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Atopic dermatitis is the most common inflammatory skin condition with a severe negative impact on patients' quality of life. The etiology of AD is complex and depends on age, genetics, the immune system, environmental factors, and the skin microbiome, with a key role for pathogenic Staphylococcus aureus in the development of severe AD. However, the composition of the skin microbiome in mild AD is understudied. Here, using metagenomic shallow shotgun sequencing, we showed that mild AD lesions did not show a significant difference in the diversity of the skin microbiome compared to samples from non-AD patients and that the relative abundance of S. aureus did not differ in these mild AD lesions. However, when we assessed other taxa, Mycobacterium ostraviense, Pedobacter panaciterrae_A and four Streptomyces species were identified with higher abundances in mild AD lesions and species of 15 genera were decreased in abundance. The highest fold decreases were observed for Paracoccus marcusii, Microbacterium lacticum, Micrococcus luteus, and Moraxella sp002478835. These microbiome compositional insights are a first step towards novel microbiome-based diagnostics and therapeutics for early intervention at the stage of mild AD and provide a path forward for the functional study of species involved in this often-overlooked patient population. [ABSTRACT FROM AUTHOR]

The varicella-zoster virus (VZV) infects >95% of the population. VZV reactivation causes herpes zoster (HZ), known as shingles, primarily affecting the elderly and individuals who are immunocompromised. However, HZ can occur in otherwise healthy individuals. We analyzed the immune signature and risk profile in patients with HZ using a genome-wide association study across different UK Biobank HZ cohorts. Additionally, we conducted one of the largest HZ human leukocyte antigen association studies to date, coupled with transcriptomic analysis of pathways underlying HZ susceptibility. Our findings highlight the significance of the major histocompatibility complex locus for HZ development, identifying 5 protective and 4 risk human leukocyte antigen alleles. This demonstrates that HZ susceptibility is largely governed by variations in the major histocompatibility complex. Furthermore, functional analyses revealed the upregulation of type I interferon and adaptive immune responses. These findings provide fresh molecular insights into the pathophysiology and activation of innate and adaptive immune responses triggered by symptomatic VZV reactivation. [ABSTRACT FROM AUTHOR]

Background: Transcriptome profiling of blood cells is an efficient tool to study the gene expression signatures of rheumatic diseases. This study aims to improve the early diagnosis of pediatric rheumatic diseases by investigating patients' blood gene expression and applying machine learning on the transcriptome data to develop predictive models. Methods: RNA sequencing was performed on whole blood collected from children with rheumatic diseases. Random Forest classification models were developed based on the transcriptome data of 48 rheumatic patients, 46 children with viral infection, and 35 controls to classify different disease groups. The performance of these classifiers was evaluated by leave-one-out cross-validation. Analyses of differentially expressed genes (DEG), gene ontology (GO), and interferon-stimulated gene (ISG) score were also conducted. Results: Our first classifier could differentiate pediatric rheumatic patients from controls and infection cases with high area-under-the-curve (AUC) values (AUC = 0.8 ± 0.1 and 0.7 ± 0.1, respectively). Three other classifiers could distinguish chronic recurrent multifocal osteomyelitis (CRMO), juvenile idiopathic arthritis (JIA), and interferonopathies (IFN) from control and infection cases with AUC ≥ 0.8. DEG and GO analyses reveal that the pathophysiology of CRMO, IFN, and JIA involves innate immune responses including myeloid leukocyte and granulocyte activation, neutrophil activation and degranulation. IFN is specifically mediated by antibacterial and antifungal defense responses, CRMO by cellular response to cytokine, and JIA by cellular response to chemical stimulus. IFN patients particularly had the highest mean ISG score among all disease groups. Conclusion: Our data show that blood transcriptomics combined with machine learning is a promising diagnostic tool for pediatric rheumatic diseases and may assist physicians in making data-driven and patient-specific decisions in clinical practice. [ABSTRACT FROM AUTHOR]

Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, and a defect of innate immunity were identified as being susceptible to RuV-associated granulomas. Hematopoietic cell transplantation was the most successful treatment in this case series resulting in granuloma resolution; steroids, and TNF-α and IL-1R inhibitors were moderately effective. In addition to M2 macrophages, neutrophils were identified by immunohistochemical analysis as a novel cell type infected with RuV. Four patterns of RuV-associated granulomatous inflammation were classified based on the structural organization of granulomas and identity and location of cell types harboring RuV antigen. Identification of conditions that increase susceptibility to RuV-associated granulomas combined with structural characterization of the granulomas may lead to a better understanding of the pathogenesis of RuV-associated granulomas and discover new targets for therapeutic interventions. [ABSTRACT FROM AUTHOR]

The role of T cell receptor (TCR) diversity in infectious disease susceptibility is not well understood. We use a systems immunology approach on three cohorts of herpes zoster (HZ) patients and controls to investigate whether TCR diversity against varicella-zoster virus (VZV) influences the risk of HZ. We show that CD4+ T cell TCR diversity against VZV glycoprotein E (gE) and immediate early 63 protein (IE63) after 1-week culture is more restricted in HZ patients. Single-cell RNA and TCR sequencing of VZV-specific T cells shows that T cell activation pathways are significantly decreased after stimulation with VZV peptides in convalescent HZ patients. TCR clustering indicates that TCRs from HZ patients co-cluster more often together than TCRs from controls. Collectively, our results suggest that not only lower VZV-specific TCR diversity but also reduced functional TCR affinity for VZV-specific proteins in HZ patients leads to lower T cell activation and consequently affects the susceptibility for viral reactivation. [Display omitted] • T cell phenotypes did not significantly differ between HZ patients and controls • CD4+ TCR diversity against VZV gE and IE63 after culture was broader in controls • T cell activation pathways after VZV peptide stimulation were lower in HZ patients • TCRs from HZ patients co-clustered more often together than TCRs from controls Boeren et al. demonstrate that susceptibility for shingles, caused by varicella-zoster virus (VZV) reactivation, correlates with reduced T cell receptor (TCR) diversity against several VZV proteins. Their results indicate that reduced T cell activation correlates with reduced affinity between VZV proteins and the VZV-specific TCR repertoire in shingles patients. [ABSTRACT FROM AUTHOR]

