Search Results (150)

Cutaneous melanoma is an aggressive cancer with an increasing incidence worldwide, highlighting the need for research into its pathogenesis. The tumor microenvironment (TME) plays a critical role in melanoma progression and consists of cellular components and an extracellular matrix (ECM) rich in cytokines and signaling molecules. The most abundant stromal cells within the TME are cancer-associated fibroblasts (CAFs), which remodel the ECM and modulate immune responses. Among immune cells, tumor-associated macrophages (TAMs) predominate, and their polarization toward the M2 phenotype supports tumor progression. Tumor-infiltrating lymphocytes (TILs) have diverse functions, including cytotoxic T-cells, helper T-cells that modulate immune response, B-cells forming tertiary lymphoid structures (TLS), and regulatory T-cells with immunosuppressive properties. Dendritic cells (DCs) also play a complex role in the TME. A notable subpopulation are mature regulatory dendritic cells (mregDCs), which contribute to immune evasion. All of these TME components may drive tumorigenesis. Advancements in melanoma treatment—including immunotherapy and targeted therapies—have significantly improved outcomes in advanced-stage disease. In parallel, emerging approaches targeting the tumor microenvironment and gut microbiome, as well as personalized strategies such as neoantigen vaccines and cell-based therapies, are under active investigation and may further enhance therapeutic efficacy in the near future. Full article

Zoonotic diseases are a persistent public health concern, especially in low- and middle-income countries like Brazil. This cross-sectional study evaluated the knowledge and perceptions of 132 high school students (70 public and 62 private) in Goiânia, Brazil, regarding zoonoses, using a structured questionnaire. Statistical analyses (Chi-square and Fisher’s exact tests) revealed significant differences (p < 0.05) between public and private school students in knowledge levels, pet care practices, and the awareness of zoonotic risks. While pet ownership was common in both groups, only 53% of private and 21% of public school students correctly defined “zoonosis.” Rabies, taeniasis, leptospirosis, tuberculosis, cysticercosis, cutaneous larva migrans, and leishmaniasis were the most frequently cited diseases, with private school students demonstrating greater recognition across all categories. However, most participants lacked detailed knowledge about transmission routes and prevention. Misconceptions—such as zoonoses affecting only low-income populations—were also identified. Preventive actions like sanitation, public education, and vaccination were commonly suggested but not consistently linked to zoonoses. These findings highlight critical educational gaps and emphasize the need to incorporate One Health principles into school curricula to improve youth understanding and support public health strategies for zoonosis prevention. Full article

Background: Reports of primary cutaneous lymphomas (CLs) following COVID-19 vaccines are extremely rare. Nevertheless, clinicians should be aware of a potential association between these events. Here, we report a case of the development and rapid progression of mycosis fungoides (MF) with lymph node involvement after COVID-19 vaccination. Case presentation: A 75-year-old female developed disseminated plaques and patches shortly after receiving the first dose of the SARS-CoV-2 mRNA vaccine. Within one month following the second dose of the mRNA vaccine, she additionally experienced rapid progression, leading to the development of tumors and inguinal lymphadenopathy. Blood and visceral involvement were excluded. The clinicopathological findings were consistent with the diagnosis of MF, and systemic methotrexate with topical treatment was implemented, resulting in remission of the lesions. Conclusions: The presented case of the development and rapid progression of MF after the SARS-CoV-2 mRNA vaccine raises the question of the possible immunomodulatory or oncomodulatory effects of mRNA vaccines. It prompted us to conduct a review outlining the mechanisms potentially causing the mRNA vaccine-associated CLs. We have performed an extensive literature search to determine an explanation for the observed phenomenon. Accumulated evidence suggests a link between CL occurrence and immunization with an mRNA vaccine. The proposed hypothesis revolves around shared signaling pathways that are enhanced by SARS-CoV-2 mRNA vaccines, thus driving the pathogenesis of MF. We want to raise clinicians’ attention to the rare side effects of COVID-19 vaccines and emphasize the need for thorough monitoring of patients with altered immunity in the course of various lymphoproliferative disorders. Full article

