Fibrotic skin disease represents a major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix. Fibroblasts are found to be ...heterogeneous in multiple fibrotic diseases, but fibroblast heterogeneity in fibrotic skin diseases is not well characterized. In this study, we explore fibroblast heterogeneity in keloid, a paradigm of fibrotic skin diseases, by using single-cell RNA-seq. Our results indicate that keloid fibroblasts can be divided into 4 subpopulations: secretory-papillary, secretory-reticular, mesenchymal and pro-inflammatory. Interestingly, the percentage of mesenchymal fibroblast subpopulation is significantly increased in keloid compared to normal scar. Functional studies indicate that mesenchymal fibroblasts are crucial for collagen overexpression in keloid. Increased mesenchymal fibroblast subpopulation is also found in another fibrotic skin disease, scleroderma, suggesting this is a broad mechanism for skin fibrosis. These findings will help us better understand skin fibrotic pathogenesis, and provide potential targets for fibrotic disease therapies.
Background Although primary hyperhidrosis (PHH) has been frequently associated with diminished quality of life, the medical consequences of the condition are less well studied. Objective The ...objective was to study the clinical presentation of PHH and to determine its relationship to cutaneous infection. Methods A retrospective case-control study of patients encountered between 1993 and 2005 with the International Classification of Diseases, Ninth Revision diagnosis code for hyperhidrosis (HH) and meeting criteria for PHH was conducted. Results Of 387 patients with PHH included, 59% were female and 41% were male; mean age was 27.3 years (range 2-72). Sites of HH included soles (50.1%), palms (45.2%), and axillae (43.4%). Distributional patterns of HH were isolated axillary (27.6%), palmoplantar (24.3%), isolated plantar (15%), axillary/palmoplantar (5.7%), isolated palmar (5.7%), and craniofacial (5.2%). Axillary HH was more common in female patients ( P = .004). The mean age of onset (18.6 ± 12.3 years) indicated a mean duration of untreated symptoms of 8.9 years. Age at onset for palmoplantar HH (11.5 ± 8 years) was significantly younger than for axillary HH (20.0 ± 8.3 years; P < .0001), whereas onset of craniofacial HH (25.4 ± 13.7 years) was older ( P < .001). Exacerbating factors included stress/emotion/anxiety (56.7%) and heat/humidity (22%). The overall risk of any cutaneous infection was significantly ( P < .0001) increased in HH compared with controls (odds ratio OR 3.2; 95% confidence interval CI 2.2-4.6). Site-specific risks of fungal infection (OR 5.0; 95% CI 2.6-9.8; P < .0001), bacterial infection (OR 2.6; 95% CI 1.2-5.7; P = .017), and viral infection (OR 1.9; 95% CI 1.2-3.0; P = .011) were all increased. Risks of pitted keratolysis (OR 15.4; 95% CI 2.0-117; P = .0003), dermatophytosis (OR 9.8; 95% CI 3.4-27.8; P < .0001), and verruca plantaris/vulgaris (OR 2.1; 95% CI 1.3-3.6; P = .0077) were particularly increased. Association with atopic/eczematous dermatitis (OR 2.9; 95% CI 1.5-55; P = .019) was observed. Limitations Retrospective design and single-institution study are limitations. Conclusions Patients with HH are at high risk of secondary infection. Management of HH may have a secondary benefit of decreasing this risk.
Summary
Background
The infection caused by the recently identified SARS‐CoV‐2, called coronavirus disease‐19 (COVID‐19), has rapidly spread throughout the world. With the exponential increase of ...patients worldwide, the clinical spectrum of COVID‐19 is being better defined and new symptoms are emerging. Numerous reports are documenting the occurrence of different cutaneous manifestations in patients with COVID‐19.
Objectives
To provide a brief overview of cutaneous lesions associated with COVID‐19.
Methods
A literature search was performed in the PubMed, Scopus and Web of Science databases up to 30 April 2020. This narrative review summarizes the available data regarding the clinical and histological features of COVID‐19‐associated skin manifestations.
Results
The literature reports showed a great heterogeneity in COVID‐19‐associated cutaneous manifestations, as well as in their latency periods and associated extracutaneous symptoms. Pathogenic mechanisms are unknown, although the roles of a hyperactive immune response, complement activation and microvascular injury have been hypothesized. Based on our experience and the literature data, we subdivided the reported cutaneous lesions into six main clinical patterns: (i) urticarial rash; (ii) confluent erythematous–maculopapular–morbilliform rash; (iii) papulovesicular exanthem; (iv) chilblain‐like acral pattern; (v) livedo reticularis–livedo racemosa‐like pattern; and (vi) purpuric ‘vasculitic’ pattern. These six patterns can be merged into two main groups: the first – inflammatory and exanthematous – includes the first three groups listed above, and the second includes the vasculopathic and vasculitic lesions of the last three groups.
