Topical Roflumilast for Plaque Psoriasis.

Roflumilast is a highly selective phosphodiesterase-4 inhibitor for the treatment of plaque psoriasis. Topical roflumilast 0.3% cream, approved by the US FDA and Health Canada for use in adolescents and adults, has proven efficacy and tolerability. It is non-steroidal, administered once-daily, and highly potent, with a unique delivery formulation. It can be used on most body areas, including the sensitive intertriginous regions and face. Herein, we review the safety and efficacy of roflumilast 0.3% cream, as demonstrated in clinical trials.

Myeloid/Lymphoid Neoplasm with FGFR1 Rearrangement Presenting with Polycythemia Vera and T-cell Acute Lymphoblastic Leukemia.

Myeloid/lymphoid neoplasm with fibroblast growth factor 1 rearrangements (MLN-FGFR1) represents a rare group of hematologic neoplasms, with approximately 100 cases reported to date. A 69-year-old woman with a history of polycythemia and leukocytosis, with negative molecular testing for JAK2, CALR, and MPL, presented with diffuse adenopathy. A lymph node (LN) biopsy revealed effacement by T-lymphoblasts, consistent with T-cell acute lymphoblastic lymphoma (T-ALL). A staging bone marrow (BM) biopsy demonstrated trilineage hyperplasia, which, taken together with the patient's elevated hemoglobin and low serum erythropoietin level, fulfilled diagnostic criteria for polycythemia vera. Karyotype and fluorescence in situ hybridization on both the BM and LN demonstrated a FGFR1 rearrangement due to t(8;13), consistent with MLN-FGFR1. Whole genome sequencing on the LN additionally identified a pathogenic frameshift mutation of ASXL1 NC_000020.11:g32434646dup NM_015338.6(ASXL1):c.1934dup p.(Gly646Trpfs) predicted to result in loss of protein function, a finding also observed in 8.1% of BM reads. Both the BM and LN harbored missense variants in HDAC4 NM_001378414.1(HDAC4):c.[2763G>A]; [2763=] p.(Met921Ile) and CHEK2 NM_007194.4(CHEK2):c.[538C>T];[538=] p.(Arg180Cys), with an unknown significance. Despite initial response to Mini-CVD + venetoclax, the patient subsequently experienced rapid clinical deterioration and death. We report the second case of MLN-FGFR1 with an ASXL1 mutation and the first case with HDAC4 and CHEK2 variants.

Luminal-Type Invasive Carcinoma in Association With Microglandular Adenosis/Atypical Microglandular Adenosis: A Case Report and Molecular Comparison.

Microglandular adenosis (MGA) is a proliferative breast lesion composed of small, uniform glands lacking a myoepithelial cell layer while still invested by the basement membrane. The glands percolate haphazardly through the breast parenchyma rather than maintaining a lobular architecture, typical of other forms of adenosis.MGA is a benign lesion though atypical forms have been well described, often in close association with carcinoma. MGA, atypical MGA (AMGA), and the vast majority of MGA-associated carcinomas (MGACA) are negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) by immunohistochemistry. In light of these findings and early molecular studies, MGA is hypothesized to represent a clonal process and nonobligate precursor of basal-type breast carcinomas. We present the case of a 58-year-old woman and the first published molecular comparison of a luminal-type invasive ductal carcinoma with its associated MGA/AMGA. Analysis of small nucleotide variants (SNVs) revealed that 63% of the SNVs identified in the MGA were present in the AMGA while only 10% of them were present in the MGACA, suggesting a direct relationship between MGA and AMGA but not MGA and MGACA.

Reducing ether lipids improves Drosophila overnutrition-associated pathophysiology phenotypes via a switch from lipid storage to beta-oxidation.

High-calorie diets increase the risk of developing obesity, cardiovascular disease, type-two diabetes (T2D), and other comorbidities. These "overnutrition" diets also promote the accumulation of a variety of harmful lipids in the heart and other peripheral organs, known as lipotoxicity. However, the mechanisms underlying lipotoxicity and its influence on pathophysiology remain unknown. Our study uses genetics to identify the role of ether lipids, a class of potential lipotoxins, in a Drosophila model of overnutrition. A high-sugar diet (HSD) increases ether lipids and produces T2D-like pathophysiology phenotypes, including obesity, insulin resistance, and cardiac failure. Therefore, we targeted ether lipid biosynthesis through the enzyme dihydroxyacetonephosphate acyltransferase (encoded by the gene DHAPAT). We found that reducing DHAPAT in the fat body improved TAG and glucose homeostasis, cardiac function, respiration, and insulin signaling in flies fed a HSD. The reduction of DHAPAT may cause a switch in molecular signaling from lipogenesis to fatty acid oxidation via activation of a PPARα-like receptor, as bezafibrate produced similar improvements in HS-fed flies. Taken together, our findings suggest that ether lipids may be lipotoxins that reduce fitness during overnutrition.

