Search Results (26)

Background/objectives: Stimulator of Interferon Genes (STING)-associated vasculopathy with onset in infancy (SAVI) is a rare autoinflammatory disorder caused by gain-of-function mutations in the TMEM173 gene. These mutations result in chronic activation of the STING pathway and excessive type I interferon production, leading to systemic inflammation, vascular abnormalities, interstitial lung disease, and skin ulcerations. Janus kinase (JAK) inhibitors, including baricitinib, have shown promise in mitigating systemic and organ-specific manifestations. However, these inhibitors broadly suppress immune pathways, potentially increasing vulnerability to infections. Case presentation: This case report describes a 21-year-old woman with SAVI (due to a heterozygous TMEM173 mutation) who developed disseminated molluscum contagiosum (MC) while receiving baricitinib therapy. Laboratory results revealed lymphopenia, low CD4/CD8 ratio, and impaired immune cell activity, suggesting compromised antiviral immunity. Discussion: Despite SAVI’s association with excessive type I interferon signaling, this chronic hyperactivation may cause immune dysregulation, exhausting T cells and natural killer cells vital for viral defense. Furthermore, baricitinib suppresses interferon signaling via the JAK-STAT pathway, reducing inflammatory damage in SAVI but also impairing antiviral responses. Moreover, MC viruses evade host immune defenses by antagonizing STING and TANK-binding kinase 1-mediated interferon activation, further contributing to infection risk. This report is the first to document MC in a SAVI patient and highlights the rare complication of disseminated MC due to impaired type I interferon signaling and immune suppression from baricitinib therapy. This case underscores the need for vigilance regarding viral infections in SAVI patients treated with JAK inhibitors. Full article

This literature review aims to comprehensively evaluate the clinical and dermoscopic presentations of common pediatric diseases among children with skin of color (SoC) while also addressing potential variations based on racial backgrounds. This review encompasses various conditions, such as nevi subtypes, viral infections, infestations, and inflammatory dermatoses, as well as hair diseases and abnormal vascular formations, occurring in pediatric populations. Overall, we identified 7 studies on nevi subtypes, 24 studies on skin infections, 6 on inflammatory dermatoses, 10 on hair diseases and disorders, and 14 on miscellaneous disorders that also satisfied our SoC- and race-specific criteria. In case of no results, we assumed that dermoscopic findings are similar between SoC adults and children, confirming the hypothesis with our cases of dark-skinned Indian child patients. Inflammatory dermatoses such as psoriasis, eczema, and cutaneous mastocytosis, as well as skin infections like cutaneous leishmaniasis, appear with brownish backgrounds or exhibit dark structures more frequently than the respective dermoscopy images of Caucasian populations. Dermoscopy traits such as erythema in tinea capitis are uncommon or even absent on a dark-colored scalp, while a dark skin tone often obscures many characteristic features, such as dark and yellow dots in alopecia areata and even parts of an intradermal parasite in the case of scabies. Race-specific traits were also observed, such as corkscrew hair in tinea capitis, primarily seen in patients of African origin. Many dermoscopic images are consistent between SoC and non-SoC in various skin lesions, including vascular anomalies, juvenile xanthogranuloma, mastocytoma, and viral skin lesions like molluscum contagiosum, as well as in various hair disorders such as trichotillomania, while tinea capitis displays the most diverse reported dermoscopic features across SoC- and race-specific studies. Full article

Background/Objectives: Cidofovir, an antiviral drug approved for cytomegalovirus retinitis, has emerged as an alternative treatment option for virally induced cutaneous and mucocutaneous conditions, as well as being trialed as a treatment for select neoplasms. In this review, we highlight the existing evidence, clinical uses, and rationale of using cidofovir for the treatment of cutaneous pathologies. Methods: A PubMed database literature search was conducted to identify relevant articles for inclusion in this review. Results: Cidofovir has several cutaneous applications in various formulations including intravenous, topical, and subcutaneous administrations. Primarily through case reports, case series, and retrospective reviews, cidofovir has demonstrated efficacy in treating a variety of virally induced conditions—verruca vulgaris, herpes simplex virus, molluscum contagiosum—as well as in adjuvant treatment for select neoplasms. The drug has shown efficacy in immunocompromised and immunocompetent adults and children alike. Conclusions: The body of literature supports the use of cidofovir as an effective and well-tolerated treatment for many viral cutaneous pathologies, and encourages further study for its use as an adjuvant therapy for neoplastic disease. Full article