SARS-CoV-2, a β-coronavirus, primarily affects the lungs, with non-specific lesions and no cytopathic viral effect in the skin. Cutaneous antiviral mechanisms include activation of TLR/IRF pathways and production of type I IFN. We evaluated the antiviral mechanisms involved in the skin of COVID-19 patients, including skin samples from 35 deceased patients who had contracted COVID-19 before the launch of the vaccine. Detection of SARS-CoV-2 in the skin was performed using transmission electron microscopy and RT-qPCR. Microscopic and molecular effects of the virus in skin were evaluated by histopathology, RT-qPCR, and immunohistochemistry (IHC). The results revealed the presence of SARS-CoV-2 and microscopic changes, including microvascular hyaline thrombi, perivascular dermatitis, and eccrine gland necrosis. There was increased transcription of TBK1 and a reduction in transcription of TNFα by RT-qPCR in the COVID-19 group. IHC revealed reduced expression of ACE2, TLR7, and IL-6, and elevated expression of IFN-β by epidermal cells. In the dermis, there was decreased expression of STING, IFN-β, and TNF-α and increased expression of IL-6 in sweat glands. Our results highlight the role of type I IFN in the skin of COVID-19 patients, which may modulate the cutaneous response to SARS-CoV-2. Full article

Cutaneous warts caused by human papillomavirus (HPV) are among the most common dermatological conditions, affecting the quality of life of numerous people. Although they are widespread, effective and reliable treatment alternatives are limited, emphasizing the necessity for novel treatment options. Intralesional immunotherapy has emerged as a promising alternative, aiming to stimulate the host immune response to achieve the clearance of both treated and distant lesions. This review explores the immunopathogenesis of cutaneous warts and provides an in-depth analysis of intralesional therapies including measles–mumps–rubella (MMR) vaccine, purified protein derivative (PPD), Bacillus Calmette–Guérin (BCG), Candida antigen, Mycobacterium w vaccine (MWV), vitamin D3, and autoinoculation. We provide a comprehensive analysis of the most promising modalities, highlighting their mechanism of action, outcomes, advantages, and limitations. Although initial data indicate that intralesional immunotherapy offers advantageous efficacy and tolerability, there is a lack of standardized treatment protocols and randomized controlled trials to endorse its broad application. Nevertheless, considering its potential to address local and distant lesions with minimal adverse effects, intralesional immunotherapy may represent a transformative approach to managing cutaneous warts. Full article

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

Background: Leishmaniasis is a vector-borne zoonotic disease caused by protozoa of the genus Leishmania. While it is endemic in the Mediterranean Basin and the Balkans, Romania remains a non-endemic country. However, climate change, increased international travel, and the documented presence of competent vectors (Phlebotomus spp.) have raised concerns about the potential emergence of autochthonous cases. Case Presentation: We report two cases of imported cutaneous leishmaniasis (CL) diagnosed in central Romania, a region without previously confirmed human or animal cases. The first case involved a 31-year-old male with a recent travel history to Spain, presenting with erythematous papules and plaques that evolved into ulcerated lesions. The diagnosis was confirmed histopathologically and by a PCR. Treatment with miltefosine was effective, with minimal hepatic toxicity and a sustained response at a six-month follow-up. The second case concerned an 11-year-old boy who had traveled to Elba, Italy. He developed ulcerative lesions that progressed rapidly and were complicated by Pseudomonas aeruginosa superinfection. Despite an initially negative smear, PCR testing of the skin lesion confirmed the presence of CL. Antifungal therapy with fluconazole led to clinical improvement; treatment was ongoing at the time of publication. Discussion: These cases highlight the diagnostic and therapeutic challenges associated with CL in non-endemic settings. The varied clinical evolution underscores the importance of considering leishmaniasis in the differential diagnosis of chronic, non-healing cutaneous lesions, particularly in patients with a travel history to endemic regions. Conclusions: Increased awareness among clinicians, supported by accurate diagnostic tools and public health surveillance, is essential to identify and manage imported leishmaniasis. Given the absence of a licensed vaccine and the growing risk of vector expansion in Eastern Europe, these cases support the WHO’s inclusion of leishmaniasis among the priority neglected tropical diseases targeted for intensified global control efforts by 2030. Full article

