Shedding Light on Photodynamic Therapy in the Treatment of Necrobiosis Lipoidica: A Multicenter Real-Life Experience.

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.

Tirbanibulin 1% Ointment for Actinic Keratosis: Results from a Real-Life Study.

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.

Photodynamic therapy for severe acne.

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.

Daylight photodynamic therapy for cutaneous leishmaniasis in a pediatric setting: A case report and literature review.

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.

Role of Capillaroscopy in Early Diagnosis of Ionizing Radiation Damage in Healthcare Professionals.

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.

The Role of Nutraceuticals and Functional Foods in Skin Cancer: Mechanisms and Therapeutic Potential.

Skin cancer is a prevalent type of cancer worldwide and has a high growth rate compared to other diseases. Although modern targeted therapies have improved the management of cutaneous neoplasms, there is an urgent requirement for a safer, more affordable, and effective chemoprevention and treatment strategy for skin cancer. Nutraceuticals, which are natural substances derived from food, have emerged as a potential alternative or adjunctive treatment option. In this review, we explore the current evidence on the use of omega-3 fatty acids and polyphenols (curcumin, epigallocatechin gallate, apigenin, resveratrol, and genistein) for the treatment of melanoma and non-melanoma skin cancer (NMSC), as well as in their prevention. We discuss the mechanisms of action of the aforementioned nutraceuticals and their probable therapeutic benefits in skin cancer. Omega-3 fatty acids, curcumin, epigallocatechin gallate, apigenin, resveratrol, and genistein have several properties, among which are anti-inflammatory and anti-tumor, which can help to prevent and treat skin cancer. However, their effectiveness is limited due to poor bioavailability. Nanoparticles and other delivery systems can improve their absorption and targeting. More research is needed to evaluate their safety and effectiveness as a natural approach to skin cancer prevention and treatment. These compounds should not replace conventional cancer treatments, but may be used as complementary therapy under the guidance of a healthcare professional.

Hidradenitis suppurativa and psoriasis: the odd couple.

Psoriasis and hidradenitis suppurativa are chronic inflammatory skin diseases that can develop together, negatively impacting on the patient's quality of life. We aimed to review the most up-to-date information regarding the epidemiology, pathogenesis, clinical presentation and possible therapeutical choices in patients with both psoriasis and hidradenitis suppurativa, thus linking these two autoimmune and autoinflammatory conditions. A narrative review of articles dating from 2017 to 2022 has been performed using the PubMed database. We analyzed the case reports and case series found in the literature regarding patients who suffered from both psoriasis and HS. Psoriasis arose before hidradenitis suppurativa in the majority of cases, while only a minority of them had hidradenitis suppurativa before psoriasis. Interestingly, some patients suffered from paradoxical hidradenitis suppurativa following biological therapy administered to treat the already present psoriasis. Lastly, new biological drugs have been marketed with great success for the outcome of psoriasis, but similar progress did not happen for hidradenitis. Novel therapeutic approaches and lines of research are needed for the treatment of these pathologies, even if concomitant, in order to improve patient's quality of life.

"Mens Sana in Cute Sana"-A State of the Art of Mutual Etiopathogenetic Influence and Relevant Pathophysiological Pathways between Skin and Mental Disorders: An Integrated Approach to Contemporary Psychopathological Scenarios.

The negative socioeconomic impact of mental health disorders and skin diseases has increased in part due to the conflict between Russia and Ukraine, which has been a fertile ground for the emergence of psychopathologies. It is firmly established that there is a direct thread of etiopathogenetic communication between skin diseases and neuropsychiatric disorders, and the literature has tried to reveal the pathophysiological mechanisms governing such bidirectionality. This paper discusses this complex network of molecular pathways that are targeted by conventional and biological pharmacological agents that appear to impact two pathological spheres that previously seemed to have little connection. This molecular discussion is supplemented with a literature review, from a clinical viewpoint, regarding skin-brain etiopathogenetic bidirectionality. We focus on post-traumatic stress disorder (PTSD), which can be considered for all intents and purposes a systemic inflammatory disease that also affects the skin. A brief overview is also provided on the diagnostic-therapeutic and follow-up potential of oxidative and inflammatory markers potentially involved in the pathophysiological mechanisms treated. The aim is to clarify how these mechanisms may be useful in defining different stress-coping strategies and thus individual phenotypes of stress sensitivity/resistance in order to promote personalized medicine in the field of psychodermatology.

Body mass index and baseline platelet count as predictive factors in Merkel cell carcinoma patients treated with avelumab.

