Drug-induced dermatomyositis after lacosamide: A case report.

Here we describe a caseof a woman who had DM after treatment withlacosamide. To our knowledge, drug-induced DMfrom lacosamide has not been reported previously

Geospatial Correlation of Amyopathic Dermatomyositis With Fixed Sources of Airborne Pollution: A Retrospective Cohort Study

Objective: Dermatomyositis (DM) may result from exogenous triggers, including airborne pollutants, in genetically susceptible individuals. The United States Environmental Protection Agency's 2011 National Air Toxics Assessment (NATA) models health risks associated with airborne emissions, available by ZIP code tabulation area (ZCTA). Important contributors include point (fixed), on-road, and secondary sources. The objective of this study was to investigate the geospatial distributions of DM and subtypes, classic DM (CDM) and clinically amyopathic DM (CADM), and their associations with airborne pollutants.Methods: This retrospective cohort study identified 642 adult DM patients from 336 unique ZCTAs. GeoDa v.1.10 was used to calculate global and local Moran's indices and generate local indicator of spatial autocorrelation (LISA) maps. All Moran's indices and LISA maps were permuted 999 times.Results: Univariate global Moran's indices for DM, CDM, and CADM prevalence were not significant, but LISA maps demonstrated differential local spatial clustering and outliers. CADM prevalence correlated with point sources (bivariate global Moran's index 0.071, pseudo-p = 0.018), in contrast to CDM (−0.0053, pseudo-p = 0.46). Bivariate global Moran's indices for DM, CDM, and CADM prevalence did not correlate with other airborne toxics, but bivariate LISA maps revealed local spatial clustering and outliers.Conclusion: Prevalence of CADM, but not CDM, is geospatially correlated with fixed sources of airborne emissions. This effect is small but significant and may support the hypothesis that triggering exposures influence disease phenotype. Important limitations are NATA data and ZCTA population estimates were collected from 2011 and ZCTA of residence may not have been where patients had greatest airborne pollutant exposure

Gottron's Papules Exhibit Dermal Accumulation of CD44 Variant 7 (CD44v7) and Its Binding Partner Osteopontin: A Unique Molecular Signature

The accumulated mucin in non-Gottron's dermatomyositis (DM) lesions is primarily chondroitin-4-sulfate (C4S), which is immunomodulatory in vitro. Gottron's papules are a particularly resistant manifestation of DM that often persist after other lesions have resolved with therapy. We examined non-Gottron's DM lesions and Gottron's papule skin biopsies for C4S, CD44 variant 7 (CD44v7), a chondroitin sulfate-binding isoform causally implicated in autoimmunity, and osteopontin (OPN), a CD44v7 ligand implicated in chronic inflammation. Gottron's papule dermis contained more C4S and CD44v7 than non-Gottron's lesions. Normal skin showed less CD44v7 over joints relative to Gottron's lesions. All DM dermis had increased OPN compared with healthy skin. Mechanically stretching cultured fibroblasts for 6hours induced CD44v7 mRNA and protein, whereas IFN-γ treatment induced OPN mRNA and protein. OPN alone did not induce CD44v7, but stretching dermal fibroblasts in the presence of OPN increased human acute monocytic leukemia cell line (THP-1) monocyte binding, which is blunted by anti-CD44v7 blocking antibody. C4S, CD44v7, and OPN are three molecules uniquely present in Gottron's papules that contribute to inflammation individually and in association with one another. We propose that stretch-induced CD44v7 over joints, in concert with dysregulated OPN levels in the skin of DM patients, increases local inflammatory cell recruitment and contributes to the pathogenesis and resistance of Gottron's papules

Pemphigus

Pemphigus vulgaris and paraneoplastic pemphigus are two subtypes of pemphigus that involve the oral mucosa. These autoimmune blistering disorders have antibodies targeted against proteins of keratinocyte adhesion, thereby causing acantholysis. Clinical findings include oral erosions and flaccid cutaneous bullae and erosions. In addition to the clinical exam, diagnostic tests including tissue biopsy, direct and indirect immunofluorescence, and enzyme-linked immunosorbent assays (ELISA) help to establish a diagnosis. Further malignancy workup in patients with suspected paraneoplastic pemphigus is warranted. Retrospective uncontrolled studies suggest that immunosuppressive agents reduce mortality in pemphigus vulgaris and cohort uncontrolled studies of rituximab, a monoclonal antibody against CD20, suggest it is an effective treatment for refractory patients. Ongoing studies will define its role in early disease

Advancing understanding, diagnosis, and therapies for cutaneous lupus erythematosus within the broader context of systemic lupus erythematosus [version 1; peer review: 3 approved]