Sequencing SARS-CoV-2 from antigen tests.

Genomic surveillance empowers agile responses to SARS-CoV-2 by enabling scientists and public health analysts to issue recommendations aimed at slowing transmission, prioritizing contact tracing, and building a robust genomic sequencing surveillance strategy. Since the start of the pandemic, real time RT-PCR diagnostic testing from upper respiratory specimens, such as nasopharyngeal (NP) swabs, has been the standard. Moreover, respiratory samples in viral transport media are the ideal specimen for SARS-CoV-2 whole-genome sequencing (WGS). In early 2021, many clinicians transitioned to antigen-based SARS-CoV-2 detection tests, which use anterior nasal swabs for SARS-CoV-2 antigen detection. Despite this shift in testing methods, the need for whole-genome sequence surveillance remains. Thus, we developed a workflow for whole-genome sequencing with antigen test-derived swabs as an input rather than nasopharyngeal swabs. In this study, we use excess clinical specimens processed using the BinaxNOW™ COVID-19 Ag Card. We demonstrate that whole-genome sequencing from antigen tests is feasible and yields similar results from RT-PCR-based assays utilizing a swab in viral transport media.

Whole-genome Sequencing of SARS-CoV-2: Using Phylogeny and Structural Modeling to Contextualize Local Viral Evolution.

INTRODUCTION: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created a global pandemic resulting in over 1 million deaths worldwide. In the Department of Defense (DoD), over 129,000 personnel (civilians, dependents, and active duty) have been infected with the virus to date. Rapid estimations of transmission and mutational patterns of virus outbreaks can be accomplished using whole-genome viral sequencing. Deriving interpretable and actionable results from pathogen sequence data is accomplished by the construction of phylogenetic trees (from local and global virus sequences) and by the creation of protein maps, to visualize and predict the effects of structural protein amino acid mutations. MATERIALS AND METHODS: We developed a sequencing and bioinformatics workflow for molecular epidemiological SARS-CoV-2 surveillance using excess clinical specimens collected under an institutional review board exempt protocol at Joint Base San Antonio, Lackland AFB. This workflow includes viral RNA isolation, viral load quantification, tiling-based next-generation sequencing, sequencing and bioinformatics analysis, and data visualization via phylogenetic trees and protein mapping. RESULTS: Sequencing of 37 clinical specimens collected at JBSA/Lackland revealed that by June 2020, SAR-CoV-2 strains carrying the 614G mutation were the predominant cause of local coronavirus disease 2019 infections. We identified 109 nucleotide changes in the coding region of the SARS-CoV-2 genome (which lead to 63 unique, non-synonymous amino acid mutations), one mutation in the 5'-untranslated region (UTR), and two mutations in the 3'UTR. Furthermore, we identified and mapped six additional spike protein amino acid changes-information which could potentially aid vaccine design. CONCLUSION: The workflow presented here is designed to enable DoD public health officials to track viral evolution and conduct near real-time evaluation of future outbreaks. The generation of molecular epidemiological sequence data is critical for the development of disease intervention strategies-most notably, vaccine design. Overall, we present a streamlined sequencing and bioinformatics methodology aimed at improving long-term readiness efforts in the DoD.

Return of Lymantria dispar dispar (gypsy moth): A case report.

An invasive moth, Lymantria dispar dispar, also known as the gypsy moth, originates from Europe and first came to Ontario, Canada, in 1969. The moth is a defoliator which feeds on oak and other deciduous trees, and less commonly, conifers. Outbreaks of Lymantria dispar dispar moth infestation occur every 7-10 years with rapid expansion of the population until there is a natural collapse due to pathogens and predators. In addition to the extensive environmental impact of defoliation of the tree canopy, the Lymantria dispar dispar moth larva (caterpillar) is responsible for causing a significant cutaneous eruption in exposed individuals. In our report, we describe six cases of Lymantria dispar dispar dermatitis which occurred in Ontario, Canada, in May of 2021. It is important for dermatologists to be aware of this potential diagnosis and to be aware of local infestation in affected areas.

