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Abstract Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disorder affecting the palms and soles. In rare cases, severe patients develop acute extra-palmoplantar lesions often accompanied by arthralgia. Such cases with extensive symptoms often necessitate systemic treatments with variable efficacy and potential side effects. Apremilast, known for its broad immune response modulation, presents promise as a therapeutic option for severe PPP with joint and extra-palmoplantar lesions. This case highlights apremilast as a potential systemic treatment for such cases with minimal side effects. Rare cases of severe palmoplantar pustulosis with rapidly developing extra-palmoplantar lesions and joint pain have been treated by immunosuppressants with variable efficacy and side effects from prolonged treatment. Our case was successfully treated with apremilast, which suggests apremilast as a potential systemic treatment for such cases.

This manuscript presents a rare case report of a patient with severe idiopathic aplastic anaemia who developed multiple subcutaneous abscesses by Corynebacterium amycolatum. The report aims to elucidate the growing significance of Corynebacterium species as pivotal pathogens in individuals with compromised immune systems. Abstract Corynebacterium amycolatum is a part of the normal skin flora and has been underestimated as a pathogen. However, in recent years, the species has gained recognition as an important pathogen causing severe infections, particularly in immunocompromised patients. Nevertheless, identifying these organisms at the species level is difficult in routine clinical microbiology, leading to limited knowledge of their clinical manifestations in infectious diseases. In this study, we report a rare case of multiple subcutaneous abscesses in a patient with severe neutropenia, wherein C.amycolatum was identified as the causative organism through genotyping tests. This case highlights the importance of this organism as an aetiological agent of severe skin infections in patients with compromised immune systems.

Atopic dermatitis (AD) is a skin disease exhibiting clinical and molecular heterogeneity, thereby jeopardizing the development of personalized treatments. Here we pursue a cross-sectional and longitudinal cohort analysis of 951 whole-skin samples, employing an unsupervised decomposition analysis to link gene expression profiles to disease severity, six distinct skin phenotypes, and blood cytokines representative of given endotypes. Specifically, type 2 and type 17 responses are associated with major skin phenotypes such as erythema and induration, while type 1 response is upregulated in lichen amyloidosis of AD patients. Longitudinal analysis of patients treated with dupilumab finds sustained gene signatures related to type 17 response in lesional skin and upregulated transcription factors in non-lesional skin of patients with poor treatment outcomes. Lastly, several extracellular matrix organization-associated genes are correlated with clinical severity and treatment response to dupilumab. Our findings thus provide potential skin and blood biomarkers for assessing endotypes and therapeutic responses in AD to pave the way for personalized medicine. Atopic dermatitis (AD) with complex manifestations and genetic associations. Here the author profile the transcriptome of 951 skin samples from patients with AD to link skin phenotypes, clinical severity, and efficacy of dupilumab treatment to specific types of immune responses and gene features to serve clues for personalized medicine.

Atopic dermatitis (AD) is a skin disease that is heterogeneous both in terms of clinical manifestations and molecular profiles. It is increasingly recognized that AD is a systemic rather than a local disease and should be assessed in the context of whole-body pathophysiology. Here we show, via integrated RNA-sequencing of skin tissue and peripheral blood mononuclear cell (PBMC) samples along with clinical data from 115 AD patients and 14 matched healthy controls, that specific clinical presentations associate with matching differential molecular signatures. We establish a regression model based on transcriptome modules identified in weighted gene co-expression network analysis to extract molecular features associated with detailed clinical phenotypes of AD. The two main, qualitatively differential skin manifestations of AD, erythema and papulation are distinguished by differential immunological signatures. We further apply the regression model to a longitudinal dataset of 30 AD patients for personalized monitoring, highlighting patient heterogeneity in disease trajectories. The longitudinal features of blood tests and PBMC transcriptome modules identify three patient clusters which are aligned with clinical severity and reflect treatment history. Our approach thus serves as a framework for effective clinical investigation to gain a holistic view on the pathophysiology of complex human diseases. Atopic dermatitis is an inflammatory skin disease featuring systemic involvement. Here authors show that the two major clinical manifestations of the disease, erythema and papulation, are distinguished by differential interplay between local skin and systemic immunity, uncovered by integrated transcriptomics.