Background: The arrival of the big-data era provides us with a chance to elaborate the spectrum and epidemiological characteristics of infectious diseases in children and adolescents aged 0–18 years in the pre-COVID-19 pandemic era. Methods: We collected data on infectious diseases in 891,981 participants from the Cheeloo Lifespan Electronic Health Research Data-library. The incidence density of each infection was calculated and stratified by age and region. The annual percentage change (APC) in incidence was estimated by logarithmic linear regression. Results: A total of 18,183 cases of 78 infections were diagnosed, with an overall incidence density of 626.33 per 100,000 person-years (PY). Of these, 6825 cases of 50 non-notifiable infectious diseases were identified. Children aged 1–3 years had the highest incidence of infections. The overall incidence revealed a significant increasing trend from 2013 to 2017 (APC = 36.9%, p < 0.05). Hand, foot, and mouth disease, pneumonia, and influenza were the three most common diseases. The incidence of pneumonia, rubella, scarlet fever, zoster, molluscum contagiosum, and syphilis increased significantly during the study period (all p < 0.05). Taian, Binzhou, and Weihai had the highest incidence of all other cities. The incidence of gastrointestinal infections increased markedly in the eastern coastal regions. Conclusions: More stress should be placed on a number of non-notifiable infectious diseases with a high burden and a significant increasing trend. Age-based and regional targeting efforts are needed to prevent and contain infectious diseases among children and adolescents. Full article

Genital warts are the most frequent sexually transmitted disease. Their clinical diagnosis is not always easy, and invasive skin biopsies for histological examination should be performed in these cases. The aim of the study was to investigate the use of non-invasive imaging techniques for the diagnosis of genital warts and their imitators. We retrospectively evaluated dermoscopy, reflectance confocal microscopy (RCM), and line-filed confocal microscopy (LC-OCT) images of nine patients with 19 warts of the mucous membranes and five patients with lesions that clinically mimic genital warts, including 12 molluscum contagiosum, 1 Fordyce’s spot and one case of multiple acquired lymphangiomas. Most genital warts (15; 79%) showed dilated vessels surrounded by a whitish halo at dermoscopy. RCM and the new device LC-OCT could identify near histologic features such as the presence of hyperkeratosis, acanthosis, papillomatosis and enlarged vessels in all genital warts. However, the identification of koilocytes, which are the hallmark for the diagnosis of warts, was still difficult using both techniques. Non-invasive imaging techniques could also offer clues for the correct diagnosis of the imitators. This study confirmed the usefulness of dermoscopy in recognizing a precise pattern in warts and showed the potential use of RCM and LC-OCT to add additional findings to the clinical and dermoscopic examination. Full article

Molluscum contagiosum (MC) is characterized by skin lesions containing the highly contagious molluscum contagiosum poxvirus (MCV). MCV primarily infects children, with one US Food and Drug Administration (FDA)-approved drug-device treatment in use but no approved medications. Assessing antivirals is hindered by the inability of MCV to replicate in vitro. Here, we use vaccinia virus as a surrogate to provide evidence of the anti-poxvirus properties of berdazimer sodium, a new chemical entity, and the active substance in berdazimer gel, 10.3%, a nitric oxide-releasing topical in phase 3 development for the treatment of MC. We show that berdazimer sodium reduced poxvirus replication and, through a novel methodology, demonstrate that cells infected with drug-treated MCV virions have reduced early gene expression. Specifically, this is accomplished by studying the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB)-blocking protein MC160 as an example of an early gene. The results provide a plausible unique antiviral mechanism of action supporting increased MCV resolution observed in patients treated with berdazimer gel, 10.3% and describe a novel methodology that overcomes limitations in investigating MCV response in vitro to a potential new MC topical medication. Full article