Long-Term Single Center Experience in Treating Plaque Psoriasis With Guselkumab.

BACKGROUND: Clinical trial data have shown guselkumab, an interleukin-23 inhibitor, to be efficacious and safe for the treatment of psoriasis. However, there is very little real-world experience using guselkumab in the community setting that has been documented. OBJECTIVES: The goal of this study was to determine real-life outcomes of guselkumab use in patients with moderate-to-severe psoriasis in a community dermatology practice. METHODS: A retrospective chart review of electronic medical records was conducted in patients with moderate-to-severe psoriasis who were prescribed guselkumab at a community dermatology office in Ontario, Canada. RESULTS: Of the 89 patients who received at least 1 dose of guselkumab, 79 had follow-up information at the time of review, with 71 patients receiving ongoing treatment. In our cohort of patients, 73.3% achieved clinically significant clearance of psoriasis with a global assessment of clear or almost clear defined as a body surface area involvement of <1%. Guselkumab was generally well tolerated and caused no serious adverse events. The most common reported side effects were nasopharyngitis, headaches, upper respiratory tract infections, gastrointestinal upset, and arthralgia. CONCLUSION: Overall, guselkumab was a safe and well-tolerated treatment with significant clinical improvement in our patient population.

Inflammatory bowel disease in patients with psoriasis treated with interleukin-17 inhibitors.

BACKGROUND: Interleukin 17 (IL-17) inhibitors provide an excellent treatment option for patients with psoriasis and psoriatic arthritis, resulting in high levels of efficacy for skin clearance and joint improvement. Safety has also been established in clinical trials for this group of biologic agents; however, rare case reports of exacerbation or induction of inflammatory bowel disease (IBD) have been reported in the literature. No causal relationship has been established. When IL-17 inhibitors were investigated for the management of IBD, no benefit was found and worsening of disease was noted for some patients. IBD is more common in patients with psoriasis and, therefore, it remains unknown if these drugs cause de novo IBD or if the reported cases of IBD in patients on IL-17 therapy is due to the background risk in this predisposed population who may have already had an underlying or subclinical disease. METHODS/RESULTS: A literature search was conducted for the terms 'IL-17 inhibitor,' 'ixekizumab,' 'secukinumab,' 'brodalumab' and 'inflammatory bowel disease,' 'ulcerative colitis,' and 'Crohn's disease' in PubMed and Google Scholar. Cases of new-onset or exacerbation of IBD were identified in the literature along with postmarketing pharmacovigilance data. These cases will be reviewed in this paper. CONCLUSIONS: IL-17 inhibitors have proven efficacy for the treatment of psoriasis and psoriatic arthritis with a strong safety profile. However, rare cases of IBD onset and exacerbation in patients on IL-17 inhibitors have been reported in the literature, highlighting the need to select patients and therapeutic choices appropriately when treating this population.

The Use of Biologic Therapy in the Treatment of Acrodermatitis Continua of Hallopeau: A Review.

Acrodermatitis continua of Hallopeau is a rare subtype of pustular psoriasis that presents as a sterile, pustular eruption commonly in the finger tips and toes. This disease inflicts both the skin and nail bed, and causes severe disfigurement of the distal phalanges. Because it is a variant of pustular psoriasis, acrodermatitis continua of Hallopeau is commonly managed with antipsoriatic medications. Common approaches to treatment include topical therapy (corticosteroids, vitamin D analogs, and calcineurin inhibitors), systemic therapy, and in more severe cases, biologic therapy. This review will discuss how acrodermatitis continua of Hallopeau is diagnosed and how it is managed, with a particular emphasis on the use of biologics.

Assessing the Cellular Immune Response of the Fruit Fly, Drosophila melanogaster, Using an In Vivo Phagocytosis Assay.

