Actinic Keratoses: A Prospective Pilot Study on a Novel Formulation of 4% 5-Fluorouracil Cream and a Review of Other Current Topical Treatment Options.

BACKGROUND: Actinic keratosis (AK) is one of the most common skin diseases, with a low risk of progression into invasive squamous cell carcinoma. We aim to assess efficacy and safety of a novel formulation of 5-Fluorouracil (5-FU) 4% with once daily application for the treatment of multiple AKs. METHODS: A pilot study was performed on 30 patients with a clinical and dermoscopic diagnosis of multiple AKs, enrolled between September 2021 and May 2022 at the Dermatology Departments of two Italian hospitals. Patients were treated with 5-FU 4% cream once daily for 30 consecutive days. The Actinic Keratosis Area and Severity Index (AKASI) was calculated before starting therapy, and at each follow-up, to assess objective clinical response. RESULTS: The cohort analyzed included 14 (47%) males and 16 (53%) females (mean age: 71 ± 12 years). A significant decrease in AKASI score at both 6 and 12 weeks (p < 0.0001) was observed. Only three patients (10%) discontinued therapy, and 13 patients (43%) did not report any adverse reactions; no unexpected adverse events were observed. CONCLUSIONS: In the setting of topical chemotherapy and immunotherapy, the new formulation of 5-FU 4% proved to be a highly effective treatment for AKs and field cancerization.

COVID 19-associated chilblain-like acral lesions among children and adolescents: an Italian retrospective, multicenter study.

BACKGROUND: Since the COVID-19 pandemic started, great interest has been given to this disease, especially to its possible clinical presentations. Besides classical respiratory symptoms, dermatological manifestations occur quite often among infected and non-infected patients, particularly in children. A prominent IFN-I response, that is generally higher in children compared to adults, may not only cause chilblain lesions, but it could also prevent infection and viral replication, thus justifying the negative swab results, as well as the absence of relevant systemic symptoms in positive cases. Indeed, reports have emerged describing chilblain-like acral lesions in children and adolescents with either proven or suspected infection. METHODS: Patients aged from 1 to 18 years old were enrolled in this study from 23 Italian dermatological units and were observed for an overall period of 6 months. Clinical pictures were collected along with data on the location and duration of skin lesions, their association with concomitant local and systemic symptoms, presence of nail and/or mucosal involvement, as well as histological, laboratory and imaging findings. RESULTS: One hundred thirty-seven patients were included, of whom 56.9% were females. Mean age was 11.97±3.66 years. The most commonly affected sites were the feet (77 patients, 56.2%). Lesions (48.5%) featured cyanosis, chilblains, blisters, ecchymosis, bullae, erythema, edema, and papules. Concomitant skin manifestations included maculo-papular rashes (30%), unspecified rashes (25%), vesicular rashes (20%), erythema multiforme (10%), urticaria (10%) and erythema with desquamation (5%). Forty-one patients (29.9%) reported pruritus as the main symptom associated with chilblains, and 56 out of 137 patients also reported systemic symptoms such as respiratory symptoms (33.9%), fever (28%), intestinal (27%), headache (5.5%), asthenia (3.5%), and joint pain (2%). Associated comorbid conditions were observed in 9 patients presenting with skin lesions. Nasopharyngeal swabs turned out positive in 11 patients (8%), whereas the remainder were either negative (101, 73%) or unspecified (25, 18%). CONCLUSIONS: COVID-19 has been credited as the etiology of the recent increase in acro-ischemic lesions. The present study provides a description of pediatric cutaneous manifestations deemed to be potentially associated with COVID-19, revealing a possible association between acral cyanosis and nasopharyngeal swab positivity in children and teenagers. The identification and characterization of newly recognized patterns of skin involvement may aid physicians in diagnosing cases of asymptomatic or pauci-symptomatic COVID patients.

Pilomatrix Carcinoma: Report of Two Cases of the Head and Review of the Literature.

