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The endocannabinoid system is composed by a complex and ubiquitous network of endogenous lipid ligands, enzymes for their synthesis and degradation, and receptors, which can also be stimulated by exogenous compounds, such as those derived from the Cannabis sativa. Cannabis and its bioactive compounds, including cannabinoids and non-cannabinoids, have been extensively studied in different conditions. Recent data have shown that the endocannabinoid system is responsible for maintaining the homeostasis of various skin functions such as proliferation, differentiation and release of inflammatory mediators. Because of their role in regulating these key processes, cannabinoids have been studied for the treatment of skin cancers and melanoma; their anti-tumour effects regulate skin cancer progression and are mainly related to the inhibition of tumour growth, proliferation, invasion and angiogenesis, through apoptosis and autophagy induction. This review aims at summarising the current field of research on the potential uses of cannabinoids in the melanoma field.
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Canabinoides , Melanoma , Neoplasias Cutâneas , Humanos , Canabinoides/uso terapêutico , Canabinoides/farmacologia , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Endocanabinoides/metabolismo , Endocanabinoides/uso terapêutico , Animais , Apoptose/efeitos dos fármacosRESUMO
Necrobiosis Lipoidica (NL) is a dermatological condition characterized by the development of granulomatous inflammation leading to the degeneration of collagen and subsequent formation of yellowish-brown telangiectatic plaques usually localized on the pretibial skin of middle-aged females. Due to its rarity and unclear etiopathogenesis, therapeutic options for NL are not well-standardized. Among them, photodynamic therapy (PDT) is an emerging tool, although its efficacy has primarily been evaluated in single case reports or small case series. This study reports the real-life experience of a cohort of NL patients treated with PDT at the Section of Dermatology of the University Hospital of Messina and Reggio-Emilia. From 2013 to 2023, 17 patients were enrolled -5 males (29%) and 12 females (71%) aged between 16 and 56 years (mean age: 42 ± 13 years), with a median duration of NL of 8 years. The overall complete clearance (>75% lesion reduction) was 29%, while the partial clearance (25-75% lesion reduction) was 59%, with 12% being non-responders. This study adds to the little amount of evidence present in the literature regarding the effectiveness of PDT in the treatment of NL. Variability in treatment responses among patients underscores the need for personalized protocols, optimizing photosensitizers, light sources, and dosimetry. The standardization of treatment protocols and consensus guidelines are essential to ensure reproducibility and comparability across studies.
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Asteraceae , Necrobiose Lipoídica , Fotoquimioterapia , Feminino , Masculino , Pessoa de Meia-Idade , Humanos , Adolescente , Adulto Jovem , Adulto , Necrobiose Lipoídica/tratamento farmacológico , Reprodutibilidade dos Testes , PeleRESUMO
Background and Objectives: Tirbanibulin 1% ointment is a novel synthetic anti-proliferative agent that inhibits tubulin polymerization. It is approved for treating actinic keratosis (AK) on the face and scalp in adults. It has demonstrated good efficacy, an adequate safety profile and excellent patient adherence in the phase 3 clinical trials, however data about its real-life efficacy and safety are lacking. Here we report the experience of the dermatology unit of the University Hospital of Messina. Materials and Methods: We performed a spontaneous open-label, prospective non-randomized study to assess the effectiveness and safety of tirbanibulin 1% ointment for the treatment of 228 AKs in 38 consecutive patients-28 males (73%) and 10 females (26%)-aged between 52 and 92 years (mean age: 72 ± 8.92 years). Results: Total clearance was recorded in 51% of lesions, while partial clearance was recorded in 73% of lesions. An excellent tolerability profile and high compliance rate were observed, with no treatment discontinuation due to the onset of adverse events. Conclusion: Our real-life experience confirms the effectiveness and safety of tirbanibulin ointment for the treatment of AKs.
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Acetamidas , Ceratose Actínica , Morfolinas , Piridinas , Adulto , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Ceratose Actínica/tratamento farmacológico , Estudos Prospectivos , Pomadas/uso terapêutico , Cooperação do Paciente , Resultado do TratamentoRESUMO
Infantile perianal pyramidal protrusion (IPPP) is a benign condition generally noted in childhood but may persist for several years. Dermoscopy may help to distinguish it from other conditions, particularly genital warts. We report six cases of IPPP and describe the dermoscopic features that will distinguish these lesions from verrucae.