The molecular landscape of cutaneous melanoma is complex and heterogeneous, and a deeper understanding of the genesis and progression of the tumor driven by genetic alterations is essential for the development of effective diagnostic and therapeutic strategies. Molecular diagnostics and the use of biomarkers are increasingly playing a role in treatment decisions. However, further research is urgently needed to elucidate the relationships between complex genetic alterations and the effectiveness of target therapies (although BRAF mutation is still the only targeted genetic alteration). Further research is required to exploit other targetable genetic alterations such as NRAS, KIT or rare mutations. Treatment guidelines for cutaneous melanoma are continually evolving based on data from recent and ongoing clinical trials. These advancements reflect changes mainly in the optimal timing of systemic therapy and the choice of combination therapies increasingly tailored to molecular profiles of individual tumors. Mono- or combination immunotherapies demonstrated unprecedented success of melanoma treatment; still, there is room for improvement: though several factors of primary or acquired resistance are known, they are not part of patient management as biomarkers. The novel developments of cancer vaccines to treat melanoma (melanoma-marker-based or personalized neoantigen-based) are encouraging; introduction of them into clinical practice without proper biomarkers would be the same mistake made in the case of first-generation immunotherapies. Full article

The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing, with UV radiation being the main cause. Other risk factors are age, sex, skin type and immunosuppression. Human papillomaviruses (HPVs) are associated with benign and malignant skin tumours. In contrast to anogenital and oropharyngeal carcinomas, which are caused by alpha papillomaviruses, the HPV types associated with cSCC belong to the beta-HPV genus. These viruses infect the skin epithelium and are widespread in skin samples from healthy people. It is assumed that HPV amplifies the DNA damage caused by UV radiation and disrupts the repair mechanisms of the cells, without remaining permanently detectable in the tumour tissue, the so-called hit-and-run theory. The HPV status of tumours appears to have a positive influence on prognosis and response to therapy due to increased immune infiltration, in particular by tissue-resident memory T cells and activation of immune effector cells. This favours responses to immunotherapies such as PD-1/PD-L1 inhibitors, whereas immunosuppression may promote a pro-carcinogenic effect. In conclusion, the role of beta HPV in the development of cSCC appears to be closely associated with the immune status of the host. Depending on the immune status, beta HPV can play either a protective or a tumour-promoting role, and in view of the increasing incidence of skin cancer worldwide, enhancing the immune response against virus-infected keratinocytes, e.g., through HPV vaccination, could represent a promising approach for the prevention and therapy of squamous cell carcinomas. Full article

The human papillomavirus (HPV) has been associated with the carcinogenesis of cutaneous squamous cell carcinoma (cSCC), especially in immunosuppressed patients. This article reviews the microbiology of HPV and its role in tissue tropism, invasion, and oncogenesis. It also describes possible HPV oncogenic ability due to the inactivation of the host p53 and retinoblastoma protein (pRb) by HPV oncoproteins E6 and E7, producing a suppression of cell cycle checkpoints and uncontrolled cell proliferation that may eventually result in invasive carcinoma. We will focus on β-HPV types and their role in epidermodysplasia verruciformis (EV), as well as α types and their ability to cause cutaneous and mucosal pathology. We also intend to examine the clinical characteristics of cSCC related to HPV and host immunosuppression conditions such as solid organ transplant in order to provide management guidelines for patients with cSCC associated with HPV based on available data. Other topics addressed in this article include particular locations of cSCC, such as nails; the prognosis; the recurrence; therapeutic modalities; and the role of HPV vaccines. Full article

Introduction: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with significant morbidity. Although cutaneous squamous cell carcinoma (cSCC) is a rare complication, it has serious consequences, particularly when associated with high-risk human papillomavirus (HPV) infections. This study examines two cases of HPV-16-induced cSCC in patients with long-standing HS and explores the potential role of HPV vaccination in preventing such malignancies. Methods and results: We report on two male patients with severe HS (Hurley stage III) and cutaneous squamous cell carcinoma with positive detection of HPV DNA in the tumour tissue. Conclusions: HPV vaccination may offer a preventive approach to cSCC in HS patients by reducing high-risk HPV infections. Incorporating vaccination into the management of HS, particularly in high-risk individuals, could potentially reduce the incidence of malignant transformation and improve long-term outcomes. Further research is warranted to validate these findings and refine prevention strategies. Full article