BACKGROUND: Pilomatrix carcinoma (PC) is a rare skin tumor arising from hair follicle matrix cells. It is locally aggressive with a high rate of local recurrence after surgical excision. Few cases in the literature have been described and the management is not well defined. OBJECTIVES: The aim of this study was to present two cases of PC located on the head and review the relevant literature about epidemiology, clinical and dermoscopic evaluation, characteristics of local and distant metastases, local recurrence rate and management of this rare skin tumor. METHODS: We consulted databases from PubMed, Research Gate and Google Scholar, from January 2012 to November 2022. We reviewed the literature and reported two additional cases. RESULTS: We selected 52 tumors in middle-aged to older patients located mostly on the head. Dermoscopy evaluation was rarely performed in the pre-operative diagnostic setting. The most definitive treatment was wide local excision, but local recurrences were common. In total, we observed 11 cases of recurrences and 9 patients with locoregional or distant metastases. Four patients received adjuvant radiotherapy, two patients needed chemotherapy and local cancer therapy and one patient received radiochemotherapy. CONCLUSION: Our reports and the review of the literature can provide a better awareness and management of this rare tumor.

Vascular Diameter as Clue for the Diagnosis of Clinically and/or Dermoscopically Equivocal Pigmented and Non-Pigmented Basal Cell Carcinomas and Nodular Melanomas.

Background and objectives: Dermoscopy is a useful tool for the early and non-invasive diagnosis of skin malignancies. Besides many progresses, heavily pigmented and amelanotic skin tumors remain still a challenge. We aimed to investigate by dermoscopy if distinctive morphologic characteristics of vessels may help the diagnosis of equivocal nodular lesions. Materials and Methods: A collage of 16 challenging clinical and dermoscopic images of 8 amelanotic and 8 heavily pigmented nodular melanomas and basal cell carcinomas was sent via e-mail to 8 expert dermoscopists. Results: Dermoscopy improved diagnostic accuracy in 40 cases. Vessels were considered the best clue in 71 cases. Focusing on the diameter of vessels improved diagnosis in 5 cases. Conclusions: vascular diameter in addition to morphology and arrangement may be a useful dermoscopic clue for the differential diagnosis of clinically equivocal nodular malignant tumors.

The supernova remnant SN 1006 as a Galactic particle accelerator.

The origin of cosmic rays is a pivotal open issue of high-energy astrophysics. Supernova remnants are strong candidates to be the Galactic factory of cosmic rays, their blast waves being powerful particle accelerators. However, supernova remnants can power the observed flux of cosmic rays only if they transfer a significant fraction of their kinetic energy to the accelerated particles, but conclusive evidence for such efficient acceleration is still lacking. In this scenario, the shock energy channeled to cosmic rays should induce a higher post-shock density than that predicted by standard shock conditions. Here we show this effect, and probe its dependence on the orientation of the ambient magnetic field, by analyzing deep X-ray observations of the Galactic remnant of SN 1006. By comparing our results with state-of-the-art models, we conclude that SN 1006 is an efficient source of cosmic rays and obtain an observational support for the quasi-parallel acceleration mechanism.

Non-Melanoma Skin Cancer Clearance after Medical Treatment Detected with Noninvasive Skin Imaging: A Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVES: Non-melanoma skin cancer (NMSC) treated with nonsurgical therapies can be monitored with noninvasive skin imaging. The precision of dermoscopy, reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) in detecting clearance is unclear. We aim to report the proportion of persisting tumors identified with noninvasive technologies available in the literature. METHODS: A systematic literature search was conducted on the PubMed and Cochrane Public Library Databases for articles published prior to November 2021. Statistical analyses were conducted with MedCalc 14.8.1 software. RESULTS: A total of eight studies (352 lesions) reporting noninvasive imaging for NMSC clearance following nonsurgical treatment were included. Most (n = 7) reported basal cell carcinoma (BCC), and one study reported squamous cell carcinoma (SCC) clearance. A meta-analysis of the BCC clearance revealed that the summary effect for RCM was higher, as compared to the other techniques. Interestingly, the sensitivity and specificity for OCT were 86.4% (95% CI: 65.1-97.1) and 100% (95% CI: 94.8-100.0), respectively, whilst, for RCM, they reached 100% (95%CI: 86.8-100) and 72.5% (95% CI: 64.4-79.7), respectively. CONCLUSIONS: Routine clinical examination and dermoscopy underperform when employed for NMSC clearance monitoring, although they represent the first approach to the patient. OCT and RCM seem to improve the detection of persistent BCC after medical treatment.

