Search Results (89)

Psoriasis is a chronic immune-mediated inflammatory skin disorder characterized by keratinocyte hyperproliferation, impaired epidermal barrier function, and immune dysregulation. The Th17/IL-23 axis plays a central role in its pathogenesis, promoting the production of key pro-inflammatory cytokines such as IL-17, IL-23, and TNF-α, which sustain chronic inflammation and epidermal remodeling. Emerging evidence suggests that SARS-CoV-2 may trigger new-onset or exacerbate existing psoriasis, likely through viral protein-induced activation of toll-like receptors (TLR2 and TLR4). This leads to NF-κB activation, cytokine release, and enhanced Th17 responses, disrupting immune homeostasis. Erythrodermic psoriasis (EP), a rare and severe variant, presents with generalized erythema and desquamation, often accompanied by systemic complications, including infection, electrolyte imbalance, and hemodynamic instability. In a murine model of SARS-CoV-2 infection, we found notable cutaneous changes: dermal collagen deposition, hair follicle destruction, and subcutaneous adipose loss. Parallel findings were seen in a rare clinical case (only the third reported case) of EP in a patient with refractory psoriasis, who developed erythroderma after off-label initiation of dupilumab therapy. The patient’s histopathology closely mirrored the changes seen in the SARS-CoV-2 model. Histological evaluations also reveal similarities between psoriasis flare-ups following dupilumab treatment and cutaneous manifestations of COVID-19, suggesting a shared inflammatory pathway, potentially mediated by heightened type 1 and type 17 responses. This overlap raises the possibility of a latent connection between SARS-CoV-2 infection and increased psoriasis severity. Since the introduction of COVID-19 vaccines, sporadic cases of EP have been reported post-vaccination. Although rare, these events imply that vaccine-induced immune modulation may influence psoriasis activity. Our findings highlight a convergence of inflammatory mediators—including IL-1, IL-6, IL-17, TNF-α, TLRs, and NF-κB—across three triggers: SARS-CoV-2, vaccination, and dupilumab. Further mechanistic studies are essential to clarify these relationships and guide management in complex psoriasis cases. Full article

Mpox (MPX), caused by the Monkeypox virus (MPXV), is a zoonotic orthopoxvirus infection with increasing global relevance due to sustained human-to-human transmission. While primarily known for cutaneous and systemic involvement, emerging evidence suggests that MPX may also disrupt endocrine function. This narrative review aims to synthesize current clinical, experimental, and epidemiological findings on MPX-related endocrine complications. We explore the potential impact of MPXV on the thyroid, adrenal glands, and gonads, and discuss the underlying mechanisms, clinical manifestations, and implications for patient management. MPX has been implicated in viral-induced subacute thyroiditis, with cases exhibiting thyrotoxicosis followed by hypothyroidism, likely mediated by direct viral infiltration or immune dysregulation. Additionally, MPX may contribute to adrenal insufficiency through viral invasion, immune-mediated destruction, or hypothalamic–pituitary–adrenal (HPA) axis dysfunction, exacerbating metabolic and inflammatory complications. MPXV’s persistence in testicular tissue raises concerns about reproductive health, with potential implications for fertility, hormone production, and viral transmission. The virus may also modulate host steroid pathways through interactions with glucocorticoid, androgen, and estrogen receptors, influencing immune responses and disease severity. Given these findings, clinicians should maintain vigilance for endocrine dysfunction in MPX patients, particularly in immunocompromised individuals. The role of steroid therapy in MPX remains complex, requiring careful balancing of its anti-inflammatory benefits against potential risks of viral persistence and immune suppression. Further research is essential to clarify MPX’s endocrine impact and optimize management strategies. Full article