Leishmania is a protozoan parasite causing a spectrum of pathologies in humans grouped under the name leishmaniasis. Clinical outcomes range from the self-healing cutaneous form to the visceral one that is fatal in the absence of treatment. The leishmaniases are endemic in 98 countries in the tropics, subtropics, and Southern Europe, where 3 million new cases and more than 50,000 deaths are recorded yearly. Control of this disease is challenging as there is no approved vaccine coupled with toxic chemotherapeutics and the development of parasite resistance to some available drugs. It is, therefore, evident that the identification of new control methods, including new therapeutics, should be strongly encouraged. In the present study, thiol organic compounds were synthesized and tested for their activity against Leishmania major, the causative agent of human cutaneous leishmaniasis. Of the 21 compounds tested, 13 were active against L. major promastigotes in vitro at 100 μg/mL. Selected compounds tested in a dose-response assay showed activity at concentration as low as 25 μg/mL, a level of activity similar to that of Amphotericin B, a drug of choice for the treatment of human leishmaniasis. Structure–activity analysis shows that the addition of certain substituents, such as a methoxy group, to a compound that is biologically active renders it inactive. Together, our data demonstrate that functionalized thiols have an in vivo anti-Leishmania activity that is directly linked to their chemical structure. Full article

Bacillus anthracis is a deadly pathogen that under unfavourable conditions forms highly resistant spores which enable them to survive for a long period of time. Spores of B. anthracis are transmitted through the contaminated soil or animal products and enter to the host through the skin, lungs or oral route and can cause cutaneous, injection, inhalation and gastrointestinal anthrax, respectively. The disease is caused by the toxin which is produced by them once they germinate within the host cell. Anthrax toxin is the major virulence factor which has the ability to kill the host cell. The role of protein kinases and phosphatases of B. anthracis in toxin production and other virulence related properties have also been reported. There are two vaccines, BioThrax and CYFENDUS^TM, which are approved by the FDA-USA to prevent anthrax disease. Recently, anthrax toxin has also been shown to be a potential candidate for cancer therapeutics. Through present review, we aim to provide insights into sporulation, transmission and pathogenesis of B. anthracis as well as the current state of its prevention, treatment, vaccines and possible therapeutic uses in cancer. Full article

HPV-associated dermatological diseases include benign lesions like cutaneous warts and external genital warts. In addition, HPV infection is associated with the development of epithelial skin cancers, in particular cutaneous squamous cell carcinoma (cSCC). In contrast to anogenital and oropharyngeal cancers caused by mucosal HPV types of genus alpha papillomavirus, cSCC-associated HPV types belong to the genus beta papillomavirus. Currently available HPV vaccines that target mucosal HPV types associated with anogenital cancer and genital warts are type-specific and provide no cross-protection against beta HPV. When implementing vaccination to beta HPV to prevent skin tumors, it must be considered that acquisition of these HPV types occurs early in childhood and that the risk for cSCC increases with growing age and decreasing immune surveillance. Thus, individuals considered for beta HPV vaccination usually have pre-existing infection and are largely immunocompromised. On the other hand, worldwide increasing incidence rates of epithelial skin cancer reflect an urgent need for skin cancer prevention measures. Based on the pathogenic involvement of beta HPV, vaccination may represent a promising prevention strategy. Indeed, various procedures of prophylactic and therapeutic vaccination have been developed, and some of them have shown efficiency in animal models. Thus far, however, none of these vaccine candidates has been approved for application in humans. Full article

Cutaneous leishmaniasis (CL), caused by protozoan parasites of the Leishmania genus, is prevalent in tropical and subtropical regions, with important morbidity, particularly in low- to middle-income countries. Current systemic treatments, including pentavalent antimonials and miltefosine, are associated with significant toxicity, reduced efficacy, and are frequently ineffective in cases of severe or chronic CL. Immunotherapies leverage the immune system to combat microbial infection and offer a promising adjunct or alternative approach to the current standard of care for CL. However, the heterogeneous clinical presentation of CL, which is dependent on parasite species and host immunity, may require informed clinical intervention with immunotherapies. This review explores the clinical and immunological characteristics of CL, emphasising the current landscape of immunotherapies in in vivo models and clinical studies. Such immune-based interventions aim to modulate immune responses against Leishmania, with additive therapeutic effects enabling the efficacy of lower drug doses and decreasing the associated toxicity. Understanding the mechanisms that underlie immunotherapy for CL provides critical insights into developing safer and more effective treatments for this neglected tropical disease. Identifying suitable therapeutic candidates and establishing their safety and efficacy are essential steps in this process. However, the feasibility and utility of these treatments in resource-limited settings must also be considered, taking into account factors such as cost of production, temperature stability, and overall patient access. Full article