Spotlight on the treatment armamentarium of concomitant psoriasis and inflammatory bowel disease: a systematic review.

BACKGROUND: Psoriasis and inflammatory bowel diseases share common immunological pathomechanisms and therefore similar treatment options. OBJECTIVE: To assess already existing therapies and their efficacy versus adverse effects and paradoxical reactions in patients presenting with either disease or both. DATA SOURCES: A systematic search of the PubMed and Science.gov databases was performed for the period 2018-2020. Only articles in English were selected. Search terms included a combination of keywords: adalimumab, infliximab, etanercept, golimumab, certolizumab, ustekinumab, guselkumab, vedolizumab, secukinumab, ixekizumab, brodalumab, acitretin, cyclosporine, methotrexate, apremilast, mycophenolate mofetil, sulfasalazine, hydroxyurea, azathioprine, 6-thioguanine, tacrolimus, leflunomide and fumaric acid esters in combination with each of the following: paradoxical, psoriasis, psoriatic arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis. Other potentially relevant articles were identified by manually checking the references of the included literature. STUDY SELECTION: Recent reviews and meta-analyses, pooled analyses, cohort studies, observational studies, care reports were all included. CONCLUSIONS: Psoriasis and IBD can be treated concurrently as they share common inflammatory pathways. TNF-α inhibitors and IL-12/23 have been successful in treating both psoriasis and IBD. IL-17 inhibitors are recognized treatments for psoriasis but have the potential to exacerbate IBD. Newer molecules require further clinical trials and real-life studies in order to confirm their efficacy and safety.

Analysis of clinical factors as possible predictors of response to omalizumab and relapse after treatment discontinuation in chronic spontaneous urticaria.

Omalizumab is a monoclonal anti-IgE antibody which is effective in chronic spontaneous urticaria (CSU), although clinical response appears to be variable in the real-life setting. The aim of this study was to evaluate whether the response of CSU to omalizumab and disease relapse are associated with individual and/or clinical characteristics of patients. We retrospectively evaluated the clinical records of 124 patients treated with omalizumab for moderate to severe CSU refractory to antihistamines. Disease activity was assessed using the urticaria activity score over the last 7 days (UAS7). After 24 weeks of treatment, 91% of patients showed complete remission (UAS7 = 0) or good control (UAS7 < 7) of CSU. Omalizumab was re-administered in 45 patients because of recurrence of moderate to severe symptoms at week 8 after treatment discontinuation or later, and clinical results achieved with retreatment were similar to those observed in the first course. Among the parameters included in our analysis (age and sex of patients, documented history of atopy or autoimmune thyroid disease, CSU duration and baseline severity, concurrent angioedema, and association with chronic inducible urticaria), none was associated with response to omalizumab in our study population. Similarly, these parameters did not significantly differ between patients who experienced CSU relapse and those without relapse. Predictors of response to omalizumab treatment in CSU patients are still unclear, and further studies are needed to evaluate the presence of baseline factors that can influence treatment outcome.

Clinical and Dermoscopic Features of Melanocytic Lesions on the Face Versus the External Ear.

INTRODUCTION: Melanoma of the external ear is a rare condition accounting for 7-20% of all melanomas of the head and neck region. They present classical features of extra-facial melanomas clinically and dermoscopically. In contrast, facial melanomas show peculiar patterns in dermoscopy. OBJECTIVES: To evaluate whether there are clinical and/or dermoscopic differences in melanocytic lesions located either at the external ear or on the face. METHODS: In this retrospective study we reviewed an image database for clinical and dermoscopic images of melanomas and nevi located either on the face or at the level of the external ear. RESULTS: 65 patients (37 men; 63.8%) with 65 lesions were included. We found no significant differences in comparing face melanomas with melanomas at the level of the external ear, neither clinically nor dermoscopically. However, we provided evidence for differences in some clinical and dermoscopic features of melanomas and nevi of the external ear. CONCLUSIONS: In this study, we reported no significant differences in comparing melanomas on the face with melanomas of the external ear, both clinically and dermoscopically. Furthermore, we provided data on clinical and dermoscopic differences comparing nevi and melanoma of the external ear.