Bullous pemphigoid (BP) is a rare autoimmune disease, primarily affecting elderly individuals, that significantly impacts the patient’s quality of life. In contrast, psoriasis vulgaris (PV) is a common, chronic, immune-mediated skin condition recognized as a systemic T-cell-mediated disorder. We aim to present the case of a patient suffering from a dermatologic association of BP and PV, which unveiled hepatitis C viral infection as a potential trigger and led to complex therapeutic challenges. A literature review is also included, exploring previous cases of overlapping BP and PV, along with a discussion of the unique pathogenic mechanisms and an analysis of the available therapeutic options. The patient, a 53-year-old male with a seven-year history of PV, presented with tense bullae overlying the psoriatic papules and plaques, with a generalized distribution. The presence of hepatitis C infection was considered a potential trigger for the concurrent presentation of BP and PV. Recent GWASs have demonstrated a potential causal relationship between PV and the subsequent development of BP, suggesting shared genetic susceptibility and immune pathways. However, the exact mechanisms driving this transition remain incompletely understood. Our case is particularly relevant as it exemplifies how environmental triggers—such as chronic hepatitis C infection—together with chronic cutaneous inflammation may act as cofactors in this process, possibly through the ‘epitope spreading’ phenomenon. This case underlines the importance of identifying triggering factors in patients with overlapping autoimmune diseases and reinforces the need for future research to further elucidate the pathogenic link between genotype and phenotype, in order to improve personalized therapeutic strategies. Full article

Orf virus (ORFV) is the type species of Parapoxvirus of the Poxviridae family that induces cutaneous pustular skin lesions in sheep and goats, and causes zoonotic infections in humans. Pattern recognition receptors (PRRs) sense pathogen-associated molecular patterns (PAMPs), leading to the triggering of the innate immune response through multiple signalling pathways involving type I interferons (IFNs). The major PAMPs generated during viral infection are nucleic acids, which are the most important molecules that are recognized by the host. The induction of type l IFNs leads to activation of the Janus kinase (JAK)-signal transducer activator of transcription (STAT) pathway, which results in the induction of hundreds of interferon-stimulated genes (ISGs), many of which encode proteins that have antiviral roles in eliminating virus infection and create an antiviral state. Genetic and functional analyses have revealed that ORFV, as found for other poxviruses, has evolved multiple immunomodulatory genes and strategies that manipulate the innate immune sensing response. Full article

Reticular erythematous mucinosis (REM) is a rare form of primary cutaneous mucinosis, often linked to viral infections, inflammatory conditions, ultraviolet radiation, radiotherapy, malignant disorders, or an underlying immune dysfunction. It typically affects middle-aged women and manifests as symmetrical erythematous macules, papules, or plaques that exhibit a reticular and annular configuration, mainly on the midline of the thorax or dorsum. Although these regions represent the most prevalent sites, atypical occurrences have been noted. We report an unusual case of REM in a pediatric female patient with an ongoing history of B-cell acute lymphoblastic leukemia. The physical examination revealed an atypical distribution of REM lesions, symmetrically affecting the gluteal region and proximal thighs. Establishing a definitive diagnosis required a meticulous correlation between clinical, dermoscopic, and histopathologic findings. To our knowledge, this is the first documented case of REM in a patient with acute lymphoblastic leukemia. Our study underlines the importance of including REM in the differential diagnosis of persistent erythematous lesions, particularly in immunocompromised patients or those with a history of malignancy. Furthermore, we provide a comprehensive literature review, emphasizing the etiology, risk factors, pathogenetic mechanisms, diagnostic challenges, and different therapeutic options for REM. Full article