Human papillomavirus (HPV) is the most prevalent sexually transmitted infection (STI) worldwide, with popular screening methods including the Papanicolaou test and HPV genotyping. However, in clinical practice, coinfections with other pathogens are often underestimated. Therefore, our study aims to describe the prevalence of STIs and vaginosis in urogenital samples from patients who had been tested exclusively for HPV genotyping. Methods: This analytical, prospective, cross-sectional study included 408 males and females. Eligible participants had positive and negative HPV genotyping test results and agreed to early detection or had HPV antecedents. They provided the same urogenital samples used for HPV detection and, through our multiplex in-house PCR assay, we screened for Candida spp., Ureaplasma spp., Trichomonas vaginalis, Neisseria gonorrhoeae, Chlamydia trachomatis, herpes simplex virus 1 and 2 (HSV), Mycoplasma spp., molluscum contagiosum virus (MCV), Treponema pallidum, Haemophilus spp., Staphylococcus aureus, and Klebsiella spp. The subsequent statistical analysis aimed to reveal correlations between HPV genotypes and the identified pathogens. Results: Of the participants, 72.1% (n = 294) tested positive for HPV genotypes. HR-HPV (high-risk HPV) genotypes comprised 51 (8.1%), 66 (7.1%), and 58 (6.1%). Haemophilus spp., Ureaplasma spp., Candida spp., Staphylococcus aureus, and Mycoplasma spp. frequently co-occurred with HPV infection (p < 0.05). Gender-based variations were notorious for Ureaplasma spp., Mycoplasma spp., and MCV (p < 0.05). Coinfections were prevalent (43.9%), with a positive HPV result elevating the risk for Trichomonas vaginalis, Mycoplasma spp., Staphylococcus aureus, HSV, and MCV (OR > 1, p < 0.05). HPV 16 correlated with HSV and Ureaplasma spp., while HPV 6 was linked with HSV and MCV (p < 0.05). Conclusions: This screening strategy uncovered significant coinfections and associations between HPV genotypes and pathogens, underscoring the importance of routine screening to explore clinical implications in urogenital health. Full article

Unusual viral skin infections might be the first clinical manifestation in children with an inborn error of immunity (IEI). We performed a prospective study from 1 October 2017 to 30 September 2021, at the Department of Pediatric Infectious Diseases and Clinical Immunity of Ibn Rochd University Hospital-Casablanca. During this period, on 591 patients newly diagnosed with a probable IEI, eight of them (1.3%), from six independent families, had isolated or syndromic unusual viral skin infections, which were either profuse, chronic or recurrent infections, and resistant to any treatment. The median age of disease onset was nine years old and all patients were born from a first-degree consanguineous marriage. By combining clinical, immunological and genetic investigations, we identified GATA2 deficiency in one patient with recalcitrant profuse verrucous lesions and monocytopenia (1/8) and STK4 deficiency in two families with HPV lesions, either flat or common warts, and lymphopenia (2/8), as previously reported. We also identified COPA deficiency in twin sisters with chronic profuse Molluscum contagiosum lesions, pulmonary diseases and microcytic hypochromic anemia (2/8). Finally, we also found one patient with chronic profuse MC lesions and hyper IgE syndrome, (1/8) and two patients with either recalcitrant profuse verrucous lesions or recurrent post-herpetic erythema multiforme and a combined immunodeficiency (2/8) with no genetic defect identified yet. Raising clinicians awareness that infectious skin diseases might be the consequence of an inborn error of immunity would allow for optimized diagnosis, prevention and treatment of patients and their families. Full article