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Dermoscopia , Neoplasias Cutâneas , Humanos , Períneo/patologia , Neoplasias Cutâneas/patologiaRESUMO
Immunosenescence is a complex multifactorial phenomenon consisting of wide-ranging remodeling of the immune system during the life span, resulting in an age-related qualitative-quantitative decline of immune cells and cytokines. A growing body of evidence in the international literature is highlighting the etiopathogenetic role of skin immunosenescence in the onset of various dermatologic conditions. Skin immunosenescence also serves as an interesting watershed for the onset of system-wide conditions in the context of allergic inflammation. Moreover, in recent years, an increasingly emerging and fascinating etiopathogenetic parallelism has been observed between some mechanisms of immunosenescence, both at cutaneous and systemic sites. This would help to explain the occurrence of apparently unconnected comorbidities. Throughout our review, we aim to shed light on emerging immunosenescent mechanisms shared between dermatologic disorders and other organ-specific diseases in the context of a more extensive discussion on the etiopathogenetic role of skin immunosenescence. A promising future perspective would be to focus on better understanding the mutual influence between skin and host immunity, as well as the influence of high inter-individual variability on immunosenescence/inflammaging. This can lead to a more comprehensive "immunobiographic" definition of each individual.
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Imunossenescência , Humanos , Inflamação/patologia , Pele/patologia , Citocinas , Comorbidade , EnvelhecimentoRESUMO
Canonical and non-canonical Wnt signaling pathways are involved in cell differentiation and homeostasis, but also in tumorigenesis. In fact, an exaggerated activation of Wnt signaling may promote tumor growth and invasion. We summarize the most intriguing evidence about the role of Wnt signaling in cutaneous carcinogenesis, in particular in the pathogenesis of non-melanoma skin cancer (NMSC). Wnt signaling is involved in several ways in the development of skin tumors: it may modulate the inflammatory tumor microenvironment, synergize with Sonic Hedgehog pathway in the onset of basal cell carcinoma, and contribute to the progression from precancerous to malignant lesions and promote the epithelial-mesenchymal transition in squamous cell carcinoma. Targeting Wnt pathways may represent an additional efficient approach in the management of patients with NMSC.
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Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Via de Sinalização Wnt , Proteínas Hedgehog , Neoplasias Cutâneas/patologia , Carcinoma Basocelular/genética , Carcinoma Basocelular/patologia , Inflamação , Carcinogênese , Microambiente TumoralRESUMO
Background and Objectives: Chronic ionizing radiation has biological effects on exposed healthcare workers, particularly on the skin. Capillaroscopy of the nail bed represents an easy, low cost, and non-invasive test to obtain information on the effects of chronic radiation exposure in healthcare workers. The aim of this study was to evaluate which capillaroscopic parameters are most associated with biological damage by chronic radiation exposure. Materials and Methods: We conducted a case-control study, in which cases were represented by healthcare workers exposed to ionizing radiations and controls by healthy subjects. We recorded anamnestic and personal data, including age and gender, before capillaroscopic examination of proximal nail folds of the fingers of both hands. Ten morphological qualitative/quantitative parameters were taken into consideration, assigning each of them a score on a scale from 0 to 3 (0 = no changes, 1 = <33% abnormal capillaries, 2 = 33-66% of abnormal capillaries, 3 = >66% of abnormal capillaries, for single magnification field at 200×). The parameters evaluated were: changes in the length, distribution and density of capillary loops, reduced visibility, decreased flow, visibility of the sub-papillary plexus, and presence of morphological atypia, such as ectasia, tortuosity, hemorrhage, and signs of neoangiogenesis. Results: We enrolled 20 cases and 20 controls. The two groups did not differ significantly for gender and age. Cases differed from controls in a statistically significant way for the following parameters: decreased capillary length (number of shortened capillaries) (p < 0.05), increased visibility of the subpapillary venous plexus (p < 0.05), tortuosity (p < 0.01), neoangiogenesis (p < 0.01), and ectasias (p < 0.001). Conclusions: We found that some capillaroscopic parameters, such as variability in length of capillaries, visibility of subpapillary venous plexus, presence of ectasias, tortuosity, and neoangiogenesis signs, are particularly associated with exposure to ionizing radiation in healthcare professionals. Alterations of these parameters may represent capillaroscopic clues of biological damage by chronic radiation exposure in healthcare professionals. Based on these observations, capillaroscopy may provide clinical data useful to the prevention and follow-up of radiation-exposed healthcare professionals.
