine peptides of twelve-amino-acid in length which target the C-terminal half of the human aryl hydrocarbon receptor, including the region where coactivators bind. Eight 12mer peptides, in the form of GFP fusion, suppressed the ligand-dependent transcription of six AHR target genes (cyp1a1, cyp1a2, cyp1b1, ugt1a1, nqo1, and ahrr) in different patterns in Hep3B cells, whereas the AHR antagonist CH-223191 suppressed all these target genes similarly. Three of the 12mer peptides (namely 11-3, 1-7, and 7-3) suppressed the 3MC-induced, CYP1A1-dependent EROD activity and the ROS production caused by benzo[a]pyrene. These 12mer peptides suppressed the AHR function synergistically with CH-223191. In conclusion, we provide evidence that targeting the C-terminal half of the human aryl hydrocarbon receptor is a viable, new approach to selectively block the receptor function.

Silver Ink Formulations for Sinter-free Printing of Conductive Films.

Inkjet printing offers an attractive method for the deposition of metal interconnects in electronic systems and enables a low-cost, environmentally friendly route to manufacture. However, virtually all current metal inkjet processes require post-deposition sintering treatments to achieve the optimum electrical conductivity, because the growth mechanism involves coalescence of discrete nanoparticles. A manufacturing process that reduces the number of steps by directly printing silver, removing the need to sinter the printed metal, would be highly advantageous. Here we describe a, sinter-free process that results in the direct printing of crystalline silver. This process exploits the chemistries developed for Atomic Layer Deposition (ALD), to form the basis of a new ink formulation, which we term; Reactive Organometallic inks (ROM). These ROM ink formulations are capable of depositing low temperature, high conductivity metal films, without the need for subsequent sintering treatments. To reduce the temperature for direct formation of metallic Ag, we have added an alcohol as a catalytic reducing agent to dissociate the organometallic component. Silver films printed from our novel ROM ink, on a glass substrate at 120 °C, are electrically conductive with a typical resistivity as low as 39.2% that of bulk silver, without the need for sintering.

Diagnosis and treatment of leprosy type 1 (reversal) reaction.

Leprosy is a chronic granulomatous infection caused by the organism Mycobacterium leprae that primarily affects the skin and peripheral nerves. Leprosy has several distinct clinical presentations ranging from moderate to severe, with the extent of disease generally depending on the host's immune response to the infection. Treatment typically involves antimicrobials (eg, clofazimine, dapsone, rifampin). Once treatment is started, an important aspect of patient care is the recognition of possible reversal reactions. We report the case of a 44-year-old man who repeatedly developed physical findings consistent with a type 1 (reversal) reaction after undergoing multiple treatments for leprosy. A discussion of leprosy along with its clinical manifestations, treatment methods, and management of reversal reactions also is provided.

Using the Physician Global Assessment in a clinical setting to measure and track patient outcomes.

IMPORTANCE: In dermatology, the development of objective, standardized quality measures that can be used in a clinical setting is important to be able to respond to the needs of payers and credentialing and licensure bodies and to demonstrate dermatologic value. OBJECTIVE: To examine the feasibility of using Physician Global Assessment (PGA) scores to collect and track patient acne and psoriasis outcomes over time. DESIGN, SETTING, AND PARTICIPANTS: The PGA severity scores were included on physicians' billing sheets for patients with acne and psoriasis seen at a tertiary care center outpatient dermatology clinic from June 2011 through October 2012. A subset of patients from 5 clinics completed Patient Global Assessments (PtGAs) between November 2011 and May 2012. Thirty dermatology clinicians saw a total of 2770 patients with acne and 1516 patients with psoriasis in clinic, recording PGA scores for each patient. The PtGA scores were collected from 52 and 103 patients with acne and psoriasis, respectively, within the larger sample. MAIN OUTCOMES AND MEASURES: Longitudinal PGA severity scores were collected for acne and psoriasis. The PGA severity scores were analyzed over time, with the hypothesis that patient scores for both acne and psoriasis would improve between the initial and follow-up visits. The PtGA scores from a subset of clinics and dates were compared with PGA scores to assess within-clinic reliability, with the hypothesis that there would be good agreement between clinician and patient assessments. RESULTS: New patient PGA outcomes showed considerable improvement over time. At 3-month follow-up, 14.6% of the acne cohort was graded as effectively clear, compared with 2.1% at baseline (P < .001). Similarly, at 3-month follow-up, 22.3% of the psoriasis cohort was graded as effectively clear, compared with 3.1% at baseline (P < .001). Additionally, interobserver agreement between PGA and PtGA scores was good (acne, κ = 0.68; psoriasis, κ = 0.70). CONCLUSIONS AND RELEVANCE: The PGA can be readily incorporated into practice to track patient acne and psoriasis outcomes over time, representing an opportunity for dermatologists to evaluate performance and validate practice guidelines.