In all animals, innate immunity provides an immediate and robust defense against a broad spectrum of pathogens. Humoral and cellular immune responses are the main branches of innate immunity, and many of the factors regulating these responses are evolutionarily conserved between invertebrates and mammals. Phagocytosis, the central component of cellular innate immunity, is carried out by specialized blood cells of the immune system. The fruit fly, Drosophila melanogaster, has emerged as a powerful genetic model to investigate the molecular mechanisms and physiological impacts of phagocytosis in whole animals. Here we demonstrate an injection-based in vivo phagocytosis assay to quantify the particle uptake and destruction by Drosophila blood cells, hemocytes. The procedure allows researchers to precisely control the particle concentration and dose, making it possible to obtain highly reproducible results in a short amount of time. The experiment is quantitative, easy to perform, and can be applied to screen for host factors that influence pathogen recognition, uptake, and clearance.

Acrodermatitis continua of Hallopeau successfully treated with adalimumab: A case report.

Acrodermatitis continua of Hallopeau is a chronic, inflammatory, and relapsing condition that presents as pustules of the fingers and toes, often with nail involvement. This condition is infrequently reported, difficult to treat, and often misdiagnosed. Various anti-psoriatic therapies have been used, but literature is limited to case studies with equivocal results. Biological therapy is revolutionizing the management of many dermatologic conditions and is believed to be a promising option for acrodermatitis continua of Hallopeau patients who have failed conventional therapy. We report the 4-year treatment course of a 70-year-old woman with acrodermatitis continua of Hallopeau that was initially unsuccessful with conventional treatments but successfully treated with the tumor necrosis factor alpha inhibitor adalimumab, in combination with alitretinoin and clobetasol propionate. This case adds to the current understanding of acrodermatitis continua of Hallopeau and the potential of biological therapy, in our case, adalimumab, for acrodermatitis continua of Hallopeau management. Literature should continue growing to ascertain the safety and efficacy of biologic therapy for patients with acrodermatitis continua of Hallopeau.

The Splicing Factor RNA-Binding Fox Protein 1 Mediates the Cellular Immune Response in Drosophila melanogaster.

The uptake and destruction of bacteria by phagocytic cells is an essential defense mechanism in metazoans. To identify novel genes involved in the phagocytosis of Staphylococcus aureus, a major human pathogen, we assessed the phagocytic capacity of adult blood cells (hemocytes) of the fruit fly, Drosophila melanogaster, by testing several lines of the Drosophila Genetic Reference Panel. Natural genetic variation in the gene RNA-binding Fox protein 1 (Rbfox1) correlated with low phagocytic capacity in hemocytes, pointing to Rbfox1 as a candidate regulator of phagocytosis. Loss of Rbfox1 resulted in increased expression of the Ig superfamily member Down syndrome adhesion molecule 4 (Dscam4). Silencing of Dscam4 in Rbfox1-depleted blood cells rescued the fly's cellular immune response to S. aureus, indicating that downregulation of Dscam4 by Rbfox1 is critical for S. aureus phagocytosis in Drosophila To our knowledge, this study is the first to demonstrate a link between Rbfox1, Dscam4, and host defense against S. aureus.

Hidradenitis suppurativa with SAPHO syndrome maintained effectively with adalimumab, methotrexate, and intralesional corticosteroid injections.

INTRODUCTION: Hidradenitis suppurativa and synovitis, acne, pustulosis, hyperostosis, osteitis syndrome are chronic, debilitating diseases involving apocrine gland-bearing skin inflammation and bone inflammation, respectively. Although both often present with multiple comorbidities, single patient co-presentation is rare. METHODS/RESULTS: This study reports the 8-year treatment course of a 40-year-old man with hidradenitis suppurativa and synovitis, acne, pustulosis, hyperostosis, osteitis syndrome, and reviews relevant literature. Initial oral and topical antibiotics had little effect. Intralesional corticosteroid injections were effective for localized inflammatory lesions but insufficient for hidradenitis suppurativa control. Adalimumab initiation and local excision of a persistent HS lesion led to stabilization. Adalimumab provided dramatic back pain improvement. Synovitis, acne, pustulosis, hyperostosis, osteitis was diagnosed; adalimumab continuation with subsequent methotrexate addition resulted in hidradenitis suppurativa-synovitis, acne, pustulosis, hyperostosis, osteitis control. CONCLUSIONS: Literature regarding comorbid hidradenitis suppurativa and synovitis, acne, pustulosis, hyperostosis, osteitis syndrome therapy is scarce but growing. Adalimumab, methotrexate, intralesional corticosteroid, and lifestyle changes successfully maintained a severe hidradenitis suppurativa-synovitis, acne, pustulosis, hyperostosis, osteitis-syndrome case. Further studies beyond a case-based review could yield more definitive treatment plans.