Fordyce spots (FS) are heterotopic sebaceous glands affecting mostly oral and genital mucosa, commonly misdiagnosed with sexually transmitted infections. In a single-center retrospective study, we aimed to assess the ultraviolet-induced fluorescencedermatoscopy (UVFD) clues of Fordyce spots and their common clinical simulants: molluscum contagiosum, penile pearly papules, human papillomavirus warts, genital lichen planus, and genital porokeratosis. Analyzed documentation included patients’ medical records (1 September–30 October 2022) and photodocumentation, which included clinical images as well as polarized, non-polarized, and UVFD images. Twelve FS patients were included in the study group and fourteen patients in the control group. A novel and seemingly specific UVFD pattern of FS was described: regularly distributed bright dots over yellowish-greenish clods. Even though, in the majority of instances, the diagnosis of FS does not require more than naked eye examination, UVFD is a fast, easy-to-apply, and low-cost modality that can further increase the diagnostic confidence and rule out selected infectious and non-infectious differential diagnoses if added to conventional dermatoscopic diagnosis. Full article

In west and central Africa, monkeypox occurs mainly in older children, adolescents and young adults. In two large epidemiology studies of monkeypox outbreaks, the investigators observed a sizable number of coinfections of chickenpox (varicella) and monkeypox. Based on a review of the literature, we propose that chickenpox (human herpesvirus-3 infection) is a risk factor for acquisition of monkeypox infection. Our hypothesis states that the chickenpox skin lesion provides an entry site for the monkeypox virus, which is harbored on a fomite in the environment of the patient. The fact that monkeypox can enter via a scratch or abrasion is a known mechanism of spread for three other poxviruses, including mousepox (ectromelia), orf and molluscum contagiosum. There are many similarities in pathogenesis between certain poxviruses and chickenpox, including a viremia with a cellular stress response leading to high levels of the IL-6 cytokine. One very revealing observation in the two epidemiology studies was that the number of pox as well as the severity of disease in children with chickenpox and monkeypox coinfection was not greater than found in children with monkeypox alone. Based on the above observations, we conclude that, when chickenpox precedes monkeypox, priming of the immune system by the earlier chickenpox infection moderates the severity of the secondary infection with monkeypox. This conclusion also has important public health implications about chickenpox surveillance. Full article

That cidofovir, an acyclic nucleoside phosphonate (ANP), was inhibitory to the replication of poxviruses was first demonstrated by De Clercq et al.. That its active metabolite, the diphosphate, was found to be inhibitory to the molluscum contagiosum (M. contagiosum) DNA polymerase was demonstrated by Watanabe and Tamaki. Twelve different independent observations have then indicated that cidofovir administered intravenously, topically or intralesionally is efficacious in the treatment of M. contagiosum mostly in immunosuppressed patients. Full article

Although other co-viral infections could also be considered influencing factors, cervical human papillomavirus (HPV) infection is the main cause of cervical cancer. Metagenomics have been employed in the NGS era to study the microbial community in each habitat. Thus, in this investigation, virome capture sequencing was used to examine the virome composition in the HPV-infected cervix. Based on the amount of HPV present in each sample, the results revealed that the cervical virome of HPV-infected individuals could be split into two categories: HPV-dominated (HD; ≥60%) and non-HPV-dominated (NHD; <60%). Cervical samples contained traces of several human viral species, including the molluscum contagiosum virus (MCV), human herpesvirus 4 (HHV4), torque teno virus (TTV), and influenza A virus. When compared to the HD group, the NHD group had a higher abundance of several viruses. Human viral diversity appears to be influenced by HPV dominance. This is the first proof that the diversity of human viruses in the cervix is impacted by HPV abundance. However, more research is required to determine whether human viral variety and the emergence of cancer are related. Full article