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Capilares , Angioscopia Microscópica , Humanos , Estudos de Casos e Controles , Pessoal de Saúde , Diagnóstico Precoce , Atenção à SaúdeRESUMO
High-mobility Group Box 1 (HMGB1) is a nuclear protein that plays a key role in acute and chronic inflammation. It has already been studied in several diseases, among them melanoma. Indeed, HMGB1 is closely associated with cell survival and proliferation and may be directly involved in tumor cell metastasis development thanks to its ability to promote cell migration. This research aims to assess the role of this molecule in the pathogenesis of human melanoma and its potential therapeutic role. The research has been conducted on the PubMed database, and the resulting articles are sorted by year of publication, showing an increasing interest in the last five years. The results showed that HMGB1 plays a crucial role in the pathogenesis of skin cancer, prognosis, and therapeutical response to therapy. Traditional therapies target this molecule indirectly, but future perspectives could include the development of new target therapy against HMGB1, thus adding a new approach to the therapy, which has often shown primary and secondary resistance. This could add a new therapy arm which has to be prolonged and specific for each patient.
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Proteína HMGB1 , Melanoma , Neoplasias Cutâneas , Proteína HMGB1/metabolismo , Humanos , Inflamação/metabolismo , Melanoma Maligno CutâneoRESUMO
Interleukin (IL)-37 and IL-33 are among the latest cytokines identified, playing a role in several inflammatory conditions, spanning from systemic conditions to tumors to localized diseases. As newly discovered interleukins, their role is still scarcely understood, but their potential role as therapeutic targets or disease activity markers suggests the need to reorganize the current data for a better interpretation. The aim of this review is to collect and organize data produced by several studies to create a complete picture. The research was conducted on the PubMed database, and the resulting articles were sorted by title, abstract, English language, and content. Several studies have been assessed, mostly related to atopic dermatitis and immunologic pathways. Collective data demonstrates a pro-inflammatory role of IL-33 and an anti-inflammatory one for IL-37, possibly related to each other in an IL-33/IL-37 axis. Although further studies are needed to assess the safety and plausibility of targeting these two interleukins for patients affected by skin conditions, the early results indicate that both IL-33 and IL-37 represent markers of disease activity.
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Dermatite Atópica , Hipersensibilidade , Humanos , Interleucina-33/metabolismo , Pele/metabolismo , Interleucinas/metabolismo , Hipersensibilidade/metabolismo , Dermatite Atópica/tratamento farmacológico , Citocinas/metabolismoRESUMO
Interleukin 31 belongs to the IL-6 superfamily, and it is an itch mediator already studied in several diseases, comprising atopic dermatitis, allergic pathologies, and onco-hematological conditions. This research aims to assess the role of this cytokine in the pathogenesis of these conditions and its potential therapeutic role. The research has been conducted on articles, excluding reviews and meta-analysis, both on animals and humans. The results showed that IL-31 plays a crucial role in the pathogenesis of systemic skin manifestations, prognosis, and itch severity. Traditional therapies target this interleukin indirectly, but monoclonal antibodies (Mab) directed against it have shown efficacy and safety profiles comparable with biological drugs that are already available. Future perspectives could include the development of new antibodies against IL-31 both for humans and animals, thus adding a new approach to the therapy, which often has proven to be prolonged and specific for each patient.
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Dermatite Atópica , Interleucinas , Animais , Anticorpos Monoclonais/uso terapêutico , Dermatite Atópica/patologia , Humanos , Inflamação/tratamento farmacológico , Interleucina-33/uso terapêutico , Prurido/tratamento farmacológico , Prurido/patologiaRESUMO
Triple-combination therapy with elexacaftor, tezacaftor and ivacaftor has been recently approved for cystic fibrosis patients with at least one F508del mutation in the transmembrane conductance regulator of the cystic fibrosis gene. Among the adverse events of elexacaftor, tezacaftor and ivacaftor, the cutaneous ones have been rarely reported, mainly dealing with urticarial-like rashes. On this topic, we report two cases of Malassezia folliculitis following triple therapy administration in two young females. In the first patient, a papulopustular rush appeared before the folliculitis while in the second patient it was not preceded by other skin manifestations. The diagnosis was confirmed both by dermoscopy and histology. The prompt response to systemic antimycotic drugs provided further evidence for the causative role of Malassezia, requiring no discontinuation of cystic fibrosis therapy. We could hypothesize that the triple regimen treatment may induce changes in the skin microbiome, potentially able to favor colonization and proliferation of Malassezia species. Physicians should be aware of such associations to allow prompt diagnosis and early interventions, avoiding useless drug removal.