Conclusions
The possible presence of cutaneous findings leading to suspect COVID‐19 puts dermatologists in a relevant position. Further studies are needed to delineate the diagnostic and prognostic values of such cutaneous manifestations.
What is already known about this topic?
The infection caused by the SARS‐CoV‐2, called coronavirus disease‐19 (COVID‐19), has rapidly spread throughout the world, becoming pandemic.
The heterogeneous spectrum of COVID‐19‐associated cutaneous manifestations is based on preliminary reports of different types of skin lesions, leading to a need for clarity.
What does this study add?
A summary of the clinical and histological features of COVID‐19‐associated skin manifestations is provided.
Six main clinical patterns can be identified: (i) urticarial rash; (ii) confluent erythematous–maculopapular–morbilliform rash; (iii) papulovesicular exanthem; (iv) chilblain‐like acral pattern; (v) livedo reticularis–livedo racemosa‐like pattern; and (vi) purpuric ‘vasculitic’ pattern.
Plain language summary available online
Environmental air pollution encompasses various particulate matters (PMs). The increased ambient PM from industrialization and urbanization is highly associated with morbidity and mortality ...worldwide, presenting one of the most severe environmental pollution problems. This article focuses on the correlation between PM and skin diseases, along with related immunological mechanisms. Recent epidemiological studies on the cutaneous impacts of PM showed that PM affects the development and exacerbation of skin diseases. PM induces oxidative stress via production of reactive oxygen species and secretion of pro-inflammatory cytokines such as TNF-α, IL-1α, and IL-8. In addition, the increased production of ROS such as superoxide and hydroxyl radical by PM exposure increases MMPs including MMP-1, MMP-2, and MMP-9, resulting in the degradation of collagen. These processes lead to the increased inflammatory skin diseases and skin aging. In addition, environmental cigarette smoke, which is well known as an oxidizing agent, is closely related with androgenetic alopecia (AGA). Also, ultrafine particles (UFPs) including black carbon and polycyclic aromatic hydrocarbons (PAHs) enhance the incidence of skin cancer. Overall, increased PM levels are highly associated with the development of various skin diseases via the regulation of oxidative stress and inflammatory cytokines. Therefore, anti-oxidant and anti-inflammatory drugs may be useful for treating PM-induced skin diseases.
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Human microbiome studies have revealed the intricate interplay of host immunity and bacterial communities to achieve homeostatic balance. Healthy skin microbial communities are dominated by bacteria ...with low viral representation
, mainly bacteriophage. Specific eukaryotic viruses have been implicated in both common and rare skin diseases, but cataloging skin viral communities has been limited. Alterations in host immunity provide an opportunity to expand our understanding of microbial-host interactions. Primary immunodeficient patients manifest with various viral, bacterial, fungal, and parasitic infections, including skin infections
. Dedicator of cytokinesis 8 (DOCK8) deficiency is a rare primary human immunodeficiency characterized by recurrent cutaneous and systemic infections, as well as atopy and cancer susceptibility
. DOCK8, encoding a guanine nucleotide exchange factor highly expressed in lymphocytes, regulates actin cytoskeleton, which is critical for migration through collagen-dense tissues such as skin
. Analyzing deep metagenomic sequencing data from DOCK8-deficient skin samples demonstrated a notable increase in eukaryotic viral representation and diversity compared with healthy volunteers. De novo assembly approaches identified hundreds of novel human papillomavirus genomes, illuminating microbial dark matter. Expansion of the skin virome in DOCK8-deficient patients underscores the importance of immune surveillance in controlling eukaryotic viral colonization and infection.
Since the start of the COVID-19 pandemic, multiple studies have reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with dermatological manifestations.1 However, ...data on duration of signs and symptoms for the myriad dermatological manifestations of COVID-19 are lacking. ...58% of providers reported that patients had ongoing COVID-19 dermatological manifestations at the time of case entry. ...the duration of dermatological manifestations reported here probably underestimates both average duration and the number of long-hauler patients. Since the onset of the COVID-19 pandemic, appreciation for persistent morbidity beyond the acute phase of disease has increased.4,10 To our knowledge, our data represent the largest dataset to date on persistent skin signs and symptoms of COVID-19 and the duration for several distinct skin manifestations.
