Cutaneous lupus erythematosus after treatment with paclitaxel and bevacizumab for metastatic breast cancer: a case report

Abstract Introduction The monoclonal anti-vascular endothelial growth factor antibody bevacizumab is increasingly used in the treatment of several malignant tumors. The usual side effects of this drug are hypertension and proteinuria. Paclitaxel is widely used in the treatment of breast cancer and head and neck carcinomas. Neither of these two drugs typically causes skin disorders. Paclitaxel-related cutaneous lupus erythematosus has been described before, but in earlier cases patients had a history of autoimmune disease. Case presentation We report a case of a 65-year-old Caucasian woman who presented with cutaneous lupus erythematosus after receiving paclitaxel-bevacizumab combination treatment as first-line therapy for metastatic breast cancer. Her cutaneous symptoms and increased serum anti-SSA and anti-SSB antibodies disappeared shortly after the discontinuation of therapy. Conclusion We conclude that cutaneous lupus erythematosus can also be seen in patients without earlier anamnesis of autoimmune disorders and that, furthermore, bevacizumab might cause atypical cutaneous side effects.</p

The desmosome and pemphigus

Desmosomes are patch-like intercellular adhering junctions (“maculae adherentes”), which, in concert with the related adherens junctions, provide the mechanical strength to intercellular adhesion. Therefore, it is not surprising that desmosomes are abundant in tissues subjected to significant mechanical stress such as stratified epithelia and myocardium. Desmosomal adhesion is based on the Ca2+-dependent, homo- and heterophilic transinteraction of cadherin-type adhesion molecules. Desmosomal cadherins are anchored to the intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic structures subjected to regulation and are therefore targets of signalling pathways, which control their molecular composition and adhesive properties. Moreover, evidence is emerging that desmosomal components themselves take part in outside-in signalling under physiologic and pathologic conditions. Disturbed desmosomal adhesion contributes to the pathogenesis of a number of diseases such as pemphigus, which is caused by autoantibodies against desmosomal cadherins. Beside pemphigus, desmosome-associated diseases are caused by other mechanisms such as genetic defects or bacterial toxins. Because most of these diseases affect the skin, desmosomes are interesting not only for cell biologists who are inspired by their complex structure and molecular composition, but also for clinical physicians who are confronted with patients suffering from severe blistering skin diseases such as pemphigus. To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

The Thomsen-Friedenreich Antigen-Binding Lectin Jacalin Interacts with Desmoglein-1 and Abrogates the Pathogenicity of Pemphigus Foliaceus Autoantibodies In Vivo

Pemphigus foliaceus (PF) is an autoimmune skin blistering disease mediated by pathogenic autoantibodies against the desmosomal core glycoprotein desmoglein 1 (Dsg1). This study demonstrated that the O-glycan-specific plant lectin jacalin binds Dsg1 and inhibits the interaction of Dsg1/PF IgG. N-glycosylation is not involved in the interaction of Dsg1/jacalin or Dsg1/PF IgG. Subcutaneous injection of jacalin into neonatal mice drastically reduced PF IgG deposition at the epidermal cell surface and blocked PF IgG-induced skin blisters, both clinically and histologically. Interestingly, another plant lectin peanut agglutinin (PNA), which shares the same carbohydrate specificity toward the O-linked carbohydrate structure known as Thomsen-Friedenreich antigen (TF antigen, Galβ1-3GalNAcα-O-Ser/Thr), also bound Dsg1 and blocked the skin blistering. In contrast, the plant lectin vicia villosa-B4 (VVL-B4), which shares the carbohydrate specificity toward the O-linked monosaccharide known as Thomsennouveau antigen (Tn antigen, GalNAc-α1-O-Ser/Thr) did not bind Dsg1 and did not show a protective effect against the disease induced by the autoantibodies. Collectively, these results suggest that the binding of jacalin to O-linked TF carbohydrate motifs on Dsg1 impairs the Dsg1/PF autoantibody interactions and abrogates its pathogenicity in vivo. TF-specific binding ligands may have a potential therapeutic value for PF

Genetic architecture of human plasma lipidome and its link to cardiovascular disease

Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 x10(-8)), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD

Psoriasis Causes Significant Economic Burden to Patients

INTRODUCTION: Psoriasis results in expenses to patients from many cost sources. Psoriasis treatments may result in considerable time and traveling costs, yet many studies fail to account for these costs. The objective of this study was to evaluate the multidimensional economic burden of psoriasis to patients. METHODS: The study was based on 232 Finnish patients with psoriasis or psoriatic arthritis visiting a tertiary level dermatological clinic during a 1-year study period between October 1, 2009 and September 30, 2010. The data were based on a patient questionnaire, clinical data from the medical records and reimbursement data from the Finnish Social Insurance Institution. Item costs were based on true costs charged from the patients and all time cost estimates were based on the Human Capital Approach method. RESULTS: 199 patients with psoriasis and 33 with psoriatic arthritis were included in the study. Total costs were higher for patients receiving traditional systemic medications or phototherapy than those not receiving such treatment. Travel costs and travel time costs accounted for more than 60% of the costs of phototherapy. Skin care at home was time consuming and thus caused significant burden to patients. The majority of the visit costs arose from hospital visits and only a small proportion were attributed to visiting primary health care providers. CONCLUSION: Visit charges and other patient co-payments were estimated to play a minor role in the total cost of psoriasis incurred by patients, while travel costs and lost time comprised the majority of the costs, which should not be omitted in future studies regarding costs of treatments. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13555-014-0053-2) contains supplementary material, which is available to authorized users