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Fibrose Cística , Foliculite , Malassezia , Aminofenóis , Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Fibrose Cística/tratamento farmacológico , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/farmacologia , Regulador de Condutância Transmembrana em Fibrose Cística/uso terapêutico , Combinação de Medicamentos , Feminino , Foliculite/induzido quimicamente , Foliculite/tratamento farmacológico , Humanos , Mutação , QuinolonasRESUMO
Acne is an inflammatory cutaneous disease affecting the pilosebaceous unit and hair follicles on the face, neck, back, and chest, with a typical onset in adolescence and, in some cases, persisting into adulthood. Systemic treatments with antibiotics or isotretinoin present many limitations, like antimicrobial resistance phenomena and teratogenicity, which appear more relevant in the pediatric population, both for the treatment-related risks and for the reticence of the parents. Photodynamic therapy (PDT) has already shown encouraging results in the treatment of acne in adult patients, with good aesthetic results compared to other therapies and few side effects. However, its use is still not standardized in the pediatric population. On this topic, we report our experience with PDT in a young patient affected by dorsal acne. After five sessions of ALA-PDT at monthly intervals, a remarkable improvement of the lesions was observed, with the healing of the inflamed nodules and pustules, resolution of the painful symptoms, and an acceptable cosmetic outcome. Our case is paradigmatic of the potentiality of PDT to treat difficult and resistant-to-treatment lesions. Despite being time-consuming, this procedure has been demonstrated to be safe and well-tolerated. Lastly, the therapy is also well accepted by parents, due to its minimal invasiveness and mild side effects, compared to the other therapeutic options.
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Acne Vulgar , Fotoquimioterapia , Criança , Adulto , Adolescente , Humanos , Fármacos Fotossensibilizantes/uso terapêutico , Ácido Aminolevulínico/uso terapêutico , Fotoquimioterapia/métodos , Administração Cutânea , Acne Vulgar/tratamento farmacológicoRESUMO
Immuno-correlated dermatological pathologies refer to skin disorders that are closely associated with immune system dysfunction or abnormal immune responses. Advancements in the field of artificial intelligence (AI) have shown promise in enhancing the diagnosis, management, and assessment of immuno-correlated dermatological pathologies. This intersection of dermatology and immunology plays a pivotal role in comprehending and addressing complex skin disorders with immune system involvement. The paper explores the knowledge known so far and the evolution and achievements of AI in diagnosis; discusses segmentation and the classification of medical images; and reviews existing challenges, in immunological-related skin diseases. From our review, the role of AI has emerged, especially in the analysis of images for both diagnostic and severity assessment purposes. Furthermore, the possibility of predicting patients' response to therapies is emerging, in order to create tailored therapies.
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INTRODUCTION: Tirbanibulin 1% ointment has been licensed to treat non-hyperkeratotic actinic keratosis (AKs) on the face and scalp in adults to ensure excellent patient tolerability due to the mild side effects and the brief application time compared to other topical therapies on the market. A growing body of evidence suggests that, beyond their primary function, the treatments for AKs and the cancerization field may inadvertently confer substantial cosmetic benefits to patients. METHODS: We report a single-center retrospective case series of patients referred to the Dermatology Unit of the University Hospital of Messina, Italy, between February and December 2023 seeking treatment for AKs in the context of photodamaged areas in which the application of tirbanibulin 1% ointment induced, besides clearance of AKs, anti-aging effects on both skin texture and solar lentigos. RESULTS: Seven patients affected by Olsen grade 1-2 AKs experienced a powerful rejuvenating effect in the treated areas, with a marked efficacy in skin lightening and clearance of solar lentigo. CONCLUSIONS: Tirbanibulin 1% ointment seems able to improve skin aging as a desirable side effect at the site of application for AKs on chronic photodamaged skin. Such preliminary observation needs further confirmation in real-life studies on larger cohorts of patients, to explain the pathogenic mechanisms responsible for such aesthetically relevant results.