The association between question type and the outcomes of a Dermatology eConsult service.

BACKGROUND: eConsult is a web based service that facilitates communication between primary care providers (PCPs) and specialists, which can reduce the need for face-to-face consultations with specialists. One example is the Champlain BASE (Building Access to Specialist through eConsultation) service with dermatology being the largest specialty consulted. METHODS: Dermatology eConsults submitted from July 2011 to January 2015 were reviewed. Post eConsult surveys for PCPs were analyzed to determine the number of traditional consults avoided and perceived value of eConsults. The time it took the PCP to receive a reply and the amount of time reported by the specialist to answer eConsult were proactively recorded and analyzed. A subset of 154 most recent eConsults was categorized for dermatology content and question type (e.g. diagnosis or management) using a validated taxonomy. RESULTS: A total of 965 eConsults were directed to dermatology from 217 unique PCPs. The majority of eConsults (64%) took the specialist between 10 and 15 minutes to answer. The overall value of this service to the provider was rated as very good or excellent in 95% of cases. In 49%, traditional in-person assessments were avoided. In the subset of the most recent cases, diagnosis was the most common question type asked (65.2%) followed by management (29%) and drug treatment (10.6%). The top five subject areas (40%) were: Dermatitis, Infections, Neoplasm, Nevi, and Pruritus. CONCLUSION: eConsults was feasible and well received by PCPs, which improves access to dermatology care with a potential to reduce wait times for traditional consultation.

First Presentation of Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome in Pregnancy.

BACKGROUND: Reed's syndrome, also known as hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome, is an autosomal dominant condition in which affected individuals may develop cutaneous leiomyomas, uterine fibroids, and renal cell carcinoma. OBJECTIVE: This report describes a unique case of HLRCC because it presented in pregnancy with development of cutaneous pilar leiomyomas. METHODS: Review of the literature for previous cases of Reed's syndrome during pregnancy including PubMed and Medline search. RESULTS: Genetic testing of this patient demonstrated a mutation in the fumarate hydratase (FH) gene. Review of the literature showed only 1 previous case series that described the onset of cutaneous lesions during pregnancy. CONCLUSION: This case serves as a reminder that there may exist a correlation between pregnancy and the first manifestation of cutaneous lesions in patients with HLRCC, and thus an increased clinical suspicion is warranted during this period.

Delay in Diagnosis of Congenital Linear Scleroderma until Adulthood.

BACKGROUND: Scleroderma encompasses a spectrum of disorders characterized by thickening of the skin and subcutaneous tissue with increased collagen deposition. Linear scleroderma is subdivided into progressive hemifacial atrophy and en coup de sabre subtype. OBJECTIVE: We report a case of congenital linear scleroderma identified in an adult, misdiagnosed since birth as birth trauma. METHODS: We completed a review of the literature for similar cases using PubMed and Medline. RESULTS: This is the first report of congenital linear scleroderma en coup de sabre diagnosed in an adult following an initial misdiagnosis of birth trauma. The sequelae of linear scleroderma can be significant as it can result in gtrth retardation, muscle atrophy, contractures, limb length discrepancy, and disfigurement. CONCLUSIONS: This report emphasizes the importance of educating practitioners about linear scleroderma. Early recognition is key as a delay in diagnosis can result in potentially preventable, irreversible gtrth defects and disfigurements.

Delay in Diagnosis of Congenital Linear Scleroderma until Adulthood.

BACKGROUND: Scleroderma encompasses a spectrum of disorders characterized by thickening of the skin and subcutaneous tissue with increased collagen deposition. Linear scleroderma is subdivided into progressive hemifacial atrophy and en coup de sabre subtype. OBJECTIVE: We report a case of congenital linear scleroderma identified in an adult, misdiagnosed since birth as birth trauma. METHODS: We completed a review of the literature for similar cases using PubMed and Medline. RESULTS: This is the first report of congenital linear scleroderma en coup de sabre diagnosed in an adult following an initial misdiagnosis of birth trauma. The sequelae of linear scleroderma can be significant as it can result in growth retardation, muscle atrophy, contractures, limb length discrepancy, and disfigurement. CONCLUSIONS: This report emphasizes the importance of educating practitioners about linear scleroderma. Early recognition is key as a delay in diagnosis can result in potentially preventable, irreversible growth defects and disfigurements.