Varicella-zoster virus is an α-herpes virus with a double-stranded DNA genome, which causes two main clinical pictures: varicella or chickenpox and herpes zoster. Chickenpox is the primary infection, predominantly affecting children, and it presents with fever and a cutaneous eruption consisting of a vesicular, pruritic, and painful rash. Herpes zoster is a viral infection that typically develops in adulthood as a result of the reactivation of the varicella-zoster virus. If acquired during pregnancy, chickenpox may be responsible for serious complications for the mother, the fetus, or the newborn. The most frequent complication of primary varicella-zoster virus infection in mothers is varicella pneumonia, while encephalitis and hepatitis are rare. The effects on the fetus due to chickenpox infection depend on the stage of pregnancy when the mother becomes infected. If the infection occurs during the first trimester, it does not increase the risk of miscarriage. However, if the infection occurs during the first or second trimester, it may cause fetal varicella syndrome or congenital varicella syndrome. During pregnancy, if the varicella-zoster virus reactivates, it usually does not cause harm to the fetus or lead to any birth defects. However, it may increase maternal morbidity due to herpes zoster and its complications. In the case of primary varicella-zoster virus infection in pregnant women, about 20% of newborns may get neonatal or infantile herpes zoster without any complications. However, it is recommended to start early treatment of herpes zoster in pregnant women as it is believed to accelerate the healing process of skin lesions and alleviate pain, reducing both its duration and severity. Through this narrative review, we discuss the approach to the optimal management of varicella-zoster virus infection during pregnancy. 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: Mycosis fungoides (MF) represents the most prevalent entity of cutaneous T cell lymphoma (CTCL). The MF aetiopathogenesis is incompletely understood, due to significant transcriptomic heterogeneity and conflicting views on whether oncologic transformation originates in early thymocytes or mature effector memory T cells. Recently, using clinical specimens, our group showed that the skin microbiome aggravates disease course, mainly driven by an outgrowing, pathogenic S. aureus strain carrying the virulence factor spa, which was shown by others to activate the T cell signalling pathway NF-κB. Methods: To explore the role of the skin microbiome in MF aetiopathogenesis, we here performed RNA sequencing, multi-omic data integration of the skin microbiome and skin transcriptome using Multi-Omic Factor Analysis (MOFA), virome profiling, and T cell receptor (TCR) sequencing in 10 MF patients from our previous study group. Results: We observed that inter-patient transcriptional heterogeneity may be largely attributed to differential activation of T cell signalling pathways. Notably, the MOFA model resolved the heterogenous activation pattern of T cell signalling after denoising the transcriptome from microbial influence. The MOFA model suggested that the outgrowing S. aureus strain evoked signalling by non-canonical NF-κB and IL-1B, which in turn may have fuelled the aggravated disease course. Further, the MOFA model indicated aberrant pathways of early thymopoiesis alongside enrichment of antiviral innate immunity. In line with this, viral prevalence, particularly of Epstein–Barr virus (EBV), trended higher in both lesional skin and the blood compared to nonlesional skin. Additionally, TCRs in both MF skin lesions and the blood were significantly more likely to recognize EBV peptides involved in latent infection. Conclusions: First, our findings suggest that S. aureus with its virulence factor spa fuels MF progression through non-canonical NF-κB and IL-1B signalling. Second, our data provide insights into the potential role of viruses in MF aetiology. Last, we propose a model of microbiome-driven MF aetiopathogenesis: Thymocytes undergo initial oncologic transformation, potentially caused by viruses. After maturation and skin infiltration, an outgrowing, pathogenic S. aureus strain evokes activation and maturation into effector memory T cells, resulting in aggressive disease. Further studies are warranted to verify and extend our data, which are based on computational analyses. Full article

Viral outbreaks are common in the sport community. Data regarding the prevalence of plantar warts, genital warts, herpes simplex type 1 (herpes labialis), herpes zoster, and genital herpes in competitive swimmers are lacking in the literature. The purpose of this study was to determine the prevalence of those viral infections among young competitive swimmers participating in Greek swimming clubs. Swimmers’ parents and adult swimmers were asked to complete an anonymous questionnaire. In total, 1047 swimmers enrolled in this study. The measured parameters included gender, age, times of infections, and seasons when athletes may be more susceptible to infections. Practicing information such as type of swimming facility, number of training years, average hours of daily training, behaviors in swimming practice, and sunlight exposure was also recorded. All infections showed a significant difference in relation to “age” and “years of training”. The gender significance was observed in herpes labialis (p = 0.016) and plantar warts (p = 0.05). The prevalence of all infections in swimmers who use outdoor facilities was higher. Certain behaviors such as walking barefoot on a pool deck and sharing swimming equipment correlate with herpes simplex and plantar warts. Virus infections can affect swimmers of all ages. In our study, plantar warts and herpes labialis are more common in swimmers. Herpes zoster and sexually transmitted viruses are rarer and affect adult swimmers. The impact of cutaneous infections on swimmers can affect performance and well-being. Effective prevention and management are essential to avoid complications. Proper hygiene, medical guidance, and treatment reduce swimmers’ exposure to skin viruses. Full article