In this paper, we report the resurgence of lumpy skin disease (LSD) in Kurgan Oblast, Russia, in 2018. The majority of the outbreaks were silent with no mortality and congregated within an area with ...a radius of about 30 km located 1–50 km away from the national border with Kazakhstan. Following primary molecular diagnosis, LSD virus (LSDV) isolates were analyzed using a panel of PCR assays targeting different genetic loci, namely,
LSD008
(vaccine),
LSDV126
(field), and
GPCR
(vaccine and field), for differentiation and genotype assignment. All isolates were positive for the vaccine genotype of
GPCR
and negative for the other field targets tested. A PCR assay with melt curve analysis utilizing
LSD008
, developed in this work, indicated that the strains melted with a profile similar to those of field strains. Surprisingly, sequence analysis of the
RPO30
and
GPCR
genes aligned the Kurgan/2018 isolate with KSGP O-240 at the
GPCR
locus, but with Saratov/2017 at the RPO30 locus. The latter cluster forms an association with a sub-cluster of the field strains comprising the South African KSGP O-240 strain and NI-2490 strain. Due to these incongruent phylogenetic patterns, the sequences of three additional loci ORF19 (Kelch-like protein), ORF52 (putative transcriptional elongation factor), and ORF87 (mutT motif protein) were investigated. Phylogenetic analysis of these additional loci placed the strain Kurgan/2018 in either vaccine or field groups, strongly suggesting a novel recombinant profile. This is another piece of evidence exposing the potential for recombination in capripoxviruses and the ignored danger of using live homologous vaccines against LSD. The necessity to revise the PCR-based strategy differentiating infected from vaccinated animals is discussed. The potential scenarios of incursion and the contribution of the KSGP/NI-2490-like strain to the emergence of the recently identified vaccine-like recombinant are discussed.
During the coronavirus disease 2019 pandemic, several acral chilblain-like lesions were observed in young patients with suspected, but mostly unconfirmed, infection with severe acute respiratory ...syndrome coronavirus 2. The histopathologic aspect of these lesions is as yet poorly known.
To investigate the pathologic features of chilblain-like lesions.
Biopsies were obtained from 17 cases of chilblain-like lesions during the coronavirus disease 2019 pandemic in France and were studied by routine histologic examination, immunohistochemistry, and direct immunofluorescence. The patients had suspected but unconfirmed infection with severe acute respiratory syndrome coronavirus 2 (negative nasopharyngeal polymerase chain reaction and serologic test results).
Chilblain-like lesions showed many features in common with those reported in idiopathic and autoimmune-related chilblains, including epidermal necrotic keratinocytes, dermal edema, perivascular and perieccrine sweat gland lymphocytic (predominantly CD3/CD4+) inflammation, and frequent vascular changes (endothelialitis, microthromboses, fibrin deposition, and immunoreactant deposits on vessels).
Chilblain-like lesions show histopathologic features similar to those of idiopathic and autoimmune-related chilblains, with a high rate of vascular changes and direct immunofluorescence positivity. The role of severe acute respiratory syndrome coronavirus 2 in the development of these puzzling lesions remains to be elucidated.
VEXAS (vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic) syndrome is a disease with rheumatologic and hematologic features caused by somatic variants in UBA1. Pathogenic ...variants are associated with a broad spectrum of clinical manifestations. Knowledge of prevalence, penetrance, and clinical characteristics of this disease have been limited by ascertainment biases based on known phenotypes.
To determine the prevalence of pathogenic variants in UBA1 and associated clinical manifestations in an unselected population using a genomic ascertainment approach.
This retrospective observational study evaluated UBA1 variants in exome data from 163 096 participants within the Geisinger MyCode Community Health Initiative. Clinical phenotypes were determined from Geisinger electronic health record data from January 1, 1996, to January 1, 2022.
Exome sequencing was performed.
Outcome measures included prevalence of somatic UBA1 variation; presence of rheumatologic, hematologic, pulmonary, dermatologic, and other findings in individuals with somatic UBA1 variation on review of the electronic health record; review of laboratory data; bone marrow biopsy pathology analysis; and in vitro enzymatic assays.
In 163 096 participants (mean age, 52.8 years; 94% White; 61% women), 11 individuals harbored likely somatic variants at known pathogenic UBA1 positions, with 11 of 11 (100%) having clinical manifestations consistent with VEXAS syndrome (9 male, 2 female). A total of 5 of 11 individuals (45%) did not meet criteria for rheumatologic and/or hematologic diagnoses previously associated with VEXAS syndrome; however, all individuals had anemia (hemoglobin: mean, 7.8 g/dL; median, 7.5 g/dL), which was mostly macrocytic (10/11 91%) with concomitant thrombocytopenia (10/11 91%). Among the 11 patients identified, there was a pathogenic variant in 1 male participant prior to onset of VEXAS-related signs or symptoms and 2 female participants had disease with heterozygous variants. A previously unreported UBA1 variant (c.1861A>T; p.Ser621Cys) was found in a symptomatic patient, with in vitro data supporting a catalytic defect and pathogenicity. Together, disease-causing UBA1 variants were found in 1 in 13 591 unrelated individuals (95% CI, 1:7775-1:23 758), 1 in 4269 men older than 50 years (95% CI, 1:2319-1:7859), and 1 in 26 238 women older than 50 years (95% CI, 1:7196-1:147 669).
This study provides an estimate of the prevalence and a description of the clinical manifestations of UBA1 variants associated with VEXAS syndrome within a single regional health system in the US. Additional studies are needed in unselected and genetically diverse populations to better define general population prevalence and phenotypic spectrum.
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