As of July 2022, more than 16,000 laboratory-confirmed monkeypox (MPX) cases have been reported worldwide. Until recently, MPX was a rare viral disease seldom detected outside Africa. MPX virus (MPXV) belongs to the Orthopoxvirus (OPV) genus and is a genetically close relative of the Variola virus (the causative agent of smallpox). Following the eradication of smallpox, there was a significant decrease in smallpox-related morbidity and the population’s immunity to other OPV-related diseases such as MPX. In parallel, there was a need for differential diagnosis between the different OPVs’ clinical manifestations and diseases with similar symptoms (i.e., chickenpox, herpes simplex). The current study aimed to provide a rapid genetic-based diagnostic tool for accurate and specific identification of MPXV and additional related vesicle-forming pathogens. We initially assembled a list of 14 relevant viral pathogens, causing infectious diseases associated with vesicles, prone to be misdiagnosed as MPX. Next, we developed an approach that we termed rapid amplicon nanopore sequencing (RANS). The RANS approach uses diagnostic regions that harbor high homology in their boundaries and internal diagnostic SNPs that, when sequenced, aid the discrimination of each pathogen within a group. During a multiplex PCR amplification, a dA tail and a 5′-phosphonate were simultaneously added, thus making the PCR product ligation ready for nanopore sequencing. Following rapid sequencing (a few minutes), the reads were compared to a reference database and the nearest strain was identified. We first tested our approach using samples of known viruses cultured in cell lines. All the samples were identified correctly and swiftly. Next, we examined a variety of clinical samples from the 2022 MPX outbreak. Our RANS approach identified correctly all the PCR-positive MPXV samples and mapped them to strains that were sequenced during the 2022 outbreak. For the subset of samples that were negative for MPXV by PCR, we obtained definite results, identifying other vesicle-forming viruses: Human herpesvirus 3, Human herpesvirus 2, and Molluscum contagiosum virus. This work was a proof-of-concept study, demonstrating the potential of the RANS approach for rapid and discriminatory identification of a panel of closely related pathogens. The simplicity and affordability of our approach makes it straightforward to implement in any genetics lab. Moreover, other differential diagnostics panels might benefit from the implementation of the RANS approach into their diagnostics pipelines. Full article

According to previous studies, the increased risk of cutaneous infectious disorders in patients with atopic dermatitis (AD) is related to impaired epidermal function, abnormal systemic immune function, and lower antimicrobial peptides. In this study, we analyzed the association between AD and cutaneous infectious disorders in the real world using sequential pattern mining (SPM). We analyzed National Health Insurance data from 2010–2013 using SPM to identify comorbid cutaneous infectious diseases and the onset durations of comorbidities. Patients with AD were at greater risk for molluscum contagiosum (adjusted odds ratio (aOR), 5.273), impetigo (aOR, 2.852), chickenpox (aOR, 2.251), otitis media (aOR, 1.748), eczema herpeticum (aOR, 1.292), and viral warts (aOR, 1.105). In SPM analysis, comorbidity of 1.06% shown in molluscum contagiosum was the highest value, and the duration of 77.42 days documented for molluscum contagiosum was the shortest onset duration among all the association rules. This study suggests that AD is associated with an increased risk of cutaneous infectious disorders. In particular, care should be taken regarding its high relevance with impetigo, molluscum contagiosum, and otitis media, which may help in preventing AD from worsening through appropriately preventing and managing the condition. Full article

Since ancient times, people have tattooed their skin for various reasons. In the past, tattoos were associated with low social status; nowadays, tattoos are very popular and are considered a form of art. However, tattoos are associated with various clinical problems, including immune reactions, inflammatory disorders, infections, and even skin cancer. Epidemiological and clinical data of infections on tattoos are scarce. Tattoo-related infections are mostly bacterial; only a few localized viral infections have been reported so far and are caused by molluscum contagiosum virus (MCV), human papillomavirus (HPV), and herpes simplex virus (HSV). In most cases, the lesions were strictly confined to the area of the tattoo. In this review, we have analysed reported cases of viral infections localized on tattoos and discussed the possible mechanisms involved in the occurrence of these infections. Full article