Staphylococcus aureus is frequently isolated from active lesions of atopic dermatitis (AD) patients. We reported that 17%–22% of S. aureus isolated from AD patients produced a novel superantigen staphylococcal enterotoxin Y (SEY). Unlike many S . aureus superantigens that activate T cells via T-cell receptor (TCR) Vß, SEY activates T cells via TCR Vα and stimulates cytokine secretion. Staphylococcus argenteus was isolated from AD patients during the surveillance for S. aureus . Phylogenetic comparison of the genome indicated that the isolate was very similar to S. aureus causing skin infections. The isolate encoded a SEY-like protein, designated SargEY, which, like SEY, activated T cells via the TCR Vα. ST2250 is the only lineage positive for SargEY gene. ST2250 S. argenteus harboring a superantigen SargEY gene may be a novel staphylococcal clone that infects human skin and is involved in the exacerbation of AD.

Rituximab can cause immediate and delayed immune reactions, including rituximab-induced serum sickness (RISS). However, the temporal and mechanistic relationship between these reactions is unclear. We report a case in which RISS developed several days after rituximab-induced anaphylaxis. A 70-year-old woman with stage I mucosa-associated lymphoid tissue lymphoma was initially treated with weekly rituximab monotherapy. Four days after the third infusion, she developed fever, nonpruritic erythema, and arthralgia, which resolved spontaneously. When rituximab was re-administered, she immediately developed symptoms consistent with anaphylaxis, prompting treatment discontinuation. One year later, rituximab was re-started due to slight disease progression. The infusion induced nasal congestion and hoarseness but was completed under hydrocortisone. Eight days later, she presented with fever, widespread pruritic plaques, vomiting, diarrhea, and hypotension. Laboratory testing revealed elevated inflammatory markers without evidence of bacterial infection. Human anti-chimeric antibody levels were markedly elevated (> 5000 ng/mL). Intradermal testing with rituximab induced both an immediate wheal and a delayed erythematous flare lasting several days, indicating coexisting immediate-type hypersensitivity and RISS. This case demonstrates that RISS may occur several days after the resolution of rituximab-induced anaphylaxis. When immediate reactions occur after rituximab administration, patient education to ensure prompt reporting of delayed reactions is essential. Skin testing supported the identification of sequential immediate and delayed rituximab hypersensitivity in this case.

Transcribed cis-regulatory elements (tCREs), such as promoters and enhancers, are fundamental to modulate gene expression and define cell identity. The detailed mapping of tCREs at single-cell resolution is essential for understanding the regulatory mechanisms that govern cellular functions. Prior tCRE catalogs, limited by bulk analysis, have often overlooked cellular heterogeneity. We have constructed a tCRE atlas using single-cell 5-RNA-seq, capturing over 340,000 single-cells from 23 human tissues and annotating more than 175,000 tCREs, substantially enhancing the scope and granularity of existing cis-regulatory element annotations in the human genome. This atlas unveils patterns of gene regulation, revealing connections between broadly expressed promoters and cell type-specific distal tCREs. Assessing trait heritability at single-cell resolution with a novel tCRE module-based approach, we uncovered the nuanced trait-gene regulatory relationships across a continuum of cell populations, offering insights beyond traditional gene-level and bulk-sample analyses. Our study bridges the gap between gene regulation and trait heritability, underscoring the potential of single-cell analysis to elucidate the genetic foundations of complex traits. These insights set the stage for future research to investigate the impact of genetic variations on diseases at the individual level, advancing the understanding of cellular and molecular basis of trait heritability.Competing Interest StatementThe authors have declared no competing interest.Footnotes* https://doi.org/10.6084/m9.figshare.c.6926944