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Malignant cutaneous melanoma is the leading cause of death for skin cancer to date, with globally increasing incidence rates. In this epidemiological scenario, international scientific research is exerting efforts to identify new clinical strategies aimed at the prognostic amelioration of the disease. Very promising and groundbreaking in this context is the scientific interest related to alarmins and their pioneering utility in the setting of the pathogenetic understanding, diagnosis, prognosis, and therapy for malignant cutaneous melanoma. However, the scientific investigations on this matter should not overlook their still well-presented dual and contradictory role. The aim of our critical analysis is to provide an up-to-date overview of the emerging evidence concerning the dichotomous role of alarmins in the aforementioned clinical settings. Our literature revision was based on the extensive body of both preclinical and clinical findings published on the PubMed database over the past 5 years. In addition to this, we offer a special focus on potentially revolutionary new therapeutic frontiers, which, on the strength of their earliest successes in other clinical areas, could inaugurate a new era of personalized and precision medicine in the field of dermato-oncology.
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Alarminas , Melanoma Maligno Cutâneo , Melanoma , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/patologia , Melanoma/diagnóstico , Melanoma/terapia , Melanoma/patologia , Prognóstico , Alarminas/metabolismo , Biomarcadores Tumorais/metabolismo , Pele/patologiaRESUMO
Cutaneous leishmaniasis (CL) is a vector-borne infection caused by the obligate intracellular parasites of the Leishmania genus. Children are more frequently affected due to increased exposure to sandflies and underdeveloped immune system. Currently, there is a lack of consensus on the most effective treatment approach for CL since most drugs are accompanied by numerous limitations, including adverse effects, toxicity, and onset of antimicrobial resistance phenomena. These limitations appear more relevant in the pediatric population, both for the treatment-related risks and for the reticence of the parents. Photodynamic therapy (PDT) has been increasingly employed in numerous inflammatory and infectious diseases, owing to its tissue selectivity and excellent cosmetic outcomes. On this topic, we report our experience with daylight-PDT (DL-PDT) therapy in a difficult-to-treat area like the facial region in a child with a six-month history of CL. Our case is paradigmatic of the potentiality of PDT to treat difficult lesions in a pediatric setting. However, its use has not yet been standardized either for the treatment of leishmania, with high variability in the number of sessions and time intervals. Specific protocols for pediatric patients should be better standardized in randomized clinical trials in order to provide clear indications for clinicians.
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Leishmania , Leishmaniose Cutânea , Fotoquimioterapia , Humanos , Criança , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Leishmaniose Cutânea/tratamento farmacológico , Resultado do Tratamento , Ácido Aminolevulínico/uso terapêuticoRESUMO
Group 2 innate lymphoid cells (ILC2s) are lymphoid cells that are resident in mucosal tissues, especially the skin, which, once stimulated by epithelial cell-derived cytokines, release IL-5, IL-13, and IL-4, as the effectors of type 2 immune responses. This research aims to evaluate the role of ILC2s in the pathogenesis of skin diseases, with a particular focus on inflammatory cutaneous disorders, in order to also elucidate potential therapeutic perspectives. The research has been conducted in articles, excluding reviews and meta-analyses, on both animals and humans. The results showed that ILC2s play a crucial role in the pathogenesis of systemic skin manifestations, prognosis, and severity, while a potential antimelanoma role is emerging from the new research. Future perspectives could include the development of new antibodies targeting or stimulating ILC2 release. This evidence could add a new therapeutic approach to inflammatory cutaneous conditions, including allergic ones.
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Genital warts (GWs) are the most common sexually transmitted infections worldwide, caused by the human papillomavirus (HPV). The increasing prevalence of GWs in children has renewed the interest in therapeutic management which still presents a unique challenge, being influenced by many variables including size, quantity, and location of warts, as well as the presence of comorbidities. Conventional photodynamic therapy (C-PDT) has already shown encouraging results in the treatment of viral warts in adult patients, but its use is still not standardized in the pediatric population. On this topic, we report our experience with C-PDT in a difficult-to-treat area like the perianal region in a 12-year-old girl affected by Rett syndrome, an X-linked dominant neurological disorder, with a 10-month history of florid genital condylomatosis. After the third session of C-PDT, complete clearance of the lesions was achieved. Our case is paradigmatic of the potentiality of PDT to treat difficult lesions in difficult patients. Despite being expensive and time-consuming, this procedure has been demonstrated to be safe and well-tolerated. Lastly, the therapy is also well accepted by parents, due to its minimal invasiveness and the few side effects, compared to the other therapeutic options.