Background: Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer, associated with a worse prognosis. The Immune Checkpoint Inhibitors (ICIs) avelumab and pembrolizumab have been recently approved as first-line treatment in metastatic MCC (mMCC). The clinical observation of improved outcomes in obese patients following treatment with ICIs, known as the "obesity paradox", has been studied across many types of tumors. Probably due to the rarity of this tumor, data on mMMC patients are lacking. Patients and methods: This is an observational, hospital-based, study to investigate the role of Body Mass Index (BMI) as predictive biomarker of ICI response in mMCC patients treated with avelumab as first-line treatment. The study population included the patients treated from February 2019 to October 2022 in an Italian referral center for rare tumors. Clinico-pathological characteristics, BMI, laboratory parameters (NLR and platelet count), and response to avelumab were analyzed from a MCC System database prospectively collected. Results: Thirty-two (32) patients were included. Notably, the presence of pre-treatment BMI ≥ 30 was significantly associated with longer PFS [BMI < 30 Group: median PFS, 4 months (95% CI: 2.5-5.4); BMI ≥ 30 Group: median PFS, not reached; p<0.001)[. Additionally, the median PFS was significantly higher in patients with higher PLT (median PFS: 10 months in the "low PLT" Group (95% CI: 4.9, 16.1) vs 33 months (95% CI: 24.3, 43.2) in the "high PLT" Group (p=0.006). The multivariable Cox regression model confirmed these results. Conclusion: To our knowledge, this is the first study that investigates the predictive role of BMI in MCC patients. Our data were consistent with the clinical observation of improved outcomes in obese patients across other tumor types. Thus, advanced age, a weakened immune system, and the obesity-associated "inflammaging", are key factors that could impact the cancer immune responses of mMCC patients.

Photodynamic therapy for intergluteal warts in a child affected by Rett syndrome.

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.

Immunosenescence and Skin: A State of Art of Its Etiopathogenetic Role and Crucial Watershed for Systemic Implications.

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.

Potential Role of Innate Lymphoid Cells in the Pathogenesis and Treatment of Skin Diseases.

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.

Rosmarinus officinalis and Skin: Antioxidant Activity and Possible Therapeutical Role in Cutaneous Diseases.

The rosemary plant, Rosmarinus officinalis L., one of the main members of the Lamiaceae family, is currently one of the most promising herbal medicines due to its pharmaceutical properties. This research aimed to evaluate the antioxidant role of Rosmarinus officinalis and its bioactive compounds on the skin, with a focus on the newly emerging molecular mechanisms involved, providing extensive scientific evidence of its anti-inflammatory, antimicrobial, wound-healing and anticancer activity in dermatological practice. The search was conducted on articles concerning in vitro and in vivo studies in both animals and humans. The results obtained confirm the antioxidant role of R. officinalis. This assumption derives the possibility of using R. officinalis or its bioactive elements for the treatment of inflammatory and infectious skin pathologies. However, although the use of rosemary in the treatment of skin diseases represents a fascinating line of research, future perspectives still require large and controlled clinical trials in order to definitively elucidate the real impact of this plant and its components in clinical practice.

Prognostic role of soluble PD-1 and BTN2A1 in overweight melanoma patients treated with nivolumab or pembrolizumab: finding the missing links in the symbiotic immune-metabolic interplay.

Individual response to immune checkpoint inhibitors (ICIs) is currently unpredictable in patients with melanoma. Recent findings highlight a striking improvement in the clinical outcomes of overweight/obese patients treated with ICIs, which seems driven, at least in part, by programmed cell death protein 1 (PD-1)-mediated T-cell dysfunction. A putative role of butyrophilins (BTNs) is under investigation as a novel mechanism of cancer immune evasion and obesity-associated inflammation. This study investigates the role of baseline plasma levels of soluble PD-1 (sPD-1), soluble programmed cell death ligand 1 (sPD-L1), BTN2A1 (sBTN2A1), BTN3A1 (sBTN3A1), along with body mass index (BMI), as predictive biomarkers of immunotherapy response in metastatic melanoma patients treated with nivolumab or pembrolizumab as first-line treatment. In all, 41 patients were included in the study. The baseline plasma level of sPD-1 was significantly lower, and the sBTN2A1 was significantly higher, in long-responder patients to nivolumab or pembrolizumab (median sPD-1: 10.3 ng/ml versus 16.6 ng/ml, p = 0.001; median sBTN2A1: 4.4 ng/ml versus 3.77 ng/ml, p = 0.004). Lower levels of sPD-1 and higher levels of sBTN2A1 were also significantly associated with better overall response rate. Notably, when we further stratified the study cohort using BMI along with sPD-1, patients with BMI ⩾ 25 and sPD-1 < 11.24 ng/ml had longer time to treatment failure after PD-1 inhibitor than other subgroups of patients (p < 0.001). Circulating sPD-1 and sBTN2A1 detection, along with BMI, could give more insights into the immune-metabolic interactions underlying the benefit observed in overweight/obese patients, improving the use of dynamic, noninvasive, biomarkers for patient selection.

Dermoscopy features of infantile perianal pyramidal protrusion.

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.

Wnt Signaling Pathways: From Inflammation to Non-Melanoma Skin Cancers.

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.

Oxidative Stress and Phototherapy in Atopic Dermatitis: Mechanisms, Role, and Future Perspectives.

Atopic dermatitis is a chronic inflammatory skin disease in which the overproduction of reactive oxygen species plays a pivotal role in the pathogenesis and persistence of inflammatory lesions. Phototherapy represents one of the most used therapeutic options, with benefits in the clinical picture. Studies have demonstrated the immunomodulatory effect of phototherapy and its role in reducing molecule hallmarks of oxidative stress. In this review, we report the data present in literature dealing with the main signaling molecular pathways involved in oxidative stress after phototherapy to target atopic dermatitis-affected cells. Since oxidative stress plays a pivotal role in the pathogenesis of atopic dermatitis and its flare-up, new research lines could be opened to study new drugs that act on this mechanism, perhaps in concert with phototherapy.