Clinical and dermoscopic characterization of pediatric Spitz nevi of the ear.

Spitz nevi of special sites, such as the ear, appear rarely and pose a challenge with worrisome clinical, dermoscopic, or histopathological features. Our aim was to evaluate the morphological findings of a series of Spitz nevi of the ear in order to obtain more knowledge about their clinical-dermoscopic patterns. Of a total of six cases, three main dermoscopic structures were found: pseudonetwork, structureless areas, and cobblestone pattern. Our preliminary findings suggest that dermoscopy may be helpful in improving the diagnostic accuracy of Spitz nevus of the ear and minimize surgery in a sensitive location.

Basal cell carcinoma and dermal nevi of the face: comparison of localization and dermatoscopic features.

BACKGROUND: Basal cell carcinoma (BCC) and dermal nevi located on the face can easily be confused on clinical examination. Little is known about the different preferential localizations of these entities, and a systematic analysis of dermatoscopic features for differential diagnosis is lacking. METHODS: Clinical and dermatoscopic images of BCCs and dermal nevi were retrospectively evaluated to study their relation to various face anatomical areas, BCC histotype, classic and nonclassic dermatoscopic BCC criteria, as well as typical dermatoscopic criteria for dermal nevi. RESULTS: We examined 118 BCCs and 77 dermal nevi, all having histopathological confirmation. BCCs were most frequently located on the lateral side of the forehead (12.7%), nasal dorsum (10.2%) and nasal ala (9.3%), while dermal nevi were found predominantly on the buccal area (11.8%), scalp (11.8%), and perioral region (10.8%). The prevalent dermatoscopic criteria for BCC were the classic arborizing vessels (94.1%) and arborizing microvessels (89%). The most common BCC histotype on the face was sclerodermiform (47.5%), followed by nodular (28%) and superficial (24.6%). CONCLUSIONS: This study shows that BCCs are preferentially located on the lateral side of the forehead, nasal dorsum and nasal ala, while dermal nevi of the face are preponderantly located on the buccal area, scalp, and perioral region. The dermatoscopic features confirmed the frequency of classic and nonclassic criteria for BCCs already demonstrated in other studies. No significant site-specific features were observed for either BCCs or dermal nevi.

Neoadjuvant Therapy for Non-melanoma Skin Cancer: Updated Therapeutic Approaches for Basal, Squamous, and Merkel Cell Carcinoma.

OPINION STATEMENT: Recently introduced systemic therapies for locally advanced and metastatic non-melanoma skin cancers (NMSCs) are paving the way for neoadjuvant approach. Although none of the therapeutic options has currently gained indication in this setting, neoadjuvant approach for NMSCs is an open field and we are likely to see huge developments in the near future. Targeted therapy with sonic hedgehog pathway inhibitors is very effective in locally advanced or multiple basal cell carcinomas while immunotherapy with immune checkpoint inhibitors appears to be promising for advanced cutaneous squamous cell carcinoma and Merkel cell carcinoma. To date, targeted therapy and immunotherapy represent the frontiers in NMSC therapeutic management and, according to recent studies, good results can be achieved.

Impact of the COVID-19 Pandemic on Dermatology Practice Worldwide: Results of a Survey Promoted by the International Dermoscopy Society (IDS).