Introduction: Viral infections cause oxygen deprivation, leading to hypoxia or anoxia in certain tissues. The limitation of mitochondrial respiration is one of the major events during hypoxia that induces alternative metabolic activities and increased levels of certain biomolecules such as nitric oxide (NO) metabolites. In this study, we aimed to investigate the role of NO metabolites and hypoxia in HPV infection. Materials and Methods: We included 36 patients with palmoplantar warts and 36 healthy subjects and performed serum determinations of NO metabolites (direct nitrite, total nitrite, nitrate, and 3-nitrotyrosine) and HIF1α, a marker of hypoxia. Results: We found elevated serum levels in NO metabolites and HIF1α, and decreased direct nitrite/nitrate ratios in patients with warts versus controls. Additionally, we identified statistically significant positive correlations between NO metabolites and HIF1α levels, except for 3-nitrotyrosine. Conclusions: Our findings show that HPV infection causes hypoxia and alterations in NO metabolism and suggest a link between wart development and cellular stress. Our research could provide new insights for a comprehensive understanding of the pathogenesis of cutaneous HPV infections. Full article

The development of keratinocytic skin tumors, presumably attributable to paradoxical activation of the MAPK pathway, represents a relevant side effect of targeted therapies with BRAF inhibitors (BRAFis). The role of cutaneous papillomavirus infection in BRAFi-associated skin carcinogenesis, however, is still inconclusive. Employing the Mus musculus papillomavirus 1 (MmuPV1) skin infection model, the impact of BRAFis and UVB exposure on papillomavirus induced skin tumorigenesis was investigated in immunocompetent FVB/NCrl mice. Systemic BRAF inhibition in combination with UVB light induced skin tumors in 62% of the MmuPV1-infected animals. In contrast, significantly fewer tumors were observed in the absence of either BRAF inhibition, UVB irradiation or virus infection, as demonstrated by lesional outgrowth in 20%, 5% and 0% of the mice, respectively. Combinatory exposure to BRAFis and UVB favored productive viral infection, which was shown by high numbers of MmuPV1 genome copies and E1^E4 spliced transcripts and an abundance of E6/E7 oncogene mRNA and viral capsid proteins. BRAF inhibition, but not viral infection or UVB light, activated ERK1/2, whereas γH2AX expression, inducible by UVB light, remained unaltered by BRAFis. These results provide experimental evidence that BRAF inhibition and UVB irradiation synergistically promote MmuPV1-induced skin tumor development in vivo. This indicates an alternative pathway by which papillomavirus skin infection may contribute to BRAFi-associated skin tumorigenesis. Full article

CMV is a ubiquitous DNA virus that establishes infection and results in 40–100% seropositivity. Viral replication occurs following an acquired primary infection (or reinfection) or by the reactivation of life-long latency. In immunocompetent patients, CMV infection is mostly asymptomatic or mild and self-limited. However, an extensive review of the literature published up to April 2024 reveals that despite immunocompetence, CMV can cause a very large variety of clinical syndromes in any part of the gastrointestinal tract (the most common pattern), the central or peripheral nervous system, and the eyes, as well as hematological, pulmonary, cardiac, and cutaneous disease. Not uncommonly, more than one system is involved, and though the disease is often self-limited, treatment with intravenous ganciclovir or oral valganciclovir may be required, and in isolated cases, fatalities may occur. Thus, a potential CMV infection should be considered in the differential of myriad syndromes in non-immunocompromised patients. Associated systemic symptoms (fever, sweats, and weight loss), lymphocytosis, and hepatitis are not uncommon and can be a useful clue. Some populations, such as critically ill patients in intensive care, pregnant women, elderly patients, and those with inflammatory bowel disease, may be more susceptible. Moreover, the potential of past, latent CMV infection (i.e., CMV seropositivity) to be associated with significant cardiovascular morbidity and all-cause mortality years later is intriguing and requires further study. All these data indicate the outstanding importance of developing a vaccine against CMV, which hopefully will become available in the foreseeable future. Meanwhile, a solid diagnosis of active CMV infection can be quickly established (or ruled out) by widely available serology tests and PCR amplification, and clinicians in all disciplines need to be more aware of the diverse guises of CMV infection and remember to consider it in any host, including an immunocompetent one. Full article