Cutaneous lupus erythematosus (CLE) is an autoimmune disease that can be associated with systemic lupus erythematosus (SLE) symptoms. The pathogenesis of both CLE and SLE is multifactorial, involving genetic susceptibility, environmental factors, and innate and adaptive immune responses. Despite the efficacy of current medications, many patients remain refractory, highlighting the necessity for new treatment options. Unfortunately, owing to challenges related in part to trial design and disease heterogeneity, only one new biologic in the last 50 years has been approved by the US Food and Drug Administration for the treatment of SLE. Thus, although SLE and CLE have a similar pathogenesis, patients with CLE who do not meet criteria for SLE cannot benefit from this advancement. This article discusses the recent trials and emphasizes the need to include patients with single-organ lupus, such as CLE, in SLE trials

Lenalidomide Therapy in Treatment Refractory Cutaneous Lupus Erythematosus: Histologic and Circulating Leukocyte Profile and Potential Risk of a Systemic Lupus Flare

Background Lenalidomide is a thalidomide analogue that may serve as an adjunctive therapy for treatment refractory cutaneous lupus erythematosus (CLE). Objectives We evaluate the use of lenalidomide in CLE and describe the skin and circulating leukocyte profile of treatment refractory patients before and after treatment. Patients/Methods Five subjects were treated with lenalidomide in an unblinded open-label study. Immunohistochemistry of skin was performed for T-cell markers, glycosaminoglycans and CXCL10, an interferon (IFN)-inducible chemokine, before and after treatment. Immunophenotyping and measurement of IFN-inducible genes from peripheral blood mononuclear cells was also performed before and after treatment. Results Four subjects demonstrated clinical improvement of their skin, however one of these responders subsequently developed symptoms of systemic lupus erythematosus. Small changes in rare circulating leukocyte subsets, plasmacytoid dendritic cells and regulatory T-cells, were observed with treatment and may correlate with clinical response. Treatment was associated with increased circulating HLA-DR expression and decreased markers of IFN-mediated pathways, regardless of clinical response. Limitations Our results are limited by small sample size and the measurement of rare populations of circulating cell subsets. Conclusions Lenalidomide may have utility as therapy for severe, treatment refractory CLE. However, our preliminary data suggest that lenalidomide may activate T-cells and trigger systemic disease in some CLE patients. We also saw a unique histologic and circulating leukocyte phenotype in the nonresponding subject. Further characterization of the skin and circulating leukocyte profile of treatment refractory patients will improve our understanding of CLE

Undergraduate student experiences in remote lab courses during the COVID-19 pandemic

The 2020&ndash;2021 academic year was a unique time for many instructors who had to adapt their courses to be conducted remotely due to the COVID-19 pandemic. This was especially challenging for physics lab courses, which usually emphasize hands-on experiments. Although many courses have now returned to in-person teaching, the possibility remains of future disasters necessitating similar remote courses. It is important to understand how undergraduate students experienced remote physics lab courses during the pandemic, including what aspects of the courses contributed to positive student outcomes. To investigate this, we surveyed over 5000 students from 24 different institutions, asking how the students engaged with their physics lab courses during the 2020&ndash;2021 academic year. Here, we describe the frequency with which the students performed various class activities, aspects of the course environment, challenges the students faced, aspects of the courses the students found enjoyable, and some student outcomes. We further study the impact of the course activities and course environment on four of the outcomes (self-reported learning of lab skills, self-reported learning of concepts, course enjoyment, and development of a sense of community). We find that students who were provided clear expectations, had enough time for their coursework, frequently worked in groups, and frequently had access to guidance from their instructors were more likely to report positive outcomes. This work demonstrates the importance of certain aspects of lab courses for several desirable outcomes in remote lab courses during a pandemic, with findings that may transfer to in-person or remote lab courses in the future. &nbsp;</p

A Pacific sojourn: Anna Kavan and the New Zealand connection 1941-2

This article examines Anna Kavan’s sojourn in New Zealand from February 1941 to November 1942 in the company of the pacifist playwright Ian Hamilton. Living in the most remote of the ex-British colonies reinforced Kavan’s ontological sense of homelessness and wish to disidentify from British society, yet the colony’s anglophone orientation offered familiarity within the strange and alien. The geography, landscapes and communities of its Pacific islands encouraged a reshaping of her imaginative engagement with otherness. Referring to Kavan’s recently published diary, ‘Five Months Further or What I Remember ab[ou]t New Zealand’, the essay argues that the New Zealand ‘experience’ encouraged her use of tropes of the Gothic and uncanny as she grappled with issues of distance, homelessness and disjunctive reality. The discussion focuses on the alternative/parallel world that New Zealand represents in stories published in I Am Lazarus (1945). It identifies experimental techniques associated with Gothic fiction by which Kavan registers the overlapping dualisms of war-torn London and idyllic rural New Zealand, and represents memory through framing devices and defamiliarizing rhetorical tropes as a distancing activity interrupting the present moment: dream sequences, irruptions into and splittings of reality, space and time reversals, doublings of self/other, disjunctive non sequiturs and ghostly mirror imaging