INTRODUCTION: The International Dermoscopy Society (IDS) conducted an online survey to investigate the impact of coronavirus disease 2019 (COVID-19) outbreak on the daily practice of dermatologists working with skin cancer patients, to collect data regarding the frequency of skin manifestations noticed by the members, and to obtain information about the use of teledermatology during the pandemic. METHODS: All IDS members were asked to fill in a questionnaire, sent by email. A questionnaire available in English was sent to all IDS members (≈16.0000 members) by email. The questionnaire was anonymous, with a compiling time of less than 5 minutes. The survey was open for 30 days (from April 24, 2020 to May 24, 2020) and it could only be filled out once. RESULTS: Overall, 678 dermatologists responded to the questionnaire; 334 members stated that there has been a reduction of more than 75% in daily work activity during the pandemic, 265 dermatologists worked fewer days per week, and 118 experienced telemedicine for the first time. Acrodermatitis was the most frequently observed skin manifestation (n = 80) followed by urticarial rash (n = 69), morbilliform rash (n = 53) and purpuric manifestation (n = 40). In regard to the role of teledermatology, 565 dermatologists reported an increased number of teleconsultations, and the number of melanomas diagnosed during the pandemic was practically 0 for 385 (56.78%) of respondents. CONCLUSION: This survey highlights that the outbreak had a negative impact on most dermatology services, with a significant reduction in consultation time spent for chronic patients, and an increased risk of missed melanoma and nonmelanoma skin cancer (NMSC) diagnosis. Moreover, our study confirms earlier findings of a wide range of skin manifestations associated with COVID-19.

Effectiveness and tolerability of treatment for isolated actinic keratoses: A retrospective comparison between cryotherapy, CO2 laser and 5-fluorouracil 0.5%/salicylic acid 10.

Actinic keratoses (AK) have been described as either intraepithelial keratinocytic dysplasia that can evolve into invasive squamous cell carcinoma (SCC) or as in situ SCC that can progress into an invasive form. A retrospective study was conducted to compare outcomes of three different topical therapies for patients with single AK (<4): cryotherapy, CO2 laser and 5-fluorouracil 0.5%/salicylic acid 10%. We included 72 patients who presented at the Dermatology Clinic of Maggiore Hospital of Trieste between 1 November 2019 and 31 January 2020 for the treatment of AKs. All treatments led to a significant reduction in the average diameter of AK. Pain felt by patients was significantly lower after 5-FU 0.5%/SA 10%. Side effects appeared similarly distributed among the three groups, with erythema and crusts being the most frequent. Aesthetic outcomes were highest in the 5-FU 5%/SA 10% group, as evaluated by both the patient and the operator. Cryotherapy, CO2 laser and 5-FU 5%/SA 10% were all effective, with no significant efficacy differences among them. Additionally, 5-FU 5%/SA 10% was proved to have the best aesthetic result and to cause the least pain, while necessitating long-term administration. This should be taken into account for patients with low pain tolerance and low treatment adherence. Cryotherapy and CO2 laser have the advantage of requiring a single session, which might be more suitable for uncooperative patients.

An overview on the role of CO2 laser in general dermatology.

Among different laser types, the carbon dioxide (CO2 ) laser remains one of the most used by dermatologists. Its usefulness has been demonstrated both for therapeutic and cosmetic purposes. This review aims to provide an overview of the applications of CO2 laser in dermatology, focusing on the treatment of infective, neoplastic, and antiaesthetic lesions.

Novel Therapeutic Approaches and Targets for the Treatment of Hidradenitis Suppurativa.

BACKGROUND: Hidradenitis Suppurativa (HS) is a chronic, recurrent and disabling inflammatory skin condition, clinically characterized by nodules, bullae, abscesses, fistulae, and draining sinus tracts mainly located in axillae, inguinal folds, inframammary region and buttocks, often leading to pain, scarring, disfigurement and decreased quality of life. Due to its complex nature, with still no completely elucidated etiology and pathogenesis, the management of HS can be challenging. In fact, many patients do not respond to the traditionally available systemic treatments, including antiinflammatories, antibiotics and surgery. Research has provided new insights into the mechanisms of HS, mainly investigating the inflammatory cytokine pathways underlying the disease. METHODS: We review the current knowledge on newer therapeutic approaches and targets for the treatment of HS, through a PubMed-based literature search. RESULTS: In this setting, studies on tumor necrosis factor-α, IL-1ß, IL-10, and the IL-23/T-helper (Th) 17 and IL12/Th1 axes in immune dysregulation in HS have helped in developing new regimens. Inhibitor of phosphodiesterase 4 and laser treatments have shown clinically meaningful efficacy with good short-term safety and tolerability. CONCLUSION: Target therapy has revolutionized the treatment of moderate to severe HS, based on the inhibition of specific molecular or cellular targets, directly involved in the pathogenesis of the condition.