Viral infections caused by exposure to viruses such as Epstein–Barr, cytomegalovirus, or Parvovirus B19 have always been considered predisposing environmental factors for the onset of autoimmune diseases. More recently, autoimmune mechanisms such as molecular mimicry, T-cell activation, transient immunosuppression and inflammation have also been observed in cases of SARS-CoV-2 infection. Several newly diagnosed autoimmune disorders have been reported post-COVID-19, such as COVID-19-associated multisystemic inflammatory syndrome in children (MIS-C), type 1 diabetes mellitus, systemic lupus erythematosus, or rheumatoid arthritis. In this article, we present a new case of paediatric systemic lupus erythematosus (SLE) with haematological (macrophage activation syndrome), renal (stage 2), cutaneous (urticarial vasculitis) and digestive involvement, onset three and a half months post-COVID-19. In the dynamics, de novo infection generated by Epstein–Barr exposure was associated. The diagnosis was confirmed based on EULAR/ACR 2019 criteria. The aim of the article is to present a possible correlation between SARS-CoV-2 and Epstein–Barr as extrinsic factors in triggering or activating paediatric systemic lupus erythematosus. Keywords: paediatric systemic lupus erythematosus; post-COVID-19; Epstein–Barr; SARS- CoV-2; case report; paediatric patient. Full article

Dengue virus (DENV) is a continuing global threat that puts half of the world’s population at risk for infection. This mosquito-transmitted virus is endemic in over 100 countries. When a mosquito takes a bloodmeal, virus is deposited into the epidermal and dermal layers of human skin, infecting a variety of permissive cells, including keratinocytes, Langerhans cells, macrophages, dermal dendritic cells, fibroblasts, and mast cells. In response to infection, the skin deploys an array of defense mechanisms to inhibit viral replication and prevent dissemination. Antimicrobial peptides, pattern recognition receptors, and cytokines induce a signaling cascade to increase transcription and translation of pro-inflammatory and antiviral genes. Paradoxically, this inflammatory environment recruits skin-resident mononuclear cells that become infected and migrate out of the skin, spreading virus throughout the host. The details of the viral–host interactions in the cutaneous microenvironment remain unclear, partly due to the limited body of research focusing on DENV in human skin. This review will summarize the functional role of human skin, the cutaneous innate immune response to DENV, the contribution of the arthropod vector, and the models used to study DENV interactions in the cutaneous environment. Full article

A natural monkeypox virus infection may not induce sufficient neutralizing antibody responses in a subset of healthy individuals. The aim of this study was to evaluate monkeypox virus-neutralizing antibodies six months after infection and to assess the virological factors predictive of a poor immunological response. Antibodies were assessed using a plaque reduction neutralization test at six months from mpox infection; mpox cutaneous, oropharyngeal, and anal swabs, semen, and plasma samples were tested during infection. Overall, 95 people were included in the study; all developed detectable antibodies. People who were positive for the monkeypox virus for more days had higher levels of antibodies when considering all tested samples (p = 0.029) and all swabs (p = 0.005). Mpox cycle threshold values were not predictive of antibody titers. This study found that the overall days of monkeypox virus detection in the body, irrespective of the viral loads, were directly correlated with monkeypox virus neutralizing antibodies at six months after infection. Full article