Background Octylisothiazolinone ( OIT) is used as an antifungal agent by the leather industry. Objectives To show sensitization to OIT from leather, and to highlight the potential implications when cross-reactivity between OIT and methylisothiazolinone ( MI) is studied. Methods Two patients with allergic contact dermatitis caused by a leather belt and shoes, respectively, were patch tested with methylchloroisothiazolinone ( MCI)/ MI, MI, MCI, OIT, and benzisothiazolinone ( BIT). High-performance liquid chromatography with ultraviolet detection ( HPLC-UV) was used to detect isothiazolinone derivatives in leather goods. Additionally, files of OIT-sensitized patients, observed at the KU Leuven department during the period 1990-2015, were retrospectively analysed. Results Both patients had been primarily sensitized to OIT, but the diagnosis in one of them could be achieved only when a higher patch test concentration of OIT (1000 ppm pet.) was used. HPLC-UV confirmed the presence of OIT in their leather goods. Non-relevant sensitization to MI was noted in both cases. Four additional cases of OIT sensitization from leather could be retrieved from the KU Leuven database. Conclusions Non-occupational sensitization to OIT from leather may occur. Patch test concentrations of >250 ppm pet. may be necessary for diagnosis, and to show cross-reactivity with MI. Safer use limits for OIT in the leather industry may be needed. [ABSTRACT FROM AUTHOR]

The article describes the case of two 23-year-old female patients who were diagnosed with allergic contact dermatitis (ACD) caused by "ozonated" olive oil contained in a pharmaceutical ointment. It notes that the first patient had been using Neomycolog ointment to treat cracked lips and angular cheilitis, while the second patient was using Farmaline ointment to treat foot dermatitis. It cites that both patients were given topical corticosteroid medications to address the allergies.

The article presents case study of a 50-year-old atopic female patient who was diagnosed with contact allergy caused by stannous fluoride in toothpaste. It mentions that Anti-caries, bacteriostatic and even bactericidal properties, aiding in the prevention of plaque formation and gingivitis, have been attributed to it. It presents information on stannous fluoride-containing toothpaste.

Hypersensitivity reactions to drugs account for 15% of all adverse drug reactions and represent an important health problem with significant morbidity and mortality. This article describes the current applications and perspectives of the basophil activation test by flow cytometry in the diagnosis of immediate-type drug allergy, with particular focus on its diagnostic performance in allergy to neuromuscular blocking agents, antibiotics and NSAIDs and on future applications. INSET: Key issues. [ABSTRACT FROM AUTHOR]

Objectives. The contribution of IL-17-producing Th17 cells to the pathogenesis of T-cell-mediated inflammatory disorders such as RA and atopic dermatitis (AD) has to be viewed in relation to the role of Th1/Th2 cells and long-recognized key cytokines like TNF. We aimed to study the frequency and migration-associated phenotype of peripheral Th17, Th1 and Th2 cells in healthy individuals, RA and AD patients, and to study the influence of anti-TNF therapy in RA.Methods. Intracellular IL-17, IFN-γ and IL-4 production and CC-chemokine receptor CCR4 and CCR6 expression were analysed flow cytometrically in peripheral memory Th cells from healthy individuals, AD and RA patients. The latter were grouped by disease activity and presence or absence of adalimumab therapy. In RA patients initiating anti-TNF therapy, cytokine production by in vitro-stimulated peripheral mononuclear cells was measured by cytometric bead array.Results. The peripheral Th17 cell frequency is elevated in AD but not in RA. In RA, Th17 cells and IL-17 production increase after anti-TNF therapy, irrespective of disease activity. Th1 cells and IFN-γ production are elevated in remission and under anti-TNF therapy. CCR6 expression is up-regulated in Th17 cells, but RA patients in remission under anti-TNF therapy have significantly lower expression than those with active disease.Conclusions. The increase in peripheral Th17 cells in RA patients after anti-TNF therapy is accompanied by a decrease in Th17-specific CCR6 expression, which might prevent homing of these potentially pro-inflammatory cells to the synovium. [ABSTRACT FROM PUBLISHER]

The article presents a case study of a non atopic 42-year-old male patient who is admitted to the hospital due to recurrent, chronic, and itchy dermatitis in his anogenital region in Belgium. It cites that the patient used wet wipes for his intimate hygiene. Moreover, patch testing reveals positive of papulovestcular reactions.

The article presents a case study a 36-year-old non-atopic female with facial and eyelid dermatitis caused by steareth-10 present in makeup-removing wet wipes. It mentions that Patch tests were performed with the Belgian baseline series, a cosmetic series, and with the patient's own cosmetics. It also discusses the residual presence of stearyl alcohol in these wipes.

The article presents a case study of a 31-year-old woman with facial dermatitis due to daily use of new anti-wrinkle day cream for several weeks. She had erythematous and swollen face along with bacterial super infection caused due to itching and burning sensation. She had performed patch test with Belgian baseline series, cosmetic series, and her own cosmetic products after cessation of her systematic corticosteroid treatment. The article discusses impact of thioctic acid in cosmetics on skin.

A letter to the editor is presented in response to the article "Exploring the link between pholcodine exposure and neuromuscular blocking agent anaphylaxis," by A. M. Brusch and colleagues in the 2014 issue.